PMID- 20734096 TI - A FOXG1 mutation in a boy with congenital variant of Rett syndrome. AB - Mutations in the FOXG1 gene have been shown to cause congenital variant of Rett syndrome. To date, point mutations have been reported only in female patients. We screened the entire coding region of the gene for mutations in 50 boys with congenital encephalopathy, postnatal microcephaly, and complex movement disorders, a clinical picture very similar to that described in girls with FOXG1 mutations. We found one boy carrying the de novo c.256_257dupC frameshift mutation. He presented the association of postnatal microcephaly, severe axial dystonia with severe feeding difficulties with protruding tongue movements during the first year of life that subsequently evolved into dyskinetic movement disorders with hand stereotypies. In contrast to his severe motor impairment, he developed nonverbal communication skills and relative good eye contact. Brain MRI showed frontal gyral simplification with dramatic myelination delay most prominent in both frontal lobes. Altogether the presentation in this male patient is highly reminiscent of that observed in FOXG1-mutated females with the congenital variant of Rett syndrome. This new case confirms the prediction that congenital variant of Rett syndrome should be found also in males, with the characteristic hallmarks consisting of postnatal microcephaly, dyskinetic movement disorder with Rett-like features, i.e., hand stereotypies, and frontal gyral simplification with myelination delay. FOXG1 screening should be considered in individuals with these clinical features. PMID- 20734097 TI - Low doses of 3-nitropropionic acid in vivo induce damage in mouse skeletal muscle. AB - Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases and in some well-described myopathies. In the present study, we evaluated muscle changes in vivo after blocking the mitochondrial complex II of the respiratory chain by using 3 nitropropionic acid (3-NP). This neurotoxin has been used as a pharmacological tool in animal models to address some of the metabolic modifications that might underlie central neurodegeneration; however, changes in peripheral musculature have not been documented. We believe that skeletal muscles must be affected because their integrity highly depends on oxidative metabolism. Therefore, histochemical, ultrastructural, and biochemical changes were studied in the muscles of mice treated with low doses of 3-NP (15 mg/kg, i.p., for 5 days). 3-NP treated mice displayed changes in alkaline phosphatase (APase), succinic dehydrogenase (SDH), and cytochrome c oxidase (COX) levels in the gracilis and gastrocnemius muscles. These changes were statistically significant for APase and SDH in both muscles and for COX only in the gastrocnemius. No significant alterations in acetylcholinesterase (AChE) expression were observed in either muscle. Analysis of the muscle ultrastructure revealed mitochondrial atrophy as well as sarcomere and nuclei disorganization. At the biochemical level, nitric oxide (NO) and lipid peroxidation (LPO) changed in the muscles of 3-NP-treated mice, suggesting metabolic alterations due to oxidative stress. Early damage in the striatal tissue and behavioral modifications are also documented. PMID- 20734098 TI - Assessment of mycobacteremia detection as a complementary method for the diagnosis of tuberculosis in HIV-infected patients. AB - The purpose of this investigation was to assess the usefulness of mycobacteremia detection in human immunodeficiency virus (HIV) patients with suspected tuberculosis. The study included 47 patients with suspected tuberculosis and confirmed HIV infection. A first blood sample was incubated in a BACTEC 9050 MB system, while white blood cells isolation was performed on a second blood specimen before incubation in a BACTEC MGIT 960 system. The third specimen was taken from the affected organs of each patient according to their clinical profile. Twelve (25.5%) patients were positive for mycobacterial infection identified by any of the methods used. Ten (21.2%) were positive for Mycobacterium tuberculosis and 2 (4.3%) for M. avium. Six patients were diagnosed by the culture of specimen from affected organs only, whilst three other patients were positive exclusively for blood cultures. Three additional patients were diagnosed by both methods. Four patients with negative cultures were ultimately diagnosed with tuberculosis by measuring the adenosine deaminase levels. Mycobacteremia detection can be used to increase the sensitivity of the diagnosis of tuberculosis and other mycobacteria in patients with HIV. However, it cannot be used as the sole diagnostic method. Clinical specimen cultures do not provide 100% diagnostic accuracy and it is, therefore, critical to further improve the mycobacteria detection sensitivity. PMID- 20734099 TI - An inconspicuous fallopian-tube carcinoma clinically manifested as a rectovaginal septal tumor: a pitfall for diagnosis and treatment. AB - We report an unusual metastasis of an inconspicuous fallopian-tube carcinoma to the rectovaginal septum in a 67-year-old woman. The 4-cm tumor of serous adenocarcinoma was identified in the rectovaginal space with intact vaginal and rectal mucosa. The patient underwent an abdominoperineal resection with adjacent rectum and the bilateral uterine annexes, which were macroscopically intact. Unexpectedly, invasive and intraepithelial serous adenocarcinoma in fallopian tube fimbria was microscopically observed, suggesting that the fallopian fimbria was the origin of the rectovaginal septum tumor. The clonality of these two tumors was confirmed by the presence of an identical single nucleotide point mutation in TP53. The patient received six cycles of adjuvant paclitaxel and carboplatin combination chemotherapy. There was no sign of recurrence after 17 months of treatment. This case study demonstrates that the fallopian-tube carcinoma, which exhibited minimal growth in the primary site, has the potential to metastasize to the retroperitoneal space and suggests that the fallopian-tube fimbria must be closely examined in cases of adenocarcinoma of unknown origin. PMID- 20734100 TI - Anisotropic effects of the levator ani muscle during childbirth. AB - Pelvic floor dysfunction and pelvic organ prolapse have been associated with damage to the levator ani (LA) muscle, but the exact mechanisms linking them remain unknown. It has been postulated that factors such as vaginal birth and ageing may contribute to long-term, irreversible LA muscle damage. To investigate the biomechanical significance of the LA muscle during childbirth, researchers and clinicians have used finite element models to simulate the second stage of labour. One of the challenges is to represent the anisotropic mechanical response of the LA muscle. In this study, we investigated the effects of anisotropy by varying the relative stiffness between the fibre and the matrix components, whilst maintaining the same overall stress-strain response in the fibre direction. A foetal skull was passed through two pelvic floor models, which incorporated the LA muscle with different anisotropy ratios. Results showed a substantial decrease in the magnitude of the force required for delivery as the fibre anisotropy was increased. The anisotropy ratio markedly affected the mechanical response of the LA muscle during a simulated vaginal delivery. It is apparent that we need to obtain experimental data on muscle mechanics in order to better approximate the LA muscle mechanical properties for quantitative analysis. These models may advance our understanding of the injury mechanisms of pelvic floor during childbirth. PMID- 20734101 TI - Will the next generation of PACS be sitting on a cloud? AB - Cloud computing has gathered significant attention from information technology (IT) vendors in providing massively scalable applications as well as highly managed remote services. What is cloud computing and how will it impact the medical IT market? Will the next generation of picture archiving and communication systems be leveraging cloud technology? PMID- 20734102 TI - Identification of a bacterial inhibitor against g-type lysozyme. AB - Lysozymes are antibacterial effectors of the innate immune system in animals that hydrolyze peptidoglycan. Bacteria have evolved protective mechanisms that contribute to lysozyme tolerance such as the production of lysozyme inhibitors, but only inhibitors of chicken (c-) and invertebrate (i-) type lysozyme have been identified. We here report the discovery of a novel Escherichia coli inhibitor specific for goose (g-) type lysozymes, which we designate PliG (periplasmic lysozyme inhibitor of g-type lysozyme). Although it does not inhibit c- or i-type lysozymes, PliG shares a structural sequence motif with the previously described PliI and MliC/PliC lysozyme inhibitor families, suggesting a common ancestry and mode of action. Deletion of pliG increased the sensitivity of E. coli to g-type lysozyme. The existence of inhibitors against all major types of animal lysozyme and their contribution to lysozyme tolerance suggest that lysozyme inhibitors may play a role in bacterial interactions with animal hosts. PMID- 20734103 TI - B-MYB delays cell aging by repressing p16 (INK4alpha) transcription. AB - p16 ( INK4alpha ), an inhibitor of cyclin-dependent kinase 4 and 6, has been proposed to play an important role in cellular aging and in premature senescence. The expression of the p16 ( INK4alpha ) is primarily under transcriptional control. Our previous data showed that a negative regulation element lies in its promoter. In that element, a MYB-binding site (MBS) was uncovered by transcription analysis. Here, we report that MBS is a negative regulation element and B-MYB binds to this site in vivo. In human embryonic lung fibroblast cells, B MYB downregulated p16 ( INK4alpha ) expression, whereas knocking down of B-MYB upregulated it. Evidence also showed that overexpression of B-MYB in cells could increase the number of utmost passage and decrease G1 block, whereas knocking down of B-MYB could impair their replicative ability. This study provides evidence of the capacity of B-MYB not only to regulate p16 ( INK4alpha ) expression but also the phenotypic consequence on cellular senescence. PMID- 20734105 TI - Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA regulated nuclear export and biological function. AB - The mitogen-activated protein kinase-activated protein kinase-5 (MK5) resides predominantly in the nucleus of resting cells, but p38(MAPK), extracellular signal-regulated kinases-3 and -4 (ERK3 and ERK4), and protein kinase A (PKA) induce nucleocytoplasmic redistribution of MK5. The mechanism by which PKA causes nuclear export remains unsolved. In the study reported here we demonstrated that Ser-115 is an in vitro PKA phosphoacceptor site, and that PKA, but not p38(MAPK), ERK3 or ERK4, is unable to redistribute MK5 S115A to the cytoplasm. However, the phospho-mimicking MK5 S115D mutant resides in the cytoplasm in untreated cells. While p38(MAPK), ERK3 and ERK4 fail to trigger nuclear export of the kinase dead T182A and K51E MK5 mutants, S115D/T182A and K51E/S115D mutants were able to enter the cytoplasm of resting cells. Finally, we demonstrated that mutations in Ser 115 affect the biological properties of MK5. Taken together, our results suggest that Ser-115 plays an essential role in PKA-regulated nuclear export of MK5, and that it also may regulate the biological functions of MK5. PMID- 20734104 TI - Cartilage biology, pathology, and repair. AB - Osteoarthritis is one of the most common forms of musculoskeletal disease and the most prominent type of arthritis encountered in all countries. Although great efforts have been made to investigate cartilage biology and osteoarthritis pathology, the treatment has lagged behind that of other arthritides, as there is a lack of effective disease-modifying therapies. Numerous approaches for dealing with cartilage degradation have been tried, but enjoyed very little success to develop approved OA treatments with not only symptomatic improvement but also structure-modifying effect. In this review we discuss the most recent findings regarding the regulation of cartilage biology and pathology and highlight their potential therapeutic values. PMID- 20734106 TI - Single-cell analysis of S. cerevisiae growth recovery after a sublethal heat stress applied during an alcoholic fermentation. AB - Interest in bioethanol production has experienced a resurgence in the last few years. Poor temperature control in industrial fermentation tanks exposes the yeast cells used for this production to intermittent heat stress which impairs fermentation efficiency. Therefore, there is a need for yeast strains with improved tolerance, able to recover from such temperature variations. Accordingly, this paper reports the development of methods for the characterization of Saccharomyces cerevisiae growth recovery after a sublethal heat stress. Single-cell measurements were carried out in order to detect cell-to cell variability. Alcoholic batch fermentations were performed on a defined medium in a 2 l instrumented bioreactor. A rapid temperature shift from 33 to 43 degrees C was applied when ethanol concentration reached 50 g l-1. Samples were collected at different times after the temperature shift. Single cell growth capability, lag-time and initial growth rate were determined by monitoring the growth of a statistically significant number of cells after agar medium plating. The rapid temperature shift resulted in an immediate arrest of growth and triggered a progressive loss of cultivability from 100 to 0.0001% within 8 h. Heat-injured cells were able to recover their growth capability on agar medium after a lag phase. Lag-time was longer and more widely distributed as the time of heat exposure increased. Thus, lag-time distribution gives an insight into strain sensitivity to heat-stress, and could be helpful for the selection of yeast strains of technological interest. PMID- 20734107 TI - Cellulase production using different streams of wheat grain- and wheat straw based ethanol processes. AB - Pretreatment is a necessary step in the biomass-to-ethanol conversion process. The side stream of the pretreatment step is the liquid fraction, also referred to as the hydrolyzate, which arises after the separation of the pretreated solid and is composed of valuable carbohydrates along with compounds that are potentially toxic to microbes (mainly furfural, acetic acid, and formic acid). The aim of our study was to utilize the liquid fraction from steam-exploded wheat straw as a carbon source for cellulase production by Trichoderma reesei RUT C30. Results showed that without detoxification, the fungus failed to utilize any dilution of the hydrolyzate; however, after a two-step detoxification process, it was able to grow on a fourfold dilution of the treated liquid fraction. Supplementation of the fourfold-diluted, treated liquid fraction with washed pretreated wheat straw or ground wheat grain led to enhanced cellulase (filter paper) activity. Produced enzymes were tested in hydrolysis of washed pretreated wheat straw. Supplementation with ground wheat grain provided a more efficient enzyme mixture for the hydrolysis by means of the near-doubled beta-glucosidase activity obtained. PMID- 20734108 TI - Dose modification of alemtuzumab in combination with dexamethasone, cytarabine, and cisplatin in patients with relapsed or refractory peripheral T-cell lymphoma: analysis of efficacy and toxicity. AB - BACKGROUND: There is still no consensus on the role of alemtuzumab as a salvage therapy for relapsed or refractory peripheral T-cell lymphoma (PTCL). We studied the efficacy and toxicity of combination treatment of alemtuzumab, dexamethasone, cytarabine, and cisplatin (A-DHAP) for treating PTCL. METHODS: We enrolled 24 patients with relapsed or refractory PTCL. Each patient received DHAP plus alemtuzumab every 3 weeks for up to three cycles. Two alemtuzumab dosages of 70 mg or 40 mg were used per cycle. After A-DHAP treatment, the responders underwent autologous stem cell transplantation. RESULTS: The overall response rate was 50.0% (12 of 24 patients), including five complete responders and seven partial responders. Analysis of the responses according to histological type showed a higher objective response rate for PTCL-unspecified (69.2%: four complete responders, five partial responders) than for extranodal NK/T cell lymphoma (12.5%, one partial responder). The median overall survival (OS) after enrollment was 6.0 months (95% confidence interval: 4.20-7.80 months), and the median response duration of responders was 2.93 months (95% confidence interval: 0.93 4.93 months). The overall response rate and OS did not differ significantly according to the dosage of alemtuzumab (70 mg vs. 40 mg, P > 0.05). The most frequent side effect was grade 3/4 leukopenia. Non-disease-related death occurred more frequently in patients who received 70 mg of alemtuzumab. CONCLUSIONS: The combination of alemtuzumab plus DHAP might be effective salvage chemotherapy for PTCL, and 40 mg of alemtuzumab appears to be a more tolerable dosage when used in combination with DHAP. PMID- 20734109 TI - Salarin C, a member of the salarin superfamily of marine compounds, is a potent inducer of apoptosis. AB - The continuous emergence of new diseases and the development of drug-resistant cancers necessitate the development of new drugs with novel mechanisms of action. The richest marine source of natural anti-cancer products has been soft-bodied organisms that lack physical defenses against their predators, and hence rely on chemical defense mechanisms using cytotoxic secondary metabolites. Bio-guided (brine shrimp test) separation of CHCl(3)-CH(3)OH (1:1) extract from the Madagascar Fascaplysinopsis sp. sponge provided several new compounds. Here we focused on the biological activity of a panel of novel natural compounds, salarins A-J. Of these, salarin C was the most potent inhibitor of proliferation, as demonstrated on the K562 leukemia cell line. Salarin C-treated K562 cells underwent apoptotic death as monitored by cell-cycle analysis, annexin V/propidium iodide staining, cleavage of poly-ADP-ribose polymerase (PARP) and caspase 3, and caspase 9 levels. The experimental approach described herein is an essential step towards identifying the cellular pathway(s) affected by salarin C and producing potent synthetic derivatives of salarin C with potential future uses as basic research tools and/or drugs and drug leads. PMID- 20734110 TI - A pilot study of S-1 plus cisplatin versus 5-fluorouracil plus cisplatin for postoperative chemotherapy in histological stage IIIB-IV (M0) gastric cancer. AB - BACKGROUND: Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer. METHODS: Following curative resection, 41 stage IIIB-IV (M0) gastric cancer patients were assigned to SP (eight 14-day cycles of S-1 [40 mg/m(2) twice daily] plus cisplatin [60 mg/m(2) day 1] administered every 3 weeks) or FP (six 3-day cycles of FU [1 g/m(2) per day] plus cisplatin [80 mg/m(2) day 1] every 4 weeks). Doses were reduced based on predefined criteria. RESULTS: Patient characteristics were balanced between the two arms. In total, 124 cycles of SP (N = 20, median = 7, range 1-8) and 113 cycles of FP (N = 21, median 6, range 1-6) were administered. The median relative dose intensity per patient was 75% (49.99-100%) for S-1, 100% (75-100%) for cisplatin in SP, and 100% (64-100%) for 5-FU, 100% (60-100%) for cisplatin in FP. The relative dose intensity of FP was stable, while that of SP decreased during treatment. After median follow-up of 7.9 months (3.8-14.55), the median RFS was not reached. Relapse occurred in two (10%) patients on SP and five (23.8%) in the FP arm (P = 0.24). The incidence of grade 3-4 granulocytopenia was 36.8% with SP and 14.3% with FP. Grade 3-4 non-hematologic toxicities included fatigue (5.2% with SP vs. 4.8% with FP), vomiting (10.5% with SP vs. 0% with FP), and infection (5.2% with SP vs. 0% FP). CONCLUSION: S-1 plus cisplatin was feasible and tolerable as adjuvant treatment for stage IIIB-IV (M0) gastric cancer. However, because of decreased relative dose intensity during treatment, further study is warranted to determine optimal dosage and combination. PMID- 20734111 TI - Biorefining of precious metals from wastes: an answer to manufacturing of cheap nanocatalysts for fuel cells and power generation via an integrated biorefinery? AB - Bio-manufacturing of nano-scale palladium was achieved via enzymatically-mediated deposition of Pd from solution using Desulfovibrio desulfuricans, Escherichia coli and Cupriavidus metallidurans. Dried 'Bio-Pd' materials were sintered, applied onto carbon papers and tested as anodes in a proton exchange membrane (PEM) fuel cell for power production. At a Pd(0) loading of 25% by mass the fuel cell power using Bio-Pd( D. desulfuricans ) (positive control) and Bio-Pd( E. coli ) (negative control) was ~140 and ~30 mW respectively. Bio-Pd( C. metallidurans ) was intermediate between these with a power output of ~60 mW. An engineered strain of E. coli (IC007) was previously reported to give a Bio-Pd that was >3-fold more active than Bio-Pd of the parent E. coli MC4100 (i.e. a power output of >110 mW). Using this strain, a mixed metallic catalyst was manufactured from an industrial processing waste. This 'Bio-precious metal' ('Bio PM') gave ~68% of the power output as commercial Pd(0) and ~50% of that of Bio Pd( D. desulfuricans ) when used as fuel cell anodic material. The results are discussed in relation to integrated bioprocessing for clean energy. PMID- 20734112 TI - Optimizing 19F NMR protein spectroscopy by fractional biosynthetic labeling. AB - In protein NMR experiments which employ nonnative labeling, incomplete enrichment is often associated with inhomogeneous line broadening due to the presence of multiple labeled species. We investigate the merits of fractional enrichment strategies using a monofluorinated phenylalanine species, where resolution is dramatically improved over that achieved by complete enrichment. In NMR studies of calmodulin, a 148 residue calcium binding protein, 19F and 1H-15N HSQC spectra reveal a significant extent of line broadening and the appearance of minor conformers in the presence of complete (>95%) 3-fluorophenylalanine labeling. The effects of varying levels of enrichment of 3-fluorophenylalanine (i.e. between 3 and >95%) were further studied by 19F and 1H-15N HSQC spectra, 15N T(1) and T(2) relaxation measurements, 19F T(2) relaxation, translational diffusion and heat denaturation experiments via circular dichroism. Our results show that while several properties, including translational diffusion and thermal stability show little variation between non-fluorinated and >95% 19F labeled samples, 19F and 1H 15N HSQC spectra show significant improvements in line widths and resolution at or below 76% enrichment. Moreover, high levels of fluorination (>80%) appear to increase protein disorder as evidenced by backbone 15N dynamics. In this study, reasonable signal to noise can be achieved between 60-76% 19F enrichment, without any detectable perturbations from labeling. PMID- 20734113 TI - Conformational dependence of 13C shielding and coupling constants for methionine methyl groups. AB - Methionine residues fulfill a broad range of roles in protein function related to conformational plasticity, ligand binding, and sensing/mediating the effects of oxidative stress. A high degree of internal mobility, intrinsic detection sensitivity of the methyl group, and low copy number have made methionine labeling a popular approach for NMR investigation of selectively labeled protein macromolecules. However, selective labeling approaches are subject to more limited information content. In order to optimize the information available from such studies, we have performed DFT calculations on model systems to evaluate the conformational dependence of (3)J (CSCC), (3)J (CSCH), and the isotropic shielding, sigma(iso). Results have been compared with experimental data reported in the literature, as well as data obtained on [methyl-(13)C]methionine and on model compounds. These studies indicate that relative to oxygen, the presence of the sulfur atom in the coupling pathway results in a significantly smaller coupling constant, (3)J (CSCC)/(3)J (COCC) approximately 0.7. It is further demonstrated that the (3)J (CSCH) coupling constant depends primarily on the subtended CSCH dihedral angle, and secondarily on the CSCC dihedral angle. Comparison of theoretical shielding calculations with the experimental shift range of the methyl group for methionine residues in proteins supports the conclusion that the intra-residue conformationally-dependent shift perturbation is the dominant determinant of delta(13)Cepsilon. Analysis of calmodulin data based on these calculations indicates that several residues adopt non-standard rotamers characterized by very large approximately 100 degrees chi(3) values. The utility of the delta(13)Cepsilon as a basis for estimating the gauche/trans ratio for chi(3) is evaluated, and physical and technical factors that limit the accuracy of both the NMR and crystallographic analyses are discussed. PMID- 20734114 TI - Influence of permeant lipophilicity on permeation across human sclera. AB - PURPOSE: The objectives of this study were to determine the effects of permeant lipophilicity on permeant uptake into and transport across human sclera for transscleral delivery. METHODS: Model permeants with a wide range of lipophilicities were selected and studied with human sclera. Uptake experiments were carried out to measure permeant partitioning into the sclera. Transport experiments were performed in side-by-side diffusion cells, and the permeability coefficients and transport lag times of the permeants across the sclera were evaluated. RESULTS: Permeants with higher lipophilicity showed higher partition coefficients to human sclera, and the apparent transport lag time also increased significantly as the permeant lipophilicity increased. No correlation between the permeability coefficients and lipophilicity of the model permeants was observed in this study with human sclera. A hypothesis on the different findings between the present and previous studies was proposed. CONCLUSIONS: Permeants with higher lipophilicity exhibited stronger binding to human sclera and would therefore lead to larger permeant partitioning to the sclera and longer transport lag time. The steady-state permeability coefficients of the permeants were not significantly affected by permeant lipophilicity. PMID- 20734115 TI - Differential distributions of CSE1L/CAS and E-cadherin in the polarized and non polarized epithelial glands of neoplastic colorectal epithelium. AB - Colorectal glands are important functional organs in colorectal tissue and are also the origin of colorectal carcinomas. Epithelial cell polarization of colorectal glands is related to structural integrity and physiological functions of colorectal glands as well as colorectal carcinoma formation. The cellular apoptosis susceptibility (CSE1L/CAS) protein has been shown to induce polarity formation of human colorectal cells in cell culture. E-cadherin expression in epithelial cells is crucial for the establishment and maintenance of epithelial cell polarity. In this study we examined the distributions of CSE1L and E cadherin in the epithelial glands of normal and neoplastic colorectal epithelium and correlated these to polarity formation in the colorectal glands. Our results showed that CSE1L was differentially stained in the epithelial glands of neoplastic colorectal epithelium, and the staining was related to gland epithelial cell polarization and E-cadherin distribution. CSE1L was associated E cadherin in GST pull-down experiments and immunoprecipitation assays. Basolateral staining of CSE1L and E-cadherin were seen in the polarized glands of normal and neoplastic colorectal epithelium. Absence of basolateral CSE1L staining in neoplastic epithelium glands was associated with loss of gland epithelial cell polarity, and this was parallel with E-cadherin staining. The non-polarized areas in epithelium glands showed a patchy staining for CSE1L and E-cadherin. These results indicate that examination of CSE1L and E-cadherin distribution in colorectal epithelium glands may be valuable for evaluating the malignance of colorectal disease. PMID- 20734116 TI - Reversal of neuromuscular blockade by sugammadex does not affect EEG derived indices of depth of anesthesia. AB - OBJECTIVE: According to previous studies neuromuscular blockade may affect the depth of anesthesia. One theory states that neuromuscular blockade prevents disturbing EMG signals, arousing from the muscles of the forehead, from falsely elevating bispectral index (BIS)-levels. According to the afferentation theory signals generated in muscle stretch receptors, accessing the brain through afferent nerve pathways, induce arousal. By blocking these signals neuromuscular blockade would increase depth of anesthesia. Arousal has previously been associated with neostigmine reversal. This study investigates the possible effect of sugammadex on the level of anesthesia as defined by BIS and spectral entropy levels. METHODS: Thirty elective patients were enrolled. All patients received propofol and remifentanil by target controlled infusion and an intermediate level neuromuscular blockade induced and maintained by bolus doses of rocuronium. Depth of anesthesia was monitored by BIS and spectral entropy. The patients were given 2 mg/kg sugammadex 5 min after finishing of surgery. Propofol and remifentanil infusions were kept unchanged for another 10 min while BIS and entropy values were recorded. RESULTS: Mean BIS and EntropyTM values remained unchanged after reversal of the rocuronium block. The mean averaged BIS, state entropy and response entropy values were 31.7 +/- 9.9, 35.3 +/- 12.9 and 36.8 +/- 13.3 before and 32.0 +/- 11.9, 36.3 +/- 15.9 and 38.4 +/- 18.0 after sugammadex administration, respectively. CONCLUSIONS: Sugammadex does not affect level of anesthesia as determined by BIS or entropy levels. PMID- 20734117 TI - Anesthesia information management systems: a review of functionality and installation considerations. AB - The functionality and rate of implementation of Anesthesia Information Management Systems (AIMS) has markedly risen over the past decade. These systems have now become much more than the generic automated record keepers, originally proposed and developed in the 1980s. AIMS have now become complex integrated systems, which have been shown to improve patient care and, in some cases, the financial performance of a department. Although the underlying technology has improved greatly over the past 5 years, the process of selecting and completing an AIMS installation still presents a number of challenges, and must be approached carefully in order to maximize the benefits provided by these systems. PMID- 20734118 TI - Acid-base chemistry of plasma: consolidation of the traditional and modern approaches from a mathematical and clinical perspective. AB - OBJECTIVE: Debate still exists as to whether the Stewart (modern) or traditional model of acid-base chemistry is best in assessing the acid-base status of critically ill patients. Recent studies have compared various parameters from the modern and traditional approaches, assessing the clinical usefulness of parameters such as base excess, anion gap, corrected anion gap, strong ion difference and strong ion gap. To compare the clinical usefulness of these parameters, and hence the different approaches, requires a clear understanding of their meaning; a task only possible through understanding the mathematical basis of the approaches. The objective of this paper is to provide this understanding, limiting the mathematics to a necessary minimum. METHOD: The first part of this paper compares the mathematics of these approaches, with the second part illustrating the clinical usefulness of the approaches using a patient example. RESULTS: This analysis illustrates the almost interchangeable nature of the equations and that the same clinical conclusions can be drawn regardless of the approach adopted. CONCLUSIONS: Although different in their concepts, the traditional and modern approaches based on mathematical models can be seen as complementary giving, in principle, the same information about the acid-base status of plasma. PMID- 20734119 TI - What were you thinking?: individuals at risk for Huntington Disease talk about having children. AB - Most of the research on reproduction in those at risk for Huntington Disease (HD) has focused on the impact of genetic testing on reproductive decision-making. The main goal has been to determine whether discovering one is a carrier of the HD mutation changes an individual's or couple's decision to start a family or to have more children. The purpose of this qualitative study was to examine reproductive decision-making in a sample of individuals at risk for HD who have chosen not to pursue genetic testing. PHAROS (Prospective Huntington At Risk Observational Study) is a multi-site study that aims to establish whether experienced clinicians can reliably determine the earliest clinical symptoms of HD in a sample of individuals at 50% risk who have chosen not to pursue genetic testing. Data for this article were obtained from unstructured open ended qualitative interviews of a subsample of individuals participating in the PHAROS project. Interviews were conducted at six PHAROS research sites across the United States. In this paper, the research team used qualitative descriptive methods to construct and explore reproduction decision-making in three groups of people: 1) those who knew of their risk and decided to have children; 2) those who had children before they knew of their risk, and 3) those who chose not to have children based on their risk. We discuss the delicate balance health care professionals and genetic counselors must maintain between the benefits of providing hope and the dangers of offering unrealistic expectations about the time in which scientific advances actually may occur. PMID- 20734120 TI - Exposure to platelets promotes functional properties of endothelial progenitor cells. AB - Recent evidence indicates that endothelial progenitor cells (EPCs) have an important role in the process of repair following vascular injury, and that platelets mediate their recruitment to sites of injury. Platelets and EPCs can interact and bind directly. However, there is limited information on the effect of platelets on EPC function following this interaction. We, therefore, aimed to assess the in vitro effect of platelets on functional properties of EPCs. Human EPCs were isolated from donated Buffy coats and purified on a magnetic separation column specific for CD133. They were incubated either on fibronectin matrix, or co-incubated with washed platelets (isolated from healthy volunteers), for 7 days. Number of EPC colony forming units (CFU) was quantified, and endothelial cell lineage confirmed by immunostaining. Functional properties of the cultured cells were evaluated by MTT--proliferation assay and migration assay using the Boyden chamber. Co-incubation of EPCs with platelets compared to incubation of EPCs alone (on fibronectin matrix) resulted in higher number of CFUs after 7 days (6.5 +/- 1.3 vs. 3.5 +/- 0.5 CFUs/well, respectively, P = 0.005). In addition, co incubation of EPCs with platelets versus EPCs alone was associated with higher proportion of living cells, by the MTT assay (0.2 +/- 0.01 vs. 0.12 +/- 0.04 MTT 570 nm respectively, P = 0.003), and higher number of migrated EPCs, assessed by the migration assay (1400 +/- 212 vs. 580 +/- 180 migrated cells/2000 cells, respectively, P < 0.0001). In vitro exposure to platelets promotes the capacity of EPCs to form colonies, proliferate and migrate. Therefore, the interaction with platelets appears to augment EPC functional properties. PMID- 20734121 TI - White-rot fungal conversion of wheat straw to energy rich cattle feed. AB - In order to improve the digestibility and nutrient availability in rumen, wheat straw was subjected to solid state fermentation (SSF) with white-rot fungi (i.e. Pleurotus ostreatus and Trametes versicolor) and the fermented biomass (called myco-straw) was evaluated for biochemical, enzymatic and nutritional parameters. The fungal treatment after 30 days led to significant decrease (P < 0.05) in cell wall constituents viz, acid detergent fiber (ADF), neutral detergent fiber (NDF), hemicellulose, lignin and cellulose to the extent of 35.00, 38.88, 45.00, 37.48 and 37.86%, respectively in P. ostreatus fermented straw, while 30.04, 33.85, 39.90, 31.29 and 34.00%, respectively in T. versicolor fermented straw. However, maximum efficiency of fermentation in terms of low carbohydrate consumption per unit of lignin degradation, favoring cattle feed production was observed for P. ostreatus on the 10th day (17.12%) as compared with T. versicolor on the 30th day (16.91%). The myco-straw was found to contain significantly high (P < 0.05) crude protein (CP; 4.77% T. versicolor, 5.08% P. ostreatus) as compared to control straw (3.37%). Metabolizable energy (ME, MJ/kg DM), percent organic matter digestibility (OMD) and short chain fatty acids (SCFAs; mmol) production also increased considerably from control straw (4.40, 29.91 and 0.292) to a maximum up to P. ostreatus fermented straw (4.92, 33.39 and 0.376 on 20th day) and T. versicolor fermented straw (4.66, 31.74 and 0.334 on 10th day), respectively. Moreover, the myco-straw had lower organic carbon and was rich in nitrogen with lower C/N ratio as compared to control wheat straw. Results suggest that the fungal fermentation of wheat straw effectively improved CP content, OM digestibility, SCFAs production, ME value and simultaneously lowered the C/N ratio, thus showing potential for bioconversion of lignin rich wheat straw into high energy cattle feed. PMID- 20734122 TI - Inside interrogation: the lie, the bluff, and false confessions. AB - Using a less deceptive variant of the false evidence ploy, interrogators often use the bluff tactic, whereby they pretend to have evidence to be tested without further claiming that it necessarily implicates the suspect. Three experiments were conducted to assess the impact of the bluff on confession rates. Using the Kassin and Kiechel (Psychol Sci 7:125-128, 1996) computer crash paradigm, Experiment 1 indicated that bluffing increases false confessions comparable to the effect produced by the presentation of false evidence. Experiment 2 replicated the bluff effect and provided self-reports indicating that innocent participants saw the bluff as a promise of future exoneration which, paradoxically, made it easier to confess. Using a variant of the Russano et al. (Psychol Sci 16:481-486, 2005) cheating paradigm, Experiment 3 replicated the bluff effect on innocent suspects once again, though a ceiling effect was obtained in the guilty condition. Results suggest that the phenomenology of innocence can lead innocents to confess even in response to relatively benign interrogation tactics. PMID- 20734123 TI - Recognizing excellence in Maternal and Child Health (MCH): 2009 National MCH Epidemiology Awards. PMID- 20734124 TI - Preconception health: awareness, planning, and communication among a sample of US men and women. AB - It is important to educate both men and women about preconception health (PCH), but limited research exists in this area. This paper examines men's and women's awareness of exposure to PCH information and of specific PCH behaviors, PCH planning, and PCH discussions with their partners. Data from Porter Novelli's 2007 Healthstyles survey were used. Women and men of reproductive age were included in the analysis (n = 2,736) to understand their awareness, planning, and conversations around PCH. Only 27.9% of women and men reported consistently using an effective birth control method. The majority of men (52%) and women (43%) were unaware of any exposure to PCH messages; few received information from their health care provider. Women were more aware than men of specific pre-pregnancy health behaviors. Women in the sample reported having more PCH conversations with their partners than did men. PCH education should focus on both women and men. Communication about PCH is lacking, both between couples and among men and women and their health care providers. PCH education might benefit from brand development so that consumers know what to ask for and providers know what to deliver. PMID- 20734125 TI - Genetic reassortment between high-virulent and low-virulent Dobrava-Belgrade virus strains. AB - The tri-segmented RNA genome of hantaviruses facilitates genetic reassortment by segment swapping when cells are co-infected with different virus strains. We found efficient in vitro reassortment between members of two different genetic lineages of the Dobrava-Belgrade virus species, the weakly virulent DOBV-Aa and highly virulent DOBV-Af. In all reassortants, S and L segments originated from the same parental strain, and only the M segment was exchanged. To identify functional differences between the parental strains DOBV-Aa and DOBV-Af in cell culture and to compare them with the reassortants, we studied elements of the innate immunity in virus-infected cells. The contrasting phenotypes of the parental viruses were maintained by the reassortants carrying the respective S and L segments of the parental virus and were not influenced by the origin of the M segment. PMID- 20734126 TI - Short sleep mediates the association between long work hours and increased body mass index. AB - This study examined whether short sleep duration, physical activity and time spent sitting each day mediated the association between long work hours and body mass index (BMI). Participants included 16,951 middle aged Australian adults who were employed in full time work (i.e. >=35 h a week). Data on BMI, sleep duration, work hours and other health and demographic variables were obtained through a self-report questionnaire. A multiple mediation model was tested whereby sleep duration, physical activity and amount of time spent sitting were entered as potential mediators between work hours and BMI. The results demonstrated that short sleep partially mediated the association between long work hours and increased BMI in males. In females, long work hours were indirectly related to higher BMI through short sleep. The results provide some support for the hypothesis that long work hours could contribute to obesity via a reduction in sleep duration; this warrants further investigation in prospective studies. PMID- 20734127 TI - Maltreatment, MAOA, and delinquency: sex differences in gene-environment interaction in a large population-based cohort of adolescents. AB - The present study investigated a possible interaction between a functional polymorphism in the MAOA gene promoter (MAOA-VNTR) and childhood maltreatment in the prediction of adolescent male and female delinquency. A cohort of 1,825 high school students, 17-18 years old, completed an anonymous questionnaire during class hours which included questions on childhood maltreatment, sexual abuse, and delinquency. Saliva samples were collected for DNA isolation, and analyzed for the MAOA-VNTR polymorphism. Self-reported maltreatment was a strong risk factor for adolescent delinquent behavior. The MAOA genotype also showed a significant main effect when controlled for maltreatment. Boys with a short variant and girls with one or two long variants of the polymorphism showed a higher risk for delinquency when exposed to maltreatment. Our results confirm previous findings of an interaction between the MAOA-VNTR polymorphism and self-reported maltreatment. Results for boys and girls differ according to MAOA-VNTR genotype and direction of phenotypic expression. PMID- 20734128 TI - Non-homologous sex chromosomes of birds and snakes share repetitive sequences. AB - Snake sex chromosomes provided Susumo Ohno with the material on which he based his theory of how sex chromosomes differentiate from autosomal pairs. Like birds, snakes have a ZZ male/ZW female sex chromosome system, in which the snake Z is a macrochromosome much the same size as the bird Z. However, the gene content shows clearly that the snake and bird Z chromosomes are completely non-homologous. The molecular aspect of W chromosome degeneration in snakes remains largely unexplored. We used comparative genomic hybridization to identify the female specific region of the W chromosome in representative species of Australian snakes. Using this approach, we show that an increasingly complex suite of repeats accompanies the evolution of W chromosome heteromorphy. In particular, we found that while the python Liasis fuscus exhibits no sex-specific repeats and indeed, no cytologically recognizable sex-specific region, the colubrid Stegonotus cucullatus shows a large domain on the short arm of the W chromosome that consists of female-specific repeats, and the large W of Notechis scutatus is composed almost entirely of repetitive sequences, including Bkm and 18S rDNA related elements. FISH mapping of both simple and complex probes shows patterns of repeat amplification concordant with the size of the female-specific region in each species examined. Mapping of intronic sequences of genes that are sex-linked in both birds (DMRT1) and snakes (CTNNB1) reveals massive amplification in discrete domains on the W chromosome of the elapid N. scutatus. Using chicken W chromosome paint, we demonstrate that repetitive sequences are shared between the sex chromosomes of birds and derived snakes. This could be explained by ancestral but as yet undetected shared synteny of bird and snake sex chromosomes or may indicate functional homology of the repeats and suggests that degeneration is a convergent property of sex chromosome evolution. We also establish that synteny of snake Z-linked genes has been conserved for at least 166 million years and that the snake Z consists of two conserved blocks derived from the same ancestral vertebrate chromosome. PMID- 20734129 TI - Neuroprotective effects of active ingredients isolated from Pegasus laternarius on cultured cerebral neurons. AB - Seamoth (Pegasus laternarius Cuvier) is extensively used to treat various diseases on the coastland of Guangdong Province in China, such as scrofula, cough, and diarrhea. The total extract of Pegasus laternarius (EP) was subjected to column chromatography to acquire three different constituents (EPC1, EPC2, and EPC3). Cerebral neuron injury was induced by glutamate, H2O2, and serum deprivation. After treating with or without different extracts, cell viability was assessed with the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and cell apoptosis was analyzed with Hoechst 33258 staining and agarose gel electrophoresis. We also determined the levels of lactate dehydrogenase (LDH), maleic dialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The results showed that both EP and EPC2 promoted the outgrowth of cultural neurons, increased antioxidant enzyme activity, and protected neurons from neuronal injury or apoptosis induced by glutamate, H2O2, and serum deprivation. EPC1 and EPC3 had little or no effect on neurons. These results suggest that the active ingredients obtained from Pegasus laternarius have potential neuroprotective effects on injured neurons by promoting the outgrowth of cultured neurons, increasing the activity of intracellular antioxidants, and exerting antiapoptotic effects. This neuroprotection may be attributable to specific active ingredients, such as taurine, novel ceramide, and cholesterol. PMID- 20734130 TI - Child internalizing symptoms: contributions of child temperament, maternal negative affect, and family functioning. AB - Research has traditionally focused on the role of genetic and environmental variables in the development and maintenance of childhood internalizing disorders. Temperament variables, such as negative affect and effortful control have gained considerable interest within the field of developmental psychopathology. Environmental factors such as mother-child interactions and family cohesion have also been linked with internalizing disorders. The current study examines the relationship between child negative affect, effortful control, maternal negative affect, family functioning, and internalizing symptoms in a sample of preschool-aged children using a path analysis approach. Sixty-five children, aged 3-5 years and their mothers completed measures on child temperament, family environment, maternal personality, and child internalizing symptoms. Results support a complex model for the influence of both direct and indirect factors on internalizing symptoms in preschool-aged children. PMID- 20734131 TI - No evidence for an association of human papillomavirus and breast carcinoma. AB - Breast cancer represents a serious public health problem worldwide, for its high incidence, morbidity, mortality, and its high cost treatment. It is known that breast cancer is a multifactorial disease, possessing various risk factors, among which include hormonal factors, genetic and environmental. The role of viruses in breast carcinogenesis is controversial. This study aims to evaluate the expression of HPV 6, 11, 16, and 18 by polymerase chain reaction (PCR) in invasive ductal breast carcinoma. We analyzed 90 women diagnosed with invasive ductal breast carcinoma, of which the extracted DNA was amplified, quantified and tested for DNA subtypes 6, 11, 16, and 18 by PCR. The research carried out in 79 samples of HPV DNA, proved negative. Our study demonstrates no association between the most prevalent types of HPV and breast cancer. PMID- 20734132 TI - Multimodal exercise improves quality of life of women being treated for breast cancer, but at what cost? Randomized trial with economic evaluation. AB - To evaluate the efficacy and economic efficiency of a multimedia, multimodal physical activity program for women undergoing adjuvant therapy following surgery for breast cancer. We conducted a randomized trial with concurrent incremental cost-effectiveness analysis and blinded baseline, 3, 6 and 12-month follow-up assessments amongst women undergoing adjuvant therapy following surgery for breast cancer (n = 89). The intervention was a multimedia, multimodal exercise program comprising strength, balance and endurance training elements. The control was sham flexibility and relaxation program delivered using similar materials. The primary outcome was health-related quality of life (EQ-5D & VAS, EORTC C30, BR23). Economic outcomes included direct health care costs and productivity gains and losses. Participants in the intervention group demonstrated greater improvement in health-related quality of life between baseline and the 3-month assessment [mean (sd) EQ-5D VAS (0-100) baseline: 72.6 (15.6), 3 month: 80.6 (11.6)] when compared to control group participants [baseline: 77.5 (13.5), 3 month: 74.1 (20.6), P = 0.006] and also improved more in terms of physical function [mean (sd) EORTC C30 physical function scale intervention (0-100) baseline: 84.9 (14.8), 3 month: 86.9 (10.7), control baseline: 91.3 (9.6), 3 month: 86.7 (14.9), P = 0.02]. These improvements were not sustained beyond this point. Upper limb volumes were also lower amongst intervention group participants. However, there was low probability that the intervention would be both less costly and more effective than the control condition (range probability = 0.05-50.02% depending on approach). Provision of multimodal exercise programs will improve the short-term health of women undergoing adjuvant therapy for breast cancer but are of questionable economic efficiency. PMID- 20734133 TI - Glycans as receptors for influenza pathogenesis. AB - Influenza A viruses, members of the Orthomyxoviridae family, are responsible for annual seasonal influenza epidemics and occasional global pandemics. The binding of viral coat glycoprotein hemagglutinin (HA) to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of these viruses. Scientists believe that a switch in the binding specificity of HA from Neu5Acalpha2-3Gal linked (alpha2-3) to Neu5Acalpha2-6Gal linked (alpha2-6) glycans is essential for the crossover of the viruses from avian to human hosts. However, studies have shown that the classification of glycan binding preference of HA based on sialic acid linkage alone is insufficient to establish a correlation between receptor specificity of HA and the efficient transmission of influenza A viruses. A recent study reported extensive diversity in the structure and composition of alpha2-6 glycans (which goes beyond the sialic acid linkage) in human upper respiratory epithelia and identified different glycan structural topologies. Biochemical examination of the multivalent HA binding to these diverse sialylated glycan structures also demonstrated that high affinity binding of HA to alpha2-6 glycans with a characteristic umbrella-like structural topology is critical for efficient human adaptation and human-human transmission of influenza A viruses. This review summarizes studies which suggest a new paradigm for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis. PMID- 20734135 TI - A 6-year survey of pathological conditions of slaughtered animals at Zango abattoir in Zaria, Kaduna State, Nigeria. AB - A 6-year retrospective study (2000-2005) of animals slaughtered at the Zango abattoir in Zaria, Kaduna State, Nigeria was carried out to determine disease conditions encountered in slaughtered animals. Records kept at the abattoir were analysed. A total of 69,307 cattle, 3,820 goats and 1,763 sheep were slaughtered for the period under study. Of the 69,307 cattle slaughtered for the period, 22,459 (32.41%) were males and 46,848 (67.59%) were females, while 1,763 sheep were slaughtered comprising of 506 (28.70%) males and 1,257 (71.30%) females, and 3,820 goats made up of 1,212 (31.73%) males and 2,608 (68.27%) were females. The major disease and/or pathological conditions were helminthosis (fascioliasis, haemonchosis and paramphistomosis) 16.20%, Streptothricosis 4.15%, Pericarditis 2.20%, liver cirrhosis 2.08%, abscesses 1.04%, pneumonia 0.14%, nephritis 0.05% and Contagious Bovine Pleuropneumonia, Tuberculosis and Nocardiosis 0.01% each. Out of the 15,075 infected organs, 13,314 (88.38%) were partially salvaged while 1,751 (11.6%) whole organs were condemned. A total of 1,239 pregnant cows, 221 pregnant ewes and 637 pregnant does were slaughtered, representing a foetal wastage of 2.65% for cattle, 17.58% for sheep and 24.43% for goats. The result of this study apart from serving as an indicator of field disease condition also demonstrates cases of serious losses in production due to slaughter of pregnant animals especially for sheep and goats. PMID- 20734136 TI - A new two-pulse synthesis model for digital volume pulse signal analysis. AB - Analysis of digital volume pulse (DVP) signal measured by photoplethysmograph (PPG) technique is a low cost non-invasive method of obtaining vital information related to arterial conditions. In this paper, we present a new two-pulse synthesis (TPS) model for deriving arterial parameters, useful for noninvasive assessment of human vascular health. The model is based on the use of Rayleigh function. Relevance of the proposed model is established by applying it on a sample set of 113 PPG signals, obtained form healthy and treated hypertensive subjects. The TPS model compares well with the conventional methods in determining parameters such as pulse transit time or foot-to-foot delay (D), reflection index (RI), stiffness index (SI) and pulse wave velocity (PWV). A new parameter, viz. differential pulse spread (DPS) has also been introduced for DVP signals using the model. The differential pulse spread provides a new dimension to estimate the process of arterial degeneration. PMID- 20734137 TI - Sleepwalking, a possible side effect of antipsychotic medication. AB - Two case examples and a review of the sleep literature illustrate the potential of antipsychotic medication to trigger sleepwalking episodes in the context of schizophrenia. Causative hypotheses are briefly reviewed, as well as risk factors, differential diagnosis, and management. Sleepwalking may contribute to delusions, aggression, and accidental suicide. It is important to investigate sleep disorders in schizophrenia. They are not rare and may contribute to behavior that increases the stigma and isolation of individuals with schizophrenia. PMID- 20734138 TI - The pharmaceutical care of patients with type 2 diabetes mellitus. AB - OBJECTIVE: To evaluate the efficiency of pharmaceutical care on the control of clinical parameters, such as fasting glycaemia and glycosylated haemoglobin in patients with Type 2 Diabetes mellitus. SETTING: This study was conducted at the Training and Community Health Centre of the College of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. METHODS: A prospective and experimental study was conducted with 71 participants divided in two groups: (i) pharmaceutical care group (n=40), and (ii) the control group (n=31). The distribution of patients within these groups was made casually, and the patients were monitored for 12 months. MAIN OUTCOME MEASURE: Values for fasting glycaemia and glycosylated haemoglobin were collected. RESULTS: Mean values of fasting glycaemia in the pharmaceutical care group were significantly reduced whilst a small reduction was detected in the control group at the same time. A significant reduction in the levels of glycosylated haemoglobin was detected in patients in the pharmaceutical care group, and an average increase was observed in the control group. Furthermore, the follow-up of the intervention group by a pharmacist contributed to the resolution of 62.7% of 142 drug therapy problems identified. CONCLUSION: In Brazil, the information provided by a pharmacist to patients with Type 2 Diabetes mellitus increases compliance to treatment, solving or reducing the Drug Therapy Problem and, consequently, improving glycaemic control. PMID- 20734139 TI - Latino immigrants with depression: an initial examination of treatment issues at a community clinic. AB - The objective of this study is to investigate specific characteristics that may affect the psychological treatment retention of Latinos diagnosed with depression in a community mental health clinic that provides culturally responsive services. Thirty-six Latino clients participated in the pilot study. Descriptive statistics were generated on acculturation, acculturative stress, familismo (the importance of the family), specific demographic variables, and other factors potentially related to treatment outcome. Two specific groups were compared: regular attendees (RAs; n = 18) and premature terminators (PTs; n = 18). RAs were significantly less likely to be employed, and more likely to have medications prescribed at the clinic compared to PTs. Acculturation, acculturative stress, and familismo did not differentiate between groups but were found to characterize the entire sample. The results support the premise that psychological treatment combined with medication keeps clients in treatment. Knowledge of perceived and actual barriers encountered by Latino clients are necessary to guide community based mental health clinics in developing effective service delivery alternatives that will enhance treatment engagement. PMID- 20734140 TI - Heterogeneity in breast and cervical cancer screening practices among female Hispanic immigrants in the United States. AB - This study examined differences in cervical and breast cancer (CC and BC) screening among a heterogeneous group of Hispanic women. Data from 247 women (mean age = 38.7 +/- 13.3) from Mexico, the Dominican Republic, Puerto Rico, and countries throughout Central and South America regarding participation in Pap smears, mammography, clinical breast exam (CBE) and breast self-exams (BSE), CC and BC knowledge, and acculturation were analyzed. Differences in CBE and BSE screening behaviors were found based on country of origin (P < .01). However, after adjusting for the independent variables, only acculturation and knowledge remained significant correlates to BSE and CBE (P < .01). Dominican women had higher BC knowledge scores (P < .01) adhered most to BC screening guidelines. Heterogeneity in BC and CC screening was found among Hispanic sub-groups and suggests that health promotion programs should be tailored appropriately, particularly among recent immigrants. PMID- 20734141 TI - Reflections on Breughel's "Icarus" from a Kohutian perspective. PMID- 20734142 TI - Sensitization of human bladder tumor cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis with a small molecule IAP antagonist. AB - Urothelial carcinoma of the bladder accounts for approximately 5% of all cancer deaths in humans. The large majority of bladder tumors are non-muscle invasive at diagnosis, but even after local surgical therapy there is a high rate of local tumor recurrence and progression. Current treatments extend time to recurrence but do not significantly alter disease survival. The objective of the present study was to investigate the tumoricidal potential of combining the apoptosis inducing protein TNF-related apoptosis-inducing ligand (TRAIL) with a small molecule inhibitor of apoptosis proteins (IAP) antagonist to interfere with intracellular regulators of apoptosis in human bladder tumor cells. Our results demonstrate that the IAP antagonist Compound A exhibits high binding affinity to the XIAP BIR3 domain. When Compound A was used at nontoxic concentrations in combination with TRAIL, there was a significant increase in the sensitivity of TRAIL-sensitive and TRAIL-resistant bladder tumor lines to TRAIL-mediated apoptosis. In addition, modulation of TRAIL sensitivity in the TRAIL-resistant bladder tumor cell line T24 with Compound A was reciprocated by XIAP small interfering RNA-mediated suppression of XIAP expression, suggesting the importance of XIAP-mediated resistance to TRAIL in these cells. These results suggest the potential of combining Compound A with TRAIL as an alternative therapy for bladder cancer. PMID- 20734143 TI - Gluten-free breads and cookies of raw and popped amaranth flours with attractive technological and nutritional qualities. AB - Gluten-free bakery foodstuffs are a challenge for technologists and nutritionists since alternative ingredients used in their formulations have poor functional and nutritional properties. Therefore, gluten-free bread and cookies using raw and popped amaranth, a grain with high quality nutrients and promising functional properties, were formulated looking for the best combinations. The best formulation for bread included 60-70% popped amaranth flour and 30-40% raw amaranth flour which produced loaves with homogeneous crumb and higher specific volume (3.5 ml/g) than with other gluten-free breads. The best cookies recipe had 20% of popped amaranth flour and 13% of whole-grain popped amaranth. The expansion factor was similar to starch-based controls and the hardness was similar (10.88 N) to other gluten-free cookies. Gluten content of the final products was around 12 ppm. The functionality of amaranth-based doughs was acceptable although hydrocolloids were not added and the final gluten-free products had a high nutritional value. PMID- 20734144 TI - Antihyperglycemic, antihyperlipidemic and antiglycation effects of Byrsonima crassifolia fruit and seed in normal and streptozotocin-induced diabetic rats. AB - The hypoglycemic effects of hexane, chloroform and methanol extracts from fruits and seeds of Byrsonima crassifolia were evaluated by oral administration to normoglycemic and streptozotocin-induced severe diabetic rats (SD). The anti diabetic effect was examined by blood glucose, triglycerides, lipid peroxidation, total cholesterol levels in the serum, glycogen content of liver and skeletal muscles, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and oxidized glutathione (GSSG) levels. The most active extracts were obtained with hexane. Hexane and chloroform extracts from fruits and seeds of Byrsonima crassifolia increased the levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase (G6Pase) and the plasma insulin levels. They also decreased glucokinase (GK) and TBAR (thiobarbituric acid assay). In conclusion, Byrsonima crassifolia possesses significant antihyperglycemic properties after 4 h of a single oral dose. It can also improve hyperlipidemia and hyperinsulinemia in streptozotocin-induced diabetic rats. Both extracts exhibited significant inhibitory activity against AGEs (advanced glycation end products) formation with IC(50) values ranging from 94.3 to 138.7 MUg/ml. Therefore, B. crassifolia can be considered as a potential safe anti-diabetic agent. PMID- 20734145 TI - Fully automated high-quality NMR structure determination of small (2)H-enriched proteins. AB - Determination of high-quality small protein structures by nuclear magnetic resonance (NMR) methods generally requires acquisition and analysis of an extensive set of structural constraints. The process generally demands extensive backbone and sidechain resonance assignments, and weeks or even months of data collection and interpretation. Here we demonstrate rapid and high-quality protein NMR structure generation using CS-Rosetta with a perdeuterated protein sample made at a significantly reduced cost using new bacterial culture condensation methods. Our strategy provides the basis for a high-throughput approach for routine, rapid, high-quality structure determination of small proteins. As an example, we demonstrate the determination of a high-quality 3D structure of a small 8 kDa protein, E. coli cold shock protein A (CspA), using <4 days of data collection and fully automated data analysis methods together with CS-Rosetta. The resulting CspA structure is highly converged and in excellent agreement with the published crystal structure, with a backbone RMSD value of 0.5 A, an all atom RMSD value of 1.2 A to the crystal structure for well-defined regions, and RMSD value of 1.1 A to crystal structure for core, non-solvent exposed sidechain atoms. Cross validation of the structure with (15)N- and (13)C-edited NOESY data obtained with a perdeuterated (15)N, (13)C-enriched (13)CH(3) methyl protonated CspA sample confirms that essentially all of these independently-interpreted NOE based constraints are already satisfied in each of the 10 CS-Rosetta structures. By these criteria, the CS-Rosetta structure generated by fully automated analysis of data for a perdeuterated sample provides an accurate structure of CspA. This represents a general approach for rapid, automated structure determination of small proteins by NMR. PMID- 20734146 TI - Robotic-assisted resection of adrenal aldosteronoma. PMID- 20734147 TI - Resection margins in ultrasound-guided breast-conserving surgery. AB - BACKGROUND: Few published studies have shown the benefits of intraoperative ultrasound in avoiding inadequate margins in breast-conserving surgery. The aim of this study is to quantify intraoperative ultrasound margin size and assess its relationship to tumor size, multifocality, palpability, histology, and presence of intraductal component. METHODS: Patients with breast cancer undergoing breast conserving surgery in whom the operating surgeon visualized the tumor by ultrasound were included. Ultrasound margins measured intraoperatively were prospectively recorded and compared with pathology margins. RESULTS: Forty-five patients with 48 tumors were included. Twenty five patients (56%) had palpable tumors. Pathologic mean tumor size was 1.9 cm [95% confidence interval (CI) 1.6 2.2 cm, range 0.5-4.8 cm]. There was good correlation between closest margins recorded by ultrasound and pathology margins (r = 0.4674, P < 0.0008). Fourteen patients (31%) had margins re-excised intraoperatively, 12 of them in the direction of the closest pathological margin. Three patients (7%), all of whom had intraoperative re-excision, had a second operation for involved margins without residual cancer on pathological examination of the reoperative specimens. Ultrasound margins >=0.5 cm achieved adequate pathology margins of >=0.2 cm in 95% of margins. Overestimation of pathology margins by ultrasound measurement was significantly affected by multifocality (P = 0.0473). Tumor size, palpability, invasive lobular histology, and presence of ductal carcinoma in situ (DCIS) did not cause significant overestimation of pathology margins by ultrasound. CONCLUSIONS: Intraoperative ultrasound may help maintain a low level of reoperation after breast-conserving surgery. Ultrasound margins <0.5 cm should be re-excised intraoperatively. Reliability of ultrasound in predicting the closest pathology margins was diminished in patients with multifocal tumors. PMID- 20734148 TI - Reduced expression of reelin (RELN) gene is associated with high recurrence rate of hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the world's top five causes of cancer-related deaths. Current treatments available ameliorate HCC; however, current therapy fails to completely treat and prevent HCC, as shown by its high recurrence rate. Recently developed genome-wide gene-expression profile analyses can now robustly detect many candidate genes that are modified by HCC. Here we attempt to identify novel genes displaying altered gene expression profiles when comparing healthy tissue with HCC by means of a double-combination array previously developed. METHODS: Double-combination array analysis of gene expression profiles and single nucleotide polymorphism arrays were performed on each HCC tissue sample. Subsequently, samples from 48 HCC patients were subjected to quantitative real-time reverse transcription polymerase chain reaction and methylation-specific polymerase chain reaction. RESULTS: The reelin (RELN) gene was detected as a pertinent tumor suppressor gene by means of this method. Of the 48 clinical samples obtained, 34 (79.2%) displayed reduced RELN expression in tumor tissue, and the expression level of tumor tissues clearly reduced compared with that of corresponding normal tissues (P = 0.002). Eighteen (37.5%) of 48 tumor tissues were found to be hypermethylated on the RELN gene promoter. Moreover, analysis of clinical data revealed an inverse correlation between RELN expression and HCC recurrence. CONCLUSIONS: The present study indicates that our in-house double-combination array is an effective and convenient technique in detecting novel genes with altered expression in disease. We suggest RELN is a key regulatory gene associated with the recurrence of HCC. PMID- 20734149 TI - Clinical value of radiographic staging in patients diagnosed with AJCC stage III melanoma. AB - BACKGROUND: Patients with American Joint Committee on Cancer (AJCC) stage III melanoma represent patients with high risk of systemic relapse. This study evaluates the clinical utility of standardized radiographic staging. METHODS: Consecutive asymptomatic patients underwent standardized radiographic staging workup within 6 weeks of diagnosis. True- and false-positive rates and number of additional examinations generated after a positive initial report were quantified. All suspicious findings were further studied by biopsy and/or by clinical or radiologic assessment. RESULTS: Fifty-eight patients underwent complete radiographic staging. Nineteen (33%) had ulcerated primary tumors. Forty two patients (73%) presented with clinically negative lymph nodes that were positive on sentinel lymph node biopsy. Lymph node involvement was classified as N1a in 54%, N2a in 19%, N2b in 3%, and N3 in 22% of patients. Among 204 staging examinations in 58 patients, 52 (25%) were initially reported as positive. Three percent of all examinations proved truly positive; 23% were falsely positive. Analyzed per patient, in 37 (64%) of 58 patients, at least one examination was initially reported as positive. However, only 3 patients (5%) had a true-positive and 34 (59%) had at least one false-positive report. The positive reports of the staging scans generated 45 additional examinations (0.78 per patient). CONCLUSIONS: Radiographic staging in asymptomatic patients with stage III melanoma detects a low number of patients with unsuspected systemic disease. The ratio of falsely to truly positive is approximately 11:1. Radiographic screening should only be considered in patients with high-risk prognostic features or symptoms, or in the context of clinical trials. PMID- 20734150 TI - STC2: a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. AB - BACKGROUND: We sought to identify genes associated with the progression and metastasis of esophageal squamous-cell cancer by comparing the expression profiles of normal, primary cancer, and metastatic cancer cells isolated with laser microdissection. METHODS: Oligo microarray analysis identified several lymph node-specific, metastasis-related genes. STC2 (stanniocalcin 2), which was overexpressed in esophageal cancer cases, was chosen for further characterization. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to explore the clinicopathologic significance of STC2 expression status in 70 cases. Additionally, the functional role of STC2 in esophageal cancer was studied by the attenuation of STC2 in an esophageal cancer cell line. RESULTS: Laser microdissection and oligo microarray analysis identified 63 candidate genes. Among them, STC2 showed higher expression in cancer tissue than in corresponding normal tissue (P < 0.001). STC2 expression was significantly correlated with lymph node metastasis, lymphatic invasion, and distant metastasis (P = 0.005, 0.007, and 0.038, respectively). Patients whose tumors had high STC2 expression had a worse 5-year survival rate than patients whose tumors had a low STC2 expression level (P = 0.016). STC2 transfected cells had a significantly higher proliferation rate than control cells (P < 0.001). Additionally, STC2 transfected cells were more invasive in vitro (P < 0.001) than control cells. These findings were validated by means of RNA interference assays. CONCLUSIONS: We identified lymph node-specific, metastasis-related genes in esophageal cancer cells. One of these, STC2, may be associated with lymph node metastasis, making it a potential prognostic marker for esophageal cancer patients. PMID- 20734151 TI - Significance of lymph node retrieval from the terminal ileum for patients with cecal and ascending colonic cancers. AB - BACKGROUND: For patients with cecal and ascending colonic cancers, the significance of regional lymph node (LN) metastasis at the terminal ileum has not been elucidated. We analyzed its metastatic patterns and significance. METHODS: The records of patients with cecal and ascending colonic cancers receiving standard radical right hemicolectomy with D3 LN dissection between 2000 and 2010 were collected. The regional LNs were grouped according to the Japanese Classification of Colorectal Carcinoma. The regional LNs supplied by ileocolic vessels were further divided into 201-A (terminal ileal side) and 201-B (colonic side). The clinicopathologic characteristics of all cases showing positive for metastasis in 201-A LN were analyzed. RESULTS: Forty-seven cases of cecal and 56 cases of ascending colonic cancer were included. Seven cases had 201-A-positive LNs: five (10.6%) in cecal cancers and two (3.6%) in ascending colonic cancers. They all had distant metastases (P < 0.001), and the incidences were significantly correlated with the numbers of metastatic LNs (P < 0.05). There was no 201-A-positive LN noted among patients with stage I to III disease. Poor prognosis was noted for patients with a 201-A-positive LN. CONCLUSIONS: Both cecal and ascending colonic cancers have a potential for LN metastasis at the terminal ileum. These cases are exclusively stage IV and have poor prognosis. PMID- 20734152 TI - Variation in lymph node evaluation in rectal cancer: a Dutch nationwide population-based study. AB - BACKGROUND: For adequate staging and subsequent accurate estimation of prognosis, a sufficient number of lymph nodes (LNs) has to be evaluated. This study aimed to identify factors associated with adequate nodal evaluation and to determine its relationship with survival. METHODS: Data from all patients with stage I to III rectal carcinoma who underwent surgical treatment and who were diagnosed in the period 2000 to 2006 were retrieved from the Netherlands Cancer Registry. Multilevel logistic analysis was performed to examine the influence of relevant factors on the number of evaluated LNs. Kaplan-Meier and Cox regression analyses were used to analyze the association with overall survival. RESULTS: The number of evaluated LNs was determined for 10,788 (91%) of 11,818 tumors. Median number of evaluated LNs was 7, ranging from 4 to 11 between pathology laboratories. The proportion of patients with positive LNs increased with increasing number of evaluated LNs. Men, younger patients, tumors with deeper invasion and nodal involvement, patients without preoperative radiotherapy who underwent a low anterior resection, and patients whose LNs were evaluated in an academic pathology laboratory were more likely to have >=12 LNs evaluated. After adding these factors to the model, unexplained variation between pathology laboratories and between hospitals remained. The overall survival increased with increasing number of evaluated LNs. CONCLUSIONS: A large variation in LN evaluation among patients with rectal cancer was revealed. Improvement in LN evaluation by both hospitals and pathology laboratories could improve staging, leading to more reliable estimation of prognosis. PMID- 20734153 TI - Quantification of iron-labeled cells with positive contrast in mouse brains. AB - PURPOSE: To quantify small amounts of iron-labeled cells in mouse brains with magnetic resonance imaging (MRI). PROCEDURES: Iron-labeled cells (from 500 to 7,500) were stereotaxically transplanted into the brain of living mice that were subsequently imaged with MRI at 4.7 T. We compared four quantitative methods: (1) T2 relaxometry, (2) T2* relaxometry, (3) the volume of the cloverleaf hypointense artifact generated on T2*-weighted images, and (4) the volume of the cloverleaf hyperintense artifact generated on positive contrast images. RESULTS: The methods based on relaxometry, whether T2 or T2*, did not correlate with the number of injected cells. By contrast, those based on measurement of cloverleaf artifact volume, whether using negative or positive enhancement, showed a significant linear relationship for the given range of cells (R [0.92-0.95], p < 0.05). CONCLUSIONS: T2* artifact volume imaging (negative or positive) appears promising for the quantification of magnetically labeled cells following focal injection in the brain. PMID- 20734154 TI - Sleep apnea monitoring and diagnosis based on pulse oximetry and tracheal sound signals. AB - Sleep apnea is a common respiratory disorder during sleep, which is described as a cessation of airflow to the lungs that lasts at least for 10 s and is associated with at least 4% drop in blood's oxygen saturation level (S(a)O(2)). The current gold standard method for sleep apnea assessment is full-night polysomnography (PSG). However, its high cost, inconvenience for patients, and immobility have persuaded researchers to seek simple and portable devices to detect sleep apnea. In this article, we report on developing a new method for sleep apnea detection and monitoring, which only requires two data channels: tracheal breathing sounds and the pulse oximetry (S(a)O(2) signal). It includes an automated method that uses the energy of breathing sounds signals to segment the signals into sound and silent segments. Then, the sound segments are classified into breath, snore, and noise segments. The S(a)O(2) signal is analyzed automatically to find its rises and drops. Finally, a weighted average of different features extracted from breath segments, snore segments and S(a)O(2) signal are used to detect apnea and hypopnea events. The performance of the proposed approach was evaluated on the data of 66 patients recorded simultaneously with their full-night PSG study, and the results were compared with those of the PSG. The results show high correlation (0.96, P < 0.0001) between the outcomes of our system and those of the PSG. Also, the proposed method has been found to have sensitivity and specificity values of more than 91% in differentiating simple snorers from obstructive sleep apnea patients. PMID- 20734155 TI - Intestinal lengthening in adult patients with short bowel syndrome. AB - INTRODUCTION: Limited information regarding the usefulness of bowel lengthening in adult patients with short bowel syndrome is available. METHODS: Retrospective review of a single center series of intestinal lengthening over 15-year period in patients >= 18 years old. RESULTS: Twenty adult patients underwent Bianchi (n = 6) or serial transverse enteroplasty (STEP) (n = 15). Median age was 38 (18-66) years and 11 were female. Indications were (a) to increase the enteral caloric intake thereby reduce or wean parenteral nutrition (PN) (n = 14) or (b) for bacterial overgrowth (n = 6). Twelve patients required additional procedures to relieve the anatomical blockade. Median remnant bowel length prior to surgery, length gained and final bowel length was 60, 20, and 80 cm, respectively. Survival was 90% with mean follow-up of 4.1 years (range = 1-7.9 years). Two patients died during follow-up. Intestinal transplant salvage was required in one patient 4.8 years after STEP. Overall, of 17 patients, ten (59%) patients achieved enteral autonomy and were off PN. Of seven patients who are on PN, three patients showed significant improvement in enteral caloric intake. All except one showed significant improvement in symptoms of bacterial overgrowth. CONCLUSIONS: Bowel lengthening is technically feasible and effectively leads to weaning from PN in more than half of the adult patients. Lengthening procedures may be an underutilized treatment for adults with short bowel syndrome. PMID- 20734157 TI - Biliary epithelial metastasis of squamous carcinoma of the anus. AB - INTRODUCTION: The liver and biliary tree are common sites of initial metastasis for many primary tumors. However, we recently encountered a patient who presented with biliary-tree tumor encasement as a first metastasis from squamous carcinoma of the anus. METHODS: To our knowledge, this has not been previously described in the literature. CONCLUSIONS: As obstructive jaundice is a relatively common presenting sign in the emergency room and in general surgical clinics, we thus recommend early consideration of metastatic disease as a differential diagnosis in patients post-chemoradiotherapy for anal carcinoma who present with obstructive jaundice. PMID- 20734159 TI - Systemic investigation of a brain-centered model of the human energy metabolism. AB - The regulation of the human energy metabolism is crucial to ensure the functionality of the entire organism. Deregulations may lead to severe pathologies such as diabetes mellitus and obesity. The decisive role of the brain as active controller and heavy consumer in the complex whole-body energy metabolism is the object of recent research. Latest studies suggest the priority of the brain energy supply in the competition between brain and body periphery for the available energy resources. In this paper, a systemic investigation of the human energy metabolism is presented which consists of a compartment model including periphery, blood, and brain as well as signaling paths via insulin, appetite, and ingestion. The presented dynamical system particularly contains the competition for energy between brain and body periphery. Characteristically, the hormone insulin is regarded as central feedback signal of the brain. The model realistically reproduces the qualitative behavior of the energy metabolism. Short time observations demonstrate the physiological periodic food intake generating the typical oscillating blood glucose variations. Integration over the daily cycle yields a long-term model which shows a stable behavior in accordance with the homeostatic regulation of the energy metabolism on a long-time scale. Two types of abstract constitutive equations describing the interaction between compartments and signals are taken into consideration. These are nonlinear and linear representatives from the class of feasible relations. The robustness of the model against the choice of the representative relation is linked to evolutionary stability of existing organisms. PMID- 20734158 TI - A challenge for the future: aging and HIV infection. AB - Older individuals (>=50 years of age) are increasingly becoming a new at-risk group for HIV-1 infection and, together with those surviving longer due to the introduction of anti-retroviral therapy (ART), it is predicted that more than half of all HIV-1-infected individuals in the United States will be greater than 50 years of age in the year 2015. Older individuals diagnosed with HIV-1 are prone to faster disease progression and reduced T-cell reconstitution despite successful virologic control with anti-retroviral therapy (ART). There is also growing evidence that the T-cell compartment in HIV-1(+) adults displays an aged phenotype, and HIV-1-infected individuals are increasingly diagnosed with clinical conditions more commonly seen in older uninfected persons. As aging in the absence of HIV infection is associated with alterations in T-cell function and immunosenescence, the combined impact of both HIV-1 infection and aging may provide an explanation for poorer clinical outcomes observed in older HIV-1 infected individuals. Thus, the development of novel therapeutics to stimulate immune function and delay immunosenescence is critical and would be beneficial to both the elderly and HIV-1-infected individuals. PMID- 20734160 TI - Gabapentin completely attenuated the acute morphine-induced c-Fos expression in the rat nucleus accumbens. AB - A growing body of evidence suggests the existence of a functional interaction between gabapentin (GBP)-morphine system. However, the neuro-anatomical sites and molecular mechanism of action of gabapentin-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not clear. Therefore, we examined the combined effects of GBP morphine on acute morphine-induced c-Fos expression in rat nucleus accumbens. The combined effect of GBP-morphine was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of morphine (10 mg/kg), saline (control), and co-injection of GBP (150 mg/kg) with morphine (5 mg/kg) was administered under anesthesia. The deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde 2 h after drugs administration. Serial 40 MUm thick sections of brain were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase-antiperoxidase detection protocol. The present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (5 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (5 mg/kg, i.p.)-induced c-Fos expression in the rat nucleus accumbens shell. Present results showed that GBP-morphine combination action prevented the acute morphine induced c-Fos expression in rat nucleus accumbens. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine induced activation of rat nucleus accumbens shell. PMID- 20734161 TI - Raf-1 kinase inhibitory protein expression in thyroid carcinomas. AB - Raf-1 kinase inhibitory protein (RKIP) has been implicated in several fundamental signal transduction pathways that control cellular growth, differentiation, apoptosis and migration. RKIP is reduced in a variety of human carcinomas, but RKIP expression in thyroid carcinomas has not been analyzed at the protein level. In this study, we examined the immunohistochemical expression of RKIP in various subtypes of thyroid carcinoma. Immunostaining for RKIP was performed on 104 cases of primary thyroid carcinoma (40 papillary, 29 follicular, 11 medullary, 11 poorly differentiated, and 13 anaplastic carcinomas) and 26 cases of nodal metastatic tumor (17 papillary, 4 medullary, and 5 anaplastic carcinomas). Normal thyroid tissue and all cases of follicular, papillary, and medullary carcinomas showed uniform, strong cytoplasmic immunoreactivity for RKIP. With the exception of one case, poorly differentiated carcinomas also revealed strong RKIP expression. In contrast, RKIP expression was completely absent in all anaplastic carcinomas. The transition zone from the differentiated carcinoma component (strong RKIP expression) to the anaplastic carcinoma component (no RKIP expression) demonstrated a completely opposite pattern of RKIP immunoreactivity. This reduction of RKIP expression in anaplastic carcinoma was statistically significant (P < 0.0001). Additionally, RKIP expression of nodal metastatic tumors corresponded with that of primary tumors: metastatic papillary and medullary carcinomas showed uniform, strong cytoplasmic RKIP immunoreactivity, in contrast, in metastatic anaplastic carcinomas, RKIP expression was completely absent. RKIP expression is significantly reduced in anaplastic thyroid carcinoma as compared to other subtypes of thyroid carcinoma. Further studies are necessary to elucidate the precise mechanism of RKIP action in anaplastic thyroid carcinoma. PMID- 20734162 TI - TP receptor activation and inhibition in atherothrombosis: the paradigm of diabetes mellitus. AB - Patients with type 2 diabetes mellitus are characterized by increased incidence of cardiovascular events and enhanced thromboxane-dependent platelet activation. Urinary enzymatic TXA(2) metabolites (such as 11-dehydro-TXB(2)), reflecting the whole TXA(2) biosynthesis by platelet and extra-platelet sources, are significantly increased in diabetes with the absolute post-aspirin values of 11 dehydro-TXB(2) in diabetics being comparable to non-aspirated controls and such residual TXA(2) biosynthesis despite low-dose aspirin treatment is predictive of vascular events in high-risk patients. Thus, elevated urinary 11-dehydro-TXB(2) levels identify patients who are partially insensitive to aspirin and who may benefit from alternative antiplatelet therapies or treatments that more effectively block in vivo TXA(2) production or activity. Potential mechanisms relatively insensitive to aspirin include extraplatelet, nucleate sources of TXA(2) biosynthesis, possibly triggered by inflammatory stimuli, or lipid peroxidation with enhanced generation of F2-isoprostane (reflecting ongoing in vivo oxidative stress) than can activate platelets via the platelet TP receptor thus escaping inhibition by aspirin. In fact, aspirin does not inhibit isoprostane formation. Moreover, intraplatelet or extraplatelet thromboxane generation may be only partly inhibited by aspirin under certain pathological conditions, at least at the usual low doses given for cardiovascular protection. TXA(2) receptors (TP) are expressed on several cell types and exert antiatherosclerotic, antivasoconstrictive and antithrombotic effects, depending on the cellular target. Thus, targeting TP receptor, a common downstream pathway for both platelet and extraplatelet TXA(2) as well as for isoprostanes, may be an useful antithrombotic intervention in clinical settings, such as diabetes mellitus characterized by persistently enhanced thromboxane-dependent platelet activation. PMID- 20734163 TI - Diabetes mellitus impairs the response to intra-arterial chemotherapy in hepatocellular carcinoma. AB - Diabetes mellitus is associated with a poorer outcome in patients with hepatocellular carcinoma. The impact of diabetes mellitus on the treatment of hepatocellular carcinoma, especially chemotherapy, is uncertain. Intra-arterial chemotherapy is one of the therapeutic options of unrespectable hepatocellular carcinoma. To clarify this point, we analyze the therapeutic effect of intra arterial chemotherapy in unrespectable hepatocellular carcinoma patients with or without diabetes mellitus. Fifty-two patients with advanced hepatocellular carcinoma underwent intra-arterial chemotherapy with cisplatin and fluorouracil. Tumor response was assessed by computed tomography. An in vitro hepatocellular carcinoma cell line, Hep G2, was evaluated for the cytotoxic effect of cisplatin and fluorouracil in different concentrations of insulin and glucose mimicking diabetic conditions. Fifty-two patients were included, 14 had diabetes and 38 were non-diabetics. Non-diabetic patients had a lower rate of progressive disease (16% vs. 43%, P=0.039). The median time to progression was significantly longer in non-diabetics compared with the diabetic counterpart (a median of 206 days vs. 88 days, P=0.02). In the hepatocellular carcinoma cell line, Hep G2, insulin rather than glucose was more important for promoting cell proliferation and enhancing the drug resistance of cisplatin or fluorouracil. Our study showed that intra-arterial chemotherapy for unrespectable hepatocellular carcinoma was less effective in diabetic patients than the non-diabetic counterpart in terms of the progression-free rate and time to disease progression survival. PMID- 20734164 TI - Approach to polyarthritis. AB - A child with polyarthritis is always a diagnostic challenge for the treating physician. By definition, polyarthritis, taken in context as a subgroup of juvenile idiopathic arthritis, is defined as inflammation of more than 4 joints on physical examination. Though the exact incidence and prevalence of polyarthritis in childhood is not known, it is not uncommon in pediatric practice. Polyarthritis can be a clinical manifestation of diverse disease processes and the differential diagnosis is understandably very broad. It can be caused directly by an infectious agent or indirectly by immune mechanisms, may be a component of a systemic disease process or may be idiopathic. The presentation can be acute or chronic. It can represent a benign self limiting illness requiring no specific treatment or may be a severely disabling condition with significant morbidity and, in some cases, even mortality. While in some situations it may be possible to arrive at a provisional clinical diagnosis right at the outset, in others the diagnosis gradually evolves over a period of time. As in most other arthritides, the most important aspects of the diagnosis are a thorough history and a detailed clinical examination. Relevant laboratory investigations can help in facilitating the diagnosis but can often also mislead the treating physician. Hereby we present a clinical approach to a child with polyarthritis. PMID- 20734165 TI - Global developmental delay and its determinants among urban infants and toddlers: a cross sectional study. AB - OBJECTIVE: To estimate the prevalence of global developmental delay among children under 3 years of age and study the determinant factors. METHODS: Cross sectional descriptive study was conducted in field practice areas of the Department of Community Medicine, JN Medical College, Aligarh, India. A total of 468 (243 boys and 225 girls) children aged 0-3 years were included. Developmental screening was performed for each child. A multitude of biological and environmental factors were analysed. RESULTS: As many as 7.1% of the children screened positive for global developmental delay. Maximum delay was observed in the 0-12 months age group (7.0%). Undernutrition and prematurity were the two most prevalent etiological diagnoses (21% each). Stunting and maternal illiteracy were the microenvironmental predictors on stepwise binary logistic regression while prematurity and a history of seizures emerged significant biological predictors. CONCLUSIONS: Developmental delay can be predicted by specific biological and environmental factors which would help in initiating appropriate interventions. PMID- 20734166 TI - Herlyn- Werner- Wunderlich syndrome: a rare urogenital anomaly masquerading as acute abdomen. PMID- 20734167 TI - Unusual presentations of posterior fossa tumors in children. PMID- 20734168 TI - Neonatal amoebiasis. AB - The authors report a case of neonatal amebiasis presenting with vomiting, refusal to feeds, abdominal distension and mucoid stools. The diagnosis was made on the basis of clinical appearance of stools and the presence of Entameba Histolytica. The purpose of this report is to alert to the possibility of amoebiasis in newborns, if baby presents with NEC like picture in an endemic area and to send the stool sample immediately to examine for trophozoites, especially because the diarrheal stool starts autolyzing within 30 min of defecation. This 14-day-old newborn, who was possibly infected with orally given jaggery solution is presented. He was successfully treated with intravenous tinidazole. PMID- 20734169 TI - Childhood lupus: experience from Eastern India. AB - OBJECTIVE: To delineate the clinical behavior of SLE in children from Eastern India and to the differences in disease pattern. METHODS: In the present study, all 44 patients of pediatric SLE who were diagnosed over a period of 5 years in our pediatric rheumatology clinic were followed prospectively. The resultant database was analyzed using standard statistical methods. RESULTS: about 3.9% of all rheumatology cases dealt with in the clinic in the last five yrs (n=1063) were sle. the number of children in 5-8 yrs and 8-12 yrs age groups were 13 and 27, respectively. the overall female (n=35) to male (n=9) ratio in this study was 3.8:1. renal, hematological and neuropsychiatric features were most common major organ manifestations(54%,54% and 25% respectively). joints and skin were the most common minor organs involved. two case were ana negative sle. among the typical features of ana negative disease, only nephritis was found in these patients. anti dsdna was positive in 50 % cases (n=21). c3 levels were studied in all cases with nephritis (n=22) and 68 % (n=15) had hypocomplementemia. anti ro and anti la antibodies were positive in two cases of neonatal lupus. APLA, ANTI SM antibody AND ANTI U1RNP were negative in the cases where testing was done: CONCLUSIONS: This study has tried to delineate the disease trends of childhood lupus from Eastern India. Certain important trends have emerged which are different from other contemporary Indian and International observations. PMID- 20734170 TI - Recognizing and improving health care disparities in the prevention of cardiovascular disease in women. AB - Innate differences in gender physiology result in unique exposures, risk, and protection that are specific to women. Recognition and appreciation of these differences results in better treatment adaptations for women and better outcomes. Disparities between genders in the treatment of major cardiovascular risk factors still exist and are mostly secondary to underestimating or misunderstanding a woman's risk. Preventive therapies are less often recommended to women. Women are more likely to be diagnosed and treated for hypertension, but are less likely to reach treatment goals. High-risk women-including diabetic women-are less likely to be on lipid-lowering agents and reach a low-density lipoprotein level less than 100 mg/dL. Diabetic women are less likely to achieve a hemoglobin A(1c) level less than 7%. Through understanding these disparities, health care providers will be better able to screen female patients and institute evidence-based therapies for the prevention of cardiovascular disease. PMID- 20734171 TI - Periodic Fever syndromes. AB - The periodic syndromes represent a heterogeneous group of disorders that can be very difficult for practicing physicians to diagnosis and treat. This article presents an orderly approach to hyperimmunoglobulin D syndrome; tumor necrosis factor receptor-1 periodic syndrome; familial Mediterranean fever; periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome; and cryopyrin associated periodic syndromes by highlighting the disease presentation, diagnosis, pathogenesis, and treatment. Recent advances are also discussed. PMID- 20734172 TI - Augmentation enterocystoplasty in overactive bladder: is there still a role? AB - Overactive bladder (OAB) is a highly prevalent syndrome defined as "urinary urgency, usually accompanied by frequency and nocturia with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology." It is known to generate a large degree of bother and can lead to significant morbidity. Augmentation cystoplasty (AC) historically has been reserved for patients refractory to conservative management. Over time, the treatment options for OAB have grown. We now have multiple pharmacological agents approved by the US Food and Drug Administration to treat OAB. In addition, neuromodulation and botulinum toxin now are viable options for patients who have suboptimal outcomes after treatment with anticholinergics and/or pelvic floor behavioral therapy. This may suggest that AC no longer is utilized as a mainstay therapy for OAB. However, despite these many possible treatment options, AC remains an important, time-tested tool in the armamentarium of the urologist to combat the patient with refractory OAB. PMID- 20734173 TI - State-of-the-art issues in Hodgkin's lymphoma survivorship. AB - The prognosis of Hodgkin's lymphoma (HL) has markedly improved as management strategies evolved. In the modern era, less than 15% of patients with early stage, non-bulky HL will relapse, and less than one third of those with advanced disease will relapse. As therapy for HL intensified, and as disease-related outcomes improved, the impact of the late effects of therapy has become increasingly important. There is a growing body of literature describing the late morbidity experienced by survivors of HL, including risks of second primary malignancy, cardiac disease, pulmonary disease, and endocrine dysfunction. Additionally, the impact of disease and treatment on psychosocial function and quality of life has been a subject of investigation, with survivors often suffering from impairment. An understanding of these risks and the management implications inherent to them is central to the care of survivors of HL. PMID- 20734174 TI - Validity of processes of change in physical activity among college students in the TIGER study. AB - OBJECTIVE: To test the factorial validity and measurement equivalence/invariance of scales used to measure processes of change derived from the Transtheoretical Model (TTM) applied to physical activity. METHODS: Confirmatory factor analysis of questionnaire responses obtained from a diverse sample (N = 1,429) of students enrolled in the Training Interventions and Genetics of Exercise Response (TIGER) Study at the University of Houston during academic years 2004-2005 through 2007 2008. Cohorts of students (N = 1,163) completed the scales at the beginning and end of each Fall semester, permitting longitudinal analysis. RESULTS: Theoretically and statistically sound models were developed that support the factorial validity of nine of the ten hypothesized 1st-order factors. A structure of nine correlated 1st order factors or a hierarchical structure of those factors subordinate to two correlated 2nd-order factors were each defensible. Multi-group invariance of each model was confirmed across race/ethnicity groups (African American, Hispanic, non-Hispanic White), gender, age, BMI levels, employment status, physical activity level, and study adherence. Longitudinal invariance across the semester was also confirmed. CONCLUSION: The scores from the scales provide valid assessments that can be used in observational studies of naturally occurring change or in interventions designed to test the usefulness of TTM processes as mediators of change in physical activity among college students. Item content and factor structure require further evaluation in other samples in order to advance TTM theory applied to physical activity. PMID- 20734175 TI - Neuropeptidomic components generated by proteomic functions in secretory vesicles for cell-cell communication. AB - Diverse neuropeptides participate in cell-cell communication to coordinate neuronal and endocrine regulation of physiological processes in health and disease. Neuropeptides are short peptides ranging in length from ~3 to 40 amino acid residues that are involved in biological functions of pain, stress, obesity, hypertension, mental disorders, cancer, and numerous health conditions. The unique neuropeptide sequences define their specific biological actions. Significantly, this review article discusses how the neuropeptide field is at the crest of expanding knowledge gained from mass-spectrometry-based neuropeptidomic studies, combined with proteomic analyses for understanding the biosynthesis of neuropeptidomes. The ongoing expansion in neuropeptide diversity lies in the unbiased and global mass-spectrometry-based approaches for identification and quantitation of peptides. Current mass spectrometry technology allows definition of neuropeptide amino acid sequence structures, profiling of multiple neuropeptides in normal and disease conditions, and quantitative peptide measures in biomarker applications to monitor therapeutic drug efficacies. Complementary proteomic studies of neuropeptide secretory vesicles provide valuable insight into the protein processes utilized for neuropeptide production, storage, and secretion. Furthermore, ongoing research in developing new computational tools will facilitate advancements in mass-spectrometry-based identification of small peptides. Knowledge of the entire repertoire of neuropeptides that regulate physiological systems will provide novel insight into regulatory mechanisms in health, disease, and therapeutics. PMID- 20734176 TI - Depressive mood is associated with ataxic and non-ataxic neurological dysfunction in SCA3 patients. PMID- 20734179 TI - Positive adenosine stress ECG in patients with a normal myocardial perfusion scan. PMID- 20734177 TI - Contributions of T-type voltage-gated calcium channels to postsynaptic calcium signaling within Purkinje neurons. AB - Low threshold voltage-gated T-type calcium channels have long been implicated in the electrical excitability and calcium signaling of cerebellar Purkinje neurons although the molecular composition, localization, and modulation of T-type channels within Purkinje cells have only recently been addressed. The specific functional roles that T-type channels play in local synaptic integration within Purkinje spines are also currently being unraveled. Overall, Purkinje neurons represent a powerful model system to explore the potential roles of postsynaptic T-type channels throughout the nervous system. In this review, we present an overview of T-type calcium channel biophysical, pharmacological, and physiological characteristics that provides a foundation for understanding T-type channels within Purkinje neurons. We also describe the biophysical properties of T-type channels in context of other voltage-gated calcium channel currents found within Purkinje cells. The data thus far suggest that one specific T-type isoform, Ca(v)3.1, is highly expressed within Purkinje spines and both physically and functionally couples to mGluR1 and other effectors within putative signaling microdomains. Finally, we discuss how the selective potentiation of Ca(v)3.1 channels via activation of mGluR1 by parallel fiber inputs affects local synaptic integration and how this interaction may relate to the overall excitability of Purkinje neuron dendrites. PMID- 20734180 TI - Local ventilation system successfully reduced formaldehyde exposure during gross anatomy dissection classes. PMID- 20734181 TI - Assessment of in vivo calculation with ultrasonography compared to physical sections in vitro: a stereological study of prostate volumes. AB - We compared three methods for the determination of prostate volume: prostate volume measured via transrectal ultrasonography (TRUS); the Cavalieri method for measuring physical sections; and volume by displacement. TRUS volumes were calculated by the prolate ellipsoid volume formula. Five patients underwent TRUS examination of the prostate prior to radical prostatectomy; specimens were measured when freshly excised. Mean prostate volume by fluid displacement, before formalin fixation was 52.8 +/- 21.5 cm(3), and after formalin fixation 50.4 +/- 20.9 cm(3). Volumes determined by the Cavalieri principle (point-counting and planimetry) were 47.8 +/- 19.3 and 49.1 +/- 20.5 cm(3); volume measured by TRUS was 42.9 +/- 21.9 cm(3). Thus TRUS underestimated prostate volume by 21.4%, but excellent agreement was found between actual volume and point counting techniques. We believe that the classic ellipsoid formula is inadequate for determining prostate volume. PMID- 20734187 TI - Hybrid origins of cultivated potatoes. AB - Solanum section Petota is taxonomically difficult, partly because of interspecific hybridization at both the diploid and polyploid levels. The taxonomy of cultivated potatoes is particularly controversial. Using DNA sequence data of the waxy gene, we here infer relationships among the four species of cultivated potatoes accepted in the latest taxonomic treatment (S. ajanhuiri, S. curtilobum, S. juzepczukii and S. tuberosum, the latter divided into the Andigenum and Chilotanum Cultivar Groups). The data support prior ideas of hybrid origins of S. ajanhuiri from the S. tuberosum Andigenum Group (2x = S. stenotomum) * S. megistacrolobum; S. juzepczukii from the S. tuberosum Andigenum Group (2x = S. stenotomum) * S. acaule; and S. curtilobum from the S. tuberosum Andigenum Group (4x = S. tuberosum subsp. andigenum) * S. juzepczukii. For the tetraploid cultivar-groups of S. tuberosum, hybrid origins are suggested entirely within much more closely related species, except for two of three examined accessions of the S. tuberosum Chilotanum Group that appear to have hybridized with the wild species S. maglia. Hybrid origins of the crop/weed species S. sucrense are more difficult to support and S. vernei is not supported as a wild species progenitor of the S. tuberosum Andigenum Group. PMID- 20734188 TI - Evaluating guidelines for critical care: a need for detail. PMID- 20734190 TI - Antibacterial mechanism of soybean isoflavone on Staphylococcus aureus. AB - Effects of different flavonoids on various bacterial strains have been extensively reported; however, the mechanism(s) of their action on bacterial cells remain largely elusive. In this study, the antibacterial mechanism of soybean isoflavone (SI) on Staphylococcus aureus is systematically investigated using 4'6-diamidino-2-phenylindole (DAPI) staining, pBR322DNA decatenation experiment mediated by topoisomerase and agarose gel electrophoresis for direct decatenation. The results of fluorescence microscopy and fluorescence spectrophotometer indicated that DAPI was integrated in Staphylococcus aureus. Additionally, the quantity of both DNA and RNA reduced to 66.47 and 60.18%, respectively, after treated with SI for 28 h. Effects of SI on topoisomerase I and II were also investigated. SI completely inhibited the pBR322DNA unwinding mediated by topoisomerase I and topoisomerase II at the concentration of 6.4 mg/ml and could denature the plasmid DNA at the concentration of 12.8 mg/ml. These results indicate that topoisomerase I and II are the most important targets by SI to restrain bacterial cell division. PMID- 20734191 TI - Favorable outcome of pediatric fulminant myocarditis supported by extracorporeal membranous oxygenation. AB - Myocarditis among pediatric patients varies in severity from mild disease to a fulminant course with overwhelming refractory shock and a high risk of death. Because the disease is potentially reversible, it is reasonable to deploy extracorporeal membranous oxygenation (ECMO) to bridge patients until recovery or transplantation. This study aimed to review the course and outcome of children with acute fulminant myocarditis diagnosed by clinical and echocardiographic data only who were managed by ECMO because of refractory circulatory collapse. A chart review of a single center identified 12 children hospitalized over an 8-year period who met the study criteria. Data were collected on demographics, diagnosis, disease course, and outcome. The patients ranged in age from 20 days to 8 years (25.5 +/- 29.6 months). Echocardiography showed a severe global biventricular decrease in myocardial function, with a shortening fraction of 12% or less. Ten children (83.3%) were weaned off extracorporeal support after 100 408 h (mean, 209.9 +/- 82.4 h) and discharged home. Two patients died: one due to multiorgan failure and one due to sustained refractory heart failure. During a long-term follow-up period, all survivors showed normal function in daily activities and normal myocardial function. The study showed that ECMO can be safely and successfully used for children with acute fulminant myocarditis diagnosed solely on clinical and radiographic grounds who need mechanical support. These patients usually have a favorable outcome, regaining normal or near normal heart function without a need for heart transplantation. PMID- 20734192 TI - Transiently crosslinked F-actin bundles. AB - F-actin bundles are prominent cytoskeletal structures in eukaryotes. They provide mechanical stability in stereocilia, microvilli, filopodia, stress fibers and the sperm acrosome. Bundles are typically stabilized by a wide range of specific crosslinking proteins, most of which exhibit off-rates on the order of 1s(-1). Yet F-actin bundles exhibit structural and mechanical integrity on time scales that are orders of magnitude longer. By applying large deformations to reconstituted F-actin bundles using optical tweezers, we provide direct evidence of their differential mechanical response in vitro: bundles exhibit fully reversible, elastic response on short time scales and irreversible, elasto plastic response on time scales that are long compared to the characteristic crosslink dissociation time. Our measurements show a broad range of characteristic relaxation times for reconstituted F-actin bundles. This can be reconciled by considering that bundle relaxation behavior is also modulated by the number of filaments, crosslinking type and occupation number as well as the consideration of defects due to filament ends. PMID- 20734193 TI - Stereotactic radiofrequency ablation. AB - PURPOSE: To describe the technique of percutaneous stereotactic radiofrequency ablation (SRFA) and its application in a patient with an unresectable multifocal intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: A 72-year-old man presented with two nodules of an ICC with a maximum diameter of 10 and 4 cm, respectively. To produce overlapping ablation areas and cover the entire tumor volume, 18 paths for the placement of radiofrequency ablation (RFA) probes at multiple locations were planned on 2D and 3D reconstructions of the computed tomographic (CT) data. The 15-gauge coaxial needles were advanced through the aiming device to the preplanned depth. A control CT fused to the planning CT data confirmed correct needle placements. RFA was performed with an impedance-based multiple-electrode RFA system. Fusion of the contrast-enhanced control CT with the planning CT showed an appropriate zone of ablation. RESULTS: Besides a mild asymptomatic pleural effusion, no complications occurred. Twenty-seven months after the first RFA, two new small distant liver metastases were successfully treated by SRFA. Currently, 38 months after diagnosis and 36 months after the first SRFA, the patient is free of detectable disease. CONCLUSION: SRFA seems to offer an effective treatment option in selected patients with even unresectable ICC. PMID- 20734194 TI - The study techniques of Asian, American, and European medical students during gross anatomy and neuroanatomy courses in Poland. AB - BACKGROUND: Past research in medical education has addressed the study of gross anatomy, including the most effective learning techniques, comparing the use of cadavers, dissection, anatomy atlases, and multimedia tools. The aim of this study was to demonstrate similarities and differences among American, Asian, and European medical students (MS) regarding different study methods and to see how these methods affected their clinical skills. METHODS: To analyze the varying study methods of European, American, and Asian MS in our program and in order to elucidate any ethnic and cultural differences a survey was conducted. A total of 705 international MS, from the Polish (PD), American (AD), and Taiwanese (TD) divisions, were asked to voluntarily participate in the questionnaire. Students were asked the following questions: which methods they used to study anatomy, and which of the methods they believed were most efficient for comprehension, memorization, and review. The questions were based on a 5-point Likert scale, where 5 was 'strongly agree', and 1 was 'strongly disagree'. RESULTS: The PD and AD preferred the use of dissections and prosected specimens to study anatomy. The TD showed less interest in studying from prosected specimens, but did acknowledge that this method was more effective than using atlases, plastic models, or CD ROMs. Multimedia tools were mainly used for radiological anatomy and review and also for correctly typing proper names of structures using exact anatomical terminology. CONCLUSION: The findings highlight the differences in study techniques among students from different ethnic backgrounds. The study approaches used in order to accomplish learning objectives was affected by cultural norms that influenced each student group. These differences may be rooted in technological, religious, and language barriers, which can shape the way MS approach learning. PMID- 20734195 TI - The description of the "Valentine" orientation of the heart. PMID- 20734196 TI - Sinus node artery originating from the posterior part of the right coronary artery. AB - PURPOSE: The purpose of the study was to examine the anatomical variations of the sinus node artery (SNA). METHODS: Gross anatomical examination, angiographic evaluation and if necessary dissection were performed in 200 human hearts derived from victims of various accidents. RESULTS: The SNA was a branch of the right coronary artery in 118 [59%] cases, the left circumflex in 78 [39%] cases and both coronary arteries in 4 [2%] cases. In one subject, the SNA was found to arise from the distal part of the right coronary artery. CONCLUSIONS: In our case, the sinus node was perfused by a SNA arising from the mid-posterior segment of the right coronary artery. Knowledge of this anatomical variation is useful for anatomists and of clinical significance for the interventional cardiologists and mainly for the cardiac surgeons in planning the surgical procedures. PMID- 20734197 TI - The clinical impact of high resolution computed tomography in patients with respiratory disease. AB - OBJECTIVE: High resolution computed tomography is widely used to investigate patients with suspected diffuse lung disease. Numerous studies have assessed the diagnostic performance of this investigation, but the diagnostic and therapeutic impacts have received little attention. METHODS: The diagnostic and therapeutic impacts of high resolution computed tomography in routine clinical practice were evaluated prospectively. All 507 referrals for high-resolution computed tomography over 12 months in two centres were included. Requesting clinicians completed questionnaires before and after the investigation detailing clinical indications, working diagnoses, confidence level in each diagnosis, planned investigations and treatments. RESULTS: Three hundred and fifty-four studies on 347 patients had complete data and were available for analysis. Following high resolution computed tomography, a new leading diagnosis (the diagnosis with the highest confidence level) emerged in 204 (58%) studies; in 166 (47%) studies the new leading diagnosis was not in the original differential diagnosis. Mean confidence in the leading diagnosis increased from 6.7 to 8.5 out of 10 (p < 0.001). The invasiveness of planned investigations increased in 23 (7%) studies and decreased in 124 (35%) studies. The treatment plan was modified after 319 (90%) studies. CONCLUSIONS: Thoracic high-resolution computed tomography alters leading diagnosis, increases diagnostic confidence, and frequently changes investigation and management plans. PMID- 20734198 TI - Avoiding varus malreduction during cephalomedullary nailing of intertrochanteric hip fractures. AB - We describe a technique for preventing varus malreduction of intertrochanteric hip fractures during fixation with a cephalomedullary nail. When the entry reamer guidewire is positioned in the fracture line, passage of the entry reamer may simply push the proximal fragment medially and the distal fragment laterally rather than ream the accurate entry path. Subsequent nail insertion will result in a varus deformity of the proximal femur. The simple technique described in this report uses a brief period of over-distraction to wedge the entry reamer guidewire against the lateral edge of the proximal fragment, permitting the reamer to cut a correct path in the lateral edge of the proximal fragment. Creation of a proper entry path is essential to maintain anatomic reduction during cephalomedullary nailing of intertrochanteric hip fractures. PMID- 20734199 TI - Composite reconstruction after proximal radial giant cell tumor resection. AB - Giant cell tumor (GCT) of bone involving the proximal radius is extremely rare. Here, the authors present the case of a 33-year-old man with an expansile, osteolytic lesion in the proximal radius, which was diagnosed by biopsy as GCT. The rarity of this lesion in the proximal radius is highlighted, and the authors describe their method of reconstruction, which involved en-bloc excision followed by reconstruction with polyethylene, pins, a screw, and bone cement. An acceptable intermediate term result was achieved. PMID- 20734200 TI - UKA after spontaneous osteonecrosis of the knee: a retrospective analysis. AB - PURPOSE: Safety and efficacy of unicompartmental knee arthroplasty (UKA) in unicompartmental osteoarthritis (OA) has been shown in large patient series. It has been matter of discussion whether or not spontaneous osteonecrosis of the knee (SONK) can successfully be treated with UKA. PATIENTS AND METHODS: A retrospective approach included 52 cases of UKA for SONK of the femoral condyles. Four implants were revised (7.7%), and seven patients had died. Nine patients were interviewed by telephone, 28 followed the invitation for clinical examination including clinical scores (KSS and WOMAC) and radiographs. Satisfaction of patients was recorded in four categories. Four patients (7.7%) were lost to follow-up. RESULTS: Average follow-up was 10.9 +/- 4.8 years (4-25). Average age at operation was 66.6 +/- 9.7 years. The KSS score increased from a preoperative 85 +/- 30 to 173 +/- 27 (p < 0.0001) at latest follow-up. WOMAC was 7.7 +/- 11.4 at latest follow-up. Of the patients with implants still in place, most patients were satisfied (21.6%) or very satisfied (75.7%) with the outcome of this surgical procedure. One patient was dissatisfied (2.7%). Kaplan-Meier analysis with implant revision as endpoint revealed a survival rate of 93.1% at 10 years and 90.6% at 15 years. DISCUSSION: This study shows that spontaneous osteonecrosis of the knee (SONK) can successfully be treated with UKA at a good mid- to long-term follow-up. PMID- 20734201 TI - GABAA receptor-mediated modulation of neuronal activity propagation upon tetanic stimulation in rat hippocampal slices. AB - Tetanic stimulation (100 Hz), which can induce long-term potentiation in synaptic connections in the hippocampal CA1 region, causes gamma-aminobutyric acid (GABA)(A) receptor-mediated long-lasting depolarization of postsynaptic neurons. However, it is not clear how this stimulation modulates neuronal activity propagation. We studied tetanic burst-induced neuronal responses in the hippocampal CA1 region by using optical-recording methods employing a voltage sensitive dye and focused on GABA(A) receptor-mediated modulation. We observed that burst stimulation induced long-lasting depolarization and progressive decrease in individual excitatory postsynaptic potentials (EPSPs). Both these effects were suppressed by picrotoxin, a GABA(A) receptor antagonist. Under whole cell voltage-clamp conditions, we observed a long-lasting inhibitory current (IPSC) and a prominent progressive decrease in the amplitude of the excitatory postsynaptic current (EPSC). Further, picrotoxin inhibited the IPSC and the progressive decrease in EPSC. The optically recorded long-lasting depolarization and progressive decrease of EPSPs were strongly dependent on the distance between the recording electrode and the stimulation site. Optical recordings performed across a wide swatch of CA1 revealed that the decrease in activity propagation was followed by facilitation of propagation after recovery and that this facilitation also depended on GABA(A) receptors. Intense activation of GABA(A) receptors is a key factor shaping the spatiotemporal patterns of high-frequency stimulation-induced responses in the CA1 region. PMID- 20734202 TI - Effects of lobeline, a nicotinic receptor ligand, on the cloned Kv1.5. AB - The goal of the present study was to examine the effects of lobeline, an agonist at nicotinic receptors, on cloned Kv channels, Kv1.5, Kv3.1, Kv4.3, and human ether-a-gogo-related gene (HERG), which are stably expressed in Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. Whole-cell patch-clamp experiments revealed that lobeline accelerated the decay rate of Kv1.5 inactivation, decreasing the current amplitude at the end of the pulse in a concentration-dependent manner with a half-maximal inhibitory concentration (IC(50)) value of 15.1 MUM. Using a time constant for the time course of drug channel interaction, the apparent association (k(+1)), and dissociation rate (k( 1)) constants were 2.4 MUMU(-1) s(-1) and 40.9 s(-1), respectively. The calculated K(D) was 17.0 MUMU. Lobeline slowed the decay rate of the tail current, resulting in a tail crossover phenomenon. The inhibition of Kv1.5 by lobeline steeply increased at potentials between -10 and +10 mV, which corresponds to the voltage range of channel activation. At more depolarized potentials a weaker voltage dependence was observed (delta=0.26). The voltage dependence of the steady-state activation curve was not affected by lobeline, but lobeline shifted the steady-state inactivation curve of Kv1.5 in the hyperpolarizing direction. Lobeline produced use-dependent inhibition of Kv1.5 at frequencies of 1 and 2 Hz, and slowed the recovery from inactivation. Lobeline also inhibited Kv3.1, Kv4.3, and HERG in a concentration-dependent manner, with IC(50) values of 21.7, 28.2, and 0.34 MUM, respectively. These results indicate that lobeline produces a concentration-, time-, voltage-, and use-dependent inhibition of Kv1.5, which can be interpreted as an open-channel block mechanism. PMID- 20734203 TI - IgA nephropathy associated with a novel N-terminal mutation in factor H. AB - Most patients with IgA nephropathy exhibit complement deposition in the glomerular mesangium. Certain cases of IgA nephropathy have been associated with reduced levels of complement factor H. A recent study could not demonstrate mutations at the C-terminal of factor H. We describe a novel heterozygous mutation in factor H, position A48S (nucleotide position 142 G > T, alanine > serine), detected in exon 2 of a 14-year-old girl with IgA nephropathy. The patient exhibited reduced levels of C3 and factor H, the latter suggesting that the mutation affected factor H secretion. The patient developed initial signs and symptoms of glomerulonephritis at the age of 9 years but presented again at the age of 14 years with weight gain, renal failure, nephrotic-range proteinuria and malignant hypertension. Blood tests suggested the development of microangiopathic hemolytic anemia (MAHA) but the renal biopsy was mostly indicative of chronic changes associated with IgA nephropathy as well as vascular changes associated with malignant hypertension. Immunofluorescence exhibited deposits of IgA, C3, and IgM. Screening of the factor H gene revealed, in addition to the mutation, three heterozygous hemolytic uremic syndrome -associated risk polymorphisms (-257 c/t, 2089 a/g, and 2881 g/t) which may have increased the patient's susceptibility to the occurrence of MAHA triggered by malignant hypertension. The combined clinical picture of IgA nephropathy and MAHA may have been partly related to the alterations in factor H. PMID- 20734204 TI - Association between height and weight catch-up growth with insulin resistance in pre-pubertal Chinese children born small for gestational age at two different ages. AB - This study was performed to test whether children born small for gestational age (SGA) with catch-up growth (CUG) could be associated with the early development of insulin resistance and the beta-cell dysfunction and to explore the impacts of height CUG and weight CUG on the insulin resistance in a Chinese population. A total of 30 children born SGA with CUG, 37 non-CUG (NCUG), and 42 born appropriate for gestational age (AGA) with normal height were recruited. Their fasting serum insulin, fasting glucose, insulin-like growth factor-1 (IGF-1) concentrations, and the homeostasis assessment model for insulin resistance (HOMA IR) and beta-cell function (HOMA%) were evaluated. The values of HOMA-IR in CUG SGA were significantly higher than that in NCUG SGA (P = 0.002) and AGA children (P = 0.036), respectively. Correlation analysis revealed that the concentrations of fasting serum insulin were positively correlated with IGF-1 (r = 0.443, P = 0.001) and Deltaheight standard deviation score (SDS; r = 0.500, P = 0.002) in <= 6-year-old SGA children, but only with Deltaweight SDS (r = 0.496, P = 0.030) in >6-year-old children. In conclusion, SGA children with CUG in height and a higher body mass index are prone to the development of insulin resistance. Higher levels of insulin were closely correlated with the postnatal height CUG in young SGA children and with the weight CUG in old children. PMID- 20734205 TI - A novel separation and enrichment method of 17beta-estradiol using aptamer anchored microbeads. AB - The estrogenic compound 17beta-estradiol (E2) is widely studied for its potential endocrine disruption effects. Due to the low level of E2 present in the environment, it is highly desirable to develop a sensitive and efficient separation and enrichment method for E2 analysis. In this paper, we proposed a novel E2 preconcentration method using anti-E2 aptamer-anchored isothiocyanate modified beads (NCS beads). The glass beads are chemically modified with primary amino group, and then treated with phenylene diisothiocyanate (PDITC) to generate an isothiocyanate group, which is reactive towards the amine group. The amino modified anti-E2 aptamer can be easily covalently immobilized onto the as prepared NCS beads. The experimental results demonstrated that the aptamer affinity microbeads could selectively retain and separate E2 compound. The effects of the operation parameters on retention of E2, including washing condition, eluting condition, the number of beads, and the incubation time were investigated. Moreover, high-performance liquid chromatography with preconcentration of E2 on the aptamer affinity microbeads was applied to detect the E2 in the spiked water samples and obtained a good recovery. PMID- 20734206 TI - Patient allocation based on preoperative assessment of pancreatic fibrosis to secure pancreatic anastomosis performed by trainee surgeons: a prospective study. AB - BACKGROUND: A fragile or non-fibrotic pancreas increases the risk of postoperative pancreatic fistula (POPF) after pancreatic head resection, whereas pancreatic fibrosis decreases the risk. The degree of pancreatic fibrosis can be estimated using the time-signal intensity curve (TIC) of the pancreas, obtained with dynamic magnetic resonance imaging (MRI). We have investigated whether trainee surgeons can perform pancreatic anastomosis safely, without the occurrence of POPF, when patients are selected carefully based on a preoperative assessment of pancreatic fibrosis. METHODS: Seventy-two consecutive patients who underwent pancreatic head resection were enrolled in this prospective trial. Dynamic contrast-enhanced MRI of the pancreas was performed preoperatively in all patients who, based on their pancreatic TIC profile, were then allocated to one of two groups: Group A comprised patients with type I pancreatic TIC, signifying a normal pancreas without fibrosis (n = 46); Group B comprised patients with type II or III pancreatic TIC, signifying a fibrotic pancreas (n = 26). An end-to-side duct-to-mucosa pancreaticojejunostomy was performed in all patients, with all patients in Group A operated on by two experienced surgeons, and all patients in Group B operated on by one of eight trainee surgeons at various stages of training. RESULTS: There was no operative mortality. POPF developed in 19 patients: 12 patients with grade A POPF and seven with grade B. All except one of the POPF occurred in Group A patients. The POPF in the one patient from Group B was grade A (p < 0.001). CONCLUSIONS: A trainee surgeon can perform a secure pancreatic anastomosis without the occurrence of POPF in patients with a pancreas displaying a fibrotic pancreatic TIC on dynamic MRI scans. PMID- 20734207 TI - The outcomes of methicillin-resistant Staphylococcus aureus infection after living donor liver transplantation in a Japanese center. AB - OBJECTIVE: The objective of this study is to present results from our review of methicillin-resistant Staphylococcus aureus (MRSA) infection in living-donor liver transplant (LDLT) recipients. METHODS: Seventy patients with primary LDLT between August 1997 and May 2007 were retrospectively reviewed. RESULTS: Overall, 9 patients (12.9%) encountered various kinds of MRSA infection after transplantation [peritonitis (6), bacteremia (6), pneumonia (3), wound infection (3), cholangitis (1)]; 4 of these 9 patients died. Of these 4 expired patients, 3 were highly urgent cases with very poor pretransplant status under ventilator support. In one patient, linezolid was effective after teicoplanin failure for severe systemic MRSA infections (bacteremia, peritonitis, cholangitis, pneumonia, and enteritis). Of the 4 patients in whom MRSA was isolated only in a nasal swab before transplantation, none developed MRSA infection after transplantation with a 3-day course of mupirocin prophylaxis. CONCLUSIONS: MRSA infection was a contributing factor in death after transplantation in cases with poor pretransplant status. Linezolid was effective even for treating systemic MRSA infection after LDLT. A short course of mupirocin prophylaxis seemed to be effective and did not have any adverse effects. PMID- 20734208 TI - Expression of MUC5AC, an early marker of pancreatobiliary cancer, is regulated by DNA methylation in the distal promoter region in cancer cells. AB - BACKGROUND AND PURPOSE: High de novo expression of MUC5AC (a gastric-type secreted mucin) is observed in many types of pancreatobiliary neoplasms, including precursor lesions. In this study, we show that the DNA methylation pattern is intimately correlated with MUC5AC expression in ten cancer cell lines (breast, lung, pancreas, and colon). METHODS: The CpG methylation status of the MUC5AC promoter from -3855 to +321 was mapped using MassARRAY analysis, which utilizes base-specific cleavage of nucleic acids. ChIP assays and micro-RNA (miRNA) microarray expression profiling were also carried out in both MUC5AC positive cells and in those with no or low MUC5AC expression. RESULTS: In the distal region from -3718 to -3670 of the promoter, MUC5AC-negative cancer cells (e.g., MDA-MB-453) were highly methylated, whereas MUC5AC-positive cells (e.g., MCF-7) had low methylation levels. The modification status of histone H3 lysine 9 (H3-K9) was also closely related to MUC5AC expression. Expression levels of miRNAs in the cancer cells were not correlated with MUC5AC expression. CONCLUSION: Our results indicate that MUC5AC is regulated by CpG methylation and histone H3-K9 modification of the MUC5AC promoter distal region, but not by miRNAs. An understanding of the epigenetic regulation of MUC5AC may be of importance for the diagnosis of carcinogenic risk in the pancreatobiliary system. PMID- 20734209 TI - Platelets prevent acute liver damage after extended hepatectomy in pigs. AB - BACKGROUND/PURPOSE: Platelets develop tissue repair and promote liver regeneration. We investigated whether platelets prevented acute liver damage after extended hepatectomy in pigs. METHODS: Thrombocytosis was induced by the following two methods; afterwards 80% hepatectomy was performed in pigs. In the first method, the pigs received administration of thrombopoietin [TPO (+) group], and they were compared with a control group [TPO (-) group]. In the second method, the pigs received a splenectomy [Sp (+) group], and theywere compared with another control group [Sp (-) group]. Platelet counts, biochemical examination of blood, and histopathological findings of the residual liver were examined. RESULTS: Serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil) levels were significantly decreased in the thrombocytotic groups compared with the control groups in the early period after hepatectomy. In the histopathological findings, hemorrhagic necrosis with a bile plug was observed in the control groups, but this phenomenon was not observed in the thrombocytotic groups. On transmission electron microscopy, the sinusoidal endothelial lining was destroyed and detached into the sinusoidal space with enlargement of Disse's spaces in the thrombocytotic groups, but these findings were not observed in the control groups. CONCLUSION: An increased number of platelets prevents acute liver damage after extended hepatectomy. PMID- 20734210 TI - Reducing the incidence of post-hepatectomy hepatic complications by preoperatively applying parameters predictive of liver function. AB - BACKGROUND/PURPOSE: To prevent or reduce hepatic complications after hepatectomy, it is important to employ preoperative predictive parameters and to determine the indications for hepatectomy. In the present study, we evaluated risk parameters in patients who underwent hepatectomy between 1994 and 2003, and selected three parameters to modify the surgical indications. Using these indications before surgery in patients who underwent hepatectomy between 2004 and 2008, we compared the prevalences of postoperative complications in the the two groups of patients. METHODS: We examined 250 consecutive patients who underwent hepatectomy for liver disease [149 in 1994-2003 (termed the early period) and 101 in 2004 to 2008 (termed the later period)]. RESULTS: In the early period, uncontrolled ascites was observed in 55 patients and hepatic failure was observed in 15 of the 149 patients. Multivariate analysis identified volume of the resected liver (> or =50%), intraoperative blood loss (> or =1500 ml), prothrombin activity (<70%), hyaluronic acid level (> or =200 ng/ml), and LHL15 (hepatic uptake ratio of technetium-99m galactosyl human serum albumin ((99m)Tc-GSA) (<0.85) as risk factors; the latter three parameters were evaluated as predictors of outcome. From 2004, we used these three parameters, in addition to the indocyanine green retention rate at 15 min (ICGR15), as criteria for indications for hepatectomy. Despite the lower prevalence of normal liver in the later period, comparisons showed decreases in the rates of uncontrolled ascites (23 vs. 37%, P = 0.03), hepatic failure (4 vs. 10%, P = 0.12), and hepatic complications (25 vs. 44%, P = 0.003) in patients in the later period compared with these rates in the previous period. CONCLUSIONS: The use of prothrombin activity, and levels of hyaluronic acid and LHL15, as parameters of functional liver reserve in the selection of candidates for surgery reduced the incidence of hepatic complications after hepatectomy. PMID- 20734211 TI - The relationship between degree of facet tropism and amount of dynamic disc bulge in lumbar spine of patients symptomatic for low back pain. AB - Facet tropism has been investigated as a predisposing factor for degenerative changes in the lumbar spine; however, no prior study has evaluated the relationship between disc bulge and facet tropism. In this study, we used kinetic magnetic resonance imaging (kMRI) to investigate the association between degree of facet tropism and amount of disc bulge in the lumbar spine in relation to age. kMRIs in the flexion, neutral, and extension positions were performed on 410 consecutive patients with low back pain. T2-weighted midsagittal and axial mid disc cuts were analyzed to measure disc bulge and facet angle. Facet asymmetry was calculated and classified as: no facet tropism, <6 degrees ; mild facet tropism, 6-11 degrees ; or severe facet tropism, >=11 degrees . Maximal static bulge (MSB), maximal dynamic bulge (MDB), and age in the facet tropism groups were compared by age subpopulations and MDB categories, defined by the positions between which the largest change in disc bulge occurs. We found the severe facet tropism group to be associated with a nearly significant increase in MSB and MDB over the no facet tropism group in the older subpopulation at the L4-L5 level only, and a larger MDB in the L4-L5 MDB category [E-N], where the greatest change in disc bulge occurs between neutral and extension positions (p = 0.013). Our findings suggest that severe facet tropism is associated with increased disc bulge at L4-L5 in only a subset of older age patients, but may in large part be due to biomechanical factors that define the [E-N] category. PMID- 20734212 TI - Peptides as toxins/defensins. PMID- 20734213 TI - The efficient synthesis of isotopically labeled peptide-derived Amadori products and their characterization. AB - Protein glycation is often a cause of diabetes-associated complications. The isotopically labeled peptide-derived Amadori products may serve as standards for quantitative determination of the glycated proteins. In this paper, we discussed various approaches to the synthesis of Amadori products labeled selectively with stable isotopes (2)H, (13)C and (18)O. PMID- 20734214 TI - Patterns of background factors related to early RA patients' conceptions of the cause of their disease. AB - The aim of the present study was to identify patterns of background factors related to the early RA patients' conceptions of the cause of the disease. Conceptions from a qualitative study formed the basis for the stratification of 785 patients from the Swedish EIRA study answering a question about their own thoughts about the cause to RA. Logistic regression analyses were used to explore the associations between patients' conceptions and relevant background factors: sex, age, civil status, educational level, anti-cyclic citrullinated peptide antibody (anti-CCP) and smoking habits. The results were presented as odds ratios (OR) with 95% confidence intervals (CI). A conception of family-related strain was strongly associated with being young (OR 0.50; 95% CI 0.33-0.78 for age 58-70 vs. 17-46), female (OR 0.38; 95% CI 0.25-0.60 for male vs. female) and having a high level of education (OR 2.15; 95% CI 1.54-3.01 for university degree vs. no degree). A conception of being exposed to climate changes was associated with being male (OR 1.99; 95% CI 1.24-3.22 for male vs. female), having a low level of education (OR 0.33; 95% CI 0.18-0.58 for university degree vs. no degree) and positive Anti-CCP (OR 1.72; 95% CI 1.03-2.87 for positive vs. negative Anti-CCP). Linking patients' conceptions of the cause of their RA to background factors potentially could create new opportunities for understanding the complexity of the aetiology in RA. Furthermore, this information is important and relevant in the care of patients with early RA. PMID- 20734215 TI - A case of refractory adult-onset Still's disease successfully controlled with tocilizumab and a review of the literature. AB - Adult-onset Still's disease (AOSD) is an uncommon systemic inflammatory disease of unknown aetiology. Up to 80% of AOSD cases can be controlled with corticosteroids; however, reports on those unresponsive to corticosteroids, conventional disease modifying drugs and biological agents, including anti-IL1 inhibitors, are emerging. We present a case of AOSD with severe poylarthritis unresponsive to corticosteroids, methotrexate, anakinra and etanercept, but successfully stabilised with a humanized monoclonal anti-IL-6 receptor antibody, tocilizumab, administered once monthly. Thereafter, we compare our case with case reports available in the literature and suggest that for anakinra refractive AOSD patients with arthritis, tocilizumab could be the drug of choice. PMID- 20734216 TI - A single-dose regimen for antimicrobial prophylaxis to prevent perioperative infection in urological clean and clean-contaminated surgery. AB - A single dose of antimicrobial prophylaxis (AMP) was administered parenterally for the prevention of perioperative infection in a total of 788 patients undergoing urological surgery, including 380 endoscopic-instrumental, 328 clean, and 80 clean-contaminated operations performed at our institute between January 2007 and December 2009. Surgical site infections (SSIs), urinary tract infections (UTIs), and remote infections (RIs) were prospectively surveyed. The definition for a single dose of AMP allowed for the administration of an additional dose of an antimicrobial during surgery if the procedure was longer than 3 h, but not for the parenteral or oral administration at the end of the procedure in the recovery room, or at a later time over a period of more than 24 h. UTI was observed in 12 (3.2%) patients after endoscopic-instrumental operation, 1 (0.3%) after clean operation, and 1 (0.9%) after clean-contaminated operation. SSI was observed in 2 (0.6%) patients after clean operation but in none after clean-contaminated operations. RI was observed in 1 (0.3%) patient after endoscopic-instrumental operation, 3 (0.9%) after clean operation, and none after clean-contaminated operations. A single-dose regimen of AMP was effective and feasible for the prevention of perioperative infections, including SSIs, UTIs, and RIs, in endoscopic-instrumental, clean, and clean-contaminated urological surgical procedures. PMID- 20734217 TI - Clinical and microbiological characteristics of Klebsiella pneumoniae isolates causing community-acquired urinary tract infections. AB - BACKGROUND: Klebsiella pneumoniae is the second most common species causing urinary tract infections (UTI). However, the host factors and virulence genes of K. pneumoniae related to UTI are poorly understood. The aim of this study was to analyze the capsular phenotype and virulence genes of K. pneumoniae isolates and host factors potentially relevant to community-acquired UTI. METHODS: Fifty-four K. pneumoniae isolates from patients with community-acquired UTI, 76 isolates from healthy adults, and 29 from patients with community-acquired pneumonia were compared. The virulence genes (rmpA, magA, uge, and wabG) and serotype (K1, K2, K5, K20, K54, or K57) were characterized by polymerase chain reaction (PCR). The modified string test was used to determine the hypermucoviscosity. RESULTS: Diabetes mellitus was the most frequent underlying disease among UTI patients (53.7%, 29/54). No predominant K serotype was found in UTI strains. The hypermucoviscosity phenotype and rmpA gene were more often found in UTI isolates than in those from healthy adults (27.8 vs. 2.6%, P < 0.01; 29.6 vs. 11.8%, P < 0.01, respectively), whereas no significant difference in the frequency of magA, uge, wabG, or serotype genes was found. The prevalence of rmpA was significantly lower in isolates from patients with immunosuppression, chronic renal insufficiency, and urinary tract obstruction. Multivariate analysis showed that immunosuppression was negatively associated with the prevalence of rmpA. CONCLUSION: Hypermucoviscosity was highly correlated with the presence of the rmpA gene in UTI strains, and rmpA may have a role in community-acquired UTI, especially in hosts without immunosuppression. PMID- 20734218 TI - Stereotactic radiosurgery for WHO grade I meningiomas. AB - Meningiomas represent a common intracranial tumor in the adult population. Although extirpation to achieve a gross total resection or at least decrease mass effect has been the mainstay of treatment, stereotactic radiosurgery has come to play an increasingly important role in the management of patients with meningiomas. Radiosurgery utilizes highly focused, beams of ionizing radiation to inactivate tumor cells. Image guidance and a steep dose fall off are critical features of this approach. The radiobiology of radiosurgery differs in certain advantageous ways from conventional radiotherapy. Radiosurgery initially was utilized to treat recurrent or residual skull base meningiomas. As success was observed in this setting, radiosurgery has gradually expanded its role so as to treat convexity meningiomas; it is also used as an upfront treatment for patients for whom clinical and neuro-imaging findings are consistent with a meningioma. Most large series demonstrate tumor control rates for patients with grade I meningiomas in excess of 85%. Neurological function is generally preserved or improved for patients with meningiomas. However, complications can occur. Longitudinal follow-up including neurologic and radiologic assessment is required. Single and multisession stereotactic radiosurgery will likely play an expanded role in the treatment of patients with meningiomas. PMID- 20734219 TI - Meningioma mouse models. AB - Meningiomas, although mostly benign, may sometimes present aggressive features and raise issues concerning alternative treatment options besides surgery. In order to gain new insights in meningioma biology and develop alternative treatments, several meningioma mouse models have been engineered during the past two decades. As rodents very rarely develop spontaneous meningiomas, animal models have been first developed by implanting human meningioma cells derived from a primary tumor and meningioma cell lines subcutaneously into athymic mice. Induction of de novo meningiomas in rodents with mutagens, such as nitrosourea, has also been reported. Advances in our understanding of molecular genetics of meningioma have pinpointed the central role of NF2 tumor suppressor gene in the pathogenesis of those tumors. These discoveries have led to the creation of a genetically engineered model utilizing conditional mutagenesis to specifically inactivate the mouse Nf2 gene in arachnoidal cells, resulting in the formation of intracranial meningothelial hyperplasia and meningiomas and thus reproducing the main mechanism of human meningeal tumorigenesis. This powerful new technology significantly improves on prior models and may open avenues of investigation never before possible in meningioma research. We present here a review of current meningioma mouse models used in translational therapeutics with associated imaging and pre-clinical studies. PMID- 20734220 TI - Overexpression of PPARgamma can down-regulate Skp2 expression in MDA-MB-231 breast tumor cells. AB - Skp2 is frequent amplified and overexpressed in breast cancer, making it a potential molecular target for cancer therapy. The objective of this study was to examine the effect of PPARgamma overexpression on Skp2 expression in breast cancer cell lines. First, we investigated the role of PPARgamma and Skp2 in human breast cancer progression. Immunohistochemical analysis of 70 specimens on formalin-fixed paraffin sections was performed. Furthermore in vitro, Western blot analysis was used to study the relationship between PPARgamma and Skp2. We found that the expression of PPARgamma and Skp2 expression was inverse correlation whether in vivo or in vitro. In addition, PPARgamma overexpression can down-regulate the expression of Skp2 mRNA and protein in breast cancer cells. PPARgamma overexpression decreased breast cancer cell proliferation and induced spontaneous apoptosis even in the absence of exogenous ligand. These PPARgamma overexpressing cells were dramatically more sensitive to PPARgamma ligand-induced apoptosis compared with parental or Myc-control transfected cells. Overexpressing of Skp2 partially reversed PPARgamma's pro-apoptotic and anti-proliferative abilities. These results suggested that PPARgamma's pro-apoptotic and anti proliferative abilities appear to be triggered at least in part by the modulation of Skp2. PMID- 20734221 TI - Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism. AB - Vascular endothelial growth factor-C (VEGF-C) has a well-defined action on neoplastic lymphangiogenesis and angiogenesis through VEGF receptor-3 (VEGFR-3) and VEGFR-2, respectively, which are generally expressed in endothelial cells. The function of the VEGF-C/receptors pathway in tumor cell types is largely unknown. In this study, we examined the expression and role of VEGF-C/receptors in gallbladder cancer (GBC) cells. We examined the expression of VEGF-C in 50 surgical specimens from gallbladder cancer and three human gallbladder cancer cell lines. Both siRNA and neutralizing antibody to deplete the expression of VEGF-C were used to characterize the biological effect of VEGF-C in GBC NOZ cells. Furthermore, we examined the expression of its receptors, VEGFR-3 and VEGFR-2, in three human GBC cell lines. Our results are as follows: The expression of VEGF-C in the invasive marginal portion was significantly higher than the expression in the central portions. All the three GBC cell lines expressed VEGF-C. Treatment of NOZ cells with VEGF-C siRNA or a neutralizing antibody suppressed cell proliferation and invasion. Moreover, all the three GBC cell lines expressed VEGFR3, but only the NOZ cells expressed VEGFR-2 mRNA. Treatment of NOZ cells with a VEGFR-3 neutralizing antibody suppressed cell invasion, but treatment of NOZ cells with a VEGFR-2 neutralizing antibody suppressed cell proliferation and invasion. In conclusion, GBC cells express both VEGF-C and its receptors. VEGF-C may have a role in the progressive growth and invasion of human GBC through an autocrine mechanism. PMID- 20734222 TI - Similarity-dissimilarity plot for visualization of high dimensional data in biomedical pattern classification. AB - In pattern classification problems, feature extraction is an important step. Quality of features in discriminating different classes plays an important role in pattern classification problems. In real life, pattern classification may require high dimensional feature space and it is impossible to visualize the feature space if the dimension of feature space is greater than four. In this paper, we have proposed a Similarity-Dissimilarity plot which can project high dimensional space to a two dimensional space while retaining important characteristics required to assess the discrimination quality of the features. Similarity-dissimilarity plot can reveal information about the amount of overlap of features of different classes. Separable data points of different classes will also be visible on the plot which can be classified correctly using appropriate classifier. Hence, approximate classification accuracy can be predicted. Moreover, it is possible to know about whom class the misclassified data points will be confused by the classifier. Outlier data points can also be located on the similarity-dissimilarity plot. Various examples of synthetic data are used to highlight important characteristics of the proposed plot. Some real life examples from biomedical data are also used for the analysis. The proposed plot is independent of number of dimensions of the feature space. PMID- 20734223 TI - Data envelopment analysis model for the appraisal and relative performance evaluation of nurses at an intensive care unit. AB - The appraisal and relative performance evaluation of nurses are very important and beneficial for both nurses and employers in an era of clinical governance, increased accountability and high standards of health care services. They enhance and consolidate the knowledge and practical skills of nurses by identification of training and career development plans as well as improvement in health care quality services, increase in job satisfaction and use of cost-effective resources. In this paper, a data envelopment analysis (DEA) model is proposed for the appraisal and relative performance evaluation of nurses. The model is validated on thirty-two nurses working at an Intensive Care Unit (ICU) at one of the most recognized hospitals in Lebanon. The DEA was able to classify nurses into efficient and inefficient ones. The set of efficient nurses was used to establish an internal best practice benchmark to project career development plans for improving the performance of other inefficient nurses. The DEA result confirmed the ranking of some nurses and highlighted injustice in other cases that were produced by the currently practiced appraisal system. Further, the DEA model is shown to be an effective talent management and motivational tool as it can provide clear managerial plans related to promoting, training and development activities from the perspective of nurses, hence increasing their satisfaction, motivation and acceptance of appraisal results. Due to such features, the model is currently being considered for implementation at ICU. Finally, the ratio of the number DEA units to the number of input/output measures is revisited with new suggested values on its upper and lower limits depending on the type of DEA models and the desired number of efficient units from a managerial perspective. PMID- 20734224 TI - Electrogenic plasma membrane H+-ATPase activity using voltage sensitive dyes. AB - Fast responding voltage sensitive dyes, RH421 and di-4-ASPBS, were used to study the electrogenic properties of plant plasma membrane proton pumps on sealed plasma membrane vesicles extracted by two-phase partitioning from Beta vulgaris and Avena sativa cv Swan root material. Fluorescence spectroscopy in the presence of the dye RH421 (10.8 nM) was sufficiently sensitive to detect electrogenic activity of the extracted plant vesicles. The dye detection system could detect inhibition of electrogenic activity of vesicles by vanadate (75 MUM) and stimulation by nigericin (0.5 MUM). The newly developed dye di-4-ASPBS was less sensitive to detecting the electrogenic proton pump activity. This study represents an important innovation in plant biophysics as this class of fast responding voltage sensitive dyes have never to our knowledge been used to study electrogenic proton pump activity derived from plant membranes and represents a novel approach for carrying out such studies. PMID- 20734225 TI - Brief report: Schema consistent misinformation effects in eyewitnesses with autism spectrum disorder. AB - A number of studies have demonstrated schema-related misinformation effects in typical individuals, but no research to date has examined this with witnesses with autism spectrum disorder (ASD), despite their impaired ability to generate core elements that define everyday events. After witnessing slides depicting a bank robbery, 16 adults with ASD and 16 matched comparison individuals were exposed to post-event misinformation that was either schema typical or atypical. Consistent with previous work, the comparison group went onto report more schema typical misinformation than atypical misinformation. However, so too did the ASD group, suggesting that individuals with ASD do have understanding of the causal links between events, persons and actions, an important finding from both theoretical and applied perspectives. PMID- 20734226 TI - HIV infection, sexual behaviors, sexual networks, and drug use among rural residents in Yunnan Province, China. AB - This cross-sectional study examined HIV prevalence, sexual behaviors, sexual networks, and drug use among 591 participants from a rural community in Yunnan Province, China. Face-to-face interviews were conducted to collect information about sexual behavior, drug use, and sexual networks. Blood samples were collected and tested for HIV. Of the participants, 52.6% were male and 62.6% were Jingpo minority. The HIV prevalence was 5.5% overall and highest among the Jingpo minority (7.7%). Most participants were sexually experienced and 32.5% had had multiple sex partners. About 18.8% had used drugs, with the highest proportion among the Jingpo minority. HIV infection was independently correlated with drug use among males and with multiple sexual partnerships among females. A total of 336 independent sexual network components (mostly small, linear, and acyclic) were constructed. Eighty-percent were dyads involving two members and 20% involved three to 71 members. Coupled with the promotion of condom use, gender- and network-specific efforts are needed for HIV prevention targeting ethnic minorities in Yunnan. PMID- 20734227 TI - Longitudinal association of HIV conspiracy beliefs with sexual risk among black males living with HIV. AB - Research is needed to identify culturally relevant factors that may contribute to sexual risk among African Americans. We investigated HIV-specific medical mistrust as one such cultural factor, often exhibited as conspiracy beliefs about HIV (e.g., "AIDS was produced in a government laboratory"), which may be indicative of general suspicion of HIV treatment and prevention messages. Over a 6-month time-period, we measured endorsement of HIV conspiracy beliefs three times and frequency of condom use monthly among 181 HIV-positive African American males. A hierarchical multivariate repeated-measures logistic random effects model indicated that greater belief in HIV conspiracies was associated with a higher likelihood of reporting unprotected intercourse across all time-points. An average of 54% of participants who endorsed conspiracies reported unprotected intercourse, versus 39% who did not endorse conspiracies. Secondary prevention interventions may need to address medical mistrust as a contributor to sexual risk among African Americans living with HIV. PMID- 20734228 TI - Minimally invasive assessment of tumor angiogenesis by fine needle aspiration and flow cytometry. AB - The development of a new, less invasive, and more rapidly implemented method of quantifying endothelial cell density in tumors could facilitate experimental and clinical studies of angiogenesis. Therefore, we evaluated the utility of tumor fine needle aspiration (FNA) coupled with flow cytometry for assessment of tumor angiogenesis. Samples were obtained from cutaneous tumors of mice using FNA, then immunostained and assessed by flow cytometry to determine the number of CD31(+) endothelial cells. Results of the FNA/flow cytometry technique were compared with quantification of tumor microvessel density using immunohistochemistry. The ability of the FNA/cytometry technique to quantify the effects of anti-angiogenic therapy and to monitor changes in tumor angiogenesis over time in individual tumors was also determined. We found that endothelial cell percentages determined in tumor tissue aspirates by flow cytometry correlated well with the percentages of endothelial cells determined in whole tumor digests by flow cytometry and with tumor microvessel density measurements by immunohistochemistry. Moreover, we found that repeated FNA sampling of tumors did not induce endothelial cell changes. Interestingly, by employing repeated FNA sampling of the same tumors we were able to observe a sudden and marked decline in tumor angiogenesis triggered when tumors reached a certain size. Thus, we conclude that the FNA/flow cytometry technique is an efficient, reproducible, and relatively non-invasive method of rapidly assessing tumor angiogenesis, which could be readily applied to evaluation of tumor angiogenesis in clinical settings in humans. PMID- 20734229 TI - 2-deoxyribose deprives cultured astrocytes of their glutathione. AB - High concentrations of 2-deoxy-D-ribose (2dRib) have been reported to cause oxidative stress and to disturb the glutathione (GSH) metabolism of various cell types. Exposure of astrocyte-rich primary cultures to millimolar concentrations of 2dRib or its stereoisomer 2-deoxy-L-ribose, but not the incubation with ribose, 2-deoxyglucose, glucose, fructose or saccharose, lowered the cellular GSH content in a time and concentration dependent manner. After exposure for 4 h to 30 mM 2dRib the cells contained 2dRib in a concentration of about 24 mM. Under these conditions 2dRib did not compromise cell viability and the ability of the cells to synthesise GSH, nor were the cellular ratio of glutathione disulfide (GSSG) to GSH and the extracellular concentrations of GSH or GSSG increased. These data demonstrate that 2dRib deprives viable cultured astrocytes of GSH and suggest that a cellular reaction of GSH with 2dRib or its metabolites is involved in the deprivation of astrocytic GSH. PMID- 20734230 TI - Thiamine and oxidants interact to modify cellular calcium stores. AB - Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimer's disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant. The current experiments first tested directly whether thiamin could act as an antioxidant, and then examined the physiological relevance of the antioxidant properties on oxidant sensitive, calcium dependent processes that are altered in AD. The first group of experiments examined whether thiamin could diminish reactive oxygen species (ROS) or reactive nitrogen species (RNS) produced by two very divergent paradigms. Dose response curves determined the concentrations of t-butyl-hydroperoxide (t-BHP) (ROS production) or 3 morpholinosydnonimine ((SIN-1) (RNS production) to induce oxidative stress within cells. Concentrations of thiamine that reduced the RNS in cells did not diminish the ROS. The second group of experiments tested whether thiamine alters oxidant sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. On the other hand, thiamine diminished the effect of RNS on CCE. These data are consistent with thiamine diminishing the actions of the RNS, but not ROS, on physiological targets. Thus, both experimental approaches suggest that thiamine selectively alters RNS. Additional experiments are required to determine whether diminished thiamine availability promotes oxidative stress in AD or whether the oxidative stress in AD brain diminishes thiamine availability to thiamine dependent processes. PMID- 20734231 TI - The Patient Assessment of Chronic Illness Care questionnaire: evaluation in patients with mental disorders in primary care. AB - The Chronic Care Model provides evidence-based recommendations to improve the care for patients with chronic conditions. The Patient Assessment of Chronic Illness Care questionnaire (PACIC) is an instrument to evaluate the patient's perspective on receipt of care delivered in the five domains patient activation, delivery system, goal setting, problem solving, and follow-up. The aim of this study was to assess the psychometric characteristics of the PACIC in 442 primary care patients with major depression. The psychometric properties were good. We found possible ceiling effects in the two subscales 'patient activation' (12.9%) and 'problem solving/contextual' (8.9%), as well as floor effects in 'goal setting/tailoring' (4.6%). The Cronbach's alpha coefficient for the total scale was excellent (0.91). We found two major factors, which we labeled according to the PACIC domains as composite factors 'patient activation and problem solving' as well as 'goal setting and coordination'. The perspective of patients with mental disorders, such as depression, on primary chronic illness care can be assessed adequately by the PACIC. PMID- 20734232 TI - Carotenoid biosynthesis in diatoms. AB - Diatoms are ubiquitous and constitute an important group of the phytoplankton community having a major contribution to the total marine primary production. These microalgae exhibit a characteristic golden-brown colour due to a high amount of the xanthophyll fucoxanthin that plays a major role in the light harvesting complex of photosystems. In the water column, diatoms are exposed to light intensities that vary quickly from lower to higher values. Xanthophyll cycles prevent photodestruction of the cells in excessive light intensities. In diatoms, the diadinoxanthin-diatoxanthin cycle is the most important short-term photoprotective mechanism. If the biosynthetic pathways of chloroplast pigments have been extensively studied in higher plants and green algae, the research on carotenoid biosynthesis in diatoms is still in its infancy. In this study, the data on the biosynthetic pathway of diatom carotenoids are reviewed. The early steps occur through the 2-C-methyl-D: -erythritol 4-phosphate (MEP) pathway. Then a hypothetical pathway is suggested from dimethylallyl diphosphate (DMAPP) and isopentenyl pyrophosphate (IPP). Most of the enzymes of the pathway have not been so far isolated from diatoms, but candidate genes for each of them were identified using protein similarity searches of genomic data. PMID- 20734233 TI - Speckle tracking: distinction of physiologic from pathologic LVH? PMID- 20734234 TI - ASCI 2010 appropriateness criteria for cardiac magnetic resonance imaging: a report of the Asian Society of Cardiovascular Imaging cardiac computed tomography and cardiac magnetic resonance imaging guideline working group. AB - There has been a growing need for standard Asian population guidelines for cardiac CT and cardiac MR due to differences in culture, healthcare system, ethnicity and disease prevalence. The Asian Society of Cardiovascular Imaging, as the only society dedicated to cardiovascular imaging in Asia, formed a cardiac CT and cardiac MR guideline working group in order to help Asian practitioners to establish cardiac CT and cardiac MR services. In this ASCI cardiac MR appropriateness criteria report, 23 Technical Panel members representing various Asian countries were invited to rate 50 indications that can frequently be encountered in clinical practice in Asia. Indications were rated on a scale of 1 9 to be categorized into 'appropriate' (7-9), 'uncertain' (4-6), or 'inappropriate' (1-3). According to median scores of the 23 members, the final ratings for indications were 24 appropriate, 18 uncertain and 8 inappropriate with 22 'highly-agreed' (19 appropriate and 3 inappropriate) indications. This report is expected to have a significant impact on the cardiac MR practices in many Asian countries by promoting the appropriate use of cardiac MR. PMID- 20734235 TI - Prevalence and extent of coronary artery disease determined by 64-slice CTA in patients with zero coronary calcium score. AB - The purpose of the study was to assess the presence and extent of atherosclerosis determined by 64-slice CTA in patients with 0 coronary calcium score (CACS) and to evaluate the affect of demographic features and risk factors on the atheroma burden of these patients. 883 cases (378 (42.8%) male, 505 (57.2%) female, mean age 51.28) with zero CACS were included in the study. Cases underwent CTA because of carrying risk factors or having chest pain or atypical symptoms. A non enhanced CT scan was obtained for calcium scoring immediately before CTA in all cases. CT examinations were performed by 64-slice scanner (Toshiba, Aquillon 64, Toshiba Medical Systems, Otowara, Japan). Coronary artery disease (CAD) was graded according to CTA findings and five groups were defined. In 703 cases (79.6%) CTA was normal while 180 (20.4%) cases had positive CTA findings and 43 cases (4.9%) had CTA obstructive lesion. Cases with positive CTA findings were significantly older than those with normal CTA Diabetes was a significant risk factor of CAD in both male and female cases. Dyslipidemia was associated with CAD in males and family history of CAD was a significant risk factor for females with positive CTA findings. This study demonstrated that considerable amount of patients with zero CAC score have positive CTA findings. Age and diabetes are the risk factors, which were associated with positive CTA findings in both sexes. Dyslipidemia was a significant risk factor in males and family history of CAD in females. Especially in patients with risk factors CTA is better than CAC scoring in determining the atheroma burden. PMID- 20734236 TI - Thymoma associated with malignancies may herald a hereditary cancer syndrome. AB - Two probands with thymoma and other primary malignancies with multiple cancer patients in the family are described. Types of malignancies, pattern of pedigree and age of the patients do not match the known familial cancer syndromes. One proband was a very rare case with five discrete primary malignancies; TP53 sequencing and karyotyping did not reveal any mutations. These cases suggest thymoma associated malignancies may herald a hereditary cancer syndrome. PMID- 20734237 TI - Lower efficacy in the utilization of dietary ALA as compared to preformed EPA + DHA on long chain n-3 PUFA levels in rats. AB - We made a comparative analysis of the uptake, tissue deposition and conversion of dietary alpha-linolenic acid (ALA) to its long chain metabolites eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with preformed EPA + DHA. Diets containing linseed oil [with ALA at approximately 2.5 (4 g/kg diet), 5 (8 g/kg diet), 10 (16 g/kg diet), 25% (40 g/kg diet)] or fish oil [with EPA + DHA at approximately 1 (1.65 g/kg diet), 2.5 (4.12 g/kg diet), 5% (8.25 g/kg diet)] or groundnut oil without n-3 polyunsaturated fatty acids (n-3 PUFA) were fed to rats for 60 days. ALA and EPA + DHA in serum, liver, heart and brain increased with increments in the dietary ALA level. When preformed EPA + DHA were fed, the tissue EPA + DHA increased significantly compared to those given ALA. Normalized values from dietary n-3 PUFA to tissue EPA + DHA indicated that 100 mg of dietary ALA lead to accumulation of EPA + DHA at 2.04, 0.70, 1.91 and 1.64% of total fatty acids respectively in liver, heart, brain and serum. Similarly 100 mg of preformed dietary EPA + DHA resulted in 25.4, 23.8, 15.9 and 14.9% of total fatty acids in liver, heart, brain and serum respectively. To maintain a given level of EPA + DHA, the dietary ALA required is 12.5, 33.5, 8.3 and 9.1 times higher than the dietary EPA + DHA for liver, heart, brain and serum respectively. Hence the efficacy of precursor ALA is lower compared to preformed EPA + DHA in elevating serum and tissue long chain n-3 PUFA levels. PMID- 20734239 TI - The effects of vanadium (V) absorbed by Coprinus comatus on bone in streptozotocin-induced diabetic rats. AB - The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats were given physiological saline, and VACC-treated rats were administered VACC intragastrically at doses of 0.18 mg vanadium/kg body weight once daily. Treatments were performed over a 12-week period. At sacrifice, one tibia and one femur were removed, subjected to micro computed tomography (micro-CT) for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. Another femoral was used for mechanical testing. In addition, bone samples were collected to evaluate the content of mineral substances in bones. Treatment with VACC increased trabecular bone volume fraction in diabetic rats. Vanadium-treated animals had significant increases in ultimate load, trabecular thickness, and osteoblast surface. However, vanadium treatment did not seem to affect bone stiffness, bone energy absorption, trabecular separation, and osteoclast number. P levels in the femurs of diabetic rats treated with VACC were significantly higher than those of diabetic animals. Ca levels in diabetic and diabetic rats treated with vanadium showed no obvious changes. In conclusion, our results provide an important proof of concept that VACC may represent a powerful approach to treating or reversing diabetic osteopathy in humans. PMID- 20734238 TI - A high legume low glycemic index diet improves serum lipid profiles in men. AB - Clinical studies have shown that fiber consumption facilitates weight loss and improves lipid profiles; however, the beneficial effects of high fermentable fiber low glycemic index (GI) diets under conditions of weight maintenance are unclear. In the Legume Inflammation Feeding Experiment, a randomized controlled cross-over feeding study, 64 middle-aged men who had undergone colonoscopies within the previous 2 years received both a healthy American (HA) diet (no legume consumption, fiber consumption = 9 g/1,000 kcal, and GI = 69) and a legume enriched (1.5 servings/1,000 kcal), high fiber (21 g/1,000 kcal), low GI (GI = 38) diet (LG) in random order. Diets were isocaloric and controlled for macronutrients including saturated fat; they were consumed each for 4 weeks with a 2-4 week break separating dietary treatments. Compared to the HA diet, the LG diet led to greater declines in both fasting serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (P < 0.001 and P < 0.01, respectively). Insulin-resistant (IR) subjects had greater reductions in high density lipoprotein cholesterol (HDL-C; P < 0.01), and triglycerides (TAG)/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. Insulin-sensitive (IS) subjects had greater reductions in TC (P < 0.001), LDL-C (P < 0.01), TC/HDL-C (P < 0.01), and LDL-C/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. In conclusion, a high legume, high fiber, low GI diet improves serum lipid profiles in men, compared to a healthy American diet. However, IR individuals do not achieve the full benefits of the same diet on cardiovascular disease (CVD) lipid risk factors. PMID- 20734240 TI - Effects of zinc glycine chelate on oxidative stress, contents of trace elements, and intestinal morphology in broilers. AB - Three hundred and sixty healthy Ross * Ross 1-day-old broilers were used to study the effects of zinc glycine chelate (Zn-Gly) on oxidative stress, contents of trace elements, and intestinal morphology. All broilers were randomly assigned to six treatment groups, which replicates three times. Diets were as follows: (1) control (containing 29.3 mg zinc (Zn)/kg basic diet (0-21 days) and 27.8 mg Zn/kg (22-42 days)); (2) basic diet plus 30 mg Zn/kg from Zn-Gly; (3) basic diet plus 60 mg Zn/kg from Zn-Gly; (4) basic diet plus 90 mg Zn/kg from Zn-Gly; (5) basic diet plus 120 mg Zn/kg from Zn-Gly; and (6) positive control, basic diet plus 120 mg Zn/kg from zinc sulfate (ZnSO(4)). The results showed that the addition of 90 or 120 mg/kg Zn-Gly led to an improvement of activity of Cu/Zn superoxide dismutase and glutathione peroxidase and a reduction of malondialdehyde content in livers at 21 and 42 days. With 90 mg/kg Zn-Gly, the content of sera zinc increased by 17.55% (P < 0.05) in 21-day broilers and 10.77% (P > 0.05) in 42-day broilers compared with that of the control. Adding 120 mg/kg Zn-Gly or ZnSO(4) to broilers' diets greatly enhanced the content of zinc in feces at 21 days (P < 0.05) and at 42 days (P < 0.05). For 42-day chickens, increased villus height and decreased crypt depth of the jejunum could be observed in the second growth stage of broilers fed with 90 mg/kg Zn-Gly. Also, intestinal wall thickness decreased (P < 0.05). In addition, adding 90 mg/kg Zn-Gly to the diet markedly elevated villus length of duodenum and decreased crypt depth of ileum (P < 0.05) in 42-day broilers. PMID- 20734241 TI - Assessment of molybdenum status in soil and forage for ruminant production under semiarid environmental conditions in Sargodha, Pakistan. AB - The present investigation was carried out to determine the molybdenum (Mo) status of soil and forage at the Livestock Experimental Station, Khizer abad, Sargodha, Pakistan. This site falls under semiarid climatic conditions. Soil and forage samples were collected on a monthly basis during the winter season (from October through January) and analyzed after wet digestion to determine the effect of sampling intervals on Mo content as well as its transfer from soil to forage during the whole study period. The effect of sampling intervals on soil Mo content was found to be highly significant, but in contrast, this effect on forage Mo was nonsignificant. The Mo content of soil was found to be highly sufficient to meet the requirement of forage crops, whereas those of forage at the borderline of the ruminant requirement is insufficient. It is expected that with time, further depletion of Mo in the pasture soil due to interaction with Cu and other antagonistic elements may take place, which could finally lower Mo levels in the forage being used for rearing livestock. Thus, at some stage in the future, addition of standard fertilizers enriched with Mo to the soils may be required at the livestock farm. PMID- 20734242 TI - Abstracts of the Neurocritical Care Society 8th Annual Meeting. September 15-18, 2010. San Francisco, California, USA. PMID- 20734243 TI - Advanced imaging assessment of posterior circulation stroke before and after endovascular intervention. AB - BACKGROUND: Perfusion-computed tomography (CTP) is a relatively new technique that allows rapid semiquantitative noninvasive evaluation of cerebral perfusion aiding in the diagnosis of cerebral ischemia and infarction. There is a paucity of data on its application within the posterior circulation, especially, the brainstem. We describe a case of basilar artery thrombosis with cerebellar and brainstem CTP mismatch and discuss possible future applications of CTP for acute posterior fossa circulation and infarction. METHODS: Case report. RESULTS: Successful use of CTP to aid in decision to proceed with neurointervention in acute basilar artery occlusion and confirm its resolution after mechanical clot retrieval. CONCLUSION: Perfusion-computed tomography can successfully be used to define cerebral ischemia and infarction within the posterior fossa and aid in decisions to proceed with neurointervention. PMID- 20734244 TI - Prognostic factors of spinal cord decompression sickness in recreational diving: retrospective and multicentric analysis of 279 cases. AB - BACKGROUND: This study aims to determine the potential risk factors associated with the development of severe diving-related spinal cord decompression sickness (DCS). METHODS: Two hundred and seventy nine injured recreational divers (42 +/- 12 years; 53 women) presenting symptoms of spinal cord DCS were retrospectively included from seven hyperbaric centers in France and Belgium. Diving information, symptom latency after surfacing, time interval between symptom onset and hyperbaric treatment were studied. The initial severity of spinal cord DCS was rated with the Boussuges severity score, and the presence of sequelae was evaluated at 1 month. Initial recompression treatment at 2.8 ATA with 100% oxygen breathing or deeper recompression up to 4 or 6 ATA with nitrogen or helium-oxygen breathing mixture were also recorded. RESULTS: Twenty six percent of DCS had incomplete resolution after 1 month. Multivariate analysis revealed several independent factors associated with a bad recovery: age >= 42 [OR 1.04 (1-1.07)], depth >= 39 m [OR 1.04 (1-1.07)], bladder dysfunction [OR 3.8 (1.3-11.15)], persistence or worsening of clinical symptoms before recompression [OR 2.07 (1.23 3.48)], and a Boussuges severity score >7 [OR 1.16 (1.03-1.31)]. However, the time to recompression and the choice of initial hyperbaric procedure did not significantly influence recovery after statistical adjustment. CONCLUSIONS: Clinical symptoms of spinal cord DCS and their initial course before admission to the hyperbaric center should be considered as major prognostic factors in recovery. A new severity score is proposed to optimize the initial clinical evaluation for spinal cord DCS. PMID- 20734246 TI - Positron emission tomography inter-scanner differences in dopamine D2 receptor binding measured with [11C]FLB457. AB - OBJECTIVE: It is well known that the positron emission tomography (PET) system is subject to inter-scanner differences of regional radioactivity distribution. In the present study, the effect of inter-scanner difference of regional radioactivity on estimated binding potential (BP(ND)) of [11C]FLB457 using the simplified reference tissue model (SRTM) was investigated. METHODS: Each of the 11 subjects was given two PET scans using [11C]FLB457, one each with both SET 3000 GCT/X (Shimadzu) and with ECAT EXACT HR+ (Siemens/CTI). In order to assess regional differences between the two scanners, estimated BP(ND) values in six volumes of interest (VOIs) by SRTM method were compared in both individual PET space and anatomical template space after anatomical normalization. Statistical voxel-by-voxel paired t test of BP(ND) images between SET-3000 GCT/X and ECAT EXACT HR+ was also performed. RESULTS: Shapes of time-activity curves of the two PET scanners were slightly different in each VOI, with estimated BP(ND) values from ECAT EXACT HR+ appearing greater in the cerebral cortical regions and thalamus than that of SET-3000 GCT/X in both individual PET space and anatomical template space after anatomical normalization. Statistical voxel-by-voxel analysis showed similar tendency to BP(ND) value estimation, with greater BP(ND) values from ECAT EXACT HR+ than from SET-3000 GCT/X. CONCLUSIONS: We demonstrated the inter-scanner differences in dopamine D(2) receptor binding measured with [11C]FLB457. In particular, statistically significant differences of BP(ND) in certain regions were observed between two PET scanners, despite the subject groups being the same. Our results suggest that we reconsider the effect of the scanner model on the measurement of receptor binding. PMID- 20734245 TI - Follicle-stimulating hormone regulation of microRNA expression on progesterone production in cultured rat granulosa cells. AB - MicroRNAs (miRNAs) regulate gene expression post-transcriptionally by interacting with the 3' untranslated regions of their target mRNAs. Previously, miRNAs have been shown to regulate genes involved in cell growth, apoptosis, and differentiation, but their role in ovarian granulosa cell follicle-stimulating hormone (FSH)-stimulated steroidogenesis is unclear. Here we show that expression of 31 miRNAs is altered during FSH-mediated progesterone secretion of cultured granulosa cells. Specifically, 12 h after FSH treatment, miRNAs mir-29a and mir 30d were significantly down-regulated. However, their expression increased after 48 h. Bioinformatic analysis used to predict potential targets of mir-29a and mir 30d revealed a wide array of potential mRNA target genes, including those encoding genes involved in multiple signaling pathways. Taken together, our results pointed to a novel mechanism for the pleiotropic effects of FSH. PMID- 20734247 TI - Themes and variation of N. S. Thompson--song. AB - Nick Thompson studied many animals over the course of his career, including non human primates, dogs, crows, human babies, and mockingbirds. Amidst such variation, Nick maintained a common focus. He sought to provide more accurate and truthful representations of the particular phenomenon of interest. His writings on mentalism, design, anthropomorphism and use of metaphor have provided fellow scientists with insight and helped advance his field of study. PMID- 20734248 TI - The Nrf2-Keap1 cellular defense pathway and heat shock protein 70 (Hsp70) response. Role in protection against oxidative stress in early neonatal unilateral ureteral obstruction (UUO). AB - Perturbation of renal tubular antioxidants and overproduction of reactive oxygen species may amplify the proinflammatory state of renal obstruction, culminating in oxidative stress and tubular loss. Here, we analyzed the heat shock protein 70 (Hsp70) response and the function and signal transduction of NF-E2-related protein 2 (Nrf2) transcription factor on oxidative stress modulation in obstruction. Rats were subjected to unilateral ureteral obstruction or sham operation and kidneys harvested at 5, 7, 10, and 14 days after obstruction. Hsp70 expression and Nrf2 activity and its downstream target gene products were assessed. After 10 and 14 days of obstruction, enhanced lipid peroxidation through higher thiobarbituric acid reactive substances levels and increased oxidative stress resulted in reduced total antioxidant activity and enhanced nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity were demonstrated. This was accompanied by decreased inducible Hsp70 expression and a progressive reduction of nuclear Nrf2 and its target gene products glutathione S transferase A2 (GSTA2) and NADPH/quinone oxidoreductase 1 (NQO1), whereas the Nrf2 repressor Kelch-like ECH-associated protein-1 (Keap1) was upregulated. By contrast, on early obstruction for 7 days, lack of increased oxidative markers associated with higher inducible Hsp70 protein levels and a rapid nuclear accumulation of Nrf2, Keap1 downregulation, and mRNA induction of the identified Nrf2-dependent genes, NQO1 and GSTA2, were shown. For these results, we suggest that the magnitude of cytoprotection in early obstruction depends on the combined contribution of induced activation of Nrf2 upregulating its downstream gene products and Hsp70 response. Impaired ability to mount the biological response to the prevailing oxidative stress leading to renal injury was shown in prolonged obstruction. PMID- 20734250 TI - Growth protocols for model plants in developmental biology. AB - Arabidopsis is the dominating model species for plant developmental biology, but other species serve as models for processes that cannot be studied in Arabidopsis, such as compound leaf or wood formation, or to test the universality of developmental mechanisms initially identified in Arabidopsis. Research in plant developmental biology depends critically on robust growth protocols that will support reproducible development. Here, protocols are given to grow Antirrhinum, Arabidopsis, Brachypodium, maize, Medicago, Petunia, rice, and tomato in the laboratory. PMID- 20734249 TI - Inducers of chemical hypoxia act in a gender- and brain region-specific manner on primary astrocyte viability and cytochrome C oxidase. AB - Oxygen is the ultimate electron acceptor for mitochondrial respiration, a process catalyzed by cytochrome c oxidase (COX). In mammals, oxygen concentration regulates gene transcription of COX subunit IV isoforms. Here, we demonstrate that chemical hypoxia, i.e. inhibition of mitochondrial respiration by application of the COX inhibitors cobalt, cyanide, and azide, affects COX isoform IV-1 and IV-2 transcription in a gender- and brain region-specific way. After treatment with cyanide and cobalt, female cortical and mesencephalic astrocytes, respectively, revealed an up-regulation of COX IV-2 which was accompanied by increased ROS production and necrotic cell death. In male astrocytes, the ratio of COX IV-1/COX IV-2 was lowest after treatment with cobalt and paralleled by highest levels of ROS production and necrosis. These results support the view of a causal correlation of COX IV-2 transcription with cellular oxidative stress and cell death and highlight a gender specificity of these effects. By comparing three toxins, cobalt represented the most potent inducer of overall cell death and resembled most closely the previously observed effects of oxygen deprivation on decreasing the cox4i1/cox4i2 ratio. Overall, an increased sensitivity of male compared with female cell viability towards the toxins was detected. These regulatory responses might be causative for the known gender specificity of toxic and neurodegenerative processes in the brain. PMID- 20734251 TI - Grafting as a research tool. AB - Grafting as a means to connect different plant tissues has been enormously useful in many studies of long-distance signalling and transport in relation to regulation of development and physiology. There is an almost infinite number of pairwise graft combinations that can be tested, typically between two different genotypes and/or between plants previously exposed to different environmental treatments. Grafting experiments are especially powerful for unambiguous demonstration of spatial separation of source and target, including genetic complementation of mutant phenotypes across a graft union, direct detection of transmitted molecules in receiving tissue or vascular sap, and activation or suppression of molecular targets due to signal transmission. Although grafting has a long history in research, only in the past decade has it been applied extensively to the Arabidopsis model. This chapter compares the main Arabidopsis grafting methods now available and describes seedling grafting in detail. Information is also provided on grafting of other common research model species, together with outlines of some successful applications. PMID- 20734252 TI - Virus-induced gene silencing as a reverse genetics tool to study gene function. AB - Reverse genetics has proven to be a powerful approach to elucidating gene function in plants, particularly in Arabidopsis. Virus-induced gene silencing (VIGS) is one such method and achieves reductions in target gene expression as the vector moves into newly formed tissues of inoculated plants. VIGS is especially useful for plants that are recalcitrant for transformation and for genes that cause embryo lethality. VIGS provides rapid, transient knockdowns as a complement to other reverse genetics tools and can be used to screen sequences for RNAi prior to stable transformation. High-throughput, forward genetic screening is also possible by cloning libraries of short gene fragments directly into a VIGS plasmid DNA vector, inoculating, and then looking for a phenotype of interest. VIGS is especially useful for studying genes in crop species, which currently have few genetic resources. VIGS facilitates a rapid comparison of knockdown phenotypes of the same gene in different breeding lines or mutant backgrounds, as the same vector is easily inoculated into different plants. In this chapter, we briefly discuss how to choose or construct a VIGS vector and then how to design and carry out effective experiments using VIGS. PMID- 20734253 TI - The CRE/lox system as a tool for developmental studies at the cell and tissue level. AB - Targeted gene manipulation has been used in the last few decades for better understanding of gene function. Most often mutant or overexpression genotypes are analyzed, but in many cases these are not sufficient to obtain a detailed picture on the mode of action of the corresponding protein. For example, many mutations result in pleiotropic or early phenotypic effects thereby affecting the whole organism. Conditional complementation or deletion of the gene under study in a specific cell or tissue can elucidate its exact role in a specific region within a certain time frame. Implementation of several site-specific recombination systems such as CRE/lox has created powerful tools to study the role of many genes at the cellular level. In this chapter, we describe in detail protocols for the application of a two-vector based CRE/lox system, enabling controlled timing and position of gain or loss of function clonal analyses. PMID- 20734254 TI - Inducible gene expression systems for plants. AB - Several systems for induction of transgene expression in plants have been described recently. Inducible systems were used mainly in tobacco, rice, Arabidopsis, tomato, and maize. Inducible systems offer researchers the possibility to deregulate gene expression levels at particular stages of plant development and in particular tissues of interest. The more precise temporal and spatial control, obtained by providing the transgenic plant with the appropriate chemical compound or treatment, permits to analyze also the function of those genes required for plant viability. In addition, inducible systems allow promoting local changes in gene expression levels without causing gross alterations to the whole plant development. Here, protocols will be presented to work with five different inducible systems: AlcR/AlcA (ethanol inducible); GR fusions, GVG, and pOp/LhGR (dexamethasone inducible); XVE/OlexA (beta-estradiol inducible); and heat shock induction. PMID- 20734255 TI - Trichome development in Arabidopsis. AB - Arabidopsis trichomes are giant single epidermal cells that are easily accessible for genetic, genomic and cell-biological analysis. They have therefore become a convenient model system to study developmental and physiological processes. Trichome studies are greatly facilitated by methods specifically applicable for this particular cell type. In addition, it is very important to use conventions and definitions that have been developed to make studies comparable and capture the relevant aspects. This chapter will highlight these two aspects of trichome analysis. PMID- 20734256 TI - Phenotyping the development of leaf area in Arabidopsis thaliana. AB - The study of leaf expansion began decades ago and has covered the comparison of a wide range of species, genotypes of a same species and environmental conditions or treatments. This has given rise to a large number of potential protocols for today's leaf development biologists. The final size of the leaf surface of a plant results from the integration of many different processes (which may be quantified by various developmental variables) at different organizational levels, such as, the duration and the rate of leaf production by the plant, the duration and the rate of individual leaf expansion, and also cell production and expansion in the leaf. There is much evidence to suggest that the magnitude of a variable at one organizational scale cannot be inferred to another scale because of different feedbacks from one scale to another. This chapter offers a series of protocols, which are the most commonly used in plant developmental biology, to assess quantitatively leaf expansion both at the scale of the shoot and the individual leaf. The protocols described here are for the comparison of Arabidopsis thaliana genotypes, but can be easily adapted to compare leaf expansion under different environmental conditions and in other dicotyledonous plants. PMID- 20734257 TI - Analyzing shoot apical meristem development. AB - The shoot apical meristem of Arabidopsis thaliana contains a reservoir of pluripotent stem cells that functions as a continuous source of new cells for organ formation during development. The SAM forms during embryogenesis, when it becomes stratified into specific cell layers and zones that can be delineated based on morphological and molecular criteria. The primary SAM produces all the aerial structures of the adult plant, and alterations in SAM organization or function can have profound effects on vegetative and reproductive plant morphology. Such SAM-specific defects can be identified, evaluated, and quantified using specialized microscopic and histological techniques. PMID- 20734258 TI - Analyzing floral meristem development. AB - Flowers contain the male and female sexual organs that are critical for plant reproduction and survival. Each individual flower is produced from a floral meristem that arises on the flank of the shoot apical meristem and consists of four organ types: sepals, petals, stamens, and carpels. Because floral meristems contain a transient stem-cell pool that generates a small number of organs composed of a limited number of cell types, they are excellent model systems for studying stem-cell maintenance and termination, cell fate specification, organ morphogenesis, and pattern formation. PMID- 20734259 TI - Female gametophytic mutants: diagnosis and characterization. AB - In plants, gametes are formed in multicellular haploid structures, termed gametophytes. The female gametophyte of most higher plants comprises seven cells, which develop from a single haploid spore through nuclear proliferation and subsequent cellularization. The female gametophytic cells differentiate into four distinct cell types, which play specific roles during fertilization and seed formation thereby ensuring reproductive success. In recent years many new techniques and cell type-specific marker lines have been established, making the female gametophyte an attractive system to study mechanisms of reproduction as well as cell specification. The following chapter describes a basic protocol for, first of all, recognizing a female gametophytic mutant and subsequently analyzing the phenotype on a morphological, molecular, and functional level. PMID- 20734260 TI - Pollen tube development. AB - Pollen tubes grow rapidly in a strictly polarized manner as they transport male reproductive cells through female flower tissues to bring about fertilization. Vegetative pollen tube cells are an excellent model system to investigate processes underlying directional cell expansion. In this chapter, we describe materials and methods required for (1) the identification of novel factors essential for polarized cell growth through the isolation and analysis of Arabidopsis mutants with defects in pollen tube growth and (2) the detailed functional characterization of pollen tube proteins based on transient transformation and microscopic analysis of cultured tobacco pollen tubes. PMID- 20734261 TI - Analysis of root meristem size development. AB - Plant post-embryonic development takes place in the meristems. In the root of the model plant Arabidopsis thaliana, stem cells organized in a stem-cell niche in the apex of the root meristem generate transit-amplifying cells, which undergo additional division in the proximal meristem and differentiate in the elongation/differentiation zone. For meristem maintenance, and therefore continuous root growth, the rate of cell differentiation must equal the rate of generation of new cells: how this balance is achieved is a central question in plant development. We have shown that maintenance of the Arabidopsis root meristem size is established by a balance between the antagonistic effects of cytokinin, which promotes cell differentiation, and auxin, which promotes cell division. Cytokinin antagonizes auxin in a specific developmental domain (the vascular tissue transition zone) from where it controls the differentiation rate of all the other root tissues. Here, we describe protocols to analyze development of root meristems. PMID- 20734262 TI - Phenotypic characterization of photomorphogenic responses during plant development. AB - Light is one of the most important exogenous factors regulating plant development throughout the entire life cycle. Light is involved in the breaking of seed dormancy, the regulation of photomorphogenic seedling development, the adaptation of plant morphology toward spectral composition of incident light, and the transition to flowering. Plants have evolved with several photoreceptor families that sense UV-A, blue, red, and far-red light. Here, basal methods to measure light-regulated changes in plant morphology and pigment accumulation will be described. The methods include the determination of apical hook angle and cotyledon opening, the measurement of stem elongation, the determination of leaf surface area, the measurements that characterize light-controlled transition to flowering, and the determination of anthocyanin and chlorophyll accumulation. Furthermore, different light programs are listed that can be used to test for the functional involvement of separate light response modes controlling photomorphogenic plant development. PMID- 20734263 TI - Kinematic analysis of cell division and expansion. AB - Plant growth is readily analysed at the macroscopic level by measuring size and/or mass. Although it is commonly known that the rate of growth is determined by cell division and subsequent cell expansion, relatively few studies describing growth phenotypes include studies of the dynamics of these processes. Kinematic analyses provide a powerful and rigorous framework to perform such studies and have been adapted to the specific characteristics of various plant organs. Here we describe in detail how to perform these analyses in root tips and leaves of the model species Arabidopsis thaliana and in the leaves of the monocotyledonous crop species, Zea mays. These methods can be readily used and adapted to suit other species in most laboratories. PMID- 20734264 TI - Flowering time control. AB - A dramatic change in the life cycle of plants is the transition to flowering, which is triggered by both environmental signals, such as temperature and photoperiod, and endogenous stimuli. The dicotyledonous annual plant Arabidopsis thaliana is widely used as a model organism to study how these different signals are integrated into a developmental response. The existence of a diverse collection of Arabidopsis flowering time mutants is particularly useful to understand the genetics of flowering time control. This chapter gives an overview of flowering time analysis, including protocols to measure flowering time in Arabidopsis and wheat. For Arabidopsis, the experimental design necessary to assign flowering time mutants to a specific pathway is described. PMID- 20734265 TI - mRNA detection by whole mount in situ hybridization (WISH) or sectioned tissue in situ hybridization (SISH) in Arabidopsis. AB - Gene expression can be analyzed at high spatial resolution via RNA in situ detection methods. For many tissues and species, these will be performed on sections of embedded and fixed plant material. When very small or fragile tissues, such as embryos or roots are being investigated, whole mount methods can be employed. Protocols for both approaches are described in detail. PMID- 20734266 TI - Immunolocalization of proteins in plants. AB - Rapid advances in the field of plant biology, especially in plant cell biology, have created the need for methods that allow the localization of proteins in situ at subcellular resolution. Although in many cases recombinant proteins with fluorescent proteins can fulfill this task, antibody-based immunological detection of proteins is a complementary technique, which avoids the risk of inducing side effects by a fusion protein, such as misexpression, mistargeting, altered stability, or toxicity. Moreover, recombinant protein techniques are applicable only to a rather limited set of model plants. The immunolocalization protocols presented here can be used to display protein localization patterns in different tissues of various plant species. This chapter describes a whole mount immunolocalization protocol, which has been extensively used in Arabidopsis roots and some above-ground tissues, and that also works in other species. Additionally, for bulky or hard tissue types, a variation of this protocol for paraffin-embedded sections is given. PMID- 20734267 TI - Detection of small non-coding RNAs. AB - Gene expression is regulated at several levels in plants, and one of the most recently discovered regulatory layers involve short RNAs. Short RNAs are produced through several pathways and target either mRNAs or genomic DNA. Different classes of short RNAs have slightly different sizes and detection of their accumulation is an important step in validating and studying non-coding short RNAs. Northern blotting is routinely used to detect short RNAs because it gives information about both the amount and size of the analysed short RNAs. Choice of the right RNA extraction protocol is crucial when short RNAs are being studied, because several routinely used commercial RNA extraction kits do not yield any short RNAs. This chapter describes optimised RNA extraction methods, which give good yields of short RNAs, and separation, transfer and hybridisation protocols to study the accumulation of short RNAs. PMID- 20734268 TI - Quantitative real time PCR in plant developmental biology. AB - Gene expression patterns are important determinants of a cell's state, and changes in the expression profile indicate adaptation processes as a response to developmental transitions or environmental changes. Assaying gene expression can, therefore, help to elucidate mechanisms of determination and differentiation, as well as signaling networks. Several methods have been employed to determine transcript levels. The most quantitative and widely used technique is reverse transcription coupled to quantitative real time polymerase chain reaction (RT qPCR). Live observation of fluorescence and, therefore, product increase during RT-qPCR allows the accurate determination of differences between initial template amounts. This is in contrast to the end-point analysis of conventional PCR, where initial differences in template amounts are usually masked because the analysis is done at the plateau phase. In the plateau phase, differences can no longer be distinguished due to inherent characteristics of PCR (e.g., loss of activity of the polymerase or because reaction components become limiting) that cause a drop in amplification efficiency, so that product accumulation levels out. Real time PCR circumvents this problem by shifting the analysis to an earlier stage of the amplification reaction. PMID- 20734269 TI - Luciferase and green fluorescent protein reporter genes as tools to determine protein abundance and intracellular dynamics. AB - To get insight into molecular mechanisms governing plant development, the dynamics of abundance and cellular localisation of signalling components need to be understood. Luciferase and green fluorescent protein (GFP)-derived reporters are suitable markers to determine dynamic signalling processes in vivo. Here, analysis of phytochrome A (phyA) photoreceptor dynamics during early seedling development is used as an example of how in vitro and in vivo luciferase assays as well as GFP-imaging can be used to probe signalling dynamics. PMID- 20734270 TI - Fluorescence-activated cell sorting in plant developmental biology. AB - Understanding the development of an organ requires knowledge of gene, protein, and metabolite expression in the specific cell types and tissues that comprise the organ. Fluorescence-activated cell sorting (FACS) is an efficient method to isolate specific cells of interest, and the information gained from this approach has been integral to plant developmental biology. The Benfey lab has developed this method to examine gene expression profiles of different cell types in the Arabidopsis root under both standard and stress conditions. In addition to gene expression, downstream applications of FACS include proteomic and metabolite analysis. This is a powerful method to examine biological functions of specific cell types and tissues with a systems biology approach. PMID- 20734271 TI - Laser microdissection of paraffin-embedded plant tissues for transcript profiling. AB - High-resolution cellular analysis will help answer many important questions in plant biology including how genetic information is differentially used to enable the formation and development of the plant body. By comparing transcriptome data from distinct cell types during various stages of development, insight can be obtained into the transcriptional networks that underpin the attributes and contributions of particular cells and tissues. Laser microdissection (LM) is a technique that enables researchers to obtain specific cells or tissues from histological samples in a manner conducive to downstream molecular analysis. LM has become an established strategy in many areas of biology and it has recently been adapted for use with many types of plant tissue. PMID- 20734272 TI - Utilizing bimolecular fluorescence complementation (BiFC) to assay protein protein interaction in plants. AB - Protein function is often mediated by the formation of stable or transient complexes. Here we present a method for testing protein-protein interactions in plants designated bimolecular fluorescence complementation (BiFC). The advantages of BiFC are its simplicity, reliability, and the ability to observe protein protein interactions in different cellular compartments including membranes. BiFC is based on splitting the yellow fluorescent protein (YFP) into two nonoverlapping N-terminal (YN) and C-terminal (YC) fragments. Each fragment is cloned in-frame with a gene of interest, enabling expression of a fusion protein. Reconstitution of the fluorescing YFP chromophore takes place upon interaction of protein pairs that are coexpressed in the same cells. PMID- 20734273 TI - The split luciferase complementation assay. AB - A split luciferase complementation assay to study protein-protein interactions within Arabidopsis protoplasts in 96-well plates is described in this protocol. Two proteins of interest, a bait and prey, which are genetically fused to amino- and carboxy-terminal fragments of Renilla luciferase, are transiently expressed in protoplasts. Physical interactions of these bait and prey proteins reconstitute some of the luciferase activity and result in light emission in the presence of the luciferase substrate. This luminescence is then measured by a microplate luminometer. Amounts of the bait protein accumulated in the protoplasts can be estimated by Western blotting using an antibody that recognizes the amino-terminal fragment of Renilla luciferase. The most advantageous aspect of this assay is its capacity of detecting both association and dissociation of a protein pair of interest in a large-scale format. PMID- 20734274 TI - Co-immunoprecipitation and protein blots. AB - Knowledge about the identity of the interacting partners is important for the understanding of the function and the cellular activity of a given protein. Here we describe co-immunoprecipitation and pull-down as methods that are widely used for the identification and characterization of protein-protein interactions. These methods are well suited to find or confirm the interaction among multiple proteins, given the availability of a specific antibody for or a tagged version of the protein of interest. PMID- 20734275 TI - Probing protein-protein Interactions with FRET-FLIM. AB - The quantification of molecular interactions or conformational changes can conveniently be studied by using Forster Resonance Energy Transfer (FRET) as a spectroscopic ruler. The FRET phenomenon describes the transfer of energy from a donor to an acceptor molecule, if they are in close proximity (<10 nm). The most straightforward method to measure FRET is Fluorescence Lifetime Imaging Microscopy (FLIM). In this chapter, we will describe an application of FRET using FLIM to monitor the hexamer formation of CrFP/eYFP-labeled Arabidopsis thaliana cell division cycle protein (AtCDC48) expressed in plant protoplasts. PMID- 20734276 TI - Plant chromatin immunoprecipitation. AB - Development of multicellular organisms is based on specialized gene expression programs. Because chromatin establishes the environment for transcription, understanding composition and dynamics of chromatin is an important part of developmental biology. The knowledge about chromatin has been greatly advanced by the chromatin immunoprecipitation (ChIP) technique, because ChIP allows to map the position of proteins as well as modifications of DNA and histones to specific genomic regions. Although ChIP has been applied to a wide range of model organisms, including Arabidopsis, it remains a challenging technique, and a careful experimental setup including appropriate positive and negative controls are required to obtain reliable results. Here, we describe a ChIP protocol adapted for material from Arabidopsis, which we routinely apply in our laboratory, and we discuss required controls and methods for data analysis. PMID- 20734277 TI - Immunocytological analysis of chromatin in isolated nuclei. AB - All cells in a multicellular organism have the same genetic constitution, yet their appearance and function may differ enormously, due to differences in the nuclear program. Central in the establishment of this cell diversity are epigenetic marks, which are largely based on covalent modifications of histones and methylated cytosine residues in the DNA sequence. The study of these epigenetic factors in individual cells requires the microscopic visualization of chromatin components. Here we describe a number of protocols to study chromatin in isolated nuclei. PMID- 20734278 TI - Bisulphite sequencing of plant genomic DNA. AB - DNA methylation is a prominent epigenetic mark and extensively found within plant genomes. It has two major roles- first, defending the genome against invasive DNA and second, regulation of gene expression. Since the first report of 5 methylcytosine found in wheat germ, many improvements in detection of methylated cytosine residues have been made and genome-wide methylation maps for Arabidopsis thaliana are now available. The development of fast, reproducible, and single base pair resolving detection methods for DNA methylation at defined loci advanced our understanding of the establishment and maintenance of DNA methylation patterns. Bisulphite conversion of unmethylated cytosine residues followed by detection methods such as sequencing of distinct loci has become accepted as the gold standard for detecting 5-methylcytosines. Treatment of single-stranded DNA with bisulphite under acidic conditions leads to the conversion of cytosine residues to uracil whereas 5-methylcytosine is less sensitive and remains unchanged. Here, a detailed protocol for bisulphite conversion, primer design, and optimization of PCR conditions is given. Specific requirements for plant DNA are discussed. PMID- 20734279 TI - Bach flower remedies: a systematic review of randomised clinical trials. AB - Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos. PMID- 20734280 TI - Bilateral total knee arthroplasty in a patient with hemophilia A, high inhibitor titre and aneurysma spurium of the popliteal artery. A case report. AB - The authors report on bilateral simultaneous knee arthroplasty in a 40-year-old male patient with haemophilia A, high inhibitor titre and an aneurysma spurium of the right popliteal artery. Both knees showed a fixed flexion deformity of 20 degrees. To build up haemostasis, treatment with activated prothrombin complex concentrate (APCC) and recombinant activated factor seven (rFVIIa) was initiated preoperatively. A tourniquet was used on both sides during the operation and factor VIII (FVIII) was administered to further correct coagulopathy. On the eleventh postoperative day the patient complained of increasing pain and pressure in the right knee. An ultrasound suggested aneurysm, which was confirmed by substraction angiography. Under the protection of rFVIIa the aneurysm could be coiled and further rehabilitation was uneventful. At one year post-op the patient presented a range of motion of 90/5/0 degrees for both knees and had returned to full time office work. This case indicates that haemophiliacs with high antibody titre and destruction of both knees can be operated on in one session in order to diminish the operative risk of two consecutive surgical procedures, thus allowing an effective rehabilitation programme. Because of the significant frequency of popliteal aneurysms, preoperative angiography is recommended. PMID- 20734281 TI - Premature deaths in Switzerland from 1995-2006: causes and trends. AB - PURPOSE: Mortality expressed as potential years of life lost (PYLL) underscores premature and preventable mortality. We analysed causes of and trends in premature death in Switzerland to highlight the areas which provide the greatest potential outcome for preventive measures. METHODS: Premature mortality rates and trends from 1995-2006 were examined by reviewing potential years of life lost between age 1 and 70, as the upper age limit, considering 4 main categories: circulatory diseases, cancer, external causes of mortality and other causes, and 19 specific causes of death. Trends were assessed using join point analysis with PYLL expressed as age-standardised rate. The analysis was based on the official death certification files provided by the Swiss Federal Statistical Office. RESULTS: Age adjusted PYLL rates decreased for all categories of causes, but the decline in cancers was modest compared to circulatory diseases and external causes. The strongest downward trends were observed for AIDS, traffic accidents and ischaemic heart disease. In women breast cancer contributed most to the decline of premature mortality but remains the first cause of early death. Lung cancer in women is the only cause of premature mortality with rising trends. CONCLUSIONS: Past efforts in prevention, early detection and treatment, but also a healthier lifestyle and other factors, have very probably contributed to the considerable reduction in the rate of potential years of life lost, but the rising rate of premature mortality caused by lung cancer in women is of concern. Persistent efforts in prevention and early detection are required to further reduce premature death and its burden on society. PMID- 20734282 TI - [The repeatability of forced expiratory manoeuvres in 4- to 6-year-old children with intermittent bronchial asthma in healthy and in exacerbated status]. AB - INTRODUCTION: The question about the repeatability of forced expiratory manoeuvres in childhood lung function testing is of scientific and clinical interest. The following study investigated to what extent children >= 4 to < 7 years of age with intermittent bronchial asthma are able to produce reproducible lung function measurements on the one hand in the healthy status and on the other hand in an exacerbated status. METHOD: 64 children at the age of >= 4 to < 7 years with intermittent preschool bronchial asthma performed lung function measurements in the healthy status and again in an exacerbated status. FEV (1) values from the measurements were analysed according to ATS/ERS guidelines concerning repeatability. RESULTS: According to the new ATS/ERS guidelines 74.6 % of the children could perform at least 2, and 59.3 % could perform 3 repeatable measurements in the healthy status. In the exacerbated status this was 87.5 % and 68.8 %, respectively. There were no significant differences between the healthy and the exacerbated status and between the age groups. Compared to former repeatability criteria, children of this age group can perform significantly more reproducible measurements (p < 0.0001). CONCLUSION: The ATS/ERS guidelines from 2007 simplify the repeatability of forced expiratory manoeuvres in children at >= 4 to < 7 years of age compared to the former criteria. Repeatability is not reduced in the exacerbated status. 74.6 % of children in this age group can produce repeatable lung function measurements. PMID- 20734283 TI - [Does additive spongiosaplasty improve outcome after surgical therapy for solitary enchondroma in the hand?]. AB - INTRODUCTION: The necessity of spongiosaplasty in the treatment of solitary enchondroma in the hand has been a subject of controversial discussions for several years. Over a period of 10 years the authors performed single curettage without spongiosaplasty. The aim of this study was to investigate our results and to compare these findings with those of other studies. PATIENTS AND METHOD: Over the last 10 years we have treated 106 patients with solitary enchondroma of the hand by single curettage without bone grafting. All patients underwent postoperative radiological examination. The mean follow-up was 34 months. The results of the X-ray investigation were examined retrospectively concerning the recurrence rates and the Hasselgren score. RESULTS: Two patients (1.9%) have experienced radiological changes according to Hasselgren score IV. One patient (0.8%) demonstrated radiological III degrees changes according to score of Hasselgren. Including the patient with the radiological changes according to Hasselgren score III, the overall recurrence rate was 2.8%. DISCUSSION: After comparing our results with those of other studies, we conclude that additional bone-grafting does not improve the recurrence rate of solitary enchondromas of the hand. PMID- 20734286 TI - ["Manufacturers should see the chances!" (interview by Dr. Berhard Epping)]. PMID- 20734306 TI - Formal synthesis of the anti-angiogenic polyketide (-)-borrelidin under asymmetric catalytic control. AB - Borrelidin (1) is a polyketide that possesses extremely potent anti-angiogenesis activity. This paper describes its formal total synthesis by the most efficient route to date. This modular approach takes optimal benefit of asymmetric catalysis and permits the synthesis of analogues; in addition, the high yields and selectivities obtained eliminate the need for separation of stereoisomers. The upper half of borrelidin has been accessed by iterative copper-catalysed asymmetric conjugate addition of methylmagnesium bromide, whereas synthesis of the lower half of the molecule was achieved by relying on asymmetric hydrogenation and cross-methathesis as key steps. PMID- 20734307 TI - Reactivity of gold nanobelts with unique {110} facets. AB - Gold nanobelts were synthesized by directional solidification of the Fe-Au eutectoid followed by selective phase dissolution. Cleaning from organic molecules was performed in alkaline solution by PbO(2) deposition/dissolution to avoid surface reconstruction. The electrochemical behaviour of the Au nanobelts was determined by structure-sensitive electrochemical reactions, and the findings confirm the results obtained by selected area electron diffraction (SAED). The underpotential deposition (UPD) of lead under alkaline conditions and cyclic voltammograms (CVs) in sulphuric acid revealed an unusual large amount of (110) domains (>65%). Finally, after cleaning the Au nanobelts showed a higher and stable electrocatalytic behaviour toward methanol oxidation in alkaline media. The possible mechanism and the potential applications of the Au nanobelts are discussed. PMID- 20734308 TI - Thermodynamics of hydrogen adsorption on metal-organic frameworks. AB - Interaction between adsorbed hydrogen and the coordinatively unsaturated Mg(2+) and Co(2+) cationic centres in Mg-MOF-74 and Co-MOF-74, respectively, was studied by means of variable-temperature infrared (VTIR) spectroscopy. Perturbation of the H(2) molecule by the cationic adsorbing centre renders the H--H stretching mode IR-active at 4088 and 4043 cm(-1) for Mg-MOF-74 and Co-MOF-74, respectively. Simultaneous measurement of integrated IR absorbance and hydrogen equilibrium pressure for spectra taken over the temperature range of 79-95 K allowed standard adsorption enthalpy and entropy to be determined. Mg-MOF-74 showed DeltaH(0)=-9.4 kJ mol(-1) and DeltaS(0)=-120 J mol(-1) K(-1), whereas for Co-MOF-74 the corresponding values of DeltaH(0)=-11.2 kJ mol(-1) and DeltaS(0)=-130 J mol(-1) K(-1) were obtained. The observed positive correlation between standard adsorption enthalpy and entropy is discussed in the broader context of corresponding data for hydrogen adsorption on cation-exchanged zeolites, with a focus on the resulting implications for hydrogen storage and delivering. PMID- 20734309 TI - Structural basis for the improved potency of peroxisome proliferator-activated receptor (PPAR) agonists. AB - The need to develop safer and more effective antidiabetic drugs is essential owing to the growth worldwide of the diabetic population. Targeting the PPAR receptor is one strategy for the treatment of diabetes; the PPAR agonists rosiglitazone and pioglitazone are already on the market. Here we report the identification of a potent PPAR agonist, 15, whose PPARgamma activation was more than 20 times better than that of rosiglitazone. Compound 15 was designed to incorporate an indole head with a carboxylic acid group, and 4-phenylbenzophenone tail to achieve a PPARgamma EC(50) of 10 nM. Compound 15 showed the most potent PPARgamma agonist activity among the compounds we investigated. To gain molecular insight into the improved potency of 15, a structural biology study and binding energy calculations were carried out. Superimposition of the X-ray structures of 15 and agonist 10 revealed that, even though they have the same indole head part, they adopt different conformations. The head part of 15 showed stronger interactions toward PPARgamma; this could be due to the presence of the novel tail part 4-phenylbenzophenone, which could enhance the binding efficiency of 15 to PPARgamma. PMID- 20734310 TI - Effect of maximal voluntary contraction on the amplitude of the compound muscle action potential: implications for the interpolated twitch technique. AB - The compound muscle action potential (M(MAX)) during a maximal voluntary contraction (MVC) may be measured to determine if the motor nerve has been supramaximally stimulated during the interpolated twitch technique (ITT). Ten males performed isometric knee extension MVCs. M(MAX) for the vastus medialis was recorded during MVC and rest. To examine the effect of stimulating electrode movement, the M(MAX) of the thenar group and antidromic sensory nerve action potentials (SNAPs) to the third digit were recorded in a separate experiment. M(MAX) during MVC was reduced by 18% (P < 0.0001) and 43% (p < 0.0001) for the quadriceps and thenar group, respectively. The SNAP amplitude was not different between rest and MVC (P = 0.18). Reduction of M(MAX) during MVC suggests that some motor axons are refractory and unable to respond to a superimposed maximal stimulus. These results have implications for the sensitivity of the interpolated twitch technique. PMID- 20734311 TI - MMP-9 overexpression improves myogenic cell migration and engraftment. AB - Myoblast migration requires matrix metalloproteinase (MMP) activity but the contribution of individual MMPs or tissue inhibitors of matrix metalloproteinase (TIMPs), particularly MMP-9 and TIMP-1, is lacking. Using two clones derived for differential regulation of MMP-2, MMP-9, and TIMP-1, we correlated protein expression with cell migration. MMP/TIMP regulation was determined by zymography, western blots, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell migration was compared in vitro and after grafting into nude-mdx mouse muscles. C2M9 clones produced high MMP-9 and low MMP-2, and migrated better than C2F clones, which secreted low MMP-9, but overexpressed MMP-2 and TIMP-1. Improvement of C2F invasion by MMP-9 and inhibition of C2M9 migration by MMP-9 inhibitor I confirmed the role of MMP-9 and pointed to potential inhibition by TIMP-1. Higher complementation achieved by C2M9 grafts corroborated the beneficial effect of MMP-9 overexpression. Modulation of MMP-9 expression opens perspectives for improved efficacy of cell therapy for muscular dystrophies. PMID- 20734312 TI - Eating disorder symptomatology and substance use disorders: prevalence and shared risk in a population based twin sample. AB - OBJECTIVE: Research shows a significant association between eating disorders (ED) and substance use disorders (SUD). The objective of this study is to examine the prevalence, chronology, and possibility of shared familial risk between SUD and ED symptomatology. METHOD: Subjects included 1,206 monozygotic and 877 dizygotic adult female twins. ED symptomatology included anorexia (AN) and bulimia nervosa (BN) diagnosis, symptoms associated with diagnostic criteria, and BN symptom count. SUD included alcohol, illicit drug, and caffeine abuse/dependence. Generalized estimated equation modeling was used to examine phenotypic associations, and Choleksy decompositions were used to delineate the contribution of genes and environment to comorbidity. RESULTS: There were no significant differences between SUD prevalence in women with AN and BN. Women with BN reported BN preceded SUD development while the reverse was true for AN. Twin analyses showed possible familial overlap between BN symptomatology and all SUD examined. DISCUSSION: Results suggest an important difference in the chronology of EDs and SUDs. Women with BN may be turning to substances to dampen bulimic urges. Women with AN may be engaging in substance use initially in an effort to lose weight. Results also suggest familial factors contribute to the comorbidity between BN and SUD. PMID- 20734314 TI - Characterizing amyloid-beta protein misfolding from molecular dynamics simulations with explicit water. AB - Extracellular deposition of amyloid-beta (Abeta) protein, a fragment of membrane glycoprotein called beta-amyloid precursor transmembrane protein (betaAPP), is the major characteristic for the Alzheimer's disease (AD). However, the structural and mechanistic information of forming Abeta protein aggregates in a lag phase in cell exterior has been still limited. Here, we have performed multiple all-atom molecular dynamics simulations for physiological 42-residue amyloid-beta protein (Abeta42) in explicit water to characterize most plausible aggregation-prone structure (APS) for the monomer and the very early conformational transitions for Abeta42 protein misfolding process in a lag phase. Monitoring the early sequential conformational transitions of Abeta42 misfolding in water, the APS for Abeta42 monomer is characterized by the observed correlation between the nonlocal backbone H-bond formation and the hydrophobic side-chain exposure. Characteristics on the nature of the APS of Abeta42 allow us to provide new insight into the higher aggregation propensity of Abeta42 over Abeta40, which is in agreement with the experiments. On the basis of the structural features of APS, we propose a plausible aggregation mechanism from APS of Abeta42 to form fibril. The structural and mechanistic observations based on these simulations agree with the recent NMR experiments and provide the driving force and structural origin for the Abeta42 aggregation process to cause AD. PMID- 20734313 TI - Quality of random number generators significantly affects results of Monte Carlo simulations for organic and biological systems. AB - We have simulated pure liquid butane, methanol, and hydrated alanine polypeptide with the Monte Carlo technique using three kinds of random number generators (RNG's)-the standard Linear Congruential Generator (LCG), a modification of the LCG with additional randomization used in the BOSS software, and the "Mersenne Twister" generator by Matsumoto and Nishimura. While using the latter two RNG's leads to reasonably similar physical features, the LCG produces significant different results. For the pure fluids, a noticeable expansion occurs. Using the original LCG on butane yields, a molecular volume of 171.4 A(3) per molecule compared to about 163.6-163.9 A(3) for the other two generators, a deviation of about 5%. For methanol, the LCG produces an average volume of 86.3 A(3) per molecule, which is about 24% higher than the 68.8-70.2 A(3) obtained with the RNG's in BOSS and the generator by Matsumoto and Nishimura. In case of the hydrated tridecaalanine peptide, the volume and energy tend to be noticeably greater with the LCG than with the BOSS (modified LCG) RNG's. For the simulated hydrated extended conformation of tridecaalanine, the difference in volume reached about 87%. The uniformity and periodicity of the generators do not seem to play the crucial role in these phenomena. We conclude that, it is important to test a RNG's by modeling a system such as the pure liquid methanol with a well established force field before routinely employing it in Monte Carlo simulations. PMID- 20734315 TI - Rapid sampling of all-atom peptides using a library-based polymer-growth approach. AB - We adapted existing polymer growth strategies for equilibrium sampling of peptides described by modern atomistic forcefields with a simple uniform dielectric solvent. The main novel feature of our approach is the use of precalculated statistical libraries of molecular fragments. A molecule is sampled by combining fragment configurations-of single residues in this study-which are stored in the libraries. Ensembles generated from the independent libraries are reweighted to conform with the Boltzmann-factor distribution of the forcefield describing the full molecule. In this way, high-quality equilibrium sampling of small peptides (4-8 residues) typically requires less than one hour of single processor wallclock time and can be significantly faster than Langevin simulations. Furthermore, approximate, clash-free ensembles can be generated for larger peptides (up to 32 residues in this study) in less than a minute of single processor computing. We discuss possible applications of our growth procedure to free energy calculation, fragment assembly protein-structure prediction protocols, and to "multi-resolution" sampling. PMID- 20734316 TI - Regulation of kidney development by Shp2: an unbiased stereological analysis. AB - Genes that regulate renal branching morphogenesis are likely to indirectly regulate nephron endowment, but few have been validated to do so in vivo. PTPN11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, acts downstream of receptor tyrosine kinases to modulate the Ras-MAPK pathway and has been implicated in branching morphogenesis in vitro and in invertebrates, and is therefore a candidate in vivo regulator of nephron number. In this work, heterozygous null mutant Shp2(+/-) mice at postnatal days 30-35 were compared with their wild-type (WT) littermates using unbiased stereology to determine if, indeed, the former had decreased nephron number due to their 50% decrease in gene/protein dosage. Although there was a trend toward decreases in total glomerular (nephron) number and kidney volume in Shp2(+/-) mice compared with WT, neither difference was statistically significant (11310 vs. 12198 glomeruli, P = 0.22; 62.8 mm(3) vs. 66.0 mm(3) renal volume; P = 0.40). We conclude that loss of 50% gene/protein dosage of PTPN11/Shp2 is insufficient to affect glomerular (and thereby nephron) number in mouse kidneys in vivo. PMID- 20734317 TI - Demethylation of specific Wnt/beta-catenin pathway genes and its upregulation in rat brain induced by prenatal valproate exposure. AB - Valproate (VPA) has been used for decades in the treatment of epilepsy and migraine. However, maternal administration of VPA during pregnancy increases susceptibility to autism spectrum disorders (ASDs) in the offspring. The aim of this study was to investigate the methylation modification and its effects on the activity of Wnt/beta-catenin pathway in the rat brain prenatally exposed to VPA. We exposed the rats in early pregnancy to VPA and found that the prenatal VPA exposure, in comparison with the prenatal vehicle exposure, induced demethylation in the promoter regions of wnt1 and wnt2, but not in those of Wnt inhibitory factor-1 and Dickkopf 1, in the prefrontal cortexes and hippocampi of the offspring. Consequently, both mRNA and protein expression of wnt1 and wnt2 were increased. Furthermore, the activity of Wnt/beta-catenin pathway was upregulated, as indicated by the increased levels of beta-catenin, hence the growing expression of its target genes. This work suggested an epigenetic action via which VPA, when administered in early pregnancy, induced dysregulation of signaling pathway, further facilitating susceptibility to ASDs. PMID- 20734318 TI - Bortezomib plus thalidomide for newly diagnosed multiple myeloma in China. AB - The aim of this Phase II study was to determine the efficacy and safety of combined bortezomib and thalidomide (VT) regime as initial treatment for newly diagnosed patients with multiple myeloma (MM) in China. Thirty-four patients have been enrolled in this study and were planned to receive VT regime up to eight 21 day cycles. Bortezomib (1.3 mg/m(2) ) was given intravenously on days 1, 4, 8, and 11, while oral thalidomide (100 mg/day) was given on days 1 to 21. The primary end point was clinical response; the secondary end point was safety. Among 34 patients enrolled, 26 patients were able to complete the planned eight cycles of therapy. After eight cycles, the overall response rate was 100% (complete response 31%; near-complete response 23%; partial response 42%; minimal response 4%). The best response occurred within the first four cycles in 96% of patients. Adverse events included hematologic (53%), peripheral neuropathy (38%), fatigue (35%), gastrointestinal (45%), and fever (32%). Grade 3 nonhematologic adverse events included four patients (12%) with renal failure associated with tumor lysis syndrome, one patient (3%) with peripheral sensory and motor neuropathy that improved with VT dose reduction, and one patient (3%) with hypotension. One patient (3%) experienced Grade 4 thrombocytopenia. No patient experienced deep venous thrombosis, while 1 patient (3%) died due to acute renal failure. In conclusion, Bortezomib in combination with thalidomide is a very effective regimen for newly diagnosed MM patients and the toxicities are manageable. PMID- 20734319 TI - A critical review of objective personality inventories with sex offenders. AB - This review provides a critical analysis of the ability of multiscale inventories to distinguish between sex offender and nonoffender control groups, as well as to discriminate sex offenders from other types of offenders. In addition to expanding upon previous reviews that examined the utility of the Minnesota Multiphasic Personality Inventory (MMPI) with this population (e.g., Levin & Stava, 1987), the current review included studies that utilized other multiscale inventories commonly used in forensic practice (i.e., MMPI-2, Millon Clinical Multiaxial Inventory-III [MCMI-III], Personality Assessment Inventory) and, when possible, provides effect sizes to evaluate group differences. Based on the review, the various forms of the MMPI and MCMI are clearly the most widely used instruments in sex offender populations. The MMPI Pd scale has shown moderate to large effect sizes when distinguishing between sex offender and nonsex offender groups, but this relationship may be reflective of antisocial behavior in general rather than traits specific to sex offenders. Recommendations to standardize future research classification strategies and more effectively utilize these instruments when assessing sex offenders are also provided. PMID- 20734320 TI - Loneliness and negative life events as predictors of hopelessness and suicidal behaviors in Hispanics: evidence for a diathesis-stress model. AB - In the present study, we examined loneliness and negative life events as predictors of suicide risk (viz., hopelessness and suicidal behaviors) in a sample of 160 Hispanic adults. Consistent with expectations, we found loneliness and negative life events to be positively associated with both hopelessness and suicidal behaviors. In addition, results of conducting hierarchical regression analyses indicated that loneliness accounted for significant amounts of variance in both measures of suicide risk, ranging from 24% to 29% of the variance. The inclusion of negative life events as a predictor was found to account for additional unique variance in hopelessness (3%), but not in suicidal behaviors, beyond what was predicted by loneliness. Finally, consistent with a diathesis stress model, the Loneliness * Negative Life Events interaction was found to account for an additional 3% of the variance in both suicide risk measures. Implications of the present findings for future research on suicide risk in Hispanics are discussed. PMID- 20734321 TI - Modern adjuncts and technologies in microsurgery: an historical and evidence based review. AB - BACKGROUND: While modern reconstructive surgery was revolutionized with the introduction of microsurgical techniques, microsurgery itself has seen the introduction of a range of technological aids and modern techniques aiming to improve dissection times, anastomotic times, and overall outcomes. These include improved preoperative planning, anastomotic aides, and earlier detection of complications with higher salvage rates. Despite the potential for substantial impact, many of these techniques have been evaluated in a limited fashion, and the evidence for each has not been universally explored. The purpose of this review was to establish and quantify the evidence for each technique. METHODS: A search of relevant medical databases was performed to identify literature providing evidence for each technology. Levels of evidence were thus accumulated and applied to each technique. RESULTS: There is a relative paucity of evidence for many of the more recent technologies described in the field of microsurgery, with no randomized controlled trials, and most studies in the field comprising case series only. Current evidence-based suggestions include the use of computed tomographic angiography (CTA) for the preoperative planning of perforator flaps, the intraoperative use of a mechanical anastomotic coupling aide (particularly the Unilink(r) coupler), and postoperative flap monitoring with strict protocols using clinical bedside monitoring and/or the implantable Doppler probe. CONCLUSION: Despite the breadth of technologies introduced into the field of microsurgery, there is substantial variation in the degree of evidence presented for each, suggesting the role for much future research, particularly from emerging technologies such as robotics and modern simulators. PMID- 20734322 TI - Rosemary extracts improve flow-mediated dilatation of the brachial artery and plasma PAI-1 activity in healthy young volunteers. AB - Polyphenol antioxidants decrease the risk of atherosclerosis. The study aimed to evaluate prospectively in healthy young participants the effect of oral rosemary extracts (RE), consisting of diphenols, upon endothelial dysfunction (ED), preceding structural atherosclerosis. Nineteen healthy young volunteers were studied prospectively, who received oral RE (77.7 mg) for 21 days, consisting of active substances carnosol (0.97 mg), carnosic (8.60 mg) and rosmarinic acid (10.30 mg). Before and after RE treatment, the study evaluated fasting serum levels of plasminogen-activator-inhibitor-1 (PAI-1), vascular cell adhesion molecule 1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD), glutathione peroxidase (GPX), fibrinogen, high-sensitivity capsular reactive protein (hs-CRP), tumor-necrosis factor alpha (TNF-alpha), the lipid profile and ED, characterized as flow-mediated dilatation (FMD) in the brachial artery of < 4.5%, estimated by ultrasound measurements. After 21 days, any side effects were registered, the mean FMD increased nonsignificantly (6.51 +/- 5.96% vs 7.78 +/- 4.56%, p = 0.546) and ED decreased significantly (66.6% vs 16.6%, p = 0.040). Among the serum markers, only the mean PAI-1 level decreased significantly (4.25 +/- 1.46 U/mL vs 3.0 +/- 0.61 U/mL, p = 0.012) after 21-day RE supplementation. It is concluded that oral RE supplementation has the potential to improve serum PAI-1 activity and ED in young and healthy individuals. PMID- 20734323 TI - Development and validation of a reversed-phase HPLC method for the determination of gamma-tocotrienol in rat and human plasma. AB - gamma-Tocotrienol (gamma-T3) is a member of the vitamin E family. Recently, gamma T3 has attracted the attention of the scientific community due to its potent anticancer activity and other therapeutic benefits. The objective of this study was to develop and validate a simple and practical reversed-phase HPLC method with satisfactory sensitivity for the routine quantification of gamma-T3 in rat and human plasma. The separation of gamma-T3 from the plasma components was achieved with a C(18) reversed-phase column with an isocratic elution using a mixture of methanol, ethanol and acetonitrile (85:7.5:7.5, v/v/v) with a UV detection at 295 nm. gamma-T3 was extracted from rat and human plasma by liquid liquid extraction with an average recovery of 60%. The method proved linear in the range 100-5000 ng/mL. The inter-day precision ranged from 5.8 to 12.8% and the accuracy ranged from 92.4 to 108.5%, while the intra-day precision ranged from 0.7 to 7.9% in both rat and human plasma. This data confirm that the developed method has a satisfactory sensitivity, accuracy and precision for the quantification of gamma-T3 in plasma. To assess its applicability the method was successfully applied to the quantitative analysis for pharmacokinetic studies of gamma-T3 in rats administered a 10 mg/kg single oral dose. PMID- 20734324 TI - Self-reported competence of Estonian community pharmacists in relation to herbal products: findings from a health-system in transition. AB - Recent health-system reforms in Estonia have resulted in an increased emphasis on primary health care and evidence-based medicine. Community pharmacies are the primary source of herbal products, and pharmacists have an important role in ensuring the safe and effective use of herbal products. The objective of this study was to explore the self-reported competence of pharmacists and the self reported provision of community pharmacy services in relation to herbal products. A survey instrument was mailed to a random sample of 154 (50%) community pharmacies in Estonia in February 2005. Responses were received from 114 pharmacists and six assistant pharmacists (response rate 77.9%). Among the respondents, 64.1% self-evaluated their knowledge of herbal products as good or excellent. However, only 35.0% reported they experienced no problems in counselling about herbal products, while only 35.8% recognized the importance of continuing education. Pharmacists attached a high level of importance to providing information about herbal products' mode of action, administration, potential side-effects and interactions. There was an apparent mismatch between pharmacists' self-reported competence and their self-reported provision of advice about herbal products. Health system reforms in Estonia may need to be accompanied by enhanced training for pharmacists to provide advice about the safe and appropriate use of herbal products. PMID- 20734325 TI - Berberine protects C57BL/6J mice against ethanol withdrawal-induced hyperexcitability. AB - Berberine ([C20H18NO4](+) ), one of the major constituents of the Chinese herb Rhizoma coptidis, is an isoquinoline alkaloid. Plethora of recent reports has indicated its ability to modulate several neurotransmitter systems, especially those implicated in ethanol dependence. Thus, the influence of berberine treatment on the development and expression of ethanol dependence was tested by using the ethanol withdrawal-induced hyperexcitability paradigm. Mice were provided with a nutritionally balanced control liquid diet as the sole nutrient source on day 0; from day 1-4 (ethanol, 3% v/v), from day 5-7 (ethanol, 6% v/v) and from day 8-10 (ethanol, 10% v/v) was incorporated into the liquid diet. On day 11, the ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced hyperexcitability signs were recorded. The results revealed that acute administration of berberine (10 and 20 mg/kg, i.p.) dose-dependently attenuated ethanol withdrawal-induced hyperexcitability signs, and these results were comparable to diazepam (1.25 and 2.5 mg/kg, i.p.). Further, chronic administration of berberine (10 and 20 mg/kg, i.p.) to the ethanol diet fed mice markedly attenuated the ethanol withdrawal induced hyperexcitability signs. In conclusion, the results and evidence suggest that berberine exhibited an inhibitory influence against ethanol withdrawal induced hyperexcitability signs, which could be mediated through its neuromodulatory action. PMID- 20734326 TI - Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro. AB - While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ~ 40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved. PMID- 20734327 TI - Morelloflavone from Garcinia dulcis as a novel biflavonoid inhibitor of HMG-CoA reductase. AB - Morelloflavone, a biflavonoid from Garcinia dulcis previously shown to have hypocholesterolemic activity, was examined for its effect on HMG-CoA reductase, the rate-limiting enzyme of the cholesterol biosynthetic pathway. By using the catalytic domain of house mouse HMG-CoA reductase, morelloflavone was found to inhibit the enzyme activity by competing with HMG-CoA whereas it was non competitive towards NADPH. The inhibition constants (K(i)) with respect to HMG CoA and NADPH were 80.87 +/- 0.06 um and 103 +/- 0.07 um, respectively. Both flavonoid subunits of this compound, naringenin and luteolin, equally competed with HMG-CoA with K(i) of 83.58 +/- 4.37 um and 83.59 +/- 0.94 um, respectively, and were also non-competitive with NADPH (K(i) of 182 +/- 0.67 um and 188 +/- 0.14 um, respectively). Due to these findings, we suggest that each subunit of morelloflavone would occupy the active site of the enzyme, thereby blocking access of its substrate. The present study thus demonstrates the ability of morelloflavone from G. dulcis to inhibit HMG-CoA reductase in vitro. As a result, this biflavonoid might serve as a new candidate for the future development of hypocholesterolemic agents. PMID- 20734328 TI - Antiasthmatic action of dibenzylbutyrolactone lignans from fruits of Forsythia viridissima on asthmatic responses to ovalbumin challenge in conscious guinea pigs. AB - It was reported previously that dibenzylbutyrolactone lignans from Forsythia viridissima fruits, which are traditional medicines for the treatment of inflammatory diseases, have antiinflammatory effects. In this study, the effects on the immediate-phase response (IAR) and late-phase response (LAR) following aerosolized-ovalbumin challenge in ovalbumin-sensitized guinea-pigs were evaluated by measuring the specific airway resistance (sRaw), recruitment of leukocytes and chemical mediators in the bronchoalveolar lavage fluids (BALF) as well as a histopathological survey. Arctiin and matairesinol at 12.5 mg/kg significantly (p < 0.05) decreased sRaw by 51.83% and 43.15% in IAR and by 47.41% and 35.43% in LAR, respectively, whereas arctigenin at 25 mg/kg was significantly active, compared with the controls. Furthermore, arctiin and arctigenin dose dependently inhibited histamine, and the activities of phospholipase A2 (PLA2) and eosinophil peroxidase (EPO) in BALF, respectively, whereas matairesinol inhibited EPO and PLA2 at 12.5 mg/kg and histamine at 50 mg/kg, in addition, they moderately improved the infiltration of eosinophils, compared with controls. Dexamethasone, cromolyn and salbutamol significantly inhibited sRaw in both IAR and LAR, and the recruitment of leukocytes and chemical mediators, whereas salbutamol did not alter chemical mediators, in BALF. These results indicate the three lignans have antiasthmatic effects which were less active than those of the reference drugs. PMID- 20734329 TI - The lambda spanin components Rz and Rz1 undergo tertiary and quaternary rearrangements upon complex formation. AB - Phage holins and endolysins have long been known to play key roles in lysis of the host cell, disrupting the cytoplasmic membrane and peptidoglycan (PG) layer, respectively. For phages of Gram-negative hosts, a third class of proteins, the spanins, are involved in disrupting the outer membrane (OM). Rz and Rz1, the components of the lambda spanin, are, respectively, a class II inner membrane protein and an OM lipoprotein, are thought to span the entire periplasm by virtue of C-terminal interactions of their soluble domains. Here, the periplasmic domains of Rz and Rz1 have been purified and shown to form dimeric and monomeric species, respectively, in solution. Circular dichroism analysis indicates that Rz has significant alpha-helical character, but much less than predicted, whereas Rz1, which is 25% proline, is unstructured. Mixture of the two proteins leads to complex formation and an increase in secondary structure, especially alpha helical content. Moreover, transmission electron-microscopy reveals that Rz-Rz1 complexes form large rod-shaped structures which, although heterogeneous, exhibit periodicities that may reflect coiled-coil bundling as well as a long dimension that matches the width of the periplasm. A model is proposed suggesting that the formation of such bundles depends on the removal of the PG and underlies the Rz Rz1 dependent disruption of the OM. PMID- 20734330 TI - Molecular characterization, immunohistochemical localization and expression of a ribosomal protein L17 gene from Apis cerana cerana. AB - Ribosomal protein L17 (RPL17) is a core protein of the large (60S) ribosomal subunit and plays an important role in protein synthesis. In this report, a RPL17 gene was isolated from Apis cerana cerana, designated as AccRPL17. Alignment analysis showed that AccRPL17 exhibits high homology to other known RPL17s. Moreover, genomic sequence analysis revealed that five exons are splitted by four introns, and the position of the first intron is comparatively conservative, being localized in the 5' untranslated region. Partial putative cis-acting elements related to development were also examined. Quantitative real-time PCR showed that the highest mRNA level was detected in larvae on the fifth day. Simultaneously, immunohistochemical localization showed that AccRPL17 is primarily concentrated in muscular tissues, stigma, body wall, and the surrounding of the eye in the fifth-instar larvae. Further studies suggested that AccRPL17 might be involved in responses to abiotic stresses. This is a report attempting to analyze the expression and distribution of RPL17 in A. cerana cerana. These results indicated that AccRPL17 might play an important role in insect development, and the importance of AccRPL17 in participating in abiotic stresses is discussed. PMID- 20734331 TI - Encapsulation of ePTFE in prevascularized collagen leads to peri-implant vascularization with reduced inflammation. AB - During the typical healing response to an implanted biomaterial, vascular-rich granulation tissue forms around the implant and later resolves into a relatively avascular, fibrous capsule. We have previously shown that a microvascular construct (MVC) consisting of isolated microvessel fragments suspended in a collagen I gel forms a persistent microcirculation in lieu of avascular scar when implanted. The current study evaluated the potential for microvascular constructs to maintain a vascularized tissue environment around an implanted biomaterial. An analysis of the peri-implant tissue around bare expanded polytetrafluoroethylene (ePTFE), ePTFE embedded within a microvascular construct, or ePTFE embedded within collagen alone revealed that the presence of the MVC, but not collagen alone, promoted vascular densities comparable to that of the granulation tissue formed around bare ePTFE. The vessels within the microvascular construct surrounding the ePTFE were perfusion competent, as determined by India ink perfusion casting, and extended into the interstices of the polymer. In contrast to bare ePTFE, the presence of the MVC or collagen alone significantly reduced the number of activated macrophages in association with ePTFE. Similar results were observed for ePTFE modified to increase cellularity and prevent the formation of an avascular scar. The microvascular construct may prove effective in forming vascularized tissue environments and limiting the number of activated macrophages around implanted polymers thereby leading to effective implant incorporation. PMID- 20734332 TI - Chitosan-based gene delivery vectors targeted to the peripheral nervous system. AB - A non-toxic, targeted, simple and efficient system that can specifically transfect peripheral sensorial neurons can pave the way towards the development of new therapeutics for the treatment of peripheral neuropathies. In this study chitosan (CH), a biodegradable polymer, was used as the starting material in the design of a multicomponent vector targeted to the peripheral nervous system (PNS). Polycation-DNA complexes were optimized using imidazole- and thiol-grafted CH (CHimiSH), in order to increase transfection efficiency and allow the formation of ligand conjugated nanocomplexes, respectively. The 50 kDa non-toxic fragment from the tetanus toxin (HC), shown to interact specifically with peripheral neurons and undergo retrograde transport, was grafted to the binary complex via a bi-functional poly(ethylene glycol) (HC-PEG) reactive for the thiol moieties present in the complex surface. The targeting of the developed nanocomplexes was assessed by means of internalization and transfection studies in the ND7/23 (neuronal) vs. NIH 3T3 (fibroblast) cell lines. Targeted transfection was further confirmed in dorsal root ganglion dissociated primary cultures. A versatile, multi-component nanoparticle system that successfully targets and transfects neuronal cell lines, as well as dorsal root ganglia (DRG) primary neuron cultures was obtained for the 1.0 (w/w) HC-PEG/DNA formulation. PMID- 20734333 TI - Reaction time and accuracy in erroneous vs correct responses among dyslexic and regular readers: from letters to sentences. AB - Speed of processing (SOP) is a crucial factor in fluent reading and is measured using reading rate. This measure is commonly used to examine correct reading patterns, yet in the present study it is employed to determine whether differences in SOP exist for correct and incorrect reading. One of the characteristics of dyslexia is slow and inaccurate reading. Thus, the aim of the present study was to compare the processing time and accuracy of dyslexic and regular readers when performing errors during letter, word and sentence reading. Both groups exhibited longer reaction times for incorrect response but the dyslexics were significantly slower. Furthermore, both groups were less accurate and faster when recognizing letters as compared with reading sentences. These data suggest that incorrect responses among dyslexics follow their attempt at stimulus processing rather than impulsivity. In addition, it is suggested that the difference in the task's cognitive demands affects performance. PMID- 20734334 TI - Chemopreventive activity of Azadirachta indica on two-stage skin carcinogenesis in murine model. AB - The present study reports the chemopreventive activity of aqueous Azadirachta indica leaf extract (AAILE) in a murine two-stage skin carcinogenesis model. Skin tumors were induced by topical application of 7,12-dimethylbenz(a)anthracene (DMBA) (500 nmol/100 uL for 2 weeks) followed by 12-O-tetradecanoylphorbol-13 acetate (TPA) (1.7 nmol/100 uL of acetone, twice weekly) as a promoter. Male LACA mice were divided into four groups: control, DMBA/TPA, AAILE and AAILE + DMBA/TPA. AAILE was administered orally at a dose level of 300 mg/kg body weight thrice a week for 20 weeks. 100% tumor incidence was observed in the DMBA/TPA treated animals, whereas the AAILE + DMBA treated animals exhibited a tumor incidence of 58.3% only. A significant reduction in the mean tumor burden (54.5%) and mean tumor volume (45.6%) was observed in the mice that received AAILE along with DMBA/TPA. Topical application of DMBA/TPA to the skin resulted in well developed carcinomas associated with decreased expression of pro-apoptotic protein such as caspase 3 and enhanced expression of antiapoptotic protein such as bcl-2 when compared with the control counterparts. However, adminstration of AAILE inhibited skin carcinogenesis with induction of pro-apoptotic proteins such as bax, caspase 3, caspase 9 and inhibition of antiapoptotic proteins such as bcl 2. These results suggest that the induction of apoptosis may be one of the mechanisms underlying the chemopreventive effects of A. indica. PMID- 20734336 TI - De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. AB - Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut, and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of alpha-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension. PMID- 20734335 TI - Craniofacial birth defects: The role of neural crest cells in the etiology and pathogenesis of Treacher Collins syndrome and the potential for prevention. AB - Of all the babies born with birth defects, approximately one-third display anomalies of the head and face [Gorlin et al., 1990] including cleft lip, cleft palate, small or absent facial and skull bones and improperly formed nose, eyes, ears, and teeth. Craniofacial disorders are a primary cause of infant mortality and have serious lifetime functional, esthetic, and social consequences that are devastating to both children and parents alike. Comprehensive surgery, dental care, psychological counseling, and rehabilitation can help ameliorate-specific problems but at great cost over many years which dramatically affects national health care budgets. For example, the Center for Disease Control and Prevention estimates that the lifetime cost of treating the children born each year with cleft lip and/or cleft palate alone to be US$697 million. Treating craniofacial malformations, of which in excess of 700 distinct syndromes have been described, through comprehensive, well-coordinated and integrated strategies can provide satisfactory management of individual conditions, however, the results are often variable and rarely fully corrective. Therefore, better techniques for tissue repair and regeneration need to be developed and therapeutic avenues of prevention need to be explored in order to eliminate the devastating consequences of head and facial birth defects. To do this requires a thorough understanding of the normal events that control craniofacial development during embryogenesis. This review therefore focuses on recent advances in our understanding of the basic etiology and pathogenesis of a rare craniofacial disorder known as Treacher Collins syndrome and emerging prospects for prevention that may have broad application to congenital craniofacial birth defects. PMID- 20734337 TI - A novel EFNB1 mutation (c.712delG) in a family with craniofrontonasal syndrome and diaphragmatic hernia. AB - We report on the occurrence of congenital diaphragmatic hernia in a family with craniofrontonasal syndrome found to have a previously unreported mutation in EFNB1. The female proband presented with hypertelorism, telecanthus, bifid nasal tip, widow's peak, frontal bossing, and a widened metopic suture. Her father was noted to have hypertelorism, telecanthus, widow's peak, and a history of pectus carinatum. He was found to have a previously unreported mutation in exon 5 of EFNB1 predicted to cause premature protein truncation. The parents of the proband previously had a female fetus with congenital diaphragmatic hernia. The occurrence of congenital diaphragmatic hernia, phenotypic differences between males and females, and utility of molecular testing in craniofrontonasal syndrome are demonstrated. PMID- 20734338 TI - Caudal dysgenesis and sirenomelia-single centre experience suggests common pathogenic basis. AB - Abnormally formed lower limbs with varying degrees of fusion are the major feature of sirenomelia whereas maldeveloped lower limbs without fusion are found in association with caudal dysgenesis (CD). The relationship between these two entities has been a topic of debate for many years. The presence of a single umbilical artery originating from the abdominal aorta was considered a major feature distinguishing sirenomelia from CD. Based on this finding, the vascular steal theory was put forward as the causative mechanism of sirenomelia. CD and sirenomelia were considered to be two entirely different entities with distinct pathogenic mechanisms. However, it is now clear that a single umbilical artery can be found in some patients of CD and normal umbilical arteries in some patients of sirenomelia. The hypothesis of primary deficiency of caudal mesoderm caused by early developmental disruption suggests that sirenomelia and CD are two ends of a spectrum of maldevelopment of caudal mesoderm. In this paper we report on the clinical and pathological features of 16 patients of CD and 9 patients of sirenomelia from our institution and review the literature. This series of cases is notable for the significant association with neural tube defects, refining the renal and urogenital pathology associated with these conditions, and supporting the concept of a continuum of the disease spectrum. PMID- 20734340 TI - Experiencing positive change after a diagnosis of breast cancer: a grounded theory analysis. AB - OBJECTIVE: Recent research recognises that many individuals experience positive psychological changes following a diagnosis of cancer. Such positive change is related to well-being, and some psychological interventions have promoted such change in women with breast cancer. However, neither qualitative nor quantitative studies have adequately explained the process of this change. METHOD: This grounded theory study explored the process whereby positive emotional changes arose in 20 women (mean age 53 years) diagnosed with breast cancer. RESULTS: Most women experienced several positive changes as a result of their breast cancer. Analyses suggested that changed priorities in life and increased empathy for others emerged from the patients' reflections upon the suffering they endured during their illness. By contrast, increased self-confidence appeared to emerge from reflecting on how they managed their illness, and from concluding that they had been courageous in doing so. Factors promoting reflections included acceptance of breast cancer, ending treatments, and communication from others that emphasised rather than minimised the personal significance of cancer. CONCLUSIONS: Findings extend current trauma-processing theories and can inform the timing and design of clinical interventions to improve adjustment to breast cancer. PMID- 20734339 TI - Weight control needs and experiences among rural breast cancer survivors. AB - OBJECTIVE: Rural women are understudied in research on weight control among breast cancer survivors despite having higher obesity rates than their urban counterparts placing them at higher risk for recurrence. The purpose of this survey study was to describe weight status and methods used for weight control in rural breast cancer survivors and to examine psychosocial factors in this population associated with weight change since breast cancer diagnosis. METHODS: Women treated for breast cancer within the past 6 years at one of three rural Cancer Centers were mailed a survey with a cover letter from their oncology provider. RESULTS: Survey respondents (n=918, 83% response rate) were 96% White non-Hispanic, on average 3.2 years from treatment, and 11% reported metastatic disease. Among respondents without known metastatic disease, 68% were overweight or obese, 37% were obese, and 25% reported a weight gain exceeding 5 kg since diagnosis. Among the overweight/obese women, 61% were currently attempting weight loss, and the most common weight loss method was dieting on one's own without assistance. Psychosocial factors associated with weight gain since diagnosis included depression, fear of cancer recurrence, diminished physical strength, body image concerns, relationship changes, and financial stressors. CONCLUSIONS: The high response rate indicates a general interest in body weight issues among rural BrCa survivors, and the findings highlight the need for weight control programs in this population. Findings also indicate that factors related to poor adjustment to breast cancer are associated with weight gain among rural women. PMID- 20734341 TI - Somatic mosaicism for chromosome X and Y aneuploidies in monozygotic twins heterozygous for sickle cell disease mutation. AB - Somatic genetic variation in health and disease is poorly explored. Monozygotic (MZ) twins are a suitable model for studies of somatic mosaicism since genetic differences in twins derived from the same zygote represent an irrefutable example of somatic variation. We report the analysis of a pair of generally healthy female MZ twins, discordant for somatic mosaicism for aneuploidy of chromosomes X and Y. Both twins are heterozygous carriers of sickle cell disease mutation. Genotyping of blood DNA from both twins using Illumina Human 610 SNP array revealed a copy number imbalance for chromosome X in a proportion of cells in one twin. Fluorescent in situ hybridization (FISH) analysis confirmed monosomy X (45,X) in 7% of proband nucleated blood cells. Unexpectedly, FISH analysis of cells from the other twin revealed 45,X and 46,XY lineages, both present in 1% of cells. The mechanism behind formation of these aneuploidies suggests several aberrant chromosome segregation events in meiosis and mitoses following conception. Our report contributes to the delineation of the frequency of somatic structural genomic variation in normal MZ twins. These results also illustrate the plasticity of the human genome for tolerating large copy number changes in healthy subjects and show the sensitivity of the Illumina platform for detection of aberrations that are present in a minority of the studied cells. PMID- 20734343 TI - An aqueous extract of Curcuma longa (turmeric) rhizomes stimulates insulin release and mimics insulin action on tissues involved in glucose homeostasis in vitro. AB - Curcuma longa (turmeric) has been used widely as a spice, particularly in Asian countries. It is also used in the Ayurvedic system of medicine as an antiinflammatory and antimicrobial agent and for numerous other curative properties. The aim of this study was to investigate the effects of an aqueous extract of Curcuma longa (AEC) on tissues involved in glucose homeostasis. The extract was prepared by soaking 100 g of ground turmeric in 1 L of water, which was filtered and stored at -20 degrees C prior to use. Pancreas and muscle tissues of adult mice were cultured in DMEM with 5 or 12 mmol/L glucose and varying doses of extract. The AEC stimulated insulin secretion from mouse pancreatic tissues under both basal and hyperglycaemic conditions, although the maximum effect was only 68% of that of tolbutamide. The AEC induced stepwise stimulation of glucose uptake from abdominal muscle tissues in the presence and absence of insulin, and the combination of AEC and insulin significantly potentiated the glucose uptake into abdominal muscle tissue. However, this effect was attenuated by wortmannin, suggesting that AEC possibly acts via the insulin mediated glucose uptake pathway. In summary, water soluble compounds of turmeric exhibit insulin releasing and mimicking actions within in vitro tissue culture conditions. PMID- 20734344 TI - Can syndromic macrocephaly be diagnosed in utero? AB - OBJECTIVES: To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly. METHODS: We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10-year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated. RESULTS: Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z-score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached. CONCLUSIONS: When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign. PMID- 20734345 TI - Determination of paeoniflorin, calycosin-7-O-beta-D-glucoside, ononin, calycosin and formononetin in rat plasma after oral administration of Buyang Huanwu decoction for their pharmacokinetic study by liquid chromatography-mass spectrometry. AB - The purpose of this study was to simultaneously investigate the pharmacokinetics of five bioactive compounds in rat plasma after oral administration of Buyang Huanwu decoction (BYHWD) using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The separations were performed on a Thermo Hypersil Gold C(18) analytical column (50 * 2.1 mm, 3 um) with the column temperature kept at 30 degrees C. The quantitative analysis was performed using a quadrupole mass spectrometer detector operated under selected ion monitoring mode. A linear gradient elution of A (0.1% formic acid solution) and B (100% acetonitrile) was used at a flow rate of 0.2 mL/min. The method was validated within the concentration ranges 1.8-450, 6.0-1500, 2.0-500, 1.2-300 and 1.2-150 ng/mL for paeoniflorin, calycosin-7-O-beta-d-glucoside, ononin, calycosin and formononetin, respectively. The calibration curves were linear with correlation coefficients > 0.99. The lower limits of quantitations were < 6.0 ng/mL. The method was further applied to assess the pharmacokinetics of the five bioactive constituents of BYHWD in rat plasma. PMID- 20734346 TI - Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser. AB - For the assessment of tissue-engineered cartilage, easy and precise evaluation methods are anticipated. We have investigated the use of a fluorescent image analyser and the application of fluorescence intensity measurements to describe and evaluate a tissue-engineered cartilage-like tissue construct. We evaluated the matrix production of a tissue-engineered cartilage-like tissue (TCL) construct in vitro using the image analyser. The autofluorescence intensity of the TCL construct was determined using the image analyser driven by a software program after 1, 2, 3 and 4 weeks of culture. The autofluorescence intensity of the TCL construct gradually increased with increasing culture time. However, there was very little change in the autofluorescence intensity of gels without articular chondrocytes as controls. The relationship between the autofluorescence intensity of the TCL construct and the hydroxyproline content, reflecting the collagen content, was investigated. There was a significant correlation between the two items. Our findings demonstrate the ability of a commercial fluorescent image analyser to evaluate the matrix production of the TCL construct in vitro on the basis of objective data, such as the autofluorescence intensity. Therefore, the image analyser can be used to judge the success or failure of the in vitro culture process of TCL construct without a biopsy. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID- 20734347 TI - Systematic fetal autopsy in cases of medical termination of pregnancy due to chromosomal abnormalities: improving the quality of perinatal care? AB - OBJECTIVES: Evaluation of the clinical utility of systematically performing autopsy after termination of pregnancy (TOP) due to chromosomal abnormalities. METHODS: A retrospective study of cases of TOP due to chromosomal abnormalities was performed between 1 January 2002 and 30 September 2007, in a tertiary referral hospital. A comparative study between prenatal ultrasonographic findings and postmortem findings was performed. RESULTS: There were 57 cases of TOP due to chromosomal abnormalities. The median gestational age at TOP was 17 (range 14-24 weeks). There were 46 trisomies, 4 monosomies, 4 triploidies and 3 cases of structural anomalies. In 25 cases (43.9%) there was at least one major anomaly detected by ultrasound. In 15 cases (26.3%) additional information was obtained after fetal autopsy: in 7 cases further major structural anomalies were detected, and in 8 cases the presence of a major abnormality was not confirmed by the autopsy. CONCLUSION: Fetal autopsy may provide additional information to the ultrasonographic morphological evaluation of the fetus submitted to TOP due to chromosomal abnormalities. The combination of prenatal ultrasound and pathological examination can broaden our knowledge of the natural history of chromosomal anomalies in the earlier stages of development and eventually contribute to improve the quality of perinatal care. PMID- 20734348 TI - MR volumetry of the normal fetal kidney: reference values. AB - OBJECTIVE: The aim of this study is to provide reference values for normal fetal kidney growth based on magnetic resonance (MR) volumetry. Differences in side and gender will be investigated. METHOD: The institute's database was reviewed for all fetal MR examinations of singleton pregnancies performed between January 2003 and December 2009. Exclusion criteria for renal volumetry were presence of urogenital anomalies, intrauterine growth retardation, polymalformative disorders, oligo- or anhydramnios and maternal diabetes. On anatomical images, renal volumetry was evaluated by delineating kidneys on all slices and combining these into one volume measurement per kidney. Polynomial regression analysis was performed to examine volume evolution over gestational age (GA). RESULTS: Bilateral renal volumes of 274 MR examinations in 240 fetuses with GAs between 20 and 37 weeks were calculated. The renal volumes strongly correlated with GA (polynomial regression analysis, p < 0.001). No significant difference could be observed between the left and right renal volume and between male and female (p = 0.12 and 0.68, respectively). For fetuses GA >= 30 weeks the right kidney was slightly larger than the left side (n = 100, p = 0.039). CONCLUSION: The present study provides reference data for normal fetal renal volumes, which may enable to identify fetuses at risk to develop congenital oligonephropathy. PMID- 20734349 TI - Fetal spinal anomalies in a first-trimester sonographic screening program for aneuploidy. AB - OBJECTIVES: To review the sonographic features of spinal anomalies in first trimester fetuses presenting for screening for chromosomal abnormalities. METHODS: Fetuses with a spinal abnormality diagnosed prenatally or postnatally that underwent first-trimester sonographic evaluation at our institution had their clinical information retrieved and their sonograms reviewed. RESULTS: A total of 21 fetuses complied with the entry criteria including eight with body stalk anomaly, seven with spina bifida, two with Vertebral, Anal, Cardiac, Tracheal, Esophageal, Renal, and Limb (VACTERL) association, and one case each of isolated kyphoscoliosis, tethered cord, iniencephaly, and sacrococcygeal teratoma. One fetus with body stalk anomaly and another with VACTERL association also had a myelomeningocele, making a total of nine cases of spina bifida in our series. Five of the nine (56%) cases with spina bifida, one of the two cases with VACTERL association, and the cases with tethered cord and sacrococcygeal teratoma were undiagnosed in the first trimester. Although increased nuchal translucency was found in seven (33%) cases, chromosomal analysis revealed only one case of aneuploidy in this series. CONCLUSIONS: Fetal spinal abnormalities diagnosed in the first trimester are usually severe and frequently associated with other major defects. The diagnosis of small defects is difficult and a second-trimester scan is still necessary to detect most cases of spina bifida. PMID- 20734350 TI - Transparency and accountability. AB - EMBO Molecular Medicine is enriched by a number of innovative policies designed to enhance the editorial process: peer review process files, de-emphasis of confidential referee comments and cross-refereeing. PMID- 20734351 TI - Quantitative analysis of costunolide and dehydrocostuslactone in rat plasma by ultraperformance liquid chromatography-electrospray ionization-mass spectrometry. AB - Costunolide and dehydrocostuslactone are well-known sesquiterpene lactones contained in many plants used as popular herbs, such as Saussurea lappa and Laurus novocanariensis, and have been considered as potential candidates for the treatment of various types of tumor. In the present work, a sensitive UPLC-MS/MS for the quantification of costunolide and dehydrocostuslactone in biological matrices has been developed. The method is based on protein precipitation with acetonitrile followed by isocratic ultraperformance liquid chromatographic separation using methanol-formic acid (0.1% in water; 70:30, v/v) mobile phase. Detection was performed by ESI mass spectrometry in MRM mode with the precursor to-product ion transitions m/z 233-187 and m/z 231-185, respectively. The calibration curves of analytes showed good linearity within the established range 0.19-760 ng/mL for costunolide and 0.23-908 ng/mL for dehydrocostuslactone. The lower limits of quantification of costunolide and dehydrocostuslactone were found to be 0.19 and 0.23 ng/mL, respectively. The intra-day and inter-day presicions of this method for the entire validation were less than coefficient of variation of 7% and the accuracy was within +/-8% (relative error). The mean extraction recoveries were 73.8 and 75.3%, respectively. The method was found to be precise, accurate and specific during the study, and was successfully used to analyze the pharmacokinetics of costunolide and dehydrocostuslactone. PMID- 20734352 TI - Stability-indicating ultra-performance liquid chromatography method for the estimation of thymoquinone and its application in biopharmaceutical studies. AB - Thymoquinone (THQ) is known for its neuroprotective and anti-convulsant properties in preclinical studies. We herewith describe a simple, rapid, selective, sensitive and stability-indicating UPLC method for the estimation of THQ and its application to biopharmaceutical studies such as in vitro release from nanoparticulate system and in vivo pharmacokinetic study. The method employed gradient elution using a Waters Acquity HSS-T3 C(18) (100 * 2.1 mm, 1.8 um) UPLC column. The mobile phase consisted of water and acetonitrile, pumped at a flow rate of 0.5 mL/min. The injection volume was 5 uL and THQ was monitored at 294 nm wavelength with a total run time of 6 min. In solution as well as in plasma, the method was found to be linear (r >= 0.998), precise (CV <= 2.45%) and accurate (recovery >= 84.8%) in the selected concentration range of 0.1-0.8 ug/mL. Forced degradation studies revealed that THQ undergoes degradation under acidic, basic, oxidation and UV light stress conditions. However, the developed UPLC method could effectively resolve degradation product peaks from THQ. Further, no interference was found at the retention time of THQ from any plasma components, indicating selectivity of the developed method. For solutions, the limits of detection and quantitation of the method were found to be 0.001 and 0.0033 ug/mL, respectively; while in plasma they were 0.006 and 0.02 ug/mL, respectively. The validated method was successfully applied to quantify THQ in dissolution medium as well as oral in vivo pharmacokinetic study of THQ suspension and THQ- solid lipid nanoparticle (THQ-SLN) formulation. A 2-fold increase in the relative bioavailability was observed with the THQ-SLN compared with THQ. The results indicate that the SLN significantly increased plasma concentrations and retention within the systemic circulation. PMID- 20734353 TI - Systematic review of the literature informing the systemic lupus erythematosus indicators project: reproductive health care quality indicators. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) primarily affects women of reproductive age. Here we summarize the scientific evidence supporting recently developed quality indicators (QIs) pertaining to reproductive health. METHODS: We used a modification of the RAND/UCLA Appropriateness Method to develop QIs for SLE. We performed systematic reviews of the literature pertaining to each proposed indicator. Three indicators focusing on reproductive health were included in the final set. Relevant literature was presented to an expert panel, who rated the validity and feasibility of the indicators. RESULTS: Three QIs were rated as valid and feasible. These indicators specifically address laboratory testing during pregnancy in SLE, the treatment of antiphospholipid antibody syndrome, and counseling for drugs with teratogenic potential. CONCLUSION: We used a rigorous method to develop reproductive health QIs for SLE. In the future, these indicators can be used in the assessment and delivery of care to patients with SLE. PMID- 20734354 TI - Canonical Wnt/beta-catenin regulation of liver receptor homolog-1 mediates pluripotency gene expression. AB - Delineating the signaling pathways that underlie ESC pluripotency is paramount for development of ESC applications in both the research and clinical settings. In culture pluripotency is maintained by leukemia inhibitory factor (LIF) stimulation of two separate signaling axes: Stat3/Klf4/Sox2 and PI3K/Tbx3/Nanog, which converge in the regulation of Oct4 expression. However, LIF signaling is not required in vivo for self-renewal, thus alternate signaling axes likely mediate these pathways. Additional factors that promote pluripotency gene expression have been identified, including the direct regulation of Oct4 by liver receptor homolog-1 (Lrh-1) and beta-catenin regulation of Nanog. Here, we present genetic, molecular, and pharmacological studies identifying a signaling axis in which beta-catenin promotes pluripotency gene expression in an Lrh-1-dependent manner. Furthermore, Lrh-1 was identified as a novel beta-catenin target gene, and Lrh-1 regulation is required for maintaining proper levels of Oct4, Nanog, and Tbx3. Elucidation of this pathway provides an alternate mechanism by which the primary pluripotency axis may be regulated in vivo and may pave the way for small molecule applications to manipulate pluripotency or improve the efficiency of somatic cell reprogramming. PMID- 20734355 TI - Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. AB - Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-alpha, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL 6 and TNF-alpha, and an increased expression of IL-10. The GMSC-induced suppression of TNF-alpha secretion by macrophages appears to correlate with impaired activation of NFkappaB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing. PMID- 20734357 TI - A modified protocol for isolation and purity evaluation of a staphylococcal acidic polysaccharide by chromatography and capillary electrophoresis. AB - The extracellular slime of Staphylococcus epidermidis contains, amongst various macromolecules, an acidic polysaccharide (PS) of a molecular mass of 20 kDa with significant antigenic and biological properties. The isolation procedure used so far includes multiple fractionations in anion-exchange chromatographic columns before its final purification by gel filtration chromatography. This protocol is laborious, time-consuming and includes the risk of unnecessary loss of PS quantities. Because of the significance of this PS, a modified protocol resulting in an easier and quicker isolation procedure was developed. Furthermore, identification, purity, charge density and molecular integrity of the isolated polysaccharide were evaluated by a reverse-polarity capillary electrophoresis method. PMID- 20734356 TI - High-efficiency induction of neural conversion in human ESCs and human induced pluripotent stem cells with a single chemical inhibitor of transforming growth factor beta superfamily receptors. AB - Chemical compounds have emerged as powerful tools for modulating ESC functions and deriving induced pluripotent stem cells (iPSCs), but documentation of compound-induced efficient directed differentiation in human ESCs (hESCs) and human iPSC (hiPSCs) is limited. By screening a collection of chemical compounds, we identified compound C (also denoted as dorsomorphin), a protein kinase inhibitor, as a potent regulator of hESC and hiPSC fate decisions. Compound C suppresses mesoderm, endoderm, and trophoectoderm differentiation and induces rapid and high-efficiency neural conversion in both hESCs and hiPSCs, 88.7% and 70.4%, respectively. Interestingly, compound C is ineffective in inducing neural conversion in mouse ESCs (mESCs). Large-scale kinase assay revealed that compound C targets at least seven transforming growth factor beta (TGF-beta) superfamily receptors, including both type I and type II receptors, and thereby blocks both the Activin and bone morphogenesis protein (BMP) signaling pathways in hESCs. Dual inhibition of Activin and BMP signaling accounts for the effects of compound C on hESC differentiation and neural conversion. We also identified muscle segment homeobox gene 2 (MSX2) as a downstream target gene of compound C and a key signaling intermediate of the BMP pathway in hESCs. Our findings provide a single-step cost-effective method for efficient derivation of neural progenitor cells in adherent culture from human pluripotent stem cells. Therefore, it will be uniquely suitable for the production of neural progenitor cells in large scale and should facilitate the use of stem cells in drug screening and regenerative medicine and study of early human neural development. PMID- 20734358 TI - Encapsulated apocrine papillary carcinoma of the breast: case report with clinicopathologic and immunohistochemical study. AB - We describe a case of encapsulated papillary carcinoma (EPC), apocrine variant in a 50-year-old woman. The patient presented a cystic lesion in her right breast, measuring 8 cm in diameter, containing three solid papillary nodules. A fine needle aspiration showed isolated apocrine cells containing round nuclei, irregular nuclear membranes, fine chromatin, and prominent macronucleoli. The lesion was excised and showed a pure papillary apocrine carcinoma, which stained diffusely with GCDFP-15 and androgen receptors. The lesion was totally devoid of myoepithelial cells (smooth muscle actyn, p63, calponin, and collagen IV stains were negative). With MIB1 the proliferative activity was 10%. To the best of our knowledge, this is the first report of EPC apocrine variant with cytologic and immunohistochemical study. This lesion must be included in the list of apocrine lesions of the breast. PMID- 20734359 TI - Fetal growth and the lifetime risk of generalized anxiety disorder. AB - BACKGROUND: Anxiety disorders are thought to have their origins in early childhood, though they have not yet been studied as a potential outcome of impaired fetal growth, which has been implicated in the developmental etiologies of many psychopathologies. This study investigated the association between indicators of fetal growth and the development of generalized anxiety disorder (GAD). METHODS: Indicators of fetal growth, including birth weight (BW) and ponderal index (PI), were assessed among 682 offspring of participants in Providence, Rhode Island, site of the Collaborative Perinatal Project. Participants were interviewed as adults, and their lifetime histories of GAD were assessed using the Diagnostic Interview Schedule. We used Cox regression to estimate the association between fetal growth indicators and development of GAD. RESULTS: The lifetime risk of GAD differed between infants in the highest category of BW, PI, and all others. Newborns with birth weights below 3.5 kg (hazard ratio, HR: 2.38; CI=1.25, 4.55), in the lowest four BW Z-score quintiles (HR=2.49; CI=1.14, 5.45) or a PI in the lowest four quintiles (HR=2.33; CI=1.04, 5.00) had higher lifetime risks of GAD. CONCLUSION: In contrast to earlier studies on psychiatric outcomes in relation to fetal growth, there was no linear relationship between birth weight and GAD. Although these results generally support the hypothesis that a healthy nutritional fetal uptake, as indicated by BW and PI, is associated with better lifetime mental health, further work is needed to characterize the nature of the association between fetal growth and subsequent psychopathology. PMID- 20734360 TI - Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown safety and efficacy for treatment-resistant depression, but requires daily treatment for 4-6 weeks. Accelerated TMS, with all treatments delivered over a few days, would have significant advantages in terms of access and patient acceptance. METHODS: Open-label accelerated TMS (aTMS), consisting of 15 rTMS sessions administered over 2 days, was tested in 14 depressed patients not responding to at least one antidepressant medication. Effects on depression, anxiety, and cognition were assessed the day following treatment, then after 3 and 6 weeks. RESULTS: No seizure activity was observed and only one patient had a serious adverse event (increased suicidal ideation). Two patients failed to complete a full course of aTMS treatments, and 36% did not complete all study visits. Depression and anxiety significantly decreased following aTMS treatments and improvements persisted 3 and 6 weeks later. Response rates immediately following treatment and at 3 and 6 weeks were 43, 36, and 36%, respectively. Remission rates at the same timepoints were 29, 36, and 29%. CONCLUSIONS: Accelerated TMS demonstrated an excellent safety profile with efficacy comparable to that achieved in daily rTMS in other trials. Limitations primarily include open-label treatment and a small sample size. PMID- 20734361 TI - Virtual reality exposure therapy in anxiety disorders: a systematic review of process-and-outcome studies. AB - In recent years, virtual reality exposure therapy (VRET) has become an interesting alternative for the treatment of anxiety disorders. Research has focused on the efficacy of VRET in treating anxiety disorders: phobias, panic disorder, and posttraumatic stress disorder. In this systematic review, strict methodological criteria are used to give an overview of the controlled trials regarding the efficacy of VRET in patients with anxiety disorders. Furthermore, research into process variables such as the therapeutic alliance and cognitions and enhancement of therapy effects through cognitive enhancers is discussed. The implications for implementation into clinical practice are considered. PMID- 20734362 TI - PTSD in children and adolescents: toward an empirically based algorithma. AB - In considering potential revisions for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), describing developmental influences on symptomatic expression is a high priority. This review presents a number of options and preliminary recommendations to be considered for DSM-V. Research conducted in the past 15 years is reviewed that pertains to expressions of posttraumatic stress disorder (PTSD) symptoms in preschool and school age children and in adolescents. This research has attempted to determine the usefulness of the DSM-IV criteria for PTSD in children and adolescents. Based on the studies of preschool children, evidence supports two sets of suggestions: first, we suggest that developmental manifestations are warranted in A-D criteria of PTSD; and second, we suggest that a developmental preschool PTSD subtype is warranted that lowers the C threshold from three to one symptom. For school-age children and young adolescents, the evidence is more limited. Nevertheless, there is also evidence suggesting that modifications in PTSD criteria A-D, including fewer Cluster C symptoms, may facilitate accurate diagnosis in this age group. PMID- 20734363 TI - Depressive and anxiety disorders and the association with obesity, physical, and social activities. AB - OBJECTIVE: There is evidence of more obesity among persons with depressive and depressive and anxiety disorders. However, the nature and the underlying mechanisms of the association are still unclear. This study examines the association between depressive and anxiety disorders and obesity, physical activity, and social activity, and examines whether social and physical activity are potential influencing factors in the association between depressive and anxiety disorders and obesity. METHOD: Cross-sectional data were used from the Netherlands Study of Depression and Anxiety. A total of 1,854 women and 955 men aged 18-65 years were recruited from the community, general practices, and specialized mental health care. Depressive and anxiety disorders were determined with the Composite International Diagnostic Interview. Body mass index (BMI<30 kg/m(2) ) was used to determine obesity. Physical and social activities were measured by self-report. RESULTS: The odds of obesity adjusted for covariates was significantly higher among those with a current pure Major Depressive Disorder (MDD;odds ratio [OR] OR:1.43; 95% CI:1.07-1.92) compared to controls. Physical activity and social activities were lower among persons with depressive and anxiety disorders compared to controls. The association between MDD and obesity was influenced by social and physical activities. CONCLUSION: This study confirmed a link between depressive disorders and obesity that was influenced by lower social and physical activities among the depressed. PMID- 20734365 TI - Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized, placebo controlled trial. AB - BACKGROUND: PRIMARY OBJECTIVE: evaluate the efficacy (time to recurrence of depressive symptoms) of once daily extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy treatment to prevent relapse for major depressive disorder (MDD). METHODS: Time-to-event (maximum 52 weeks), double blind, multicenter, randomized withdrawal, placebo-controlled study of quetiapine XR (50-300 mg/day) comprising four treatment phases: enrollment (up to 28 days), open-label run-in (4-8 weeks), open-label stabilization (12-18 weeks), and randomization (up to 52 weeks). Seven hundred and seventy-six patients stabilized on quetiapine XR were eligible for randomization (Montgomery-Asberg Depression Rating Scale [MADRS] score <=12 and Clinical Global Impression-Severity of Illness [CGI-S] score <=3); 391 received quetiapine XR and 385 received placebo (same dose as last open-label visit). Primary endpoint: time to recurrence of depressive event from randomization. Secondary outcomes included changes from randomization in MADRS total, CGI-S, Pittsburgh Sleep Quality Index (PSQI) global, and Hamilton Anxiety Rating Scale (HAM-A) total scores. Adverse events were recorded throughout. RESULTS: Risk of recurrence of depressive event was significantly (P<.001) reduced by 66% (HR=.34; 95% CI: .25, .46) in patients randomized to continue with quetiapine XR versus patients randomized to switch to placebo. During the randomized phase, quetiapine XR maintained improvements in secondary outcomes (P<.001 for all): MADRS (0.15 versus 2.03), CGI-S (-0.03 versus 0.23); PSQI global (0.06 versus 1.35), and HAM-A total score (0.20 versus 1.58), respectively. The most common AEs (>10% any group) during the randomized period were headache and insomnia. CONCLUSIONS: Quetiapine XR maintenance therapy significantly reduced the risk of a depressive event in patients with MDD stabilized on quetiapine XR, with a safety and tolerability profile consistent with the known profile of quetiapine. PMID- 20734366 TI - Theoretical messenger spectroscopy of microsolvated hydronium and Zundel cations. PMID- 20734367 TI - Unprecedented molecular architectures by the controlled self-assembly of a beta peptide foldamer. PMID- 20734364 TI - Development of anxiety: the role of threat appraisal and fear learning. AB - Anxious individuals exhibit threat biases at multiple levels of information processing. From a developmental perspective, abnormal safety learning in childhood may establish threat-related appraisal biases early, which may contribute to chronic disorders in adulthood. This review illustrates how the interface among attention, threat appraisal, and fear learning can generate novel insights for outcome prediction. This review summarizes data on amygdala function, as it relates to learning and attention, highlights the importance of examining threat appraisal, and introduces a novel imaging paradigm to investigate the neural correlates of threat appraisal and threat-sensitivity during extinction recall. This novel paradigm can be used to investigate key questions relevant to prognosis and treatment. Depression and Anxiety, 2011.(c) 2010 Wiley-Liss, Inc. PMID- 20734368 TI - Cation-exchange porosity tuning in anionic metal-organic frameworks for the selective separation of gases and vapors and for catalysis. PMID- 20734369 TI - Design of living ring-opening alkyne metathesis. PMID- 20734370 TI - A DNA polymerase with increased reactivity for ribonucleotides and C5-modified deoxyribonucleotides. PMID- 20734371 TI - Intra- and interoperator reliability of manual and semi-automated measurement of fetal nuchal translucency by sonographers with different levels of experience. AB - OBJECTIVE: To compare the intra- and interoperator reliability of manual and semi automated nuchal translucency thickness (NT) measurement by sonographers with different levels of experience. METHODS: From our digital database we selected retrospectively 70 NT images without measurements and of highest quality according to the guidelines of The Fetal Medicine Foundation (FMF). Four operators (two experts who were consultants in fetal medicine, one general consultant in obstetrics and gynecology with average knowledge in obstetric ultrasound and one final-year medical student with no experience in ultrasound), having first attended the FMF's online NT measurement course, measured the fetal NT manually according to FMF guidelines and semi-automatically from the inner to inner borders of the two echogenic lines delineating the NT and from the inner border to the middle of the lower NT line. The semi-automatic measurement algorithm identifies the two NT lines within a manually chosen region of interest and standardizes the caliper placement process. Each operator was blinded to any pre-existing measurements. Each measurement was performed twice by each operator. Intraoperator repeatability was assessed by the within-operator SD and intraclass correlation coefficients (ICC). Interoperator reliability was assessed by comparison with the mean manual measurement of the experts, which was considered as the gold standard. RESULTS: The mean NT measurement of the four sonographers was between 1.9 and 2.0 mm with both the manual and the semi-automated inner inner NT measurement and it was between 2.2 and 2.3 mm with the semi-automated inner-middle method. The within-operator SDs of the manual measurement for both experts were similar and significantly lower than those of the non-experts, and all four sonographers performed similarly with the semi-automated measurement. Concerning the interoperator biases relative to the manual measurements of the experts taken as the gold standard, the manual measurements of the student and the general consultant were significantly lower, by 0.18 mm and 0.12 mm. The semi automated inner-inner measurements of all four sonographers were much closer to the gold standard, although there was still a significant underestimation (mean differences from gold standard between 0.04 and 0.06 mm). With the semi-automated inner-middle measurement there was a significant and more pronounced overestimation of fetal NT compared with the gold standard, relative biases ranging from 0.08 to 0.23 mm above it. CONCLUSION: Semi-automation of NT measurement leads to improved standardization of the NT assessment process. In particular, non-expert operators improve as the variability in their caliper placement can be reduced to the level of experts. However, the most important contributor to the inter- and intraoperator variability of NT assessment is that of image acquisition, which is not affected by semi-automation of NT measurement. PMID- 20734372 TI - Microfluidic gradient platforms for controlling cellular behavior. AB - Concentration gradients play an important role in controlling biological and pathological processes, such as metastasis, embryogenesis, axon guidance, and wound healing. Microfluidic devices fabricated by photo- and soft lithography techniques can manipulate the fluidic flow and diffusion profile to create biomolecular gradients in a temporal and spatial manner. Furthermore, microfluidic devices enable the control of cell-extracellular microenvironment interactions, including cell-cell, cell-matrix, and cell-soluble factor interaction. In this paper, we review the development of microfluidic-based gradient devices and highlight their biological applications. PMID- 20734373 TI - A miniaturized spatial temperature gradient capillary electrophoresis system with radiative heating and automated sample introduction for DNA mutation detection. AB - A miniaturized spatial temperature gradient CE system with automated sample introduction for DNA mutation detection was established. Continuous electrokinetic sample injection was achieved by combining an automated slotted vial array sample introduction device to the spatial temperature gradient CE system. The temperature gradient was produced by a radiative heating system with a single graphite block heater, and the stability of the temperature gradient was investigated. The temperature variation of each measure point was 0.12-0.21% RSD (n=7) within 6 h. A 14-cm Teflon AF-coated silica capillary was used both as the separation channel and as the liquid-core waveguide tube of fluorescence signal. Under a temperature gradient from 54.8 to 59.5 degrees C, a low range control mutation standard (209 bp) was separated within 4 min with only 5.6 nL sample consumption. Automated continuous sample introducing and changing were realized with a carryover of 3.3%. Utility of the system was further demonstrated by detecting K-ras gene mutations in paraffin tissue sections from two colorectal cancer patients. PMID- 20734374 TI - Ultrafast manipulation of self-assembled form birefringence in glass. PMID- 20734375 TI - Localized surface plasmons shed light on nanoscale metal hydrides. PMID- 20734376 TI - Ultrafine and smooth full metal nanostructures for plasmonics. AB - Full metal various nanostructures with extremely smooth surface, small feature size and high aspect ratio can be fabricated by a template stripping method with EBL-patterned PMMA layer as a template. It is further demonstrated that our method is crucial to obtain clear and abundant plasmonic modes in nanocavities with metal reflectors. PMID- 20734377 TI - Pentacene thin-film transistors encapsulated by a thin alkane layer operated in an aqueous ionic environment. AB - The encapsulation of pentacene thin-film transistors (TFTs) by a 50 nm thick layer of a long chain alkane (C44H90) enables the operation in an aqueous solution of 1 mM NaCl. It is the first time that pentacene TFTs operate successfully in a liquid environment. This opens new perspectives for biocompatible sensor devices based on pentacene TFTs. PMID- 20734378 TI - Efficiency enhancement of organic solar cells using transparent plasmonic Ag nanowire electrodes. AB - Surface plasmon enhanced photo-current and power conversion efficiency of organic solar cells using periodic Ag nanowires as transparent electrodes are reported, as compared to the device with conventional ITO electrodes. External quantum efficiencies are enhanced about 2.5 fold around the peak solar spectrum wavelength of 560 nm, resulting in 35% overall increase in power conversion efficiency than the ITO control device under normal unpolarized light. PMID- 20734379 TI - Efficient solar cells based on an easily accessible diketopyrrolopyrrole polymer. PMID- 20734380 TI - Photonic crystal devices with multiple dyes by consecutive local infiltration of single pores. PMID- 20734381 TI - Near-infrared inorganic/organic optical upconverter with an external power efficiency of >100%. PMID- 20734382 TI - Quasi-amorphous colloidal structures for electrically tunable full-color photonic pixels with angle-independency. PMID- 20734383 TI - Fully flexible solution-deposited zno thin-film transistors. PMID- 20734384 TI - Temperature-responsive polymer brushes switching from bactericidal to cell repellent. PMID- 20734385 TI - Chitosan films doped with gold nanorods as laser-activatable hybrid bioadhesives. PMID- 20734386 TI - Efficient route to hydroxymethylfurans from sugars via transfer hydrogenation. PMID- 20734387 TI - Role of p115RhoGEF in the regulation of extracellular Ca(2+)-induced choline kinase activation and prostate cancer cell proliferation. AB - Ca(2+) is a ubiquitous cellular signal which plays a central role in the regulation of cell function. To understand aberrant signaling through the Ca(2+) sensing receptor (CaR) in prostate cancer cells, we compared expression of CaR signaling components in human nonmalignant prostate epithelial cells and several prostate cancer cell lines, as well as normal human prostate and prostate tumor specimens. We found that levels of the CaR, Galpha(12) and p115RhoGEF expression are significantly up-regulated in more tumorigenic prostate cancer cells and prostate tumor specimens. By silencing CaR, Galpha(12), p115RhoGEF or choline kinase (ChoK) expression, analyzing the change in lipid profiles, blocking signaling pathways using chemical inhibitors, and co-immunoprecipitating the relevant signaling proteins, we demonstrate that p115RhoGEF, a regulator of G protein signaling (RGS) with GAP activity for Galpha(12/13) and with guanine nucleotide exchange activity for the small G protein Rho, plays an important role in the regulation of Ca(o)(2+)-induced ChoK activation and cell proliferation in more tumorigenic prostate cancer cell lines. The results demonstrate an important role of p115RhoGEF in prostate tumorigenesis and provide a potential target of cancer therapeutics. PMID- 20734388 TI - Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study. AB - Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47 34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression. PMID- 20734389 TI - Differential hypermethylation of genes in vulvar cancer and lichen sclerosus coexisting or not with vulvar cancer. AB - Squamous cell carcinoma (SCC) of the vulva is a heterogeneous disease, associated or not with vulvar lichen sclerosus (LS). The precursor role of LS in vulvar cancer is unclear. We studied the epigenetic alterations of RASSF1A, RASSF2A, p16, TSP-1 and MGMT genes in vulvar SCCs, LS associated with SCC, isolated LS and normal vulvar skin. Gene hypermethylation and human papillomavirus presence were evaluated by methylation-specific PCR and PCR/reverse line blot, respectively. High-risk human papillomavirus types were present in 16.7% of the patients with vulvar SCC. There were increasing percentages of hypermethylation of genes from isolated LS to LS associated with vulvar SCC and vulvar SCC. The genes were hypermethylated more frequently in vulvar SCC associated with LS than in those not associated with LS, MGMT and RASSF2A being unmethylated in LS not associated with vulvar SCC. TSP-1 hypermethylation was related to recurrence in patients with vulvar cancer. Conclusions are as follows: (i) the epigenetic inactivation of genes is a common event in vulvar SCC and is also present in adjacent lesions, implying a possible precursor role for these alterations; (ii) MGMT and RASSF2A hypermethylation are present exclusively in vulvar SCC and LS associated with SCC, and absent from isolated LS; and (iii) TSP-1 hypermethylation is a bad prognosis factor in vulvar SCC. PMID- 20734390 TI - The association of hormonal contraceptive use and HPV prevalence. AB - Women diagnosed with cervical cancer report longer duration and more recent use of combined oral contraceptives (COCs). It is unclear whether COC use is associated with upstream events of human papillomavirus (HPV) infection prior to development of clinical disease. The objective of our study was to assess the association of contraceptive use on the risk for prevalent HPV infection in a cohort of long-term hormonal contraceptive (HC) users. One thousand and seventy (n = 1,070) HIV-negative women aged 20-37 from Thailand enrolled in a prospective study of the natural history of HPV. Baseline HPV genotype information, recency and duration of HC use, sexual behavior, other sexually transmitted infection (STI) information and cervical cytology and histology were assessed. At enrollment, 19.8% and 11.5% of women were infected with any HPV or any high-risk (HR)-HPV, respectively. After adjustment for age, current and past sexual risk behaviors, STI history and cytology, the use of COCs for >6 years was found to be associated with an increased risk of infection with any HPV [prevalence ratio (PR): 1.88 (1.21, 2.90)] and any HR-HPV [PR: 2.68 (1.47, 4.88)] as compared to never users. Recent, long-term COC use was associated with an increased risk for prevalent HPV infection independent of sexual behavior and cervical abnormalities. No similar association was observed for recent or long duration use of progestin-only contraceptives (i.e., depomedroxyprogesterone acetate). These data suggest that COC use may impact early upstream events in the natural history of HPV infection. PMID- 20734391 TI - Oncolytic designer host defense peptide suppresses growth of human liposarcoma. AB - Sarcomas display a rare and heterogeneous group of tumors. Treatment options are limited. Host defense peptides (HDPs), effector molecules of the innate immune system, might provide a more effective treatment option. The aim of our study was to analyze the oncolytic activity and mode of action of a designer HDP. In vitro, the human liposarcoma cell line SW-872 and primary human fibroblasts as a control were exposed to [D]-K(3)H(3)L(9), a 15-mer D,L-amino acid designer peptide. Cell growth (MTT assay), proliferation (BrdU assay) and genotoxicity (TUNEL assay) were analyzed. The mode of action was examined via fluorescence-activated cell sorter (FACS) analysis and confocal laser scanning microscopy. In vivo, [D] K(3)H(3)L(9) (n = 7) was administered intratumorally in a SW-872 xenograft mouse model (Foxn1nu/nu). Phosphate buffered saline served as a control (n = 5). After 4 weeks, tumor sections were histologically analyzed with respect to proliferation, cytotoxicity, vessel density and signs of apoptosis and necrosis, respectively. In vitro, [D]-K(3)H(3)L(9) highly significantly (p < 0.01) inhibited cell metabolism and proliferation. TUNEL assay revealed corresponding genotoxicity. FACS analysis suggested induction of necrosis as a cause of cell death. The mean tumor volume of the control group exponentially increased sevenfold, whereas the mean tumor growth was negligible in the treatment group. Macroscopically, [D]-K(3)H(3)L(9) induced full tumor remission in 43% of treated animals and partial remission in 43%. Vessel density was significantly reduced by 52%. Morphological analyses supported the hypothesis of cancer cell killing by necrosis. In summary, [D]-K(3)H(3)L(9) exerts very promising oncolytic activity on liposarcoma cells. Our study demonstrates the potential of HDPs as a novel therapeutic option in future soft tissue sarcoma therapy. PMID- 20734392 TI - Antiapoptotic function of charged multivesicular body protein 5: a potentially relevant gene in acute myeloid leukemia. AB - In recent years, RNA interference (RNAi) has been widely used to uncover gene function or pathway context of novel genes. In our study, we describe a short hairpin RNA-based RNAi screening of a set of functionally uncharacterized human genes for their possible capability to inhibit apoptosis. We thereby identified a new antiapoptotic function for CHMP5 (charged multivesicular body protein 5), which was confirmed by overexpression and rescue assays. Furthermore, caspase assays showed that CHMP5 silencing induced caspase cascade activation mainly through extrinsic apoptosis pathway. Based on genome-wide expression array profiling, a possible regulatory role of CHMP5 on apoptosis-associated genes and different signaling pathways including nuclear factor kappa B was revealed. In addition, we found significantly higher CHMP5 mRNA levels in acute myeloid leukemia patients. This observation together with the antiapoptotic feature of CHMP5 suggests a possible oncogenic function for this gene in leukemogenesis. PMID- 20734393 TI - Upregulation of TRAG3 gene in urothelial carcinoma of the bladder. AB - Conventional chemotherapy is commonly used for advanced stages of bladder cancer with modest success and high morbidity. Identifying markers of resistance will allow clinicians to tailor treatment to a specific patient population. T24 tumorigenic cell line was grown orthotopically in nude mice and monitored using bioluminescence imaging and microcomputed tomography until they developed metastases. Stable sublines were then developed from primary bladder (T24-P), lung (T24-L) and bone (T24-B) tissues. Chromosomal analysis and DNA microarray were used to characterize these sublines. Real-time quantitative polymerase chain reaction and immunohistochemistry were used for validation. Epigenetic modifiers were used to study gene regulation. The cell viability was quantified with MTT assay. Chromosomal analysis revealed multiple alterations in metastatic cell lines compared to T24-P. DNA microarray analysis showed that taxol resistance associated gene (TRAG) 3 was the most upregulated gene. From real-time quantitative polymerase chain reaction and immunohistochemistry, TRAG3 was significantly higher in T24-L and T24-B than T24-P. TRAG3 gene expression is likely controlled by DNA methylation but not histone acetylation. Interestingly, T24-B and T24-L cells were more resistant than T24-P to treatment with antimicrotubule agents such as docetaxel, paclitaxel and vinblastine. TRAG3 mRNA expression was higher in 20% of patients with <= pT2 (n = 10) and 60% of patients with >= pT3 (n = 20) compared to normal adjacent tissue (p = 0.05). In addition, the median TRAG3 expression was 6.7-fold higher in >= pT3 tumors compared to <= pT2 tumors. Knowing the status of TRAG3 expression could help clinicians tailor treatment to a particular patient population that could benefit from treatment, while allocating patients with resistant tumors to new experimental therapies. PMID- 20734394 TI - Total syntheses of tubulysins. AB - The total syntheses of tetrapeptides tubulysins D (1 b), U (1 c), and V (1 d), which are potent tubulin polymerization inhibitors, are described. The synthesis of Tuv (2), an unusual amino acid constituent of tubulysins, includes an 1,3 dipolar cycloaddition reaction of chiral nitrone D-6 derived from D-gulose with N acryloyl camphor sultam (-)-9 employing the double asymmetric induction, whereas the synthesis of Tup (20), another unusual amino acid, involves a stereoselective Evans aldol reaction of (Z)-boron enolate generated from (S)-4-isopropyl-3 propionyl-2-oxazolidinone with N-protected phenylalaninal and a subsequent Barton deoxygenation protocol. We accomplished the total syntheses of tubulysins U (1 c) and V (1 d) by using these methodologies, in which the isoxazolidine ring was used as the effective protective group for gamma-amido alcohol functionality. Furthermore, to understand the structure-activity relationship of tubulysins, we synthesized tubulysin D (1 b) and cyclo-tubulysin D (1 e) from 2-Me and 20, and ent-tubulysin D (ent-1 d) from ent-2-Me and ent-20, respectively. The preliminary results regarding their biological activities are also reported. PMID- 20734395 TI - Formation of metal-assisted stable double helices in dimers of cyclic bis tetrapyrroles that exhibit spring-like motion. AB - Bidipyrrin-bridged macrocycles, prepared from Ni(II)-bridged dipyrrin-based nanorings by intramolecular oxidative biaryl coupling reactions, yielded [2+4] type Zn(II)-assisted stable twisted-ring dimers comprising two double helices. These [2+4]-type metal complexes can be optically resolved by chiral HPLC and exhibit tunable electronic and optical properties as a result of spring-like motions. The double helices behave as glue to connect two macrocycles and as the screws of hinges to form thermally responsive synchronized spring systems. PMID- 20734396 TI - How does initial treatment choice affect short-term and long-term costs for clinically localized prostate cancer? AB - BACKGROUND: Data regarding costs of prostate cancer treatment are scarce. This study investigates how initial treatment choice affects short-term and long-term costs. METHODS: This retrospective, longitudinal cohort study followed prostate cancer cases diagnosed in 2000 for 5 years using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Men age>=66 years, in Medicare fee for service, diagnosed with clinically localized prostate cancer in 2000 while residing in a SEER region, were matched to noncancer controls using age, sex, race, region, comorbidity, and survival. On the basis of treatment received during the first 9 months postdiagnosis, patients were assigned to watchful waiting, radiation, hormonal therapy, hormonal+radiation, and surgery (may have received other treatments). Incremental costs for prostate cancer were the difference in costs for prostate cancer cases versus matched controls. Costs were divided into initial treatment (months -1 to 12), long-term (each 12 months thereafter), and total (months -1 to 60). Sensitivity analyses excluded the last 12 months of life. RESULTS: A total of 13,769 prostate-cancer cases were matched to 13,769 noncancer controls. Watchful waiting had the lowest initial treatment ($4270) and 5-year total costs ($9130). Initial treatment costs were highest for hormonal+radiation ($17,474) and surgery ($15,197). At $26,896, 5-year total costs were highest for hormonal therapy only followed by hormonal+radiation ($25,097) and surgery ($19,214). After excluding the last 12 months of life, total costs were highest for hormonal+radiation ($23,488) and hormonal therapy ($23,199). CONCLUSIONS: Patterns of costs vary widely based on initial treatment. These data can inform patients and clinicians considering treatment options and policy makers interested in patterns of costs. PMID- 20734397 TI - Clinical significance of regulatory T cells and CD8+ effector populations in patients with human endometrial carcinoma. AB - BACKGROUND: A study was carried out to determine the functional attributes of CD4(+) CD25(+) regulatory T cells in cancer progression by suppressing antitumor immunity. METHODS: Triple-color flow cytometry was used to study the phenotype expression of CD4(+) CD25(+) regulatory T cells and CD8(+) T cells in the peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) of 57 cases of stage I to IV endometrial carcinoma. The expression of T cell subsets was correlated with clinical prognostic parameters. RESULTS: The prevalence of CD4(+) CD25(+) T cells was significantly higher in the TILs than PBLs. The expression of CD4(+) CD25(+) regulatory T cells in cancer milieu correlated with the tumor grade, stage, and myometrium invasion. The expression of FOXP3 and GITR in CD4(+) CD25(+) regulatory T cells was lower in PBLs than TILs. Most tumor infiltrating CD8(+) T cells were CD28(-) CD45RA(-) CD45RO(+) CCR7(-) , suggesting good terminal differentiation. Most of them had an activated role with CD69(+) CD103(+) CD152(+) . Functionally, both granzyme B and perforin were scarcely expressed in peripheral regulatory T cells but were highly expressed in peripheral regulatory T cells in the tumor microenvironment. In contrast, CD8(+) cytotoxic T cells derived from PBLs expressed both granzyme B and perforin, and at significantly higher levels than in TILs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules can be synchronously up regulated in CD8(+) cytotoxic T cells. CONCLUSIONS: Regulatory T cells in the tumor microenvironment may abrogate CD8(+) T cell cytotoxicity in a granzyme B- and perforin-dependent conduit. Decreases in both Th1 cytokines and cytotoxic enzymes are relevant for regulatory T cell-mediated restraint of tumor clearance in vivo. Of clinical significance, the expression of regulatory T cells in TILs may mediate T cell immune repression within cancer milieu and thus greatly correlate with cancer progression. PMID- 20734398 TI - Estimating recurrences prevented from using trastuzumab in HER-2/neu-positive adjuvant breast cancer in the United States. AB - BACKGROUND: Breast cancer recurrence is associated with significant morbidity, mortality, and cost. Patients with early stage HER2+ tumors are at increased risk of recurrence. The use of trastuzumab for these patients has been shown to reduce recurrences and improve overall survival. METHODS: A Monte Carlo simulation was conducted based on Surveillance, Epidemiology, and End Results incidence rates for 2005, United States Census data for 2005, and the results of key trials of the adjuvant use of trastuzumab. Patients included in this analysis had incident, HER2+, stage I to III breast cancer. The number of recurrences that could be prevented with trastuzumab, the cardiac adverse events that might occur, and the associated cost savings were estimated. RESULTS: Approximately 31,200 women had HER2+ breast cancer in 2005, of whom 7298 would have had a recurrence over the subsequent 5 years despite standard of care adjuvant treatment. If trastuzumab were added to their regimen, 2791 women might have avoided recurrence, and 948 may have had an asymptomatic or symptomatic cardiac adverse event, for a ratio of expected recurrences to cardiac adverse events of 3.2 (95% confidence interval, 1.5-5.9). In economic terms, avoidance of future breast cancer recurrences was associated with lifetime reduction in future direct and indirect costs on the order of $240 million to $1.7 billion. CONCLUSIONS: On the basis of the simulation results, targeting HER2+ tumors with trastuzumab in the adjuvant setting should prevent a significant number of women from recurrence events, with important outcomes for patients, physicians, payers, and society. PMID- 20734399 TI - Prevalence, predictors, and characteristics of off-treatment fatigue in breast cancer survivors. AB - BACKGROUND: Lack of consensus regarding how to identify cancer patients with significant fatigue has hampered research regarding cancer-related fatigue (CRF). METHODS: Specific criteria were used to identify CRF cases in women with stage 0 II breast cancer (BC group, n = 304). Women completed assessments before adjuvant therapy (baseline), end of adjuvant therapy (Post-Tx), and 6 and 42 months after end of adjuvant therapy (6 and 42 Month Post-Tx). At each, women completed a clinical interview and questionnaires assessing physical and mental health. A healthy control (HC) group with no history of BC (n = 337) completed 2 similar assessments 36 months apart. RESULTS: Off-treatment CRF prevalence was 9% and 13% at the 6 and 42 Month Post-Tx assessments, respectively. Thus, 15% of the sample evidenced off-treatment CRF with 7% evidencing delayed onset CRF. CRF at the 6 Month Post-Tx assessment was associated only with CRF at baseline (OR = 3.2) and Post-Tx assessments (OR = 3.9). CRF at the 42 Month Post-Tx assessment was associated with CRF at the Post-Tx assessment (OR = 6.1), obesity at baseline, and several baseline measures of coping in response to fatigue. Off-treatment CRF cases differed markedly from CRF noncases and healthy controls on a spectrum of health status indices (mean effect size >1.0 SD). CONCLUSIONS: Results document the prevalence of off-treatment and delayed onset CRF, suggest the utility of a cognitive-behavioral model of CRF, and support NCCN guidelines recommending monitoring fatigue across the cancer trajectory. PMID- 20734400 TI - Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies. AB - BACKGROUND: To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). METHODS: The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. RESULTS: By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). CONCLUSIONS: Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results. PMID- 20734401 TI - Prognostic significance of early lymphocyte recovery in pediatric osteosarcoma. AB - BACKGROUND: Evidence suggests early lymphocyte recovery after chemotherapy predicts superior outcome for patients with cancer, a phenomenon not previously investigated in osteosarcoma. This study determined the prognostic significance of early lymphocyte recovery for pediatric patients with osteosarcoma. PROCEDURES: We reviewed data of 19 consecutive patients treated for osteosarcoma at our institution from 1997 to 2007. After initial chemotherapy, patients were separated into two groups: early versus late lymphocyte recovery, using a threshold absolute lymphocyte count of >= 800 cells/ul on day 14 (ALC-14). RESULTS: The 5-year overall survival (OS) for our cohort was 73.7% [+/- 10.1 standard error (SE)]. Thirteen patients (68%) had an ALC-14 >= 800 cells/ul, with 12/13 alive and 5-year OS of 92.3% (+/- 7.4 SE). In contrast, six patients (32%) had an ALC-14 < 800 cells/uL, with 1/6 alive and 5-year OS of 33.3% (+/- 19.2 SE). The difference is statistically significant (P = 0.0013, log-rank test). Two patients presented with multifocal disease at diagnosis, had late lymphocyte recovery and died. One patient presented with metastatic disease, had early lymphocyte recovery and is alive. Six patients developed relapsed disease with a 5-year OS of 33.3% (+/- 19.2 SE). The majority (5/6) of patients with relapsed disease died while on active therapy. The only survivor in this group had an ALC 14 > 800 cells/ul and recently completed relapse therapy. CONCLUSIONS: These data demonstrate that early lymphocyte recovery represents a significant prognostic indicator for osteosarcoma. Early identification and risk stratification therapy based on the ALC-14 threshold may improve outcomes and our knowledge of this disease. PMID- 20734402 TI - Haemolytic uraemic syndrome in a patient with acute lymphoblastic leukaemia. AB - We describe a patient diagnosed with haemolytic uraemic syndrome (HUS) during long-term maintenance therapy for childhood acute lymphoblastic leukaemia (ALL). He rapidly developed renal failure, hypertension and profound thrombocytopenia. Despite suffering a large intracerebral haemorrhage, he made a full recovery without residual neurological or renal deficit. His case raises the question of whether ALL or its treatments predispose an individual to developing HUS. PMID- 20734403 TI - Clinical significance of serum vascular endothelial growth factor, endostatin, and leptin levels in children with lymphoma. AB - BACKGROUND: A number of clinical studies conducted in adults have demonstrated the prognostic significance of angiogenic factors in malignancies, however, only a limited number of studies have been conducted in children. The aim of this study was to determine serum vascular endothelial growth factor (VEGF), endostatin, and leptin levels in children with lymphoma and to investigate whether these factors provide prognostic information. PROCEDURE: Serum samples from 36 children with lymphoma (non-Hodgkin lymphoma (NHL) N = 21, Hodgkin lymphoma (HL) N = 15) were collected at diagnosis and during remission. Serum samples were also collected from 18 healthy children as the control group. Serum VEGF and endostatin levels were quantified by using enzyme-linked immunosorbent assay (ELISA) and serum leptin by immunoradiometric assay. RESULTS: The serum VEGF levels were found elevated in patients compared to controls (P = 0.033), while endostatin and leptin levels were lower in patients than in controls (endostatin, 43.9 +/- 5.8 ng/ml vs. 123.6 +/- 13.5 ng/ml, P < 0.001; leptin, 5 +/ 1.5 ng/ml vs. 6.7 +/- 1.2 ng/ml, P = 0.013). VEGF levels declined (pre, 151.6 +/ 55.9 pg/ml vs. post, 16.2 +/- 7.9 pg/ml, P = 0.041), while endostatin and leptin levels increased in patients who achieved remission (33 of 36 patients) when compared to pre-treatment levels (endostatin pre, 43.1 +/- 5.9 ng/ml vs. post, 65.9 +/- 6.8 ng/ml, P = 0.047; leptin, pre, 5.3 +/- 1.6 ng/ml vs. post, 9.8 +/- 2.7 ng/ml, P = 0.012). Serum VEGF, endostatin, and leptin levels were not predictive of survival. CONCLUSION: Serial measurement of serum VEGF, endostatin, and leptin levels could potentially be used to predict response to treatment or progressive disease in children with lymphoma. PMID- 20734404 TI - Oncolytic virotherapy reaches adolescence. AB - Lytic viruses kill cells as a consequence of their normal replication life cycle. The idea of harnessing viruses to kill cancer cells arose over a century ago, before viruses were even discovered, from medical case reports of infections associated with cancer remissions. Since then, there has been no shortage of hype, hope, or fear regarding the prospect of oncolytic virotherapy for cancer. Early developments in the field included encouraging antitumor efficacy both in animal studies in the 1920s-1940s and in human clinical trials in the 1950s 1970s. Despite its long-standing history, oncolytic virotherapy was an idea ahead of its time. Without needed advances in molecular biology, virology, immunology, and clinical research ethics, early clinical trials resulted in infectious complications and were fraught with controversial research conduct, so that enthusiasm in the medical community waned. Oncolytic virotherapy is now experiencing a major growth spurt, having sustained numerous laboratory advances and undergone multiple encouraging adult clinical trials, and is now witnessing the emergence of pediatric trials. Here we review the history and salient biology of the field, including preclinical and clinical data, with a special emphasis on those agents now being tested in pediatric cancer patients. PMID- 20734405 TI - Management of sialoblastoma with surgery and brachytherapy. AB - Sialoblastoma is a rare congenital or perinatal salivary gland tumor with significant variability in histological appearance and biological behavior. We reported one case of sialoblastoma occurring in the parotid gland of an 18-month old female. The tumor was excised with negative margins, and the sacrificed facial nerve was reconstructed with great auricular nerve graft. The tumor recurred 6 months after operation and was treated with (125)I seed implant brachytherapy. No recurrence was found after 21 months of follow-up. PMID- 20734406 TI - Fluorescence correlation spectroscopy, raster image correlation spectroscopy, and number and brightness on a commercial confocal laser scanning microscope with analog detectors (Nikon C1). AB - Fluorescence correlation spectroscopy (FCS) was developed in 1972 by Magde, Elson and Webb. Photon counting detectors and avalanche photodiodes have become standards in FCS to the point that there is a widespread belief that these detectors are essential to perform FCS experiments, despite the fact that FCS was developed using analog detectors. Spatial and temporal intensity fluctuation correlations using analog detection on a commercial Olympus Fluoview 300 microscope have been reported by Brown et al. (2008). However, each analog instrument has its own idiosyncrasies that need to be understood before using the instrument for FCS. In this work, we explore the capabilities of the Nikon C1, a low-cost confocal microscope, to obtain single point FCS, Raster-scan image correlation spectroscopy (RICS), and Number and Brightness data both in solution and incorporated into the membrane of giant unilamellar vesicles. We show that it is possible to obtain dynamic information about fluorescent molecules from single point FCS, RICS, and Number and Brightness using the Nikon C1. We highlighted the fact that care should be taken in selecting the acquisition parameters to avoid possible artifacts due to the detector noise. However, due to relatively large errors in determining the distribution of digital levels for a given microscope setting, the system is probably only adequate for determining relative brightness within the same image. PMID- 20734407 TI - Leaf epidermal characteristics of Cissampelos L. (Menispermaceae) species from Northeastern Brazil. AB - The morphological similarities among the species of Cissampelos are remarkable and the difficult to distinguish them as well. This article presents a comparative anatomical study of the leaves of common Northeastern Brazilian species of Cissampelos, carried out using light and scanning electron microscopy. The leaf epidermal was studied to obtain data on epidermal characteristics and to evaluate their taxonomic significance. As results, some micromorphological characters on the leaf epidermal like the cuticular waxes, the presence of papillae in epidermis and nonglandular trichomes, the anticlinal walls epidermal cells, the distribution, density and type of trichomes, and also the type and distribution of epicuticular wax proved to be the most useful characteristics to distinguish the species in taxonomic studies. PMID- 20734408 TI - Anatomical analysis of turgescent and semi-dry resurrection plants: the effect of sample preparation on the sample, resolution, and image quality of X-ray micro computed tomography (MUCT). AB - Computer tomography has been used frequently for the 3-D visualization of plant anatomical traits but sample preparation has been widely neglected. Without any preparation smaller (i.e., up to 1 * 1 cm(2) ) turgescent or semi-dry plant samples (especially leaf samples) diminish the image quality of a scan due to gradual water loss and therefore constant movement. A suitable preparation for scans of turgescent and semi-dry plant samples with a high resolution MUCT (<1-5 MUm) has to be very thin, heat-resistant (up to 35 degrees C), have a low attenuation coefficient, and should not alter the water content and structure of the sample. Several agents have been tested, but only a coating with vaseline conserved the water content of a plant sample efficiently. However, water molecules and vaseline both attenuate the X-ray beam, which decreases the image quality of scans of turgescent or semi-dry plant samples. Therefore, trade-offs between the spatial resolution, sample water content, sample size, and image quality have to be considered: larger samples have to be placed further away from the X-ray tube, which leads to a lower spatial resolution; water and preparation agents attenuate the X-ray beam, causing low-quality images which may be accompanied by motion artifacts compared to a scan of a dry sample, where no preparation is necessary. PMID- 20734409 TI - Microscopic evidences that bone marrow mononuclear cell treatment improves sciatic nerve regeneration after neurorrhaphy. AB - Cell therapy constitutes a possibility for improving nerve regeneration, increasing the success of nerve repair. We evaluate the use of mononuclear cells in the regeneration of the sciatic nerve after axotomy followed by end-to-end neurorrhaphy. Forty adult male Wistar rats (250-300 g) were divided into four groups: (1) sham, (2) neurorrhaphy: the sciatic nerve was sectioned and repaired using epineural sutures, (3) culture medium: after the suture, received an injection of 10 MUL of culture medium into the nerve, and (4) mononuclear cell: after the suture, a concentration of 3 * 10(6) of mononuclear cell was injected in epineurium region. Mononuclear cells were obtained from the bone marrow aspirates and separated by Ficoll-Hypaque method. The histological analyses were performed at the 4th postoperative day. The sciatic functional index, histological, and morphometric analyzes were used to evaluate nerve regeneration at the 6th postoperative week. Six rats were used for immunohistochemical analysis on the 4th postoperative day. In the group 4, on the fourth day, the histological analysis demonstrated a more accelerated degenerative process and an increase of the neurotrophic factors was observed. In the 6th week, all the morphometric results of the group 4 were statistically better compared with groups 2 and 3. There was a statistically significant improvement in the sciatic functional index for group 4 compared with groups 2 and 3. Mononuclear cells stimulated nerve regeneration, most probably by speeding up the Wallerian degeneration process as well as stimulating the synthesis of neurotrophic factors. PMID- 20734410 TI - Description of the immatures of workers of the ant Linepithema micans Forel (Hymenoptera: Formicidae). AB - Linepithema micans Forel is a poorly studied species that is now considered a pest in vineyards in South Brazil. Larval characters have been used in a few phylogenetic studies, and their importance greatly depends in the amount of available information on different species. This study presents a complete panorama on the external morphology of the immatures of L. micans based on observations by light and scanning electron microscopy. The number of larval instars was estimated as three based on the frequency distribution of head widths of 965 larvae. Larvae of L. micans were similar to other Linepithema Mayr in the general format of body and mandibles, presenting a dorsal abdominal protuberance, nine pairs of spiracle, and unbranched hairs. On the other hand, L. micans was unique for having shorter hairs, predominantly denticulate, intraspecific variation in the number of antennal sensilla and in the types of sensilla on the labial palps were reported. PMID- 20734411 TI - The way to a man's heart is through his liver. PMID- 20734412 TI - Bimodal magnetic-fluorescent probes for bioimaging. AB - Fluorescent optical probes have been intensively used in the area of bio-imaging. In this review article, we describe the recent advancements in the synthesis and application of bimodal magnetic-fluorescent probes for bioimaging. The bimodal probes consist of fluorescent [semiconducting quantum dots (e.g., CdSe/ZnS) or rare-earth doped (e.g., NaYF(4) :Yb,Er)] nanoparticles (NPs) and magnetic (iron oxide or gadolinium based) NPs for optical and magnetic resonance (MR) imaging. PMID- 20734413 TI - Developmental changes in the expression of Sox2 in the zebrafish brain. AB - The family of B1 Sox transcription factors plays critical roles in the early stages of development, including the central nervous system. It was demonstrated that Sox2 is expressed in repressed neural stem cells. Therefore, we decided to investigate the expression of Sox2 in the brain of zebrafish at different ages to identify potential neurogenic areas, and to establish the developmental changes they undergo. The brains were assessed by qRT-PCR, western blot, and immunohistochemistry. The maximal expression of Sox2 was found at 15 dpf progressively decreases up to 30 dpf, then increases up to 40 dpf and remains unchanged up to 180 dpf. By western blot three protein bands of 28 kDa, 34 kDa (main band), and 38 kDa were detected in the brain of 180 dpf animals. The immunolocalization of Sox2 revealed that by 15 dpf Sox2 was detected in cells of the olfactory bulb, the walls of the telencephalic and diencephalic ventricles, several nucleus in the diencephalons, and the tectum opticum; by 25-50 dpf the Sox2 positive areas were the same as above, and in the rhombencephalic ventricle and cerebellum. In adult animals Sox2 was restricted to the olfactory bulb and to cells of the telencephalic ventricle walls. Taken together present results demonstrate that the potential neurogenic areas in the brain of zebrafish are widespread than in mammals and change with development, but they are primarily concentrated around the ventricles and olfactory bulb in adults, following a similar localization as in mammals. PMID- 20734414 TI - Transmission X-ray microscopy for full-field nano imaging of biomaterials. AB - Imaging of cellular structure and extended tissue in biological materials requires nanometer resolution and good sample penetration, which can be provided by current full-field transmission X-ray microscopic techniques in the soft and hard X-ray regions. The various capabilities of full-field transmission X-ray microscopy (TXM) include 3D tomography, Zernike phase contrast, quantification of absorption, and chemical identification via X-ray fluorescence and X-ray absorption near edge structure imaging. These techniques are discussed and compared in light of results from the imaging of biological materials including microorganisms, bone and mineralized tissue, and plants, with a focus on hard X ray TXM at <= 40-nm resolution. PMID- 20734415 TI - Target of rapamycin in the oriental fruit fly Bactrocera dorsalis (Hendel): its cloning and effect on yolk protein expression. AB - Target of rapamycin (TOR), a serine/threonine protein kinase, is involved in regulating a number of growth and developmental processes of an organism, including yolk protein synthesis in insects. In this study, TOR gene was isolated, designated BdTOR (GenBank accession no. FJ167395), from the oriental fruit fly Bactrocera dorsalis (Hendel). Quantitative RT-PCR showed a higher expression of BdTOR in the pupa than in other developmental stages, as well as in ovary than in the fat body. Downregulation of BdTOR activity by rapamycin treatment and RNA interference (RNAi) in vivo resulted in a significant reduction in yolk protein transcripts in both fat body and ovary, with a substantial reduction in ovary size. However, an unexpected increase in the expression of yolk protein gene was observed in adult ovary 9 days after rapamycin treatment. Taken together, the results suggest the involvement of BdTOR in the regulation of yolk protein synthesis in B. dorsalis. PMID- 20734417 TI - Opioid system functional regulation in neurological disease management. AB - There is increasing evidence to suggest a role for the opioid system in the control of pathophysiology of neurological disorders (Alzheimer's, Parkinson's, and Huntington's diseases, spinal cord injury, epilepsy, hypoxia, and autism). Resuscitation of the altered expression of the opioid system in various neurological disorders is of therapeutic importance. Such treatment may be beneficial in ameliorating the clinical symptoms of the disorder. This Mini Review provides a brief update on opioid system regulation in neurological disorders and focuses on the opioids' pharmacological importance. PMID- 20734416 TI - The H63D HFE gene variant promotes activation of the intrinsic apoptotic pathway via mitochondria dysfunction following beta-amyloid peptide exposure. AB - Numerous epidemiological studies suggest that the expression of the HFE allelic variant H63D may be a risk factor or genetic modifier for Alzheimer's disease (AD). The H63D variant alters cellular iron homeostasis and increases baseline oxidative stress. The elevated cellular stress milieu, we have proposed, may alter cellular responses to genetic and environmental determinants of AD. Accumulation of beta-amyloid peptides (Abeta) is one of the most prominent pathogenic characteristics of AD. Several studies have demonstrated that Abeta can induce neuronal cell death through apoptosis. In this study, we provide evidence that an Abeta(25-35) fragment, which contains the cytotoxic sequence of the amyloid peptide, activates the intrinsic apoptotic pathway in SH-SY5Y human neuroblastoma cells expressing the HFE allelic variant H63D to a greater extent than in cells with wild-type (WT) HFE. Specifically, Abeta(25-35) peptide exposure significantly induced Bax translocation from the cytosol to the mitochondria in H63D-expressing cells compared with WT cells. This translocation was associated with increased cytochrome c release from mitochondria and an increase in active caspase-9 and caspase-3 activity in H63D cells. Consequently, there is increased apoptosis in cells expressing the H63D variant as opposed to cells expressing WT HFE. We also found increased amyloid precursor protein (APP) and Abeta(1-42) peptide in the mitochondrial compartment as well as increased mitochondrial stress in H63D-expressing cells compared with WT. These findings support our hypothesis that the presence of the HFE H63D allele enables factors that trigger neurodegenerative processes associated with AD and predisposes cells to cytotoxcity. PMID- 20734418 TI - Juvenile hormone III produced in male accessory glands of the longhorned beetle, Apriona germari, is transferred to female ovaries during copulation. AB - We report on juvenile hormone (JH) biosynthesis in vitro by male accessory glands (MAGs) in the longhorned beetle, Aprionona germari, accompanied by the transfer of JH from males to females during copulation. JH was extracted from the MAGs and separated by reversed-phase high-performance liquid chromatography. JH III was identified as the major JH by gas chromatography-mass spectrometry. A radiochemical assay and a non-radioactive method were used to measure the in vitro rate of JH biosynthesis by the MAGs. After 4 h of incubation with 3H methionine in the medium, the radioactivity in the MAGs substantially increased. In a separate assay, incubation of the MAGs with non-radioactive methionine for 4 h resulted in a 39% increase in JH III. Seven-day-old males were injected with medium 199 containing 3H-methionine and 24 h later they were mated with virgin females. Hemolymph and the MAGs were collected from the mated males and hemolymph, ovaries and eggs were collected from the mated females for assaying radioactive JH. The radioactivity incorporated into JH in the MAGs was transferred to the females during copulation and later transferred into their eggs. Assayed 1 h after copulation, JH III level in the MAGs decreased 42% and the content of JH III in the male hemolymph did not change, whereas the content of JH III in the female hemolymph and ovaries both increased. PMID- 20734419 TI - The expression patterns of a eukaryotic initiation factor 3 subunit H in the silk glands in Bombyx mori. AB - Eukaryotic initiation factor 3 subunit H has been characterized in many organisms, and it has been found to play many roles including help regulate translation initiation. In this work, we studied the tissue distribution and expression profiles of Bombyx mori (B. mori) eIF3 subunit H (BmeIF3h). BmeIF3h was prominently expressed in silk glands, with anterior silk glands (ASGs), middle silk glands (MSGs), and posterior silk glands (PSGs) all expressing BmeIF3h. The expression levels of BmeIF3h in MSGs and PSGs were higher than that in ASGs during 0 d and 2 d of the 5th instar larvae. The expression levels of BmeIF3h in MSGs and PSGs were up-regulated once the silk glands began to synthesize silk protein during the feeding stage of the 4th instar larvae. Immunohistochemistry showed that BmeIF3h was distributed in the cytoplasm of MSGs cells and in both the nucleus and the cytoplasm of PSGs cells. These data suggest that BmeIF3h had different action behaviors in the MSGs and PSGs related to the production of the silk glue proteins and silk fibre proteins, respectively. PMID- 20734420 TI - Adrenal incidentalomas: risk of adrenocortical carcinoma and clinical outcomes. AB - INTRODUCTION: The number of incidentally discovered adrenal lesions is increasing due to the widespread use of abdominal imaging. Although most incidentalomas are benign, larger suspicious lesions will require adrenalectomy. The aim of this study is to determine the risk of malignancy in patients undergoing surgery for adrenal incidentaloma; and to compare clinical outcomes in those with adrenocortical carcinoma (ACC) based on the mode of presentation. METHODS: A retrospective study of consecutive patients who underwent adrenalectomy between 1995 and 2008 was performed. Data were retrieved from a prospectively maintained adrenal tumor database. Those with adrenal incidentaloma were selected and histopathology reviewed. All patients with ACC (presenting with symptoms or incidentally) during the same time period were identified and clinical outcomes compared. RESULTS: Adrenalectomy was performed in 274 patients of whom 73 (27%) were characterized pre-operatively as incidentaloma. Benign, non-functioning adrenocortical adenoma was the most common histopathological finding (46 patients, 63%). There was a trend (P = 0.08) towards increased survival amongst the seven patients with ACC presenting incidentally compared to the nine patients with symptomatic ACC. CONCLUSIONS: Adrenal incidentalomas have a small but important risk of malignancy. ACC presenting as incidentaloma appear to have a more favorable prognosis than symptomatic or functioning ACC. PMID- 20734421 TI - Understanding of breast cancer concepts in an undereducated county hospital population. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine how well breast cancer patients at a County hospital understood breast cancer concepts and treatment at time of operation. METHODS: An 11 question multiple-choice examination was devised at a Flesch-Kincaid grade level of 5.8. This was administered to patients prior to undergoing their definitive cancer operation. RESULTS: Forty-one of 42 consecutive women agreed to participate in the study. Seventy-eight percent self identified as Hispanic and 64% had less than a High School education. For the question "Which surgery gives me a better chance to live?" 51% said mastectomy and lumpectomy are equal and 33% thought mastectomy was superior. Interestingly, 88% of respondents understood that screening mammograms are important. Sixty-two percent of the patients, however, did not get screening mammograms. Multivariate analysis revealed that highest level of education (P < 0.001) and employment status (P = 0.007) correlated significantly with test score. Age, insurance status, household income, and ethnicity did not significantly predict test score. CONCLUSION: Although the correct answer was the most frequently selected answer, this examination revealed deficits in the understanding of this undereducated population. Higher level of education and employment status did correlate with improved score. PMID- 20734422 TI - Role of secondary cytoreductive surgery in ovarian cancer relapse: who will benefit? A systematic analysis of 240 consecutive patients. AB - BACKGROUND AND OBJECTIVES: In contrast to primary ovarian cancer, the value of surgery in relapsed-OC (ROC) remains unclear. We evaluated surgical and clinical outcome of secondary cytoreduction in ROC. METHODS: All consecutive ROC patients who underwent secondary tumor-debulking surgery were systematically analyzed as based on a validated intraoperative documentation tool. Tumor dissemination pattern, operative and clinical outcome were evaluated. Cox-regression analysis was performed to identify independent predictors of mortality. RESULTS: Between 09/2000 and 10/2008, 240 operations were evaluated; 184 patients (81.1%) were platinum-sensitive and 43 (20%) platinum-resistant. 47.5% of the patients had ascites, while 85.8% presented a multifocal tumor dissemination pattern. In 53.8% a complete tumor resection was achieved; in another 24.2%, postoperative tumor residuals were < 1 cm. In multivariate analysis, no tumor resection (HR: 7.6; 95% CI: 2.9-19.9), ascites > 500 ml (HR: 6.76; 95% CI: 3.77-12.1), platinum resistance (HR: 3.1; 95% CI: 1.26-7.7), and initial FIGO stage IV (HR: 2.86; 95% CI: 1.16-7) were the most significant risk factors for mortality. Median OS was 42.3 months (95% CI: 24.37-60.2); 17.7 months (95% CI: 12.27-23.13); and 7.7 months (95% CI: 3.1-12.3) for patients with complete tumor resection, tumor residuals <= 1 and > 1 cm, respectively (trend P-value < 0.001). CONCLUSIONS: Absence of ascites, platinum-sensitivity, initial FIGO stage < IV, and complete tumor resection correlate with a significantly better long-term prognosis after ROC surgery. However, a significant trend of continuously improving survival associated with increasing tumor reduction rates could be identified even in patients where a complete tumor resection is not achievable. PMID- 20734423 TI - Optimizing resection for "responding" hepatic metastases after neoadjuvant chemotherapy. AB - Fifty percent of patients with colorectal cancer will develop metastases at some time during their disease, with the liver being the most common site. Recent advances in the treatment of metastatic colorectal cancer have led to a change in treatment paradigm. What follows is a review of the surgical management of hepatic colorectal metastases responding to neoadjuvant chemotherapy. In addition, the complexity of treating patients with "disappearing" colorectal liver metastases is discussed. PMID- 20734424 TI - Endogenous nitric oxide can act as beneficial or deleterious in the hypoxic lung depending on the reoxygenation time. AB - Nitric oxide (NO) has been implicated in many pathophysiological situations in the lung, including hypoxia/reoxygenation. This work seeks to clarify the current controversy concerning the double protective/toxic role of endogenous NO under hypoxia/reoxygenation situations in the lung by using a nitric oxide synthase (NOS) inhibitor, in a novel approach to address the problems raised from assaults under such circumstances. A follow-up study was conducted in Wistar rats submitted to hypoxia/reoxygenation (hypoxia for 30 min; reoxygenation of 0 h, 48 h, and 5 days), with or without prior treatment using the nonselective NOS inhibitor L-NAME (1.5 mM, in drinking water). Lipid peroxidation, apoptosis level, protein nitration, in situ NOS activity and NO production (NOx) were analyzed. This is the first work to focus on the time-course effects of L-NAME in the adult rat lung submitted to hypoxia/reoxygenation. The results showed that after L-NAME administration, in situ NOS activity was almost completely eliminated and consequently, NOx levels fell. Lipid peroxidation and the percentage of apoptotic cells rose at the earliest reoxygenation time (0 h), but decreased in the later period (48 h and 5 days). Also nitrated protein expression decreased at 48 h and 5 days posthypoxia. These results suggest that NOS-derived NO exerts two different effects on lung hypoxia/reoxygenation injury depending on the reoxygenation time: NO has a beneficial role just after the hypoxic stimulus and a deleterious effect in the later reoxygenation times. Moreover, we propose that this dual role of NO depends directly on the producer NOS isoform. PMID- 20734425 TI - Functional and histological improvement of the injured spinal cord following transplantation of Schwann cells transfected with NRG1 gene. AB - In this study, we implanted Schwann cells (SCs) transfected with Neuregulin 1 (NRG1) gene into rats with hemisection spinal cord injury, determined its effects on the repair of spinal cord injury and investigated the underlying mechanisms. Primary SCs were cultured, purified, and transfected with NRG1 gene. SCs and SCs transfected with NRG1 gene were implanted, respectively, into rats with hemisection spinal cord injury. Behavior, imaging, electrophysiology, and immuno histological analyses were performed to evaluate the effect of NRG1 gene transfected SCs on the repair of spinal cord injury. In vitro studies showed that NRG1 protein was highly expressed in SCs transfected with NRG1 gene. In addition, the receptors for NRG1, ErbB2, and ErbB4, were upregulated in a time-dependent manner. NRG1-transfected SCs secreted large amount of NRG1 proteins in vivo, which efficiently promoted the expression of ErbB2 and ErbB4 in the neurons and neuroglia cells. Moreover, the number of NSE- and GFAP-positive cells was increased. After cell transplantation, many transplanted cells survived and migrated to the areas with spinal cord injuries. The injuries were recovered in all the experimental groups, but the most significant recovery was observed in the group of rats implanted with SCs transfected with NRG1 gene. We conclude that NRG1-transfected SCs can significantly increase the effect on the repair of spinal cord injury. This repair effect is achieved via the upregulation of ErbB receptor in the target cells, increased proliferation of glial cells, and protection of neurons from apoptosis. PMID- 20734426 TI - Coexpression of serotonin and nitric oxide in the raphe complex: cortical versus subcortical circuit. AB - Several lines of evidence have implicated a direct reciprocal interaction between serotonin and nitric oxide (NO). The goal of this investigation was, therefore, to examine the coexpression of tryptophan hydroxylase (TPH; the rate limiting enzyme for the synthesis of serotonin) and neuronal NO synthase (nNOS) in the ascending cortical projecting raphe nuclei (B6-B9 subgroups), when compared with the descending spinal cord projecting raphe nuclei (B1-B3 subgroups). Our data demonstrated that: (1) a significant number of raphe-cortical projecting neurons was identified not only in the midline subgroup of dorsal raphe (B6, 7) but also in the median raphe (B8), as well as in the supralemniscal nucleus (B9); (2) serotonergic cortical projecting neurons from these three raphe nuclei exhibited a high (>80%) percentage of coexpression with nNOS immunoreactivity; (3) similarly, serotonin transporter immunoreactive fibers in the medial prefrontal cortex were also double-labeled with nNOS immunoreactivity; (4) in contrast, the descending spinal cord projecting raphe nuclei revealed only TPH but not nNOS immunoreactivity. Our present findings suggest the existence of a direct interaction between serotonin and NO in the ascending cortical projecting raphe system. In contrast, a different strategy appears to operate the descending spinal cord projecting raphe system. PMID- 20734427 TI - Clericuzio-type poikiloderma with neutropenia syndrome in three sibs with mutations in the C16orf57 gene: delineation of the phenotype. AB - We report on three sibs who have autosomal recessive Clericuzio-type poikiloderma neutropenia (PN) syndrome. Recently, this consanguineous family was reported and shown to be informative in identifying the C16orf57 gene as the causative gene for this syndrome. Here we present the clinical data in detail. PN is a distinct and recognizable entity belonging to the group of poikiloderma syndromes among which Rothmund-Thomson is perhaps the best described and understood. PN is characterized by cutaneous poikiloderma, hyperkeratotic nails, generalized hyperkeratosis on palms and soles, neutropenia, short stature, and recurrent pulmonary infections. In order to delineate the phenotype of this rare genodermatosis, the clinical presentation together with the molecular investigations in our patients are reported and compared to those from the literature. PMID- 20734428 TI - Valproic acid and ADHD symptoms in fragile X syndrome: more evidence is needed. PMID- 20734429 TI - Synergistic repression of estrogen receptor transcriptional activity by FHL2 and Smad4 in breast cancer cells. AB - Four and a half LIM domain protein 2 (FHL2) has been implicated in development and progression of various types of cancers. However, little is known about the biological function of FHL2 in breast cancer. Here, we report that FHL2 physically and functionally interacts with estrogen receptors (ERalpha and ERbeta), important regulators of breast cancer development and progression. The N terminal half LIM domain or a single LIM domain of FHL2 was sufficient for its interaction with ERalpha and ERbeta. Overexpression of FHL2 reduced ER transcriptional activity in breast cancer cells, whereas reduction of endogenous FHL2 with FHL2 small interfering RNA enhanced ER transactivation. Moreover, FHL2 cooperates with Smad4, a previously known corepressor for ERalpha, to inhibit ERalpha transcriptional activity as well as expression of the estrogen-responsive gene cathepsin D. The synergistic inhibition of ERalpha transcriptional activity by FHL2 and Smad4 may be due to enhanced interaction of Smad4 with ERalpha by FHL2, because FHL2(1-156), the FHL2 deletion mutant, which showed no synergistic effect, failed to increase such interaction. These data suggested the cooperative regulation of estrogen signaling by FHL2 and Smad4 in breast cancer cells, and might provide a new regulation mechanism underlying breast cancer development and progression. PMID- 20734430 TI - Calmodulin binding-heat shock proteins form a ring structure in the rat testis. PMID- 20734431 TI - Antegrade anterolateral thigh perforator flap advancement for soft-tissue reconstruction of the knee: case report. AB - Reconstruction of soft-tissue defects of the knee has always been a challenging task to the plastic surgeon. In some cases, local or regional flaps are too small or have limited arc of rotation for adequate coverage. Free flaps can be technically demanding and time consuming. We report for the first time an antegrade anterolateral thigh perforator flap advancement, used to reconstruct the knee soft tissue defect in a 54-year-old man. The operative procedure required skeletonizing the perforators of anterolateral thigh flap and advancing the flap in the defect. The postoperative course was uneventful with the patient returned to normal daily activity and full range of motion 3-months postoperatively. The shorter operating time with decreased donor-site morbidity make this flap as a valuable alternative for soft-tissue reconstruction of the knee. PMID- 20734432 TI - Composite skull and dura defect reconstruction using combined latissimus dorsi musculocutaneous and serratus anterior muscle-rib free flap coupled with vascularized galea transfer: a case report. AB - Recalcitrant epidural abscess following cranioplasty is a complicated problem, which becomes even more trying when large span of dura and skull bone are being replaced by alloplastic materials. A 22-year-old male underwent right fronto temporo-parietal craniectomy and duroplasty with artificial dura graft after traumatic brain injury. Epidural abscesses recurred after cranioplasty with autologous bone graft as well as with a methyl methacrylate bone plate. The massive defects of both the dura and skull bone (15 * 9 cm) caused by radical debridement were reconstructed successfully with a combined free latissimus dorsi and serratus anterior myo-osseous flap transfer plus galea flap transposition. Proper contour and adequate stability of the construct were maintained during 2 year follow up without episodes of relapsing infection. PMID- 20734433 TI - Use of vascularized jejunum flap for vaginal reconstruction: a word of caution. PMID- 20734434 TI - Delayed deepithelization of the chestwall skin: a cautious approach in perforator flap breast reconstruction. PMID- 20734435 TI - A mouse model for sleeve gastrectomy: applications for diabetes research. AB - INTRODUCTION: Discovery of enhanced glucose tolerance following bariatric surgery has sparked renewed interest in the investigation of unchartered underlying pathways of glucose homeostasis. Delineation of this pathway may ultimately be the first step in the creation of a novel therapy for type II diabetes. Nevertheless, the technical complexity and formidable nature of these surgeries coupled with the fragile nature of small rodents has made the creation of a mouse model to study these effects incredibly challenging. We have created a simplified sleeve gastrectomy mouse model to study the effects of bariatric surgery on glucose tolerance and beta cell proliferation. METHODS: Nineteen mice were randomized to undergo either sleeve gastrectomy (SG) (9) or sham operation (SH) (10). Weight and serum glucose were measured three times weekly and serum insulin measurements and pancreatic harvest were performed at the time of sacrifice. Five mice from each group were sacrificed after one week and the remainder sacrificed after one month. RESULTS: Survival of mice was 100% for both groups. The SG group demonstrated an initial drop in weight and serum glucose as compared to SH, which normalized by one month following surgery. Serum insulin levels and rate of beta cell proliferation were similar in both groups after one week and one month. CONCLUSION: The simplified sleeve gastrectomy is a technically straightforward, low-mortality technique for creating a bariatric mouse model which most faithfully replicates bariatric surgery performed in humans. This model can be a valuable tool to investigate the glucose tolerance and beta cell effects of bariatric surgery. PMID- 20734436 TI - Genetic make up and structure of Colombian populations by means of uniparental and biparental DNA markers. AB - Colombia is a country with great geographic heterogeneity and marked regional differences in pre-Columbian native population density and in the extent of past African and European immigration. As a result, Colombia has one of the most diverse populations in Latin America. Here we evaluated ancestry in over 1,700 individuals from 24 Colombian populations using biparental (autosomal and X Chromosome), maternal (mtDNA), and paternal (Y-chromosome) markers. Autosomal ancestry varies markedly both within and between regions, confirming the great genetic diversity of the Colombian population. The X-chromosome, mtDNA, and Y chromosome data indicate that there is a pattern across regions indicative of admixture involving predominantly Native American women and European and African men. PMID- 20734437 TI - Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history. AB - The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with increased cholesterol levels and heart disease. Population allele frequencies of APOE have previously been shown to vary, with epsilon4 frequencies generally increasing with latitude. We hypothesize that this trend resulted from natural selection protecting against low-cholesterol levels. In high-latitude cold environments and low-latitude hot environments, metabolic rate is elevated, which could require higher cholesterol levels. To explore this hypothesis, we compiled APOE allele frequencies, latitude, temperature, and elevation from populations around the world. epsilon4 allele frequencies show a curvilinear relationship with absolute latitude, with lowest frequencies found in the mid-latitudes where temperatures generally require less expenditure on cooling/thermogenesis. Controlling for population structure in a subset of populations did not appreciably change this pattern of association, consistent with selection pressures that vary by latitude shaping epsilon4 allele frequencies. Temperature records also predict APOE frequency in a curvilinear fashion, with lowest epsilon4 frequencies at moderate temperatures. The model fit between historical temperatures and epsilon4 is less than between latitude and epsilon4, but strengthened after correcting for estimated temperature differences during the Paleolithic. Contrary to our hypothesis, we find that elevation did not improve predictive power, and an integrated measure of the cholesterol effect of multiple APOE alleles was less related to latitude than was epsilon4 alone. Our results lend mixed support for a link between past temperature and human APOE allele distribution and point to the need to develop better models of past climate in future analyses. PMID- 20734438 TI - Fluctuating and directional asymmetry in young human males: effect of heavy working condition and socioeconomic status. AB - Many adverse environmental and genetic factors can affect stability of development during human growth. Although the level of fluctuating asymmetry (FA) may be influenced by environmental and genetic stress encountered during this period, directional asymmetry (DA) is largely attributable to differential mechanical loading during bone growth, for example, handedness. I assessed the effects of heavy working conditions and socioeconomic conditions on asymmetry levels in three groups of young human males: 1) individuals employed in the heavy industry sector (n = 104, mean age = 18.48 +/- 0.61 years), 2) individuals who had the same socioeconomic status as the laborers (n = 102, mean age = 18.39 +/- 0.58 years) but were not laborers, and 3) nonlaborers from the higher socioeconomic levels of society (n = 103, mean age = 18.43 +/- 0.67). For all subjects, hand length, hand width, elbow width, wrist width, knee width, ankle width, foot length, foot width, ear length, and ear width were measured. All measurements of the upper extremities in the labor group appeared to exhibit DA; in the other two groups only hand measurements exhibited DA. According to analysis of FA, subjects living in poor conditions exhibited more FA than their nonlaborer peers living in better conditions. In addition, biomechanical pressures due to heavy working conditions of the labor group appeared to cause increased DA in the upper extremities: DA increased with an increase in the number of years working. PMID- 20734439 TI - Upper limb kinematics and the role of the wrist during stone tool production. AB - Past studies have hypothesized that aspects of hominin upper limb morphology are linked to the ability to produce stone tools. However, we lack the data on upper limb motions needed to evaluate the biomechanical context of stone tool production. This study seeks to better understand the biomechanics of stone tool making by investigating upper limb joint kinematics, focusing on the role of the wrist joint, during simple flake production. We test the hypotheses, based on studies of other upper limb activities (e.g., throwing), that upper limb movements will occur in a proximal-to-distal sequence, culminating in rapid wrist flexion just prior to strike. Data were captured from four amateur knappers during simple flake production using a VICON motion analysis system (50 Hz). Results show that subjects utilized a proximal-to-distal joint sequence and disassociated the shoulder joint from the elbow and wrist joints, suggesting a shared strategy employed in other contexts (e.g., throwing) to increase target accuracy. The knapping strategy included moving the wrist into peak extension (subject peak grand mean = 47.3 degrees) at the beginning of the downswing phase, which facilitated rapid wrist flexion and accelerated the hammerstone toward the nodule. This sequence resulted in the production of significantly more mechanical work, and therefore greater strike forces, than would otherwise be produced. Together these results represent a strategy for increasing knapping efficiency in Homo sapiens and point to aspects of skeletal anatomy that might be examined to assess potential knapping ability and efficiency in fossil hominin taxa. PMID- 20734440 TI - Estimating body mass in subadult human skeletons. AB - Methods for estimating body mass from the human skeleton are often required for research in biological or forensic anthropology. There are currently only two methods for estimating body mass in subadults: the width of the distal femur metaphysis is useful for individuals 1-12 years of age and the femoral head is useful for older subadults. This article provides age-structured formulas for estimating subadult body mass using midshaft femur cross-sectional geometry (polar second moments of area). The formulas were developed using data from the Denver Growth Study and their accuracy was examined using an independent sample from Franklin County, Ohio. Body mass estimates from the midshaft were compared with estimates from the width of the distal metaphysis of the femur. Results indicate that accuracy and bias of estimates from the midshaft and the distal end of the femur are similar for this contemporary cadaver sample. While clinical research has demonstrated that body mass is one principle factor shaping cross sectional geometry of the subadult midshaft femur, clearly other biomechanical forces, such as activity level, also play a role. Thus formulas for estimating body mass from femoral measurements should be tested on subadult populations from diverse ecological and cultural circumstances to better understand the relationship between body mass, activity, diet, and morphology during ontogeny. PMID- 20734441 TI - Chronic constrictive pericarditis. PMID- 20734442 TI - Triage of chest pain patients in the emergency department. PMID- 20734443 TI - Late perforation by cardiac implantable electronic device leads: clinical presentation, diagnostic clues, and management. AB - Late intracardiac lead perforation is defined as migration and perforation of an implanted lead after 1 month of cardiac electronic device implantation. It is an under-recognized complication with significant morbidity and mortality, particularly if not recognized early. Two patients with late perforation caused by passive-fixation leads are reported and the clinical features of their presentation and management are reviewed. We conducted a thorough review of the available English language literature pertaining to this complication to draw relevant conclusions regarding presentation, diagnosis, and management. Early recognition of this complication is important as the indications for and numbers of patients who receive cardiac implantable electronic devices continue to expand. PMID- 20734444 TI - Periprocedural myocardial infarction: review and classification. AB - Technical and pharmacologic advances have reduced the occurrence of large periprocedural myocardial infarction (PMI) after percutaneous coronary interventions (PCI), but PMI still occurs in 6% to 18% of the cases and is associated with impaired short- and long-term survival. PMI might be due to side branch closure or flow-limiting dissection, but is most often diagnosed after apparently uncomplicated PCI and is due to atheroembolization into the microcirculation. Various definitions of PMI are used in clinical trials, but a rise in creatine kinase-MB greater than 3 to 8 times the upper limit of normal is consistently associated with worse prognosis, particularly as it reflects a more extensive and unstable atherosclerotic burden. On the other hand, data regarding the independent prognostic value of periprocedural troponin increase are conflicting. Some data suggest that PMI has a better prognosis than a spontaneously occurring myocardial infarction, and that its incidence is reduced with aggressive antiplatelet and statin therapy. PMID- 20734445 TI - Nesiritide in acute decompensated heart failure: a pooled analysis of randomized controlled trials. AB - BACKGROUND: Previous randomized controlled trials (RCTs) evaluating nesiritide for the treatment of acute decompensated heart failure (ADHF) have reported wide variances in mortality hazard ratios for nesiritide vs controls, but these individual trials were neither designed nor powered to evaluate mortality. This study used relevant data from all RCTs of nesiritide in ADHF completed as of June 2006 to independently estimate the effect of nesiritide on 30- and 180-day mortality. HYPOTHESIS: Administration of nesiritide to treat patients with ADHF does not significantly increase mortality at 30 or 180 days. METHODS: Six trials met prespecified criteria for inclusion in this analysis. Primary data from these trials were obtained from Scios Inc. (Fremont, CA). Statistical models were fitted to estimate 4 effects: dose response, differing control groups, vulnerable subgroup interactions, and time of death relative to nesiritide administration. All models included 4 baseline covariates that were significantly and independently associated with mortality. RESULTS: Complete covariate data were available in 1472 of 1538 subjects (96%). The risk-adjusted hazard ratio for mortality was 1.05 (95% confidence interval [CI]: 0.85-1.30) at 30 and 1.00 (95% CI: 0.88-1.14) at 180 days with no clear relationship to nesiritide dose. In addition to consistent results across 2 time points, no significant evidence of sensitivity to control group or baseline risk factors was found. CONCLUSIONS: Currently available data suggest nesiritide does not significantly increase mortality at 30 or 180 days. PMID- 20734446 TI - Efficacy of fractional flow reserve measurements at side branch vessels treated with the crush stenting technique in true coronary bifurcation lesions. AB - BACKGROUND: Measurement of fractional flow reserve (FFR) has been frequently used to optimize the results of coronary stenting in patients with significant narrowing of coronary arteries. HYPOTHESIS: There has been a consensus that an FFR value > 0.90 after stenting is a useful surrogate for favorable long-term clinical outcome. We evaluated the efficacy of FFR measurement at side branch vessels of true coronary bifurcation lesions that were treated with the crush stenting technique. METHODS: This study included 12 patients with significant narrowing in both a main coronary vessel and side branch vessel who underwent the crush stenting procedure. RESULTS: After crush stenting, FFR measurement was performed at the side branch vessel prior to and after kissing balloon angioplasty (KBA). FFR values increased significantly, from 0.94 +/- 0.04 pre-KBA to 0.97 +/- 0.03 post-KBA (P = 0.011). FFR values after crush stenting but prior to KBA already measured > 0.90 in 9 of the 12 patients (75%). FFR values for the remaining 3 patients were 0.88, 0.88, and 0.90, respectively. CONCLUSIONS: FFR measurement at side branch vessels of coronary bifurcation lesions treated with crush stenting may not contribute to adequate decision-making for improvement of long-term clinical outcomes. KBA should be strongly considered for patients with bifurcation lesions treated with crush stenting. PMID- 20734447 TI - Sex and race are associated with the absence of epicardial coronary artery obstructive disease at angiography in patients with acute coronary syndromes. AB - BACKGROUND: A substantial minority of patients with acute coronary syndromes (ACS) do not have a diameter stenosis of any major epicardial coronary artery on angiography ("no obstruction at angiography") of > or = 50%. We examined the frequency of this finding and its relationship to race and sex. HYPOTHESIS: Among patients with myocardial infarction, younger age, female sex and non-white race are associated with the absence of obstructive coronary artery disease at angiography. METHODS: We reviewed the results of all angiograms performed from May 19, 2006 to September 29, 2006 at 1 private (n = 793) and 1 public (n = 578) urban academic medical center. Charts were reviewed for indication and results of angiography, and for demographics. RESULTS: The cohort included 518 patients with ACS. There was no obstruction at angiography in 106 patients (21%), including 48 (18%) of 258 patients with myocardial infarction. Women were more likely to have no obstruction at angiography than men, both in the overall cohort (55/170 women [32%] vs 51/348 men [15%], P < 0.001) and in the subset with MI (29/90 women [32%] vs 19/168 men [11%], P < 0.001). Black patients were more likely to have no obstruction at angiography relative to any other subgroup (24/66 [36%] vs 41/229 [18%] Whites, 31/150 [21%] Hispanics, and 5/58 [9%] Asians, P = 0.001). Among women, Black patients more frequently had no obstruction at angiography compared with other ethnic groups (16/27 [59%] vs 17/59 [29%] Whites, 17/60 [28%] Hispanics, and 3/19 [6%] Asians, P = 0.001). CONCLUSIONS: A high proportion of a multiethnic sample of patients with ACS were found to have no stenosis > or = 50% in diameter at coronary angiography. This was particularly common among women and Black patients. PMID- 20734448 TI - Accuracy of transthoracic echocardiography for the measurement of the ascending aorta: comparison with transesophageal echocardiography. AB - BACKGROUND: There has been a substantial increase in the number of imaging studies performed to assess thoracic aortic pathology. We sought to determine the accuracy of transthoracic echocardiography (TTE) compared to transesophageal echocardiography (TEE) for measuring ascending aortic size. HYPOTHESIS: Transthoracic echocardiography is reasonably accurate for assessing ascending aortic dimension. METHODS: Fifty-two patients with or without aortic disease underwent both TTE with nonstandard views and TEE. The ascending aorta was measured at 4 levels by 2 blinded observers for each modality. Pearson's correlation coefficients were determined and Bland-Altman plots and analyses were constructed. Inter- and intraobserver variability was determined in a random subgroup of patients. RESULTS: The mean age of the group was 65.5 years old and 15% had aortic dilation >4.0 cm. A strong positive correlation between the 2 imaging modalities was seen at all levels with the highest correlation for the maximum diameter of the ascending aorta (r = 0.936, P < 0.0001). Interobserver and intraobserver variability showed a good intraclass correlation among readers and among the same reader at all levels. CONCLUSIONS: Transthoracic echocardiography using nonstandard imaging windows is accurate in comparison to TEE for measurement of the ascending aorta at multiple levels in patients with or without aortic pathology. The findings of this study provide support for selected serial follow-up of patients with aortic disease by TTE only. PMID- 20734449 TI - Comparison of C-reactive protein and albumin excretion as prognostic markers for 10-year mortality after myocardial infarction. AB - BACKGROUND: C-reactive protein (CRP) is an established prognostic marker in the setting of acute coronary syndromes. Recently, albumin excretion rate also has been found to be associated with adverse outcomes in this clinical setting. Our aim was to compare the prognostic power of CRP and albumin excretion rate for long-term mortality following acute myocardial infarction (AMI). HYPOTHESIS: To determine whether albumin excretion rate is a better predictor of long-term outcome than CRP in post-AMI patients. METHODS: We prospectively studied 220 unselected patients with definite AMI (median [interquartile] age 67 [60-74] y, female 26%, heart failure 39%). CRP and albumin-to-creatinine ratio (ACR) were measured on day 1, day 3, and day 7 after admission in 24-hour urine samples. Follow-up duration was 10 years for all patients. RESULTS: At survival analysis, both CRP and ACR were associated with increased risk of 10-year all-cause mortality, also after adjusting for age, hypertension, diabetes mellitus, prehospital time delay, creatine kinase-MB isoenzyme peak, heart failure, and creatinine clearance. CRP and ACR were associated with nonsudden cardiovascular (non-SCV) mortality but not with sudden death (SD) or noncardiovascular (non-CV) death. CRP was not associated with long-term mortality, while ACR was independently associated with outcome both in short- and long-term analyses. At C statistic analysis, CRP did not improve the baseline prediction model for all cause mortality, while it did for short-term non-SCV mortality. ACR improved all cause and non-SCV mortality prediction, both in the short and long term. CONCLUSIONS: ACR was a better predictor of long-term mortality after AMI than CRP. PMID- 20734450 TI - Trends in in-hospital outcome after percutaneous coronary intervention in the drug-eluting stents era. AB - BACKGROUND: The introduction of drug-eluting stents (DES) dramatically changed the practice of percutaneous coronary intervention (PCI) in the 2000s. Little is known about trends in in-hospital outcome after PCI in the DES era. HYPOTHESIS: The in-hospital outcomes after PCI might be continuously improved over time. METHODS: We analyzed in-hospital outcomes of 21,667 patients who underwent PCI at Fu Wai Hospital in the past 5 years. The patients were divided into 5 groups according to the time of their intervention: group 1 (June 2004 to May 2005), group 2 (June 2005 to May 2006), group 3 (June 2006 to May 2007), group 4 (June 2007 to May 2008), and group 5 (June 2008 to May 2009). RESULTS: Procedural success rates for the 5 groups were 93.6%, 95%, 94.4%, 94.2%, and 94.3%, respectively (P = 0.39). Significant reduction in in-hospital major adverse cardiac events (3.1%, 3.4%, 2.8%, 1.6%, and 1.0%, P < 0.001) and need for target vessel revascularization (2.0%, 2.2%, 1.5%, 0.4%, and 0.2%, P < 0.001) was noted over time, which was associated with a significant increase in use of DES (from 56.6% to 97.0%, P < 0.001). On multivariate analysis, use of DES, dissection during procedure, left main lesion, prior myocardial infarction, and age > or = 65 years were independent predictors of major adverse cardiovascular events. CONCLUSIONS: There were substantial reductions in in-hospital major adverse cardiac events and target-vessel revascularization over the past 5 years. This reduction was associated with the concurrent increased use of DES. PMID- 20734451 TI - Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. AB - Two cathepsin K inhibitors (CatKIs) were compared with alendronate (ALN) for their effects on bone resorption and formation in ovariectomized (OVX) rabbits. The OVX model was validated by demonstrating significant loss (9.8% to 12.8%) in lumbar vertebral bone mineral density (LV BMD) in rabbits at 13-weeks after surgery, which was prevented by estrogen or ALN. A potent CatKI, L-006235 (L 235), dosed at 10 mg/kg per day for 27 weeks, significantly decreased LV BMD loss (p < .01) versus OVX-vehicle control. ALN reduced spine cancellous mineralizing surface by 70%, whereas L-235 had no effect. Similarly, endocortical bone formation rate and the number of double-labeled Haversian canals in the femoral diaphysis were not affected by L-235. To confirm the sparing effects of CatKI on bone formation, odanacatib (ODN) was dosed in food to achieve steady-state exposures of 4 or 9 uM/day in OVX rabbits for 27 weeks. ODN at both doses prevented LV BMD loss (p < .05 and p < .001, respectively) versus OVX-vehicle control to levels comparable with sham or ALN. ODN also dose-dependently increased BMD at the proximal femur, femoral neck, and trochanter. Similar to L 235, ODN did not reduce bone formation at any bone sites studied. The positive and highly correlative relationship of peak load to bone mineral content in the central femur and spine suggested that ODN treatment preserved normal biomechanical properties of relevant skeletal sites. Although CatKIs had similar efficacy to ALN in preventing bone loss in adult OVX rabbits, this novel class of antiresorptives differs from ALN by sparing bone formation, potentially via uncoupling bone formation from resorption. PMID- 20734452 TI - Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women. AB - All people are exposed to cadmium (Cd) via food; smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. Within the population-based Swedish Mammography Cohort, we assessed urinary Cd [U-Cd, ug/g of creatinine (cr)] as a marker of lifetime exposure and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) among 2688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. In linear regression, U-Cd was inversely associated with BMD at the total body (p < .001), femoral neck (p = .025), total hip (p = .004), lumbar spine (p = .088), and volumetric femoral neck (p = .013). In comparison with women with U-Cd < 0.50 ug/g of cr, those with U-Cd >= 0.75 ug/g of cr had odds ratios (ORs) of 2.45 [95% confidence interval (CI) 1.51-3.97] and 1.97 (95% CI 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.47 (95% CI 1.46 8.23) and 3.26 (95% CI 1.44-7.38). For any first fracture (n = 395), the OR was 1.16 (95% CI 0.89-1.50) comparing U-Cd >= 0.50 ug/g of cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture, and 1.89 (1.25-2.85) for multiple incident fractures. U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures, especially in never-smokers, indicating a larger concern than previously known. PMID- 20734453 TI - An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation. AB - Discoidin domain receptor 2 (DDR2) belongs to receptor tyrosine kinase (RTK) family and is activated by collagen binding. Although the bone defects in Ddr2 null mice have been reported for a decade, the molecular mechanism remains unclear. This study sought to investigate the function and detailed mechanism of DDR2 in osteogenic and chondrogenic differentiation. Herein we found that in preosteoblastic cells, DDR2 activation was enhanced by osteogenic induction but was not paralleled with the alteration of DDR2 expression. Under differentiated condition, downregulation of endogenous DDR2 through specific shRNA dramatically repressed osteoblastic marker gene expression and osteogenic differentiation. Enforced expression of constitutively activated DDR2 increased the expression of bone markers in both undifferentiated and differentiated osteoblasts. Importantly, molecular evidence showed that DDR2 regulated the transactivity of Runx2, a master transcription factor involved in skeletal development, by modulating its phosphorylation. Analysis of candidate protein kinases indicated that extracellular signal-regulated kinase (ERK) activation is responsive to DDR2 signaling and involved in DDR2 regulation of Runx2 phosphorylation and transcriptional activity. Notably, a gain-of-function mutant of Runx2 with enhanced ERK-independent phosphorylation rescued the impaired osteogenic phenotypes observed in Ddr2-silenced cells, whereas a Runx2 mutant devoid of phosphorylation regulation by ERK inhibited DDR2 induction of osteogenesis. In addition, DDR2 facilitated Runx2 transactivation and type X collagen expression in hypertrophic chondrocytes. Thus this study reveals for the first time that DDR2 plays an essential role in osteoblast and chondrocyte differentiation. The mechanism disclosure may provide therapeutic targets for human genetic disorders caused by DDR2 deficiency. PMID- 20734454 TI - The biological function of DMP-1 in osteocyte maturation is mediated by its 57 kDa C-terminal fragment. AB - Dentin matrix protein 1 (DMP-1) is a key molecule in controlling osteocyte formation and phosphate homeostasis. Based on observations that full-length DMP-1 is not found in bone, but only cleaved fragments of 37 and 57 kDa are present, and in view of the finding that mutations in the 57-kDa fragment result in disease, we hypothesized that the 57-kDa C-terminal fragment is the functional domain of DMP-1. To test this hypothesis, a 3.6-kb type I collagen promoter was used to express this 57-kDa C-terminal fragment for comparison with full-length DMP-1 in Dmp1 null osteoblasts/osteocytes. Not only did expression of the full length DMP-1 in bone cells fully rescue the skeletal abnormalities of Dmp1 null mice, but the 57-kDa fragment also had similar results. This included rescue of growth plate defects, osteomalacia, abnormal osteocyte maturation, and the abnormal osteocyte lacunocanalicular system. In addition, the abnormal fibroblast growth factor 23 (FGF-23) expression in osteocytes, elevated circulating FGF-23 levels, and hypophosphatemia were rescued. These results show that the 57-kDa C terminal fragment is the functional domain of DMP-1 that controls osteocyte maturation and phosphate metabolism. PMID- 20734455 TI - GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice. AB - Estrogen regulation of the male skeleton was first clearly demonstrated in patients with aromatase deficiency or a mutation in the ERalpha gene. Estrogen action on the skeleton is thought to occur mainly through the action of the nuclear receptors ERalpha and ERbeta. Recently, in vitro studies have shown that the G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). GPR30-deficient mouse models have been generated to study the in vivo function of this protein; however, its in vivo role in the male skeleton remains underexplored. We have characterized size, body composition, and bone mass in adult male Gpr30 knockout (KO) mice and their wild-type (WT) littermates. Gpr30 KO mice weighed more and had greater nasal-anal length (p < .001). Both lean mass and percent body fat were increased in the KO mice. Femur length was greater in Gpr30 KO mice, as was whole-body, spine, and femoral areal bone mineral density (p < .01). Gpr30 KO mice showed increased trabecular bone volume (p < .01) and cortical thickness (p < .001). Mineralized surface was increased in Gpr30 KO mice (p < .05). Bromodeoxyuridine (BrdU) labeling showed greater proliferation in the growth plate of Gpr30 KO mice (p < .05). Under osteogenic culture conditions, Gpr30 KO femoral bone marrow cells produced fewer alkaline phosphatase-positive colonies in early differentiating osteoblast cultures but showed increased mineralized nodule deposition in mature osteoblast cultures. Serum insulin-like growth factor 1 (IGF-1) levels were not different. These data suggest that in male mice, GPR30 action contributes to regulation of bone mass, size, and microarchitecture by a mechanism that does not require changes in circulating IGF 1. PMID- 20734456 TI - Hospitalizations with healthcare-associated complicated skin and skin structure infections: impact of inappropriate empiric therapy on outcomes. AB - OBJECTIVE: Inappropriate empiric therapy worsens outcomes in certain healthcare associated infections (HCAI). We studied the association of inappropriate empiric therapy with outcomes in patients with HCA complicated skin and skin structure infections (cSSSI). DESIGN: A single-center retrospective cohort study. PATIENTS: Hospitalized with a culture-positive cSSSI. MEASUREMENTS: We defined HCA-cSSSI as having >=1 of these risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, (4) transfer from a nursing home, and inappropriate treatment as no antimicrobial therapy active against the pathogen(s) within 24 hours of obtaining culture specimen. We performed descriptive and multivariate statistics to compute the impact of inappropriate empiric therapy on outcomes. Hospital length of stay (LOS) served as primary and mortality as secondary outcomes. RESULTS: Of the 717 patients with culture positive cSSSI, 527 (73.5%) had HCAI, of whom 405 (76.9%) received appropriate treatment. A higher proportion of those receiving inappropriate than appropriate treatment had a decubitus ulcer (29.5% vs. 10.9%, P < 0.001), a device-associated infection (42.6% vs. 28.6%, P = 0.004), or bacteremia (68.9% vs. 57.8%, P = 0.028). The frequency of methicillin-resistant Staphylococcus aureus (MRSA) did not differ between the groups. The low overall unadjusted mortality rate did not vary based on initial treatment. In a multivariable analysis adjusting for potential confounders inappropriate therapy had an attributable increase in hospital LOS of 1.8 days (95% CI, 1.4-2.3). CONCLUSION: Similar to other populations with HCAI, HCA-cSSSI patients are likely to receive inappropriate empiric therapy for their infection. This early exposure is associated with a significant prolongation of the hospitalization by nearly 2 days. PMID- 20734457 TI - Clinical and economic outcomes in patients with community-acquired Staphylococcus aureus pneumonia. AB - BACKGROUND: While the clinical and economic consequences of S. aureus pneumonia in healthcare settings have been well documented, much less is known about community-acquired S. aureus pneumonia (CAP). METHODS: We retrospectively identified all patients admitted to a large US urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 hours of admission. Patients with suspected healthcare-associated pneumonia (HCAP) were excluded from the study sample, using established criteria (eg, recent hospitalization, admission from nursing home, hemodialysis). Patients were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) CAP based on initial S. aureus isolates. Initial therapy was designated "appropriate" vs. "inappropriate" based on expected susceptibility of the organism to the regimen received. RESULTS: We identified a total of 128 CAP patients with S. aureus isolates; mean (standard deviation [SD]) age was 60 (17) years. A total of 55 patients (43%) had initial cultures positive for MRSA. Patients with MRSA CAP were more likely to receive inappropriate initial therapy (24 [44%] vs. 13 [18%] for MSSA; P = 0.002). Approximately 25% of all patients underwent surgery for pneumonia, 69% received mechanical ventilation, 79% were admitted to intensive care unit (ICU), and 24% died in hospital. Mean (SD) length of stay was 17.0 (15.7) days, and total hospital charges averaged $127,922 ($154,605) per patient; there were no significant differences between patients with MRSA vs. MSSA CAP. CONCLUSION: Outcomes are poor, hospital stays are long, and costs of care are high in patients with S. aureus CAP, and do not differ between those with MRSA vs. MSSA. PMID- 20734458 TI - Association with TP53 codon 72 polymorphism and the risk of non-Hodgkin lymphoma. AB - Polymorphism of TP53 Arg72Pro is associated with many different cancers[1-4]. Few studies have investigated its role in the susceptibility to non-Hodgkin lymphoma (NHL) [5,6]. To examine the association between this polymorphism and NHL risk, we conducted a Korean large-scale, population-based case-control study (945 cases and 1,700 controls). The TP53 72CC genotype was associated with increased risk of NHL (P 5 0.04) and diffuse large B-cell lymphoma (P 5 0.04). Our findings provide evidence that the TP53 Arg72Pro is associated with an increased risk of NHL in Korea. PMID- 20734459 TI - High early mortality rate in elderly patients with multiple myeloma receiving a vincristine-doxorubicin-dexamethasone regimen. AB - Treatment-related mortality (TRM) is not uncommon in patients after the first course of vincristine-doxorubicin-dexamethasone (VAD) chemotherapy,but quite rare after melphalan-prednisolone (MP). This motivated us to compare the rates of TRM after the first course of VAD with those after the first course of MP. We retrospectively assessed survival and TRM in 179 patients treated for multiple myeloma with either MP or VAD. Survival was similar in two groups (P 50.463 in log-rank test). However, TRM was significantly higher inpatients after the first course of VAD (11 in 100 patients, 11.0%) than that after the first course of MP (1 in 79, 1.3%; P 5 0.010). Poor performance status (P 5 0.004) and advanced age (P 5 0.009) before treatment were independent significant factors associated with TRM after the first course of induction therapy. Pyogenic infection was the major cause of TRM after VAD (9 in 11, 81.8%). We concluded that VAD should be cautiously used as induction therapy in multiple myeloma patients, especially in elderly and/or those with poor performance status. PMID- 20734460 TI - Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database. AB - BACKGROUND: The incidence of rectal cancer in the United States in young patients is considered to be low. Underestimating this incidence may result in a failure to diagnose younger patients with rectal cancer in a timely manner. METHODS: The authors conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data. A total of 7661 patients with colon, rectal, and rectosigmoid cancer who were diagnosed at age <40 years were identified between 1973 and 2005. The change in incidence over time for colon and rectal/rectosigmoid cancer was calculated and the annual percent change for anatomic subsites of colorectal cancer compared. RESULTS: SEER data demonstrated an increase in the incidence of rectal cancer without any increase in colon cancer (annual percent change of 2.6% vs -0.2%). The difference was statistically significant and extended to rectosigmoid cancer, but not cancer of the sigmoid colon or descending colon (annual percent change of 2.2% vs 0.4% and -2.8%, respectively). Joinpoint analysis of the slope of the curve of rectal and rectosigmoid cancer incidence identified the beginning of the increase to be 1984. All races and both sexes demonstrated similar statistically significant increases in the incidence of rectal and rectosigmoid cancer. CONCLUSIONS: The incidence of rectal and rectosigmoid cancer appears to be increasing in patients aged <40 years. Patients presenting with rectal bleeding or other alarming signs or symptoms should be evaluated with this finding in mind. PMID- 20734461 TI - The way back. PMID- 20734462 TI - 20th Congress of CLS JEP for clinical physicians and international participation. 21 October 2009, Brno. PMID- 20734463 TI - S-100B in serum and urine after traumatic head injury in children. AB - BACKGROUND: Children with head trauma are frequently seen in many emergency units. The clinical evaluation of these patients is difficult for a number of reasons and improved diagnostic tools are needed. S-100B, a protein found in glial cells, has previously been shown to be a sensible marker for brain damage after head injury in adults, but few studies have focused on its use in children. METHODS: In this study, 111 children with head trauma were included and venous blood and urine samples were taken at arrival (S1 and U1) and 6 hours later (S2 and U2). S-100B levels were analyzed. Clinical and radiologic evaluations were performed according to hospital routine. Two groups were identified- group 1: no computed tomography (CT) scan performed ora CT scan without any sign of trauma related intracranial pathology (n = 105). Group 2: A CT scan with signs of trauma related intracranial pathology (n = 6). RESULTS: In group 1, the median (inter quartile range) serum S-100B value in S1-samples was 0.111 microg/L (0.086 0.153), and in group 2, it was 0.282 microg/L (0.195-1.44) (p < 0.01). Also, S2 values significantly differed between the two groups. Urine values were, however, not significantly differing between the groups. CONCLUSIONS: Serum S-100B values within 6 hours after head trauma in children were significantly higher in patients with intracranial pathology compared with those without intracranial complications. Identification of these high-risk patients already in the emergency department is of major importance, and we suggest that S-100B could be a valuable diagnostic tool in addition to those used in clinical practice today. PMID- 20734464 TI - Emerging excellence in neurogastroenterology and motility research in South America. PMID- 20734465 TI - Niger's hunger crisis: a legacy of lessons unlearned. PMID- 20734466 TI - Donald Berwick takes charge of Medicare and Medicaid. PMID- 20734467 TI - Overcoming the social death of dementia through language. PMID- 20734468 TI - Aggregation-induced emission in tetraphenylthiophene-derived organic molecules and vinyl polymer. AB - In this study, organic molecules of tetraphenylthiophene (TP) and the derived model compound of TP-Qu and vinyl polymer of PS-Qu with the pendant group of TP Qu were prepared and characterized to identify their photoluminescent (PL) responses toward the effect of aggregation-induced emission (AIE). During aggregate formation by adding the nonsolvent water to the THF solvent, the corresponding TP solutions greatly gained the emission intensity. In contrast, TP Qu and PS-Qu in THF/water solution mixtures emitted strongly with nearly the same emission intensity despite the composition differences on the applied THF/water mixtures. Restricted intramolecular rotation (RIR) is the key factor deciding the AIE effect in different media. With four small phenyl rotors around the central thiophene stator, the RIR of the TP molecules in dilute solution is low but increases upon aggregate formations. In contrast, the bulky C-2 quinoline rotor of the TP-Qu molecule enhances the RIR effect and its PL emissions in the aggregate and in the solution states are essentially the same (irrespective of the aggregate formation by adding nonsolvent water). With the inherent TP-Qu pendant groups, the vinyl polymer PS-Qu behaves similarly to the TP-Qu molecule; that is, solutions of PS-Qu have similar emission spectra in different solution mixtures. Several methods including PL excitation (PLE), low-temperature PL emission study, and computer simulation were used in this study to estimate the relative extents of RIR and therefore, the resulting AIE effect in all the TP derived materials. PMID- 20734469 TI - A three-step workflow procedure for the interpretation of array-based comparative genome hybridization results in patients with idiopathic mental retardation and congenital anomalies. AB - One of the aims of clinical genetics is to identify gene mutations or genomic rearrangements that may underlie complex presentations of phenotypic features, such as multiple congenital malformations and mental retardation. During the decade after publication of the first article on array-based comparative genome hybridization, this technique has supplemented karyotyping as the prime genome wide screening method in patients with idiopathic multiple congenital malformations and mental retardation. The use of this novel, discovery-based, approach has dramatically increased the detection rate of genomic imbalances. Array-based comparative genome hybridization detects copy number changes in the genome of patients and healthy subjects, some of which may represent phenotypically neutral copy number variations. This prompts the need for properly distinguishing between those copy number changes that may contribute to the clinical phenotype amid a pool of neutral copy number variations. We briefly review the characteristics of copy number changes in relation to their clinical relevance. Second, we discuss several published workflow schemes to identify copy number changes putatively contributing to the phenotype, and third, we propose a three-step procedure aiming to rapidly evaluate copy number changes on a case-by case basis as to their potential contribution to the phenotype of patients with idiopathic multiple congenital malformations and mental retardation. This workflow is gene-centered and should aid in identification of disease-related candidate genes and in estimating the recurrence risk for the disorder in the family. PMID- 20734470 TI - RISM-SCF-SEDD study on the symmetry breaking of carbonate and nitrate anions in aqueous solution. AB - The planarity of carbonate and nitrate anions was investigated in the gas and solution phases by means of the reference interaction site model self-consistent field spatial electron density distribution (RISM-SCF-SEDD) method. The computed optimized geometries and solvation structures are compared with the diffraction data. In the solution phase, the symmetry of carbonate anion is changed from D3h to C3v, whereas the planarity of nitrate anion is still retained. These are fully consistent with experimental knowledge. The classical electrostatic model was also utilized to elucidate the mechanism of the symmetry breaking. It should be emphasized that the symmetry breaking occurs not only by a specific solvent molecule attaching to the ion but by an overall electrostatic interaction between the infinite number of solvent molecules and the ion. PMID- 20734471 TI - Radioembolization for colorectal liver metastases. PMID- 20734472 TI - Journal club. A B-cell signature associated with renal transplant tolerance in humans. PMID- 20734473 TI - Journal club. Methylation determines fibroblast activation and fibrogenesis in the kidney. PMID- 20734474 TI - Journal club. Cystatin C and contrast-induced acute kidney injury. PMID- 20734475 TI - Thermo-responsive association of chitosan-graft-poly(N-isopropylacrylamide) in aqueous solutions. AB - A comb-like dual hydrophilic graft chitosan copolymer, chitosan-graft-poly(N isopropylacrylamide) (CS-g-PNIPAM), was synthesized by means of atom transfer radical polymerization (ATRP) and click chemistry. The thermo-responsive association behavior of the copolymer in dilute aqueous solutions has been investigated by laser light scattering (LLS), zeta potential, and transmission electron microscopy (TEM). The core-shell structured micelles with the hydrophobic PNIAPM as a core and the hydrophilic CS as a shell were formed at low pH (<4) and high temperature (>32 degrees C), whereas the obtained micelles became large aggregates and precipitated in alkaline solutions (pH > 7). Additionally, the low critical solution temperature (LCST) phase transitions of dense copolymer solutions in the presence of salts (NaCl and NaI) and a cationic surfactant (dodecyltrimethylammonium bromide, DTAB) respectively were studied by micro differential scanning calorimetry (DSC) and UV turbidimetry. It was found that both salts (NaCl and NaI) and DATB could shift the LCST to lower or higher temperatures from a pure copolymer solution, depending on the beneath mechanisms. PMID- 20734476 TI - [A new view on pathochemical mechanisms of prolonged peritoneal dialysis]. AB - New data on etiology, pathogenesis, clinics, quantity estimation, treatment and complications of peritoneal dialysis are observed. The role of aquaporine, nitric oxide, NO-synthase, inflammation and sepsis markers (procalcitonine, C-reactive protein) in pathochemical mechanism of peritoneal dialysis is discussed. PMID- 20734477 TI - [Problems and prospects of gene therapeutics and DNA vaccines development and application]. AB - The review is summarized foreign publications devoted to different aspects of DNA vaccines and gene therapeutics' biological safety. In spite of incomprehension in their action, numerous prototype DNA-based biopharmaceuticals are in advanced stages of human clinical trials. This review is focused on some safety concerns of gene formulations vaccines relate to toxic effects, vertical transmission possibility, genome integration complications, immunologic and immunopathologic effects and environmental spread. It is noted that necessity of national regulatory documents development related to gene therapy medicinal products is significant condition of their application to medical practice. PMID- 20734478 TI - [Immune response in patients with HCV infection on the south of western Siberia]. AB - The aim of the study was to investigate the features of immune response in patients with HCV infection on the South of Western Siberia. MATERIALS: The 130 patients with different genotips of HCV infection were investigated (95 men and 35 women). RESULTS: On the territory of the South of Western Siberia the 1 and 3 genotips of HCV infection were present especially in young men and women and 1b subtype was dominated. In patients with 1 and 3 genotips of HCV infection was occurred the massive inflammatory response with intensive necrotic proinflammatory cytokins damages of the liver tissue and high cirrotic occurring in young age. PMID- 20734479 TI - [Features of prevalence and risk factors of GERD in different age-gender groups]. AB - AIM: To study prevalence and risk factors of gastroesophageal reflux disease in different age-gender groups. MATERIAL AND METHODS: 506 men of military age, in 375 men in age 40-60 years old, 296 women in age 18-30 years old were investigated. The research included clinical examination with standard questionnaires filling and endoscopy. RESULTS: Prevalence of heartburn in men of military age was 30.4%; in men in age 40-60 years old--46.9%, (p(1-2) < 0.001), in women--24.6% (p(1-3) = 0.8). Prevalence of esophagitis in men of military age was 2.4%; in men in age 40-60 years old--4.3%, (p(1-2) = 0.1), in women--0.7% (p(1-3) = 0.07). CONCLUSION: Features of clinical manifestations and risk factors action in three different age-gender groups were established. PMID- 20734480 TI - [Use of Legalon in non-alcoholic fatty liver disease]. AB - The article presents the current understanding of the etiology, pathogenesis of nonalcoholic fatty liver disease, its basic forms, risk factors, prevalence and clinical course. Shows the data of research on the effectiveness of purely herbal product Legalon, in the treatment of non-alcoholic fatty liver disease. The 2 month course of treatment was underwent in the research team, on that background there was noted positive dynamics: cropped asthenic syndrome, pain and heaviness in the right hypochondrium, dyspepsia. In assessing of the biochemical parameters was shown a significant decrease in serum transaminases, gamma glyutamiltransaminazy level. PMID- 20734481 TI - [Bidloo Nikolai Lambertovich (1670-1735) and Pavel Zacharovich Condoidi (1710 1760) (340 - and 300 years - anniversary of birth)]. PMID- 20734482 TI - [On developing the indicators of tuberculosis mortality in Russia]. AB - In two subjects of the Russian Federation, the Orlovskaya and Tulskaya Oblast, on the basis of the study of 303 death cases of tuberculosis patients died in 2006, it is established that the actual system of collecting and processing statistic data does not provide the validity of tuberculosis mortality indicators. The most part of errors is explained by the erroneous selection and coding of initial causes of death. The directions of enhancing the validity of mortality indicators at the expense of continuous education of physicians to apply ICD-10 and the implementation of new technologies (software package ?Natality and mortality monitoring? and educational computer program "RUTENDON"). PMID- 20734483 TI - [The prevalence of concomitant diseases among in-patients on the subject of rheumatic gout]. AB - The article contains the results of the study of rate, ratio and characteristics of concomitant diseases among in-patients with various clinical anatomic forms of rheumatic gout. PMID- 20734484 TI - [The patient evaluation of quality of in-patient hematological care]. AB - The analysis of opinions of patients about the quality of hospital hematological care indicated that patients rather appreciate the quality of treatment in hematologic in-patient departments. At the same time, several problematic issues have been revealed: duration of waiting time in admission room, inadequate awareness of patients about characteristics of disease and side effects of treatment, unsatisfactory conditions of hospital stay, inadequate level of pharmaceutical provision, deontological issues. The above-mentioned proves the need in further development of hematologic beds and day in-patient stay departments' network, including home in-patient departments and inclusion into medical staff the position of psychotherapist. The improvement of management in the in-patient departments of hematological profile will provide better satisfaction of patients and higher quality of medical care. PMID- 20734485 TI - [The development of dental medical care in the Republic of Severnaya Osetiya Alaniya]. AB - The economical analysis of functioning of dental care institutions in the city of Vladikavkaz revealed that the transition from administrative to economical management through the development of self-government and economic managerial methods provide more reserves to enhance quality of dental care and interest of medical stuff in effectiveness of their activities. PMID- 20734486 TI - [The social partnership in delivering mental care]. AB - To overcome the rapid increase of mental diseases burden many health administrations and managers of curative preventive institutions have to turn to the community proposing social partnership. The article deals with the experience of successful activities of particular public organizations in the field of mental health care. The interest of public administration is noted to develop effectively this sector of social activities. PMID- 20734487 TI - [The role of theoretical and practical conferences in developing the image of curative preventive institution]. AB - In actual conditions, the development of the image of curative preventive institution is one of the major directions of activities of the administrators of medical organizations. Against the background of limited centralized financing the priority in choosing the needed approaches has to be given to the resource saving technologies, one of which is the organization of theoretical and practical conferences in a proper methodic way. Such an approach provides the information to the superior administration and the stuff of other medical institutions about organized scientific event and demonstrates the endeavor of its team to master the innovative techniques and promotes the experience sharing between colleagues. PMID- 20734488 TI - [On the development of higher medical school in the East Siberia region]. AB - The article deals with the major landmarks of the development of higher medical school in the East Siberia region from the moment of its formation up to the present time including its input into the development of public health of the region. The contribution of the prominent representatives of different clinical disciplines into the formation of theoretical and practical heritage of medicine and public health is discussed. PMID- 20734489 TI - [Influence of alcohol containing products on serum lipid spectrum]. AB - The study was undertaken to examine of influence of alcohol containing products of household chemistry on serum lipid spectrum. The research has shown, that alcohol containing products of household chemistry at the patients with Toxic hepatitis in comparison with the persons using ethyl alcohol was revealed in lower relative contents of total phospholipids, Free fatty acids, cholesterol ethers, total lysophospholipids, sphyngomyelin and higher level of free cholesterol and phosphatidylcholine. The level of total lipids at the patients with Toxic hepatitis was in 3 times higher than normal. PMID- 20734490 TI - [Neural regulation of the lung-bronchial system in norm and inflammatory bowel disease]. AB - Review focuses on respiratory manifestations of inflammatory bowel disease, identified in the form of fibrosis, emphysema, bronchiectases, and alveolitis. Pathogenesis of the bronchopulmonary complications unduced by a violations of autonomic innervation of the intestine and the bronchial system, changements of the permeability of vascular wall and alveolar epithelium, the development of autoimmune processes. PMID- 20734491 TI - [Chronic pancreatitis: quality of a life and possibilities of pharmacological correction by ethylmethylhydroxypyridine succinate]. AB - A PURPOSE OF THE STUDY: Was to define a degree of quality of a life of patients with chronic pancreatitis by means of the scale SF-36 and also to analyse influence of medicine EMGPS on a quality of a life, level of anxiety and results of clinic-biochemical factors. THE MATERIALS AND METHODS: Biochemical investigations were done on automatic analyzer, alpha-amylase of blood and urine, lipase of blood were defined, ultrasonic research was done, an anxiety was determined on the scale of Spilberg-Khanin, a quality of a life was investigated by the questionnaire SF-36. THE RESULTS: The reliable decline of pain and index of intensity of pain was revealed in the group of the observation. The reliable decline of TC, LDL was marked in a group of the observation by the 12th week and of TG in the group accepting medicine EMGPS. Also in this group the indexes of quality of a life connected with physical and psychological components of questionnaire SF-36 became better and situational anxiety went down. THE CONCLUSION: An authentic improvement of indicators of a quality of a life and factors of lipidic spectrum was got in the group of the observation where preparation EMGPS was included in the standard treatment scheme of chronic pancreatitis. PMID- 20734493 TI - Electrolyte effects on the chiral induction and on its temperature dependence in a chiral nematic lyotropic liquid crystal. AB - We present a study on the effect of added CsCl and of temperature variation on the chiral induction in a chiral nematic lyotropic liquid crystal (LC) composed of the surfactant cesium perfluorooctanoate (CsPFO), water, and the chiral dopant d-Leucine (d-Leu). The chiral induction was measured as the helical pitch P. The role of the additives CsCl and d-Leu on the phase behavior is investigated and discussed. The thermal stabilization effect of CsCl is shown to lead to an apparent salt effect on the pitch when the pitch is compared at a constant temperature. This apparent effect is removed by comparing the pitch measured for different salt concentrations at a temperature relative to the phase-transition temperatures; thus, the real salt effect on the pitch is described. High salt concentrations are shown to increase the pitch, that is, hinder the chiral induction. The effect is discussed in terms of a decreased solubilization of the amphiphilic chiral solute d-Leu in the micelles due to the salt-induced screening of the surfactant head groups and the consequential denser packing of the surfactants. The temperature variation of the pitch is investigated for all CsCl concentrations and is found to be essentially independent of the salt concentration. The temperature variation is analyzed and discussed in the context of a theoretical model taking into account specific properties of lyotropic liquid crystals. A hyperbolic decrease of the pitch is found with increasing temperature, which is known, from thermotropic liquid crystals, to stem from pretransitional critical fluctuations close to the lamellar phase. However, the experimental data confirmed the theoretical prediction that, at high temperature, that is, far away from the transition into the lamellar phase, the pitch is characterized by a linear temperature dependence which is determined by a combination of steric and dispersion chiral interactions. The parameters of the theoretical expression for the pitch have been determined by fitting the experimental data. The analysis of the salt concentration dependence of these parameters indicates that the chiral induction mechanism of d-Leu is dominated by chiral steric interactions. PMID- 20734492 TI - Emerging excellence in neurogastroenterology and motility research in mainland China. PMID- 20734495 TI - Experimental and computational thermochemical study of sulfur-containing amino acids: L-cysteine, L-cystine, and L-cysteine-derived radicals. S-S, S-H, and C-S bond dissociation enthalpies. AB - This paper reports an experimental and theoretical study of the standard (p(degrees) = 0.1 MPa) molar enthalpies of formation at T = 298.15 K of the sulfur-containing amino acids l-cysteine [CAS 52-90-4] and l-cystine [CAS 56-89 3]. The standard (p(degrees) = 0.1 MPa) molar enthalpies of formation of crystalline l-cysteine and l-cystine were calculated from the standard molar energies of combustion, in oxygen, to yield CO2(g) and H2SO4.115H2O, measured by rotating-bomb combustion calorimetry at T = 298.15 K. The vapor pressures of l cysteine were measured as function of temperature by the Knudsen effusion mass loss technique. The standard molar enthalpy of sublimation, at T = 298.15 K, was derived from the Clausius-Clapeyron equation. The experimental values were used to calculate the standard (p(degrees) = 0.1 MPa) enthalpy of formation of l cysteine in the gaseous phase, DeltafH(degrees)m(g) = -382.6 +/- 1.8 kJ x mol-1. Due to the low vapor pressures of l-cystine and since this compound decomposes at the temperature range required for a possible sublimation, it was not possible to determine its enthalpy of sublimation. Standard ab initio molecular orbital calculations at the G3(MP2)//B3LYP and/or G3 levels were performed. Enthalpies of formation, using atomization and isodesmic reactions, were calculated and compared with experimental data. A value of -755 +/- 10 kJ x mol-1 was estimated for the enthalpy of formation of cystine. Detailed inspections of the molecular and electronic structures of the compounds studied were carried out. Finally, bond dissociation enthalpies (BDE) of S-H, S-S, and C-S bonds, and enthalpies of formation of l-cysteine-derived radicals, were also computed. PMID- 20734494 TI - Molecular dynamics of ion hydration in the presence of small carboxylated molecules and implications for calcification. AB - The aspartate-rich macromolecules found at nucleation sites of calcifying organisms are widely implicated in regulating biomineral formation. Anecdotal evidence suggests that their ability to influence the onset of nucleation and composition of calcified structures may arise from effects on ion hydration. This study investigates the interactions of acidic amino acids and dipeptides with hydrated cations using molecular dynamics. By monitoring the hydration states of Mg2+, Ca2+, and Sr2+ during their approach to negatively charged molecules, we show that carboxylate moieties of Asp promote dehydration of Ca2+ and Sr2+. A contact ion pair (CIP) is not required to disrupt cation hydration, and we demonstrate that reductions and rearrangements of first shell water can begin at ion-Asp separation distances as large as approximately 4.9 A for Ca2+ and approximately 5.1 A for Sr2+. CIP formation between Ca2+ and Sr2+ and carboxylate groups decreases the total first shell coordination number from an average of 8.0 and 8.4 in bulk water to 7.5 and 8.0, respectively. The energy barrier to physically replacing waters about Ca2+ with carboxylate oxygen atoms is small (approximately 2 kcal/mol) as compared to a somewhat larger barrier for Sr2+ (approximately 4 kcal/mol). This may be explained by differences in the strength of Coulombic interactions between the cations and the Asp, resulting in different paths of approach toward Asp for Ca2+ and Sr2+. In contrast, the primary solvation shell of Mg2+ remains largely unchanged during interactions with Asp until the abrupt physical replacement of water by carboxylate oxygen atoms, which comes at a high energetic cost. These insights support the claim that carboxylated biomolecules increase the growth rate of calcite by lowering the energy barrier to Ca2+ dehydration. The findings also suggest a physical basis for the idea that ion-specific behaviors of Ca2+ and Mg2+ in cellular systems arise from a critical balance between water binding in the ion hydration shells versus their interactions with ligands present in intracellular environments. PMID- 20734496 TI - Photoinduced electron transfer occurs between 2-aminopurine and the DNA nucleic acid monophosphates: results from cyclic voltammetry and fluorescence quenching. AB - 2-Aminopurine (2AP) is a fluorescent adenine analogue that is useful in part because its substantial fluorescence quantum yield is sensitive to base stacking with native bases in ss- and ds-DNA. However, the degree of quenching is sequence dependent and the mechanism of quenching is still a matter of some debate. Here we show that the most likely quenching mechanism in aqueous solution involves photoinduced electron transfer (PET), as revealed by cyclic voltammetry (CV) performed in aprotic organic solvents. These potentials were used with spectroscopic data to obtain excited-state reduction and oxidation potentials. Stern-Volmer (S-V) experiments using the native base monophosphate nucleotides (NMPs) rGMP, rAMP, rCMP, and dTMP were performed in aqueous solution to obtain quenching rate constants kq. The results suggest that 2AP* can act as either an electron donor or an electron acceptor depending on the particular NMP but that PET proceeds for all NMPs tested. PMID- 20734497 TI - Understanding the mechanism of deacylation reaction catalyzed by the serine carboxyl peptidase kumamolisin-As: insights from QM/MM free energy simulations. AB - Quantum mechanical/molecular mechanical (QM/MM) molecular dynamics and free energy simulations are performed to study the process of the deacylation reaction catalyzed by kumamolisin-As, a serine-carboxyl peptidase, and to elucidate the catalytic mechanism. The results given here suggest that Asp-164 acts as a general acid/base catalyst not only for the acylation reaction but also for the deacylation reaction. It is shown that the electrostatic oxyanion hole interactions may be less effective in transition state stabilization for the kumamolisin-As catalyzed reaction compared to the general acid/base mechanism involving the proton transfer from or to Asp-164. The dynamic substrate-assisted catalysis (DSAC) involving His at the P1 site of the substrate is found to be less important for the deacylation reaction than for the acylation reaction in the kumamolisin-As catalyzed reaction. The proton transfer processes during the enzyme-catalyzed process are examined and their role in the catalysis is discussed. PMID- 20734498 TI - Relative role of halogen bonds and hydrophobic interactions in inhibition of human protein kinase CK2alpha by tetrabromobenzotriazole and some C5-substituted analogues. AB - To examine the relative role of halogen bonding and hydrophobic interactions in the inhibition of human CK2alpha by 4,5,6,7-tetrabromobenzotriazole (TBBt), we have synthesized a series of 5-substituted benzotriazoles (Bt) and the corresponding 5-substituted 4,6,7-tribromobenzotriazoles (Br3Bt) and examined their inhibition of human CK2alpha relative to that of TBBt. The various C(5) substituents differ in size (H and CH3), electronegativity (NH2 and NO2), and hydrophobicity (COOH and Cl). Some substituents were halogen bond donors (Cl, Br), while others were fluorine bond donors (F and CF3). Most of the 5 substituted analogues of Br3Bt (with the exception of COOH and NH2) exhibited inhibitory activity comparable to that of TBBt, whereas the 5-substituted analogues of the parent Bt were only weakly active (Br, Cl, NO2, CF3) or inactive. The observed effect of the volume of a ligand molecule pointed to its predominant role in inhibitory activity, indicating that presumed halogen bonding, identified in crystal structures and by molecular modeling, is dominated by hydrophobic interactions. Extended QSAR analysis additionally pointed to the monoanion and a preference for the N(1)-H protomer of the neutral ligand as parameters crucial for prediction of inhibitory activity. This suggests that the monoanions of TBBt and its congeners are the active forms that efficiently bind to CK2alpha, and the binding affinity is coupled with protomeric equilibrium of the neutral ligand. PMID- 20734499 TI - Investigation of an allergen adsorption on amine- and acid-terminated thiol layers: influence on their affinity to specific antibodies. AB - This work describes the controlled immobilization of a recognized allergen, beta lactoglobulin, onto gold transducers with the aim of optimizing the elaboration of a biosensor directed against allergen-produced antibodies. This protein was immobilized on both amine- and acid-terminated thiol self-assembled monolayers, and the influence on its affinity to a specific IgG was investigated. For amine terminated layers, the beta-lactoglobulin was immobilized via its surface acid functions implying an activation step with 1-ethyl-3-[3 dimethylaminopropyl]carbodiimide hydrochloride/ester of N-hydroxysuccinimide (EDC NHS). Conversely, the grafting on acid-terminated layer takes advantage of the accessible amine groups that react with the activated acidalkylthiols. The resulting layers of beta-lactoglobulin were then submitted to various concentrations of rabbit serum containing beta-lactoglobulin specific rabbit immunoglobulin (rIgG), and the antigen/antibody affinity was evaluated using modulated polarization-infrared absorption spectroscopy (PM-IRRAS) and Fourier transform surface plasmon resonance (FT-SPR). Even though for similar concentration, the amount of adsorbed beta-lactoglobulin was identical on both surfaces, atomic force microscopy (AFM) images showed a better dispersion for amine-terminated layers. Moreover, the affinity to specific IgG, estimated under static conditions by PM-IRRAS and under dynamic conditions by SPR, was different. Grafting beta-lactoglobulin via its acid groups gave an affinity constant 3 times higher than its immobilization via its amine groups despite the fact that the amount of accessible recognition sites appeared to be similar for both systems. This work underlines the importance of the involved chemical groups upon protein immobilization on their biological activity and will be essential for the construction of nondirect biosensors for detecting specific immunoglobulin E (IgE) of allergens. PMID- 20734533 TI - French soldiers and their correspondence: towards a history of writing practices in the First World War. AB - The years 1914-18 engendered a "sudden and irrepressible boulimia" of letter writing, a diluvian outpouring which defied all attempts at administrative control. The massive correspondence of French soldiers, analysed and quoted in the archives of the Commission de Controle Postal, has already been mined by war historians. They have normally used it to carry out a kind of historical opinion poll on the mood of the trenches. This article, however, focuses less on the content of soldiers' correspondence, and more on the nature and history of letter writing itself. It examines letters as letters, their frequency, their destinations and all the unwritten codes to which they are subject. At a time of newly acquired mass literacy, the poilus experienced the urgent need to write. Their "laconic writing" raises important questions about historical sources, their transparency and their silences. It also offers a perspective on the much debated integration of the peasantry into national life and culture. PMID- 20734534 TI - [The purification of recombinated granulysin and the preparation of its monoclonal antibody]. AB - AIM: To purify recombinated GNLY which is expressed by prokaryotic expression system, and to prepare the monoclonal antibody (mAb) against it. METHODS: The solvable protein was purified by affinity chromatography. And employing the fusion protein GNLY immuned BALB/c mice, using conventional hybridoma technology prepared the mAb against human GNLY. Then purified and determined for titer by indirect ELISA method, for antigenic epitopes by additive ELISA, for relative affinity index by sulfocyanate elution method, and analyzed for subclass, specificity and stability. RESULTS: We got the soluble reactive fusion GNLY, and its purity and content were 95%, 0.8 g/L, respectively. Four cell strains secreting mAb against human GNLY were screened, 6C8, 9C6, 5G7and5E5. Their neutralizing titers were 1:100-1:3 200 and (0.1 - 8) x 10(-4) in supernatant and ascites. CONCLUSIONS: We successfully purified the fusion protein of GNLY, and prepared the mAb against human GNLY, lying a certain foundation for its laboratory and clinical research. PMID- 20734536 TI - [Role of nuclear factor kappa B in cyclosporine A-induced nephrotoxicity in human tubular epithelial cell]. AB - AIM: To ascertain the role of FK-kappaB in cyclosporine A (CsA)-induced nephrotoxicity in human kidney tubular epithelial cell. METHODS: Human kidney tubular epithelial cells were treated with CsA at concentrations of 0, 0.1, 1, 10 mmol/L for 24 hours. As inhibitors of NF-kappaB, 25 micromol/L pyrrolidine dithiocarbamate (PDTC) were added respectively. Mitochondria membrane potential were detected by flow cytometry. The activation of NF-kappaB was studied by the assessment of NF-kappaB P65 measured by laser scanning confocal microscope. RESULTS: Mitochondrial membrane potential showed a decrease in the cells with CsA, but the cells with CsA + PDTC did not. Cells treated with CsA activated NF kappaB but cells in the CsA-induced damage of human kidney tubular epithelial cell. This damage is ameliorated when the activation of NF-kappaB is blockaded. PMID- 20734537 TI - [Changes and significance of T-lymphocytes subsets in severe hepatitis patients]. AB - AIM: To study the changing of blood T-lymphocytes subsets in severe hepatitis patients and its effect. METHODS: The T-lymphocytes subsets of 21 patients with severe hepatitis and 30 healthy volunteer were detected by flow cytometry. From the changes of T lymphocytes subsets we compared their related clinical prognosis of each case. RESULTS: The average CD4(+) CD8(-), CD4(-) CD8(+) lymphocytes counts in severe hepatitis group were lower than the controls groups (P <0.05). And the the CD4(+)/CD8(+) ratios were higher than the control groups (P<0.05). The CD4(+) CD8(-), CD4(-) CD8(+) lymphocytes was lower than severe hepatitis dead group than the surviving group (P<0.05). CONCLUSION: The changes of T - lymphocytes subsets especially the elevation of counts CD4(+), CD8(+) lymphocytes may be one important marker to predict the clinical prognosis. PMID- 20734538 TI - [Study of CO(2) pneumoperitoneum on the level of vWF in pregnancy rats]. AB - AIM: The goal of this paper is to study changes of von Willebrand Factor in medium and late pregnancy rats' serum during diffencet time and pressure of CO(2) pneumoperitoneum. METHODS: By solid phase phase sandwich enzyme linked immuno sorbent assay (ELISA). RESULTS: (1) We succeed to build the model of carbon dioxide pneumoperitoneum in medium pregnancy rats. (2) The time and pressure of carbon dioxide pneumoperitoneum was proportional to von Willebrand Factor in serum, they have no statistical significance (P>0.05). CONCLUSION: It is safity to operate in medium pregnancy by laparoscopic surgery. But we must control the time in 2 hours. PMID- 20734540 TI - Translational medicine: is this a matter for the clinician? PMID- 20734539 TI - [Acta Reumatologica Portuguesa: impact factor attributed in June 2010]. PMID- 20734541 TI - BioRePortAP, an electronic clinical record coupled with a database: an example of its use in a single centre. AB - AIMS: To evaluate the efficacy and safety of the treatment of psoriatic arthritis (PsA) patients with tumor necrosis factor (TNF) antagonists in the Rheumatology Department of Hospital de Santa Maria using the BioRePortAP. METHODS: The Portuguese Society of Rheumatology (SPR) developed an electronic medical chart coupled with a database for the follow up of PsA patients, the BioRePortAP, which was launched in May 2009. This evaluation was based on all the PsA patients that were on active treatment with TNF antagonists in September 2009 and were registered in the BioRePortAP. All the previous data on these patients were introduced in BioRePortAP using the prospective paper based follow up protocol that this Department was using since 1999. Only patients with more than 9 months of treatment were analyzed. RESULTS: Forty-two patients with PsA, actively treated with anti-TNF agents in September 2009, for at least 9 months, were analyzed in BioRePortAP. Twenty-three patients were male (55%) and nineteen were female (45%). The average age of these patients was 49.8+/-10.9 years old, the average disease duration was of 10.7+/-5.6 years and the mean duration of biological therapy was of 37.8+/-27.8 months. For the 81% of patients with peripheral joint disease there was a mean reduction of more than 80% in the swollen and tender joint counts, and almost 50% in the health assessment questionnaire (HAQ) value. In the 19% of the patients with axial involvement the reduction of BASDAI and BASFI was not statistically significative. On top of that, PASI score suffered a reduction of 64%. Fourteen patients (33.3%) had to switch their TNF antagonist treatment. 58.8% of the switches were due to adverse effects and 41.2% due to therapy failure. Regarding the 56 adverse reactions registered, only one was a severe reaction. The remaining adverse reactions were not severe and 67% of them were due to infections. DISCUSSION: The results of this first report of the use of the BioRePortAP in clinical practice confirm the efficacy and safety of TNF antagonist treatment in PsA. The results shown here elucidate the potential applications of BioRePortAP as a tool for efficacy and safety assessment of PsA patients treated with biotechnological drugs. PMID- 20734542 TI - Patients- and physicians- priorities for improvement. The case of rheumatic diseases. AB - OBJECTIVES: To compare the health priorities elected by patients with rheumatic diseases and by their attending rheumatologists. PATIENTS AND METHODS: We undertook a cross-sectional study among patients and rheumatologists in Portuguese rheumatology outpatient clinics. 75% of all Portuguese Rheumatology Departments agreed to participate. Rheumatologists from non-participating hospital departments were asked to collaborate through their private practices. All patients were eligible for inclusion except if they were under 18 years of age or had a mental disorder that would affect their participation. Data were collected through dedicated questionnaires. Patients were asked to indicate 3 priorities for improvement out of 12 health domains (Arthritis Impact Measurement Scale 2) regarding their rheumatic disease. Rheumatologists were asked similar questions focused around rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: 1,868 patients and 56 rheumatologists entered the study. The most commonly selected priorities by patients with rheumatic diseases were: "Rheumatic pain" (70%), "Walking and bending" (45%), and "Hand and Finger Function" (40%). The main priority for improvement among patients with RA was "Rheumatic Pain" (69%), while rheumatologists more commonly elected "Work" (55%) as their main priority for these patients. Among patients with OA, "Rheumatic Pain" was the first priority for both patients and doctors (elected by 75%, and 55% of respondents, respectively). CONCLUSIONS: Our study showed discordance between the priorities for improvement elected by patients and by their respective physicians. This was more pronounced in RA than in OA. Studying and addressing such differences may support physicians and institutions to better achieve the prime goal of incorporating and responding to patients' needs and preferences. PMID- 20734543 TI - [Health preferences measures: comparing Brazil SF-6D version with SF-36 derived versions, in patients with rheumatoid arthritis]. PMID- 20734544 TI - Development and use of touch - screen computer-assisted self interviewing in Portuguese patients with chronic immune diseases: evaluation of an electronic version of sf-36v2 . AB - AIM: The major purpose of this study was to evaluate alternative automated methods of collecting data on health related quality of life (HR-QoL). In order to achieve this, we developed a study with the following objectives: (1) to evaluated the feasibility of electronic version in patients with different chronic pathologies of the immune system using Short Form 36version2 (SF-36v2), (2) to evaluate the construct validity of SF-36v2 using the electronic data capture, and (3) to compare electronic version questionnaires with paper questionnaires in terms of patients' acceptance, data quality, and reliability. METHODS: Out-patients with chronic immune diseases (HIV infection, lupus, scleroderma, rheumatoid arthritis, Behcet and Sjogren), were randomly selected to completed electronic and paper SF-36v2 (n=50) before consultation in Clinical Immunology Unit, in Hospital Santo Antonio-Centro Hospitalar do Porto (CI-HGSA). RESULTS: There were very high correlations in SF-36v2 responses (p< .001) between the paper and electronic forms. Internal reliability coefficients (Cronbach's alpha) showed good internal consistency for all reported responses in either, computer and paper. There were no missing data in electronic version or paper. About 84% of the patients prefer to use the computer version in future. CONCLUSION: The electronic HR-QoL assessment is technically possible and it can provide reliable and valid clinically significant information which can either be used in routine care appointments. PMID- 20734545 TI - Prevalence of rheumatic occupational diseases - PROUD study. AB - INTRODUCTION: Work related musculoskeletal diseases (WRMSDs) have a huge social and economic impact being a public health problem. OBJECTIVES: To determine the prevalence of WRMSDs in Portuguese active workers. METHODS: A questionnaire was sent by regular mail to the occupational physician of 822 large dimension companies in Portugal (over 250 employees). This questionnaire was addressed to the physician and contemplated data on file from the occupational medical doctor of clinically relevant WRMSDs (rather than addressing workers complaints). A reply form and a telephone reminder were used to assure a higher number of respondents. RESULTS: Of the selected 822 companies, 515 responded (response rate of 62.3%) involving a total population of 410,496 workers. The prevalence of clinically relevant WRMSD was of 5.9% (24,269 cases). The more prevalent WRMSD were back pain with a prevalence of low back pain of 2.27% (n=9310 , 38.4% of total WRMSD). Dorsal pain 0.82% (n= 3379, 13.9% of total WRMSDs) and cervical pain 1.13% (n=4651, 19.2% of total WRMSD). Back pain accounts for 4.22% (n= 17340) and a total of 74.9% of all WRMSDs. Regarding the upper limb we found a prevalence of 1.61% (n= 6493). From this total, shoulder tendonitis was 0.59%(n= 2398, 9.9% of total WRMSDs), carpal tunnel syndrome 0.29% (n=1170, 4.8% of total WRMSDs), elbow tendonitis 0.29% (n=1202, 5% of total WRMSDs) and hand tendonitis 0.44% (n=1823, 7.5% of total WRMSDS). A lower prevalence was observed in the lower limbs with lower limb tendonitis of 0.08% (n=336, 0.01% of total WRMSDs). DISCUSSION/CONCLUSION: Our work was representative of 11% of the working Portuguese population. We have found a prevalence of clinically relevant WRMSD of 5,9%. If we extrapolate for the total of the working population we would have 220 467 workers with WRMSDs. Our data are in conflict with national social security services regarding these diseases with much lower reported diseases that proves the inefficacy of the national reporting system. There are clear differences in our data when compared with the literature. We found a higher number of back pain, and in proportion of cervical pain, and lower numbers of upper and lower limb WRMSDs. In the upper limb we found a higher level of hand tendonitis and a decrease of elbow tendonitis and carpal tunnel syndrome. This work was a first effort to characterize WRMSDs in Portugal. Due to the study design we believe that further studies aimed for higher risk populations should be performed. PMID- 20734546 TI - [Systemic lupus erythematosus presenting as autoimmune parotitis and pancreatitis - Case Report]. AB - Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease which can present from classical to atypical forms. We discuss the case of a young lady of 29 years-old recently diagnosed with SLE that manifested parotitis and pancreatitis. PMID- 20734547 TI - [Dystrophic calcinosis of the vulva in a patient with CREST syndrome]. PMID- 20734548 TI - [The importance of the abdominal ultrasound in rheumatology!]. PMID- 20734549 TI - Serum IgA deficiency in systemic lupus erythematosus. PMID- 20734550 TI - [Should we abandon vertebroplasty in the treatment of osteoporotic compression vertebral fractures?]. PMID- 20734551 TI - The unfolding story of the second demographic transition. AB - This article presents a narrative of the unfolding of the Second Demographic Transition (SDT) since the theory was first formulated in 1986. The first part recapitulates the foundations of the theory, and documents the spread of the SDT to the point that it now covers most European populations. Also for Europe, it focuses on the relationship between the SDT and the growing heterogeneity in period fertility levels. It is shown that the current positive relationship between SDT and TFR levels is not a violation of the SDT theory, but the outcome of a "split correlation" with different sub-narratives concerning the onset of fertility postponement and the degree of subsequent recuperation in two parts of Europe. The second part of the article addresses the issue of whether the SDT has spread or is currently spreading in industrialized Asian countries. Evidence gathered for Japan, South Korea, Hong Kong, Singapore, and Taiwan is presented. That evidence pertains to both the macro-level (national trends in postponement of marriage and parenthood, rise of cohabitation) and the micro-level (connections between individual values orientations and postponement of parenthood). Strong similarities are found with SDT patterns in Southern Europe, except for the fact that parenthood is still very rare among Asian cohabiting partners. PMID- 20734552 TI - Demography, Education, and Democracy: global trends and the case of Iran. AB - Reconstructions and projections of populations by age, sex, and educational attainment for 120 countries since 1970 are used to assess the global relationship between improvements in human capital and democracy. Democracy is measured by the Freedom House indicator of political rights. Similar to an earlier study on the effects of improving educational attainment on economic growth, the greater age detail of this new dataset resolves earlier ambiguities about the effect of improving education as assessed using a global set of national time series. The results show consistently strong effects of improving overall levels of educational attainment, of a narrowing gender gap in education, and of fertility declines and the subsequent changes in age structure on improvements in the democracy indicator. This global relationship is then applied to the Islamic Republic of Iran. Over the past two decades Iran has experienced the world's most rapid fertility decline associated with massive increases in female education. The results show that based on the experience of 120 countries since 1970, Iran has a high chance of significant movement toward more democracy over the following two decades. PMID- 20734553 TI - Mapping the Timing, Pace, and Scale of the Fertility Transition in Brazil. AB - Between 1960 and 2000, fertility fell sharply in Brazil, but this transition was unevenly distributed in space and time. Using Bayesian spatial statistical methods and microdata from five censuses, we develop and apply a procedure for fitting logistic curves to the fertility transitions in more than 500 small regions of Brazil over this 40-year period. Doing so enables us to map the main features of the Brazilian fertility transition in considerable detail. We detect early declines in some regions of the country and document large differences between early and late transitions in regard to both the initial level of fertility and the speed of the transition. We also use our results to test hypotheses regarding changes in the level of development at the onset of the fertility transition and identify a temporary stall in the Brazilian transition that occurred in the late 1990s. A web site with project details is at http://schmert.net/BayesLogistic. PMID- 20734554 TI - Productivity of older workers: perceptions of employers and employees. AB - What determines the perceived productivity of the older worker and how does this perception compare to the perception of the productivity of the younger worker? In this study we present evidence based on data from Dutch employers and employees. Productivity perceptions are affected by one's age and one's position in the hierarchy. The young favor the young, the old favor the old, and employers value the productivity of workers less than employees do. However, there are also remarkable similarities across employers and employees. By distinguishing the various dimensions that underlie the productivity of younger and older workers, we tested whether soft qualities and abilities-e.g., reliability and commitment are just as important as hard qualities-cognitive and physically based skills-in the eyes of both employers and employees. It appears that both employers and employees, young and old, view hard skills as far more important than soft skills. PMID- 20734555 TI - Emptying the nest: older men in the United States, 1880-2000. AB - Between 1880 and 2000, the percentage of married men 60 and older living only with their wives in empty nest households rose from 19 percent to 78 percent. Data drawn from the US census show that more than half of this transformation occurred in the 30-year period from 1940 to 1970, bookended by moderate increases between 1880 and 1940 and very modest increases after 1970. Two literatures have presented demographic, cultural, and economic explanations for the decline in elderly co-residence with their children, but none adequately accounts for a sharp change in the mid-twentieth century. Both aggregate comparisons and multivariate analysis of factors influencing the living arrangements of elderly men suggest that economic advances for all age groups in the critical 30-year period, along with trends in fertility and immigration, best explain the three stage shift that made the empty nest the dominant household form for older men by the beginning of the twenty-first century. PMID- 20734556 TI - The household registration system and migrant labor in China: notes on a debate. AB - The household registration (hukou) system in China, classifying each person as a rural or an urban resident, is a major means of controlling population mobility and determining eligibility for state-provided services and welfare. Established in the late 1950s, it was initially used to bar rural-to-urban migration. After the late 1970s reforms, an inflow of rural migrant workers was allowed into the cities to meet labor demands in the burgeoning export industries and urban services without, however, changing the migrants' registered status, thus precluding their access to subsidized housing and other benefits available to those with urban registration. While there have been many calls for reforming this system, progress has been limited. Proposed reforms have attracted increasing academic and media attention. PMID- 20734557 TI - Reexamining the Dominance of Birth Cohort Effects on Mortality. AB - The association between birth cohort and subsequent mortality has been of interest especially following publication of studies around 1930 of cohorts born up to the latter part of the nineteenth century, particularly for England and Wales. Updated results are presented for this population, together with those for two other cohorts, twentieth-century Japanese and British populations born about 1930, which have been identified as having particularly clear-cut birth cohort patterns, and which are used to underpin incorporation of cohort effects in both British official and actuarial mortality forecasts. Graphical methods used to identify cohort patterns are discussed. A number of limitations and difficulties are identified that mean that the conclusions about the predominance of cohort effects are less robust than often assumed. It is argued that alternative explanations should be considered and that the concentration on birth cohorts with particularly advantaged patterns may distort research priorities. PMID- 20734558 TI - From antiquity to Olympic revival: sports and Greek national historiography (nineteenth-twentieth centuries). AB - This study investigates the evolution of the historiography of Greek sport from the foundation of the Greek state (1830) until 1982 and its links with Greek national history, which also took shape primarily during the nineteenth century. The gradual 'nationalisation' of sport as an element of Greek national character since antiquity corresponded to changes in perceptions of the national past reflected in historiography. The ancient Olympic Games, Byzantine contests and exercises, the competitions of the klephts and armatoloi (militia soldiers) during the Ottoman rule and the modern revival of the Olympic Games were all successively integrated in a national history of sport confirming national continuity and unity. However this particular genre of national historiography did not gain academic recognition until recently. The authors of histories of physical exercise and sport were amateurs or physical education instructors and could not ensure to their work the authority of a separate discipline. PMID- 20734559 TI - Bodies that differ: mid- and upper-class women and the quest for "Greekness" in female bodily culture (1896-1940). AB - This article discusses different expressions of mid- and upper-class Greek women's use of classical antiquity in relation to female bodily culture. It focuses on two cases, connected with successive phases of the collective women's action in Greece. The first case concerns principally the conjuncture of the Athens Olympic Games of 1896. The games offered the opportunity to the Ladies' Journal, the weekly that gave expression to the first feminist group in Greece and its leading figure, C. Parren, to put forward a discourse which, by constructing a specific image of the ancient Heraia games for 'maidens', 'invents' a specific athletic-competitive 'tradition' on behalf of Greek women of their social class. The second case rejoins the same circle of women principally in the interwar years as leading figures of the Lyceum of Greek Women, the organization which distinguished itself by juxtaposing to the newly formed militant feminist organizations its 'hellenic-worthy' activity, by organizing monumental festivals in the Panathenaic Stadium, which, through displays of 'national' dances - folk and 'ancient' dances - and other ritual events, performed the 'tradition' of the nation from prehistory until today. PMID- 20734560 TI - Negotiating ethno-cultural identity: the experience of Greek and Jewish youth in Halifax. AB - This paper focuses on the lived experiences of young people growing up Greek Canadian and Jewish Canadian in Halifax, Nova Scotia. It is based on data collected in a pilot study conducted with second-generation Greek and second-, third-, and fourth-generation Jewish youth in Halifax in 2004-05. Most of the existing research on the second generation and beyond lumps together the experiences of different ethnocultural groups. Perhaps even more importantly, the existing research tends to focus almost exclusively on the second- (or third- or fourth-) generation's experiences in major urban centres. In this paper we forge new paths by exploring the experiences of ethnic youth in a smaller Canadian urban centre within a region with low concentrations of immigrant populations and ethnic groups. We thus argue for the importance and effects of the specific place of settlement on ethno-cultural identity. Family and community expectations, relations, and practices, and negotiating family and community norms within the context of the institutional norms and practices in the areas of education, employment, gender, and family relations within the broader frame of Canadian society are highlighted. A comparative analysis between the two groups is adopted throughout. PMID- 20734561 TI - New modes of becoming in transcultural glocal spaces: second-generation youth in Calgary, Winnipeg, and Toronto. AB - Second generation youth are currently the focus of much research and policy attention with respect to their integration, which is not yet well understood. Based on graphic and narrative data recently collected in three cities, Calgary, Winnipeg, and Toronto, we analyse second generation youth's patterns in glocal spaces where transcultural modes of belonging are created and lived. Our analysis focuses on attachments to locality and a continuum of mobilities of mind, body, and boundaries. The findings are interpreted in terms of the complexities of their integration processes as well as their relevance to social policy development. PMID- 20734562 TI - Second-generation youth's belief in the myth of Canadian multiculturalism. AB - Second-generation youth in Toronto, growing up in low-income neighbourhoods, interact primarily with other racialized and ethnicized people. Within this environment they do not experience racial prejudice or discrimination, appreciate the cultural diversity around them, and attribute it to Canada's ideology of multiculturalism. However, they are beginning to realize their own subjectivity in relation to the power of White people and institutions. These confident, ambitious, and globally connected young people are likely to get deeply disappointed as they uncover the myths of Canada's multiculturalism in the world beyond their ethnically concentrated schools and neighbourhoods. Acknowledging and addressing their marginality is critical to their inclusion in Canadian society. PMID- 20734563 TI - Ethnic identity among second-generation Finnish immigrant youth in Canada: some voices and perspectives. AB - This study examines the ethnic identity experiences of second-generation Finnish immigrant youth in Canada. The study draws from interviews conducted among second generation Finnish immigrant youth in Ottawa. How these individuals identify with the Finnish ethnic group and engage in ethnic culture may play a pivotal role in the continuance of Finnish culture in Canada. Therefore, it is necessary to understand not only whether second-generation Finnish immigrants identify with their ethnic group, but also how they do so. We found that the youth identified with their Finnish ethnicity on a symbolic level, participating occasionally in the local ethnic community, but not living within ethnic culture on a day-to-day basis. They identify strongly with being Canadian and have an appreciation of multiculturalism and contrast it with Finnish society when they visit Finland. PMID- 20734566 TI - Caribbean and Filipino adolescents' and parents' perceptions of parental authority, physical punishment, and cultural values and their relation to migratory characteristics. AB - This article describes the perceptions of parents and adolescents of physical punishment in relation to family and migratory characteristics. Adolescents and their parents of Caribbean (n=118) and of Filipino (n=136) heritage responded to questions on their attitude toward physical discipline, their family relations, and their socio-demographic and migratory characteristics. Data analyses show that many Caribbean (78%) and Filipino (41.9%) parents perceive that they should have the right to physically punish their children, while youth disagree with this. The dissonance between parents' and their children's attitudes is related to acculturation factors due to the earlier and more intense exposure of youth to their host society. Further studies should be conducted on the impact of the divergence between parents and their youth's opinions on the actual shifts in power in the parent-child relationship, as well as on immigrant parents' discipline strategies and on the family's adaptation to the challenges of migration. PMID- 20734567 TI - Bicultural identity formation of second-generation Indo-Canadians. AB - This article examines the bicultural identity formation and cultural experiences internalized by second-generation Indo-Canadians in their efforts to accommodate the "best of both worlds" into their lifestyle. The objectives of this article are to educate the reader to become cognizant of the bicultural issues encountered by second-generation Indo-Canadians; to demonstrate interventions suitable for the second-generation Indo-Canadian populations; and to increase the readers' understanding of bicultural identity formation. What becomes evident is that intergenerational dialogue has a profound impact on the bicultural identity formation of this population. It will serve to guide these individuals to find a third space (Bhabha 2004) or zone of proximal development (ZPD) to encourage evolvement of their bicultural identity (Cummins 1996; Gutierrez et al. 1999). PMID- 20734568 TI - Environmental liability and redevelopment of old industrial land. AB - Many communities are concerned about the reuse of potentially contaminated land (brownfields) and believe that environmental liability is a hindrance to redevelopment. However, with land price adjustments, liability might not impede the reuse of this land. This article studies state liability rules-specifically, strict liability and joint and several liability-that affect the level and distribution of expected costs of private cleanup. It explores the effects of this variation on industrial land prices and vacancy rates and on reported brownfields in a panel of cities across the United States. In the estimated equations, joint and several liability reduces land prices and increases vacancy rates in central cities. The results suggest that liability is at least partly capitalized but does still deter redevelopment. PMID- 20734569 TI - Technology trends. 4-D software may help lung cancer treatments. PMID- 20734570 TI - Oil on the water: Government regulation of a carcinogen in the twentieth-century Lancashire cotton spinning industry. AB - In the Lancashire cotton textile industry, mule spinners were prone to a chronic and sometimes fatal skin cancer (often affecting the groin). The disease had reached epidemic proportions by the 1920s, which necessitated action by the government, employers, and trade unions. In contrast to previous accounts, this article focuses on the government's reaction to mule spinners' cancer. Using official records in the National Archives, the slow introduction of health and safety measures by the government is explored in detail. Although obstructionism by the employers played a key role, one of the reasons for government inaction was the ambiguity of scientific research on engineering oils. On the other hand, prolonged scientific research suited a government policy that was framed around self regulation - a policy that had proved largely ineffective by the 1950s. PMID- 20734571 TI - [Fourth Romanian Conference of Pediatric Pneumology, April 8-10, 2010, Cluj Napoca]. PMID- 20734574 TI - Diabetes mellitus: a global health problem. PMID- 20734573 TI - Prevalence, management and control of diabetes mellitus and associated risk factors in primary health care in Portugal. AB - OBJECTIVE: To assess the prevalence, treatment and control of diabetes mellitus (DM) in primary health care users, to characterize associated cardiovascular (CV) risk factors and effectiveness of their treatment, and to estimate the clinical impact of DM on the occurrence of coronary artery disease (CAD) and stroke. METHODS: The VALSIM Study was performed in a primary care setting and involved 719 general practitioners (GPs), based on stratified distribution and proportional to the population density of each region of mainland Portugal and the islands of Madeira and the Azores. A questionnaire on sociodemographic and clinical data (previous diagnosis of DM, CAD or stroke, antidiabetic and antihypertensive medication and statins) and laboratory tests (lipids and HbA1C) was applied by participating GPs to the first two adult patients scheduled for an appointment on a given day, and blood pressure (BP) was measured. DM was defined as fasting glucose of > or = 126 mg/dl or use of antidiabetic agents. RESULTS: The study included 16,856 individuals (mean age 58.1 +/- 15.1 years; 61.6% women), of whom 3215 were identified as diabetic. The prevalence of DM adjusted for gender and age in primary health care users was 14.9%, higher in men (M: 16.8%; F: 13.2%), and increased with age. Among the diabetic population, 90.2% were being treated with antidiabetic drugs and 51.7% had HbA1C lower than 7%. Around 91% had high BP (> or = 130/80 mmHg or were taking antihypertensive medication), 39.5% were overweight, 45.1% were obese, 69.3% had abdominal obesity, 71.8% had metabolic syndrome (ATP III criteria), 12% presented CAD and 5% had past history of stroke. The association between these CV risk factors and DM was stronger in women, and the impact of DM on occurrence of CAD and stroke was also higher in women. Among diabetic hypertensives, 78.4% were being treated with antihypertensive drugs, but only 9.3% had BP < 130/80 mmHg (M: 9.5%; F: 9.1%). Of diabetic patients with CAD, 94.2% were taking antihypertensive medication, but only 9.8% had controlled BP (M: 13.7%; F: 6.1%). Although 59% of the diabetic population were being treated with statins, only 6.7% had total cholesterol < 200 mg/dl, triglycerides < 150 mg/dl and HDL-cholesterol > 60 mg/dl. Of diabetic patients with CAD, 76.5% were being treated with statins, but only 29.4% had total cholesterol < 175 mg/dl (M: 34.2%; F: 24.1%). CONCLUSIONS: The management of DM in a primary care setting in Portugal can and should be improved, since 9.8% of patients are not treated and 48.3% are not controlled. DM has a considerable clinical impact due to its strong association with CAD and stroke. The risk of stroke and CAD is much higher in diabetic women, due firstly to a stronger association of DM with other risk factors in women, and secondly to less aggressive treatment. PMID- 20734575 TI - Overview of cardiac rehabilitation in Portugal 2007-2009. AB - INTRODUCTION: Cardiovascular disease is the leading cause of death in Europe. Cardiac rehabilitation (CR) has proven benefits, particularly in mortality reduction. METHODS: The Portuguese Society of Cardiology's Study Group on Exercise Physiology and Cardiac Rehabilitation has periodically performed surveys of national cardiac rehabilitation centers, the last in 2007. A questionnaire was sent to the various centers requesting general information about the center, staff, program phases and components, type of patients and funding bodies. On the basis of Diagnosis Related Groups (DRGs), the percentage of patients rehabilitated following hospitalization for myocardial infarction was determined. Centers engaged in CR in 2009, subsequent to the 2007 survey, were briefly evaluated. RESULTS: In 2007 there were 16 centers, an increase of 14% compared to 2004. This rose to 18 in 2009, a 13% increase over 2007. The number of rehabilitated cardiac patients in 2007 was more than double that of 2004--638 and 312 patients, respectively. Of the rehabilitated patients in 2007, 50% had suffered infarction, similar to the 58% in 2004. Based on DRG data, 3% of patients discharged from hospital after myocardial infarction were admitted to a cardiac rehabilitation program. In 2004, only 1.8% of patients discharged after acute coronary syndrome or CABG underwent cardiac rehabilitation. In 2007, Portugal was second from last in Europe for cardiac rehabilitation. CONCLUSION: Despite the benefits of cardiac rehabilitation and notwithstanding improvements and growth in the number of centers and patients included in programs, cardiac rehabilitation is still underused in Portugal due to several factors, which have to be overcome. PMID- 20734576 TI - Initial experience with the Presillion stent in an unselected population: immediate and six-month outcomes. AB - INTRODUCTION: The release of a new bare metal stent (BMS), the Presillion stent, whose main innovative feature is its reduced strut thickness, has created expectations that it may reduce neointimal proliferation and consequently lower the restenosis rate. OBJECTIVE: To evaluate the efficacy and safety profile of Presillion stent implantation in an unselected population referred for coronary revascularization with BMS. METHODS: This was a prospective study of the first 20 consecutive patients undergoing implantation of at least one Presillion stent. We performed a descriptive analysis of the study population in terms of demographics, clinical context, angiographic characteristics of coronary lesions before and after angioplasty, and clinical outcome. After discharge, patients were followed up and assessed clinically at 3 and 6 months for the occurrence of MACE (cardiovascular death, myocardial infarction, stroke or revascularization). The statistical analysis consisted of calculation of means and standard deviation for continuous variables and relative proportions for categorical variables. RESULTS: The study population was predominantly male (65%), with a mean age of 68.8 years. The indication for cardiac catheterization was acute coronary syndrome in 90% and heart failure in 10% of cases. Half the patients had multivessel disease, and 34 stents, of which 26 were Presillion stents, were implanted in 29 coronary lesions. According to the ACC/AHA classification, the coronary lesions treated with Presillion stents were classified as type A in 0% of cases, type B1 in 27% and type B2 or C in 73%; 27% of these had moderate to severe calcification. The percentage of stenosis and minimal luminal diameter (MLD) before and after angioplasty were respectively 88.5 +/- 9.7% (MLD = 0.65 +/ 0.40 mm) and 10.6 +/- 4.3% (MLD = 2.58 +/- 0.36 mm). The success rate of Presillion implantation was 100%, with no significant drop in hemoglobin, additional elevation of cardiac biomarkers or deterioration in renal function after the procedure. No MACE occurred before hospital discharge. At 6-month follow-up all patients were alive, none had had stroke, two patients (10%) had had acute myocardial infarction in territories not dependent on previously treated arteries and two patients had undergone a new revascularization, but not of the target vessel. CONCLUSION: This initial experience with Presillion stents showed a high efficacy rate and an excellent safety profile that was maintained over 6 months of follow-up. Their effectiveness compared to other BMS should be demonstrated in larger-scale comparative studies. PMID- 20734572 TI - Characterization of an ambulatory population with stable coronary artery disease and importance of heart rate: the PULSAR registry. AB - AIMS: To characterize a population with stable coronary artery disease (CAD) in an outpatient setting and to evaluate the importance of resting heart rate (HR), a recently recognized prognostic risk factor. TYPE OF STUDY: A prospective and observational registry of patients with stable CAD followed mainly by cardiologists in private outpatient clinics. METHODS: Patients were selected by at least one of the following inclusion criteria: coronary angiography with at least one significant stenosis; positive stress test; previous myocardial infarction; or revascularization by angioplasty or surgery. Demographics, concomitant diseases, HR, blood pressure (BP), presence of angina and medical therapy were all recorded. Data compilation and statistical analysis were performed by a CRO independent of the sponsor and the investigators. RESULTS: Between May and October 2009, 3477 consecutive patients were included by 186 doctors. Mean age was 66.6 +/- 10.1 years and 26.3% were female, 76% had arterial hypertension, 34% diabetes, 47% previous infarction, 42% angioplasty and 25% coronary surgery. Of concomitant diseases, 13% of patients had peripheral vascular disease or erectile dysfunction. Medical therapy included antiplatelet agents (97%), lipid-lowering agents (92%), beta-blockers (72%), ACEIs (54%), nitrates (39%), calcium blockers (36%), ARBs (28%), ivabradine (24%) and trimetazidine (17%). Mean HR was 67 +/- 12 bpm and 67% of patients had HR > 60 bpm. Mean systolic BP was 134 +/- 18 mmHg and mean diastolic BP was 76 +/- 10 mmHg. Angina was present in 31.3% of patients and 53.4% had class II angina. The population with angina was more severe, 74% had HR > 60 bpm and 68% were taking beta-blockers. In patients with angina and HR > 60 bpm, beta-blocker use was only 64%. CONCLUSION: In an outpatient population with stable CAD of whom a third had angina, there was an increased number of patients with HR > 60 bpm and decreased use of beta-blockers with increasing disease severity. These findings support increased use of newly developed drugs for the treatment of stable CAD and angina. PMID- 20734577 TI - Interaction of paraoxonase-192 polymorphism with low HDL-cholesterol in coronary artery disease risk. AB - INTRODUCTION: Coronary artery disease (CAD) is the main cause of mortality in developed countries. Increased lipid peroxidation is associated with accelerated progression of atherosclerosis. Paraoxonase (PON1) is an antioxidant enzyme bound to high-density lipoprotein (HDL), which protects against lipid peroxidation and coronary artery disease. PON1 activity is under genetic control and its molecular basis is a polymorphism in the PON1 gene that shows two common isoforms: the wild Q form (192 Gln) with high ability to protect LDL from lipid peroxidation in vitro, and the mutated R (Arg) form with lower ability. AIM: To explore the interaction of the R allele of the paraoxonase gene and low HDL-cholesterol concentrations in CAD risk. METHODS: The study population consisted of 818 individuals, 298 coronary patients, aged 55.0 +/- 10.3 years, 78.9% male, and 520 age and gender matched healthy controls, aged 53.3 +/- 11.7 years, 72.5% male. Low HDL-cholesterol was defined as < 0.90 mmol/l in men and < 1.11 mmol/l in women. Comparisons of genotypes between cases and controls were performed by a chi-square test. Statistical significance was accepted at p < 0.05. Odds ratios and 95% confidence intervals for the RR genotypes and HDL-deficient subjects were computed using univariate analysis (2 x 2 tables). To determine the interaction between the RR paraoxonase genotype and HDL-deficient subjects, we used 4 x 2 epidemiologic tables and synergy measures: the additive model (Rothman's synergy index, SI) and multiplicative model (Khoury's synergy index, SIM). The relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction (Rothman) were calculated. RESULTS: The PON1 RR192 polymorphism was associated with coronary heart disease (OR = 1.61; p = 0.043) in the whole population. HDL-deficient subjects with the RR192 genotype showed increased risk for CAD (OR = 17.38; p < 0.0001) compared to those with normal HDL and RR192 (OR = 1.39; p = 0.348) and HDL-deficient subjects not carrying the RR genotype (OR = 7.79; p < 0.0001). Synergy measures were SI = 2.3, SIM = 1.6; RERI = 9.2. CONCLUSION: These data suggest the existence of a synergistic effect of the PON1 RR192 genotype (with lower antioxidant ability) and HDL-deficient subjects in risk for development of CAD. The AP due to this interaction was 0.53, meaning that 53% of CAD was explained by this interaction. PMID- 20734578 TI - RIVER: Portuguese registry to monitor unnecessary right ventricular pacing. AB - The aim of this prospective registry is to evaluate a new algorithm designed to reduce the percentage of unnecessary ventricular pacing (%VP) in patients implanted with a dual-chamber pacemaker, through a dedicated pacing mode (called AAISafeR2) operating in AAI mode with back-up ventricular pacing in DDD mode, and to describe the incidence and distribution of atrioventricular (AV) block in this population. Investigators were free to assign patients to AAISafeR2 mode or to standard DDD (if AAISafeR was contraindicated, mainly due to permanent high degree AV block). Patients underwent routine follow-up visits at 3, 6, 12, 18 and 24 months after implantation. At each follow-up visit, data were retrieved from pacemaker memories and analyzed to extract %VP and incidence of AV block. Up to December 2006, 158 patients (94 men, mean age 69 +/- 14 years) from nine Portuguese centers had been consecutively included. We also determined the distribution of AV block (according to the criteria used by the pacemaker to classify AV block and switch to DDD mode). AAISafeR was shown to be effective in reducing unnecessary VP in our patient population. The analysis also reveals a high incidence of paroxysmal AV block, often unknown at the time of implantation. There were no complications associated with AAISafeR programming. PMID- 20734579 TI - Anatomophysiologic basis of tetralogy of Fallot and its clinical implications. AB - Tetralogy of Fallot is the most frequent cyanotic congenital cardiopathy. Its physiopathology has been progressively described which has made better treatment possible. The four characteristic morphologic abnormalities are: interventricular communication, subpulmonary stenosis, biventricular origin of the aortic valve and right ventricular hypertrophy, which are the direct result of the antero cephalad deviation of the ventricular septal outlet and hypertrophy of the septoparietal trabeculations. These anatomic abnormalities result in decreased pulmonary blood flow, leading to hypoxia and cyanosis. The main determinants of pulmonary blood flow are the source of the blood flow to the lungs, the severity and functional behaviour of the subpulmonary obstruction, the right ventricular and arterial systemic pressures and the ductus arteriosus. The mechanism of cyanotic spells is not clear. Increases in infundibular contractility, peripheral vasodilatation and right ventricular mechanoreceptor stimulation are some of the proposed mechanisms. There are two surgical strategies in newborns/children: a staged approach (with a palliative procedure followed by the complete repair) or early complete repair. There are arguments for and against each of these strategies, and the debate about the ideal treatment continues. In conclusion, the correct understanding of this cardiopathy's physiopathology is essential to improving the child's treatment. This review is particularly contemporary and relevant issue because one must always bear in mind the physiopathology of the original disease in order to correctly follow-up a new patient population: adults with surgically corrected Tetralogy of Fallot. PMID- 20734580 TI - ICD defibrillation failure solved in an unusual fashion. AB - An implantable cardioverter defibrillator (ICD) is designed to sense life threatening ventricular arrhythmias and terminate them, either by rapid pacing or by delivering an electrical shock. Nowadays it is a proven therapy for both primary and secondary prevention of sudden cardiac death. The typical configuration of an ICD consists of a right ventricular sensing/defibrillator lead with two coils (one distal, located in the right ventricle, and one proximal, located at the superior vena cava-right atrium junction) and an active can, the so-called "ventricular triad". Although effective in the vast majority of patients, it could be argued that this is not the most rational arrangement in electrical terms, since the main shock vector is anteriorly displaced in relation to the greater portion of the left ventricular mass. We describe a case of an ICD defibrillation failure that was solved by placing an additional defibrillator lead in a tributary of the coronary sinus. PMID- 20734581 TI - Intraventricular gradients and acute coronary syndromes: a case report. AB - Left ventricular outflow tract obstruction (LVOTO) has traditionally been associated with hypertrophic obstructive cardiomyopathy, but can occur in other clinical scenarios such as acute myocardial infarction (AMI). In some patients, LVOTO is absent at rest, being detectable only with provocation tests such as stress echocardiography. Timely diagnosis of this phenomenon is very important, as it has therapeutic implications, and relies on clinical suspicion and on recognizing substrates in which LVOTO can occur. We report a case of syncope and AMI associated with LVOTO with systolic anterior motion of the mitral valve and a significant intraventricular gradient. PMID- 20734582 TI - Right atrial invasive thymoma. PMID- 20734583 TI - [Counterfeit and fake drugs: medications that kill]. PMID- 20734584 TI - [Precautionary principle: too much in the North, too little in the South?]. PMID- 20734585 TI - [Observations during basic care after the earthquake in Port-au-Prince, Haiti on January 12, 2010]. AB - Provision of basic health care to earthquake victims in camps in Haiti indicated that the population was in relatively good health. It also allowed early detection of possible epidemic outbreak. PMID- 20734586 TI - [Mandible dislocation: diagnosis and reduction technique "in the field"]. AB - Diagnosis of temporomandibular joint dislocation can be achieved based on clinical findings. No complementary studies are required. Reduction can be performed without specific equipment in remote areas. PMID- 20734587 TI - [Febrile algo-eruptive illness in a French foreign legionnaire returning from Djibouti: gonococcal arthritis]. AB - A French foreign legionnaire returning from Djibouti developed feverish polyarthritis with acral purpura. Diagnostic workup demonstrated gonococcemia contracted during unprotected fellatio. Based on this case report, diagnostic and therapeutic management is described. PMID- 20734588 TI - [5th French-speaking conference on HIV/AIDS (Casablanca, 28-31 March 2010)]. PMID- 20734589 TI - [Status report on public health in Mauritius in 2009]. AB - Mauritius is an island nation off the coast of Africa in the southwestern Indian Ocean. Improved socio-sanitation conditions over the past years have dramatically decreased the incidence of tropical diseases to levels comparable with those observed in developed countries. Some tropical illnesses including malaria, schistosomiasis, cysticercosis and lymphatic filariasis have been eradicated. Others such as amibiasis, typhoid fever and leprosy have become rare. However, because of the island's geographical proximity to countries with uncontrolled and suboptimal socio-sanitation conditions and its humid subtropical climate, there is a continued risk for certain vector transmitted tropical diseases such as Chikungunya and dengue. In addition, the incidence of HIV infection and AIDS has been rising rapidly since 2004 and tuberculosis remains a public health problem. Better living conditions have also been accompanied by an increase in cardiovascular and metabolic diseases that, along with cancer, are now the main causes of morbidity and mortality. PMID- 20734590 TI - [Evolution of antibiotic-resistance Staphylococcus aureus in Saint Camille Medical Centre in Ouagadougou]. AB - BACKGROUND: Monitoring the antibiotic resistance of microorganisms in a specific geographic area can be useful in developing new approaches to first-intention antibiotherapy. OBJECTIVE: The purpose of this study was to describe the evolution of resistance of Staphylococcus aureus to antibiotics routinely used at Saint Camille Medical Centre in Ouagadougou, Burkina Faso from 1996 to 2006. METHOD: Strains of S. aureus, isolated from various pathologic sources were tested to determine their susceptibility to antibiotics. Sensitivity tests were performed in accordance with the guidelines of the Antibiogram Committee of the French Society for Microbiology (version 2007). RESULTS: During the study period, 1160 staphylococci strains were isolated including 73.45% identified as S. aureus. Susceptibility tests demonstrated a significant increase in resistance to beta-lactam antibiotics. The proportion of strains showing resistance to ampicillin reached 58.29% in 2000. Resistance to these antibiotics regressed significantly from 2000 to 2006. Resistance to pristinamycin and erythromycin showed a tendency to increase while resistance to gentamicin and oleandomycin showed no statistically significant change. CONCLUSION: This study demonstrated that S. aureus was the most common Staphylococcus genus present at the center and that it was resistant to several antibiotics. Reducing use of beta-lactam probably accounted for the significant decline in resistance to this type of antibiotic. Care should also be given to the use of other antibiotics such as pristinamycin and erythromycin since resistance appears to be increasing. PMID- 20734591 TI - [Malignant pertussis: an underdiagnosed illness]. AB - PURPOSE: Malignant pertussis is a rare life-threatening illness characterized by severe respiratory failure, severe leukocytosis, and pulmonary hypertension. The purpose of this study was to determine the prevalence of malignant pertussis in infants admitted to a pediatric intensive care unit (PICU) for severe acute respiratory failure associated with severe leukocytosis. METHODS: This retrospective study was based on review of the medical charts of infants aged less than 3 months admitted to the PICU between 2006 and 2008 for severe acute respiratory failure requiring mechanical ventilation with leukocytosis greater than 50,000/mm3. Clinical and laboratory data were collected. Polymerase chain reaction (PCR) for detection of Bordetella pertussis was performed on nasopharyngeal washes (NPW) stored at -70 degrees C. RESULTS: Ten patients meeting inclusion criteria were identified. Median age was 2.1 months (range, 0.6 - 3). None of the infants had been vaccinated against pertussis. Although PCR for pertussis was positive in all ten cases, presumptive diagnosis was made in only 3 patients during hospitalization. Nine patients died within a mean of 4.7 +/- 3.3 days after admission. The cause of death was refractory shock and hypoxemia in all cases. Only one patient survived. CONCLUSION: Malignant pertussis is a severe disease that is almost always fatal. It was underdiagnosed in our PICU. Use of PCR for detection of B. pertussis, i.e., the reference method, should be promoted in developing countries. PMID- 20734592 TI - [Operation to promote use of long-lasting insecticidal nets (LLIN) in French Guiana in 2006: design, implementation and results]. AB - In 2006, the Regional Health Office (DSDS) in French Guiana undertook a major operation involving importation and distribution of long-lasting insecticide treated nets (LLIN/ITN). In collaboration with the WHO, a Vietnamese manufacturer of LLINs suited to the requirements of French Guiana was sourced. With the help of a dynamic local importer and dealer, a sales network was developed through chemist shops located all over French Guiana. This network provided wide coverage since these outlets can be found in all large communities. The selling price ranged from 15 to 23 euros depending on the model, i.e., hammock or bed size. In addition, LLINs were distributed within the framework of two special programs. First they are given to women giving birth in French Guiana and undergoing medical surveillance as part of the Mother and Child Protection program by public healthcare system. Second they are distributed in case of natural disaster or other events that could lead to an increased risk of vector-borne outbreaks. Thanks to this operation, a total of 13,882 LLINs were delivered in French Guiana from July 2006 to December 2008. This milestone operation in the fight against malaria was made possible thanks to funding granted on a one-time basis after the outbreak of dengue in 2005-2006. The structure of this operation and its survival will depend on the continued goodwill and determination of a small group of local partners who created this successful distribution campaign with no specific guidance or program from the national authorities. PMID- 20734594 TI - [Management of bluespotted stingray injuries in Djibouti from July 2008 to July 2009]. AB - Although stingray injuries have always been frequent in the Republic of Djibouti, it was not until July 2008 that the Bouffard Hospital developed a standardised management protocol. The purpose of this report is to describe that protocol and evaluate its impact on the outcome of stingray injuries based on a prospective study for the period between July 2008 and July 2009. During the study period, 12 stingray stings were treated. The treatment protocol that is based on a multidisciplinary approach involving the intensivist, anaesthesiologist, and surgeon achieved wound healing within one month. This outcome contrasts with previous publications that have generally described longer healing times with frequent infectious complications. PMID- 20734593 TI - [Stevens-Johnson syndrome and toxic epidermal necrolysis in a teaching hospital in Lome, Togo: retrospective study of 89 cases]. AB - OBJECTIVES: The purpose of this study was to document epidemiological features, outcomes, and aetiologies of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a teaching hospital in Lome, Togo. METHOD: A retrospective study of patients with SJS/TEN treated from January 2002 to April 2009 in a teaching hospital in Lome was conducted. RESULTS: During the study period, 89 patients were treated for SJS/TEN, i.e., SJS in 76 cases, TEN in 9, and overlapping SJS/TEN in 4. Mean age was 30.3 +/- 13.4 years and sex ratio (M/F) was 0.7. Serological testing for HIV was carried out in 75 patients and was positive in 41 (54.6%) including 36 patients with SJS, 3 with TEN and 2 with overlapping SJS/TEN. A total of 9 patients died including 4 with SJS, 4 with TEN and one with overlapping SJS/TEN. Six of the patients who died were HIV-infected. Complications included blindness in 3 cases, moderate dry eye syndrome in 1, vaginal synechiae in 2, synechiae of labial commeasures in 1, and hypertrophic scars in 1. Antibacterial sulphonamides (50.6%) were the most commonly implicated drugs followed by nevirapine (23.6%), non-steroidal anti-inflammatory drugs (5.6%), and anti-epileptic medications (3.4%). DISCUSSION: Our results also document the high frequency of nevirapine as a new SJS/TEN cause unrelated to antibacterial sulphonamides. With increasing access to HIV medication in sub Saharan Africa countries, practitioners should take these data into account for patient monitoring. PMID- 20734596 TI - [Primary ileostomy for typhoid-related ileal perforation: a 62-case series in Ouagadougou, Burkina Faso]. AB - OBJECTIVES: The purpose of this report is to evaluate the efficacy of primary ileostomy for treatment of typhoid-related ileal perforation based on our experience. METHODS: This retrospective study included all cases of typhoid related ileal perforation treated by primary ileostomy in the Visceral Surgery Department of the Yalgado Ouedraogo Teaching Hospital in Ouagadougou, Burkina Faso from January 2006 to June 2008. Diagnosis was based mainly on peroperative findings revealing specific anatomical lesions. There were 45 men (72.6%) and 17 women (27.4%) with a mean age of 26 years (range, 14 to 68). Asthenic forms were observed in 41 cases (66.1%) and sthenic forms in 21 (33.9%). The mean delay for seeking treatment was 6 days (range, 1 to 30 days). RESULTS: Primary ileostomy was used for treatment of typhoid-related ileal perforation in 78.5% of cases. Most cases (80.6%) involved single perforations. A temporary ileostomy was performed in 55 cases (88.7%) and terminal ileostomy was performed in 7 (11.3%). Complications were observed in 18 patients (29.03%) including suppuration of wall in 8 cases. The mean duration for re-establishing continuity and of hospital stay was 34 and 41 days respectively. Four deaths occurred due to hypovolemic shock. CONCLUSION: In our department, primary ileostomy for typhoid-related ileal perforation reduced mortality despite high morbidity. PMID- 20734595 TI - [Systemic vasculitis: study of 27 cases in Senegal]. AB - Studies on vasculitis in black Africa are rare. The purpose of this report is to describe a retrospective study of systemic vasculitis managed in the internal medicine, ORL and cardiolology departments of the Aristide le Dantec University Hospital in Dakar, Senegal from 1995 to 2007. A series of 27 cases involving 7 men and 20 women with a mean age of 49 years was compiled. Primary vasculitis included Horton disease in 3 cases, Wegener disease in 2, Takayasu disease in 1, and Buerger disease in 1. Secondary vasculitis included mixed cryoglobulinemia with Gougerot Sjogren syndrome in 7 cases, primary Goujerot syndrome in 4, rheumatoid arthritis in 3, nodosa periarteritis with hepatitis B in 2, SHARP syndrome in 1, and polymyositis in 1. The remaining two cases involved abdominal periaortitis including one associated with retrosperitoneal fibrosis and tuberculosis and the other with spondylarthropathy. Corticotherapy in combination with anticoagulants, immunosuppressive therapy, and surgery, when necessary, allowed effective management in 24 cases. The findings of this study show that systemic vasculitis can have numerous etiologies and indicate that secondary forms are the most common. Appropriate care modalities are needed to prevent severe outcome in Senegalese hospitals. PMID- 20734597 TI - [Mycetoma in Tunisia: a 15-case series]. AB - BACKGROUND: Mycetoma is a chronic infection of cutaneous and subcutaneous tissue that can be caused by fungi or bacteria. It is endemic in tropical and subtropical areas but rare in Tunisia. PURPOSE: The purpose of this report is to describe epidemioclinical features, treatment and outcomes in patients presenting mycetoma in Tunisia. PATIENTS AND METHODS: The files of all patients treated for mycetoma in the Dermatology Department of La Rabta Hospital in Tunisia from 1982 to 2006 were retrospectively reviewed. RESULTS: A total of 15 cases of mycetoma were recorded during the study period. There were 6 men and 9 women with a mean age of 53.2 years. The most common clinical presentation was infiltrated erythematous plaques with sinus tracts (fistulas). Lesions were located on the foot in 12 cases. Thirteen patients reported the presence of grains in fluid discharging from fistulas. The cause of mycetoma was actinomycetes, i.e., Actinomadura madurae, in 9 cases and fungus in 6 cases including 3 due to Madurella mycetomi and 2 to Pseudallesheria boydii. Treatment was based on oral antibiotics for actinomycetoma and oral antifungals for eumycetoma. CONCLUSIONS: Mycetoma in Tunisia is still uncommon with a slight female predominance. The foot is the most frequent location. Diagnosis can be accomplished by direct mycologic examination, culture, and histololgy. There is no consensus on treatment that is often prolonged with numerous relapses. PMID- 20734598 TI - [Diagnosis of pheochromocytoma in Yaounde (Cameroon): a study of nine cases]. AB - The aim of this study was to describe methods used for diagnosis of pheochromocytoma inYaounde, Cameroon. This retrospective study was based on analysis of the charts of patients treated in the surgical department of the Yaounde University Teaching Hospital from 1985 to 2009. Nine patients with histologically confirmed pheochromocytoma were identified. There were 8 women and 1 man with a mean age of 39.5 years (range, 12 and 66). Pheochromocytoma was associated with hypertension in 6 cases. In two women with hypertension, diagnosis was based on palpation of an abdominal tumor after caesarean section following pregnancy associated with arterial hypertension. In another woman, diagnosis was made during laparotomy for a left hypochondrial tumor. In 7 patients, diagnosis was based on laboratory findings showing high urinary levels of vanyl mandelic acid (VMA). In six patients, ultrasound examination allowed topographic diagnosis that was confirmed by CT-scan in 3 cases. Two patients presented extra-renal pheochromocytomas in the abdomen. In three patients, i.e., one third of cases, histology showed malignant features. The findings of this study indicated that diagnosis of pheochromocytoma in Yaounde be improved with the introduction MRI, scintigraphy, and modern techniques for assaying urinary methoxyderivates. PMID- 20734599 TI - [Prevalence and factors associated with low back pain among hospital staff in Ouagadougou (Burkina Faso)]. AB - OBJECTIVE: The aim of our study was to determine the prevalence, risk factors, associated with low back pain among hospital staff in a developing country. PATIENTS AND METHODS: This transversal study was conducted from March 2007 to February 2008 at Yalgado Ouedraogo Teaching Hospital in Ouagadougou (CHU-YO), Burkina Faso. RESULTS: There were 256 men and 180 women with an average age of 38 +/- 8.25 years (range, 22 to 58). Mean BMI was 25.11 +/- 4.03 Kg/m2. The prevalence of chronic low back pain was 56.4% overall, 47.3% in men and 69.4% in women. Individual risk factors included female sex (p=0.000004), age (p=0.026), and high BMI (p=0.0002). Sports activity appeared to be a protective factor (p=0,035). Professional risk factors were the number of working hours per week (p=0,005) and numbers of guards per month (p=0.014) and posture during work (p=0.01). Analysis of socioprofessional consequences revealed significant impact in 43 (17,5%) patients. The loss work hours in 2007 were estimated to 1020. Three patients had to change working stations due to disability and 82 (19%) reported restricted working capacity. CONCLUSION: The prevalence of low back pain is high among hospital staff of CHU-YO. Preventive measures are needed to reduce socioprofessional consequences. PMID- 20734600 TI - [Necrotizing fasciitis of the breast and HIV infection. A case report]. AB - Necrotizing fasciitis is a severe soft tissue infection caused by flesh-eating bacteria. It usually occurs on the lower limbs. The purpose of this report is to describe a case involving Streptococcus pyogenes on the breast of a 22-year-old African woman with HIV. PMID- 20734601 TI - [Purple extremities in black-skinned patients: blue toe syndrome as presenting sign of antiphospholipid antibody syndrome]. AB - Although acral ischemia can involve several underlying mechanisms, suspicion of lupus warrants testing for antiphospholipid antibodies in patients with blue toe syndrome. PMID- 20734602 TI - [Intrauterine device and pelvic tumor: two case reports of pelvic actinomycosis with pseudotumor from tropical zones]. AB - Pelvic actinomycosis is a rare chronic disease caused by actinomycete species. The pseudotumorous form is the most common and often leads to misdiagnosis. The purpose of this report is to describe two cases of pelvic actinomycosis involving women with a history of intrauterine contraceptive device (IUD) use. Diagnosis was based on pelvic mass and the findings of surgery undertaken for suspicion of an advanced ovarian tumor with hepatic metastasis in one case and for a tumor of the right ovary in the other case. Diagnosis was confirmed by histological examination of a biopsy specimen in the first case and of the surgical specimen (right ovariectomy) in the second case. Long-term antibiotic therapy was effective in both patients. Based on these two cases and review of the literature, discussion focuses on diagnostic pitfalls, natural course, and therapeutic options for this particular infection. PMID- 20734603 TI - [Dengue shock syndrome: decoding the pathophysiology]. AB - Considered as major human arbovirosis, dengue occurs in several clinical forms. Some forms can lead to fatal complications such as dengue shock syndrome. This hypovolemic shock cannot be predicted and specific curative treatments are still lacking, and thus management of patients with dengue is difficult. The purpose of this review is to describe state-of-the-art of the knowledge on the pathophysiology of shock syndrome and to highlight the interest of high-content screening methods in translational approaches between research and medicine for investigation of individual response during dengue shock syndrome. PMID- 20734604 TI - [Lower extremity venous thrombosis in Togo]. AB - The purpose of this report was to describe epidemiologic, clinical, and paraclinical aspects and to identify etiologic factors associated with lower extremity venous thrombosis in Lome, Togo. PMID- 20734605 TI - [Self-medication for dermatologic conditions in Lome, Togo]. AB - OBJECTIVES: The aim of this study was to describe features of self-medication for skin conditions observed at public dermatology centres in Lome, Togo. METHODS: This cross-sectional study was conducted from July 1 to September 30, 2008 in 3 public dermatology centres in Lome-Commune. All patients consulting at the study centres for the first time were recruited, interviewed and examined. RESULTS: Of 600 patients enlisted in the study, 264 (44%) had practiced self-medication. There were more women than men (sex ratio: 0.8). In most cases, products used for self-medication were recommended by a friend and/or relative (72%). Most products were obtained from either pharmacies (42.4%) or street vendors (37.9%). The average cost of self-medication was 520 FCFA (0.79 euros). Products applied by the topical route were the most common (72%) and most patients reported dissatisfaction with results (67.8%). CONCLUSION: This study demonstrates that self-medication is widely practiced for dermatologic conditions in Lome and provides insight into the circumstances, reasons and sources of self-medication. PMID- 20734606 TI - [Epidemiology of anguillulosis among public school children in Abidjan, Cote d'Ivoire]. AB - PURPOSE: Strongyloides stercoralis is a neglected soil-transmitted helminth species. In Cote d'Ivoire, as elsewhere, there is a lack of parasitologic and epidemiologic data pertaining to this parasite. The purpose of this study was to evaluate the prevalence and impact of sociodemographic factors on anguillulosis among public school children in Abidjan, Cote d'Ivoire. METHODS: Testing for Strongyloides stercoralis was performed in a random sample of 411 children from 10 public primary schools in Abidjan. Detection methods included direct examination of stool smears, the Baermann test and helminth coproculture study. RESULTS: The overall prevalence of anguillulosis was 2.7% (N=411) (IC95% = 1.34 4.73). The M/F sex-ratio was 1. No correlation was found between prevalence and sex (p = 0.12). Prevalence was higher among children who reported contact with swamps and rivers (respectively 80% and 7.9%) than those who did not report such contact (respectively 1.7% and 1.5%) (p <0.01). CONCLUSION: Contact with swamps and rivers is correlated with an increase in anguillulosis prevalence. Avoiding these areas and proper sanitation could help to reduce the prevalence of anguillulosis in Abidjan. PMID- 20734607 TI - [Castleman's disease: first case in Gabon]. AB - Castleman's disease is an atypical lymphoproliferative disorder characterized by hyperplasia of lymphoid structures with vascular proliferation. It has rarely been diagnosed in black African populations. The purpose of this report is to describe the first case in Gabon. The patient was a 47-year-old black African man. Outcome was fatal. PMID- 20734608 TI - [2007 cholera epidemic in Comoros islands: a step towards endemisation?]. AB - In 2007, a cholera epidemic occurred on two of the three islands of the Comoros archipelago: Grande Comore and Moheli. This study is based on data from the files of the 1571 patients admitted to five cholera treatment centers (CTC). The outbreak lasted for ten months. A dramatic peak was observed in July and August corresponding to the traditional wedding season during which hundreds of guests including returning diaspora gather to celebrate "Grand Marriages". Initial stool cultures identified Vibrio cholerae O1, Ogawa serotype. The in-center fatality rate was 1.85%. Poor socio-economical conditions combined with a rapid turnover of health personnel and delayed response of the health authorities could lead to endemisation. PMID- 20734609 TI - [Neurobrucellosis: description of 5 cases in Setif Hospital, Algeria]. AB - PURPOSE: Brucellosis is a major ubiquitous zoonosis transmitted from livestock to humans. It is a public health problem in developing countries. Between 2003 and 2005, the incidence of brucellosis in Algeria showed a 181% increase from 8.79 to 24.71. Between 2005 and 2007, the incidence remained almost stable. The estimated mean incidence of neurobrucellosis is 4% with clinical manifestations that are variable and often multi-focal in the same patient. The purpose of this retrospective study is to describe 5 cases of neurobrucellosis managed in our department between 2001 and 2007. MATERIALS AND METHODS: It was a retrospective study 5 patients. There were 2 women and 3 men with a mean age of 20 years. RESULTS: Neurological involvement occurred immediately in all patients. Clinical manifestations were variable with meningoencephalitis in 2, meningoencephalitis associated with a polyperipheral neuropathy in 1, meningomyeloradiculitis in 1, and acute diffuse encephalitis in 1. Definitive diagnosis was based on isolation of bacteria from a blood specimen in 1 case and detection of antibodies in blood and cerebrospinal fluid in 4. All patients were treated using a combination of 3 of the following 4 drugs: doxycycline, rifampicine, cotrimoxazole and aminoside. Treatment was associated with corticosteroid therapy in 3 cases. DISCUSSION: Neurobrucellosis can affect any part of the nervous system and can mimic any neurological disease. Early detection and treatment is the only predictor of favorable outcome of neurobrucellosis, but there is no standardized treatment protocol. Neurobrucellosis should be included in differential diagnosis for any patient presenting central or peripheral neurological manifestations especially in endemic zones. PMID- 20734610 TI - [Hematemesis in Togo: findings of a 12-month study in an intensive care unit]. AB - This prospective study was conducted over a 12-month period on patients who underwent upper digestive endoscopy for hematemesis in the medical intensive care unit (ICU) of the Tokoin University Hospital Center in Lome, Togo. A total of 44 patients with a mean age of 44 years were included. The sex-ratio was 2.61. Risk factors included use of non-steroid anti-inflammatory (NSAI) in 16 patients (36.4%) and alcohol abuse in 13 (29.6%). At the time of admission to the ICU, 21 patients (47.7%) were in hemodynamic shock and 11 (25%) presented signs of portal hypertension. The underlying etiology was peptic ulcer in 18 cases (40.9%) including 13 cases of duodenal ulcer and 5 cases of stomach ulcer, rupture of esophageal varicosities in 8 (18.2%), gastric tumor in 6 (13.6%), Mallory Weiss syndrome in 5 (11.4%), gastritis in 4 (9,1%), and esophagitis in 3 (6.8%) due to peptic inflammation in 2 and mycotic infection in 1. The mortality rate was 45.5%. The main causes of hematemesis were peptic ulcer and rupture of esophageal varicosities. The death rate was high due to inadequate care facilities. PMID- 20734611 TI - Heavy metal removal potential of dried Salvinia biomass. AB - Investigations were carried out to evaluate heavy metal adsorption capacity of Salvinia. Batch experiments showed that dry plant biomass possess good potential to adsorb heavy metals such as Ni, Co, Cr, Fe, and Cd. The metal adsorption increased with increase in initial metal concentration. The data obtained fitted well with Freundlich equilibrium isotherm. Further characterization of plant biomass showed presence of both acidic and basic surface functionalities that might facilitate binding of metal ions. Fourier transform infrared (FTIR) spectra of plant biomass suggested involvement of carbonyl (C=O), carboxyl (-COO), and hydroxyl (-OH) groups in binding heavy metals to plant biomass. The studies establish S. natans as an effective biosorbent for removing heavy metals from wastewater and further emphasize biomass utilization in wastewater treatment technologies. PMID- 20734612 TI - Chromium-induced modulation in the antioxidant defense system during phenological growth stages of Indian mustard. AB - Chromium-induced modulation in the enzymes and metabolites of antioxidants was investigated at various phenological stages of Indian mustard (Brassica juncea (L.) Czern. & Coss. cv Pusa Jai Kisan)], grown with various levels of chromium (Cr) in pots under natural environmental conditions. Chromium accumulation in the root, stem and leaves increased with the advancement in the age of the plants. Growth of Indian mustard was not affected significantly by the supply of Cr up to the levels of 400 mg kg(-1) soil. Activities of superoxide dismutase (SOD), ascorbate peroxide (APX), catalase (CAT), and glutathione reductase (GR) increased in the leaves of Cr-treated plants, when compared with control. High activities of antioxidant enzymes supported by high Cr concentrations in roots and aerial parts (except seeds) established the Indian mustard as a potential hyperaccumulator anda hypertolerant species to Cr stress. For this study, an edible crop was chosen intentionally so as to tap maximum benefit by remediating the contaminated site on one hand and getting uncontaminated seeds to raise the next generation, on the other. PMID- 20734613 TI - Analysis of arsenic in soil and vegetation of a contaminated area in Zarshuran, Iran. AB - To assess the potential for arsenic (As) hyperaccumulation of native plant species, plant and soil samples were collected from the Zarshuran area (north western Iran), which has a history of As pollution from mining. Total and water soluble As in the soil ranged from 11.2 to 6525 and from 0.004 to 13.08 mg kg( 1), respectively. Among 89 plant species, the highest foliar As concentrations were found in Isatis capadocica (up to 3000 mg kg(-1)) and Hesperis persica (up to 1500 mg kg(-1)). Over a broad range of soil As concentrations, these species maintained more than 10-fold increased foliar As concentrations and soil to leaf As transfer coefficients in comparison with all the other species sampled at the same sites. Based on these characteristics, in combination with their ability to accumulate As to concentrations exceeding 1000 mg kg(-1) on a dry weight basis in their foliage, both species should be classified as As hyperaccumulators. I. capadocica and H. persica, both Brassicacaeae, are the first terrestrial angiosperms shown to possess the As hyperaccumulation trait. Both species are fairly robust with relatively high biomass productivity and, therefore, potentially useful in on site phytoremediation, particularly I. capadocica, because of its higher robustness and As accumulation capacity. PMID- 20734614 TI - Effect of soil properties on arsenic hyperaccumulation in Pteris vittata and Pityrogramma calomelanos var. austroamericana. AB - Two arsenic (As) hyperaccumulators, Pteris vittata L. and Pityrogramma calomelanos var. austroamericana, were grown in As-contaminated soils of contrasting properties. Ferns were exposed to three levels of As in soil at concentrations of 0,600 and 2400 micromol kg(-1) for a period of 22 weeks. Plant biomass and As concentration in fronds and roots varied significantly between the two species. At 600 micromol kg(-1) As level, As hyperaccumulation was not observed in both the fern species. However at the 2400 micromol kg(-1) As level, both the species accumulated very high levels (> 1000 mg kg(-1)) of As in fronds. Arsenic concentration and uptake in fronds of both species followed the order Kurosol (Box Hill) > Vertosol (Narrabri) > Ferrosol (Robertson). In the studied soils, P. vittata possessed higher frond biomass and As accumulation, and thus was more efficient in removing soil As than P. calomelanos var. austroamericana. Soil properties such as free Fe, clay and organic matter contents appear to have affected the bioavailability of As in the studied soils. These results show that soil properties influence the As extraction efficiency of hyperaccumulating plants and must be considered in context of the phytoextraction technology of As contaminated soils. PMID- 20734615 TI - Phytoremediation of water and soil contaminated with imidacloprid pesticide by Plantago major, L. AB - Broadleaf plantain plant (Plantago major L.) was used in phytoremediation of imidacloprid insecticide in water and soils. For the Freundlich model the constant related to the biosorption capacity (Kf) of imidaclaprid were respectively, 7.94, 6.31, and 2.51 ug/g for dry roots, fruits (seeds with shells) and leaves of broadleaf plantain plant. Viable whole broadleaf plantain plant in water solution reduced imidacloprid residues by 55.81-95.17%, during 1-10 days of exposure periods compared with 13.71-61.95% in water solution without the plantain. In water solution, imidacloprid significantly accumulated in plantain roots, leaves and fruits to reach the maximum levels after 6, 1 and 3 days of treatment, respectively. The maximum levels were 15.74, 37.21, and 5.74 ug/gm, respectively. These values were decreased to 6.95, 1.46, and 0.12 ug/ gm after 10 days of treatment. The growing cells of short-rod gram-negative bacteria that isolated from the water solution containing broadleaf plantain plants was able to induce 93.34% loss of imidacloprid as a source of both carbon and nitrogen within a short period (48 hr) compared with 31.90% in un inoculated medium. Half-life (t 1/2) in soil planted with broadleaf plantain plants and in unplanted soil were found to be 4.8 and 8.4 days, respectively. PMID- 20734616 TI - Management practices and phytoremediation by native grasses. AB - Using native species for phytoremediation may be more ecologically beneficial and cost-effective than monoculture planting approaches. This study evaluated the effect of various soil amendments and management on the potential of Midwestern prairie grasses to remediate field soil contaminated with polycyclic aromatic hydrocarbons (PAHs) and other pollutants. A greenhouse investigation was conducted using six different grass species native to Ohio. Plants were grown in buckets containing topsoil and a layer of field-collected contaminated soil. Buckets were amended with commercial compost, fertilizer, or a combination of both. Replicates were watered every fourth day (frequently) or every sixth day (infrequently). Chlorophyll content were measured monthly for five months during the growing season. After five months, cores were sampled from each treatment and the total petroleum hydrocarbon (TPH) and PAH concentration of the soil determined. Native Ohio grasses reduced TPH contamination at least 87% with frequent irrigation and 90% with infrequent irrigation from buckets containing both compost and fertilizer. PAHs were dissipated to concentrations below detection limit of 1 ppm except for benzo (123) perylene and indeno (123-cd) pyrene. Results of this study suggest that it may be effective to allow contaminated sites to re-vegetate with native grasses. PMID- 20734617 TI - Hydroponic uptake and distribution of nitrobenzene in Phragmites australis: potential for phytoremediation. AB - Phragmites australis was grown hydroponically in nutrient solutions containing nitrobenzene to examine the potential for treatment of contaminated waters through phytoremediation. The hydroponic solutions and plant tissue were sampled each day during the five day growth period and tested for nitrobenzene. Plant tissue analysis included both rhizome and shoot sections of the plant. The average half lives and disappearance rate of nitrobenzene in the nutrient solution was 1.85 days and 88.10%, respectively. The levels of nitrobenzene in rhizomes and shoots of Phragmites australis increased with higher exogenous concentrations. For the highest treatment, nitrobenzene measurements in the rhizome tissue were much higher than the plant shoots until the third day. Shoot sections initially showed elevated concentrations and then decreased. This variation is presumably due to the translocation of the target compound from the rhizomes to shoots. Our findings indicate that Phragmites australis removed nitrobenzene from the hydroponic solutions and accumulated the compound within the plant tissue. This activity makes Phragmites australis a good candidate species for the phytoremediation of nitrobenzene contaminated waters. PMID- 20734618 TI - Heavy metal pollution in lentic ecosystem of sub-tropical industrial region and its phytoremediation. AB - Metals and several physicochemical parameters, from four sampling sites in a tropical lake receiving the discharges from a thermal power plant, a coal mine and a chlor-alkali industry, were studied from 2004-2005. Pertaining to metal pollution, the site most polluted with heavy metals was Belwadah, i.e., waters and sediments had the highest concentration of all the metals examined. The reference site was characterized by the presence of low concentrations of metals in waters and in sediments. Further, several wetland plants were harvested from different sites, and simultaneously, these were assessed for their metal concentration efficiency. Following the water quality monitoring and metal concentration efficiency, two-month field phytoremediation experiments were conducted using large enclosures at the discharge point of different polluted sites of the lake. Eichhornia crassipes, Lemna minor, and Azolla pinnata were frontier metal accumulators hence selected for previously mentioned field phytoremediation experiments. During field phytoremediation experiments using aquatic macrophytes, marked percentage reduction in metals concentrations were recorded. The percentage decrease for different metals was in the range of 25 67.90% at Belwadah (with Eichhornia crassipes and Lemna minor), 25-77.14% at Dongia nala (with Eichhornia crassipes, Lemna minor, and Azolla pinnata) and 25 71.42% at Ash pond site of G.B. Pant Sagar (with Lemna minor and Azolla pinnata). Preliminary studies of polluted sites are therefore useful for improved microcosm design and for the systematic extrapolation of information from experimental ecosystems to natural ecosystems. PMID- 20734619 TI - Developing selenium-enriched animal feed and biofuel from canola planted for managing Se-laden drainage waters in the westside of central California. AB - We studied the reuse of selenium (Se)-laden effluent for producing canola (Brassica napus) and subsequent bioproducts in central California. Canola was irrigated with poor quality waters [electrical conductivity (EC) of approximately 5 dS m(-1) sulfate-salinity, 5 mg B L(-1), and 0.25 mg Se L(-1)]. Typical seed yields were 2.2 metric tons ha(-1). Seeds were processed for their oil, and transesterified to produce ASTM-quality biodiesel (BD) blends. The resulting Se enriched seed cake meal (containing approximately 2 mg Se kg(-1) DM) was used in a dairy feed trial. Seventy-two Jersey and Holstein cows, 36 respectively, were fed Se-enriched canola meal as 6.2% of their daily feed ration for five weeks. Blood and milk samples were collected weekly and analyzed for total Se. This study showed that Se-enriched canola meal did not significantly increase total blood Se content in either cow breed. Milk Se concentrations did, however, significantly increase to safe levels of 59 microg Se L(-1) and 52 microg Se L( 1) in Jersey and Holstein cows, respectively. The production of BD 20 biofuels and Se-enriched feed meal from canola irrigated with poor quality waters may help sustain similar phytomanagement strategies under Se-rich conditions. PMID- 20734620 TI - Vegetation changes and partitioning of selenium in 4-year-old constructed wetlands treating agricultural drainage. AB - The knowledge of selenium (Se) partitioning in treatment wetlands and wetland vegetation management are essential for long-term effective operation of constructed wetlands treating Se-laden agricultural tile-drainage in central California. In this field study, samples from different compartments of treatment wetlands were collected and the vegetation change in each wetland cell was examined four years after the wetland's inception. The results showed that saltgrass (Distichlis spicata) and rabbitfoot grass (Polypogon monspeliensis) were less competitive than cattail (Typha latifolia) and saltmarsh bulrush (Scirpus robustus). Over 90% of the wetland cell originally vegetated with saltgrass or rabbitfoot grass was occupied by invasive plants--i.e., when invasive species were not controlled in the wetlands. More Se was likely found in sediments from vegetated regions, compared to the unvegetated areas of the wetland cell. Particularly, rhizosphere sediments accumulated about 4-fold more Se than non-rhizosphere sediments. Among the total Se retained in the wetland 90% of the total Se was partitioned in the top 10-cm layer of sediment. The Se accumulation in plant materials accounted for about 2% of the total Se mass retained in each wetland cell. This field study demonstrated that wetland plants play significant roles in the treatment of Se-laden agricultural drainage. PMID- 20734621 TI - Phytoremediation of oilfield sludge after prepared bed bioremediation treatment. AB - A field-scale experiment was carried out to compare the effectiveness of five plant species in the remediation of oily sludge. Alfalfa, tall fescue, and soybean substantially increased the removal rate of oil and grease (O&G) after 120 days of remediation. Of these, soybean treatment showed the highest removal rate of 34.2% compared with only 13.7% in the unplanted control plot. In addition to assisting with phytoremediation, soybean can also be used for energy production, for example in the production of biodiesel. Furthermore, microbial counts and community level physiological profiling using Biolog sole carbon source utilization tests were used to investigate the effect of plants on the microbial community of oily sludge. Plants selectively increased microbial counts in the rhizosphere and O&G concentrations of the sludge were negatively correlated with counts of TPH (total petroleum hydrocarbon) degraders. The acute biotoxicity of the sludge was also tested by the bacterial luminescence method and alfalfa treatments decreased the biological toxicity of the sludge compared with the unplanted control. PMID- 20734622 TI - Investigation of the water purification efficiency of flood irrigation system by using flora succession as an index. AB - A flood irrigation system was constructed to remove nutrient-based water pollutants through the various natural treatment mechanisms of plants and microorganisms. Species of plants were allowed to proliferate naturally within the system. The succession of flora was then utilized as an index to evaluate the water purification efficiency of the flood irrigation system. The natural growth of plants during the test period indicated what part of the irrigation system would recover most efficiently from nutrient-based contamination. From the first stage of observation (50 days) to the second stage (50 days), the average processing efficiencies of Nitrate Nitrogen (NO3(-)-N) and Ortho-phosphate (PO4(3 )) were improved 1.7% and 70.3%, respectively. After the 60th day, the Compositae family flourished in the system. At the same time, removal rate of Nitrate Nitrogen was increased dramatically which may be related to prevalence of the Compositae family. Trends indicate that the Ortho-phosphate concentration of the irrigated water was low, and Brachiaria mutica of Poaceae were dominant which may have lead to the phenomenon of phosphorus released in the flood irrigation system. PMID- 20734623 TI - Distribution and mobility of copper, zinc and lead in plant-sediment systems of Quanzhou Bay estuary, China. AB - The distribution, mobility and potential risks of Cu, Zn, and Pb in four typical plant-sediment co-systems of the Quanzhou Bay estuary wetland in southeast China were investigated using a sequential extraction procedure. The results show that the sediments were moderately or heavily contaminated with Zn and Pb in all four plant communities, and the plant-sediment systems could act as a sink for the heavy metals. In all investigated sediments, only a small proportion of measured heavy metals were distributed in exchangeable fraction and carbonate fraction, while the reducible fraction contained the highest amount of Zn and Pb of the total readily bioavailable fractions, and the oxidizable fraction exhibited a higher retention capacity for Zn and Cu, but lower for Pb. Alternanthera philoxeroides had the best ability to accumulate heavy metals among the four species. Phragmites communis was quite tolerant to Zn and Pb and had a good capability to transfer Zn and Pb. Aegiceras corniculatum seems to be effective in resisting heavy metal pollution, and therefore cannot serve as an indicator of contamination. The urgent need for many local enterprises is to carry out high tech cleaner production to reduce the emission of pollutants and achieve a resource-economical and environment-friendly development. PMID- 20734624 TI - Phytoremediation of pharmaceuticals--preliminary study. AB - Phytoremediation of selected pharmaceuticals (diclofenac, ibuprofen, and acetaminophen) using Armoracia rusticana and Linum usitatissimum cell cultures and by hydroponically cultivated Lupinus albus, Hordeum vulgaris, and Phragmites australis plants in laboratory conditions is described. During in vitro experiments, the best results for acetaminophen were achieved using Armoracia rusticana hairy root cultures, where 100% of the starting amount was removed from the media during eight days. Total removal of ibuprofen and diclofenac was achieved using a Linum usitatissimum suspension culture after one and six days, respectively. In the hydroponic arrangement, the best results were achieved for Lupinus, where acetaminophen was totally removed from media during two or four days in concentrations of 0.1 or 0.2 mM, respectively. The best effectiveness of ibuprofen removal (50% of starting amount) was found in case of Phragmites. Effectiveness of all tested plants for diclofenac removal was low. The best removal was achieved using Phragmites in the case of 0.2 mM concentration-67% of the starting amount and Hordeum for 0.1 mM starting concentration, 56%. PMID- 20734625 TI - Seasonal sap flow of four Salix varieties growing on the Solvay wastebeds in Syracuse, NY, USA. AB - Sap flow of four shrub willow varieties was measured to study their potential use as an evapotranspiration (ET) cover on the Solvay wastebeds to reduce deep percolation and leaching of chloride. Stem and stand-level sap flow and crop coefficients (K(c)) were different among four willow varieties measured between early June and mid November 2006. Diameter and cross sectional area had a significant impact on stand level sap flow. Peak stand-level sap flow of 7 mm d( 1) occurred in June, due to coupling of the willow with the atmosphere, and not in July or August when peak LAI was measured. The coupling also resulted in high K(c) values of 3 in June and above 2 in October with an average of 1.1-1.3 for the entire season. Our measurements confirmed the potentials of shrub willow in ET cover applications in the northeastern USA. Total transpiration for the growing season ranged between 494 mm and 533 mm, which was about 45% of the precipitation in 2006. Our calculations showed a significant difference between peak season sap flow in June, July and August and sap flow over the course of the whole growing season, which showed the need for long-term measurements. PMID- 20734626 TI - Earthworm mucus enhanced cadmium accumulation of tomato seedlings. AB - A hydroponic experiment was carried out to study the effects of earthworm (Metaphire guillemi) mucus on tomato Hezuo 903 (Lycopersicon esculentum) seedlings growth and cadmium (Cd) accumulation. The experiment included three levels of Cd addition rates (0, 5 and 10 mg L(-1)), two levels of earthworm mucus addition (20 and 40 ml per pot) treatments (EML and EMH), and the control (CK). The results showed that compared with the control earthworm mucus addition significantly increased shoot and root dry weights of tomato seedling by 13.8 44.5% and 12.4-33.2%, respectively. In contrast, high earthworm mucus addition (EMH) led to a 4% shoot weights decrease at 10 mg Cd L(-1) compared with CK. Cadmium concentrations and accumulations in both shoot and root of tomato seedlings were significantly increased (p < 0.01) with increasing Cd and earthworm mucus addition levels. Cadmium concentrations and accumulations in root were much higher than those in corresponding shoot. Present study indicated that earthworm mucus could enhance tomato seedlings growth and Cd accumulation. Our work might be not only very useful for understanding how earthworms enhance plant growth and heavy metals accumulation, but also for further application of earthworms in phytoextraction. PMID- 20734627 TI - Plant traits that enhance pollutant removal from stormwater in biofiltration systems. AB - Plants species have been shown to improve the performance of stormwater biofiltration systems, particularly in removal of N and P. Recent research has shown that plants vary in their contribution to pollutant removal but little is known about the type of plant that is best suited to use in biofilters in terms of survival, growth rate, and performance. In this study, growth responses of 20 species to applications of semi-synthetic stormwater were measured, and the roles of key plant traits in removal of N, P, and several metals were investigated. There was no evidence of negative effects of stormwater application on plant growth, and plant traits, particularly root traits, were strongly correlated negatively with N and P concentrations of effluent stormwater. The most common and strong contributors to N and P removal appeared to be the length of the longest root, rooting depth, total root length, and root mass. The plants that made the strongest contribution to pollutant removal, e.g, Carex appressa, combined these traits with high growth rates. Investigation of other plant traits (e.g, physiology), causal mechanisms, and effects of more complex planting environments (e.g, species mixtures) should further guide the selection of plants to enhance performance of biofiltration systems. PMID- 20734628 TI - Degradation of PAH in a creosote-contaminated soil. A comparison between the effects of willows (Salix viminalis), wheat straw and a nonionic surfactant. AB - The degradation of polyaromatic hydrocarbons (PAH) in an aged creosote contaminated soil in the presence of Salix viminalis was investigated in a greenhouse experiment. Phenanthrene and pyrene were degraded 100% and 80%, respectively, in the presence of plants but only 68% and 63% without plants. The effects of the nonionic surfactant Triton X-100 or the addition of straw, without plants, were also studied. The addition of straw had no effect on PAH degradation compared to the control Pyrene degradation with Triton X-100 at low concentrations (0.06 microl g(-1) DW) was comparable to that with plants but was less for anthracene and phenanthrene. The treatments with plants were, according to SIR measurements, dominated by active microorganisms (98.8% of the biomass), whereas all treatments without plants contained mostly dormant or non-growing microorganisms (1.7-2.0% active). Viable counts and active biomass were highly correlated in all treatments and demonstrated that S. viminalis greatly increased microbial populations. Dominant bacteria were grouped according to Gram, fluorescence and oxidase tests and revealed differences between treatments. The presence of S. viminalis or the surfactant enhanced PAH degradation, primarily by a rhizosphere effect on the microbial activity in the former case and by increased bioavailability in the latter case. PMID- 20734629 TI - Ability of various plant species to prevent leakage of N, P, and metals from sewage sludge. AB - The preventive effect of vegetation on nutrient and metal leakage from sewage sludge (SS) used in treatment of mine waste was investigated. In a 10-week greenhouse study, the release of ammonium, nitrate, phosphate, Cd, Cu, and Zn from SS was analyzed in the absence (control) and presence of basket willow, fireweed, reed Canary grass (RCG), and Scots pine. Plants significantly decreased the leakage by reducing the amount of leachate, and lowered the concentrations of phosphate (to 0.1 mg L(-1)), Cu (0.8 mg L(-1)), and Zn (2.2 mg L(-1)); and plants increased the pH in the leachate towards the end of the experiment. The most efficient plant was RCG that significantly decreased the total leakage of all pollutants. However, plants could not counteract high initial concentrations of ammonium and nitrate (< 400 mg L(-1) of both) and drop in pH (to 4.5), or increasing Cd release (< 9.7 microg L(-1)). RCG and fireweed used both ammonium and nitrate as nitrogen source and were more efficient in preventing nitrate leakage, compared with willow and pine that mainly used ammonium. This study indicates that introduction of RCG is a promising method for phytostabilization of SS, but that alkaline additives are needed to prevent an initial decrease in pH. PMID- 20734631 TI - Microcosm investigation on phytoremediation of Cr using Azolla pinnata. AB - The extent of Chromium (Cr) pollution in Singrauli industrial region, India was assessed and phytoremediation capacity of a small water fern, Azolla pinnata R.BR (Azollaceae) was observed to purify waters polluted by Cr under microcosm condition. Azolla pinnata endemic to India is a potential hyper-accumulator of heavy metals. During 13 days of the experiment the fern was grown in the aqueous medium containing Cr3+ and CrO4(2-) ions, each in a concentration 0.5, 1.0, and 3.0 mg L(-1). The presence of these ions caused a + 3.1 to -37.5% inhibition of Azolla pinnata growth in comparison to the control. After 13 days of the experiment, metal contents in the solution was decreased up to 70% (CrO4(2-) 3.0 mg L(-1) treatment) to 88% (CrO4(2-) 0.5 mg L(-1) treatment). In the Azolla pinnata tissues, the concentration of couple of the ionic forms of Cr under investigation ranged from 415 to 1095 mg kg(-1) dry mass (dm); the highest level being found for Cr (III) containing solution. PMID- 20734630 TI - Sexual propagation of Pteris vittata L. influenced by pH, calcium, and temperature. AB - We aimed to optimize germination and growth conditions of the arsenic hyperaccumulating fern, Pteris vittata L. Pot experiments were carried out to investigate the effects of soil pH, soil calcium (Ca) concentration, and temperature on the sexual propagation of P. vittata. At 25 degrees C, germination was both accelerated and increased by high soil pH and Ca concentration. Spores of P. vittata did not germinate on medium with a pH of 4.6. Amending strongly acid soils with 27.5 or 40 micromol/g Ca(OH)2 significantly improved the growth rate during both the germination phase and the gametophyte phase. Amending strongly acid soils with NaOH (55 micromol/g) promoted germination, but did not affect subsequent growth. Among the different temperature, germination and growth rates were higher at 25 degrees C than at 20 degrees C or 30 degrees C. The distribution of P. vittata in China might be influenced by its requirement for high pH and high Ca concentration in the soil and appropriate growth temperature to complete sexual propagation. These results provided important information for improving breeding conditions of P. vitatta and will be helpful for extending the range of areas in which P. vittata can be used for phytoremediation. PMID- 20734632 TI - Screening of poplar clones for cadmium phytoremediation using photosynthesis, biomass and cadmium content analyses. AB - Variability of cadmium tolerance and distribution in plant organs was investigated in ten selected poplar clones from different species, hybrids and genotypes. To this end, plants were exposed for three weeks to 50 microM CdSO4 in hydroponics. Cadmium accumulation in roots, stem and leaves as well as biomass production and photosynthesis maintenance varied greatly among clones. The metal mostly accumulated in roots, up to 80% in some clones, and interestingly, only 50% in some others. In general, metal tolerance reflected the degree of photosynthesis inhibition, which was higher in clones with high cadmium accumulation in leaves. Biomass production, net photosynthesis, transpiration, and pigment content were differently reduced in cadmium-treated clones with respect to control. The variability of cadmium distribution among leaves, stem, and roots provides candidate poplars for specific phytoremediation processes of contaminated waters and soils. PMID- 20734633 TI - A comparison of the dietary arsenic exposures from ingestion of contaminated soil and hyperaccumulating Pteris ferns used in a residential phytoremediation project. AB - Arsenic (As) hyperaccumulating ferns are used to phytoremediate As-contaminated soils, including soils in residential areas. This use may pose a health risk if children were to ingest these plants. Spider brake (Pteris cretica L.) plants were grown in sand spiked with arsenate, to produce tissue As concentrations (2000-4500 mg kg DW(-1)) typical of those observed in plants deployed for As phytoremediation. The fronds were subjected to a physiologically-based extraction test to estimate As bioaccessibility, which ranged from 3.4-20.5%. A scenario for human dietary exposure to As in an urban setting was then estimated for a child consuming 0.25 g DW of tissue. The calculation of dietary exposure took into account the As concentration in the fern pinnae, the bioaccessibility of As in the tissue, and the typical absorption of inorganic As by the gastrointestinal tract. The pinnae As concentrations and the calculated dietary exposures were used to create a non-linear regression model relating tissue As concentration to dietary exposure. Data from a phytoremediation project in a residential area using Pteris cretica and Pteris vittata (L.) were input into this model to project dietary As exposure in a residential phytoremediation setting. These exposures were compared to estimates of dietary As exposure from the consumption of soil. The results showed that dietary exposures to As from consumption of soil or pinnae tissue were similar and that estimates of dietary exposure were below the LOAEL value of 14 microg As kg(-1) d(-1). The results suggest that the hyperaccumulation of As in Pteris ferns during growth in moderately contaminated residential soils (e.g., < or = 100 mg As kg DW(-1)) does not represent an inherent risk or a risk substantially different from that posed by accidental ingestion of contaminated soil. PMID- 20734634 TI - [A comparative study of the prognostic pH values of the fetus in utero, generated by the "quantitative cardiotocography" computer method, and the actual pH values measured immediately after delivery]. AB - INTRODUCTION: The presented methodology for quantitative evaluation of the cardiotocographic (CTG) findings unconditionally provides essential opportunities for improving the diagnostic potential in modern obstetric practice. Current literature data concerning the clinical application of this method are scarce. Credible clinical trials are needed to determine what is the correlation between estimated and actual values of the studied variables. MATERIALS AND METHODS: A prospective study on 110 pregnant women was performed. All patients were monitored via indirect cardiotocography. The recordings were stored and analyzed by the computerized method for "quantitative cardiotocography". We compared the last prognostic fetal pH value, generated by the "quantitative cardiotocography" software during labor, with the actual pH measured from the umbilical artery (UA) of the newborn. RESULTS: For each of the stored CTG recordings we quantified the difference between the last forecast and the actual pH of the newborn. In 82% of these cases this difference was in range of -0081/+0074 from the projected results. However during the study we discovered that there is a significantly better correlation between the arithmetic average of the last 6 (six) predicted results and the actual pH of the newborn. In 85% of these cases the difference between forecast and actual pH values lies a in range of -0037/+0046. CONCLUSION: Using the arithmetic average of the last 6 (six) predicted results for pH leads to a significant increase in the clinical value of the "quantitative cardiotocography". More studied are needed if we are to find opportunities to further reduce the existing prediction variability. PMID- 20734635 TI - [Expression of activating and inhibitory receptors on peripheral blood natural killer cell subsets of women with reproductive failures]. AB - It is now apparent that immunologic implantation failure and recurrent abortions are more than likely mediated through activation of natural killer (NK) cells. The NK cell activity is mediated by a balance between activating and inhibitory receptors upon recognition of MHC class I molecules. In this study, we investigated by flow cytometry the expression of activating and inhibitory receptors on NK cells of women with reproductive failures- recurrent spontaneous abortion (RSA) and implantation failures (IF). In women with implantation failures CD56+CD16+ NK cell subset was significantly increased (p = 0.017) and CD158a expressing NK cells was significantly decreased (p = 0.027). CD161 activating receptor expressing CD56+ NK cells were significantly decreased in women with RSA (p = 0.033). These data further support an imbalance in NK cell subsets in women with reproductive failures. PMID- 20734636 TI - [Strategies for hormonal ovarian stimulation in IVF, based on materials of the centre for assisted reproduction "varna"]. AB - During a two years' period (2008-2009), 834 patients underwent IVF in the Centre. Long protocol was used where normal response was expected; for high risk patients was used protocol with antagonist and induction of ovulation with agonist or 5 000 IU HCG; and when poor response was expected, flare up protocol was applied. 363 clinical pregnancies were registered--50% for transfer and 43.4% for cycle. Experience shows that antagonist - agonist protocol reduces significantly but not completely the risk of OHSS. On poor responders, the standard short protocol shows better results than any of the recently suggested protocols. In future, the so called "controlled ovarian hyperstimulation" will be performed only in its soft version and when certain indications exist. PMID- 20734637 TI - [Methods for preoperative and intraoperative evaluation of the tumour infiltration and lymph node metastases in endometrial cancer (summarized own and foreign experience)]. AB - AIM: The preoperative and intraoperative evaluation of the depth of tumour infiltration into the myometrium and the assessment of the lymph node metastases of pelvic and paraaortal region, is used from many western oncogynaecological clinics to plan the extend of the surgical treatment. In this way is determined the need for surgical staging and the performance of pelvic and paraaortal lymph node dissection. Sometimes this evaluation differs from the final histopathological report. That is why with the present research work done for 22 years period we tried to evaluate the accuracy and efficacy of the preoperative and intraoperative evaluation of the myometrial infiltration in endometrial cancer patients. MATERIAL AND METHODS: We evaluated 460 patients radically operated without lymph node dissection and 460 patients with lymph node dissection for 22 years period. The depth of myometrial infiltration was evaluated by TVS, CT scan, MRI, and in the last 2 years with PET scan. D&C was preoperatively performed. The histological grading was preoperatively and postoperatively assessed. The depth of myometrial infiltration was evaluated (less or more than 50%). Intraoperatively the uterus was cut and gross examined visually measuring the depth of cancer invasion in the myometrium. From the statistical methods - x2, variation analysis, correlation analysis, regression analysis as well as the Wilcoxon and the log-rank test were used. RESULTS: The histopathological findings showed 346 patients with lymph node dissection-stage IA and 370 patients without lymph node dissection- stage IA. 114 patients had lymph node dissection - stage IB and 90 patients without lymph node dissection - stage IB. In 716 patients the infiltration in myometrium was less than 50% and in 204 patients the infiltration was more than 50%. The ultrasound examination (TVS) had 80% accuracy. The accuracy, sensitivity and specificity of MRI were 85%, 77% and 87% respectively The CT scan examinations were not so convincing, while the PET scan were better and were very useful. In intraoperative cutting of the uterus and its gross examination, if the infiltration of the tumour was more than 50% in the myometrium, and diameter of the tumour more than 2 cm--we performed lymph node dissection. The method was economically efficient, very easy appliciable and with high sensitivity (85%) and specificity (90%) rate. It can be easily applied in gynaecological and oncogynaecological practice. The definition of the preoperative grading was 75%. We observed differences in evaluation of preoperative and post operative grading results in low differentiated endometrial cancers (G3). CONCLUSIONS: Our research work showed that the cutting and gross examination of the tumor intraoperatively could be of benefit for evaluation of the myometrial infiltration of the tumor mostly when it was more than 50%, but also when it was less than 50% of the myometrial depth. In this way we can define the need for surgical staging especially when the infiltration of the tumour into the myometrium was more than 50% of its thickness. PMID- 20734638 TI - [Prevalence of human papillomavirus genotypes in Bulgarian women with atypical cervical lesions examined by colposcopy]. AB - INTRODUCTION: For the first time three studies describing human papillomavirus (HPV) genotype distribution in Bulgaria was presented at 15th National Conference of Oncogynecology (22-25.04.2010; V. Turnovo). Such studies are needed to predict how HPV vaccination and HPV-based screening will influence cervical cancer prevention. AIM: The aim of this study was to determine the types of human papillomavirus (HPV) distribution in Bulgarian women's population (age 16-40 years) with atypical cervical lesions examined by colposcopy. METHODS: The prevalence of type-specific HPV was searched by PCR-DNA in 176 women with positive colposcopic findings (results). RESULTS: Human papillomavirus was found in 105 (59.7%) of the women, while 71 (40.3%) were negative for this virus. From 105 positive for HPV women, 95 (90.5%) were infected with high- risk genotypes and 10 (9.5%) with low-risk genotypes. Among high-risk types, a predominance of HPV-16 (39% of infected women) was shown followed by HPV-56 (17.1%) and HPV-33 (15.2%). 45.7 percent of our patients were infected with single HPV genotype, whereas 54.3% were infected with mixtures of HPV genotypes. CONCLUSIONS: The presence of relatively high percentage of HPV types 33 and 56 and the relatively high incidence of infections with mixture of genotypes are the reasons for obligatory secondary prophylactic procedures (cytology, colposcopy and HPV detection), never.mind HPV vaccination. We find that, there is strong connection between HPV infection and positive colposcopic results. PMID- 20734639 TI - [Clinical, hormonal and metabolic characteristics of different phenotypes of polycystic ovary syndrome, in Bulgarian population]. AB - AIM: Our aim was to investigate the percentage occurrence of different phenotypes of polycystic ovary syndrome (PCOS) in a Bulgarian population, and their clinical, metabolic and hormonal characteristics. METHODS: The study included 110 women with PCOS, diagnosed according to the Europian Society of Human Reproduction & Embriology/American Society for Reproductive Medicine criteria. The women were divided into four phenotypes: hyperandrogenism (HA) + oligo-/ anovulation (OA) + polycystic ovaries at ultrasound (PCO) ( full-blown syndrome, phenotype A); HA + OA (former Institute of Health definition, phenotype B); OA + PCO (phenotype C); and HA + PCO (phenotype D). Serum levels of testosteron, immune-reactive insulin, sex hormone-binding globulin, dehydroepiandrosterone sulfate and lipid metabolism parameters were measured. Free androgen index and homeostasis model assessment of insulin resistance were calculated. Body mass index and waist- to--hip ratio were assessed. RESULTS: The percentage of phenotypes A, B, C and D in a Bulgarian Population are 53.6%, 12.8%, 11%, 22.6% respectively. The women with the classical form of PCOS (phenotypes A and B) were more obese, had more strongly expressed hyperandrogenemia, and were more insulin- resistant compared with the women of phenotypes C and D. CONCLUSION: There is a significant difference in anthropometric, hormonal and metabolic indices between the classical form and the clinical variants of PCOS in the studied Bulgarian population. PMID- 20734640 TI - [Anatomic and topographic lymphatic metastasis and sentinel lymph node mapping in early stage of cervical cancer patients']. AB - Biopsy of the sentinel lymph nodes is a method by which using a specific marking. Can be detected and examined lymph nodes that are first in the way of lymph drainage and metastasis. In some cases they give us information for the metastatic status of the whole lymph region. They are named sentinel. The conception of the sentinel lymph nodes is one of the most important and interesting achievements of the clinical oncology for the last ten years. According to her it is possible by removing and examining of one or a few lymph nodes to predict if there is or no tumor invasion in the regional lymph basin. MATERIALS AND METHODS: In the prospective study for two years period are made in clinic of Oncogynecology, Oncologic center to University Hospital of Pleven. 129 cases with proved histological invasive cancer of the uterine cervix after making a clips--biopsy or separated curettage. We applied a preoperative method for detection of the sentinel lymph nodes by using a coloring agent to all the patients included and after that, they had a different kind of operative intervention on the uterine and the lymph nodes. AIM AND GOALS: Our aim was to show the locoregional metastasing and detection of the SLNB in patients with invasive cancer of the uterine cervix, by using a coloring agents Patent blau V (PV)--which passed through surgical intervention on the uterine and pelvic or paraaortic dissection. Our goal was to clear up the anatomic topographical lymph metastasing and coloring by levels and localization in invasive cancer of the uterine cervix--regionally in pelvic lymph nodes and in paraaortic area. CONCLUSION: Sentinel lymph biopsy has its place in the detection of the lymph metastasis in cancer of the uterine cervix, and their localization shows the ways of lymph metastasis and this kind of gynecological tumors and gives an opportunity for an individual way of surgical treatment in patients with early cancer of the uterine cervix. PMID- 20734641 TI - [Dopplerometry at prolonged pregnancy]. AB - Prolonged pregnancy, associated with low amniotic fluid is a reason for the increase of fetal mortality and morbidity. There is no a define test at prolonged pregnancy which can determine which pregnancy are at a risk for adverse outcome and complications. Dopplerometry as a noninvasive method for examination of blood circulation, and especially a. cerebri media and a. umbilicalis can be used for the prediction of the outcome of prolonged pregnancy. PMID- 20734642 TI - [Three-dimensional (3D) transvaginal ultrasound--clinical implementation in benign gynecological disorders]. AB - The implementation of three-dimensional (3D) transvaginal (TV) ultrasound (US) in gynecology increases progressively. The method is successfully used in the diagnosis and differential diagnosis of benign gynecological pathology- congenital anomalies of the female reproductive system, fibroids, endometriosis, adenomyosis, endometrial polyps, pelvic inflammatory disease, adnexal masses, ectopic pregnancy, etc. This review describes the current use of 3D TV US in gynecological practice. PMID- 20734643 TI - [Congenital rhabdomyoma--prenatal diagnosis with three-dimensional ultrasound of two cases with different pregnancy outcome]. AB - Congenital rhabdomyoma is the most common benign tumor of the fetal heart. Usually it occurs as a single or multiple lesions located within the ventricles and it is often associated with tuberous sclerosis after birth. We present two cases of congenital rhabdomyoma diagnosed in the third trimester with three dimensional (3D) ultrasound. Both cases had different pregnancy outcome. PMID- 20734644 TI - [Case report of infected lymphocele]. AB - The lymphorrhea is a problem that we face in the early postoperative period in patients undergoing lymph node dissection (LND) for treatment of cervical cancer (CC). The formation of lymphocele most often in the pelvis is as a consequence. The incidence of lymphocele different, ranging from 0.4% to 58.7%. It is diagnosed most common in random checks in the asymptomatic or by presence of complains in symptoms. Ultrasound is most commonly applied together with computed axial tomography. One of the methods for treatment of symptomatic lymphocele is percutaneous drainage under ultrasonic control. As a complication of this procedure are observed cases of infection of lymphocele. PMID- 20734645 TI - [Episiotomy--obstetrics operation with strict indications or iatrogenic injury of the female pelvic floor]. AB - Episiotomy is the most common operation in obstetrics, which took its place in the obstetric's practice a long ago. According to hospital protocols or doctor's habits nowadays form 9.5 to 95% of delivering woman will have episiotomy. These results are not based on difference of process or mechanism of delivery. And in that case it seems that the true is at least somewhere between both results. Unfortunately the indications about episiotomy, described in obstetrics books, are not according "evidence-based" medicine results, but only supposing positive and negative results for the pregnant woman. Current indications for performing the episiotomy, based on the lot of researches, are fetal distress syndrome, complicated vaginal delivery (instrumental, breech or occipito-posterior delivery) and scar from poor-healed old 3rd or 4th degree rupture of the perineum. PMID- 20734647 TI - The dental office emergency. PMID- 20734646 TI - Case presentation: slight facial asymmetry. PMID- 20734648 TI - [Screening for gestational diabetes in Bulgaria--preliminary results]. AB - Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance with onset or first recognition during pregnancy. There is no data regarding the prevalence of GDM in Bulgaria. The aim of this study is to present the preliminary results from a pilot study for GDM in Bulgaria, including the prevalence and the epidemiological differences between women with or without this disorder. A 2 h oral glucose tolerance test (OGTT) with 75g glucose was performed on 330 pregnant women between 24 and 28 weeks of gestation, using ADA criteria to define pregnancies complicated by GDM. Blood glucose levels, insulin levels, HbA1c, hsCRP and lipid parameters were evaluated. GDM was found in 11.3% of the patients. Women with GDM were older than the ones without the disorder (p < 0.006), had higher fasting glucose levels (p < 0.0001), higher fasting insulin levels (p < 0.0001), higher HOMA index (p < 0.0001) and higher HbA1c (p < 0.001). There was a significant difference in body mass index (BMI) before pregnancy (p < 0.003) and at the time of screening (p < 0.001) between GDM and control groups (p < 0.001). GDM women more frequently had thyroid disease, developed early preeclampsia, had family history of type 2 diabetes mellitus and history of PCOS. In conclusion the prevalence of GDM in high risk Bulgarian population is relatively high--11.3%. This confirms the necessity of establishing of a national screening program. If financial recourses are limited selective screening in high risk patients should be considered. PMID- 20734649 TI - [Our and foreign experience in surgical treatment of CIN III-cold knife conisation versus LLETZ]. AB - AIM: Our aim was to assess the treatment results of patients with CIN III- surgically treated with cold knife cone biopsy compared with the results of treatment with LLETZ and laser conisation. MATERIALS AND METHODS: 600 patients were assessed and researched for 10 years period. Some of them were from the Specialized Hospital for Active Treatment in Oncology-Sofia, some from RHW and some from the Medical University of Varna-Cathedra of Obstetrics and Gynaecology. 350 patients were operated by the classical method- cold knife conisation, 200 by LLETZ and 50 by laser cone biopsy. RESULTS: We didn't find any difference in patients age, their cytological results and the results of their treatment. The LLETZ showed good results according to resected margins. The same good results were observed with laser conisation. Invasive disease and recurrence were observed in 150 patients--50 of them having adenocarcinoma in situ. CONCLUSIONS: Our research showed that there is no difference in the results of both groups- treated by the classical way--cold knife conisation or by LLETZ and laser conisation. PMID- 20734650 TI - [Assessment of the efficacy of the Tot'hema at anaemic status with different severity in the obstetric and gynecologic practice]. AB - Iron deficiency anaemia affect every fifth person on the planet, including the developed counties, too; the last data are that at about 700 000 000 are affected. The most common reasons for iron deficiency anemia in the obstetrics and gynecology are: pregnancy and menopause, chronic haemorrages/menorrhagiae and metrorrhagiae/dysfunctional uterine bleeding, myoma uteri, neoplastic diseases/, acute anaemias post partum and after operative interventions. The aim of the present study is to study the efficacy of the treatment of iron deficiency anemia at women with different obstetrics and gynecology pathology. PMID- 20734651 TI - [Solifenacin in treatment of the overactive bladder syndrome--diagnosis, clinical management and results]. AB - The overactive bladder syndrome (OAB) is a pathological condition that affects millions of people round the world. Its incidence increases with ageing. The main therapeutic option for OAB nowadays is anti-muscarinic drug therapy. AIM: To define and implement the diagnostic criteria, clinical guidelines in our country and to evaluate the results of Solifenacin therapy in patients with OAB. MATERIAL AND METHODS: Along a three years period (2006-2009) 163 OAB patients were analyzed followed and treated. In our group of patients 106 (65.2%) are females and 57 (34.8%)--males. The diagnosis is based mainly on the complaints of the patient, evaluated thoroughly with a detail anamnesis and questionnaires. Urodynamic studies were performed In some of the patients. The efficacy of Solifenacin therapy has been validated with the same methods used in SUNRISE and VENUS studies. RESULTS AND DISCUSSION: The mean age of female patients in our group is 63.8 years, and 65.6 years for males. The most commonly observed symptoms of OAB are urgency--88.3% and frequency--92%. Urge-incontinence is observed in 48.8% of the cases. Therapy with Solifenacin 5 and 10 mg has alleviated urgency in 82% and urge-incontinence in 88.9%. Mean number of pads used for 24 hours has decreased from 2.6 to 0.4 after therapy. CONCLUSION: Urgency is the main mandatory symptom for the diagnosis OAB. Therapy with Solifenacin 5 and 10 mg guarantees very good clinical results, and high degree of compliance of the patients. PMID- 20734652 TI - [Static volume contrast imaging (VCI)--clinical implications in obstetrics and gynecology]. AB - We present a new form of data image processing obtained through three-dimensional scanning named static volume contrast imaging (VCI) and discuss its technique and clinical implications in obstetrics and gynecology. PMID- 20734653 TI - [Agenesis of corpus callosum - a review]. AB - The subject herein discussed is malformations about which information abounds. This is due to constant improvements in approaches to obtaining such information through images generated by modern imaging technology. As the examination of structures at hand progresses, so does the possibility for precise imaging diagnostics. Agenesis of the corpus callosum is one those subtle and difficult to detect malformations which are currently becoming subjects of research. Agenesis of the corpus callosum is a brain anomaly with incidence of occurrence from 0.05 to 0.7%. It could be either observed in 49% of cases unaccompanied by other conditions or accompanied by other anomaly syndromes. This cerebral malformation is usually diagnosed post partum in children suffering from epilepsy or behaviour or cognitive disorders. In consideration of the necessity of early fetal abnormality detection and the conduct of the obstetrician in a social aspect, the above-mentioned is a prerequisite which makes discussions necessary. Constant up dating and discussions allow periodic revision and optimizations of prenatal diagnostics. PMID- 20734654 TI - [Myo-inositol in the treatment of hormonal, metabolic and reproductive features of polycystic ovary syndrome (review of the literature]. PMID- 20734655 TI - [HPV infection of the cervix and capabilities of advanced diagnostics]. AB - The purpose of this review is to indicate the biological significance of HPV infection and its link to cervical onkogenesis as an assessment of the diagnostic capabilities of modern DNA/RNA hybridization methods. PMID- 20734656 TI - [Pregnancy and malignant melanoma]. AB - The authors review on a rare pregnancy accompanying disease--Melanoma malignum. After the definition are presented the epidemiology, etiology, pathogenesis, pathomorphology, clinical forms, diagnosis, differential diagnosis, treatment and prevention. Described are the effects of the pregnancy on this malignant disease and the impact of it during the pregnancy. PMID- 20734657 TI - [Rare form of cervix carcinoma, infiltrating cervical myoma]. AB - The authors describe rare case of carcinoma colli uteri, which grows to infiltrate submucose cervical myoma. PMID- 20734658 TI - [Placenta percreta with a contribution of 1 clinical case]. AB - Placenta accreta and its variants increta and percreta is one of the biggest challenges in clinical obstetric practice. The frequency of this life-threatening abnormality in the placenta tends to increase, this trend is directly linked to increasing rates of Caesarean section. The author describes clinical case of unrecognized before birth Placenta percreta, risk factors for this condition and modern methods for timely diagnosis and behavior. PMID- 20734659 TI - [Spatio-temporal image correlation (STIC) and tomographic ultrasound imaging (TUI)--combined clinical implementation in 3D/4D fetal echocardiography]. AB - Two new forms of volume data image processing by three (3D) and four (4D) dimensional ultrasound named Spatio-Temporal Image Correlation (STIC) and Tomographic Ultrasound Imaging (TUI) are presented. The advantages and disadvantages of the combined clinical implementation of both modalities in fetal echocardiography are discussed. PMID- 20734660 TI - [Treatment of anaemia of prematurity with SS-R-Hu-erythropoietin and significance of hypoxia-inducible factor]. AB - The main cause of anaemia of prematurity is low erythropoietin levels. A few years ago hypoxia-inducible factor/HIF/gene transcriptor was established, regulating not only the synthesis of erythropoietin /EPO/, but also other growth factors as well as enzymes of anaerobic glycolysis, activated by hypoxia. OBJECTIVES: The aim of the study is to establish in clinical practice the role of hypoxia, respectively, activated HIF during treatment with erythropoietin by analyzing variations in hematological values; to examine blood lactate levels as an indicator of activated HIF and anaerobic glycolysis with Hb values 110-120 g/l; to analyze the number and impact of red blood cells transfusions on different categories of babies. STUDY DESIGN; The study includes 112 premature infants born before 34 weeks of gestation and below 1400 g. 90 babies, treated with EPO (700-1000 E/kg weekly dose in 2-3 applications, for 2-4 weeks), values of Hb g/l, Ht%, Ret%, Platelets 109/l were followed and compared. Treated babies were divided in two groups: group I--treatment (starting at Hb below 106 g/l, Ht less than 31%); group II--late prophylaxis (starting at Hb > or = 106 g/l, Ht > or = 31%). Blood lactate was examined in 22 non oxygen dependent premature babies without EPO treatment, with Hb 110-120 g/l, Ht 29-32%. RESULTS: We found that in group II during the first 7-10 days Hb decreases to 105.6 (+/- 9.4) g/l, rising up afterwards to 113.5 (+/-11.0) g/l at day 25-30. Ret reach maximal values at day 15-20 when Hb drops below 110 g/l and Ht below 31%. In group I at day 25-30 of treatment is observed a rise in Hb up to 117.3 (+/-11.3) and of Ht up to 32.7% (+/- 2.6) and no decrease of Hb and Ht values during the first 7-10 days, while Ret rise up to maximal values 6.5% (+/- 3.6) at day 7-10. With Hb levels of 116.4 (+/- 4.6) g/l we found an increase in blood lactate levels up to 2.6 (+/- 0.7) mmol/l as an indicator of relative hypoxia and activated HIF. Mean number of blood transfusions in group I is 3.01(+/- 1.7), versus 2.15 (+/- 1.7) in group II (statistically non-significant). In 29 infants in group II treatment was started at Hb 110-120 g/l and the mean number of red blood cell transfusion is 1.8 (1.5)- statistically significant difference with group I. In 32% from the treated infants we found platelets count rising above 500 x 109/l. CONCLUSIONS: The presence of hypoxia at low levels of Hb and Ht leads to more rapid activation of erythropoiesis. Nevertheless, these babies need more red blood cell transfusions due to clinical symptoms of hypoxia. Normoxia after red blood cell transfusion leads to decrease of reticulocytes count by 30% and platelets by 35% in spite of treatment. The presence of relative hypoxia with Hb 110-120 g/l u Ht 31-32% is optimal for starting treatment with EPO--levels, low enough for activation of HIF and high enough to avoid blood transfusions. PMID- 20734661 TI - [Single umbilical artery (SUA)]. AB - Single umbilical artery (SUA) is the most common abnormality of the umbilical cord. It is associated with an increased incidence of atresia of hollow organs, renal abnormalities, limb reduction defects and spontaneous abortions. The aim of our study is to establish the association of SUA with types of malformations and the corresponding pathology of pregnancy and parturition. Although our investigation is in proof of the association of SUA with anomalies of GIT, CCS and CNS, most of our cases exhibit circulatory disturbances leading to pathology of pregnancy and delivery. PMID- 20734662 TI - [Changes in bone mineral density of postmenopausal women in relation to the menstrual cycle length]. AB - There is a strong relationship between the age of menarche, the length of the menstrual cycle and menstrual bleeding and fracture risk in the postmenopausal period. OBJECTIVE: Evaluation of the menstrual cycle length and lumbar bone mineral density in postmenopausal women. MATERIALS AND METHODS: We investigated three groups of postmenopausal women (each - n = 50). The first group included women with menstrual duration of 27 days during reproductive age, the second group included postmenopausal women with menstrual duration of 28 days during the reproductive age, and the third group consisted of postmenopausal women with menstrual duration of 30 days during reproductive age. The average age of women was 58.80 +/- 0.94 y. in the first group, 60.36 +/- 5.12 y. in the second group and -61.84 +/- 0.80 y. in the third group. Age, age of menarche, number of childbirths, length of the menstrual cycle and menstrual bleeding, and lumbar bone density were assessed and registered for each woman. We used DXA in a anterior-posterior projection to assess the bone density of the lumbar spine; the obtained results are shown in gram/cm2. RESULTS: The women from the third group, with average menstrual cycle length of 30 days, reach menopause at a significantly later age, have longer menstrual cycle and shorter menstrual bleeding, and higher lumbar spine bone density, compared to the other two groups. CONCLUSION: The data from our research show that women with anamnesis for average normal menstrual cycle length of 30 days reach menopausal period at a significantly later age, have shorter menstrual bleeding, and higher lumbar spine bone density compared to those with shorter menstrual cycle duration (27 and 28 days). PMID- 20734663 TI - [Some new tendencies in diagnosis and complex treatment of vulvar cancer--our and foreign experience]. AB - INTRODUCTION: The aim of this research work was to summarize our and foreign experience in the field of diagnosis, complex treatment and prognostic factors connected with vulvar cancer. MATERIAL AND METHODS: We evaluated our and foreign experience for 10 years period (2000-2010) and evaluated 625 patients diagnosed and treated for vulvar cancer. We assessed the complex treatment, prognostic factors and some new tendencies towards more conservative surgical treatment of vulvar cancer. RESULTS: The all 5 years survival rate was 70%; 10 years survival rate was 50%. The level of recurrence was 30% (187 p.), local recurrences were 50% (93 p.), the groin recurrences were 7% (13 p.). The biggest recurrence rate was in local recurrences of the vulva. Older age and metastases in lymph nodes were independent bad prognostic factors. The stages of the lymph nodes, LVSI and the stage were connected with survival and disease free survival. The different kinds of treatment were analyzed- surgery, chemo and radiotherapy. We analyzed the tendencies towards more conservative surgical treatment connected with vulvar cancer. CONCLUSIONS: We tried to summarize our and foreign experience in the complex treatment of vulvar cancer for 10 years period. Our main idea was to show some new tendencies in the latest 10 years towards relatively more conservative treatment of this neoplasia. PMID- 20734664 TI - [The evolution of vacuum extraction in obstetrics]. AB - Vacuum extraction is one of the methods for assisted vaginal delivery. In this article the evolution of vacuum extraction in obstetrics is been discussed. Historical facts and data from the invention up to state-of-the-art vacuum systems in modern obstetrics are presented. PMID- 20734665 TI - [Prediction of adverse pregnancy outcome by first-trimester maternal serum PAPP A]. AB - Preeclampsia occurs in 2 to 5% of all pregnancies in developed countries. Together with IUGR it consists one of the leading reasons for perinatal death and childhood handicap. This is why many authors are looking for a widely usable and easy to perform test for evaluation of the patients at risk for preeclampsia an IUGR. PAPP-A is a protein complex produced by the developing trophoblast which is used as a marker for Downs' syndrome. Previous studies have shown an association between low first trimester maternal serum PAPP-A and subsequent development of pregnancy complications. PMID- 20734666 TI - [Complications in gynecologic laparoscopic surgery]. AB - Minimally invasive surgery was quickly conquered and implemented because of the proven reduction of morbidity and mortality in various surgical operations. The main advantages of laparoscopic surgery are lesser surgical trauma, better cosmetic effect, the patient's rapid recovery and return to a normal lifestyle With the advent of laparoscopic surgery were born and a new type of complications unique to it and the level of experience and knowledge of surgeon. Over time, exponentially growing interest in laparoscopic surgery, and thus perfecting it, thus increasing the number and type of surgical gynecological operations performed laparoscopic surgery. Laparoscopy continues to evolve with more complex instruments with newer instruments and energy sources in order to facilitate the work of the surgeon to reduce operative time, to increase the success of interventions and to reduce the complications. So it is important to conduct regular education and repeated training with laporoscopic techniques to decrease complications. PMID- 20734667 TI - [Transvaginal sonography of the cervix in patients with post-term pregnancy- significance, technique, predicative value]. PMID- 20734668 TI - [Isolated right aortic arch with diverticulum of Kommerell--prenatal diagnosis with spatio-temporal image correlation (STIC)]. AB - Isolated right aortic arch is a rare congenital cardiac malformation which is often diagnosed only after birth. We present a case of isolated right aortic arch with a vascular ring and diverticulum of Kommerell diagnosed prenatally at 21 weeks of gestation (w.g.) with three-dimensional ultrasound and spatio-temporal image correlation (STIC). The clinical implications, prenatal diagnosis, differential diagnosis and perinatal management in such cases are discussed. PMID- 20734669 TI - [Rupture of splenic artery aneurysm--life-threatening condition for women during pregnancy and after birth (with report of one case)]. AB - Spontaneous rupture of a splenic artery aneurysm is an uncommon and usually catastrophic event during pregnancy and puerperium. The mortality rate among pregnant women is very high at 75% with a fetus mortality rate of 95%. This report describes the clinical course of a 25-year-old woman with hemorrhagic shock four hours after elective Cesarean Section. Symptoms like hypotension, tachycardia, dyspnoe were initially suggestive of pulmonary embolism. Ultrasound demonstrated a nonechogenic mass in the abdomen suggestive of a fluid collection. Ruptured splenic artery aneurysm was recognized during the second emergency laparotomy for hemoperitoneum. Splenectomy was performed. The outcome for the patient was good. We underline that the only way to avoid a fatal event is to know and to think about this rare but very important complication in any woman with unexplained abdominal pain or with clear signs of haemorrhage during pregnancy or shortly after delivery. PMID- 20734670 TI - [Early diagnosis of Turner syndrome in a newborn]. AB - The Turner syndrome, karyotype 45,X0 in the classical form, often remains undiagnosed until significant growth retardation is presented and sexual maturation at the puberty fails to occur. The girls are as a rule with normal IQ. We report a case of an infant of a 24 years mother after two spontaneous abortions and one birth of a normal boy. The newborn girl is with IUGR, after birth we establish edema of the feet, prominent ears and systolic murmur. The echocardiography diagnoses cardiac malformation--bicuspid aortic valve and sub aortic obstruction. The chromosomal analysis shows karyotype 45,X0. We discuss the methods for prenatal and early postnatal diagnosis. In utero and in the neonatal period there are symptoms that make the diagnosis Turner syndrome probable so that chromosomal analysis should be made to confirm it. Looking for other malformations (heart, kidney, endocrine) is necessary. The early diagnosis makes possible the beginning of appropriate hormonal treatment to achieve normal growth and to induce puberty. PMID- 20734671 TI - [Early parenteral nutrition with very low and extremely low birth weight infants- practical approach]. AB - Newborn infants with birth weight 1500 g and less (VLBW/ELBW) have higher nutritional needs, but enteral feeding is often insufficient or impossible. Parenteral nutrition (PN) as an important component of intensive care with them minimizes the risk of nutritional deficiency. OBJECTIVE: To evaluate the safety and efficacy of early PN administration in VLBW/ELBW infants. STUDY DESIGN: The prospective study includes 23 newborn babies with birthweight below 1500 g who were admitted to the NICU from 01.03. to 20.04. 2009. With all babies a PN was started from the first day of life with dextrose and amino acid solutions, adding lipid solutions in gradually increasing quantity on the second day. During the first 20 days of life for each baby were calculated on a daily basis the exact quantities of energy and the essential nutritional substances as well as the balance among them. All babies were followed up for weight gain, presence or absence of complications, related with parenteral nutrition as well as for: blood sugar, acid-base status, total serum protein, electrolytes, urea, triglycerides, billirubin, alkaline phosphatase, ASAT ALAT RESULTS: We found that due to the small infusion volumes during the first days, the minimal daily needed nutrition levels are reached at day 4-5. Nutritional intake at day 7-10 in most children is enough for growth. A positive mean weight gain for the whole group 6.6 g/kg/d (SD 6.2) is observed. Negative weight gain during the first 20 days is observed only with two critically ill babies with substantial reduction of infusion volume. In 9 babies a transient increase in urea levels was observed during the first week, 5 babies had an increase in triglycerides as a symptom of bad lipid tolerance. In 7 babies on prolonged total PN an increase in alkaline phosphatase is observed. Conclusions. Early and sufficient PN in newborn babies below 1500 g guarantees the daily intake of energy and essential nutritive substances for adequate growth and is a basic component of intensive therapy. It should be corresponding to the nutritional needs as well as to the clinical condition; matching the severity of complications and carried under strict laboratory control. PMID- 20734672 TI - [Does human recombinant erythropoetin /R-HU-EPO/ treatment for anemia of prematurity have any effect on reducing the number of blood transfusions?]. AB - OBJECTIVES: The aim of the study is to establish the influence of r-hu-EPO treatment for anemia of prematurity on changes in blood count values and the number of inevitable blood transfusions in premature infants. STUDY DESIGN: The study includes 148 newborn babies--birth weight < or =1400 g, gestational age < or =34 g.w. They were divided in 2 groups: group I--treated with r-hu-EPO 1000 E/kg/week and Fe++ 3-6 mg/kg/day from week 3 after birth; group II--controls, treated only with transfusions of red blood cells. The changes in blood count values (Hb, Ht, Ery, Ret) from day 15-25 until day 60-70 were followed and analyzed, as well as the number of inevitable blood transfusions. RESULTS: A significant increase in Hb and Ht values was established with r-hu-EPO treated babies. At day 60-70 mean values of Hb are: in r-hu-EPO group 111.1 +/- 11.06 g/l; in control group 99.20 +/- 10.77 g/l (p < 0.001). At the end of the period Ht is 32.02 +/- 3.28% in babies treated with r-hu EPO versus 29.10 +/- 2.87% with controls (p < 0.005). Ret count is significantly higher from day 25-30 in r-hu EPO group (5.16 +/- 3.23%) versus controls (2.75 +/- 1.33%). Mean number of inevitable blood transfusions in r-hu-EPO treated group is significantly lower (2.06 +/- 1.62) versus controls--3.75 +/- 1.95 (p < 0.001). CONCLUSION: r-hu EPO treatment has effect on changes in Hb, Ht, Ret and reduces the number of inevitable blood transfusions for anaemia of prematurity. PMID- 20734673 TI - [Increased absolute numbers of NK cell in peripheral blood correlate to up regulated expression of HLA-DR and enhanced secretion Il-12 in infertile women]. AB - It is well known that the increased numbers of NK cells with phenotype CD3 CD16+CD56+ can execute cytotoxic effect against trophoblast cells and might be responsible at least for a part the immune mediated reproductive failures. The aim of this study is to follow up the correlations between the increased absolute numbers of NK cells, their activation status and secretion of some cytokines in infertile patients. The results obtained clearly show that in patients with increased numbers of NK cells the percentages of HLA-DR positive NK cells were significantly higher compared to the patients with normal number of NK cells. A similar correlation was revealed when the data of blood plasma where the concentrations of IL-12 were significantly higher in patients from the first group (with increased NK cells numbers). The results from our study demonstrate that the increased numbers on CD3-CD16+CD56+ NK cells is accompanied by enhanced activation of these cells and secretion of cytokines. PMID- 20734674 TI - [Fetal echocardiography: part III--the conotruncal anomalies]. AB - Conotruncal anomalies are characterized by a defect in the conotruncal septum. They represent an important group of congenital heart defects (CHD) which is associated with significant perinatal morbidity and mortality. Fetal echocardiography is a reliable diagnostic tool for CHD, but its detection rate is operator dependent and varies by centre and defect. Accurate echocardiographic diagnosis in utero permits adequate pregnancy follow-up and patient counseling with regard to prognosis and treatment options. The aim of this review is to define the major ultrasound features used in the prenatal diagnosis and differential diagnosis of the most common conotruncal anomalies encountered in fetal life. PMID- 20734675 TI - [Strategies for nutrition of the preterm infant with low and very low birth weight]. AB - According to many experts in neonatal nutrition, the goal for nutrition of the preterm infant should be to achieve a postnatal growth rate approximating that of the normal fetus of the same gestational age. Unfortunately, most preterm infants, especially those born very preterm with extremely low birth weight, are not fed sufficient amounts of nutrients to produce normal fetal rates of growth and, as a result, end up growth-restricted during their hospital period after birth. Growth restriction is a significant problem, as numerous studies have shown definitively that undernutrition, especially of protein, at critical stages of development produces long-term short stature, organ growth failure, and both neuronal deficits of number and dendritic connections as well as later behavioral and cognitive outcomes. Glucose should be provided at 6-8 mg/min/kg as soon after birth as possible and adjusted according to frequent measurements of plasma glucose to achieve and maintain concentrations >45 mg/dl but <120 mg/dl to avoid the frequent problems of hyperglycemia and hypoglycemia. Similarly, lipid is required to provide at least 0.5 g/kg/day to prevent essential fatty acid deficiency. However, the high rate of carbohydrate and lipid supply that preterm infants often get, based on the incomplete assumption that this is necessary to promote protein growth, tends to produce increased fat in organs like the liver and heart as well as adipose tissue. More and better essential fatty acid nutrition is valuable, but more organ and adipose fat has no known benefit and many problems. Amino acids and protein are essential not only for body growth but for metabolic signaling, protein synthesis, and protein accretion. 3.5-4.0 g/kg/day are necessary to produce normal protein balance and growth in very preterm infants = Aggressive parenteral nutrition (PN) including amino acids is recommended for low-birthweight infants to prevent energy and protein deficit. PN can be provided as a standard, usually commercial, formulation, representing the average needs of a large group of patients. Alternatively, an individualized PN compound adapted to the patient's needs can be prescribed and prepared, usually on a daily basis. A combination of standardized PN bags, prepared under strict standardization criteria, for most neonates. Many preterm infants are too ill to receive substantial enteral feeds and require prolonged PN. It was reported that normal gastrointestinal structure and function are lost, villi become shorter, mucosal DNA is lost, Enteral feeding always is indicated and to date nearly all studies have shown that minimal enteral feeding approaches (e.g., 'trophic feeds') promote the capacity to feed enterally. Milk has distinct advantages over formulas in avoiding necrotizing enterocolitis (NEC). Breast milk is the preferred source of nutrients for newborn infants. The most common methods used are continuous milk infusion and intermittent (bolus) milk delivery (usually every 3 h). Feeding promotes more "normal" feed-fasting and marked differences are observed in feeding tolerance and growth between continuous vs. bolus tube feeding methods. Continuous feeding is associated with more significant feeding intolerance. PMID- 20734676 TI - [Fetal fibronectin--biomarker for preterm labour]. AB - There have been many attempts to use various biomarkers, either alone or in combination, to predict preterm birth, such as serum corticotropin releasing factor, serum alpha-fetoprotein, vaginal or cervical fetal fibronectin, which is a good prognostic marker for its occurrence. In normal conditions, FFN is found at very low levels in cervico-vaginal secretions and levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. Although FFN is commonly used in labour and delivery units to help in the management of women with symptoms of preterm labor, currently there is not sufficient evidence to recommend its use as a screening method. There is a clear need for further detailed analysis and studies in this direction, given that there are already plenty of evidence showing the link between negative fFN test and a lower incidence of preterm birth before 37 week of gestation. PMID- 20734677 TI - [Oocyte and embryo donation and surrogacy. Religious, medico-social, ethical, financial and legal problems]. AB - The authors quote and discuss the postulates of the Orthodox, Jewish, Catholic and Islamic religions towards ART as well as worldwide legislations and standards and the attitude of female students of medicine in Varna. Indications of oocyte and embryo donation and surrogacy are proposed but all kinds or surrogacy should be permitted. The ART legislation and standards in Bulgaria should be thoroughly revised. PMID- 20734678 TI - [Modern tendencies in treatment of atypical glandular hyperplasia--our and foreign experience]. AB - AIM: Our aim was to summarize our and foreign experience in the field of diagnosis, progression and modern treatment of precancer of the endometrium-the atypical glandular hyperplasia. MATERIAL AND METHODS: We researched 750 cases with glandular and atypical glandular hyperplasia for 10 years period (2000 2010). The hyperplasia were followed up for progression from glandular hyperplasia into atypical glandular hyperplasia and early endometrial cancer. The hyperplasias were evaluated with or without progestagen hormonal therapy. All patients were treated by D&C before and after the hormonal treatment. RESULTS: The main symptom in all patients was the postmenopausal bleeding (72% from the cases). In 90% of the patients (675) there was obesity. Exogenous use of estrogens was found in 30% (225) of the patients. The cases with complex hyperplasia in 12% (65/525) progressed into atypical glandular hyperplasia and in 4% (21/525) progressed into endometrial cancer. The patients with atypical glandular hyperplasia in 60% (90/150) progressed into endometrial cancer. Remission was observed in 70% of the patients (194/278) with glandular hyperplasia and progestagen treatment. The remission was detected by the golden standart (D&C). The patients without hormonal treatment and with complex glandular hyperplasia have in 15% (37/247) remission. Except with progestagen therapy, we have also 15 patients treated with GnRh-analogs (Zoladex a 3.6 mg) for 3-6 months. For them we have 80% (12/15) remission. CONCLUSIONS: The glandular hyperplasia without atypical cells can be influenced by the hormonal treatment with progestagens and GnRh-analogs. Nevertheless this hormonal treatment--before and after we have to perform D&C and to follow up patients by ultrasound measuring the endometrial thickness. If the fertility plans of the patients are over and if they are in postmenopause with histological result from D&C-atypical glandular hyperplasia--we have to treat them more radically with simple total hysterectomy. PMID- 20734679 TI - [Radical surgical treatment with nerve-sparing technique in early cervical cancer -stage IA-IIA. Our and foreign experience]. AB - INTRODUCTION: We tried to make clear the role of sparing of the autonomous pelvic nerves during radical hysterectomy in cervical cancer stage IA-IIA. We compared the radicality, the possibility to introduce this type of operation, the level of local recurrence, the safety and the survival rate of these patients. METHODS: We summarized 50 scientific publications in this field. We analyzed the level of local recurrence, survival rate and safety of this surgical technique. RESULTS: The groups with or without nerve-sparing had comparable parameters and results. The sparing of the autonomous pelvic nerves from unilateral or bilateral part of the pelvis was possible in 70-85% of the patients. We found local recurrences in 5% without nerve-sparing operations and in 9,1% in radical hysterectomies with nerve sparing technique. Local recurrences in the group without sparing the nerve inervation appeared after 24 months, and in the group with nerve-sparing technique after 21 months. The duration of the operation and the blood loss were less in the group with nerve-sparing technique. The death and survival rate in both groups were equal. CONCLUSIONS: As a result of our literature review and our own experience we consider that the sparing of the autonomous pelvic nerves in radical hysterectomies in early cervical cancer can be applied without problems and safely. PMID- 20734680 TI - [Modern principles and methods in tocolytic therapy]. PMID- 20734681 TI - [Life threatening postpartal haemorrhage after rupture of the vagina, uterine cervix, caesarean section or hysterectomy]. AB - The authors discuss 10 cases--seven after vaginal and cervical rupture, 2 after Caesarean section and 1 after hysterectomy. Six of them died--5 after rupture of the vagina and cervix and one after Caesarean section. The lethal issue was avoidable in all cases because it was a result of untimely done or not done at all hysterectomy and other interventions, e.g., ligation of the hypogastric arteries, as well as of faulty surgical performance. Basic principles of surgical behavior in such cases are postulated. PMID- 20734682 TI - [Guidelines for parenteral nutrition in high risk newborn babies]. AB - High risk newborn babies, admitted and treated at the Intensive care units often have to be started on intravenous nutrition--total or partial. The guidelines which we propose are adapted to the specific needs of the various groups of critically ill newborns--daily intake of liquids and essential nutritional substances according the day of life and the birth weight, as well their variations depending on the clinical condition and the morbidity of the baby. PMID- 20734684 TI - [Care direct]. PMID- 20734683 TI - [Operative method of cervix conisation]. AB - The authors describe an operative method of cervix conisation, which they used by 41 patients in a 11-years period (1998-2009). Shearing their experience of the results they achieved, they are making some conclusions. PMID- 20734685 TI - [Diagnostic value of studying creatinine in abdominal exudates]. AB - The levels of creatinine in serum and peritoneal exudate were studied in 77 patients with acute surgical abdominal diseases. It has been found that the exudate concentration of this compound is mainly determined by its level in the serum, which allows the exudate creatinine to be studied for the diagnosis of renal failure. The creatinine concentration in the abdominal exudate in relation to that in the serum varies in urinary tract injury and in the early hours after abdominal sanitation in peritonitis. Exudate creatinine concentration increases (by 2.7-fold or more) require that the urinary tract should be revised to reveal its injury. Creatinine levels in the exudate can be determined not earlier than 8 hours after abdominal lavage. The determination of creatinine concentrations in the peritoneal exudate is a non-invasive and informative tool that enhances the quality of laboratory monitoring in emergency abdominal surgery. PMID- 20734686 TI - [Nonspecific adaptation reactions and immunological status in patients with type 2 diabetes mellitus]. AB - The clinical laboratory study of 75 patients with type 2 diabetes mellitus (T2D) has shown that most of them have elevated immunoglobulin A and G levels, the diminished activity of neutrophiles, and higher C-reactive protein and 30% of the patients show non-physiological adaptation reactions: reactivation and stress. During these reactions, there are the most pronounced changes in the immunological status and in the level of acute phase protein. The rate of nonphysiological reactions increases, immunity deteriorates, and the activity of an inflammatory process is enhanced with the longer duration of T2D, grades 2 and 3 arterial hypertension, micro- and macroangiopathies, as well as with more evident hyperglycemia and triglyceridemia. PMID- 20734687 TI - [The functional properties and oxidative modification of plasma and neutrophil proteins in community-acquired pneumonia]. AB - The functional properties of neutrophils (the activity of myeloperoxidase and the production of hydroxyl radical) were studied in community-acquired pneumonia (CAP) predominantly with the alveolar and interstitial types of lung parenchymal infiltration. Protein oxidative modification was estimated from the content of protein carbonyl derivatives in neutrophilic leukocytes and plasma and from the plasma concentration of bityrosine and oxidized tryptophan in patients with CAP. The production of hydroxyl radical and the activity of myeloperoxidase in the neutrophils of patients with CAP were increased and did not depend on the type of lung tissue infiltration. The development of oxidative stress in CAP was accompanied by the substantiation activation of protein oxidative modification processes in the neutrophilic leukocytes and plasma. PMID- 20734688 TI - [Informative value of the VCS parameters of peripheral blood neutrophils in the evaluation of status of patients with recurrent and metastatic cervical cancer]. AB - The total values of white blood cells (WBC), the absolute and relative neutrophil counts, neutrophil VCS parameters: MVNe (volume), MCNe (conductivity), and MSNe (light scattering) were studied in 70 patients with recurrent and metastatic cancer of the cervix uteri, by using a LH-500 hematology analyzer (Beckman Coulter). The blood from 35 apparently healthy women served as a control. The magnitude of changes in MVNe and in the intensity of MSNe was found to increase in patients when the level of WBC and the content of neutrophils were elevated. Neutrophil VCS parameters, MVNe and MSNe in particular, may serve as an objective and sensitive indicator of condition severity in cancer patients. PMID- 20734689 TI - [A new approach to studying anemia in patients with gynecological diseases and gynecological neoplasms]. AB - The authors have used a coefficient that characterizes the functional activity of red blood cells. Evidence is provided for the significance of the coefficient, by comparing the groups of gynecological and gynecological cancer patients. PMID- 20734690 TI - [Automated microbiological systems in a clinical laboratory: advantages and problems associated with their use]. AB - The paper gives the author's experience in using the automated microbiology systems to provide optimal working practice, which includes their choice, laboratory conditions, the purchase of optional equipment, and organizational measures to reduce the time taken for clinicians to have results. PMID- 20734691 TI - [Determination of phage resistance of E. coli cells with electrooptical analysis of cell suspensions]. AB - Changes in the electrooptical (EO) properties of cell suspensions of the E. coli strains: XL-1, BL-Ril, TG-1, K-12, B-878, and BL-21 (DE) in their contamination with the bacteriophage M13K07 were studied depending on the time of infection. The phage-induced specific changes in the EO parameters of cell suspensions were ascertained to occur only in the E. coli strains XL-1, TG-1, and K-12 whereas these changes were not seen in the cell suspensions of E. coli strains BL-Ril, B 878, BL-21 (DE). Control experiments were carried out to infect the cells with the bacteriophage, by making a standard inoculation of the dense nutrient media. The fact that the method for EO analysis of cell suspensions may be used to determine the phage resistance of microbial cells is first shown. PMID- 20734692 TI - [Clinical and diagnostic value of the determination of alveomucin in patients with community-acquired pneumonia]. AB - The study was undertaken to define the clinical and diagnostic value of the determination of the serum levels of alveomucin in patients with community acquired pneumonia and the correlation of this index with the etiological factors of the disease and its severity. The investigators used general clinical, laboratory, and instrumental studies and specific serodiagnostic assays of the pathogen and measured alveomucin levels on the principle of a double-site enzyme immunoassay. Examining the serum level of alveomucin in the examinees indicated that on admission day this index was 34% higher in the patients with community acquired pneumonia than in the healthy individuals (52.59 +/- 2.8 and 39.22 +/- 2.8 U/ml, respectively). The mean value of this index was reduced to 49.88 +/- 2.29 U/ml) in the course of the disease. A certain association was found between the study index and the clinical characteristics of the disease: a direct correlation was established between the extent of lung injury and the level of mucin antigen. An assay of serum alveomucin depending on the severity of community-associated pneumonia revealed that on the first days of admission its values did not differ significantly from that in patients with different forms of the disease. However, there were statistically significant differences in this index according to the severity of the disease in its course. Analysis of serum alveomucin values in relation to the etiology of the disease also revealed certain regularities. PMID- 20734693 TI - Bringing health research forward. PMID- 20734694 TI - Prevalence and severity of cervical squamous intraepithelial lesion in a tertiary hospital in northern Tanzania. AB - Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer deaths in Tanzanian women. Prevention of cervical cancer relies on the detection and treatment of Squamous Intraepithelial Lesion (SIL), a premalignant disease stage. Worldwide there are overwhelming reports associating SIL and HIV infection, however in Tanzania such reports are limited. A cross sectional hospital-based descriptive study was conducted to determine the prevalence and severity of SIL in 234 HIV seropositive and seronegative women aged 18-68 years old at Kilimanjaro Christian Medical Centre in northern Tanzania. A structured questionnaire was used to collect sociodemographic data. In addition, blood was collected for rapid HIV antibody testing and CD4+ T lymphocyte counts to associate with prevalence and severity of SIL from the cervical smear collections. A total of 214 subjects had smear results regarded as valid for interpretation, of which 46.3% were HIV seropositive. Overall rate of SIL was 17%. Proportion of SIL among HIV seropositive subjects was 32% versus 4% in seronegative subjects (OR = 13.3, 95% CI = 4.2-46.4). Low CD4+ T-lymphocyte cell count was associated with higher prevalence of SIL (P = 0.001). The relationship between CD4+ T-lymphocyte cell counts and the severity of cervical SIL was significant (P = 0.007). Marital status and number of lifetime sex partners were risk factors significantly associated with SIL (P = 0.004 and 0.005, respectively). SIL was not associated with age, education level, parity or age at sex debut. The prevalence and severity of cervical SIL was significantly associated with HIV infection and immunologic disease progression. These findings underscore the need for HIV screening among women with SIL, and the need for cervical cancer screening in HIV-infected women. Marital status and number of lifetime sex partners were significant risk factors associated with SIL. PMID- 20734695 TI - Rational use and effectiveness of morphine in the palliative care of cancer patients at the Ocean Road Cancer Institute in Dar es Salaam, Tanzania. AB - Morphine and other opioids is the mainstay of cancer pain management. However, considerable fears surrounding their use present barriers to pain control. The aim of this study was to assess the rational use and effectiveness of morphine for management of pain in the palliative care of cancer patients at Ocean Road Cancer Institute (ORCI) in Tanzania. A total of 100 cancer patients who were receiving morphine therapy at the ORCI were interviewed to get information on morphine use. In addition, information on the prescribed doses of morphine was obtained from medical records of 200 patients who have used morphine from September 2005 to April 2006. Both outpatients and inpatients with advanced cancer who were receiving morphine for palliative care were involved. Seven (7) palliative caregivers, including two doctors, two nurses, a pharmacist, a pharmaceutical technician and a social worker were also interviewed. Of the 100 interviewees, 37% were aware of morphine. The level of education and duration of therapy had an impact on the awareness. The results also showed that oral morphine solution was the most common route (96%) of administration. Fifty-seven percent of the patients described the doses of morphine given to be effective in relieving their pain. Although most patients (79%) experienced morphine-induced side effects, the majority (93%) were continuing with the therapy. There were no indication of irrational use of morphine and morphine-induced side effects were well managed. The majority of patients and caregivers had positive attitude towards the use of morphine. In conclusion, the study revealed that the use of morphine is acceptable among a large proportion of patients receiving palliative care and that the majority of them find the doses given effective to relieve their pain. PMID- 20734696 TI - Polycystic ovaries and associated clinical and biochemical features among women with infertility in a tertiary hospital in Tanzania. AB - The aim of this study was to determine prevalence of polycystic ovaries (PCO) and associated clinical and biochemical features among women with infertility attending gynaecological outpatient department (GOPD) at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. All women with infertility attending the GOPD from 11th September 2006 to 15th February 2007 were recruited to the study. Information on socio-demographic, obstetric and menstrual characteristics was collected. Anthropometric measurement, clinical examination of acne and hirsutism, vaginal ultrasonography for PCO and biochemical analysis of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were performed. All 102 women who attended the GOPD during the study period due to infertility were recruited. Two women were excluded after diagnosis of pregnancy made by hormonal assay and ultrasonography thus remaining with 100 women for analysis. Oligomenorrhoea and acne were significantly higher in a group of women with PCO than among women with normal ovaries. The mean hirsutism score though was not significant, was higher in women with PCO than in women with normal ovaries (5.1 +/- 2.7 vs. 4 +/- 2.4, P < 0.057). Using the Rotterdam criteria 32 (32%) women were diagnosed to have polycystic ovary syndrome (PCOS). Among these women 25 (78.1%) had PCO, 24 (75%) had signs of oligoanovulation, and 18 (56.3%) had hirsutism. Among 68 women with no PCOS, 7 (10.3%) had polycystic ovaries, 15 (22.1%) had signs of oligoanovulation and 6 (8.8%) had hirsutism. In conclusion, polycystic ovaries are common among women with infertility, however are not necessarily associated with polycystic ovary syndrome. Doctors should investigate their clients for PCOS and offer appropriate treatment. PMID- 20734697 TI - Menstrual discomfort and its influence on daily academic activities and psychosocial relationship among undergraduate female students in Nigeria. AB - Menstrual disorder is a common health problem among females in their reproductive years. It has psychosocial effects on the sufferer and her interactions with others during such periods. In Nigeria, menstrual disorder has received little research attention especially in the public health agenda. This study combines quantitative and qualitative approaches in investigating the prevalence of dysmenorrhoea and menorrhagia and their psychosocial effects by focusing on the daily activities of female undergraduates at the Obafemi Awolowo University, Ile Ife, Nigeria. A multi-stage sampling technique was employed to select 415 female undergraduates at the University. A snowball sampling technique was used in selecting 37 informants for the in-depth interviews. Results showed a high prevalence of dysmenorrhoea (64%) among respondents within 3 months prior to this study. Dysmenorrhoea was significant among female students who reported dizziness, headache, depression and irritation; and those whose menstrual disorder ever called for medical attention (P < 0.05). Similarly, menorrhagia was less frequent-(21%) than dysmenorrhoea (64%), but occurred more significantly with dizziness, headache and depression, and those whose menstrual disorderliness ever called for medical attention or even surgical intervention (P<0.05). Menstrual disorder was experienced as an objective and subjective reality among those interviewed. Both dysmenorrhoea and menorrhagia were significant predictors of psychosocial relationship of the female students (P < 0.05). Those with dysmenorrhoea reported one and a half times of depression than those without. However, menorrhagia appeared as the principal factor affecting their daily school activities and relationship with colleagues. Menstrual disorders prevalence is high among young undergraduates and appropriate enlightenment and treatment should be made available to young females. PMID- 20734698 TI - Association of water-borne diseases morbidity pattern and water quality in parts of Ibadan City, Nigeria. AB - Occurrence of diarrhoea and other water-borne diseases in cities of developing countries has been on the increase over the decades largely due to unsafe water, inadequate sanitation and poor hygiene among human population. This study examined the relationship between the spatial pattern of water-borne diseases vis a-vis water quality in parts of Ibadan City in Nigeria. Data on 1334 cases of various water-borne diseases was collected from eight public hospitals with catchments covering the study area. Three areas with relatively high incidence of water-borne diseases and another three areas with relatively low incidence were selected for water sampling and household survey. Water samples from rains, wells, and borehole were collected for physical and bacteriological analyses. A well structured questionnaire was administered to 350 residents of the selected areas to elicit information on water sourcing, handling and storage. Analysis of hospital records showed significant difference in the occurrence of water-borne diseases among residential areas (P < 0.05). Typhoid fever had the highest occurrence (39.3%) followed by bacillary dysentery and cholera. About 45% of water-borne diseases were reported in July to September. The majority (77.1%) of the respondents depended on wells as major source of domestic water. Faecal coliform contamination of water samples ranged between 0.1 x 10(4) and 1.8 x 10(4) CFU ml(-1). Furthermore, 18% of rain water and 23.6% of well water samples were positive to Vibrio cholerae, Salmonella typhi and Shigella dysenteriae. Potash alum application for domestic water treatment accounted for 68.6% explanation of waterborne diseases morbidity pattern in the study area (P < 0.05). Provision of adequate potable water remains the most important tool for preventing water-borne diseases in the study area. PMID- 20734699 TI - Users' perceptions of outpatient quality of care in Kilosa District Hospital in central Tanzania. AB - Use of users' perception in measuring quality of care has been shown to be useful in screening problems and in planning for improvement of quality of health care delivery. Traditionally, quality of care has been measured using professional standards, neglecting users' opinions which may leave psychosocial needs unattended. The objective of this descriptive cross-sectional study was to assess users' perceptions of quality of care given at outpatient department (OPD) at Kilosa District Hospital in Central Tanzania. Hospital based exit interviews were conducted to adult patients or caregivers of children attending the hospital. Focus Group Discussions were conducted among community members in selected villages within the hospital catchment area. Information on perceptions on care provider-patient interaction, cost of service, availability of medicines, equipment and health personnel was sought from the participants. Overall OPD was perceived to have several shortcomings including verbal abuse of patients by care providers, lack of responsiveness to patients' needs, delays, inadequate examination, unreliable supply of medicines, lack of confidentiality and favouritism in health care provision. Cost of service was perceived to be reasonable provided medicines were available. In conclusion, provider-patient interactions, timely services, supply of medicines and favouritism were the major factors affecting quality of service at the hospital. Efforts should be made to address the shortcomings so as to improve quality of care and users perceptions. PMID- 20734700 TI - Seroprevalence of Toxoplasma gondii infection amongst residents of Tanga district in north-east Tanzania. AB - Toxoplasmosis is a zoonotic disease, recognized as a serious public health problem worldwide. Toxoplasma gondii infection has become a major public health concern in recent years due to the ravaging HIV/AIDS pandemic. A serological survey was carried out in Tanga district of north-eastern Tanzania to assess T. gondii infection rates among occupationally-exposed groups including abattoir workers, livestock keepers, animal health workers and other groups. The survey was undertaken in November 2005 using modified Eiken latex agglutination test (LAT). Antibodies to T. gondii were detected in 91 (46%) of the 199 individuals studied. T. gondii seroprevalence was slightly higher amongst males (46.2%) than females (43.3%) although the difference was not significant (P > 0.05). Individuals, < or =20 and > or =60 years old had the highest prevalence of 60% and 61.5%, respectively. The lowest prevalence of (35.7%) was observed amongst the 50-60 years age group. The seroprevalence of toxoplasma antibodies was significantly higher amongst individuals who keep livestock (52.2%) and abattoir workers (46.3%). These results suggest exposure to T. gondii infection is present among residents of Tanga district in Tanzania and strengthen further on previous findings that consumption of raw or undercooked meat and keeping pets especially cats presents more of the risk factors than occupational groups. It also emphasizes on the necessity to create awareness of this disease, and advocate protection of risky groups from exposure to infected meat and contaminated environment. PMID- 20734701 TI - Patterns of malaria related mortality based on verbal autopsy in Muleba District, north-western Tanzania. AB - Reliable malaria related mortality data is important for planning appropriate interventions. However, there is scarce information on the pattern of malaria related mortality in epidemic prone districts of Tanzania. This study was carried out to determine malaria related mortality and establish its trend change over time in both epidemic and non-epidemic areas of Muleba District of north-western Tanzania. A verbal autopsy survey was conducted to obtain data on all deaths of individuals who died in six randomly selected villages from 1997 to 2006. Relatives of the deceased were interviewed using a standardized questionnaire. Communicable diseases accounted for about two thirds (61.9%) of deaths among > or =5 years individuals and 84.8% in < or =5 years. Non-communicable diseases accounted for 28.9% and 14.1% deaths in > or =5 years and < or =5 years, respectively. Malaria was the leading cause of deaths in all age groups (40.3%) and among children <5 years (73.8%). Infants accounted for about two third (64.5%) of all malaria related deaths in children <5 years. Peak of malaria proportional mortality was highest during malaria epidemics. Most of the malaria related deaths in this group were among 1-12 months (64.5%) followed by 13-24 months (20.9%), and 25-59 months (14.8%). Cerebral malaria accounted for 18.9% (N=32) of death related to malaria in all age groups; 12.1% (17/141) were in under-five, 42.9% (6/14) were in 5-14 years and 64.3% (9/14) in 15-70 years old. More than half of malaria related deaths (61.0%) in <5 years children were associated with severe anaemia followed by diarrhoeal disease (24.1%), cerebral malaria (12.5%) and respiratory infection (8.5%) as common conditions. The majority of the deceased caretakers first sought treatment at health facilities within 24hr of the onset of illness. Significantly a higher proportion of caretakers of the underfives in the epidemic area sought treatment within 24hr than in non-epidemic area (39.3% vs. 18.5%; P = 0.0385). In conclusion, malaria accounts for majority of deaths in Muleba district, with substantial proportion being attributed to malaria epidemics. PMID- 20734702 TI - Knowledge and practices on malaria and its control among pastoralists in Simanjiro District, northern Tanzania. AB - Community knowledge and practice related to malaria is important for the implementation of appropriate, effective and sustainable interventions. This study was carried out to assess knowledge and practices on malaria and identify factors contributing to the low mosquito net coverage in Simanjiro District in northern Tanzania. A combination of direct observation, focus group discussion (FGD) and questionnaire were employed in data collection. A sample of 200 respondents was selected randomly from 5542 people from the study village. The findings show that, although most (75%) of the respondents were informed that mosquitoes transmit malaria, the remaining quarter of respondents reserved a considerable doubt on the link between mosquitoes and malaria. Sixty five percent of the respondents were aware of the use of insecticide treated nets (ITNs). However, the coverage of any mosquito net and ITN was 12.5% and 5%, respectively. Affordability, unavailability and gender inequality were identified to be major factors associated with the low ITN coverage. The study recommends that, an advocated pluralistic approach of ITN delivery which encourages a coordinated public private alliance is required to ensure equitable and large scale distribution of ITNs in the village. PMID- 20734703 TI - Antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected Tanzanian medicinal plants. AB - The antiplasmodial, anti-trypanosomal and anti-leishmanial activity of 25 plant extracts obtained from seven Tanzanian medicinal plants: Annickia (Enantia) kummeriae (Annonaceae), Artemisia annua (Asteraceae), Pseudospondias microcarpa (Anacardiaceae), Drypetes natalensis (Euphorbiaceae), Acridocarpus chloropterus (Malpighiaceae), Maytenus senegalensis (Celastraceae) and Neurautanenia mitis (Papilonaceae), were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900 and axenic Leishmania donovani MHOM-ET 67/82. Out of the 25 extracts tested, 17 showed good antiplasmodial activity (IC50 0.04-5.0 microg/ml), 7 exhibited moderate anti-trypanosomal activity (IC50 2.3-2.8 microg/ml), while 5 displayed mild anti-leishmanial activity (IC50 8.8 9.79 microg/ml). A. kummeriae, A. annua, P. microcarpa, D. natalensis, M. senegalensis and N. mitis extracts had good antiplasmodial activity (IC50 0.04 2.1 microg/ml) and selectivity indices (29.2-2,250 microg/ml). The high antiplasmodial, moderate anti-trypanosomal and mild anti-leishmanial activity make these plants good candidates for bioassay-guided isolation of anti-protozoal compounds which could serve as new lead structures for drug development. PMID- 20734704 TI - Case studies in public-private-partnership in health with the focus of enhancing the accessibility of health interventions. AB - Various definitions have been framed for public-private partnerships (PPPs) in health depending on the desired relationship and the characteristics of the respective sectors. These relationships span from a continuum of loose relationships with narrow objectives, lack of a legal status and an absence of a formalized membership or governing body to high level institutionalization. The latter includes concrete objectives, the presence of a legal status and permanent multi-sectoral membership. The study used qualitative research methods including case studies, literature review and interview with key informants. The research undertakes an extensive literature review of various PPP models in health in scale and in scope which are aimed at advancing public health goals in developing countries. The major emphasis is on a qualitative description of some of the PPPs in the planning and implementation phases, including the challenges encountered. This background is used to analyse in-depth two case studies which are both health oriented; the first one is a national level NGO consortium with a focus on malaria and the second one is an international advocacy group with an overarching goal of protecting children against malaria through an innovative mechanism. The case study approach is used to analyze why the PPP approach was used to address malaria control and how it was implemented. Both PPPs demonstrated that relationships between the public and private sector may begin from very humble and loose beginnings. However, with perseverance from committed individuals, a vision and trustworthiness may become powerful advocates for meeting prescribed health agendas. In conclusion, three key themes (trust, sacrifice and championship) run vividly through the case studies and are significant for developing countries to emulate. PMID- 20734705 TI - Larvicidal efficacy of seed oils of Pterocarpus santalinoides and tropical Manihot species against Aedes aegypti and effects on aquatic fauna. AB - Botanical larvicides have featured prominently as alternative to synthetic chemical insecticides which are less degradable and toxic to non-target organisms. The larvicidal potentials of the seed oils of Pterocarpus santalinoides and Tropical Manihot species (TMS 30572) were investigated in the laboratory against larvae of Aedes aegypti. The seed oil of each plant was extracted using n-hexane and was graded into different concentrations; 30, 60, 90, 120 and 150 ppm. The toxicity of each of the concentrations was evaluated against 3rd instar larvae of A. aegypti and tadpoles (Buffo spp) as non target aquatic fauna. Both oils were toxic to the larvae though at higher concentrations (120 ppm and 150 ppm) after 24 hours of exposure. The oil of P. santalinoides was more toxic to the larvae (LC50 104.0 ppm and LC90 184.5 ppm) than oil of TMS (LC50 113.5 and LC90 201.2) but the difference in the lethal doses was not statistically significant (P > 0.05). However, mortality was not recorded at any of the graded concentrations in both oils against tadpoles. The results therefore suggest that the seed oils of both plants could be incorporated as botanical insecticides against mosquito vectors with high safety to non-target organisms. PMID- 20734706 TI - Trachoma and ocular Chlamydia trachomatis rates in children in trachoma-endemic communities enrolled for at least three years in the Tanzania National Trachoma Control Programme. AB - Trachoma, a blinding eye disease caused by repeated and prolonged infection with Chlamydia trachomatis, is a significant public health problem for sub-Saharan Africa. Tanzania has had a National Trachoma Task Force since 1999, working on trachoma control in endemic districts. The objective of this study was twofold: first, to determine the current status of infection and clinical trachoma in these districts in Tanzania, and second, to determine if a combination of clinical signs could be used as a surrogate for infection. We conducted a survey for trachoma and infection with C. trachomatis in 75 villages in eight districts of Kongwa, Kilosa, Mpwapwa, Bahi, Kondoa, Manyoni, Monduli and Iramba in Tanzania, which have previously been shown to be endemic. In each village, a random sample of households, and of children within households, was taken for examination. Trachoma was graded using the World Health Organization system, which we expanded, and a swab taken to determine presence of infection. The rates of trachoma ranged from 0% in Iramba District to 15.17% in Monduli District, with large variation in villages within districts. Infection rates were generally lower than trachoma rates, as expected, and most districts had villages with no infection. A combination of clinical signs of trachoma in children, when absent, showed very high specificity for identifying villages with no infection. We conclude that these signs might be useful for monitoring absence of infection in villages, and that districts with trachoma prevalence between 10% and 15% should have village level rapid surveys to avoid unnecessary mass treatment. PMID- 20734707 TI - Prevalence and causes of low vision among schoolchildren in Kibaha District, Tanzania. AB - Low vision is a major cause of morbidity and has profound effects on the quality of life for many people as it inhibits/reduces mobility and economical well being of the affected individuals and their families. The objective of the study was to determine the magnitude and causes of low vision among primary school children in Kibaha district in Tanzania. Primary schoolchildren were recruited for the study. The inclusion criterion was individual child with low vision of less than 6/18. Visual examination was used for screening the children to identify those with vision less than 6 /18. Snellen's chart was used to measure visual acuity of the children with low vision. A total of 400 (6-17 years) schoolchildren were screened. Thirty-eight (9.5%) had low vision. The prevalence of low vision was statistically higher (N = 33; 87%) among 12-17years old than among 6-11 years old (13%) (P < 0.05). Of the 38 children with low vision, the prevalence in females (68%) was statistically higher than in males (32%). There were multiples causes of low vision among affected children. Congenital anomalies accounted for the largest proportion (65%) of the causes of low vision. In twenty-three (60%) of the children (12-17 years), low vision was due to retinopathies. Fifty-five percent of the children with refractive error were aged between 6-11 years. Among the cases, 8 (54%) had low vision caused by uncorrected refractive errors while the rest (46%) were due to other types of refractive errors. Two children had corneal scars; one with central and another with whole corneal scar. In conclusion, prevalence of low vision among schoolchildren in Kibaha district is high and increases with age. The main causes are congenital anomalies. There is need for an early detection of the possible causes and appropriate treatment to reduce the condition among schoolchildren. It is therefore important that the district Council Health Management Team establishes school eye screening programme for early detection and treatment. It is equally important to strengthen advocacy programme targeting schoolchildren, teachers and caregivers on the public health importance of low vision. PMID- 20734708 TI - Community directed approach beyond ivermectin in Tanzania: a promising mechanism for the delivery of complex health interventions. AB - The Community Directed Intervention (CDI) is currently used for Ivermectin distribution for the treatment of onchocerciasis in Africa. This study was carried out to determine the extent to which the CDI process can be used for the delivery of other health interventions with different degrees of complexity. The study was conducted in five districts of Kilosa, Muheza, Lushoto, Korogwe and Ulanga in Tanzania and involved communities, health facility and district healthcare providers. Implementation of CDI across these health interventions involved addressing six major processes, namely, stakeholder processes, health system dynamics, engaging communities, empowering communities, engaging CDI implementers and broader system effects. Community and health systems changes were triggered, such that the inherent value of community involvement and empowerment could be internalized by communities and health workers, leading to a more receptive health system. The CDI process was accepted at the community levels as many were willing and ready to adopt the approach. Health workers at community levels were readily available and supportive of the process. Additionally, noted were the verified willingness and ability of community implementers to deliver multiple interventions; confirmed efficiency of CDI leading to cost savings at health systems level; increasing interest of the health system in CDI; interest of health workers in the process of integrated planning. However, there were factors that may have a negative influence on the CDI process. Drug and supply policy for CDI process was lacking at the national and district levels and the presence of parallel community-based programmes that provide financial incentives for community members to run them discouraged Community-directed distributors who in most cases are volunteers. In conclusion, the results have clearly and evidently demonstrated the potential of CDI approach for effectively and efficiently control of other diseases such as malaria, tuberculosis and childhood illnesses. The study has provided unique information on the feasibility and effectiveness of integrated delivery of interventions at the community level. PMID- 20734709 TI - HIV/AIDS risk factors and economic empowerment needs of female sex workers in Enugu Urban, Nigeria. AB - While successes are recorded in the developed world with respect to control of HIV/AIDS, the dream of halting and reversing its spread seems to be a mirage in most parts of the developing world. The forces that drive the transmission of HIV/AIDS in Nigeria, as in many other resource poor societies include the activities of high-risk groups. Commercial sex workers remain a major source of HIV/AIDS transmission in Nigeria. The knowledge, attitude and practice (KAP) of HIV/AIDS among female sex workers (FSWs) faced with the threat of contracting HIV/AIDS were assessed. A total of 135 FSWs from four most popular brothels in Enugu were interviewed with a structured interview schedule. Six focus group discussion (FGD) sessions were held with FSWs from neighbouring communities. FSWs in Enugu were of diverse socioeconomic backgrounds. They were however mostly in their productive ages of 16-47, with a mean age of 26.9 years. Poverty was the common reason for sex work. Some engaged in sex work to provide their school needs and those of other dependants. The respondents were aware of HIV/AIDS and dread being infected by it because of the stigma and absence of cure. Three percent do not use condom at all. Others use unorthodox methods (e.g. douching with salt solution immediately after sex), if a client refuses to use condom. Condom use depended on the client's choice. Misconceptions exist among the respondents on mode of transmission. Perceptual factors, more than demographic differences played great role in the attitude of the FSWs towards HIV/AIDS. Steps need to be taken to improve on the level of knowledge of HIV/AIDS among the respondents. This should cut across socio-demographic lines and should target the perceptual factors, which tended to provide adequate explanation for the attitude of the respondents to HIV/AIDS. The FSWs should be provided with income earning skills to improve their income earner ability and make them self-reliant. PMID- 20734710 TI - Three years of HIV/AIDS care and treatment services in Tanzania: achievements and challenges. AB - The Tanzania HIV Care and Treatment Plan was launched in October 2004 aiming at providing 440,000 AIDS patients with antiretroviral drugs (ARVs) and track disease progression in 1.2 million HIV+ persons by the end of the 2008. This paper is intended to provide information to stake holders of the achievements and challenges of the HIV Care and Treatment Plan since its inception in 2004. Facility patient reports are aggregated at district and then regional level before being sent to the national level where they are aggregated to form a national report. By December 2007, 210 health facilities were offering HIV care and treatment services in Tanzania. About 123,147 (5%) of the 2,636,785 estimated people living with HIV and AIDS were enrolled, and 71,439 (13.6%) of the estimated 527,357 AIDS cases commenced ART. More females than males started ART, F:M ratio being 3:2. Most (49%) patients were started ART due to low CD4 counts (< 200). About 6,618 patients had their initial ARV regimen changed due to starting anti-TB treatment 679 (10%), peripheral neuropathy 812 (12%), skin rash 378 (6%), and stock out 247 (4%) or other reasons (18%), while 2,653 (42%) had no reason recorded. The proportion of patients still alive and on ART at 6, 12 and 24 months after initiation of treatment was 60%, 60%, and 50%, respectively, while those collecting ARVs on schedule was 34%, 25% and 10% respectively. About 3,084 patients developed TB after starting ART, of whom 1,557 (approximately 50%) patients during the first three months of treatment. During the three years (2004 2007) of HIV care and treatment services in Tanzania, there has been an increase in the number of CTC facilities, geographical coverage of services, the number of enrolled patients and those on ART. However, the set target for ART services has not been achieved and there are significant geographical variations in these achievements, which do not correspond with either population density or disease burden. Efforts should be made to i) ensure equitable accessibility when scaling up ART services in Tanzania, ii) improve the recording and reporting system and iii) armonize the activities of various stakeholders. PMID- 20734711 TI - Inverted CD4+/CD8+ ratio associated with AIDS event and death in HIV-1 infected individuals in Nasarawa State, Nigeria. AB - The current guidelines for the use of antiretroviral therapy in Nigeria places emphasis on the use of CD4+ enumeration to take decision of initiating antiretroviral therapy and HIV disease monitoring. CD4+ counts are known to be inherently inconsistent and therefore could be misleading. This study was undertaken to analyze the CD4+/CD8+ ratio vis-a-vis CD4+ in HIV-1 infected individual in North Central Nigeria and to correlate these immunological parameters to AIDS event and death in relation to gender and age of patients. Cell counts were carried out using a Fluorescence Activated Cell Sorter (FACS) that quantifies CD4+ and CD8+ T lymphocytes as absolute numbers of lymphocytes per microL of blood and the CD4+/CD8+ T lymphocyte ratio recorded in an automated fashion. A total of 290 HIV-1 positive persons were enrolled for this study. The median CD4+/CD8+ ratio were 0.05, 0.27, 0.64 in patients with CD4+ counts of < 50, 51-200, > 350 respectively. CD4+/ CD8+ of 0.05 and 0.27 were corresponding predictors of AIDS-related event and death. Patients with > 0.64 are predictive of better disease prognosis and low progression to AIDS. The CD4+/CD8+ were minimally higher in female patients with a median CD4+/CD8 ratio of 0.27. The age distribution of our patients at point of first entry was not found to influence CD4+/CD8+ ratios. These findings provide basic and critical CD4+/CD8+ cut-off values in predicting HIV disease progression and an alternative to absolute CD4+ counts at predicting the onset of HIV related disease. These data are useful to determine when intervention with antiretroviral therapy is needed and to determine the likelihood of virological failure. PMID- 20734712 TI - Relative prevalence of methicilline resistant Staphylococcus aureus and its susceptibility pattern in Mulago Hospital, Kampala, Uganda. AB - Methicilline resistant Staphylococcus aureus (MRSA) strains are becoming increasingly multiresistant, and have recently developed resistance to vancomycin, which has been used successfully to treat MRSA for many years. In vitro determination of resistance patterns of S. aureus is critical in terms of administering suitable antimicrobial treatments. The objective of this study was to determine the relative prevalence of MRSA among S. aureus isolates from surgical site infections and their antibiotic susceptibility pattern in Mulago Hospital, Kampala, Uganda. One hundred eighty eight pus swabs were collected from patients with surgical site infections. Swabs were inoculated for culture at the Microbiology Laboratory of the Faculty of Medicine, Makerere University. S. aureus isolates were identified using standard procedures and tested for oxacillin resistance according to methods of the National Committee for Clinical Laboratory Standards. Out of the 188 specimens, 54 (28.7%) grew S. aureus. Seventeen (31.5%) of the S. aureus isolates were confirmed as MRSA by PCR. Resistance rates of MRSA were 88.2% for trimethoprim-sulfamethoxazole, 88.2% for erythromycin, 58.8% for gentamycin, 70.6% for ciprofloxacin, and 88.2% for chloramphenicol. All isolates were found to be sensitive to vancomycin and clindamycin though the D-test was found to be positive in 82.4% of the isolates. In our region, although methicillin resistance increased in S. aureus strains, because of the unavailability and the high cost of alternative antibiotics, gentamycin is still suggested as an alternative for treatment of S. aureus infections. These results however indicate that vancomycin seemed to be the only antimicrobial agent effective against MRSA and it could be the drug of choice in treating multidrug resistant MRSA infection. PMID- 20734713 TI - Prevalence of urinary tract infection among pregnant women at Bugando Medical Centre, Mwanza, Tanzania. AB - Urinary tract infections (UTI) are the most common bacterial infections during pregnancy and these infections. Untreated UTI can be associated with serious obstetric complications. This cross-sectional study was carried out to determine the prevalence of UTI among symptomatic and asymptomatic pregnant women attending Bugando Medical centre (BMC) in Mwanza, Tanzania. A total of 247 pregnant women were enrolled, of these 78 (31.5%) were symptomatic and 169 (68.4%) asymptomatic. UTI was diagnosed using mid stream urine (MSU) culture on standard culture media and urinalysis was done using rapid dip stick. The prevalence of bacteriuria among symptomatic and asymptomatic pregnant women were 17.9% and 13.0% respectively, with no significant difference between the two groups (p = 0.307). Using univariate analysis there was no association of parity (p = 0.825), gestational age (p = 0.173), education (p = 0.615), age (p = 0.211) and marital status (p = 0.949) with bacteriuria. The sensitivity and specificity of urine dipstick was 38.9% and 86.7% respectively. Escherichia coli (47.2%) and Enterococcus spp (22.2%) were the most commonly recovered pathogens. The rate of resistance of Escherichia coli to ampicillin, tetracycline, sulfamethaxazole/trimethoprim, gentamicin, ciprofloxacin, nitrofurantoin, ceftriaxone, and imipenem were 53%, 58.8%, 64.7%, 5.9%, 11.8%, 5.9%, 29.4% and 0%, respectively. In conclusion, asymptomatic bacteriuria among pregnant women is prevalent in our setting and majority of Escherichia coli are resistant to ampicillin, tetracycline, SXT and ceftriaxone. Due to low sensitivity of rapid dip stick, routine urine culture and susceptibility testing is recommended to all pregnant women at booking. PMID- 20734714 TI - [Modern characteristics of epidemiology and prevention of community-acquired pneumonia in military staff]. AB - AIM: To study the effectiveness of system for prevention of community-acquired pneumonia (CAP) in military teams and determine the main ways for its improvement. MATERIALS AND METHODS: Data on incidence of CAP in military staff during 1993 - 2008 were used. Analysis of morbidity was performed using classical methods of epidemiological analysis. RESULTS: Registered incidence of CAP in military staff was 5 - 7 times higher compared with average incidence in adult population of the country. Main factors determining realization of CAP epidemic process mechanisms in military teams were revealed. Two-fold and more rise in incidence of CAP and acute respiratory infection in military recruits is forecasted for 2010. Effect of use of Pneumo 23 vaccine for freshmen recruits is grounded. CONCLUSION: Immunization of military staff with Pneumo 23 vaccine considered effective and needed component in complex of prophylactic measures performed in troops. PMID- 20734715 TI - [Molecular genetics typing of Brucella circulating in several provinces of Mongolia]. AB - AIM: Comparative molecular-genetic typing of Brucella strains isolated in Mongolia from different animal species as well as from humans. MATERIALS AND METHODS: Twenty-one strains of Brucella isolated from different hosts in 7 provinces of Mongolia were typed. Conventional phenotypic methods, genotyping by PCR with primers for genus- and species-specific differentiating targets of Brucella genes as well as multiple locus variable number tandem repeats analysis (MLVA) with 12 pairs of primers bounding locus variable tandem repeats of different length (from 134 bp to 8 bp). RESULTS: Phenotypic identification and genotyping by PCR using primers for differentiating DNA markers allowed to attribute 14 isolates to B. melitensis biovar 2, and 7 - to B. abortus biovar 3. By using the MLVA method, connection of MLVA genotypes of 9 Brucella isolates with their reservoir hosts (sheep, cows) was shown providing their circulation in Khentii, Bulqan, and Khubsgul provinces bordering with Russia. Nine isolates from different hosts (camel, yaks, goats, sheep) isolated in Ovorkhangai, Dundgovi, and Dornogovi provinces, which have not border with Russia, had closely related MLVA genotypes indicating an opportunity of migration of pathogenic Brucella species to not-typical hosts. CONCLUSION: Molecular-genetic typing of Brucella isolated in Mongolia was done for the first time; levels of their genetic relation and diversity were demonstrated. Circulation of Brucella isolated with specific MLVA genotypes was connected to territories of specific Mongolian provinces. The study proved migration of Brucella to not-typical hosts. Comparative study of isolates circulating in frontier with Mongolia areas of Russia (Irkutsk region, Tyva and Buryat Republics) are necessary to perform. PMID- 20734716 TI - [Heat-shock protein enhances immunogenicity of E7 oncoprotein of human papillomavirus included in chimeric construction (E7 HPV-HSP70)]. AB - AIM: To study the effect of chimeric E7 protein of human papillomavirus type 18 on activation of adaptive immunity in absence of adjuvant. MATERIALS AND METHODS: Chimeric protein was genetically engineered and represents the protein molecule consisting of full-size E7 oncoprotein and heat-shock protein 70 (HSP70) of Mycobacterium tuberculosis in one polypeptide chain. Antibody titers as well as isotypes and subisotypes of immunoglobulins were measured by ELISA in sera of immunized animals. RESULTS: It was shown that studied construction E7 (HPV-18) HSP70 significantly increases titers of antibodies to E7 protein of HPV type 18 and have cross-reactive antigenic activity with E7 protein of HPV type 16. Immunization with chimeric protein resulted in increase of IgG1 and IgG2b levels and decrease of IgG2a and IgM levels. CONCLUSION: . Oncoprotein E7 included in chimeric construction with HSP70 could be used for further studies on development of therapeutic vaccine for treatment of cervical cancer and precancerous lesions. Skew of immune response to Th2 type after intraperitoneal administration of the studied construction points to necessity for control of immunity during such studies. PMID- 20734717 TI - [Immunogenic and protective characteristics of surface antigens 6 and d of Burkholderia pseudomallei]. AB - AIM: Extraction of complex of Burkholderia pseudomallei antigens 6+d (Ag6+d) and study of its immunogenic and protective characteristics. MATERIALS AND METHODS: Studied antigens were obtained from acrtone-dried cells of B. pseudomallei 57576. Experiments were performed on white mouse model. Microbiological, immunochemical as well as immunological methods were used in the study. RESULTS: It was shown that antigenic complex 6+d has a glycoprotein nature and corresponds to high polymeric catode-moving antigen 6 with molecular mass 500 kDa and anode-moving antigen d with molecular mass 40 - 55 kDa. Immunogenic and protective characteristics of surface antigenic complex 6+d was studied. It was noted that Ag6+d caused reliable stimulating effect on cellular arm of immune system of white mice appeared in activation of delayed-type hypersensitivity reactions, enhanced phagocytic activity of polymorphonuclear macrophages as well as increased expression of Fc-receptors on macrophages and neutrophils. CONCLUSION: Observed stimulation of cellular immunity by surface antigens was confirmed during study of their protective characteristics on the model of experimental meloidosis in white mice. PMID- 20734718 TI - [Protective properties of candidate genetically engineered vaccines against avian influenza viruses constructed on the basis of recombinant adenoviral vectors]. AB - AIM: To design and study the properties of candidate vaccines against avian influenza based on recombinant adenoviral vectors expressing H5 hemagglutinin. MATERIALS AND METHODS: Recombinant adenoviral vectors were constructed as described in "Stratagene" (Ad Easy Adenoviral Vector System). For immunization of animals, recombinant candidate vaccines were administered intranasally twice. Titer of hemagglutinating antibodies were measured by hemaglutination inhibition assay. RESULTS: It was demonstrated that administration of vaccines to animals completely protects them from a lethal dose challenge with H5N2 influenza virus. Protective effect of vaccines remained for 6 months after immunization. Additionally, highly effective cross-protection of the immunized animals against heterologous strain of H5 influenza virus was demonstrated. CONCLUSION: Obtained results show good prospects for usage of recombinant adenoviral vectors as a basis for development of new generation effective vaccines against influenza. PMID- 20734719 TI - [Assessment of effectiveness of immunization against Hib-infection]. AB - AIM: To assess effectiveness of Act-HIB vaccine forprevention of acute respiratory diseases. MATERIALS AND METHODS: Nine hundred immunized children 1 - 5 years old as well as not immunized children of the same age were followed-up. Criteria for clinical effectiveness of the vaccine were rate of acute respiratory infection episodes, duration of disease episode, and rate of complications development. Level of nasopharyngeal coverage were also studied by bacteriological tests of nasopharyngeal secretion samples. RESULTS: Obtained data showed that immunization leads to increase of host's resistance capabilities, decrease of acute respiratory disease incidence and changes in structure of complications due to infection. CONCLUSION: Prevention of Hib-infection using Act HIB vaccine leads to decrease of acute respiratory disease rates and severity of infections. Total incidence of acute respiratory infections in children aged 1 - 5 years decreased by 27%, whereas incidence of pneumonia, bronchitis, and sinusitis - by 50%. Vaccination resulted in decrease of antibiotic use, number of pediatric consultations. PMID- 20734720 TI - [Regulatory effect of complex of natural cytokines and antimicrobial peptides on murine macrophages infected with multidrug-resistant Mycobacterium tuberculosis]. AB - AIM: To study the effect of complex of natural cytokines and antimicrobial peptides (CNCAP) included in preparation Superlymph on growth of multidrug resistant Mycobacterium tuberculosis CN-37 on the modem of murine peritoneal macrophages (MPh) cultivated in vitro. MATERIALS AND METHODS: Effect of CNCAP on peritoneal MPh of tuberculosis-susceptible mice C57BL/6 infected by M. tuberculosis CN-37 was studied using ex vivo model. Macrophages were preliminary incubated with CNCAP during one day. M. tuberculosis growth was assessed on 7th day by PCR. RESULTS: Preliminary incubation of infected MPh with CNCAP resulted in inhibition of M. tuberculosis CN-37 growth. CONCLUSION: Superlymph activates macrophages which lead to enhanced bactericidal action of MPh on M. tuberculosis CN-37. PMID- 20734721 TI - [Development of panel of monoclonal antibodies for detection of CagA cytotoxin of Helicobacter pylori]. AB - AIM: To obtain and study of immunochemical characteristics of monoclonal antibodies (MAbs) to CagA cytotoxin of Helicobacter pylori employing recombinant fragments of CagA protein. MATERIALS AND METHODS: Standard methods of construction and selection of hybridomas, different variants of immunoenzyme analysis and immunoblotting were used. Molecular genotyping of H. pylori cultures by amplification of cagA gene fragments was performed. RESULTS: Panel of MAbs recognizing 4 different linear epitopes on the CagA molecule, three of which are localized in conservative parts of cytotoxin and one--in variable region of CagA, was developed. On the basis of two obtained antibodies, system of two-center immunoenzyme assay for quantitative detection of CagA protein which is characterized by high sensitivity and specificity, was developed. Obtained MAbs allow to differentiate CagA-positive and CagA-negative strains of H. pylori by immunochemical methods. CONCLUSION: Employing pure recombinant fragments of CagA protein, first panel of MAbs to CagA cytotoxin of H. pylori was developed and characterized. Obtained MAbs open perspectives for study of the H. pylori cytotoxin molecule and construction of immunodiagnostic assays aimed on detection of CagA antigen. PMID- 20734722 TI - [Features of cytokine levels in serum of patients with tick-borne borreliosis with different clinical signs]. AB - AIM: To assess levels of several cytokines in blood of patients with tick-borne borreliosis (Lyme disease) with different clinical variants of the disease. MATERIALS AND METHODS: Study of complex of proinflammatory cytokines (IFNalpha, IL-1beta, IFNgamma, IL-2, IL-4, IL-8) during course of the disease was performed by solid-phase ELISA using domestic diagnostic kits (Scientific Manufacturing Organization "Proteinovyi Contur", "Cytokine" Ltd., Saint Petersburg). Levels of TNFalpha was determined by ELISA using commercial kits "Boehringer Manheim" (Austria). RESULTS: Performed comparative clinico-laboratory analysis demonstrated increased levels of LL-2, IL-4, and IL-8 in patients during acute phase of tick-borne borreliosis that could point to host's response on bacterial infection. It should be noted that in patients with arthritis levels of LL-4 and IL-2 remained high during recovery phase that probably determined by possible persistence of Borrelia burgdorferi. CONCLUSION: Further research of cytokines during Lyme borreliosis could have important diagnostic and prognostic value. PMID- 20734723 TI - [Usage of real time polymerase chain reaction for diagnostics of different tick borne infections]. AB - AIM: To create and test the complex of polymerase chain reaction-based methods for detection of pathogens vectored by ticks in clinical and environmental samples. MATERIALS AND METHODS: Real time PCR methods with hybridization fluorescent detection were developed for detection of tick-borne encephalitis virus, Borrelia burgdorferi sensu lato, Anaplasma phagocytophillum, Erlichia muris/E. chaffeensis, and B. miyamotoi. First four methods were combined in one assay in multiprime format. Efficacy of the assay was assessed by testing of blood samples from patients with tickborreliosis (166 patients), tick-born encephalitis (22 patients) and mixed infection tick-borne encephalitis + borreliosis (21 patients) from Sverdlovsk region. RESULTS: It was shown that using PCR-based assay for testing the blood samples obtained during admission, it was possible to determine the etiology of disease in 39% of patients, whereas on the basis of serological data diagnosis, as a rule, is made not earlier than on 2nd week of therapy. False-positive results of PCR diagnostics were not observed. Infections caused by Anaplasma or Erlichia were not observed. It was shown that > 50% of cases of tick borreliosis without erythema were caused by B. miyamotoi, whereas B. burgdorferi sensu lato predominated as a causative agent of erythemic form of borreliosis. CONCLUSION: Proposed complex of methods is useful for rapid diagnostics of tick-borne infections including previously unknown infection caused by B. miyamotoi. PMID- 20734724 TI - [Molecular genetic tools for etiologic diagnostics of disseminated lung tuberculosis]. AB - AIM: Improvement of etiologic diagnostics of disseminated lung tuberculosis (DLT) and determination of Mycobacterium tuberculosis (MBT) drug susceptibility on the basis of molecular genetic methods. MATERIALS AND METHODS: Samples from respiratory tract of patients with DLT were studied using real time polymerase chain reaction and the "TB-BIOCHIP" assay developed by Institute of Molecular Biology. Methods of spoligotyping and reverse hybridization were used for identification, genotyping and express-detection of drug resistance of MBT to rifampicin in sputum samples stained for bacterioscopy. RESULTS: In 76 (41.5%) of 183 patients with radiological signs of DLT, DNA of tuberculosis complex mycobacteria was detected in respiratory tract samples (specificity 87.7%); mutations in genes rpoB, katG, inhA as well as region ahpC-oxyR associated with resistance to rifampicin and isoniazide were revealed in 67% and 79.5% of patients with DLT respectively. In 48.8% of sputum samples, DNA of MBT of epidemically significant genotype Beijing associated with multidrug resistance of MBT in Russia was identified. CONCLUSION: Molecular genetic methods allow to use both fresh and archived respiratory tract specimens for rapid verification of DLT diagnosis during oligobacillar forms of tuberculosis as well as timely prescribe and correct the treatment regimen of the patient according to individual drug susceptibility spectrum of the agent. PMID- 20734725 TI - [Laboratory model of hyperlipidemia]. AB - AIM: Approbation of laboratory model of hyperlipidemia induced by multiple administration of poloxamer 407 to hybrid mice (C57BL/6 x DBA/2) F1. MATERIALS AND METHODS: Two-month-old female mice (C57B1/6 x DBA/2)F1 were used for experiments. Level of dyslipidemia was assessed measuring cholesterol level in serum by method with cholesteroloxidase. RESULTS: Dosages and timing of administration of the compound for inducing stable moderate hypercholesterolemia were selected. It was discovered that dyslipidemia induced by this method accompanied by reliable increase of neutrophils count in peripheral blood of animals. CONCLUSION: Hyperlipidemia induced in mice by administration of poloxamer 407 could be used for convenient experimental model for complex studies of immune system functions during pathophysiologic conditions associated with lipid metabolism disorders. PMID- 20734726 TI - [Structure and matter of modern epidemiology]. AB - Key questions related to definitions of the object, subject field and methods of epidemiology. Definition and characteristic of epidemiological approach to study human diseases are formulated. Structure and matter of modern epidemiology as a basic medical science belonging to prophylactic medicine field are reviewed. PMID- 20734727 TI - [Current views on pathogenicity and immunogenicity factors of Bacillus anthracis]. AB - Bacillus anthracis is an etiological agent of extremely dangerous zooanthroponosis - anthrax. To date, significant volume of scientific data about structure, molecular nature, characteristics, genetic determination, regulation and action mechanisms of main pathogenicity factors of B. anthracis and its immunogenicity is accumulated. For study of integral picture ofpathogenesis and immunogenesis such global methodologies as complex analysis of structure and functions ofgenome, on the one hand, and studies of fine mechanisms of interactions of genes or certain parts of protein molecules, on the other, were used. PMID- 20734728 TI - [Pneumococcal infection is a vaccine-preventable disease now]. AB - Analysis of pneumococcal disease burden in Russia, which is a serious threat to children's and adults' health and which was underrecognized until last decade, is presented. Extrapolating data about etiologic structure of pneumonia and meningitis on published incidence figures, we can estimate the incidence of pneumococcal pneumonia in children in Russia: 490 per 100,000 for children aged 1 month - 15 years, and 1060 per 100,000 for children aged 1 month - 4 years. For complicated forms, these figures are 90 and 181 per 100,000 respectively. Mean incidence of pneumococcal meningitis is 8 per 100,000 children aged < 5 years with variations from 2 to 15 depending from region. Estimated overall incidence of pneumococcal bacteremia in children < 5 years in Russia is 100 per 100,000. Despite of antibacterial therapy, bacteremic forms of pneumococcal infection lead to death in 15 - 20% of adult patients, whereas in elderly this figure amounts 40%. These data demonstrate the importance of wider use of both polysaccharide and conjugated pneumococcal vaccines licensed in Russia. PMID- 20734729 TI - [Change of host's behavior including man under the influence of parasites]. AB - Directed modulation of hosts' behavior favouring transmission of pathogen was noted in many parasites and, above all, in helminthes, which life cycle includes the consequent change of several hosts. It turned out that parasites use the same neuromediators for change of behavior of both mammals and hosts belonging to other animal classes. In fishes as well as in mammals, monoamines neurotransmitters assist in brain functioning. Norepinephrine, dopamine and serotonin affect the alimentation, motion activity, aggression and social behaviour. Changes in concentration ratio of serotonin and its metabolites in invaded species were more pronounced, which pointed to directed effects of pathogens on serotonin activity. The same effect of some pathogens on human behaviour does not have selective significance because humans are not an essential link in life cycle of many parasites. Although the mentioned effect on behaviour could lead to negative consequences. For examples, persons with latent toxoplasmosis are significantly more frequent become members or victims of traffic accidents due to decreased ability for concentration of attention. PMID- 20734730 TI - [The evolution of the etiological structure of shigellosis]. PMID- 20734731 TI - [Definitions in epidemiology--the language of science]. PMID- 20734732 TI - [Evaluation of the efficiency of measures to reduce the influence of risk factors on human health]. AB - 65% of the region's population is covered by the complex monitoring and control of environmental factors. Chemical contamination of drinking water with iron, manganese, boron, or nitrates makes a 60% contribution to anthropogenic load. Implementation of the measures of a special urban program could reduce the proportion of the drinking water, which did not meet the hygienic standards by sanitary chemical indicators, in Voronezh from 10.2% in 1999 to 8.5% in 2008 and halve the concentration of manganese and iron. PMID- 20734733 TI - [Karyological and immunological parameters in children under conditions of varying ambient air pollution]. AB - The cytological status, proliferation, and apoptosis of the buccal epithelium and the level of secretory immunoglobulin A were studied in 90 children living in a large ferrous metallurgy center (Tula). There were increases in the degree of cytogenetic impairments, a change in cell kinetic processes, and a reduction in local immunity in children in a more polluted area. There was a high significant correlation of karyological and immunological parameters with some chemical ambient air pollutants. PMID- 20734735 TI - [Evaluation of exposure of the Moscow population to ambient air pollution by carcinogenic substances]. AB - The rapid growth of motor transport in Moscow has led to a substantial increase in the volumes of pollutant emissions into the city's air. As of 2007, the motor transport fleet of the city approximated 3 million units annually consuming about 5 million tons of motor fuel. Carcinogenic substances, such as formaldehyde and benzene, are supervised in the ambient air of Moscow. To evaluate their adverse effect on human health, carcinogenic risks are calculated from their annual average concentrations. The levels of total carcinogenic risks from the impact of the average concentrations of formaldehyde and benzene in the period 2005 to 2007 in all areas correspond to the maximum permissible (alarm) risk that requires measures to improve ambient air. According to the results of the investigation, health promotion measures are recommended to the Government of Moscow. PMID- 20734734 TI - [Toxic and genetic risk assessments in children of Gornaya Shoria]. AB - This comprehensive study assessed a number of environmental factors that were potentially able to induce genotoxic effects in man. A set of radiological, physicochemical, and bioindication techniques was used to estimate the quality of water, air, and soil in the places of residence and education of children and adolescents from the boarding school of the town of Tashtagol and schoolchildren from the village of Krasnoye, Kemerovo Region. Excess radon levels in the air of living spaces and classes, a small excess of the maximum allowable concentration of gross forms of heavy metals in individual soil samples, and high toxic effects in the Drosophila gametes exposed to air samples were revealed in the Tashtagol children having higher genotoxic effects in the lymphocyte than those in the Krasnoye village ones. The findings suggest that the marked genotoxic effects recorded over a long time in the lymphocytes of children and adolescents living in Tashtagol may be associated with the complex influence of the above factors. It is north supplementing further investigations by an extended chemical analysis of water, air, snow, and soil samples taken in the places of residence and education of children. PMID- 20734736 TI - [Estimation of morbidity rates in relation to living conditions]. AB - The scientific and practical evaluation of the cumulative influence of environmental factors on human health presents certain difficulties as the establishment of the level of individual health is methodologically inadequately developed. By employing the clinical studies only, the existing prophylactic medical examination system enables one to detect only the early signs of diseases. Estimating the level of human health should be complemented with criteria for prenosological diagnosis along with the assessment of individual living conditions to enhance the objectivity of determining the population's health status and to elaborate hygienically founded prophylactic measures. PMID- 20734737 TI - [Features of homeostasis in children from industrially developed areas]. AB - The goal of the investigation was to detect and assess the specific features of abnormal biochemical and immunological parameters in children living in the industrially developed areas in order to solve the tasks of early diagnosis and to enhance the efficiency of prevention of the chronic pattern of gastroduodenal diseases. It was found that children with increased contamination of biological media had more active inflammatory reactions with a trend towards the chronic pattern of an inflammatory process, altered antioxidant defense and a more common chronic inflammatory process in the biliary tract, and more significant cytolysis syndrome with gallbladder concentration dysfunction. PMID- 20734738 TI - [Prevention of acute chemical poisonings as a hygienic problem]. AB - Acute exposures, more than 98% of which now occur under household conditions, are an important constituent of the chemical load of the urbanized environment on man and causes of a considerable group of non-communicable diseases, such as chemical poisonings. The cardinal way of their prevention is toxicological monitoring that allows authorities of all levels to use information on the quantitative and qualitative characteristics of acute chemical poisoning in this area and to set up an adequate system of prophylactic measures, including the optimization of toxicological care to the population. Nationwide measures to regulate human contacts with toxicants are of great importance. A system of informing (primarily sanitary education) all sectors of society about possible toxic effects of various-application chemical substances and their safe handling regulations system is to be modernized. PMID- 20734739 TI - [Risk for environment-induced diseases due to air pollution from motor vehicles in road-patrol officers]. AB - The paper describes risk factors for environment-induced diseases in road-patrol (RP) officers under the existing working conditions: noise and chemical ambient air pollution from motor vehicles. There is evidence for a significant increase in the incidence of diseases of the cardiovascular and nervous system, sense organs, digestive and endocrine metabolic systems in the State Road Safety Inspectorate officers who are directly engaged in traffic management. Potential and real risks from motor transport to the health of RP roads have been estimated. Recommendations on optimizing the working conditions are given. PMID- 20734740 TI - [The psychophysiological status and personality traits in teachers of the Magadan Region]. AB - The paper considers the specific features of the psychoemotional sphere and the properties of the nervous system, and psychophysiological reactions in teachers dwelling in different areas of the Far North-East of Russia. It has been established that the Magadan Region's teachers show a high psychoemotional tension, weakness, inertness, and instability of nervous processes. Asthenization, anxiety, and neurotic states along with decreased central nervous system performance were more pronounced in teachers living in the remote settlement of Evensk when natural, climatic, and social conditions become more severe. PMID- 20734741 TI - [Impact of the use of alcoholic beverages on lipid metabolic parameters in Northern Water Basin workers]. AB - The nature of changes in lipid metabolic parameters was studied in the sailors, river transport workers, and fishermen of the Northern Water Basin in relation to the specific features of their working conditions and the frequency of drinking alcoholic beverages. It was shown that there was imbalance in the levels of lipid parameters, which was more pronounced in sailors and river transport workers. PMID- 20734742 TI - [Experience in improving the working conditions and health status of workers at a large chemical plant]. AB - Working conditions were studied at a chemical plant manufacturing nitrogen compounds. The leading adverse industrial factor was found to be chemical as ambient air pollution from ammonia, nitric dioxide and oxide, and other substances. The plant's administration constantly keeps the working conditions and health status of workers under control. The sanitary laboratory monitoring noxious industrial factors has been operating at the plant for tens of years. Scheduled improvement of working conditions leads to their gradual improvement. Periodic medical examinations of workers exposed to adverse working conditions, timely treatment of patients (by showing in those with gastroduodenal ulcer diseases as an example), diets, medicines, etc. result in the workers' better health. PMID- 20734743 TI - [Estimation of adaptive capacities in Magnitogorsk children from the activity of some detoxification enzymes]. AB - The paper provides the first fragment of a multiparameter study analyzing the influence of environmental pollution, the social and psychological features of a family, and some endogenous factors on genome stability and sensitivity in a developed ferrous metallurgy town. It also gives data on the urine and serum activity of the lysosomal enzyme N-acetyl-b-D-glucosaminidase (NAG) and the serum activity of catalase in an organized contingent of apparently healthy children (n = 178; 6 kindergartens) aged 5-7 years, who live permanently in Magnitogorsk at different distances from the metallurgical works. More than 70% of children selected for examination were found to have average normal levels of activity of the enzymes studied. According to the average levels of enzyme activity, there were only 2 kindergartens (both from the left-bank region). In the children from the left-bank area, enzyme activities varied more greatly, which suggests the higher prevalence of tense adaptation. Correlation analysis revealed association between the children's serum activity of enzymes and some components of snow pollution. It is anticipated that the found changes in serum activities of N acetyl-beta-D-glucosaminidase and catalase may be determined by individual differences in a child's response to ambient air pollutants. PMID- 20734744 TI - [Influence of climatic and geographic factors on the environmental distribution of heavy metals and children's health]. AB - The authors have studied the environmental distribution of salts of heavy metals (cadmium and nickel) under the influence of climatic and geographic factors and formation of geochemical anomalies. They also examined regularities in the accumulation of heavy metals in children's biosubstrates (hair, urine) and the nature of impact of their levels on the physical development of children in the organized collective bodies (preschool institutions) located in anomalous areas. PMID- 20734745 TI - [An association of the occupational risk factors from greenhouses with allergic diseases in their female workers' children: results of analysis]. AB - The paper analyzes an association between occupational risk factors in the female workers of greenhouses and allergic diseases in their children. The major factors contributing to the occurrence of allergic disease in children are their maternal employment in greenhouses with harmful working conditions, much dust in an apartment, a family history of allergic diseases, and unfavorable family lifestyle. PMID- 20734746 TI - [Determination of volatile fatty acids in blood for the evaluation of multiple factor environmental exposure]. AB - The paper considers problems in the assay of volatile fatty acids in blood by capillary gas chromatography using a flame ionization detector. The blood levels of different volatile fatty acids were analyzed in children with environment induced chronic gastroduodenitis with secretory failure. The performed studies allowed the authors to recommend that the altered blood levels of volatile fatty acids as an indicator of the environment-modified influence of poor environmental factors on the course of the disease. PMID- 20734747 TI - [Laboratory monitoring of pesticide residues in the environment]. AB - The paper presents the results of laboratory monitoring pesticide residues in the environment in the Republic of Mordovia in 2000 to 2007. It gives examples how to determine organic chlorine pesticides in the foodstuffs and environment, by stating the concentrations of ingredients. The entry route of pesticides and their action on human beings are shown. The main preventive measures are indicated for persons handling pesticides. PMID- 20734748 TI - [Evaluation of the status of experimental animals after chronic sulfur steam inhalation]. AB - Bronchoalveolar lavage (BAL) and the hepatorenal system were studied on albino rats in one-month regeneration period after 4-month chronic sulfur vapor in a dose of 1.76 and 12.68 microg/m3. Cytomorphological studies were used to detect the cumulative properties of sulfur: there were pathological processes in the hepatocytes; the light hepatocytes showed small-canalicular adipose degeneration, reduced dark cells, and increased degenerated light cells. There was a rise in the count of neutrophilic leukocytes, suggesting the progression of an inflammatory process in the regeneration period. The secretory function of the renal tubules exhibited destructive changes in the small and large light tubular cells; protein dystrophy was to a greater extent encountered in small tubular cells in the regeneration period. PMID- 20734749 TI - [Hygienic assessment of biologically rigid linear alkylbenzene sulfonates]. AB - It has been found that there are both biologically rigid and biologically soft homologues in the homologous series of linear alkylbenzene sulfonates (LABS). It is shown that absorption of LABS molecules from aqueous to activated sludge phase may serve as a determinant that should be used to refer a homologue to as rigid or soft surfactants. The biodegradability, detergency, and toxicity of LABS were ascertained to be related to the size of molecular alkyl molecular substitute. It has established that the fractional compositions of linear alkobenzenes should be changed for the synthesis of LABS that have the maximum detergency, a high biodegradability rate, and a low toxicity. PMID- 20734750 TI - [The 120th anniversary of the Department of Hygiene, Siberian State Medical University]. PMID- 20734751 TI - Complex nature of enterococcal pheromone-responsive plasmids. AB - Pheromone-responsive plasmids constitute a unique group of approximately 20 plasmids identified, as yet, only among enterococcal species. Several of their representatives, e.g. pAD1, pCF10, pPD1 and pAM373 have been extensively studied. These plasmids possess a sophisticated conjugation mechanism based on response to sex pheromones--small peptides produced by plasmid-free recipient cells. Detailed analysis of regulation and function of the pheromone response process revealed its great complexity and dual role--in plasmid conjugation and modulation of enterococcal virulence. Among other functional modules identified in pheromone plasmids, the stabilization/partition systems play a crucial role in stable maintenance of the plasmid molecule in host bacteria. Among them, the par locus of pAD1 is one of the exceptional RNA addiction systems. Pheromone-responsive plasmids contribute also to enterococcal phenotype being an important vehicle of antibiotic resistance in this genus. Both types of acquired vancomycin resistance determinants, vanA and vanB, as well many other resistant phenotypes, were found to be located on these plasmids. They also encode two basic agents of enterococcal virulence, i.e. aggregation substance (AS) and cytolysin. AS participates in mating-pair formation during conjugation but can also facilitate the adherence ofenterococci to human tissues during infection. The second protein, cytolysin, displays hemolytic activity and helps to invade eukaryotic cells. There are still many aspects of the nature of pheromone plasmids that remain unclear and more detailed studies are needed to understand their uniqueness and complexity. PMID- 20734752 TI - Evaluation of quantitative PCR measurement of bacterial colonization of epithelial cells. AB - Microbial colonization is an important step in establishing pathogenic or probiotic relations to host cells and in biofilm formation on industrial or medical devices. The aim of this work was to verify the applicability of quantitative PCR (Real-Time PCR) to measure bacterial colonization of epithelial cells. Salmonella enterica and Caco-2 intestinal epithelial cell line was used as a model. To verify sensitivity of the assay a competition of the pathogen cells to probiotic microorganism was tested. The qPCR method was compared to plate count and radiolabel approach, which are well established techniques in this area of research. The three methods returned similar results. The best quantification accuracy had radiolabel method, followed by qPCR. The plate count results showed coefficient of variation two-times higher than this of qPCR. The quantitative PCR proved to be a reliable method for enumeration of microbes in colonization assay. It has several advantages that make it very useful in case of analyzing mixed populations, where several different species or even strains can be monitored at the same time. PMID- 20734753 TI - The molecular evidence of Babesia microti in hard ticks removed from dogs in Warsaw (central Poland). AB - The purpose of this study was to specify the occurrence and prevalence of Babesia microti in hard ticks removed from dogs in Warsaw (central Poland). Among 590 collected ticks, 209 were identified as Ixodes ricinus, and 381 as Dermacentor reticulatus. B. microti DNA was detected in 11 out of 590 (1.86%) samples of ticks. The DNA of the parasite was detected only in lysates from female I. ricinus ticks (11 out of 193; 5.7%). The result of this study is the first evidence of B. microti in I. ricinus ticks in Warsaw. PMID- 20734754 TI - Modulation of IAA production in cyanobacteria by tryptophan and light. AB - Cyanobacteria represent less a investigated group of prokaryote, in terms of their plant growth promoting potential, especially in relation to the production of phytohormones. The present investigation was aimed towards analyzing growth kinetics, indole acetic acid (IAA) production and acetylene reduction activity (ARA) as an index of nitrogen fixation in two selected cyanobacterial strains belonging to the genus Anabaena, as influenced by tryptophan supplementation and light:dark conditions. Interesting observations were recorded in terms of enhancement of IAA production accompanied by protein and chlorophyll accumulation in the two cyanobacterial strains grown in media without tryptophan and incubated under light:dark or continuous light conditions. Colorimetric and chromatographic analyses supported the observations that tryptophan is not essential as a precursor for IAA biosynthesis in these cyanobacteria. Further study is in progress to identify genes involved in the tryptophan independent pathway for IAA biosynthesis. PMID- 20734755 TI - Purification and characterization of an extracellular protease from Bacillus subtilis EAG-2 strain isolated from ornamental plant nursery. AB - Bacillus subtilis EAG-2 strain isolated from an ornamental plant nursery produced a highly active extracellular protease. It was purified to apparent homogeneity by successive purification steps. The SDS-gel of purified protease revealed a single band of 27 KDa on 10% polyacrylamide gel. Proteolytic activity was confirmed by using two different zymographic methods. Interestingly, the enzyme showed two clear activity bands in both cases. The optimum proteolysis for this protease was observed at pH 8.5 and 65 degrees C. The enzyme was highly stable up to 80% after 30-50 degrees C for 60 minutes. It also remained stable at pH 6.5 9.0 after 4 hours of incubation at 37 degrees C. Its activity was reduced to 16% and 25% by PMSF and APMSF which indicates its relation to serine proteases. An increase in activity was noticed in the presence of Ca(+2), Zn(+2) and Ba(+2). On the other hand, it worked effectively with different natural substrates. Hence EAG-2 protease might be a useful contribution to the enzyme industry in Pakistan based upon its distinctive properties. PMID- 20734756 TI - Optimization of medium composition for enhancing growth of Lactobacillus rhamnosus PEN using response surface methodology. AB - Response surface methodology was used to optimize media components such as carbon and nitrogen (simple and complex) sources, mineral agents and growth factors (B vitamins, amino acids) for enhancing the biomass production of Lactobacillus rhamnosus PEN. For screening experiment the following carbon sources were selected: glucose, glucose+pyruvate, glucose+citrate, glucose+lactate, galactose, fructose, lactose, sucrose, maltose, lactulose, fructooligosaccharides, maltodextrins DP 4-7 and DP 13-17. Nitrogen sources such as yeast extract, meat extract and peptone K were used in lower concentrations than in MRS medium which served as a control. All experiments were run at 37 degrees C for 24-48 h under stationary conditions. Constituents chosen after the first screening experiments were further screened by the Plackett-Burman design. Glucose and sodium pyruvate, meat extract, potassium phosphate, sodium acetate, and ammonium citrate were chosen as promising medium components for further optimization studies. By solving the regression equation and analyzing the response surface carton, optimal concentrations of the components were determined as: glucose (13.4 g/l), sodium pyruvate (3.4 g/l), meat extract (7.2 g/l), potassium phosphate (2.0 g/I), sodium acetate (5.0 g/1) and ammonium citrate (2.0 g/l). In comparison to MRS broth the optimal medium contained fewer ingredients and in modified amounts but Lb. ihamnosus PEN showed better growth activity. Biomass concentration (as dry cell weight) of bacteria cultivated in optimal medium at bioreactor conditions was 5.5 g/l after 16 h of incubation, being higher in comparison with bacterial growth in MRS medium (1.9 g/l) under the same conditions. Moreover, the new medium was less expensive. PMID- 20734757 TI - Metabolic activity of moulds as a factor of building materials biodegradation. AB - This paper presents the effect of building materials on the growth and metabolic activity of moulds. In cultures of Aspergillus and Penicillium moulds grown on a model medium with the addition of building materials, the biomass of mycelium, its cellular components--glucan, chitin, ergosterol and the spectrum of enzymes and organic acids produced in the medium were investigated. It was found that on the medium with wallpaper moulds produced more biomass and extracellular enzymes, mainly glycolytic ones. On medium with mortar the growth of mycelium was impeded, production of biomass was 60% smaller, the quantity of chitin, glucan and ergosterol decreased 13-41%, and the activity of most enzymes was reduced; however the moulds intensively produced organic acids: malic, succinic and oxalic acid. The largest acid production activity was found in medium with addition of mortar; moulds produced the greatest variety of acids and in greater quantities than in the control medium. Metabolic activity of the moulds depends on the type of building material, and may lead to biodeterioration of these materials. PMID- 20734758 TI - Resistance for anti-tuberculosis drugs in central Black Sea region of Turkey. AB - One of the primary aims in tuberculosis (TB) management is to detect new cases as early as possible, and instigate the most appropriate therapy, for which it is important to know the characteristics of TB drug resistance in society. The aim of our study was to determine the resistance status of tuberculosis in the Samsun region of Turkey. To achieve that, the medical records of 1,029 pulmonary tuberculosis patients admitted to Samsun Chest Diseases and Chest Surgery Hospital between 2004 and 2006 were analyzed for drug resistance characteristics. In order to define the problem, isolates were tested on Lowenstein-Jensen medium. For drug susceptibility testing, isoniazid (I), streptomycin (S), ethambutol (E), rifampicin (R) and the radiometric Bactec 460 TB system were used. Eighty-six percent (86%) of the cases (623/721) were new patients, and 13.5% (98/721) were previously treated cases. One hundred and thirty-four (134) of the 721 patients (18.6%) had resistance to one or more drugs. Resistance to any drug was determined in 16.9% (105/623) cases of new patients. I resistance was 13.2%, any R resistance was 2.9%, and multi-drug resistance (MDR) was 1.9%. In previously treated cases, resistance to any drug was 29.6%, any I resistance was 26.5%, any R resistance was 15.3%, and MDR was 13.3%. It was concluded that resistance to anti-tuberculosis drugs is an important problem in Samsun. PMID- 20734759 TI - False negative results in high viremia parvovirus B19-samples tested with real time PCR. AB - Extremely high viremia is observed during some viruses infection, especialy in immunocompromised patients. False negative results of Parvovirus B 19 DNA tests performed with real-time PCR in high viremic samples are reported. The way of fluorescence diagrams analysis and algorithm of positive result confirmation to exclude such phenomenon are proposed. PMID- 20734760 TI - The first case of a Staphylococcus pseudintermedius infection after joint prosthesis implantation in a dog. AB - We have reported a bacterial infection in a dog with progressive dysplasia of the hips. Orthopedic surgery was performed. Seven weeks prior to the surgery, the patient was bitten by another dog. The postimplantation wound exuded for four days after the surgery. Microbiological analysis performed by standard identification techniques showed the presence of Staphylococcus intermedius, but an additional molecular analysis indicated S. pseudintermedius. This was followed by an evaluation of antibiotic susceptibility of the strain which showed cefoxitin, ciprofloxacin, clindamycin, trimethoprim/sulfamethoxazole, doksycycline, erythromycin, and gentamicin resistance. Minimal inhibitory concentration (MIC) values for selected antibiotics were reported. Resistance for cefoxitin indicates that methicillin resistant S. pseudintermedius (MRSP) strains were present in individual macroorganisms, but they can expand and persist the colonization of other hosts. PMID- 20734761 TI - Determination of diagnostic value of Toxoplasma gondii recombinant ROP2 and ROP4 antigens in mouse experimental model. AB - The aim of this study was to test the potential diagnostic usefulness of recombinant Toxoplasma gondii rhoptry antigens, ROP2 and ROP4, with respect to toxoplasmosis detection and infection phase distinction in laboratory mouce by determining specific serum IgM and IgG antibodies with the use of indirect ELISA technique. The mice antibody response to ROP antigens was significantly higher in the IgM than in the IgG class with the peak on the turn of acute and latent infection, whereas the response to recombinant SAG1 antigen, used as control, revealed preferential synthesis of IgG antibodies with the highest absorbance values measured during latent toxoplasmosis. PMID- 20734762 TI - [Diversity and evolution of LTR retrotransposons in the genome of Phanerochaete chrysosporium (Fungi: Basidiomycota)]. AB - The diversity of mobile elements, in particular LTR retrotransposons, in basidiomycetes fungi has been poorly studied. Using complete genomic sequences, we have for the first time screened the genome of the lignin-degrading fungus Phanerochaete chrysosporium for LTR retrotransposons. A surprisingly high diversity of LTR retrotransposons was found. Twenty-three novel mobile elements from two superfamilies, Pseudoviridae and Metaviridae, were described. The proportion of LTR retrotransposons in the P. chrysosporium genome is low, constituting only about 3%. Nevertheless, LTR retrotransposons of P. chrysosporium represent a dynamic part of the genome, which is evidenced by the presence of intact copies with signs of recent transposition and numerous solo LTR elements. Phylogenetic and structural analyses detected mobile elements having characteristics that had been previously unknown for other LTR retrotransposons. PMID- 20734763 TI - [Sequence analysis of the yadA, inv, and ail genes and their expression in the main and nonmain Yersinia pestis subspecies and Yersinia pseudotuberculosis]. AB - The nucleotide sequences of the inv, yadA, and ail adhesin-invasin genes were analyzed in 24 strains of the main and nonmain Yersinia pestis subspecies, which were isolated from natural plague foci in Russia and neighbor countries, and ten Y. pseudotuberculosis strains. All of the five plague agent subspecies (main, caucasica, altaica, ulegeica, and hissarica) had the inv and yadA genes altered by insertion of the IS element and a single nucleotide deletion, respectively, as was earlier observed for the Y. pestis strains KIM and CO92. Consequently, the strains lacked functional activity of the Inv and YadA proteins. The ail gene of the main and ulegeica subspecies had a missense mutation, which replaced Val138 with Phe in the Ail protein. The strains of the caucasica subspecies had an AGT insertion in the ail gene, resulting in Ser148 insertion in the polypeptide chain. The changes in the ail sequence probably exerted no effect on ail expression, since the strains of all subspecies were resistant to blood serum complement. PMID- 20734764 TI - [Genetic analysis of the Hsm3 protein domain structure in yeast Saccharomyces cerevisiae]. AB - Gene HSM3 encodes the Hsm3 protein involved in the minor branch in the system responsible for the correction of mismatched bases in DNA structure and controls replicative and reparative spontaneous mutagenesis in yeast Saccharomyces cerevisiae. Spontaneous and UV-induced mutagenesis was studied in three mutant alleles of gene HSM3, and repair effectivity of artificial heteroduplexes was assessed in DNA molecule. The resuts of these studies allowed establishment of the protein domain structure of protein Hsm3 and functions of each domain: the N terminal domain is responsible for binding to mispaired bases, and the C-terminal domain ensures the interaction with other proteins involved in the system of mismatched base correction. PMID- 20734765 TI - [IXR1 and HMO1 genes jointly control the level of spontaneous mutagenesis in yeast Saccharomyces cerevisiae]. AB - The yeast genes IXR1 and HMO1 encode proteins belonging to the family of chromatin nonhistone proteins, which are able to recognize and bind to irregular DNA structures. The full deletion of gene IXR1 leads to an increase in cell resistance to the lethal action of UV light, gamma-rays, and MMS, increases spontaneous mutagenesis and significantlly decreases the level of UV-induced mutations. It was earlier demonstrated in our works that the hmo 1 mutation renders cells sensitive to the lethal action of cisplatin and virtually does not affect the sensitivity to UV light. Characteristically, the rates of spontaneous and UV-induced mutagenesis in the mutant are increased. Epistatic analysis of the double mutation hmo 1 ixr1 demonstrated that the interaction of these genes in relation to the lethal effect of cisplatin and UV light, as well as UV-induced mutagenesis, is additive. This suggests that the products of genes HMO1 and IXR1 participate in different repair pathways. The ixr1 mutation significantly increases the rate of spontaneous mutagenesis mediated by replication errors, whereas mutation hmo 1 increases the rate of repair mutagenesis. In wild-type cells, the level of spontaneous mutagenesis was nearly one order of magnitude lower than that obtained in cells of the double mutant. Consequently, the combined activity of the Hmo 1 and the Ixr1 proteins provides efficient correction of both repair and replication errors. PMID- 20734766 TI - [The order of the bs, Skdh, and Aadh1 genes in chromosome 5R of rye Secale cereale L]. AB - Segregation analysis was performed in the progenies obtained in analyzing crosses of hybrids of spring and winter accessions of rye Secale cereale L. and wild S. montanum subsp. anatolicum (Grossh.) Tzvel. (syn. S. strictum (J. Presl) J. Presl). The test genes controlled the brittle stem (bs), the allelic variants of aromatic alcohol dehydrogenase (Aadh 1) and shikimate dehydrogenase (Skdh), and the growth habit (Vrn 1). A linkage was observed in the inheritance of the brittle stem and the aromatic alcohol dehydrogenase and shikimate dehydrogenase alloenzymes. The order of genes was established to be bs-Skdh-Aadh 1, and the genetic distances were estimated to be bs-(9.0%)-Skdh, bs-(10.8%)-Aadh 1, and Skdh-(5.3%)-Aadh 1. The recombination coefficient between the Skdh and Aadh 1 genes varied from 2.2 to 18.2%, averaging 5.3%. The growth habit was inherited independently of the bs-Skdh-Aadh 1 linkage group. PMID- 20734767 TI - [Analysis of storage proteins (prolamines, puroindolines and waxy) in common wheat lines Triticum aestivum L. x (Triticum timopheevii Zhuk. x Triticum tauschii) with complex resistance to fungal infections]. AB - Storage proteins (prolamines, puroindolines, and Waxy) were studied in common wheat introgression lines obtained with the use of the Saratovskaya 29 (S29) cultivar line and synthetic hexaploid wheat (Triticum timopheevii Zhuk. x T. tauschii) (Sintetik, Sin.) and displaying complex resistance to fungal infections. Comparative analysis of storage proteins in the introgression lines of common wheat Triticum aestivum L. and in the parental forms revealed the only line (BC5) having a substitution at the Gli-B2 locus from Sintetik. Hybrid lines subjected to nine back crosses with the recurrent parental form S29 and selections for resistance to pathogens can be considered as nearly isogenic for the selected trait and retaining the allelic composition of (1) prolamines responsible for the bread-making qualitiy, (2) puroindolines associated with grain texture, and (3) Waxy proteins responsible for nutritive qualities. These lines are valuable as donors of immunity in breeding programs without the loss of the quality of flour and grain as compared to the S29 line and are also important in searching for genes determining resistance to leaf and stem rust and to powdery mildew. The amphiploid has a number of characters (silent Glu-A 1 locus and Ha genotype) that can negatively affect the quality of flour and grain and thus should be taken into account when choosing this donor. PMID- 20734768 TI - [Chromosome organization of Ty1-copia-like retrotransposons in the tomato genome]. AB - Ty1-copia-like retrotransposons were discovered in all studied plants and form a considerable fraction of their genomes. PCR amplification of a pool of fragments of the reverse transcriptase gene of Ty1-copia-like retrotransposons of the tomato genome was conducted and their physical organization in mitotic and meiotic chromosomes was studied. The method of fluorescence in situ hybridization revealed the location of retrotransposons in the pericentromeric heterochromatin and their absence in the nucleolus organizer region. Knowledge of physical distribution of retrotransposons in the tomato genome is important when constructing molecular markers on their basis. Comparative analysis of chromosomal location of retrotransposons in different plant species extends our knowledge of the plant genome evolution. PMID- 20734769 TI - [Semisterile meiotic mutant sy11 with heterologous chromosome synapsis in rye Secale cereale L]. AB - A study was made of the expression and inheritance of the sy11 mutation, which alters homologous chromosome synapsis in meiotic prophase I of rye. The abnormal phenotype proved to be determined by a recessive allele of a single sy11 gene. Univalents and multivalents were observed in homozygotes for the mutant allele. Analysis of the synaptonemal complex revealed a combination of homologous and nonhomologous synapsis in the mutant. The nonhomologous synapsis frequency significantly decreased in the course of meiotic prophase I in the mutant. The number of chiasmata per bivalent in metaphase I was 1.1 x 0.01 versus 1.8 x 0.01 in wild-type plants, and the number of univalents was 2.7 x 0.06 versus 0.5 x 0.05 in wild-type plants. As a result, a broad range of abnormalities was observed at subsequent stages of meiosis and led to the formation of defective microspores. Mutant plants were semisterile. PMID- 20734770 TI - [Studying of genetic basts of cotton forms breeding with kleystogamic type of the flower]. AB - Experimental works Nave been carried for definition of output of the cross pollination within cotton sorts and hybrids as initial background for researches in generic and breeding aspects of the hasmo and kleystogamic features of the flowers. As the result the low which defines the rate of vicinizm from 0.53 to 15.36% was stipulasted because defined cross pollination took place and brought to biological contamination of the from, line and gene collection and as the result the froms lost their genetic integrity and became geterozygotic, geterogenetic. Different types of splitting within the classesas 3 : 1, 15 : 1 with phenotype of monogenic (3 : 1) and digenic (15 : 1) differences of the accumulative polymerization were defined during studyng of the genetic control of the flower type of the interspecies hybrids of G. hirsutum L. and G.barbadense L. They possessed correspondently the following gene types: 1 : 2 : 1 (1Cg1Cg1cg2cg2 : 2Cg1cg1cg2cg2 : 1cg1cg1cg2cg2) and 1 : 2 : 2 : 4: : 1 : 2 : 1 : 2 : 1 -1) Cg1Cg1Cg2Cg2 - 1 ; 2) Cg1Cg1cg2cg2-2; 3) Cg1cg1Cg2Cg2-2; 4) Cg1cg1Cg2cg2-4; 5) Cg1Cg1cg2cg-1; 6) Cg1cg1cg2cg2-2; 7) cg1cg1Cg2Cg2-1; 8) cg1cg1Cg2cg2-2; 9) cg1cg1cg2cg2-1, were 1-8 possessed hazmogamic and the 9th class possessed kleystogamic gene type with double recessive. On its bases gene types with individual phenotype expression were defined in F2 and their correlation with the most important morphobilogical and agricultural important featureas was studied. Special attention has been given to the productivity of hybrid individuals and this is bases for developing of the new sorts of intensive type. Forms, families, lines, gene cjllections and sorts with isogenic and without isogenic determination of these features with hazmo and kleystogamic types of the flowers of G. hirsutum L. and G. barbadense L. prototypes were defined as the result of our researches based on untraditional methods of investigations of the hazmo and kleystogamic types of the flowers which do not have analogs in world cotton breeding. PMID- 20734771 TI - [Screening of population genetic SCAR markers for mykiss Parasalmo (Oncorhynchus) mykiss from Kamchatka]. AB - Using AP-PCR, the genome of Kamchatka mykiss (Parasalmo (O.) mykiss) was examined. Polymorphic fragments, implying geographic differences among the samples, were selected, cloned, and sequenced. Based on these sequences, longer, specific SCAR primers were selected and constructed. Using the BLAST software program, the sequences were analyzed for analogy to those from the GenBank database. It seemed likely that all sequences obtained belonged to earlier unexamined repeated sequences, variable in the populations of the species of interest. A total of seven SCAR markers, characterized by population-significant variability of the DNA products in Kamchatka geographic group of rainbow trout were constructed. These markers can be used for further investigation of the species Parasalmo (O.) mykiss. The SCAR marker sequences were deposited in GenBank under the accession numbers EU805500 to EU805506. PMID- 20734772 TI - [Multiplicity of B microchromosomes in a Siberian population of mice Apodemus peninsulae (2n = 48 + 4-30 B chromosomes)]. AB - Differentiation of four Siberian populations of East-Asian (Korean) field mice (Apodemus peninsulae) inhabiting the basin of the mid-stream of the Yenisei River was carried out according to the variants of the B chromosome system. A multiplicity of B microchromosomes (from 4 to 30) was found for the first time in all 26 mice from the left shore of the Yenisei River in the mid-stream area. All of them probably belong to a population with B microchromosomes. It is likely that in this population further reorganization of B microchromosomes into B macrochromosomes typical of this species does not occur. Two mice from this population had a large number of B chromosomes (26) earlier not observed in this species. In one mouse, the modal number of B microchromosomes was 30. This is a new maximum number of B chromosomes in this mouse species. PMID- 20734773 TI - [Comparative FISH analysis of C-positive blocks of centromeric chromosomal regions of pygmy wood mice Sylvaemus uralensis (Rodentia, Muridae)]. AB - The composition and homology of centromeric heterochromatin DNA has been compared in representatives of the Asian race and two chromosomal forms (Eastern European and Southern European) of the European race of the pygmy wood mouse Sylvaemus uralensis by means of in situ hybridization with metaphase chromosomes of microdissection DNA probes obtained from centromeric C-blocks of mice of the Southern European chromosomal form and the Asian race. Joint hybridization of both DNA probes yielded all possible variants of centromeric regions in terms of the presence of repetitive sequences homologous to those of some or another dissection region, which indicates a diversity of centromeric regions differing in DNA composition. However, most variations of the fluorescent in situ hybridization (FISH) patterns are apparently related to quantitative differences of repetitive elements of the genome. Experiments with the DNA probe obtained from the genome of the Southern European form of the pygmy wood mouse have shown that the number of intense FISH signals roughly corresponds to the number of large C-segments in representatives of the European race, which is characterized by a large amount of the centromeric C-heterochromatin in the karyotype. However, intense signals have been also detected in experiments on hybridization of this probe with chromosomes of representatives of the Asian race, which has no large C blocks in the karyotype; thus, DNA sequences homologous to heterochromatic ones are also present in nonheterochromatic regions adjacent to C-segments. Despite the variations of the numbers of both intense and weak FISH signals, all chromosomal forms/races of S. uralensis significantly differ from one another in these characters. The number of intense FISH signals in DNA from the samples of pygmy wood mice from eastern Turkmenistan (the Kugitang ridge) and southern Omsk oblast (the vicinity of the Talapker railway station) was intermediate between those in the European and Asian races, which is apparently related to a hybrid origin of these populations (the hybridization having occurred long ago in the former case and recently in the latter case). PMID- 20734774 TI - [Genetic structure of silver crussian carp Carassius (superspecies auratus) (Linnaeus, 1758) colonies from the Middle Dnieper basin]. AB - Population genetic structure of silver Prussian carp from the Middle Dnieper basin was established by means of biochemical gene marking and cytometric analysis. In addition to diploid goldfish Carassius auratus, which was the basic species of bisexual colonies, a number of biotypes of triploid silver Prussian carp C. gibelio were identified. These biotypes either formed isolated unisexual populations, or were an admixture to the bisexual colonies. In addition, in bisexual colonies, triploid females of non-clonal origin were identified. Despite the fact that all forms of C. gibelio reproduced by means of gynogenesis, some of them (C. gibelio-1) formed isolated unisexual populations, while the others (C. gibelio-2, -3, and -4) usually coexisted with C. auratus. PMID- 20734775 TI - [The use of the ISSR-PCR method for identifying domesticated animal breeds and species, inferring their population structures, and assessing gene pool similarity]. AB - The use of multilocus intermicrosatellite assay (ISSR-PCR) in combination with the method of k-clustering of population structures (Structure v2.2. program) has become a basis for a battery of tests of molecular genetic examination and for studying the gene pool of domesticated animal species. Possibilities are reviewed for analysis of the population structures of domesticated species at different levels (interspecific, interbreed, and intrabreed levels), for assessment of similarity of gene pools of breeds (intrabreed groups), as well as for identification of breeds and estimation of their consolidation, purity, and genealogical relationships. PMID- 20734776 TI - [Genomic instability in chidren born after the Chernobyl nuclear accident (in vivo and in vitro studies)]. AB - Analysis of peripheral blood lymphocytes in children born after the accident at the Chernobyl Nuclear Power Plant in the period from 1987 to 2004 (permanent residents of territories contaminated with radionuclides, n = 92; and children of irradiated fathers-liquidators, n = 88)) revealed increased levels of aberrant cells (ACs) and aberrations of the chromosomal type as compared to the control (P < 0.05). In three subgroups of children with different initial AC frequencies (children with high AC frequencies, > or = 3%; children with medium AC frequencies, 2%; and children with low AC frequencies, > or = 1%), the levels of aberrations of the chromosomal type are increased as compared to the control (P < 0.05). The levels of aberrant cells and chromosome aberrations (CAs) in the subgroup of children with > or = 3% frequencies significantly differ from those in the subgroup of children with > or = 1% AC frequencies. No dependence of the AC and CA frequencies on the year of birth after the Chernobyl accident was revealed. After fractional and single gamma-irradiation (137Cs) of blood in vitro in the 10-30 cGy dose range, the average CA frequencies in the first and second mitoses increased in a similar way depending on the initial AC frequencies in the children and parents. All these results suggest an individual character ofgenomic instability induced by low radiation doses and its transgenerational phenomenon in the organisms of children. PMID- 20734777 TI - [The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men]. AB - The frequency and spectrum of mutations and the IVS8- T polymorphism of the CFTR gene have been studied in a sample of 963 in Russian infertile men. Mutations have been found in 48 out of 1926 analyzed chromosomes (2.5%) in the heterozygous state (n = 46) and in the compound heterozygote L138ins/N1303K (n = 1/n = 1). A CFTR gene mutation was combined with the 5T allele (mutCFTR/5T) in 11 patients. The following mutations have been found: F508del (n = 18), CFTRdele2,3 (21kb) (n = 9), W1282X (n = 7), 2143delT (n = 4), 3849+10kbC>T (n = 2), L138ins (n = 2), 1677delTA (n = 1), 2184insA (n = 1), 3821delT (n = 1), G542X (n = 1), N1303K (n = 1), and R334W (n = 1). The F508del mutation is the most frequent; it has been detected in 37.5% of the affected chromosomes. The total proportion of four mutations (F508del, CFTRdele2,3 (21kb), W1282X, and 2143delT) is about 79% of all mutations found. The 5T allele has been found in 10.9% infertile men and 4.8% of control men. Significant differences in the frequency of the IVS8-5T variant of the CFTR gene have been found between these groups (p = 0.005), as well as between infertile patients without mutations and control men (p = 0.019). In total, the mutations and/or 5T allele have been found in 14.6% of the patients examined. These data indicate increased frequencies of the mutations of the CFTR gene and its allele variant IVS8-5T in Russian infertile men. PMID- 20734778 TI - [A new possibility of dihaploid lines us: enriching-restoring breeding scheme]. AB - Enriching-restoring breeding design based on dihaploid lines usage for the complete or partial collection of favorable alleles responsible for heterosis in a homozygous line is proposed. The efficiency of the scheme was checked via the mathematical model considering complicating factors. PMID- 20734779 TI - [Phosphodiesterase 4D (PDE4D) gene polymorphism in patients with acute stroke from Moscow]. AB - Two PDE4D gene polymorphisms [SNP41 (rs152312 and SNP87 (rs 2910829)] were studied in patients with acute stroke (n = 577) and in control sample (n = 270). Significant differences in the genotype and allele frequency distribution were found between these samples for polymorphism SNP41. We showed that the AA and AG genotypes of SNP41 polymorphism were associated with higher risk of acute stroke development in the Moscow population (OR = 1.6). No association of SNP87 polymorphism with the disease was observed. PMID- 20734780 TI - [Tanatogenetic aspects of brain injury associated with hemorrhagic shock in human]. AB - Cadaverous brains of 21 men and women were available for investigation. All the subjects died in a hospital from hemorrhagic shock (HS) caused by stab injuries to internal organs and blood vessels. In 9 cases, blood and urine contained no traces of ethyl alcohol; it was detected in the blood of 12 cases (1.0-3.8 per thousand). Histological methods were used to examine field 6 of the brain hemispheres, the wall of the third ventricle with a fragment of pituitary, the wall of the fourth ventricle with the adjacent portion of medulla oblongata, and pia mater. It was shown that impossibility of reperfusion of cerebral vessels, especially those involved in microcirculation, plays the leading role in tanatogenesis associated with hemorrhagic shock. "Blockade" of the brain vascular system results in metabolic disturbances in neurons and neuroglia and their lesions regarded as the immediate cause of death. Acute alcohol intoxication concomitant with hemorrhagic shock accelerates tanatogenesis due to serious changes in the brain vascular system, neurons, and neuroglia. PMID- 20734781 TI - [Forensic medical examination of wounds inflicted by the teeth of a dog]. AB - Trasologic characteristics of individual types of the dog's teeth and morphological features of skin wounds inflicted by a bite are presented. The data obtained may be used to discriminate these injuries from other wounds caused by sharp objects. PMID- 20734782 TI - [Quantitative characteristic of the relief of skin wound edges]. AB - This paper reports results of a morphometric study on the relief of skin wound edges with a limited contact surface resulting from an injury by sharp and hard objects. It is maintained that quantitative characteristic of the relief of skin wound edges can be used as an objective indicator of the properties of the object with which a given wound was inflicted. PMID- 20734784 TI - [Criteria for the establishment of the cause and effect relationship between a mechanical lesion and its fatal outcome in injured subjects who died at the scene of the accident]. AB - Criteria for the establishment of the cause and effect relationship between a mechanical lesion and its fatal outcome in injured subjects who died at the scene of the accident are considered in the context of their application for the purpose of forensic medical practice. It is believed that universalization of approaches to the solution of this problem would decrease the frequency of mistakes in expert documents. PMID- 20734783 TI - [Comparative morphological characteristics of changes in the liver in case of poisoning with alcohol-containing liquids in human and following subacute treatment of animals with ethyl and propyl alcohols, ethylene glycol and their mixtures]. AB - The authors present results of comparative morphological studies of changes in the liver after intoxication with alcohol-containing liquids in human and following subacute treatment of animals with ethyl and propyl alcohols, ethylene glycol and their mixtures. It was shown that poisoning caused by individual chemical substances and their mixtures induced significantly different changes in the liver of animals. The mixtures produced much more serious toxic lesions in the parenchymal tissue than individual spirits (including development of necrotization foci) and contributed to enhanced mortality of experimental animals. The morphological picture of the liver in human subjects poisoned by a mixture of alcohols resembled that after intoxication with carbon tetrachloride and was consistent with the changes in people who had died during episodes of mass poisoning with surrogate alcoholic beverages and alcohol-containing liquids. PMID- 20734785 TI - [Osteometric determination of ordinal localization, sex, and body length in man from skeletonized lumbar vertebrae]. AB - Dimensional characteristics of lumbar vertebrae (L1-L5) were obtained by examination of three osteologic collections containing a total of 304 male and 181 female vertebrae. The multimetric (14 parameters) discriminative analysis has demonstrated that the highest accuracy of ordinal localization based on the general diagnostic model (L1-L5) was obtained for L5 (93.76%) and the lowest one for L2 (56.45%). Correction of the results using several discrimination models improved the accuracy of classification to 76.65% (L1), 81.61% (L2), 79.82% (L3), and 81.99% (L4). Diagnosis of gender identity of isolated lumbar vertebrae by multimetric discriminative analysis proved to be possible in 87.7-88.8% of the cases; this figure amounted to 93.8% if the totality of these vertebrae was included in the analysis. The accuracy of body length measurements using multiple regression equations was estimated at +/- 6.22-6.45 cm for individual vertebrae and +/- 0.62 cm based on the complete set of them. In all these cases, sex and age of the subjects should be taken into consideration. It is concluded that the proposed methods can be used in forensic medical practice for the identification of skeletonized bone remains. PMID- 20734786 TI - [A new approach to the determination of glycogen concentration in various tissues and comments on the interpretation of its results]. AB - A simple specific method for the detection of glycogen concentration in various tissues without disintegration of its structure is described. The method includes staining of glycogen molecules with iodine. The results of determination do not depend on the presence of polysaccharides because they are not stained with iodine but release reducing sugars during hydrolysis. Glycogen content is calculated from the calibration curve. PMID- 20734787 TI - [The use of the deuterated internal standard for morphine quantitation for the purpose of doping control by gas chromatography with mass-selective detection]. AB - The objective of this study was to demonstrate the possibility to use deuterated compounds as internal standards for the quantitative analysis of morphine by gas chromatography with mass-selective detection for the purpose of doping control. The paper is focused on the problems associated with the use of deuterated morphine-D3 as the internal standard. Quantitative characteristics of the calibration dependence thus documented are presented along with uncertainty values obtained in the measurements with the use of deuterated morphine-D6. An approach to the assessment of method bias associated with the application of morphine-D6 as the deuterated internal standard is described. PMID- 20734788 TI - [Application of near-infrared spectroscopy for differential detection of neuroleptics, derivatives of benzamides]. AB - A method is proposed for the detection of neuroleptics including benzamide derivatives, such as amisulpride, sulpiride, and tiapride with the use of spectroscopy in the near infrared region. The method may be used for the purpose of forensic medical examination and chemico-toxicological studies. Specifically, it allows three characteristics of benzamide derivatives to be identified that make possible reliable discrimination between them. PMID- 20734789 TI - [Extraction of alpha-cypermethrin from aqueous methanol solutions]. AB - Alpha cypermethrin was extracted from aqueous methanol solutions using hydrophobic organic solvents. The efficiency of extraction was shown to depend on the chemical nature of the solvent, the water to methanol ratio, and saturation of the aqueous methanol layer with an electrolyte. Optimal extraction of alpha cypermethrin was achieved using toluene as the solvent under desalinization conditions. The extraction factor for the removal of the sought amount of alpha cypermethrin from the water-methanol solution (4:1) using various solvents was calculated. PMID- 20734790 TI - [Specific features of toxicological profile of gemcitabine, an antitumour agent from the group of anti-metabolites]. AB - Gemicitabine (2',2'-difluorodesoxycitidine) is a relatively new medicinal product from the group of anti-metabolites used as the first line therapy of pancreatic cancer, non-pulmonary cancer, and breast cancer. However, analysis of its toxicity spectrum revealed a large number of adverse events associated with the clinical application of this product. This fact is ascribed to the narrow range of therapeutic usages of this cytostatic preparation (from 25 mg/kg to 27 mg/kg). This paper is designed to summarize the available data on hematological, gastrointestinal, pulmonary, and cardiotoxicity of gemcitabine. They may be useful for the improvement of control over gemcitabine toxicity, correction of its dosage regime, and efficacious prevention of the most serious side effects. PMID- 20734791 TI - [Results of the five-year (2004-2008) experience with the management of forensic medical activities in the North-Western Federal Okrug (district) of the Russian Federation]. PMID- 20734792 TI - [A new approach to forensic medical typing of human mitochondrial DNA with the use of mass-spectrometric analysis of amplified fragments: PLEX-ID automated genetic analysis system]. AB - A new approach to typing human mitochondrial DNA (mtDNA) is described using multiplex PCR in combination with genetic analysis assisted by high performance mass-spectrometry based on an automated PLEX-ID ESI-TOF analyzer (Abbot Molecular, USA). The proposed test-system is designed for DNA analysis in a standard 96-well plate and allows to simultaneously treat up to 12 samples. All stages of the analysis are fully automated, from preparation and purification of amplicons to quality control and interpretation of final results. The in-built software makes possible comprehensive analysis of the data obtained including decoding of primary results; search for, comparison and registration of polymorphism profiles in relevant databases, both directly in the nucleotide composition format and indirectly in the form of nucleotide sequences. The entire process from sample preparation to final report takes less than 8 hours to be completed. It is concluded that the PLEX-ID analytical system may be used to resolve complex problems due to the possibility to combine gene typing and individualization of the biological sample in the framework of a single analytical process starting from the sampling procedure. PMID- 20734793 TI - [Forensic medical criteria for the assessment of causes of sudden death in young children]. PMID- 20734794 TI - [Carcinogenic aging]. AB - There are data that show that under the influence of chemical carcinogens of various classes (polycyclic aromatic hydrocarbons, nitroso compounds, aromatic amines), mutagens, ionizing radiation, extremely low frequency radio waves, constant illumination, tobacco smoking, the development premature hotmonal metabolic disturbances in the main homeostatic systems (nervous, endocrine, immune and energy) similar to these developed during the normal aging have a place. These disturbances facilitate the realization of promotion and progression stages ofcarcinogenesis. Geneticall modified animals (mutants, transgenic or knockout) open new opportunity for the analyses of the role of separate genes in the relationships between natural and accelerated by the exposure to environmental factors aging. The increase in tumor incidence usually observed in genetically modified mice with phenotypical features of premature or accelerated aging whereas in animals revealed the delayed aging the increase of tumor latensy and/or decrease of tumor incidence have observed. The treatment with geroprotectors of member of populations at risk of accelerated aging induced by environmental factors may serves as effective means of primary cancer prevention. PMID- 20734795 TI - [The age dynamics of spontaneous and induced in vitro chromosome aberrations in human lymphocytes under natural and radiation induced senescence]. AB - The frequency of translocations, detected by FISH in lymphocytes of control donors increased with increasing age as quadratic function. This process is elevated in persons exposed to radiation at low-doses. It means that the level of translocations could be used as an indicator of biological age. Moreover the frequency of translocations should be taken into account when biological reconstruction of absorbed dose is carried out. The frequency of dicentrics, detected by FISH and FPG methods increased with age in both groups compared and in equal rate, the linear model being fit the data best. The rate of age-increase for translocations is much higher than for dicentrics. Chromosomal radiosensitivity of lymphocytes in vitro tends to increase with age in control group and significantly decrease--in exposed one, that is low-dose radiation exposure changes the character of age dependence of cytogenetic radiosensitivity. PMID- 20734796 TI - [Reliability of electron-transport membranes and the role of oxygen anion radicals in aging: stochastic modulation of the genetic program]. AB - All biomolecular constructions and nanorecators are designed to perform preset functions. All of them operate with limited reliability, namely, for each and every device or bionanoreactor normal operation alternates with accidental malfunctions (failures). Timely preventive maintenance replacement (prophylaxis) of functional elements in cells and tissues, the so-called turnover, is the main line of assuring high system reliability of organism as a whole. There is a finite number of special groups of genes (reliability assuring structures, RAS) that perform supervisory functions over the preventive maintenance. In a hierarchic pluricellular organism, RAS are genetic regulatory networks of a special group of cells, like hypothalamic neurons in the suprachiasmatic nucleus of mammals. Of the primary importance is limited reliability of mitochondrial nanoreactors, since the random malfunctions of electron transport chains produce reactive anion-radicals of oxygen (superoxide radical, O2*(-)). With time, O2*(-) radicals initiate accumulation of irreparable damages in RAS. When these damages accumulate up to preset threshold level, a fatal decrease in reliability of RAS occurs. Thus, aging is the stochastic consequence of programmed deficiency in reliability of biomolecular constructions and nanoreactors including the genetically preset limit of the system reliability. This reliability approach provides the realistic explanation of the data on prolongation of life of experimental animals with antioxidants as well as the explanation of similar "hormetic" effects of ionizing radiation in low doses. PMID- 20734797 TI - [Investistigation of the role of heterogenety individual radiosensitivity in estimation of radiation indused ageing]. AB - The influence of heterogeneity in individual radiosensitivity on estimation of ageing using survival curve is considered. Quadratic deviation of the rate of ageing from the true value in estimated by imitation modeling techniques. The Gompertz model for spontaneous mortality and gamma-frailty model for heterogeneity are used. Simulation performed at different values of radiation effect and heterogeneity variance. It is shown that inclusion heterogeneity in the model is not efficient for large values of heterogeneity variance. For moderate values of heterogeneity variance model with heterogeneity produces more accurate results in comparison with the model without heterogeneity. PMID- 20734798 TI - [Telomere shortening is the main mechanism of natural and radiation aging]. AB - Adduced proofs of the telomere shortening are the main or even the sole mechanism of the natural and radiation aging. All apparent contradictions, primary, the absence of exact inverse correlation between residual telomere length and the donor age are explained within the frames of the telomere theory. We try to explain in what way telomere shortening might be the cause of aging and longevity restriction. We also show the inability of the oxidative theory to explain a number of indisputable facts easily explained by the telomere theory, such as unlimited growth of tumor sells or why a new-born child starts to age from zero level rather than the level reached by the cells of his parents at the moment of conception. We postulate that if oxidative damage was entirely absent, telomeres would, nevertheless, shorten with each mitotic cycle because such is the mechanism of DNA replication, and aging would be in progress, which we invariantly observe in the presence of any antioxidants. But if telomeres do not shorten, as happens in transformed cells because telomerase works there, aging does cease and the transformed cells show no senescence. We also observe it in spite of the damaging effect of reactive oxygen species which may be even more than in normal cells. PMID- 20734800 TI - [Incomplete membrane restoration and radiation ageing]. AB - An suggestion is put forward according to which the incomplete restoration of membranes in irradiated brain cells can self-perpetuate, down regulate their activity and accelerate ageing. PMID- 20734799 TI - [Comparative study of aging, UV treatment, and radiation on cataract formation]. AB - Four randomized groups of male mice F1 (C57Black/CBA) were investigated: a) UV irraidated (UV-A, 15 min daily during 9 months, dose 5.6 + 1.2 W/m2), b) gamma rays irradiated (2 Gy), single, c) influence for combination of UV- and gamma rays treatment, d) aging. The lens opacities were measured on 7th and 10th month. The expert method based on six grade scale was used for cataract measure. On 7th month the median of lens opacities were Aging group = 0; UV-irradiated group = 2.5; gamma-irradiated group = 4.75; gamma- and UV-irradiated group = 6.0. The difference between all groups was significant (p < 0.004, Kruskall-Wallis ANOVA test). The Conover post hock test has shown the significant difference for all comparison pairs (p < 0.002) with the exception of UV-irradiated group, gamma irradiated group, gamma- and UV-irradiated group. On 10th month the lens opacities were strongly increased: Aging group = 2.5; UV-irradiated group = 5.0; gamma-irradiated group = 6.5; gamma- and UV-irradiated group = 7.5 (median). The difference between groups was significant (p < 0.0001, Kruskall-Wallis ANOVA test). The Conover post hock test has shown the significant difference for all comparison pairs (p <0.003) with the exception ofthe UV-irradiated group and gamma-irradiated group. The formation of the specific lens opacities for any group was not found. Morphology and protein composition have been investigated on 10th month. The results of morphological changes study show destructive and degenerative impairments of capsule, epithelium cells and lens fibers. However, no specific changes related to some particular actions have been found. In addition, there were no specific changes of protein composition of both water soluble and water-insoluble fractions estimated with Differential Gel Electrophoresis technique. Obtained data mean that aging, UV-treatment, and gamma radiation causes the similar changes of lens. It was supposed that UV-treatment or/and gamma-radiation act as an aging factor on the lens. PMID- 20734801 TI - [Infringement of the seasonal rhythm of fluctuations of the oxidized and methylated guanine's contents in urine of mice after the irradiation]. AB - The lifetime research of the oxidized and methilated guanine's contents in urine of intact and radiated mice was carried out. For statistical processing of results we used the method of the trial periods. This method has been created by A.A. Konradov, but has not been published during a life of the author. It has allowed finding out oscillatory part of age-related dependences. For intact animals the most probable (p = 0.001) is the period of 7 months. The infringement of a seasonal rhythm of fluctuations of oxidized and methilated guanine's concentration in urine is marked for the radiated mice. It is specific feature of the radiation-accelerated ageing. PMID- 20734802 TI - [Non-canonical role of external factors in ageing occurrence]. AB - Environment makes essential impact on the longevity of bio-objects and the reliability of functioning of their organisms not only directly, but by means of inducing this or that mode of vital activity. Assumption is grounded, according to which rate of ageing depends on degree of a deviation of qualitative quantitative characteristics of the environment from the borders of certain evolutionary habitual standard ecological niche, which is peculiar to each species. The analysis of the collected data allows us to assume a reality of conditions at which zero rate of ageing is possible. PMID- 20734803 TI - [From Carrel to Hayflick and back or what we got from the 100 years of cytogerontological studies]. AB - The history of experimental-gerontological studies on cultured cells is reviewed. Comparative analysis of cytogerontological investigations and/or gerontological theories of Weismann, Carrel, Hayflick, and the paper author is carried out. It is emphasized that in XX century the theories' nature has changed abruptly many times. It is concluded that at the moment it is almost impossible to explain with the help of the cytogerontological studies' results how multicellular organisms age. The necessity of obligatory combination of experiments on cultured cells with fundamental gerontological investigations, including survival curve analysis for humans or experimental animals is supposed. PMID- 20734804 TI - [FOXO tanscription factor role in radiation adaptive response and hormisis in Drosophila melanogaster]. AB - Previously we put forward a hypothesis about the role of FOXO-dependent mechanisms of stress-response gene activation after irradiation in radiation hormesis (Moskalev, 2008). To testify this assumption we analyze the influence of gamma-irradiation on duration of larvae development and imago lifespan in Drosophila strains with different FOXO function activity. We revealed that in FOXO hypomorphic allele homozygote strains the hormesis and adaptive response (increasing of larvae stage duration and longevity) were absent, in contrast to B wild type strain Canton-S and FOXO-heterozygotes. PMID- 20734805 TI - [Mutant copies of mitochondrial DNA in tissues and plasma of X-rays exposed mice]. AB - With violations of the mitochondrial genome associated wide range of degenerative diseases, the development of tumor pathology, aging and the processes of cell death. We investigated the levels of mitochondrial DNA (mtDNA) with mutations and their total content in the tissues of the brain, and spleen of mice exposed to X rays at doses of 1-5 Gy, and depending on the post-radiation time (8-28 days). These same mice were analyzed for the level of mutant copies of the extra cellular mtDNA (ec-mtDNA) and its total content in blood plasma. Mutations were determined by means of CEL-I endonuclease (mismatch-specific enzyme) cleavage of heteroduplexes, obtained by hybridization of PCR amplicons of mtDNA (D-loop region) of irradiated and control mice. The changes of total amount of mtDNA (ND4 gene) copies vs. nuclear DNA (GAPDH gene) measured by real-time PCR method. The results showed that in the tissues of the brain, and of the spleen of irradiated mice (with a maximum at 8 days after exposure) the level of mutant mtDNA copies, with a subsequent decline to a 28-day post-radiation time dramatically increased. Was shown that mutagenesis of mtDNA in the brain and spleen tissues of irradiated mice, well as mutagenesis of nuclear genes, has a linear dependence on the dose X rays. In contrast, mutant nuclear genes, the majority of mutant mtDNA copies is eliminated from the tissues of the brain and of the spleen, while maintaining them at the same level of total content of mtDNA within 28 days after irradiation in mice. The results show that during this post-radiation time in the plasma of irradiated mice high levels of ec-mtDNA with mutations, with a maximum at the 14th day in the total circulating DNA maintained. These data suggest that the mutant copies of mtDNA eliminated from tissues cells of irradiated animals in the post-radiation period. Elevated levels of ec-mtDNA with mutations in the plasma can be considered as a potential marker for the assessment of radiation injury of organism. PMID- 20734806 TI - [The comet assay application in radiobiological investigations]. AB - The analysis of the literature data on application of the gel electrophoresis of individual cells ("comet assay") in radiobiological investigations was carried out. The descriptions of various variants of the method are presented; its alkaline version is in more detail considered. The works concerning to induction and DNA damage repair of single stranded and double stranded DNA breaks, DNA alkali labile sites, crosslinks, DNA bases damage, cellular radiosensitivity and revealing of apoptotic cells were analyzed. The application of the method at biomonitoring of DNA damage level in cells of the person and the animals exposed to genotoxic agents, including ionizing radiation is described. The analysis of the literary data testifies to perceptivity of development and further uses of this method in radiobiological researches. PMID- 20734807 TI - [The relationship between genotypes and frequencies of chromosome aberrations in human lymphocytes under irradiation in vivo and in vitro]. AB - The data on the variability of an elevated level of the frequencies of chromosome aberrations for a group of liquidators of the Chernobyl Nuclear Station accident depending on genotypes by candidate loci are presented. The genotyping was carried out by sites, which previously showed the associations with the cytogenetic variability in control experiments. It was shown that, for a group of liquidators heterozygote by site SOD2 C47T, the control level of the frequency of chromosome aberrations is not exceeded significantly. At the tendency level, the frequency of aberrations for liquidators was reduced for double homozygotes by deletions of genes GSTM1-GSTT1 and for homozygotes by the minor allele of site CYP1A1 T606G that is in an accordance with the results of experiments with the control sampling. The elevated level of chromosome aberrations for liquidators, as a whole, is observed for genotypes, which are characteristic of an elevated level of spontaneous aberrations, and it does not completely correspond to genotypes with the elevated radiosensitivity of chromosomes. PMID- 20734808 TI - [Some radiobiological effects in higher plants growing at the territory of the East Ural radioactive trace]. AB - The spontaneous level of cytogenetic damage in three plant species (Achyrophorus maculatus (Scop.) L., Plantago lanceolata L., Plantago media L.) growing at the territory of East Ural radioactive trace was studied. The radiation resistance of plants from radioactive and control nonpolluted sites was determined. The effects of additional fractionated irradiation by different doses and the role of antioxidant systems in the formation of radioprotector effect were examined. It was shown that the level of mutation process in the plant populations growing at the radiation polluted sites is increased compared to the control populations from the pure territory. The additional acute gamma-irradiation of seeds collected from the polluted and pure territories showed the improved radiation resistance of the plants from the polluted territory. In the control population of A. maculatus in the versions with a one-hour interval between fractions, the radiation effect follows the additivity principle; in the same time, at a one-day interval between fractions, a highly significant radioprotective effect manifested most clearly in the experimental population is induced. For higher plants, the enhanced effectiveness of the functioning of antioxidant systems in plants growing at radiation polluted territories was first shown. Thus, the radioprotector mechanisms of low-dose chronic and preliminary irradiation are similar and one of these mechanisms is the activation of antioxidant systems in plants growing under conditions of chronic low-intensity irradiation for long periods of time. PMID- 20734809 TI - [What is the damage gamma-irradiation on solutions-cryoconservants at 77 K?]. AB - Originating under the gamma-radiation action at 77 K on glassy phosphate solutions (6 mol/l) of glycerol and glycero-1-phosphate, H-atoms have motility by virtue of tunneling effect and react with the stabilized radicals of a matrix (OH /H2O+) and with solutes: at storage them in liquid nitrogen the radicals of separation H from carbon atoms C1 and C2 will be derived. According to the assessment maximal radiation "damage" is plotted to the investigated system for year, approximately 1 mol/l. PMID- 20734810 TI - [Estimation of UV light dose concomitant to ionizing irradiation]. AB - A simple approach to the estimation of UV light dose produced by Cerenkov emission and concomitant irradiation of biological objects with ionizing radiation was suggested. The approach was applied to determine the dependencies of UV light dose (equivalent to 254 nm) accompanied 100 Gy of ionizing radiation on the energy of sparsely ionizing radiation and on the volume of the exposed Escherichia coli cells suspension. It was revealed that the relative excitation contribution to the total lethal effect and the value of the UV dose was greatly increased with an increase in the energy of ionizing radiation and the volume of irradiated suspensions. It is concluded that these observations are in agreement with the supposition that Cerenkov emission is responsible for the production of UV light damage and the phenomenon of photoreacrivation observed after ionizing exposure of bacterial and yeast cells hypersensitive to UV light. A possible synergistic interaction of the damages produced by ionizations and excitations as well as a probable participation of UV component of ionizing radiation in the mechanism of radiation hormesis and adaptive response observed after ionizing radiation exposure is discussed. PMID- 20734811 TI - Condition stabilization for Aspergillus niger FCBP-198 and its hyperactive mutants to yield high titres of alpha-amylase. AB - A number of substrates were tested for the cultivation of microorganisms to produce a host of enzymes. The effect of different substrates (wheat and rice straw, sugar cane waste, wood waste), incubation temperatures (20-40 degrees C), initial pH levels (3.5-9.0), incubation periods (0-72 hours) and nitrogen sources (ammonium sulfate, urea, peptone, yeast extract, sodium nitrate) on growth and alpha-amylase activity was studied for the native and mutant strains. Maximum enzyme activity was observed at 1.5% wheat straw for Aspergillus niger FCBP-198 and An-Ch-4.7 and at 2% wheat straw for An-UV-5.6, with sodium nitrate as a principle nitrogen source. The optimum temperature for maximum enzyme activity was 30 degrees C for the parental strain, while An-UV-5.6 and An-Ch-4.7 thrived well at 32.5 degrees C. The best conditions of pH and incubation duration were 4.5 and 48 hours, respectively, for all the strains. Mass production under preoptimized growth conditions demonstrated the suitability of wheat straw for swift mycelial colonization and viability. PMID- 20734812 TI - Pectinase production by a Brazilian thermophilic fungus Thermomucor indicae seudaticae N31 in solid-state and submerged fermentation. AB - Thermophilic organisms produce thermostable enzymes, which have a number of applications, justifying the interest in the isolation of new thermophilic strains and study of their enzymes. Thirty-four thermophilic and thermotolerant fungal strains were isolated from soil, organic compost, and an industrial waste pile based on their ability to grow at 45 degrees C and in a liquid medium containing pectin as the only carbon source. Among these fungi, 50% were identified at the genus level as Thermomyces, Aspergillus, Monascus, Chaetomium, Neosartoria, Scopulariopsis, and Thermomucor. All isolated strains produced pectinase during solid-state fermentation (SSF). The highest polygalacturonase (PG) activity was obtained in the culture medium of thermophilic strain N31 identified as Thermomucor indicae-seudaticae. Under SSF conditions on media containing a mixture of wheat bran and orange bagasse (1:1) at 70% of initial moisture, this fungus produced the maximum of 120 U/ml of exo-PG, while in submerged fermentation (SmF) it produced 13.6 U/ml. The crude PG from SmF was more thermostable than that from SSF and exhibited higher stability in acidic pH. PMID- 20734813 TI - Genotyping of Aeromonas hydrophila by box elements. AB - PCR-based DNA fingerprinting techniques were evaluated to genotype eight diseased, particularly normal and environmental isolates of Aeromonas hydrophila. PCR-based fingerprinting method has an advantage of having repetitive sequence also called Box elements that are interspersed throughout the genome in diverse bacterial species. The BOX-PCR fingerprinting technique was evaluated for the discrimination of different isolates of A. hydrophila. All the studied isolates have shown major banding patterns ranged from 500-3000 bp. These finding could be advantageous to investigate the strain level specific fingerprints of A. hydrophila as potential genotypic markers. PMID- 20734814 TI - [Bioethical aspects of experiments on the animals]. AB - The principles of humane attitude toward laboratory animals, the main rules of defense and application of vertebral animals in scientific investigations, which are coordinated with European convention content, were presented. Recommendations for organization and activities of bioethics committees and commissions, which conduct the expert estimation of scientific investigations, using laboratory animals, were presented. PMID- 20734815 TI - [New directions of hypertermic surgery in experiment]. AB - Mechanisms of influence of thermal stream towards living biological tissues were studied. Bacteriological investigations of infected, purulent wounds before and after their thermostream processing were conducted. There was substantiated the possibility of the method usage for sanation of subfascial massively infected purulent wounds. PMID- 20734816 TI - [The state and perspectives of using hydrostream technologies in surgical practice]. AB - The work is devoted to experimental investigation and clinical application of domestic apparatus for hydrostream dissection of tissues, the schemes and principle of its working are adduced. The methods of the operations performance in experimental animals are discussed. The processes, occurring in tissues under a liquid stream action in various terms after the operation were studied. The expediency of application in abdominal surgery of a liquid stream under high pressure was noted. The results of clinical exploitation of the apparatus proposed are adduced. PMID- 20734817 TI - [Cryosurgery in diffuse hepatic diseases]. AB - Comparative studying, using histological and biomicroscopic methods, of the dosed cryohepatodestruction (CHD), periarterial cryodenervation of hepatic artery (CDHA) and their concomitant application influence on the dynamics of hepatic restoration processes in experimental cirrhosis was performed. The investigations were done on 215 male rats owing body mass 200-280 g in a not changed and pathologically changed liver. There was shown, that CDHA promotes changes in hepatic tissue microhemocirculation, as well as the enhancement of the sinusoidal vessels diameter and relative square of vascular bed. CHD stimulates the reparative processes course in a pathologically changed organ. There was established, that while simultaneous application of two cryosurgical methods, the velocity and grade of restoration processes in cirrhotically-changed liver are enhanced in comparison with such indices changes while separate usage of these two methods. PMID- 20734818 TI - [Application of thermostream method in the surgical treatment of infectious pancreatic diseases]. AB - Application of thermostream method secures a safe sterilization in infected pancreatic affection. It was confirmed by the results of 9 operations, performed on pigs with follow-up to 270 days. Thermal influence toward infected pancreatic tissue was delivered using hot air stream during 20 sec for 1 cm2 area in temperature 140 degrees C. Interstitial oedema is local after thermostream processing of pancreas, the reversible structural-functional changes were revealed in the organ tissues, localized aside from the influence zone. According to bacteriological investigations data obtained, microflora was absent. Successful clinical trial of thermostream method in patients with infected pancreatic affection in an acute necrotic pancreatitis permits to recommend its wide application in surgical practice. PMID- 20734819 TI - [Experiment study of multimicrovacuolar absorbing collagenic system and its role in trophic processes of nonsynovial part of the tendons]. AB - The arterial inflow disorder and occurrence of an acute and subsequent chronic ischemia constitutes frequent complication of a hand and fingers trauma. One of the consequences of ischemic damage of tissues is formation of a flexor contracture of fingers, involving the flexors tendons. In extrasheath zone the blood supply is secured by paratendon--a connective tissue, taking part in the tendons sliding. According to data, obtained during morphological investigation of paratendon in laboratory animals, there was established its principal similarity with multimicrovacuolar collagenic absorbing system of a man. She constitutes a spatial porous structure, packed with cellular elements and vessels. While simulation in experimental conditions of the blood flow disorders, which in physiological environment is secured by paratendon, alike in disorder of the bone-tendon and muscle-tendon pathways of blood supply, there were revealed the coarse changes in the tendon structure and pronounced adhesion of tendons with loss of their sliding capacity, what had permitted to consider the paratendon blood circulation a dominating one. PMID- 20734820 TI - [Ultrastructural changes of vascular endothelium in patients with chronic ischemia of the extremities after conduction of multipotent stromal cells from adipose tissue transplantation]. AB - Taking into account the impossibility of performance in some situations of reconstructive operative interventions on arteries, it is necessary to look for new methods of indirect revascularization for the extremities ischemia. Adipose tissue constitutes an accessible and sufficient source of multipotent stromal cells (MSC). Experimental investigations were made in a frame of preclinical trial on laboratory animals with the extremity ischemia simulation, and there was proved the essential stimulation of angiogenesis processes after transplantation performance of stromal-vascular fraction of adipose tissue. The work objective was to study the influence of own adipose tissue MSC transplantation on vascular endothelium changes in patients, suffering chronic ischemia of the extremities. Using electron microscopy method there was proved on microstructural level, that in clinical environment the patients, suffering chronic ischemia of the extremities of various etiology, gain undoubted effect of MSC autotransplantation performed with the objective to stimulate the processes of angiogenesis in the ischemic affection region. PMID- 20734821 TI - [Efficacy of sulfargin in the local treatment of patients with burns]. AB - Efficacy of preparation Sulfargin application in injured persons, suffering burns, was studied. There was established, that application of preparation Sulfargin in local treatment of burns promotes reduction of inflammatory reaction severity in the affection zone and support of functional capacities of phagocytic cells on optimal level. PMID- 20734822 TI - [Structure of the sweat glands in essential axillar hyperhidrosis and after its surgical treatment]. AB - The structure of sweat glands in their skin portions in axillar regions was investigated in essential hyperhydrosis and after its treatment using mechanical curettage, performed solely or in combination with ultrasonic destruction. There was shown, that hyperhydrosis is accompanied by the sweat glands canaliculus secretory portion enlargement and their diameter as well. Additionally, the secretory epithelium area is practically enhanced twice as in a control and its thickness - in 1.5 times. Curettage is accompanied with removal, along with hypoderma, of majority of the sweat glands terminal portions and, due to evolvement of a dense connective tissue regenerate, prophylaxes their regeneration with a staged hypotrophy of residual secretory portions. The combined application of curettage with ultrasonic destruction, during treatment of hyperhydrosis, secures more prominent, alike while only curettage performance, reduction of terminal parts of sweat glands. It takes place on background of the inflammatory reaction reduction and the connective tissue subtle regenerate formation. Surgical methods of treatment, alike botulotoxin injections, secures more pronounced and persistent reduction of sweat glands in hyperhydrosis. PMID- 20734823 TI - [Endoscopic removal of the gastric bandage migrated into the gastric cavity]. PMID- 20734824 TI - [Pathological anatomy in A/H1N1 influenza]. AB - Forty autopsy cases died from A/H1N1 influenza in Moscow, the Moscow Region, and Chita were analyzed. Major changes were found to develop in the trachea and lung. The lung showed the pattern of exudative and proliferative stages of diffuse alveolar lesion. In addition, the signs of viremia-associated infectious-toxic shock, as suggested by pronounced changes in the brain, kidneys, liver, spleen, adrenals, and lymph nodes were revealed. Bacterial bronchopneumonia was detected only in 20% of cases. PMID- 20734825 TI - [Ultrastructural characteristics of hepatocellular carcinoma]. AB - The results of a complex (histological and electron microscopic) study of surgical specimens from 22 patients (15 men and 7 women aged 17 to 72 years) are presented. The histological study diagnosed low-, moderate, and high-grade hepatocellular carcinoma in 5, 12, 5 patients, respectively. The electron microscopic study established that low-grade cancer cells preserved to a greater extent the principal specific ultrastructural organization that was characteristic of normal hepatocytes. The moderate-grade type was presented as different ratio of tumor cells of various grades. At the same time, the degree of ultrastructural differentiation of tumor cells did not depend on the histological (trabecular, solid) structure of the tumor. The high-grade type was characterized by the signs of significant cell structural and functional rearrangement; changes in the number, sizes, and shape of intracellular masses (a nucleus, mitochondria, endoplasmic network, lysosomes). Moreover, the destruction of the intracellular matrix and vascular basal membrane, reduced contacts between the tumor cells with the latter being attached to the thinned vascular wall underlie local infestation and neoplastic metastasis. PMID- 20734826 TI - [Extracranial meningioma: morphological and histogenetical aspects and relations with perineurioma]. AB - The clinicomorphological, immunohistochemical, and ultrastructural characteristics of 11 cases of extracranial meningioma versus 79 soft tissue perineuriomas were studied. There were significant similarities (cell morphology, immunoprofile, ultrastructural features of perineurial differentiation) of both entities. Considering the point of view that arachnoid and perineurial cells are anatomically, embryologically, and functionally related, it is most possible that extracranial meningiomas may be derived from perineurial cells (or their progenitor cell) rather than from displaced arachnoid cells. PMID- 20734827 TI - [Association of the degree of differentiation and the mitotic activity of intracranial meningiomas with age and gender]. AB - Intensive work is under way to detect the direct and indirect signs that can be used to predict the behavior of a tumor process with greater or lesser assurance. The authors have studied different aspects of the clinical course and recurrence of intracranial meningiomas, investigated the morphological features of their individual forms, their mitotic activity and, on this basis, considered the degree of differentiation and prediction of a recurrence. The findings should be the basis for searching for parallels between morphological, demographic, and clinical characteristics. Such a comprehensive study and search for mutually determining links between the findings will shed light upon a diversity of problems that are of theoretical and practical value. PMID- 20734828 TI - [Endothelial cell changes preceding the formation of intimal erosions in coronary arteries and aorta in atherosclerosis in humans]. AB - The cytological technique was used to study autopsy specimens from 39 patients aged 35-85 years. Above the atherosclerotic strips and plaques there were multiple destruction microfoci (MDMs) of endothelial cells (EC), which were divided into three types. EC MDMs were detected in the aortic intima in 79.5% of the patients. A total of 107 MDM of different types were found in 63.2% of cases. A total of 53 MDMs were identified. The detection rate for EC MDMs in the aorta and coronary arteries in acute and recurrent myocardial infarction was 1.3 and 2 times greater than that in large-focal and diffuse small-focal cardiosclerosis. EC microfocal destruction is a sign of progressive atherosclerosis and may be a critical step in the transition from stable endothelized to eroded plaque and thrombosis. PMID- 20734829 TI - [Thyroid morphofunctional changes in acute experimental endotoxicosis in rats]. AB - The aim of the study was to investigate morphofunctional changes in the thyroid and its hormonal status of Wistar rats with non-thyroid illnesses caused by acute endotoxicosis. The latter was simulated, by administering the sublethal dose of lipopolysaccharide. Thyroid morphological and morphometric studies on disease days 1 and 7 established that the earliest sign of non-thyroid illnesses was the dissociation of synthetic processes and thyroglobulin release into the lumen of a follicle and its resorption, i.e. desynchronization of the phases of a cell secretory cycle and dissociation of the directionality of morphodynamic processes in the central and peripheral zones of thyroid lobes. Recovery of the unidirectionality of these processes may be interpreted as a sign that suggests the regression of non-thyroid illnesses. PMID- 20734830 TI - [Morphology of pancreatic serous cystadenomas]. AB - The paper presents the results of a morphological study of 20 pancreatic serous cystadenomas, including 14 microcystic and 6 oligocystic ones (18 women and 2 men aged 32-72 years). Histochemical and ultrastructural studies have shown that epithelial cells contain glycogen granules in the cytoplasm. An immunohistochemical study has indicated a positive reaction of CA 19-9, low molecular weight cytokeratins (7, 8, 18, 19), and epithelial membrane antigen. PMID- 20734831 TI - [Interdigitating dendritic cell sarcoma]. AB - The paper presents a case of the extremely rare tumor--interdigitary dendritic cell sarcoma in a 47-year-old woman with buccal soft tissue lesion that has been immunohistochemically and electron microscopically verified. PMID- 20734832 TI - [Logistic support and means for reducing the current costs in a pathology laboratory]. AB - The basic reagents that are most commonly used for histological tissue specimen treatment have undergone technical-and-economic assessment in terms of cost optimization. The presented data may be useful for experts to make decision on the current logistical support of pathology laboratories. PMID- 20734834 TI - [Pathologists--Nobel Prize laureates]. PMID- 20734835 TI - [Boris Semenovich Doinikov--a distinguished Russian neuromorphologist and neurologist (on his 130th birthday)]. PMID- 20734833 TI - [Modification of a histochemical technique for detection of nucleolar organizer regions in histological specimens]. AB - The authors modified the method for silver staining of argyrophilic nucleolar organizer regions (AgNORs). This modification eliminates defects of an original technique. The method accelerates the staining and prevents fallout of deposits. The modification is recommended for wide application. PMID- 20734836 TI - [Morphological and biochemical criteria for cell death]. AB - The state-of-the-art of classifications of and criteria for cell death in the light of the 2009 recommendations of the Nomenclature Committee on Cell Death is presented as a lecture. Motivation is given for the necessity of using the unified criteria in the description of cell death and more than one study in its verification. The major structural and biochemical signs of four typical types of cell death--apoptosis, autophagia, keratinization, and necrosis are compared. Data are given on the major atypical forms of cell death--mitotic catastrophe, anoikis, exitotoxicity, Wallerian degeneration, paraptosis, pyroptosis, pyronecrosis, and entosis. PMID- 20734837 TI - [Role of vascular disorders in the pathogenesis of ulcerative colitis and its complications]. AB - Mucous membrane circulatory disorders in ulcerative colitis (UC) are accompanied by significant capillary plethora with endothelial nuclear swelling in the capillaries and minor veins. Some cases show the development of secondary endophlebitis with thrombi occurring in individual veins. Occasionally, there is deep vein thrombosis in the leg with pulmonary embolism. Portal vein thromboembolism is very rarely observed during autopsy. The development of extensive deep mucous membrane ulcers gives rise to destruction of the vessels of the submucous plexis and its recurrent branchlets feeding the circular muscle layer. Impaired microcirculation is confirmed by the presence of myocytic dystrophic or necrotic changes. There are large transmural ischemic necroses in the area of toxic dilatation. Connective tissue foci develop in chronic UC at the site of ischemic necroses. Long longitudinal ulcers seen in nonspecific UC and Crohn's disease are likely to be ischemic, the course of which is long contraction of tenia with vein compression. PMID- 20734838 TI - [Development of the theory of cardiac innervation during ontogenesis in health and disease]. AB - The paper describes the mediatory stage of prenatal development of cardiac innervation and the phenomenon of early involution of sympathetic nerve plexuses in postnatality, which has been established while analyzing early autopsies by neurohistochemical studies. lmmunocytochemical, luminescence, and ultrastructural techniques have defined changes in the stages of their formation and development of the above early involution. Complex (neurohistochemical and electrophysiological) studies quantified groups of age-related cardiac innervation changes in health. Cardiac rhythm variability was electrophysiologically studied in 43 subjects aged 18-71 years. Cardiac desympathization is shown to develop after 40 years of age. Age-related changes in cardiac regulatory mechanisms should be taken into account on studying visceral systems in coronary heart disease, atherosclerosis, and sudden cardiac death, and during cardiac transplantation. Immunohistochemical study has revealed an increase in nitric oxide expression in the human cardiac nervous apparatus. PMID- 20734839 TI - [Blood plasma zinc and copper concentrations in patients with purulent soft tissue wounds]. AB - The paper considers postoperative imbalance of the trace elements zinc and copper in 40 surgical patients aged 47.2 +/- 17.1 years who have extensive purulent soft tissue wounds (PSTW). In 90% of the patients with PSTW, plasma Zn++ levels were much lower than the reference values (the normal value was 11.1-19.5 micromol/l) while in 47.5%, serum Zn++ was in the range of less than 7 micromol/l, which is a poor prognostic factor. There was a negative correlation between the level of Zn++ and that of C-reactive protein (CRP) and a positive correlation between the former and the magnitude of a reduction in transferrin (TF) as a marker of protein-energy malnutrition. Plasma Cu/Zn ratio is shown to be of very clinical importance. The higher this ratio (normal ratio 0.9-1.13) is, the more severe the general condition of patients with PSTW, the higher CRP values (above 120 mg/l; normal value 0-6 mg/l), and the lower TF levels are. In patients with PSTW, zinc level and Cu/Zn ratio may act as an independent predictor of a grave condition during a systemic inflammatory reaction. PMID- 20734840 TI - [Nonfermentative gram-negative bacteria: isolation rates and antibiotic sensitivity]. AB - The isolation rates of nonfermentative gram-negative bacteria (NFGNB) are analyzed in the inpatients treated at the B. V. Petrovsky Russian Surgery Research Center in 2005-2009 and antibiotic resistance trends in nosocomial strains of NFGNB are traced in the above period. The study of the etiological structure of nosocomial infections has shown that the past 2 years (2008 and 2009) were marked by a clear tendency for the preponderance of gram-positive coccal pathogens (46.8 and 53.9%) with a considerable (1.5-2-fold) reduction in the proportion of representatives of enterobacteria (31.5 and 24.5%) and NFGB (13.4 and 11.3%), but with an increase in the proportion of fungi up to 7.1 and 8.6%, respectively. Among the NFGNBs, P. aeruginosa remains ohe of the most common pathogens for nosocomial infections although its portion in the number of all etiologically significant microorganisms was substantially reduced (from 13% in 2005 to 4.6% in 2009). It continues to remain one of the most common causative agents for infections of the urinary tract (e.g., after renal transplantation) and upper and lower respiratory tract (e.g. nosocomial pneumonia) and for those developing after surgical interventions (postoperative wound suppuration discharged along the drainages, from a T-sized tube, etc.). Among the NFGNBs, Acinetobacter spp. was the second frequently isolated pathogen, the isolation rate for which also decreased from 7.9% in 2005 to 2.6% in 2009. Polymyxin B and carbapenems (imipenem, meropenem, and doripenem) showed the highest activity against the vast majority of the test strains; however, there was an absolutely clear declining trend in the proportion of carbapenem-sensitive strains among virtually all the NFGNBs under study. According to the proportion of imipenem-, meropenem-, and doripenem-sensitive nosocomial P. aeroginosa strains (66.7, 46.6, and 44.7%, respectively), doripenem had the least activity. Acinetobacter spp. strains sensitive to these drugs showed the same trend (85.1, 51.2, and 39.2%, respectively). Meropenem and doripenem were equally active against B. cepacia strains, each demonstrated 50% sensitivity. As compared with meropenem, doripenem had a preferential activity against only O. anthropi (75 and 57.1% sensitivity, respectively). All the three carbapenems were inactive against S. maltophilia. PMID- 20734841 TI - [Paradoxical dynamics in the values of bispectral index for bilateral registration in a patient during parastem tumor removal (a clinical case)]. AB - The paper describes an unusual clinical case. During a neurosurgical operation (removal of parastem tumor (neuroma) on the right side), bilateral registration of the bispectal index (BSI) in order to monitor a hypnotic component of anesthesia showed that the tumor removal stage was marked by a paradoxical reaction of the BSI as an increase in its values up to 70-80% (corresponds to the patient's emergence) on the right, ipsilaterally, with the preserved low BSI values on the left--30-40%. Possible explanations of the observed are considered. PMID- 20734843 TI - [Pathomorphology of the lung in severe influenza A/H1N1]. AB - Thirty-five autopsy cases of influenza A/HIN1 in Moscow were analyzed. Primary pathological changes were found in the trachea and lung. The lung showed a pattern of the exudative and proliferative stages of diffuse alveolar damage. In addition, there were signs of infectious-toxic shock associated with viremia, as suggested by pronounced changes in the brain, kidneys, liver, spleen, adrenals, and lymph nodes. Bacterial bronchopneumonia was detected in only 20% of cases. PMID- 20734842 TI - [Experience in treating severe viral respiratory infection caused by influenza A (H1N1)]. AB - The authors present their experience in treating 142 patients with severe viral respiratory infection caused by influenza A (H1N1), describe its clinical picture, and identify major syndromes observed in the treatment of these patients at an intensive care unit. A rapid development of acute respiratory distress syndrome, significant hypoxemia and hypercapnia with the low efficiency of various therapeutic measures and hence progressive organ dysfunction determine the essence of the severe course of the disease. Uniform guidelines for intensive care in this patient population are presented. PMID- 20734844 TI - [Prevention and treatment of postoperative pain syndrome in extensive thoracoabdominal oncological surgery]. AB - A procedure has been developed and tested to prevent and treat postoperative pain syndrome during extensive thoracoabdominal surgery for esophageal cancer. The procedure is based on the preventive (12 hours before anesthesia and surgery) application of Durogesic (fentanyl transdermal therapeutic system (TTS)) at an opioid release rate of 50 microg/h for 72 hours. By the end of surgery and anesthesia when intravenous injection of fentanyl is stopped, analgesia continues to be maintdined due to its therapeutic dose coming from TTS. This prevents the development of acute opioid tolerance, hyperalgesia, and destabilization state in the early postanesthetic period and creates the basis for continuous multimodal postoperative analgesia in combination with nonopioid components (lornoxicam, perfalgan) and with none or minimal need for the injectable opioid. This allows an operated patient to have a comfort and stable state. A further investigation on the comparative assessment of the developed procedure with other variants of perioperative systemic and combined anesthesia-analgesia is to be conducted. PMID- 20734845 TI - [Difficult tracheal intubation: comparative assessment of the value of prognostic indices in using Macintosh and Truview laryngoscopes]. AB - The paper describes the experience in using three predictive criteria, such as Mallampati test, Patila test, and ULBT test, to evaluate tracheal intubation and compares their predictive validity. The experience in applying Macintosh and Truview laryngoscopes to patients with predicted difficult tracheal intubation (DTI) is also depicted. A combination of three above predictive procedures is a reliable predictor of DTI (r = 0.5; p < 0.05). Therefore their combination may be recommended for clinical use to predict DTI. No significant correlation was obtained between the other criteria of DTI and the difficulties during intubation at the first attempt (p > 0.05). There was no statistical significant correlation between the used type of a laryngoscope and the rate of effective/ineffective intubations at the first attempt (r = 0.34; p > 0.05). PMID- 20734846 TI - [Hemodynamic efficacy of modified gelatin in patients with acute blood loss and sepsis]. AB - The paper presents the results of a clinical trial using the new modified gelatin based drug hemofusin to correct dyshidria in patients with blood loss and sepsis. Based on the findings, the authors provide evidence for the high clinical efficacy of this drug and the expediency of its incorporation into a complex of infusion therapy in this patient contingent. PMID- 20734847 TI - [Effect of hyperosmolar solutions on partial pressure of oxygen in arterial blood]. AB - The study was undertaken to define the effect of hyperosmolar solutions on arterial blood oxygen levels. Analysis of arterial blood oxygenation after hyperosmolar solution infusions revealed a drop in partial pressure of oxygen (132.14 +/- 70.36, 120.0 +/- 66.48, and 119.24 +/- 70.10 mm Hg). At the same time there was a reduction in the extravascular lung water index (p < 0.05) as compared with the baseline values (7.93 +/- 2.17, 7.31 +/- 1.7), and Z62 +/- 1.99 ml/kg), respectively. This effect is particularly marked in a group of patients in whom the arterial blood content of oxygen is in the lower normal range. To evaluate and eliminate the above effect in reducing the arterial blood level, it is necessary to estimate respiratory indices during hyperosmolar solution infusion. PMID- 20734848 TI - [Inhalation anesthesia: view of the problem]. PMID- 20734849 TI - [Anesthesia during diagnostic endoscopic interventions in the outpatient setting]. AB - The review of the literature is devoted to the urgent problem of today- anesthetic maintenance of diagnostic endoscopic studies. The authors of the review have attempted to systematize the results of numerous publications to provide a deeper insight into the existing problems and perspectives in this field of anesthesiology, which can facilitate an anesthesiologist in his/her decision on anesthesia to be performed in diagnostic endoscopy. PMID- 20734850 TI - [The specific features of anesthesia in female patients with nervous system diseases--are neuraxial anesthesia methods safe?]. PMID- 20734851 TI - [Medical and social importance of oncologic morbidity and mortality in able bodied residents of technogenic peripheral regions]. AB - Using comparative analysis of levels, structure and dynamics of oncologic morbidity over 1992-2004, the author estimated medical, social and economic damage caused by oncologic mortality in Navoi region of Uzbekistan Republic. Findings are that total loss of man-years, connected with oncologic mortality, in Navoi region equalled to 3700 man-years in 2004. Average number of years lost by one died with malignancy equals 14.1 years in males, at able-bodied age--11.6 years, in females--18.3 and 11.8 years respectively. Results show that economic damage due to malignancies is formed from the oncologic mortality, the transitory disablement and the disability due to malignancies in working population, as well as from expenses of medical care for oncologic patients. PMID- 20734852 TI - [Contemporary features of occupational morbidity formation in major machinery enterprise]. AB - The author studied occupational morbidity among workers exposed to occupational hazards at major machinery enterprise in Bashkortostan Republic since 1997 to 2006, in reference to occupation, sex, age, length of service, type and conditions of work. The article covers hygienic evaluation of work conditions and their influence on occupational morbidity formation. PMID- 20734853 TI - [Occupational and non-occupational factors influencing health state of small and medium business workers]. AB - Complex study of work conditions and health parameters of workers engaged into small and medium business proved that preserved and better health of these workers, prevention of occupational and occupationally mediated diseases necessitate federal and regional complex system of measures including legal basis, database on work conditions and their influence on small and medium business workers' health, occupational medicine training for employers and employees, more active involvement of medical institutioins into screening for occupational diseases. PMID- 20734855 TI - [Work and health of comprehensive school teachers nowadays]. AB - The authors analyzed occupaitional and non-occupational psycho-social factors for comprehensive school teachers, evaluated their health state according to self estimation and to thorough medical examinations conducted in prophylactic examinations. Findings are that the major working hazard for the teachers is work intensity: about 80% of the teachers consider the work physically exhausting and nearly 90% assume the work exhausting morally. High prevalence of general non infectious diseases and health state complaints necessitates regular periodic medical examinations for teachers. PMID- 20734856 TI - [Intensity of industrial load and work intensity as risk factors for internal affairs officers]. AB - The study covered Bashkortostan Republic Internal Ministry staffers including special mission unit, criminal police, road police, minors crime unit, district police officers. Intellectual load assessment assigned work of the examinees to 3.2 class of work conditions, as the work is connected with time and information deficit, with increased responsibility for outcome. According to emotional load parameters including degree of responsibility for the activities outcome and importance of mistakes, risk for life, responsibility for safety of others and number of conflicts caused by professional activities, the work should be assigned to hazardous and dangerous category. PMID- 20734854 TI - [Criteria of ecologic safety for serum levels of heavy metals in humans]. AB - To evaluate ecologically allowable level of serum metals content in humans for making regional background normal level, the number of heavy metal ions should be determined in healthy human serum and simultaneously homeostasis parameters (hemolysis, biochemistry, immunologic) should be measured--clinically normal limits of these parameters are responsible for safe levels of of the heavy metals in human body. The suggested levels of metals in healthy human serum could serve as clinical MACs. PMID- 20734857 TI - [Occupational stress in young military officers]. AB - Occupational stress was studied in 220 police officers through their self evaluation. The most stressful factors of the examinees' activities were identified. Liability to stress appeared to differ in some factors and depend on the age. The data obtained should be considered in the activities organization and in rehabilitation and prophylactic measures aimed to avoid negative behavioral aspects in police officers and to prevent somatic diseases. PMID- 20734858 TI - [Rehabilitation tactics for able-bodied patients with distant effects of thoracic spinal injury due to occupational factors]. AB - The author analyzed efficiency of complex approach to rehabilitation for patients with complicated occupational injuries of thoracic spine. Practical application of the suggested tactics in 87 able-bodied patients of municipal multifield hospital significantly improved results of rehabilitation. PMID- 20734859 TI - [Using music in work therapy complex in able-bodied patients with spinal injury]. AB - The authors analyzed results of using music in work therapy rehabilitation complex in able-bodied patients with spinal injury. Efficiency of the therapy was demonstrated. Findings are that the patients demonstrate positive change in views, interests, desires, attitude to the personal condition and surroundings, tendency to overcome the disease, to realize compensatory resources of the body, more motivation to work--that serves as a good basis for further work rehabilitation of the patients. PMID- 20734860 TI - [Discriminant function analysis in the assessment of laboratory test data in the correction of traditional therapy for mild icteric form of viral hepatitis B in children with food allergy]. AB - The purpose of this investigation was to define the efficiency of inclusion of antihistamines (suprastin or tavegil), enzyme drugs (pancreatin or mesim forte) and their combinations into therapy for a mild icteric form of acute viral hepatitis B (VHB) in children with food allergy (FA). Among the examinees, there were 61 children with FA who had experienced a mild icteric form of VHB and who received traditional therapy at the age of 3-14 years. Of them, 36 children were additionally given antihistamines (n = 7), enzyme drugs (n = 20), and their combination (n = 9). About half the children (47.54%) were boys. Blood samples were biochemically tested in children for bilirubin and enzymes 1, 3, 6, 9, and 12 months after their hospital discharge. The similar laboratory tests were carried out in 20 healthy children--a comparison (control) group. Analysis of discriminant functions stated the high efficiency of inclusion of enzyme drugs, or antihistamines in particular, or their combinations with enzyme drugs, that considerably reduce the time it takes to normalize the complexes of the indices of a blood biochemical test for bilirubin and enzymes. PMID- 20734861 TI - [Free radical oxidation-antioxidant defense system upon exposure to industrial chemical pollutants]. AB - The paper gives the results of studying the free radical oxidation-antioxidant defense (FRO-AOD) system in the blood, saliva, and urine of workers from the petrochemical industry OAO "Salavatnefteorgsintez". The FRO-AOD system has been ascertained to be considerably changed in the plasma, tear, and urine of persons contacting a mixture of petrol and Grade BP-1 solvent with organic solvents and aromatic hydrocarbons and a mixture of 1,2-dichloroethane with chlorinated hydrocarbons under industrial conditions. PMID- 20734862 TI - [Free radical oxidation and the mechanisms of antioxidant defense in normal cells and tumor diseases (a lecture)]. AB - The paper gives update on free radical oxidation and an antioxidant defense system in normal cells and cancers. It describes steps of oxidative stress: the emergence of free radicals, the development of chain reactions, and their inhibition by enzymatic and nonenzymatic reactions. A role of iron is shown in lipid peroxidation. The characteristics of major natural antioxidants and their implication in the regulation of the oxidant-antioxidant system in oncological care are given. PMID- 20734863 TI - [Urokinase-type plasminogen activator and its inhibitor type 1 in the diagnosis of evolving complications in coronary heart disease]. AB - Fibrinolytic system components are important in the regulation of thrombogenesis therefore the aim of the investigation was to compare the level of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) in the monocytes of patients with stable coronary heart disease (CHD) and acute coronary syndrome (ACS) to reveal an association of the content of these proteins with the severity of disease, by applying two different techniques: immunocytochemistry and flow cytofluorimetry. The counts of uPA- and PAI-1-expressing monocytes were equal in each case and accounted for 81.9-99.9% in all groups. At the same time, the level of PAI-1 was higher than that of uPA and significantly higher in patients with ACS than in those without ACS and in the controls. No significant differences were found in uPA levels between the ACS and stable CHD groups; however, it was significantly higher in the patient groups than in the control one. The detection of the higher expression of PAI-1 in the peripheral blood monocytes of patients with ACS suggests that it can be used as a marker of disease severity. PMID- 20734864 TI - [Metabolic mechanisms underlying reparative action of metal-dependent spectral light flux from a hollow cathode lamp (experimental study)]. AB - The objective of the present study was to evaluate the influence of serial irradiation of experimental animals with a visible light flow showing spectral lines of copper and manganese on the rate of reparative processes and the associated metabolic events. The cathode of the lamp that contained both microelements generated the light flux possessed of significant biological activity. Specifically, it accelerated reduction of the wound surface area and optimized regulation of carbohydrate metabolism in the lipid peroxidation system by insulin and cotisol. The light flux emitted by the cathode containing only one of the two elements (either copper or manganese) produced a similar but less pronounced effect. PMID- 20734865 TI - [Effect of the pulse shape on electrostimulation of excitable tissues]. AB - This paper is devoted to the consideration of the mechanisms of electrostimulation of excitable tissues used in remedial medicine. Community of biophysical principles underlying the Weiss-Lapique and Dubois-Reymond laws is emphasized. The action of stimulating pulses on biological tissues and its consequences are analysed with reference to their shape (rectangular, triangular, and exponential). It is shown that the shape of the accommodation curve depends on the shape of stimulating pulses and physiological conditions of the tissue. PMID- 20734866 TI - [Pulsed low-frequency electrotherapy of vibration disease associated with osteoarthrosis]. AB - The study involving 185 patients with vibration disease and concomitant osteoarthrosis has demonstrated the positive influence of pulsed low-frequency currents in combination with hydrogen sulphide baths on the clinical course of the disease. This combined therapy produced good immediate and late post treatment results. The data obtained suggest high efficiency of differential application of complex-modulated pulsed and fluctuating currents in patients with vibration disease. It is concluded that amplipulse therapy is the method of choice for the management of this pathology in the absence of apparatuses emitting pulsed currents in the running way regime. PMID- 20734867 TI - [Adaptive training with electromyographic feedback after elimination of traumatic defects of wrist and fingers]. AB - The objective of this work was to analyse the efficiency of adaptive training with electromyographic biological feedback in the early period after reconstruction of fingers depending on the character of wrist defects, the method of their correction, and etiology of the injury. Unique techniques were proposed for the training. Their effectiveness was evaluated based on clinical observations, results of electromyographic and biomechanical studies that demonstrated a significant increase of EMG amplitudes for different groups of wrist and forearm muscles during basic thumb movements (p = 0.05-0.0003) and changes of major biomechanical parameters (p = 0.007-0.000008) in the course of adaptive training with electromyographic biological feedback depending on EMG amplitude. PMID- 20734868 TI - [The concept of afferent therapy and prevention of morbidity with reference to balneotherapeutics]. AB - The concept of afferent therapy and prevention of morbidity is discussed in the context of integrative medicine in application to balneotherapeutics. It is maintained based on the results of neurophysiological investigations including exposure of the patients to natural and preformed physical factors that the concept in question provides a "neurophysiological clue" for the understanding of pathogenesis of many diseases and a rationale for the prescription of adequate therapeutic modalities to manage them. PMID- 20734869 TI - [Differential application of ophthalmostimulation for the prevention of dysadaptation problems in athletes]. AB - The efficiency of single-pulse ophthalmostimulation (OPS) with the use of photodiodes emitting red, orange, green, and blue light was evaluated in 26 athletes. Results of the study indicate that OPS in the green-blue spectral range may be recommended as a preventive treatment for athletes of the normal- or low energetic status in the state of activation reaction and disposed to sympatheticotony if they are at risk of developing dysadaptatiive disorders. Ophthalmostimulation by the red light is indicated for athletes of high-energetic status who exhibit training reaction and parasympathetic type of responsiveness. PMID- 20734870 TI - [The influence of respiratory relaxation training on psychological reserves in patients with chronic somatic diseases]. AB - Comparative analysis of dynamics of the psychological status of 25 patients with chronic somatic diseases is presented. The patients were subjected to psychocorrection by respiratory relaxation training (RRT). The control group comprised 26 patients with the same problems undergoing no RRT. The evaluation was based on MMPI (Mini-Mult variant), STAI, Beck's depression inventory, quality of life inventory, and stress tolerance self-assessment scale. Respiratory relaxation training enhanced psychological reserves of the patients by reducing the anxiety and tension levels, modulating hypochondriac mood, by increasing psychological resistance to stress. These changes resulted in marked improvement of the quality of life. The efficiency of respiratory relaxation training in patients with elevated levels of impulsivity and demonstrativity proved lower than in patients with depressive disorders. PMID- 20734872 TI - [Sanatorium and spa treatment of patients with isolated and combined pathology of the cardiovascular system and metabolism]. AB - The present study involved 720 patients with metabolic syndrome, diabetes mellitus, coronary heart disease, hypertensive disease, and various combinations of these conditions examined in the course of sanatorium and spa treatment. The patients received either traditional or modified therapy. The latter modality included climato-balneotherapy, hypoxytherapy, bioresonance therapy, and hypercapnotherapy supplemented by the intake of Arfazetin herbal tea, Magnerot tablets, and Chvizhepse mineral water. Results of the study indicate that the proposed combined treatment had more pronounced curative effect compared with traditional therapy in patients of all groups included in this study. PMID- 20734871 TI - [Significance of the commonest risk factors of chronic non-infectious cardiovascular diseases in patients of a multi-field sanatorium]. AB - Ninety three patients admitted for the treatment at the Central Military sanatorium, Russian Ministry of Defense, in the city of Kislovodsk, underwent medical examination for the evaluation of significance of the most frequent risk factors of developing pre-nosological and nosological forms of chronic non infectious cardiovascular diseases. Results of the study suggest high prognostic value of excess body weight and diagnostic importance of the relative number of patients with maximum arterial pressure figures above the normal ones. The main risk factor among characteristics of lipid metabolism is atherogenicity index followed by total cholesterol level. Blood levels of triglycerides, low and very low density lipoproteides are of smaller importance as risk factors of chronic non-infectious cardiovascular diseases while the prognostic value of the high density lipoproteide concentration is negligible. PMID- 20734873 TI - [Radiopharmaceuticals in urological clinic: clinical and cost analysis]. AB - Side effects of radiopharmaceuticals (RP) used in urological clinics, their incidence rate and cost are analysed basing on the cost in inpatient RP application in patients with different forms of pyelonephritis. RP cost in such cases reaches up to 1/4 of the money spent on medication. Ways of optimal cost effect RP use are proposed. PMID- 20734874 TI - [Chronic pyelonephritis in workers of chemical industry: pathogenesis and treatment]. AB - The examination of 500 workers engaged in the production of chemicals detected chronic pyelonephritis in 81 (16%) of them. Such occupational hazards as furnace charge dust, fly-powder, calcium petre in the air, intensify their toxic action on workers in high temperature and humidity (54-67%) at workplace and provoke pyelonephritis. An experimental model of pyelonephritis was developed in animals exposed to the above environmental hazards. Ceruloplasmin added to combined treatment of chronic pyelonephritis relieves endotoxicosis by reducing content of middle-mass molecules in blood plasma. PMID- 20734875 TI - [Modified percutaneous nephrolithotripsy as monotherapy in stag-horn nephrolithiasis with complex stereometric configuration]. AB - Percutaneous nephrolithotripsy (PN) was used as monotherapy in modification with one additional nephroscopic approach in surgical treatment of 57 patients suffering from stag-horn nephroliths with complicated stereometric configuration. According to classification of stag-horn concrements, C3 and C4 groups comprised 36 (63.1%) and 21 (36.9%) patients, respectively. The greater part of the stone was removed through a standard percutaneous approach regarding the angle of a rigid nephroscope, the other part of the concrement was evacuated through an additional transcutaneous approach for a small-diameter nephroscope. A mean duration of the operation was 60-150 min. The internal stent-catheter was not installed. Residual concrements were detected in 2 (5.6%) and 4 (19%) cases, in C3 and C4, respectively. The presence of residual fragments is explained by complicated stereometric configuration, high density of the concrements, technical difficulties in surgical intervention. As in such cases residual fragments were clinically significant, they were destroyed ub fragments and eliminated according to the "second look" technique in early postoperative period (day 3-4) through nephrostomic fistulas. All the patients were discharged from the hospital in satisfactory condition on postoperative day 5-9. This modification has advantages: one-stage removal of the stone, low invasiveness and traumatism. PMID- 20734876 TI - [Botulinum toxin type A in patients with overactive bladder]. AB - The aim of the study was to investigate safety and efficacy of intradetrusor injection of 100 units of botulinum toxin type A in 26 patients with refractory overactive bladder. The diagnostic scheme consisted of 72 h diary, laboratory tests, ultrasound investigation with measurement of residual urine, urodynamic investigation and neurological examination. The patients were divided into 3 groups: 14 patients with idiopathic detrusor overactivity (DO), 9 with neurogenic DO, and 6 with overactive bladder without DO. 100 units of botulinum toxin type A mixed with 20 ml of normal saline were injected into the detrusor sparing the trigone. Clinical and urodynamic evaluations were performed before the injection and 1, 3 and 6 months after it. The patients with idiopathic DO and overactive bladder without DO showed improvement of such clinical symptoms as frequency, urgency, nocturia and urgent incontinence which lasted for at least 6 months. Patients with neurogenic DO had improvement of the clinical symptoms only for one month after treatment. We had no patients who exhibited acute urinary retention or residual urine. Thus, 100 units of botulinum toxin type A injected into the detrusor is an effective, safe and well tolerated treatment for patients with idiopathic DO and overactive bladder without DO in whom an anticholinergic medication has failed. PMID- 20734877 TI - [Retroperitoneal lymphadenectomy in disseminated non-seminoma germinogenic testicular tumors after chemotherapy in patients with elevated serum tumor markers]. AB - Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm- 40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease. PMID- 20734878 TI - [A complex approach to prediction of long-term results of urinary bladder cancer treatment]. AB - Our investigations proved that the risk of bladder cancer relapse increases after organ-preserving treatment in exposure to exogenic and endogenic epidemiological factors. A significant deterioration of the prognosis as concerns a recurrence and lethal outcome risk is significantly related with some clinical and morphological characteristics of the tumor. The correlation-regression analysis has revealed a complex of the most significant independent factors which made a basis for a developed mathematic model of bladder cancer prognosis and a computer program for bladder cancer patients survival. PMID- 20734879 TI - [Ejaculatory disorders in some regions of the Russian Federation]. AB - Ejaculatory disorders are one of the most frequent sexual dysfunction. To study this problem in different climatic regions, we made a population-based trial with participation of 543 Russian men (149 from the south of Russia, 394 from Siberia). Correlation of ejaculatory disorders with IELT duration, a testosterone level, comorbid chronic prostatitis was estimated. We found that 59.2% of young men had normal ejaculation but only 20% of men over 50 years of age. In the latter group of patients delayed ejaculation predominated. 43.6% of the southerners and 33.5% of the Siberians had premature ejaculation, and 6.1 and 16.9%--delayed ejaculation, respectively; 26.7 and 31.2% were hypogonadal, respectively. Ejaculation was normal in 74.6% men with a normal testosterone level. Hypogonadal patients had premature ejaculation in 48.2% cases, delayed ejaculation in 28.3%. Of the total 543 men, 67.2% had chronic prostatitis. Only 46% of patients with chronic prostatitis had normal ejaculation, 43.3% had premature ejaculation and 10.7% had delayed ejaculation. Thus, in cold climate delayed ejaculation occurs more often, in the South premature ejaculation predominates. A low testosterone level as well as chronic prostatitis resulted in ejaculatory disorders. There are significant differences in ejaculation between young and old men, whose living in the South and Siberia, eugonadal and hypogonadal. Therefore, when characterizing a copulative act as "normal" it is necessary to take into account age, comorbidity, region of living and other factors. PMID- 20734880 TI - [Sexual and reproductive function in males with somatotropinoma]. AB - The examination of 72 males with somatotropinoma has found that 65% of such patients have hypogonadism which is essential in pathogenesis of sexual dysfunction and spermatogenetic disorders. However, hypogonadism in males with somatotropinoma does not provoke sexual dysfunction in most the cases. High production of somatotropic hormone and insulin-like growth factor 1 in somatotropinoma leads to prostatic hyperplasia which is not accompanied with a rise of a PSA level and symptoms of infravesical obstruction. PMID- 20734881 TI - [Etiology, pathogenesis and diagnosis of urgent voiding]. PMID- 20734882 TI - [Pelvic stress pain: neurologist's outlook on the problem of prostatodinia]. PMID- 20734883 TI - 'Heparin-induced thrombocytopenia (HIT): a case study'. PMID- 20734884 TI - Factor X deficiency. PMID- 20734885 TI - A tale of two biomarkers: the use of troponin and CK-MB in contemporary practice. PMID- 20734887 TI - Acinetobacter baumannii and MRSA contamination on reusable phlebotomy tourniquets. AB - OBJECTIVE: A study was undertaken to determine the incidence of Acinetobacter baumannii and methicillin resistant Staphylococcus aureus (MRSA) contamination on reusable phlebotomy tourniquets at Wilford Hall Medical Center, Lackland AFB, TX. DESIGN: Reusable tourniquets (n=200) were collected after being used for one day in the outpatient blood collection center (n=100) or during morning blood collection rounds on inpatient wards (n=100). Tourniquets were cultured and growth was screened for A. baumannii and S. aureus. A. baumannii isolates were identified using colonial morphology, oxidase, and GNI+ card on Vitek Legacy. S. aureus isolates were identified and screened for MRSA using colonial morphology, catalase, Staphaurex, and Oxacillin screening agar. RESULTS: Each outpatient tourniquet was used on an average of 33 patients and each inpatient tourniquet was used on an average of 11 patients. The overall contamination rate was 9% (18/200). A. baumannii was isolated from 11% (11/100) of the outpatient tourniquets and 3% (3/100) of the inpatient tourniquets. Methicillin-susceptible S. aureus was isolated from 2% (2/100) of the outpatient tourniquets and 3% (3/100) of the inpatient tourniquets. No MRSA was isolated. One ou'tpatient tourniquet had both A. baumannii and methicillin-susceptible S. aureus. CONCLUSIONS: Reusable tourniquets could serve as a potential reservoir for bacterial pathogens. PMID- 20734886 TI - Metastatic renal cell carcinoma with metabolic syndrome--a case report. AB - Renal cell carcinoma (RCC) affects patients by proliferating in the renal tubules, resulting in renal failure and concomitant urinalysis findings of blood, protein, casts, and abnormal cells in the urine. If untreated, it can spread to the lymph nodes, liver, and lungs. There is currently no proven tumor marker for RCC. The clinical case reported here describes the clinical laboratory findings in a patient with 2 common co-morbidities (metabolic syndrome and alcoholism), who was found to have metastatic renal cell carcinoma at autopsy. Understanding the clinical chemistry of metastatic carcinoma in the presence of common co morbidities is important for earlier diagnosis and treatment of patients who are most likely to develop these conditions. PMID- 20734888 TI - CLS to higher education administrator: the price they paid. AB - OBJECTIVES: To identify the barriers and/or obstacles these women experienced during their career paths as women clinical laboratory scientists who transitioned to higher education administration. To identify how being a woman influenced their careers as higher education administrators. METHODS: A multi site case study design was selected for this qualitative research involving a purposive sample of eight research participants. Data collection was guided by ten open-ended questions in seven face-to-face and one telephone semi-formal interviews. SETTINGS AND PARTICIPANTS: The purposive sample included women clinical laboratory scientists who held a current higher education administrative position at the dean's level, including associate and assistant dean positions, in a university setting. The participants were located in eight higher education institutions in Nebraska, Illinois, Ohio, Tennessee, Missouri, and Texas. MAIN OUTCOMES MEASURES: The price women pay, gender considerations, a need for balance, existence/absence of the glass ceiling for women in higher education administration. RESULTS: Making personal sacrifices, struggling with gender stereotypes, being a woman, knowing you are okay, and possessing the ability to separate the personal from the professional were identified by this group of women as challenging experiences as they obtained and maintained a position as a higher education administrator. Additionally, they described the need for balance, a support system, and how they successfully managed their marriage, family, and career. The participants presented conflicting statements concerning PMID- 20734889 TI - Graduate education in clinical laboratory science is the glass half full or half empty? AB - OBJECTIVE: To evaluate the 2007 and 1990 data on the number and characteristics of programs offering graduate level degrees in Clinical Laboratory Science. DESIGN/SETTING/PARTICIPANT: Data were collected from published sources (Directory of Graduate Programs for Clinical Laboratory Practitioners) and analyzed at the University of Minnesota. Specific data regarding the kinds of advanced programs and the number of graduates per year, the number of program openings and closures, program requirements were collected, as well as data regarding the number and employment of graduates of Master's degree programs at two long standing public institutions. INTERVENTION: Not Applicable. MAIN OUTCOME MEASURE: The tabulation of degree, program, and graduate data, together with the first position taken by graduates of two M.S. programs. RESULTS: The numbers of graduate level programs and graduates decreased between 1990 and 2007, from 39 to 28 identified Master's level programs, but with only a slight increase from two to five doctoral programs. Several prominent and historically important Master's level programs have closed since the first edition (1990) of the Directory. Detailed analysis of the data from two Master's level programs showed that the first positions for graduating students were predominantly research related and in the same state as the degree-granting institution. CONCLUSION: The number of advanced programs and graduates are relatively small in clinical laboratory science; however M.S. graduates are successful in obtaining positions. These positions are predominantly geographically related to the degree-granting institution, indicating an intellectual and economic impact of the programs in the regions they are located. PMID- 20734890 TI - Scholarly activities of the most productive CLS faculty and schools in the U.S.A. AB - OBJECTIVES: To assess the research and scholarship of the most productive clinical laboratory science faculty and schools in the United States. DESIGN: In 2008 a national study involving 106 college and university CLS programs was conducted to determine which faculty members were most productive in research activities. A questionnaire was sent electronically to all faculty (n=448) of 106 NAACLS accredited programs. Data from 275 respondents (61%), from 93 programs (89%) were analyzed. SETTING: The study took place at The Ohio State University with collaboration from the University of Minnesota. PARTICIPANTS: Clinical laboratory science faculty within a four-year university or college sponsoring a NAACLS-accredited CLS program, were invited to participate. MAIN OUTCOME MEASURES: To quantitate faculty scholarly productivity by point assessment, to assess the top 10% of faculty based on funding, publications, abstracts, presentations, books and chapters, and to identify the 15 highest ranking institutions in terms of their collective faculty research contributions. CONCLUSIONS: The top 10% of clinical laboratory science faculty (n=28) are performing almost 50% of scholarship in the profession, with major contributions in funding garnered and international presentations. These individuals also generally hold a doctorate, are full professors and tenured. Among the 15 highest ranked colleges and universities with CLS programs, and by cumulative faculty contributions, most are classified as research institutions. PMID- 20734891 TI - Online education and technology introduction. PMID- 20734892 TI - Using technology in resource limited countries for competency based education and training. AB - Competency based education and training (CBET) helps to prepare graduates of medical laboratory science programs for the specific needs of the workforce. This is especially important in resource-limited countries where shortage of laboratory personnel creates a large demand for skilled graduates. Internet and other technology can be useful to teach specific tasks in CBET. Even in resource limited countries, technology can be used in the implementation of competency based education and training curricula in medical laboratory programs. PMID- 20734893 TI - Moving from face-to-face to online teaching. AB - Transitioning from face-to-face to online teaching can be challenging but is also rewarding. It is challenging to create a sense of social presence so that the online student feels a part of the learning community. It is difficult to assess the level of student learning and to regularly communicate with them without being face-to-face. Online students may require constant feedback and clarifications on difficult concepts which can be very time consuming for the faculty. The paper will discuss creative instructional strategies that will help faculty overcome some of the challenges and make their transition from face-to face to online teaching an easier process. Advantages and rewards of online teaching are also discussed. PMID- 20734894 TI - Table 1 disputed. "What goes around, comes around: a review of circulating tumor cells". PMID- 20734895 TI - Diseases without borders. Handle exotic diseases with this lab pocket guide. PMID- 20734896 TI - Develop a competitive business strategy. PMID- 20734897 TI - Addressing management issues. Cranky employee creates chaos. PMID- 20734899 TI - Once is not enough: volunteering abroad brings repeated rewards. PMID- 20734898 TI - What investors look for in a genomics venture. PMID- 20734900 TI - Optimize the lab's test menu: how molecular dx can impact the bottom line. PMID- 20734901 TI - Meaningful use of health information. PMID- 20734902 TI - Lab safety is automatic at Greiner Bio-One. PMID- 20734903 TI - Team agreement, competition boost record for on-time starts. PMID- 20734904 TI - What comes next for SCIP measures? PMID- 20734905 TI - Data sparks on-time improvements. PMID- 20734907 TI - Breakthroughs on wrong-site surgery. PMID- 20734906 TI - Robotics: little data, much debate. PMID- 20734908 TI - Don't overlook reprocessing instructions. PMID- 20734909 TI - Meeting an ASC's financial targets. PMID- 20734910 TI - Isolation and characterization of hexavalent chromium-reducing rhizospheric bacteria from a wetland. AB - Scirpus americanus Pers. occurs naturally in "San German," a pond that serves as a receptor of industrial wastewater in Guanajuato, Mexico. This plant accumulates metals mainly in the root: concentrations (mg/kg) of Cr, As, Cd and Se were 970, 49, 41, and 85 respectively. Analysis of rhizosphere samples indicated bacterial population of 10(8) cfu g(-1) in media with 0.2 mM Cr(VI) and 10 mM sodium gluconate. Thirteen isolates were obtained and phylogenetic analyses (16S rRNA) indicated they corresponded to genera of Agrobacterium, Arthrobacter, Microbacterium, Curtobacterium, Rhodococcus, Xanthomonas and Pseudomonas. Cr(VI) reduction was evaluated using the diphenyl carbazide method. The isolates accomplished 5-40% (20 microM) of reduction in assays of resting cell and tolerated 0.5-5.0 mM Cr(VI). Eight strains used nitrate and thirteen used iron and chromium as electron acceptors to grow under anaerobic conditions. Cr(VI) reduction by five strains occurred at pH values (7-9) and NaCl concentrations (0.5-1.0 M) in basal medium. A mixed culture of strains (S17 and S28) reached a chromium removal of 100% at 0.2 mM Cr(VI) initial concentration. Aerobically, this consortium was capable of 93.8% Cr(VI) reduction of 81 microg L(-1) Cr(VI) of the industrial effluent, indicating their possible use in environmental cleanup. PMID- 20734911 TI - Assessing phytotoxicity of heavy metals in remediated soil. AB - Copper (Cu), zinc (Zn) and chromium (Cr) are pollutants that usually are accumulated in soils. Their toxicity can be decreased by applying amendments. We proposed to evaluate changes in Cu, Zn, and Cr availability, due to the application of amendments, through chemical analysis and phytotoxicity tests. The phytotoxicity test was carried out using species belonging to Sesbania genus; plant parameters were measured 48, 72, 96, and 168 hours after the start of incubation. The treatments included enriched soil, in addition to biosolid compost and triple superphosphate. Cu and Zn amounts were higher in treatments without amendments, indicating immobilization on the part of these. The amounts of Cr tended to decrease with amendments application. The amendments increased pH values and decreased EC; however, this had no impact on the results. No relationship was found among pH, EC, and plant parameters. Different behaviors were observed. S. virgata showed germination seed delay. In addition, while in S. virgata the IG increased during the assay, in S. punicea it diminished. The application of compost, fertilizer or both combined could be of interest for contaminated soils remediation. The use of chemical analysis and phytotoxicity tests allowed to estimate heavy metal availability and the effect on both Sesbania species. PMID- 20734912 TI - Response of Eucalyptus camaldulensis to irrigation with the Hudiara drain effluent. AB - A pot experiment was conducted to evaluate the effects of the industrial effluent of the Hudiara drain on the growth and element accumulation by Eucalyptus camaldulensis at early growth stage. Plants were irrigated for 18 months with effluent diluted with tap water at 0% (T0), 25% (T1), 50% (T2), 75% (T3), and 100% effluent (T4). Results showed that the maximum growth in terms of stem height (260 cm), number of branches (29), stem fresh weight (436.67 g), stem dry weight (203.33 g), total seedling length (344 cm), number of leaves (825), leaf fresh weight (195 g), and leaf dry weight (100 g) were recorded in plants treated with T2. However, maximum seedling collar diameter (2.25 cm), root fresh weight (230 g), and root dry weight (103.33 g) were observed in T3 treated plants. On the other hand, seedlings attained maximum root length (100.67 cm) at T1 treatment. Chlorophyll a, chlorophyll b and total chlorophyll increased up to T2, declining beyond that treatment. The accumulation of Na, Cd, and Cr in tissues increased with increasing concentrations of the effluent. However, the increase in effluent concentration decreased K and P in roots, and increased Fe in roots and stems, while T1 and T2 increased Mg in stems. The results suggest that mixing the wastewater of the Hudiara drain with tap water (50:50v/v) benefits the growth of E. camaldulensis. PMID- 20734913 TI - Expression of the phytochelatin synthase TaPCS1 in transgenic aspen, insight into the problems and qualities in phytoremediation of Pb. AB - The response of Populus tremula x tremuloides cv. Etrepole transgenic lines expressing the phytochelatin synthase TaPCS1 for Pb tolerance and accumulation was studied. In a hydroponic experiment, the concentrations of Pb in plants did not differ significantly between any of the transgenic lines assayed and the wild type (wt) plants, with any of the Pb solutions tested. However, total biomass and Pb accumulation were significantly higher in transgenic lines (PTa3, PTa5, PTa10) than in the control (wt) line when the plants were grown in solutions containing 0.75 and 1.5 mM Pb. The PTa3 and PTa5 lines accumulated 1.7 times more Pb than the wt plants. A concentration of 3.0 mM Pb was found to be toxic for both transgenic and wt plants. Biomass production was higher in transgenic lines PTa3 and PTaS than in the wt plants growing in M4 mining soil, accumulating more Pb and Zn than in the wt plants. When the plant material was grown in soil M15, none of the parameters differed significantly between the transgenic and wt plants. The different response in soils M4 and M15 indicated that the physicochemical properties of the soil play a determinant role in the phytoremediation potential. PMID- 20734914 TI - Enzymatic activity of a mine soil varies according to vegetation cover and level of compost applied. AB - We applied three doses of compost from mixed municipal solid waste (0, 15, and 30 g kg(-1) of soil) to a soil developed on pyrite mine wastes. Part of the soil was planted with young Erica australis L. collected at the mine; part was fertilized with N-P-K-Mg and sown with Dactylis glomerata L .Bare soil without mineral fertilization was included in the experiment, as well. Compost application to bare soil increased pH, provided plant nutrients, and enhanced the activity of the six soil enzymes tested. Growth of D. glomerata, and E. australis was stimulated in compost-amended soil compared with unamended controls. The presence of D. glomerata led to the greatest activities of soil acid phosphatase, beta glucosidase, and cellulase compared with bare soil or with soil with E. australis. The presence of E. australis increased the activities of protease and cellulase in amended soil, compared with control, but it impaired dehydrogenase, fl-glucosidase, and acid phosphatase activities. These negative impacts probably derived from phenolic compounds known to be released from roots of this species. The survival strategy of this species seems to include a small need for P in the shoots, and the release of exudates that impair microbial activity and P cycling. PMID- 20734916 TI - Effect of organic matter additions on uptake of weathered DDT by Cucurbita pepo ssp. pepo cv. Howden. AB - Greenhouse studies were conducted to assess the impact of organic matter additions on plant uptake of DDT [2,2-bis(chlorophenyl)-1,1,1-trichloroethane] from weathered soil. Cucurbita pepo ssp. pepo cv. Howden pumpkins were grown in 100 g of DDT contaminated soil ([DDT] - 1100 ng/g) mixed with equal volumes of either clean soil, perlite, vermiculite, peat, potting soil, or granular activated carbon (GAC) to give total organic carbon contents of 2.4%, 2.5%, 2.6%, 11.5%, 12.2%, and 27.3%, respectively. As in other studies, root DDT concentrations were significantly lower in soils with high organic matter. Root bioaccumulation factors (BAF = [DDT]root/[DDT]soil) approximated this trend. Root concentrations correlated with organic matter concentrations and not with soil DDT concentrations. Conversely, shoot DDT concentrations, shoot BAFs and translocation factors (TLF = BAF(shoot)/BAF(root)) were not significantly different between treatment groups, except for plants grown in GAC/DDT soil. This suggests that amendments with a range of organic matter contents may be added to improve soil conditions at industrial sites without significant adverse effects on phytoextraction potential of C. pepo ssp. pepo. PMID- 20734915 TI - The effect of arbuscular mycorrhizal fungi and phosphate amendement on arsenic uptake, accumulation and growth of Pteris vittata in As-contaminated soil. AB - This study investigated the contributions of mixed arbuscular mycorrhizal fungi (AMF) inoculum-i.e., mixed populations of indigenous mycorrhiza (Glomus intraradices, Glomus geosporum, Glomus mosseae) (IM) isolated from arsenic (As) contaminated soil and non-indigenous mycorrhiza such as G. mosseae (GM), which possess metal tolerance characteristics-and the addition of phosphate rock (PR) towards the uptake and accumulation of As by Pteris vittata (As hyperaccumlator) grown in As-contaminated soil. Regardless of As levels added to soil, plant growth was substantially improved in amended treatments when compared with the control. In addition, root surface area (0 mg/kg As: 15.2 cm2; 150 mg/kg As: 16.9 cm2; 300 mg/kg As: 20.7 cm2), chlorophyll contents (0 mg/kg As: 1.16 mg/g; 150 mg/kg As: 1.46 mg/g; 300 mg/kg As: 1.81 mg/g) and As translocation factor (0 mg/kg As: 0; 150 mg/kg As: 4.29; 300 mg/kg As: 5.22) in P. vittata of PR+IM/GM were also increased. Such combination could further enhance plant growth (indicated by higher N, P and chlorophyll contents) and As uptake by P. vittata. PMID- 20734917 TI - Cytotoxic compounds from Poecilocerus pictus feeding on Calotropis gigantea. AB - Poecilocerus pictus, an aposematic insect, feeds on Calotropis gigantea (Asclepiadaceae) and sequesters cardiac glycosides which are used in chemical defense. The aim was to characterize the components of the methanolic extracts of P. pictus and C. gigantea and investigate preferential cytotoxicity of the insect extract, if any, on human cancer cell lines. Comparative chemical characterization by HPTLC, UV and IR studies revealed the presence of cardenolides in both the extracts and biotransformation of some of the ingested cardenolides in the insect extract. Cytotoxicity testing of the insect extract on human and murine normal and cancer cell lines indicated a time and dose dependent inhibition of A549 and COLO205 with a 48 hour IC50 of < 5 microg/ml, but no effect on normal cell line W138 or murine cell lines. Lymphotoxicity and genotoxicity experiments on human peripheral blood lymphocytes tested negative. DNA ploidy analysis on COLO205 indicated 36% apoptosis induction by 10 microg/ ml of insect extract. In brief, our studies established that the methanolic extract of P. pictus contained ingested cardenolides, of which some were biotransformed. Within a range of concentrations, P. pictus extract suppressed viability in A549 and COLO205 cells but not in normal cells, lymphocytes or murine cells. It induced apoptosis in COLO205. The insect extract discriminated human cancer from normal cells, inhibited cancer cell viability specifically and may represent a vital lead for a chemotherapeutic drug. PMID- 20734918 TI - DLBS1425, a Phaleria macrocarpa (Scheff.) Boerl. extract confers anti proliferative and proapoptosis effects via eicosanoid pathway. AB - Phaleria macrocarpa (Scheff.) Boerl. (Thymelaeaceae), an Indonesian native plant, has been used to treat various diseases in Indonesia. DLBS1425, a standardized extract of flesh fruit of Phaleria macrocarpa, is hypothesized to have anti cancer activities. Anti-proliferative and induction of apoptosis conferred by DLBS1425 on breast cancer cells, MDA-MB-231 and MCF-7 cells were investigated. DLBS1425 showed an inhibition of proliferation in both cell lines. Induction of apoptosis was shown by DNA fragmentation, activation of caspase 9, and regulation of Bax and Bcl-2 at the mRNA level. DLBS1425 downregulated COX-2, cPLA2, and VEGF C mRNA expressions. DLBS1425 also down-regulated c-fos and HER-2/neu mRNA expression in TPA- or fatty acid-induced MDA-MB-231 cells. These findings demonstrate that DLBS1425 has anti-proliferative, anti-inflammatory, and anti angiogenic properties, which make it pharmacologically ideal for the prevention and/or treatment of breast cancer. PMID- 20734919 TI - The differential expression of hCNT1 and hENT1 i n breast cancer and the possible impact on breast cancer therapy. AB - hCNT1 and hENT1, two members of the human nucleoside transporter families, expression levels were investigated, in normal and in breast tumour tissues, together with effects of gemcitabine cytotoxicity and in vivo tumour growth in MDA-MB-231 cells. hCNT1 and hENT1 levels were lower in tumour samples than in normal background tissue (p < 0.48). hENT1 levels decreased significantly with patient prognosis (disease free versus died from breast cancer, p = 0.047) although hCNT1 expression did not (disease free versus died from breast cancer, p = 0.97). Immunohistochemical staining of hCNT1 and hENT1 was stronger in normal than tumour tissue. hCNT1 knockdown caused MDA-MB-231 cells to be less sensitive to Gemcitabine compared with wild type and control plasmid cells (25% killed vs 88% and 90%). MDA MB-231 deltahENT1 (p = 0.139) and MDA MB-231deltahCNT1 (p = 0.033) tumours showed reduced growth compared with wild type, [71.99 +/- 39.81 mm3 MDA MB-231WT, 40.58 +/- 20.61 mm3 MDA MB-231 deltahCNT1 tumours, 51.58 +/- 49.29 mm3 MDA MB-231deltahENT1, 79.55 +/- 63.08 mm3 PEF and 57.92 +/- 21.67 mm3 GFP controls]. This study shows variability in hCNT1 and hENT1 expression in tumour and normal human breast tissue with different expression patterns related to patient prognosis and clinical outcome. The level of expression of CNT1 was closely linked to the cell's responsiveness to chemotherapeutic treatments. PMID- 20734921 TI - Role of stem cell research in therapeutic purpose--a hope for new horizon in medical biotechnology. AB - While the WHO's general alignment for malignancies & diabetic impacts only one quarter of the world's population, the Indian population is negatively skewed outside of such malignancies & diabetic range. Stem cells (SCs) are undifferentiated highly specialized kinds of cell types having capacity to renew itself, found in different tissue or organ. SCs are capable of dividing for long period of time to furnish grow different cell types with specific functions. It took about twenty years to gain knowledge of how to grow embryonic stem cell in vitro. The primary roles of adult stem cells in a living organism are to renew or maintain and repairthe injured tissue in which they are found. SCs are classified in to two categories on the basis of their origin and their functional properties. First the embryonic stem cells originate from the inner cell mass of the blastocyst, while second is of adult stem cells. Another category of stem cells are the amniotic fluid derived embryonic cells (AFEc) having equally important cells which transform into various types of tissues present in fat, bone, muscles, liver and blood vessels. The main advantage of AFEc is to use these cells without or disturbing or touching embryo. Embryonic stem cell expresses specific markers of self renewal and pluripotency including transcription factor like SOX-2, LIF etc. Bone--marrow contains two kinds of stem cells, one haemotopoietic which form the blood and second stroma which form mixed cell population like bone, cartilage fat and fibrous connective tissue. Cellular differentiation of stem cells is inimitable and based on either intrinsic or extrinsic signals and during migration cancer stem cell loses cell polarity which leads to epithelial to mesenchymal transition (ENT). These signals named genes which carry coded instructions (novel molecules) for all the structure and function. External signals are chemical molecules secreted by other neighboring cell through physical contact (paracrine regulation). Efforts are being done to grow both embryonic and adult stem cells using "tissue culture engineering" in vitro. SCs could be used for various therapeutic purposes like Parkinson's patients, Alzheimer's disease & other neurological disorders patients, repairing for damaged heart muscles and for type I diabetes patients as an alternative source of chemotherapy including trauma patients which is not only expensive but lack of side effect too. PMID- 20734922 TI - Developing a novel fiber optic fluorescence device for multiplexed high throughput cytotoxic screening. AB - The need for new pharmacological agents is unending. Yet the drug discovery process has changed substantially over the past decade and continues to evolve in response to new technologies. There is presently a high demand to reduce discovery time by improving specific lab disciplines and developing new technology platforms in the area of cell-based assay screening. Here we present the developmental concept and early stage testing of the Ab-Sniffer, a novel fiber optic fluorescence device for high-throughput cytotoxicity screening using an immobilized whole cell approach. The fused silica fibers are chemically functionalized with biotin to provide interaction with fluorescently labeled, streptavidin functionalized alginate-chitosan microspheres. The microspheres are also functionalized with Concanavalin A to facilitate binding to living cells. By using lymphoma cells and rituximab in an adaptation of a well-known cytotoxicity protocol we demonstrate the utility of the Ab-Sniffer for functional screening of potential drug compounds rather than indirect, non-functional screening via binding assay. The platform can be extended to any assay capable of being tied to a fluorescence response including multiple target cells in each well of a multi well plate for high-throughput screening. PMID- 20734920 TI - Clinicopathological predictors of lymphatic metastasis in HNSCC: implications for molecular mechanisms of metastatic disease. AB - Lymphatic metastasis is associated with up to a 50% decrease in survival, yet the molecular mechanisms driving their establishment remain poorly understood. This study assessed clinicopathological characteristics correlated to nodal metastasis among patients with head and neck squamous cell carcinoma for the identification of pathways on which to focus molecular studies. Pathology records were queried for cases diagnosed with invasive squamous cell cancer of the upper aerodigestive tract between 1993 and 2003. Charts and pathology reports were scored for 16 characteristics. The univariate association of each variable with lymph node status was assessed. Based on the univariate analysis, a multiple logistic regression model was developed to assess the simultaneous association of variables with lymph node status. Of the 644 cases identified, 234 had a surgical specimen analyzed. All variables were scored for 185 of the 234 cases. Multivariate stepwise regression analysis identified clinical stage (p = 0.0269), pathologic stage (p = 0.0162), grade (p = 0.0094), lymphovascular invasion (p = 0.0393), and family history of cancer (p = 0.0079) as independently predictive of lymphatic metastases. Our study confirms that grade, pathologic stage, clinical stage, and lymphovascular invasion are predictors of regional metastasis. These correlations suggest that studying the molecular mechanisms of differentiation, interstitial pressure at the primary tumor site, and peritumoral lymphangiogenesis may provide insight into lymphatic metastasis. Additionally, we identified family history of cancer as a new predictor of lymphatic metastasis. Thus, genetic analysis of families with cancer, irrespective of type, may identify genes important for regional metastasis. PMID- 20734923 TI - EGFR signaling is differentially activated in patient-derived glioblastoma stem cells. AB - Evidence suggests that stem-like cells are responsible for initiation, maintenance and recurrence of solid tumors, including Glioblastoma Multiforme (GBM). GBM is an intractable, highly lethal tumor of the central nervous system. Although epidermal growth factor receptor (EGFR) is highly expressed in many GBMs, anti-EGFR therapies have been unsuccessful as treatment. Few studies have examined EGFR activation in GBM stem cells (GSCs) to determine if patient specific GSCs are amenable to anti-EGFR therapy pre-clinically. We hypothesized that EGFR activation in GSCs varied between patients and was an important determinant of responsiveness to anti-EGFR therapy. Cell cycle and apoptosis analysis was performed on tumor-spheres by immuncytochemistry in the presence and absence of the AG1478. Second messenger pathways operative in these processes were elucidated by immunoblotting. EGFR activated AKT and inactivated GSK3beta in EGFR+/PTEN+ GSCs. AG1478 and erlotinib significantly decreased the total number of tumor-spheres that EGFR+/ PTEN+ GSCs generated and the rate of sphere formation. Inhibition of EGFR signaling by AG1478 increased GSC senescence and apoptosis, likely via inhibition of AKT and activation of GSK3beta. Sphere formation by EGFR-/ PTEN- GSCs was independent of EGF stimulation, but dependant on B27 growth supplement. Our data suggest that EGFR+/PTEN+ GSCs are susceptible to anti-EGFR therapy in vitro. PMID- 20734924 TI - Anti-breast cancer activity of curcumin on the human oxidation-resistant cells ZR 75-1 with gamma-glutamyltranspeptidase inhibition. AB - Since curcumin, a polyphenol extracted from the rhizomes of Curcuma longa L. (Zingiberaceae), has been proposed for breast cancer chemoprevention, the aim of the present work was to determine if it had anti-tumour effects on mammary cells which are resistant to oxidative damage. ZR-75-1 cells were treated with curcumin and copper(II) sulphate in order to evaluate cell death and gamma glutamyltranspeptidase (GGTP) activity. Curcumin was cytotoxic in a dose dependent manner (loss of viability with lactate-dehydrogenase release) with apoptotic effects on ZR-75-1 cells. Also, curcumin displayed an antioxidant effect only on the copper-oxidized cells. The GGTP activity was decreased in a dose-dependent manner by curcumin, with the changes in this parameter accounting for neoplastic inhibition (direct relation between the enzyme activity and cellular viability). Summing up, our results suggest that curcumin induced apoptosis in ZR-75-1 with an antioxidant activity performed on those treated with copper(II) sulphate, which should be explored more thoroughly with the involvement of the GGTP enzyme activity as biomarker of their malignancy. PMID- 20734925 TI - Sindbis virus and cancer therapy. PMID- 20734926 TI - A DFT analysis of thermal decomposition reactions important to natural products. AB - The thermal decomposition reactions of several important natural flavor and fragrance chemicals have been investigated using density functional theory (DFT, B3LYP/6-31G*). Retro-aldol reactions of glucose, fructose, hernandulcin, epihernandulcin, [3]-gingerol, and [4]-isogingerol; retro-carbonyl-ene reactions of isopulegol, lavandulol, isolyratol, and indicumenone; and pyrolytic syn elimination reactions of linalyl acetate, alpha-terpinyl acetate, and bornyl acetate, have been carried out. The calculations indicate activation enthalpies of around 30 kcal/mol for the retro-aldol reactions and for retro-carbonyl-ene reactions, comparable to pericyclic reactions such as the Cope rearrangement and electrocyclic reactions, and therefore important reactions at elevated temperatures (e.g., boiling aqueous solutions, gas-chromatograph injection ports). Activation enthalpies for pyrolytic eliminations are around 40 kcal/mol and are unlikely to occur during extraction or GC analysis. PMID- 20734927 TI - Novel terpenoids from the New Zealand liverworts Jamesoniella colorata and Bazzania novae-zelandiae. AB - Diethylether extracts of New Zealand liverworts Jamesoniella colorata and Bazzania novae-zelandiae were investigated to reveal novel terpenoids. The former extract afforded a new modified clerodane-type diterpenoid, and the latter gave a degraded clerodane (rearranged drimane) type sesquiterpenoid. The structures of those new compounds were established by 2D NMR spectra. PMID- 20734928 TI - Two new C20-diterpenoid alkaloids from Delphinium anthriscifolium var. savatieri. AB - Further phytochemical investigation of the whole herb of Delphinium anthriscifolium var. savatieri resulted in the isolation of two new C20 diterpenoid alkaloids, anthriscifolmines I (1) and J (2). The structures of the two new alkaloids were elucidated on the basis of spectral data, including 2D NMR and HRESIMS. PMID- 20734929 TI - Cytotoxic activity of quassinoids from Eurycoma longifolia. AB - Twenty-four quassinoids isolated from Eurycoma longifolia Jack were investigated for their cytotoxicity against a panel of four different cancer cell lines, which includes three murine cell lines [colon 26-L5 carcinoma (colon 26-L5), B16-BL6 melanoma (B16-BL6), Lewis lung carcinoma (LLC)] and a human lung A549 adenocarcinoma (A549) cell line. Among the tested compounds, eurycomalactone (9) displayed the most potent activity against all the tested cell lines; colon 26-L5 (IC50 = 0.70 microM), B16-BL6 (IC50 = 0.59 microM), LLC (IC50 = 0.78 microM), and A549 (IC50 = 0.73 microM). These activities were comparable to clinically used anticancer agent doxorubicin (colon 26-L5, IC50 = 0.76 microM; B16-BL6, IC50 = 0.86 microM; LLC, IC50 = 0.80 microM; A549, IC50 = 0.66 microM). PMID- 20734930 TI - Antifungal activity of saponin-rich extracts of Phytolacca dioica and of the sapogenins obtained through hydrolysis. AB - A saponin-rich extract of Phytolacca dioica L. berries, its acid hydrolysate, and its major aglycone, phytolaccagenin, were assayed for antifungal activity against ATCC standard cultures of Candida albicans and Cryptococcus neoformans, and against clinical isolates of these fungi. The activity of the extract was either low or negligible, but the hydrolysate, containing the sapogenins, including phytolaccagenin, and also pure phytolaccagenin, showed promising antifungal potency. Hydrolysis of a natural product extract is shown to be a useful modification leading to improved bioactivity. PMID- 20734931 TI - New lupane-type triterpenoid saponins from leaves of Oplopanax horridus (Devil's Club). AB - Two new lupane type saponins, along with one known saponin were isolated from leaves of Oplopanax horridus (Devil's Club). The structures of the two new compounds were elucidated as 3alpha-hydroxy-lup-20(29)-ene-23, 28-dioic acid-3-O beta-D-glucopyranoside (2) and 24-nor-3-oxo-lup-20(29)-en-28-oic acid-28-O-alpha L-rhamnopyranosyl(1''' --> 4")-beta-D-glucopyranosyl(1" --> 6')-beta-D glucopyranoside (3) on the basis of spectroscopic analysis and chemical evidence. The known compound was identified as 3alpha-hydroxy-lup-20(29)-ene-23, 28-dioic acid (1) by comparison of its spectral data with those reported. Compound 1 was isolated for the first time from the title plant. PMID- 20734932 TI - Triterpene saponins from Cyclamen persicum. AB - A new triterpene saponin 3-O-beta-D-glucopyranosyl-(1 --> 4)-alpha-L arabinopyranosyl-16alpha-hydroxy-13beta,28-epoxy-oleanan-30-al (1), along with four known triterpene glycosides (2-5) were isolated from Cyclamen persicum. Their structures were characterized by a combination of 1D- and 2D-NMR (1H-1H COSY, TOCSY, NOESY, HSQC, and HMBC) and MS spectrocopic data. The cytotoxicity of compounds 2 and 4 was evaluated using two human colon cancer cell lines HT-29 and HCT 116. PMID- 20734933 TI - Cytotoxic pentacyclic triterpenoids from Combretum oliviforme. AB - Four pentacyclic triterpenoids were obtained from the leaves of Combretum oliviforme Chao, 3beta-hydroxyolean-12-en-28-oic acid (1), 23-O-[alpha-L-(4' acetylrhamnopyranosyl)]-imberbic acid (2), 23-acetoxy-3beta-acetylimberbic acid 29-methyl ester (3), and 23-O-[alpha-L-rhamnopyranosyl]-1,3beta-diacetylimberbic acid (4). Hydrolysis of 2 and 4 gave 23-hydroxyimberbic acid (5). The structures were elucidated by NMR, electrospray ionization mass spectrometry (ESIMS) and comparison with literature data. Compounds 1, 2, 3 and 4 were isolated from C. oliviforme Chao leaves for the first time and 3 for the first time from any natural source. All compounds were tested in vitro for their activity against human lung cancer cell line SPC-A-1, human erythroleukaemic line K562 and human gastric cancer SGC-7901 cells. Compounds 1, 3, 4 and 5 had cytotoxic activity for the three cell lines with IC50 0.69-69.68 microM. These results suggest that the presence of acetyl group in the triterpene aglycone structure plays an essential role for cytotoxic activity. PMID- 20734934 TI - Preparative separation of four major bufadienolides from the Chinese traditional medicine, Chansu, using high-speed counter-current chromatography. AB - A preparative, high-speed, counter-current chromatographic (HSCCC) method for the isolation and purification of bufadienolides from Chansu was successfully developed by using stepwise elution with a two-phase solvent system composed of n hexane: chloroform: methanol: water (4:1:2.5:5 and 4:1:4:5, v/v). A total of 7.5 mg of cinobufotalin (1), 8.0 mg of bufalin (2), 14.0 mg of cinobufagin (3) and 9.5 mg of resibufogenin (4) were obtained in a one-step separation from 80 mg of the crude extract with purities of 93.2%, 98.7%, 99.2%, and 99.4%, respectively. The chemical structures were determined from 1H NMR and 13C NMR spectroscopic data. PMID- 20734935 TI - Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Eschscholzia californica (Papaveraceae). AB - The roots and aerial parts of Eschscholzia californica Cham. (Papaveraceae) were extracted with ethanol. Repeated column chromatography, preparative TLC, and crystallization led to the isolation of fourteen isoquinoline alkaloids, the structures of which were determined on the basis of spectroscopic techniques and by comparison with literature values. One of the compounds isolated, 1-(3-hydroxy 4-methoxybenzyl)-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline (14), has not previously been isolated from a natural source. All isolated compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibition activity. None of the compounds isolated significantly inhibited both HuAChE and HuBuChE, but the two benzylisoquinoline alkaloids, reticuline 9 and 14, showed promising inhibitory activity against HuBuChE. PMID- 20734936 TI - In vitro testing for genotoxicity of indigo naturalis assessed by micronucleus test. AB - In the field of cosmetic dyes, used for coloring the hair and skin, there is a clear tendency to replace the widely used synthetic dyes by natural colorants, such as henna and mixtures of henna with indigo. The aim of this study was to estimate the genotoxicity of water and DMSO solutions of indigo naturalis (prepared from Indigofera tinctoria leaves) using the cytokinesis-blocked micronucleus (CBMN) assay in the human metabolically active HepG2 cell line. The cytotoxic effects of indigo solutions were first assessed by propidium iodide and fluorescein-diacetate simultaneous staining. For both solutions, cytotoxicity was always under 10%. Data obtained in the CBMN assay (for all concentrations tested) indicated that the frequency of MN (micronuclei) in exposed cells was no higher than the control. Both the water and DMSO solutions showed the same behavior. These results indicate that indigo naturalis exhibits neither cytotoxicity, nor genotoxicity for all concentrations tested, which may justify excluding indigofera and its components from the list of carcinogenic agents. PMID- 20734937 TI - Metabolites from Withania aristata with potential phytotoxic activity. AB - A series of apocarotenoids (1-8) and one carotenoid (9) were isolated from the leaves of Withania aristata. In addition, the tetraacetylated apocarotenoid glucosides 10-12 were obtained by acetylation, with derivative 9 hydroxymegastigma-4,6E-dien-3-one 9-O-beta-D-glucopyranoside tetraacetate (10) being described for the first time. The structures have been determined by spectroscopic and spectrometric means, mainly NMR and ESI-MS, and comparison with data reported in the literature. These metabolites were evaluated on a systematic phytotoxicity assay using the etiolated wheat coleoptile bioassay. Compounds 1-3, 9 and 12 were further assayed for their phytotoxicity on the target species Lepidium sativum, Lactuca sativa, Lycopersicum esculentum and Allium cepa. Among the assayed compounds, lutein (9) showed the most significant values for phytotoxicity, followed by the non-glycosylated apocarotenoids (6S, 9R) vomifoliol (1) and 9-hydroxymegastigma-4,6E-dien-3-one (2). PMID- 20734938 TI - Bioassay-guided isolation and quantification of the alpha-glucosidase inhibitory compound, glycyrrhisoflavone, from Glycyrrhiza uralensis. AB - The EtOAc extract of the roots of Glycyrrhiza uralensis exhibited alpha glucosidase inhibitory activity. Bioassay-guided fractionation resulted in the isolation of an active prenylflavonoid, glycyrrhisoflavone. Its structure was elucidated by NMR and MS analyses. A simple method to prepare glycyrrhisoflavone from the 95% EtOH extract of the roots of G. uralensis was developed by combination of Diaion HP-20 column chromatography (CC), silica gel CC, and preparative HPLC. An HPLC-PDA method was developed for quantitative determination of glycyrrhisoflavone in the roots of G. uralensis. The sample was extracted with MeOH and analyzed using a reversed-phase column with isocratic elution with CH3CN H2O (0.06% trifluoroacetic acid) (42:58) at a flow rate of 1.2 mL/min, a column temperature of 40 degrees C, and a detection wavelength of 260 nm. The method allowed the determination of glycyrrhisoflavone in the concentration range of 5 500 microg/mL. The relative standard deviation values of the precision and repeatability were 0.3% and 2.0%, respectively. The limits of detection and quantification were 0.5 microg/mL and 5 microg/mL, respectively. The relative recovery rate was 100.2 +/- 1.8%. Based on the validation results, the HPLC determination method was found to be precise, accurate, and time conservative. This method was applied successfully to nine different root samples of G. uralensis. The amounts of glycyrrhisoflavone in these samples were 15-93 mg/100 g of dried powdered plant material. PMID- 20734939 TI - Xanthones, biflavanones and triterpenes from Pentadesma grandifolia (Clusiaceae): structural determination and bioactivity. AB - Stem bark, roots, leaves and fruits of Pentadesma grandifolia Baker f. (Clusiaceae) have been analyzed for the presence of xanthones, biflavonoids and triterpenoids. Isolated and identified structures include the xanthones cowagarcinone B (1) and alpha-mangostin (2), further the two biflavanones 3,8" binaringenin (3) and the corresponding 3,6"-binaringenin (4), which is here reported as natural constituent for the first time. Structures were determined by NMR and mass spectrometry, as well as by 13C-NMR CSEARCH and SPECINFO database systems. The triterpenes lupeol (5), beta-amyrin (6) and betulin (7) were also encountered. Compounds 2 - 4 exhibited antifungal activity against Cladosporium sphaerospermum. Results are discussed in context to organ-specific accumulation and to other bioactivities that may relate to the ethnomedicinal uses of this species. PMID- 20734940 TI - Gmelinoside I, a new flavonol glycoside from Limonium gmelinii. AB - Gmelinoside I (1), a new flavonol glycoside, was isolated and chemically characterized as 3,5,7,3',4',5'-hexahydroxy-3-O-alpha-D-galactopyranosylflavone from the aerial part of Limonium gmelinii Kuntze (Plumbaginaceae).. Other compounds were identified as (-)-epigallocatechin-3-O-gallate, myricetin, myricetin-3-O-alpha-L-rhamnopyranoside, myricetin-3-O-beta-D-galactoside-6"-O gallate and caprolactam. The antibacterial, antifungal and antileishmanial activities of the isolated compounds were evaluated. Myricetin showed moderate antileishmanial activity. PMID- 20734941 TI - 2-Arylbenzofuran neolignans from the bark of Nectandra purpurascens (Lauraceae). AB - The toluene extract of the stem bark of N. purpurascens (R&P) Mez. contained a large amount of these 2-arylbenzofurans including methyl 7-methoxy-2-(3,4 methylenedioxyphenyl)benzofuran-5-carboxylate (2), a new benzofuran, along with three known compounds identified as kumatakenin (1), 5-(2-propenyl)-7-methoxy-2 (3,4-methylenedioxyphenyl)benzofuran (3), and egonoic acid (4). The structure of the new compound was established on the basis of spectroscopic analysis. PMID- 20734942 TI - Coumarins from Seseli hartvigii. AB - Linear-type furocoumarins, 5-[(2"E,6"R)-6"-hydroxy-3",7"-dimethylocta-2",7" dienyloxy]psoralen and 5-[(2"E,6"S)-6"-hydroxy-3",7"-dimethylocta-2",7" dienyloxy]psoralen (1) were first isolated from whole plants of Seseli hartvigii together with one new natural product 6-(3'-methyl-2'-oxo-3'-butenyl)-7 methoxycoumarin (2), and four known compounds (tamarin, bergaptol, notoptol, and a mixture of beta-sitosterol and stigmasterol). The structure of 1 was elucidated by extensive spectroscopic analysis and chemical conversion. The modified Mosher's method and HPLC were applied to determine its stereochemistry. Both R- and S-configurations exist in 1; after modification by Mosher's reagent, they were effectively separated, and their ratio was deduced to be 59% and 41%, respectively. PMID- 20734943 TI - Spartinoxide, a new enantiomer of A82775C with inhibitory activity toward HLE from the marine-derived Fungus Phaeosphaeria spartinae. AB - The fungus Phaeosphaeria spartinae is an endophyte of the marine alga Ceramium sp. Investigation of this marine-derived fungus led to the isolation of spartinoxide (1), which is the enantiomer of the known compound A82775C (2). Additionally, the known metabolites 4-hydroxy-3-prenyl-benzoic acid (4) and anofinic acid (5) were obtained. The structures of all compounds were established from extensive spectroscopic investigations. Compounds 1, 4 and 5 were assayed against the enzymes human leukocyte elastase (HLE), trypsin, acetylcholinesterase and cholesterolesterase. Compounds 1 and 4 showed potent inhibition of HLE with IC50 values of 1.71 +/- 0.30 microg/mL (6.5 microM) and 1.67 +/- 0.32 microg/mL (8.1 microM), respectively. PMID- 20734944 TI - The first total synthesis of aspergillusol A, an alpha-glucosidase inhibitor. AB - The first total synthesis of aspergillusol A, an alpha-glucosidase inhibitor, was accomplished in an overall high yielding reaction sequence. A convergent synthetic approach was adopted; the erythritol segment of the molecule was derived from L-arabinose, whereas hydroxyphenylpyruvic acid oxime was built up from 4-hydroxybenzaldehyde. PMID- 20734945 TI - The effect of a phytosphingosine-like substance isolated from Asterina pectinifera on involucrin expression in mite antigen-stimulated HaCaT cells. AB - The aim of the present study was to investigate the effect of phytosphingosine (PS) on mite antigen-induced terminal differentiation abnormalities in HaCaT cells. For this purpose, a PS-like substance was isolated from Asterina pectinifera (starfish PS) using high-performance liquid chromatography and was partially characterized through 1H NMR analysis. The level of involucrin expression in HaCaT cell was measured by immunoblotting assay. Our results showed that PS treatments remarkably up-regulated the involucrin expression, which is known as a terminal differentiation marker in the epidermal mite antigen-treated HaCaT cells. This indicates that starfish PS could regulate mite antigen-induced terminal differentiation fluctuation in the epidermis. Taken together, the results suggest that starfish PS might be a useful therapeutic agent for atopic dermatitis. PMID- 20734946 TI - Chemical composition of fatty acid and unsaponifiable fractions of leaves, stems and roots of Arbutus unedo and in vitro antimicrobial activity of unsaponifiable extracts. AB - The chemical composition of the fatty acid and unsaponifiable fractions of the leaves, stems and roots of Arbutus unedo L. were determined using gas chromatography and gas chromatography-mass spectrometry. The fatty acid fractions of the leaves, stems and roots contained 38.5%, 31.3% and 14.1% palmitic acid, respectively, along with other long-chain fatty acids (up to C22). The chemical composition of the unsaponifiable fractions differed: the leaf and stem fractions contained high levels of aliphatic (32.1% and 62.6%, respectively) and terpenic compounds (49.6% and 25.7%, respectively), and the root fraction mainly contained esters, of which the most abundant was benzyl cinnamate (36.6%). The antimicrobial activities of the unsaponifiable fractions against nine species of microorganisms were assessed. The unsaponifiable leaf and stem extracts inhibited the growth of Klebsiella pneumoniae, Enterococcus faecalis and Candida albicans. PMID- 20734947 TI - Poly[3-(3,4-dihydroxyphenyl)glyceric acid] from Anchusa italica roots. AB - Elucidation of the main structural unit of a water-soluble, high-molecular weight preparation from the crude polysaccharides of Anchusa italica Retz. roots has been carried out. According to 13C NMR, 1H NMR and 2D heteronuclear 1H/13C HSQC spectral data, the main structural element of the high-molecular, water-soluble preparation was a regularly substituted polyoxyethylene chain, namely poly[oxy-1 carboxy-2-(3,4-dihydroxyphenyl)ethylene]. Most carboxylic groups of this caffeic acid-derived polymer of A. italica are methylated. PMID- 20734948 TI - New metabolite from Viburnum dilatatum. AB - Chemical investigation of the fruit of Viburnum dilatatum Thunb resulted in the isolation and characterization of a new phenolic glycoside (1), to which the name jiamizioside E was assigned. Its structure was established by chemical and spectroscopic means. PMID- 20734949 TI - Two new glycosides from Conyza bonariensis. AB - Studies on Conyza bonariensis (L.) Cronq. led to the isolation of two new glycosides trivially named as erigeside E and F (1-2), along with two new source compounds; benzyl-beta-D-glucopyranoside (3) and 2-phenylethyl-beta-D glucopyranoside (4). Compounds 1, 3, and 4 are aromatic glycosides, while compound 2 is an alkyl glycoside. Their structures were elucidated through mass spectrometric, and 1D- and 2D-NMR spectroscopic techniques, including 1H NMR, 13C NMR, HMQC, HSQC and HMBC. PMID- 20734950 TI - K+(ATP) channels-independent analgesic action of Crotalus durissus cumanensis venom. AB - The effect was investigated of the K+ channel blocker, glibenclamide, on the ability of Crotalus durissus cumanensis venom (CDCM) to promote peripheral antinociception. This was measured by formalin-induced nociception in male Swiss mice. CDCM (200 and 300 microg/kg) produced an antinociceptive effect during phase 2 in the formalin test. The effect of CDCM (200 microg/kg) was unaffected by the ATP-sensitive K+ channel blocker glibenclamide (2 mg/kg). These results suggest that CDCM is effective against acute pain. However, the ATP-sensitive K+ channels pathway is not contributable to the antinociceptive mechanism of CDCM. PMID- 20734951 TI - Isothymol in Ajowan essential oil. AB - Ajowan is a popular spice that is used in folk medicine in Algeria. Most studies reported that thymol is the main component of the seed oil. Isothymol was reported to be a constituent of essential oil isolated from aerial parts. Using plants harvested in five different locations in north western Algeria, every two weeks during the flowering stage, we demonstrated that isothymol was the major component when the plant was collected near the sea at low altitude and at the beginning of the flowering stage. In other cases, thymol is the predominant constituent. PMID- 20734953 TI - Chemical composition of the essential oil of leaves and roots of Ottoa oenanthoides (Apiaceae) from Merida, venezuela. AB - Essential oils extracted by hydrodistillation from leaves and roots of Ottoa oenanthoides Kunth (Apiaceae) were analyzed by GC/MS. The oils, obtained in yields of 0.10% and 0.66%, respectively, each contained four compounds, which were identified from their mass spectra and retention indices (RI). The major compound identified was 2-methoxy-8-methyl-1,4-naphthalindione (59.9% leaves, and 62.8%, roots), followed by 7-methoxy-1-naphthol (18.3% leaves and 17.3% roots), 2 naphthalenol (18.6% leaves and 15.0% roots), and 3-methoxy-2-naphthalenol (3.1% leaves and 2.1% roots). To the best of our knowledge, this is the first time that naphthalene derivatives have been reported for any species of the Apiaceae family. PMID- 20734952 TI - GC-MS analysis of the essential oils of ripe fruits, roots and flowering aerial parts of Elaeoselinum asclepium subsp. meoides growing in Sicily. AB - The compositions of the essential oils obtained by hydrodistillation of the ripe fruits, flowering aerial parts and roots of Elaeoselinum asclepium (L.) Bertol subsp. meoides (Desf.) Fiori (Apiaceae) were determined by GC-MS analysis. All the analyzed parts were very rich in alpha-pinene (77.1%, 92.2% and 60.8%, respectively). Other compounds detected in appreciable amounts were beta-pinene (4.3%, 4.0% and 8.2%), and sabinene (11.9% in ripe fruits; 12.8% in aerial parts). The plant synthesizes different classes of monoterpenes, including pinane, camphane, thujane, menthane, and fenchane derivatives, besides some acyclic monoterpenes. Trace amounts of sesquiterpenes and diterpenes were also detected. PMID- 20734954 TI - Volatile profiles of Artemisia alba from contrasting serpentine and calcareous habitats. AB - GC and GC-MS analyses of the essential oils of two populations of Artemisia alba Turra, wild-growing on calcareous and serpentine substrates, enabled the identification of 227 different components. Volatile profiles of the two samples differed significantly and only 48 components were in common to both oils. Major constituents of the oils were as follows: germacrene D (38.3%) in the serpentinophyte A. alba (sometimes regarded as A. alba ssp. saxatilis or A. saxatilis) oil and spathulenol (11.8%), artemisia ketone (10.1%), camphor (7.5%) and 1,8-cineole (7.4%) in A. alba (from calcareous habitat) oil. The noted differences were observable on the class level as well: with 73% the sesquiterpenoids (48.2% hydrocarbons, 24.5% oxygen or sulfur containing) were the most abundant compound class in A. saxatilis oil, while the other oil was dominated by monoterpenoids, comprising ca. 60% of the oil (2.1% hydrocarbons and 54.7% oxygenated). Additionally, the serpentinophyte yielded ca. four times less essential oil. These results pointed out to the fact that the type of substrate (soil) could have an important influence on the biosynthesis of A. alba volatiles (genetically predetermined or environmental), especially in the case of populations grown on serpentine rock, characterized by a deficiency of water and indispensable mineral elements. PMID- 20734955 TI - Volatile constituents of two rare subspecies of Thymus praecox. AB - Hydrodistilled essential oil and the corresponding headspace volatiles of Bosnian wild growing Thymus praecox ssp. polytrichus (A. Kern. Ex Borbas) Jalas and Thymus praecox ssp. skorpilii (Velen.) Jalas were subjected to capillary GC-MS analysis. This work presents a detailed essential oil analysis of these two rare Thymus subspecies from Bosnia, as well as the very first report on their headspace composition. Eighty-seven volatile constituents were identified in four samples. Two alcohols were the major constituents in the essential oil of T. praecox ssp. polytrichus, a monoterpene, linalool (13.9%), and a sesquiterpene, (E)-nerolidol (10.4%), while linalyl acetate (36.7%) and linalool (22.7%) were the most abundant volatiles in the corresponding headspace sample. Oxygenated monoterpenes (57.5%) predominate in the essential oil of T. praecox ssp. skorpilii with linalyl acetate (28.7%) and linalool (14.4%) as the main representatives. Headspace sample of this subspecies also showed richness in linalyl acetate (52.4%), while the second most abundant compound was alpha-pinene (14.5%), a monoterpene hydrocarbon. PMID- 20734956 TI - Antiproliferative and cytotoxic effects on malignant melanoma cells of essential oils from the aerial parts of Genista sessilifolia and G. tinctoria. AB - Genista species (family Leguminosae) show interesting biological properties. In this paper we describe the biological activity of the essential oils extracted from the aerial parts of G. sessilifolia DC. and G. tinctoria L. against M14 human melanoma cells, testing several biochemical parameters, such as cell vitality, cell membrane integrity and genomic DNA fragmentation. In addition, we report for the first time the study of the composition of the essential oil obtained from G. tinctoria. The most abundant components of the oil were carbonylic compounds such as (E)-beta-ionone (9.1%), dihydroactinidiolide (7.3%), nonanal (5.1%) and hexahydrofarnesylacetone (4.3%). The essential oils from aerial parts of both G. sessilifolia and G. tinctoria showed interesting potential anticancer activity, suggesting the presence of active compounds. PMID- 20734957 TI - Chemical composition and antibacterial activity of the essential oil of Retrohpyllum rospigliosii fruits from Colombia. AB - The essential oil from fruits of Retrophyllum rospigliosii (Pilger) C.N. Page grown in Colombia was analyzed by GC and GC/MS. Ninety-one compounds were identified, of which the most prominent were limonene (37.7%) and alpha-pinene (16.3%). The in vitro antibacterial activity of the essential oil was studied against seven bacterial strains using the disc diffusion method. The strongest activity of the oil was against the Gram-positive bacterium Bacillus cereus. PMID- 20734958 TI - Essential oil composition and insecticidal activity of Blumea perrottetiana growing in southwestern Nigeria. AB - The essential oil from the aerial parts of Blumea perrottetiana was obtained by hydrodistillation and analyzed by GC-MS. The volatile oil is dominated by 2,5 dimethoxy-p-cymene (30.0%) and 1,8-cineole (11.0%) with lesser amounts of sabinene (8.1%), delta-cadinene (5.3%) and (E)-caryophyllene (3.9%). The essential oil demonstrated notable insecticidal activity against the red flour beetle, Tribolium castaneum, consistent with traditional uses of the plant as an insecticide and anthelmintic. PMID- 20734959 TI - Chemical composition, antibacterial and antioxidant activity of the essential oil of Bupleurum longiradiatum. AB - The essential oil from the roots of Bupleurum longiradiatum, obtained by hydro distillation was analyzed by gas chromatography/mass spectrometry (GC/MS) and evaluated for antimicrobial activity and antioxidant activity. Fifty-one compounds were identified, representing 99.3% of the total oil. The major constituents were thymol (7.0%), butylidene phthalide (6.8%), 5-indolol (5.6%), heptanal (5.3%), 4-hydroxy-2-methylacetophenone (5.3%), 4,5-diethyl-octane (5.3%), bormeol (5.1%) and hexanoic acid (5.1%). The oil was tested against 4 bacteria at different concentrations using disc diffusion and 96-well dilution methods. The inhibition zones and minimum inhibitory concentration values for bacterial strains were in the range of 7.0-18.0 mm and 250 -500 microg/mL, respectively. The in vitro antioxidant activity was assessed by DPPH radical scavenging and inhibition of lipid peroxidation methods. The oil showed a potent free radical scavenging activity, as evidenced by the low IC50 value for DPPH radical (566.2 microg/mL) and inhibition of lipid peroxidation (induced by FeSO4, H2O2 and CCl4) with IC50 values of 275.2 microg/mL, 296.9 microg/mL and 118.7 microg/mL, respectively. PMID- 20734960 TI - Composition and antimicrobial and anti-wood-decay fungal activities of the leaf essential oils of Machilus pseudolongifolia from Taiwan. AB - The hydrodistillated leaf essential oil of Machilus pseudolongifolia was analyzed to determine its composition and yield. Seventy compounds were identified, the main components being beta-eudesmol (26.8%), alpha-cadinol (20.8%), viridiflorene (8.9%), alpha-caryophyllene (5.3%), globulol (4.6%) and beta-caryophyllene (4.2%). Oxygenated sesquiterpenes (60.1%) and sesquiterpene hydrocarbons (31.4%) were the predominant groups of compounds. The leaf oil exhibited excellent antimicrobial and anti-wood-decay fungal activities. PMID- 20734961 TI - Key enzymes of triterpenoid saponin biosynthesis and the induction of their activities and gene expressions in plants. AB - Triterpenoid saponins are one of the key active components of many medicinal plants. The biosynthetic pathway of triterpenoid saponins in higher plants and a lot of experimental results both indicated that the key enzymes involved in triterpenoid saponin synthesis are squalene synthase (SS), squalene epoxidase (SE), lupeol synthase (LS), dammarenediol synthase (DS), beta-amyrin synthase (beta-AS), cytochrome P450-dependent monooxygenase (PDMO), and glycosyltransferase (GT). The activities and coding genes of the key enzymes could be induced by a range of factors in various plant species. However, the effects of the factors on the content and composition of the triterpenoid saponins in specific plants are not certainly coincident, and different factors appear to induce the gene expressions of the key enzymes by different signal pathways and at different levels. This paper could provide a reference for strengthening the triterpenoid saponin-synthesizing capability of specific medicinal plants at enzyme and/or gene expression levels in order to improve the plants' commercial values. PMID- 20734962 TI - Tracheal non-Hodgkin's lymphoma masquerading as benign granulation tissue: a report of two cases. AB - Primary tracheal non-Hodgkin's lymphoma (NHL) is rare, with fewer than 30 cases reported to date. We review the clinical presentation, evaluation, and treatment of 2 cases of tracheal NHL mimicking granulation tissue. The first patient was a 67-year-old man with myelodysplastic syndrome and Crohn's disease who had a recurring lesion of the proximal trachea causing significant airway obstruction. The second patient was a 47-year-old man with a history of multiple intubations who presented with dyspnea and stridor due to circumferential tracheal stenosis. In both cases, bronchoscopy revealed abundant granulation tissue, and the initial biopsy results indicated benign disease. However, after requests from the diagnostic team to rule out lymphoma, additional immunohistochemical stains and polymerase chain reaction testing confirmed NHL. Radiotherapy was initiated. The first patient responded well and remains disease-free after 4 years. The second patient died of airway obstruction due to severe distal tracheal stenosis. Recurrent granulation tissue should raise the suspicion of malignancy and prompt further tissue evaluation for evidence of lymphoma. Steroids for airway compromise may cause progression to mature stenosis as prednisone is used in the treatment of lymphoma. Localized disease involving the central airways may be treated successfully with limited chemotherapy and radiotherapy. PMID- 20734963 TI - Myiasis of the external and middle ear. AB - Aural myiasis is a rare otolaryngological disease typically seen in poor hygienic conditions and medically disabled patients. We present a case of aural myiasis in a healthy woman who had no apparent risk factors for infestation and required extensive surgical intervention. We also discuss the literature of documented otolaryngological cases of myiasis and effective therapies. In our patient, symptoms of otalgia, otorrhea, and tinnitus resolved after multiple attempts at extraction resulted in successful eradication of larvae. The patient required tympanoplasty to reconstruct the damaged external and middle ear. Physicians should have a clinical suspicion of aural myiasis in patients with a travel history and an atypical presentation of acute otalgia and otorrhea. PMID- 20734964 TI - Arytenoid adduction for correcting vocal fold asymmetry: high-speed imaging. AB - OBJECTIVES: We hypothesized that high-speed digital imaging provides a quantitative method to evaluate the effect of arytenoid adduction for the correction of asymmetric and irregular vocal fold vibration in unilateral vocal fold paralysis. METHODS: Six subjects with unilateral vocal fold paralysis participated in the study (4 male, 2 female; mean [-SD] age, 52.5 +/- 21.3 years). Videokymographic and laryngotopographic methods for image analysis were performed for high-speed recordings of vocal fold vibration for visualizing the glottal vibratory patterns, and for quantifying the frequency of vibration of each vocal fold, respectively. Comparisons of the paralyzed and the normal vocal folds were made before and after arytenoid adduction. RESULTS: Analysis of the laryngotopographs revealed 2 distinct frequencies of vibration for the paralyzed and the contralateral vocal folds for all subjects before surgery. After arytenoid adduction, the vibration frequencies became identical or nearly identical in all subjects. CONCLUSIONS: Asymmetric vibration in vocal fold paralysis was exemplified by differences in vibration frequency between the vocal folds. The present data showed that after arytenoid adduction the vibration frequencies and the vibratory patterns of the contralateral vocal folds approached symmetry. This surgical procedure could improve the functional symmetry of the larynx for phonation. PMID- 20734965 TI - Bone-anchored hearing aids in patients with acquired and congenital unilateral inner ear deafness (Baha CROS): clinical evaluation of 56 cases. AB - OBJECTIVES: We performed an evaluation of the audiological and subjective benefits of the bone-anchored hearing aid (Baha) as a device for transcranial routing of sound (Baha CROS) in 56 patients with unilateral inner ear deafness. METHODS: We performed a prospective clinical follow-up study in a tertiary referral center. Previously reported results of 29 patients were supplemented with a second series of 30 patients with unilateral inner ear deafness; 3 patients dropped out during the evaluation. Audiometric measurements were taken before and after Baha CROS fitting. Subjective benefits were quantified with 4 different patient questionnaires. RESULTS: The sound localization results in a well-structured test setting were not differentiable from chance. The 5 patients with congenital hearing loss showed better scores in the unaided sound localization measurements. Overall, most patients reported some subjective improvement in their capacity to localize sounds with the Baha CROS in daily life. The main effect of the Baha CROS was to alleviate the head shadow effect during the speech-in-noise test. CONCLUSIONS: Poor sound localization in this larger series of patients confirms the findings of previous studies. Improvements in the speech-in-noise scores corroborated the efficacy of the Baha CROS in alleviating the head shadow effect. The 4 different patient questionnaires revealed subjective benefit and satisfaction in various domains. PMID- 20734966 TI - Relationship between postoperative recurrence rate and eosinophil density of nasal polyps. AB - OBJECTIVES: Nasal polyps develop as a result of chronic inflammation, mostly accompanied by pronounced eosinophil leukocyte infiltration. In this study we aimed to investigate the relationship between eosinophil density in nasal polyps and the postoperative recurrence rate of this disease. METHODS: Forty-two patients who underwent endoscopic sinus surgery for massive nasal polyposis by one surgeon were included in the study. The eosinophil leukocyte densities in nasal polyps were determined retrospectively on histologic slides by use of computer-assisted image analysis software. The patients were assigned to group 1, in whom nasal polyps contained up to 3 eosinophils per 1,000 microm2, and group 2, in whom nasal polyps contained 4 or more eosinophils per 1,000 microm2. The postoperative recurrence rates of nasal polyps were compared in the two groups. RESULTS: There were 20 patients in group 1 and 22 patients in group 2. Postoperative polyp recurrence was detected in 5 of 20 patients (25.0%) in group 1 and in 18 of 22 patients (81.8%) in group 2 during the 30-month postoperative followup period (p < 0.05). CONCLUSIONS: The eosinophil density of nasal polyps can be used to get an estimate of the postoperative recurrence risk. Eosinophil rich nasal polyps have a higher postoperative recurrence rate. PMID- 20734967 TI - Vocal function exercises for presbylaryngis: a multidimensional assessment of treatment outcomes. AB - OBJECTIVES: Presbylaryngis, or aging of the larynx, can adversely affect vocal function and quality of life in the elderly. This preliminary investigation examined the effects of vocal function exercises, a physiologic voice therapy approach, as a primary treatment for presbylaryngis. METHODS: Nine consecutive elderly patients with presbylaryngis (2 female, 7 male) underwent a 6-week course of voice therapy employing vocal function exercises. Pretherapy-versus posttherapy comparisons were made of self-ratings of voice handicap and phonatory effort level, as well as auditory-perceptual voice assessments, acoustic analyses, and visual-perceptual evaluations of laryngeal images. RESULTS: After treatment, patients reported significant reductions on Voice Handicap Index scores, phonatory effort levels, and voice disorder severity. Blinded listeners rated the posttreatment voices as significantly less breathy and strained. However, comparison of pretreatment and posttreatment maximum phonation times, acoustic measures, and laryngeal images did not reveal significant changes. CONCLUSIONS: These preliminary data suggest that vocal function exercises produce significant functional and perceptual improvements in voice, and deserve further attention as a treatment for elderly patients with presbylaryngis. PMID- 20734968 TI - Initial clinical experience with balloon dilation in revision frontal sinus surgery. AB - OBJECTIVES: The purpose of this study was to determine whether balloon dilation is effective in revision frontal sinus surgery. METHODS: We retrospectively reviewed all patients who had previously undergone endoscopic frontal sinus surgery and had persistent sinusitis. All patients then underwent balloon dilation of the frontal ostium. Outcome measurements included endoscopic patency of the frontal ostium, Lund-Mackay scores, culture-positive postoperative infections, and subjective persistence of symptoms. RESULTS: Twenty-four frontal ostia and recesses were dilated in 13 patients. The mean follow-up was 13 months (range, 7 to 19 months). During follow-up, 21 of 24 ostia (86%) remained patent and 3 required additional procedures. Postoperative computed tomography scans were performed an average of 12 months after dilation (range, 6 to 18 months) in 9 patients (17 sinuses). The average Lund-Mackay score was 1.35 before dilation and 0.87 at follow-up (p = 0.0076), with 41% of sinuses (7 of 17) displaying radiographic improvement. The average number of postoperative infections was 2.07 (range, 0 to 7). Frontal headaches persisted in 38% of patients (5 of 13) at follow-up. CONCLUSIONS: Balloon dilation of the frontal ostia has a posttreatment patency rate comparable to those of other endoscopic revision techniques. Although it may not fully address the frontal sinus disease of all patients, it is a less invasive technique that may be helpful for some patients. PMID- 20734969 TI - Hemoglobin monitoring in head and neck cancer patients undergoing radiotherapy. AB - OBJECTIVES: Anemia is a well-recognized factor for local recurrence and decreased survival in cancer patients undergoing radiotherapy. Additionally, lower hemoglobin (Hb) levels have a negative impact on radiotherapy efficacy and response rates. The objective of this audit was to investigate how frequently Hb levels were observed in head and neck cancer patients receiving radiotherapy within a multidisciplinary team setting. METHODS: We performed a retrospective first-cycle audit in a university hospital in Glasgow that is a tertiary referral center for head and neck cancer. Included were 78 patients with head and neck cancer who were undergoing radiotherapy. Online laboratory services and clinical case sheets were checked for each patient to monitor the frequency of observation of Hb levels before, during, and after radiotherapy. RESULTS: Of these 78 patients, only 49 had their Hb level checked before radiotherapy treatment, only 9 during radiotherapy, and only 27 after completion of radiotherapy treatment (p < 0.0001). Of the 49 patients with preradiotherapy Hb levels available, 24% were found to be anemic; none of these patients had their Hb monitored during radiotherapy, and only 4 had Hb levels recorded after completion of treatment. CONCLUSIONS: This audit has highlighted that despite evidence emphasizing that anemia in cancer is an independent prognostic factor for recurrence, there is no formal protocol for Hb monitoring in head and neck cancer patients undergoing radiotherapy. The audit has also demonstrated that Hb monitoring is infrequently performed and that subsequent observation of the Hb level is suboptimal. PMID- 20734970 TI - Carotid blowout in patients with head and neck cancer. AB - OBJECTIVES: The objective was to review the clinicopathologic features of carotid blowout syndrome (CBS) in patients with head and neck cancer (HNC) and present a management algorithm. METHODS: We reviewed all HNC patients with a diagnosis of CBS seen at our tertiary cancer hospital from 1994 to 2009 and performed a retrospective review of all English-language studies documenting CBS cases within the past 15 years. RESULTS: Eight patients with HNC developed CBS at our institution, and another 132 HNC patients were presented in 21 studies. Patients with CBS typically have a history of radiotherapy (89%), nodal metastasis (69%), and neck dissection (63%). This disease usually occurs proximal to the carotid bifurcation and is commonly associated with soft tissue necrosis in the neck (55%) and mucocutaneous fistulas (40%). Half of CBS patients present with sentinel bleeding, but 60% of patients will develop a life-threatening hemorrhage requiring emergent intervention. Over 90% of patients with CBS were treated with endovascular therapy, and surgical ligation was rarely indicated. The morbidity and mortality rates of patients with CBS are significant; only 23% have survived without evidence of disease. CONCLUSIONS: Carotid blowout syndrome is uncommon and can be rapidly fatal without prompt diagnosis and intervention. Although endovascular treatment within the carotid system can have a significant risk of mortality and neurologic morbidity, it has become the treatment of choice for CBS. PMID- 20734971 TI - Postoperative complications of powered intracapsular tonsillectomy and monopolar electrocautery tonsillectomy in teens versus adults. AB - OBJECTIVES: This study was performed to determine whether teens have different rates of posttonsillectomy hemorrhage, admission for dehydration, or recurrent tonsillitis compared to adults. Specifically, these parameters were compared within two groups: patients who underwent powered intracapsular tonsillectomy (PIT) and those who underwent monopolar electrocautery tonsillectomy (MET). METHODS: In a retrospective review of 579 patients at least 12 years of age from January 2000 to July 2006 in a tertiary referral center, outcome measures of reoperation for hemorrhage, readmission or emergency room visit for dehydration, and postoperative tonsillitis were compared for 200 patients 12 to 19 years of age and 379 patients more than 19 years of age. These outcome measures in teens were compared to those in adults who had tonsillectomy by the same technique (101 teens who underwent PIT compared to 117 adults who underwent PIT, and 99 teens who underwent MET compared to 262 adults who underwent MET). Outcome measures were also compared within the PIT and MET groups based on the indication for surgery (chronic tonsillitis, tonsillar hypertrophy, or both). RESULTS: In comparing teens to adults who underwent the same technique (PIT versus PIT, or MET versus MET), no statistically significant differences existed in the incidence of hemorrhage, dehydration, or postoperative tonsillitis. Greater hemorrhage rates for adults who underwent MET compared to teens, however, almost met statistical significance (p = 0.053). Analyzing complication rates by indication within the PIT and MET groups exclusively revealed higher rates of hemorrhage in adults who underwent the MET technique for the indication of chronic tonsillitis. Within the PIT comparison, no significant differences were found on the basis of indication for surgery. CONCLUSIONS: Teenage patients who undergo tonsillectomy should be considered unique as far as complication rates are concerned. Comparison of technique-specific complication rates between adults and teens showed no significant differences in either the PIT or MET groups, although adults who underwent MET had greater hemorrhage rates that almost met significance (p = 0.053). Adults who were undergoing tonsillectomy for chronic tonsillitis were more likely than teens to encounter postoperative hemorrhage if they underwent the MET technique. PMID- 20734972 TI - Congenital cholesteatoma: posterior lesions and the staging system. AB - OBJECTIVES: We described the characteristics of congenital cholesteatoma in Japanese patients and assessed whether the staging system is useful for predicting the rate of residual disease, the need for reexploration, and surgical outcomes. METHODS: We performed a retrospective chart analysis of 23 consecutive patients with congenital cholesteatoma. RESULTS: The proportion of cases with anterior-superior quadrant involvement was significantly lower in the Asian group than in Western patients. The total residual rate was 26%, and there was a positive association between stage and residual rate, ranging from 0% in stage I and II to 44% in stage IV. Canal wall-up tympanomastoidectomy was the most frequent procedure (57%), and 61% had reexploration. CONCLUSIONS: Congenital cholesteatoma in Asia is less likely to involve the anterior-superior quadrant than in Western patients. The 4-stage system was useful for predicting residual rates, even in patients in whom anterior-superior quadrant involvement was less common. Postoperative hearing was significantly related to the stages. A routine second-look procedure may be unnecessary in the early stages, whereas reexploration would be better performed in advanced stages. Endoscopy might reduce residual disease and the need for reexploration in the near future. PMID- 20734973 TI - Effect of Burow's solution on the guinea pig inner ear. AB - OBJECTIVES: We examined the changes in the inner ear hair cells following intratympanic injection of Burow's solution. METHODS: Thirty-one albino guinea pigs with a normal Preyer's reflex were used. Burow's solution was applied and allowed to remain on the round window membrane for 30 minutes (30-minute group), 1 hour (1-hour group), or 2 hours (2-hour group). Seven days later, the left temporal bone was removed. Auditory brain stem responses were recorded at 4, 8, and 20 kHz before application of Burow's solution and again immediately before decapitation. The cochlea and utricle were dissected, stained with rhodamine phalloidin, and examined under a fluorescence microscope. RESULTS: The postoperative auditory brain stem response thresholds at 20 kHz in the 1-hour group and those at 8 and 20 kHz in the 2-hour group were increased significantly compared to the baseline thresholds. Surface preparations of the organ of Corti revealed no hair cell loss in the 30-minute group, loss of outer hair cells in the lower half of the basal turn in half of the animals in the 1-hour group, and loss of outer hair cells in the basal turn in almost all animals in the 2-hour group. In the 2-hour group, the microthin sections of the round window membrane showed degeneration of the outer epithelium. CONCLUSIONS: The retention of Burow's solution on the round window membrane for 2 hours induces degeneration of the outer epithelium and damage to the cochlear outer hair cells. PMID- 20734974 TI - Generation of a manganese specific restriction endonuclease with nicking activity. AB - A typical feature of type II restriction endonucleases (REases) is their obligate sequence specificity and requirement for Mg(2+) during catalysis. R.KpnI is an exception. Unlike most other type II REases, the active site of this enzyme can accommodate Mg(2+), Mn(2+), Ca(2+), or Zn(2+) and cleave DNA. The enzyme belongs to the HNH superfamily of nucleases and is characterized by the presence of a betabetaalpha-Me finger motif. Residues D148, H149, and Q175 together form the HNH active site and are essential for Mg(2+) binding and catalysis. The unique ability of the enzyme to cleave DNA in the presence of different metal ions is exploited to generate mutants that are specific to one particular metal ion. We describe the generation of a Mn(2+)-dependent sequence specific endonuclease, defective in DNA cleavage with Mg(2+) and other divalent metal ions. In the engineered mutant, only Mn(2+) is selectively bound at the active site, imparting Mn(2+)-mediated cleavage. The mutant is impaired in concerted double-stranded DNA cleavage, leading to accumulation of nicked intermediates. The nicking activity of the mutant enzyme is further enhanced by altered reaction conditions. The active site fluidity of REases allowing flexible accommodation of catalytic cofactors thus forms a basis for engineering selective metal ion-dependent REase additionally possessing nicking activity. PMID- 20734976 TI - Role of symmetry breaking on the optical transitions in lead-salt quantum dots. AB - The influence of quantum confinement on the one- and two-photon absorption spectra (1PA and 2PA) of PbS and PbSe semiconductor quantum dots (QDs) is investigated. The results show 2PA peaks at energies where only 1PA transitions are predicted and 1PA peaks where only 2PA transitions are predicted by the often used isotropic k x p four-band envelope function formalism. The first experimentally identified two-photon absorption peak coincides with the energy of the first one photon allowed transition. This first two-photon peak cannot be explained by band anisotropy, verifying that the inversion symmetry of the wave functions is broken and relaxation of the parity selection rules has to be taken into account to explain optical transitions in lead-salt QDs. Thus, while the band anisotropy of the bulk semiconductor plays a role in the absorption spectra, especially for the more anisotropic PbSe QDs, a complete model of the absorption spectra, for both 1PA and 2PA, must also include symmetry breaking of the quantum confined wave functions. These studies clarify the controversy of the origin of spectral features in lead-salt QDs. PMID- 20734977 TI - Signal-to-noise ratio in carbon nanotube electromechanical piezoresistive sensors. AB - The signal-to-noise ratio (SNR) of piezoresistive transducers based on carbon nanotube field effect transistors (CNFETs) is an essential yet unexplored performance metric. Here, we show that the SNR of CNFET piezoresistors made of small band gap semiconducting SWNTs (SGS-SWNTs) depends strongly on the gate bias voltage. The SNR is found by combining low frequency 1/f noise with the piezoresistive signal. We find that SGS-CNFET piezoresistors are best operated at device off-state, where strain resolution is maximal. PMID- 20734978 TI - Molecular doping and subsurface dopant reactivation in si nanowires. AB - Impurity doping in semiconductor nanowires, while increasingly well understood, is not yet controllable at a satisfactory degree. The large surface-to-volume area of these systems, however, suggests that adsorption of the appropriate molecular complexes on the wire sidewalls could be a viable alternative to conventional impurity doping. We perform first-principles electronic structure calculations to assess the possibility of n- and p-type doping of Si nanowires by exposure to NH(3) and NO(2). Besides providing a full rationalization of the experimental results recently obtained in mesoporous Si, our calculations show that while NH(3) is a shallow donor, NO(2) yields p-doping only when passive surface segregated B atoms are present. PMID- 20734979 TI - Niobium-doped titania nanoparticles: synthesis and assembly into mesoporous films and electrical conductivity. AB - Crystalline niobium-doped titania nanoparticles were synthesized via solvothermal procedures using tert-butyl alcohol as a novel reaction medium, and their assembly into mesoporous films was investigated. The solvothermal procedure enables the preparation of crystalline doped and undoped nonagglomerated titania nanoparticles, whose size can be controlled from 4 to 15 nm by changing the reaction temperature and time. The anatase lattice of these particles can incorporate more than 20 mol % of Nb ions. The nanoparticles can be easily dispersed at high concentrations in THF to form stable colloidal suspensions and can be assembled into uniform porous mesostructures directed by the commercial Pluronic block copolymer F127. The resulting mesoporous films show a regular mesostructure with a d spacing of about 17 nm, a uniform pore size of about 10 nm with crystalline walls, a high porosity of 43%, and a large surface area of 190 m(2) cm(-3). Substitutional doping with niobium ions drastically increases the electrical conductivity of the titania particles. The electrical conductivity of as-prepared nanoparticles containing 20 mol % of Nb is 2 x 10(-5) S cm(-1); it increases to 0.25 S cm(-1) after treatment at 600 degrees C in nitrogen. PMID- 20734980 TI - CCl3CN: a crucial promoter of mCPBA-mediated direct ether oxidation. AB - The direct oxidation of ether sp(3) C-H bonds using the new reagent system mCPBA/CCl(3)CN/MeCN has been developed. CCl(3)CN in MeCN drastically alters the reactivity of m-chloroperbenzoic acid (mCPBA), and chemoselective transformation of methyl ethers to ketones was realized under mild conditions. Radical-based mCPBA-mediated oxidation was suggested as the reaction mechanism. The present new reaction expands the utility of methyl ethers as stable synthetic precursors of carbonyl compounds and of mCPBA as a radical-based C-H oxidizing agent. PMID- 20734981 TI - One-pot AgOAc-mediated synthesis of polysubstituted pyrroles from primary amines and aldehydes: application to the total synthesis of purpurone. AB - A simple and efficient method for the synthesis of 1,3,4-trisubstituted or 3,4 disubstituted pyrroles has been developed. The reaction represents the first time that pyrroles are synthesized directly from readily available aldehydes and amines (anilines) as starting materials. This method has been successfully applied to the rapid synthesis of purpurone. PMID- 20734982 TI - Aryl(sulfonyl)amino group: a convenient and stable yet activated modification of amino group for its intramolecular displacement. AB - Aryl(sulfonyl)amino groups, readily derived from sulfonyl- or arylamines by standard methods as well as the recently introduced methods of sulfonylation and arylation, proved to be good leaving groups in intramolecular substitution reactions by various nitrogen, oxygen, and carbon nucleophiles. PMID- 20734983 TI - N-annulated perylene fused porphyrins with enhanced near-IR absorption and emission. AB - N-Annulated perylene fused porphyrins 1 and 2 were synthesized by oxidative dehydrogenation using a Sc(OTf)(3)/DDQ system. These newly synthesized hybrid molecules are highly soluble in organic solvents and exhibit remarkably intense near-IR absorption, as well as detectable photoluminescence quantum yields, all of which are comparable to or even exceed those of either meso-beta doubly linked porphyrin dimer/trimer or bis/tri-N-annulated rylenes. PMID- 20734984 TI - Yeast alpha-glucosidase inhibition by isoflavones from plants of Leguminosae as an in vitro alternative to acarbose. AB - In the course of searching for new classes of alpha-glucosidase inhibitors originated from natural resources, 11 kinds of isoflavones, i.e., medicarpin (1), formononetin (2), mucronulatol (3), (3R)-calussequinone (5), (3R)-5' methoxyvestitol (6), tectorigenin (7), biochanin A (8), tuberosin (9), calycosin (10), daidzein (11), and genistein (12), as well as a flavone, liquritigenin (4), were isolated as active principles responsible for the yeast alpha-glucosidase inhibitory activity from two leguminous plant extracts, i.e., the heartwood extract of Dalbergia odorifera and the roots extract of Pueraria thunbergiana. Each components (1-12) demonstrated a significantly potent inhibition on yeast alpha-glucosidase in a dose dependent manner when the p-nitrophenyl-alpha-D glucopyranoside was used as a substrate in vitro. The concentration required for 50% enzyme inhibition (IC50) were calculated as 2.93 mM (1), 0.51 mM (2), 3.52 mM (7) 0.35 mM (8), 3.52 mM (9), 0.85 mM (11), and 0.15 mM (12) when that of reference drug acarbose was evaluated as 9.11 mM, in vitro. However, isoflavone glycosides, i.e., puerarin (13), daidzin (14), formononetin-7-O-beta glucopyranoside (15), and genistin (16), exhibited a relatively poor inhibitory activity on yeast alpha-glucosidase as compared with the corresponding isoflavone (2, 11, 12), respectively. PMID- 20734986 TI - Stability of lutein in wholegrain bakery products naturally high in lutein or fortified with free lutein. AB - Lutein is a yellow pigment found in common foods that promotes the health of eyes and skin and is associated with reduced risk of age-related macular degeneration and cataracts. In the present study, selected high-lutein wheat and corn were milled into wholegrain flours by two mills to improve flour uniformity. The high lutein and lutein-fortified wholegrain flours were processed into breads, cookies, and muffins to study lutein stability during baking and subsequent storage. Lutein and its isomers were separated, identified, and quantified by LC UV/vis and LC-MS following extraction with water-saturated 1-butanol. Baking resulted in a significant reduction in all-trans-lutein and the formation of cis lutein and cis-zeaxanthin isomers. Subsequent storage at ambient temperature had a slight impact on the content of all-trans-lutein. Effects of processing were more pronounced in lutein-fortified products, and the degradation rate of lutein was influenced by concentration and baking recipe. Fortified cookies and muffins showed greater lutein reduction compared with bread. Despite the significant reduction in lutein, the fortified bakery products still possessed reasonable amounts per serving that would enhance daily intake and consumption of wholegrain foods. PMID- 20734985 TI - Hispidulin sensitizes human ovarian cancer cells to TRAIL-induced apoptosis by AMPK activation leading to Mcl-1 block in translation. AB - Whether hispidulin, a flavone from traditional Chinese medicine, can modulate the anticancer effects of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), the cytokine currently in clinical trials was investigated. In the present study, we found that hispidulin potentiated the TRAIL-induced apoptosis in human ovarian cancer cells and converted TRAIL-resistant cells to TRAIL-sensitive cells. When examined for its mechanism, we found that hispidulin was highly effective in activation of caspases 8 and caspase 3 and consequent poly(ADP-ribose) polymerase (PARP) cleavage. Moreover, we found that hispidulin downregulated the expression of Mcl-1, Bcl-2, and Bcl-xL. Whereas the downregulation of Bcl-2 and Bcl-xL was less pronounced, the downregulation of Mcl 1 was quite dramatic and was time-dependent. This sensitization is controlled through the adenosine monophosphate (AMP)-activated protein kinase (AMPK), which is the central energy-sensing system of the cell. Interestingly, we determined that AMPK is activated upon hispidulin treatment, resulting in mammalian target of rapamycin (mTOR) inhibition leading to Mcl-1 decrease. Therefore, our results show a novel mechanism for the sensitization to TRAIL-induced apoptosis linking hispidulin treatment to Mcl-1 downexpression. In addition, this study provides a rationale for the combined use of death receptor (DR) ligands with AMPK activators or mTOR inhibitors in the treatment of human cancers. PMID- 20734987 TI - Plant-growth regulator, imidazole-4-carboxamide, produced by the fairy ring forming fungus Lepista sordida. AB - Rings or arcs of fungus-regulated plant growth occur often on the floor of woodlands, in agricultural areas, and in grasslands worldwide. These rings are commonly called "fairy rings". A plant-growth regulating compound was isolated from a fairy ring forming fungus, Lepista sordida , and its chemical structure was identified as imidazole-4-carboxamide (ICA) by spectroscopic analyses including single-crystal X-ray diffraction techniques. ICA inhibited the growth of turfgrass and rice seedling. On the other hand, in a greenhouse experiment, this compound increased rice grain yield by 26% compared with control. PMID- 20734988 TI - Acceleration of nucleophilic CH activation by strongly basic solvents. AB - (IPI)Ru(II)(OH)(n)(H(2)O)(m), 2, where IPI is the NNN-pincer ligand, 2,6 diimidizoylpyridine, is shown to catalyze H/D exchange between hydrocarbons and strongly basic solvents at higher rates than in the case of the solvent alone. Significantly, catalysis by 2 is accelerated rather than inhibited by increasing solvent basicity. The evidence is consistent with the reaction proceeding by base modulated nucleophilic CH activation. PMID- 20734990 TI - Quantitative analysis of protein complex constituents and their phosphorylation states on a LTQ-Orbitrap instrument. AB - Cellular functions are largely carried out by noncovalent protein complexes that may exist within the cell as stable modules or as assemblies of dynamically changing composition, whose formation and decomposition are triggered in response to extracellular stimuli. The protein constituents of complexes often exhibit post-translational modifications such as phosphorylation that can impact their ability to interact with other proteins and thus to form multicomponent complexes. A complete characterization of a particular protein complex thus requires determining both, the identity of interacting proteins and their covalent modifications, in terms of attachment sites and stoichiometry. We have previously developed a protocol which identifies genuine constituents of partially purified protein complexes and concurrently determines their phosphorylation sites and levels in a single LC-MS/MS analysis performed on a MALDI-TOF/TOF instrument (Pflieger, D.; Junger, M. A.; Muller, M.; Rinner, O.; Lee, H.; Gehrig, P. M.; Gstaiger, M.; Aebersold, R. Mol. Cell. Proteomics 2008 , 7 , 326 - 346). The method combines fourplex iTRAQ labeling (isobaric tags for relative and absolute quantification) and phosphatase treatment of peptide samples derived from the tryptic digestion of isolated complexes. To test the performances of this method with nanoESI and different peptide fragmentation modes, possibly better suited for the identification of phosphorylated sequences than MALDI-TOF/TOF-MS, we have implemented it on the nanoESI-LTQ-Orbitrap instrument. The model protein beta-casein was used to optimize the conditions with respect to sensitivity and quantitative accuracy: a combination of CID fragmentation in the linear ion trap and Higher energy Collision Dissociation (HCD) appeared optimal to obtain reliable and robust identification and quantification data. The optimized conditions were then applied to identify and estimate the respective levels of phosphorylation sites on the purified, autoactivated tyrosine kinase domain of Fibroblast Growth Factor Receptor 3 (FGFR3-KD) and to analyze complexes formed around the insulin receptor substrate homologue CHICO immunopurified from Drosophila melanogaster cells that were either stimulated with insulin or left untreated. These new analyses allowed us to improve the assignment of the phosphorylation sites of some peptides previously detected by MALDI-TOF/TOF analysis and to identify additional phosphorylated sequences in CHICO and in the insulin receptor. PMID- 20734989 TI - Plasmon-induced inactivation of enteric pathogenic microorganisms with Ag AgI/Al2O3 under visible-light irradiation. AB - The plasmon-induced photocatalytic inactivation of enteric pathogenic microorganisms in water using Ag-AgI/Al(2)O(3) under visible-light irradiation was investigated. The catalyst was found to be highly effective at killing Shigella dysenteriae (S. dysenteriae), Escherichia coli (E. coli), and human rotavirus type 2 Wa (HRV-Wa). Its bactericidal efficiency was significantly enhanced by HCO(3)(-) and SO(4)(2-) ions, which are common in water, while phosphate had a slightly positive effect on the disinfection. Meanwhile, more inactivation of E. coli was observed at neutral and alkaline pH than at acid pH in Ag-AgI/Al(2)O(3) suspension. Furthermore, the effects of inorganic anions and pH on the transfer of plasmon-induced charges were investigated using cyclic voltammetry analyses. Two electron-transfer processes occurred, from bacteria to Ag nanoparticles (NPs) and from inorganic anions to Ag NPs to form anionic radicals. These inorganic anions including OH(-) in water not only enhanced electron transfer from plasmon-excited Ag NPs to AgI and from E. coli to Ag NPs, but their anionic radicals also increased bactericidal efficiency due to their absorbability by cells. The plasmon-induced electron holes (h(+)) on Ag NPs, O(2)(*-), and anionic radicals were involved in the reaction. The enhanced electron transfer is more crucial than the electrostatic force interaction of bacteria and catalyst for the plasmon-induced inactivation of bacteria using Ag AgI/Al(2)O(3). PMID- 20734992 TI - Desymmetrization of meso-cyclic imides via enantioselective monohydrogenation. AB - meso-Cyclic imides are monohydrogenated to form the corresponding hydroxy lactams in 88-97% ee using trans-[Ru((R)-BINAP)(H)(2)((R,R)-dpen)] and related compounds as catalysts with base in THF. The hydrogenation proceeds with high enantiogroup- and chemoselectivity, and it is a desymmetrization reaction, forming up to five stereogenic centers in one reaction. Conversion of a hydroxy lactam into the corresponding iminium ion followed by addition of indene extended the number of stereogenic centers from 5 to 7. PMID- 20734991 TI - The red and the black. AB - "Pigmentation, which is primarily determined by the amount, the type, and the distribution of melanin, shows a remarkable diversity in human populations, and in this sense, it is an atypical trait."--E. J. Parra. Melanin is found throughout the human body, skin, eye, brain, hair, and inner ear, yet its molecular structure remains elusive. Researchers have characterized the molecular building blocks of melanin but have not been able to describe how those components fit together in the overall architecture of the pigment. Melanin is categorized into two distinct classes, pheomelanin (red) and eumelanin (black). Although these classes share a common biosynthetic origin, specific molecular reactions occurring early in pigment production differentiate these two types. Pure eumelanin is found throughout nature, which has allowed researchers to characterize and quantify its chemical properties. However, pure pheomelanin is not observed in nature and rarely makes up more than ~25% of the total melanin present. In this Account, we explore our current understanding of the structure and reactivity of the red and black pigments. Epidemiological studies of skin and ocular cancers suggest that increasing relative proportions of pheomelanin correlate with increased risk factors for these diseases. Therefore, understanding the factors that control the relative abundance of the two pigments has become increasingly important. Consequently, researchers have worked to elucidate the chemistry of pheomelanin to determine whether the pigment could cause these cancers and, if so, by what mechanisms. The photoactivation of oxygen by pheomelanin in the UV-A range could contribute to the development of UV induced cancers: recent measurement of the surface photoionization threshold of intact melanosomes reveals a lower photoionization potential for pheomelanin than eumelanin. A complementary study of intact human melanosomes isolated from different colored irides reveals that the absorption coefficient of the melanosome decreases with increasing pheomelanin content. These results suggest that the epidemiological data may simply result from an increased exposure of the underlying tissues to UV light. PMID- 20734993 TI - Rationally designed fluorescence turn-on sensors: a new design strategy based on orbital control. AB - Herein, we explore a new strategy in the chemo-sensor field for fluorescence amplification upon binding with metal ions based on controlled participation of the nitrogen lone pair orbital. The basic architecture of the sensor entails a fluorophore, the sp(2) hybridized nitrogen lone pair (-C?N-), and a chelator site referred to as the control part. Though nonplanar and nonfluorescent, compound IC1 achieved pseudo planarity from binding with Zn(2+) as indicated by the increased fluorescence signal. Its other analogue (IC2) is also planar, and unlike IC1-Zn(2+) was fluorescent with a lack of binding affinity to metal ions. The time-dependent density functional theory (TDDFT) calculations revealed that the fluorescence amplification was due to the blocking of the nitrogen lone pair orbital; unlikely geometrical rearrangements were insignificant. This could indicate a breakthrough concept in the future design of fluorescent turn-on sensors. PMID- 20734995 TI - Electronic coupling between two cyclometalated ruthenium centers bridged by 1,3,6,8-tetra(2-pyridyl)pyrene (tppyr). AB - A new cyclometalating bridging ligand 1,3,6,8-tetra(2-pyridyl)pyrene was designed and synthesized through 4-fold Suzuki couplings between 1,3,6,8-tetrabromopyrene and 2-pyridylboronate. A bis-cyclometalated bisruthenium complex bridged by this ligand showed the presence of an electronic coupling between individual metal centers, as indicated by electrochemical and spectroscopic studies. PMID- 20734997 TI - A modified physiological BCS for prediction of intestinal absorption in drug discovery. AB - In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 degrees C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects. PMID- 20734996 TI - Proteomic analysis of protein-protein interactions within the Cysteine Sulfinate Desulfinase Fe-S cluster biogenesis system. AB - Fe-S cluster biogenesis is of interest to many fields, including bioenergetics and gene regulation. The CSD system is one of three Fe-S cluster biogenesis systems in E. coli and is comprised of the cysteine desulfurase CsdA, the sulfur acceptor protein CsdE, and the E1-like protein CsdL. The biological role, biochemical mechanism, and protein targets of the system remain uncharacterized. Here we present that the active site CsdE C61 has a lowered pK(a) value of 6.5, which is nearly identical to that of C51 in the homologous SufE protein and which is likely critical for its function. We observed that CsdE forms disulfide bonds with multiple proteins and identified the proteins that copurify with CsdE. The identification of Fe-S proteins and both putative and established Fe-S cluster assembly (ErpA, glutaredoxin-3, glutaredoxin-4) and sulfur trafficking (CsdL, YchN) proteins supports the two-pathway model, in which the CSD system is hypothesized to synthesize both Fe-S clusters and other sulfur-containing cofactors. We suggest that the identified Fe-S cluster assembly proteins may be the scaffold and/or shuttle proteins for the CSD system. By comparison with previous analysis of SufE, we demonstrate that there is some overlap in the CsdE and SufE interactomes. PMID- 20734999 TI - Self-propagating molecular assemblies as interlayers for efficient inverted bulk heterojunction solar cells. AB - Here we report the first use of self-propagating molecule-based assemblies (SPMAs) as efficient electron-transporting layers for inverted organic photovoltaic (OPV) cells. P3HT-PCBM cells functionalized with optimized SPMAs exhibit power conversion efficiencies approaching 3.6% (open circuit voltage = 0.6 V) vs 1.5% and 2.4% for the bare ITO and Cs(2)CO(3)-coated devices, respectively. The dependence of cell response parameters on interlayer thickness is investigated, providing insight into how to further optimize device performance. PMID- 20734998 TI - Proliferation inhibition, DNA damage, and cell-cycle arrest of human astrocytoma cells after acrylamide exposure. AB - Acrylamide (ACR) has been recognized as a neurological and reproductive toxin in humans and laboratory animals. This study aimed to determine the effects of ACR induced DNA damage on cell cycle regulation in human astrocytoma cell lines. Treatment of U-1240 MG cells with 2 mM ACR for 48 h resulted in a significant inhibition of cell proliferation as evaluated by Ki-67 protein expression and MTT assay. The analysis of DNA damage with the comet assay showed that treatment of the cells with 0.5, 1, and 2 mM ACR for 48 h caused significant increases in DNA damage by 3.5-, 4-, and 14-fold, respectively. Meanwhile, analysis of cell-cycle arrest with flow cytometry revealed that the ACR treatments resulted in significant increases in the G(0)/G(1)-arrested cells in a time- and dose dependent manner. Expression of DNA damage-associated/checkpoint-related signaling molecules, including phosphorylated-p53 (pp53), p53, p21, p27, Cdk2, and cyclin D(1), in three human astrocytoma cell lines (U-1240 MG, U-251 MG, and U-87 MG) was also analyzed by immunoblotting. Treatment of the three cell lines with 2 mM ACR for 48 h caused marked increases in pp53 and Cdk2, as well as decreases in cyclin D(1) and p27. Moreover, increases in p53 and p21 were detected in both U-1240 and U-87 MG cells, whereas no marked change in p53 and a decrease in p21 were observed in U-251 MG cells. To address the involvement of ataxia telangiectasia mutated/ATM-Rad3-related (ATM/ATR) kinase in the signaling of ACR-induced G(0)/G(1) arrest, caffeine was used to block the ATM/ATR pathway in U-1240 MG cells. Caffeine significantly attenuated the ACR-induced G(0)/G(1) arrest as well as the expression of DNA damage-associated/checkpoint-related signaling molecules in a dose-dependent manner. This in vitro study clearly demonstrates the critical role of ATM/ATR in the signaling of ACR-induced cell cycle arrest in astrocytoma cells. PMID- 20735000 TI - Tetramolecular DNA quadruplexes in solution: insights into structural diversity and cation movement. AB - The present study expands the notion that the simple oligonucleotide sequence d(TG(4)T) in solution forms a tetramolecular G-quadruplex having a parallel orientation of the four strands and four G-quartets with all of the residues in the anti orientation. NMR experiments have revealed the equilibrium of two monomeric forms with a ratio between 85:15 and 70:30 in the presence of K(+), Na(+), and (15)NH(4)(+) ions. The major form consists of four G-quartets, whereas the minor form exhibits an additional T-quartet at the 5' end. An analogous oligonucleotide with U at the 5' end adopts a dimeric structure of G-quadruplex units in the presence of K(+) and (15)NH(4)(+) cations but not in the presence of Na(+) ions, where monomeric forms are present. Three (15)NH(4)(+) ion binding sites between the four G-quartets within the major monomeric form have been identified, while an additional (15)NH(4)(+) ion binding site between the G- and T-quartets at the 5' end of the minor form has been established. The dimeric d[(UG(4)T)(4)](2) G-quadruplex exhibits eight (15)NH(4)(+) ion binding sites, two of them between the U- and G-quartets. (15)NH(4)(+) ions have been shown to move faster between the interior of the tetramolecular structures and the bulk solution in comparison with the monomolecular and bimolecular G-quadruplexes. However, cation movement is slowed by the presence of a T-quartet at the 5' end. PMID- 20735002 TI - On the need to redesign the CDM carbon trading program. PMID- 20735001 TI - Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics. AB - Syntheses and structure-activity relationships (SAR) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene transrepression and transactivation. Collagen induced arthritis studies in mouse have demonstrated that in vitro dissociated compounds (R)-16 and (R)-37 have steroid-like anti-inflammatory properties with improved metabolic side effect profiles, such as a reduced increase in body fat and serum insulin levels, compared to steroids. PMID- 20735003 TI - Arsenic contamination of the environment-food chain: a survey on wheat as a test plant to investigate phytoavailable arsenic in Italian agricultural soils and as a source of inorganic arsenic in the diet. AB - Seven hundred and twenty-six samples of wheat grains from the majority of Italian agricultural areas were pooled into 141 composite samples, homogeneous with respect to geographical origin and wheat variety. The average arsenic concentration of the pooled samples was 9 ng g(-1), with a range of 2-55 ng g(-1) (dry weight basis). The spread of arsenic concentrations (coefficient of variation of 91%) was related to spatial variability associated with geochemical and environmental factors. Temporal variability was investigated by a 3-year longitudinal study on 7 wheat cultivars grown in 22 areas of central and northern Italy. Average year-to-year variation in arsenic levels was low, and the average of the coefficients of variation was 23%. These results show that mapping of phytoavailable arsenic in agricultural soils can be done by measuring arsenic concentration in representative samples of wheat grains. Arsenic speciation in the grain showed that As(III) and As(V) were the major As compounds, highlighting the importance of wheat as a source of inorganic arsenic in the diet. PMID- 20735004 TI - Optoelectrofluidic sandwich immunoassays for detection of human tumor marker using surface-enhanced Raman scattering. AB - A sandwich immunoassay is a powerful tool for identifying a specific substance in a biological sample. However, its heterogeneous strategy always requires repetitive liquid handlings and long processing time. Here an optoelectrofluidic immunoassay platform for simple, fast, and automated detection of human tumor marker based on surface-enhanced Raman scattering (SERS) has been developed. By using a conventional optoelectrofluidic device and a liquid crystal display module, simple and quantitative detection of human tumor marker, alpha fetoprotein, in a ~500 nL sample droplet has been automatically conducted with lower detection limit of about 0.1 ng/mL within 5 min. This study depicts the first practical application, for protein detection, of the optoelectrofluidic manipulation technology. This image-driven immunoassay platform opens a new way for simple, fast, automated, and highly sensitive detection of antigens. PMID- 20735007 TI - Calorimetric and structural studies of tetrabutylammonium chloride ionic clathrate hydrates. AB - Three ionic clathrate hydrates of different water content are formed in the binary system tetrabutylammonium chloride-water. The data on heats of fusion of these hydrates measured by DSC are presented. Single-crystal and powder X-ray diffraction studies of ionic clathrate hydrates of tetrabutylammonium chloride have been carried out. Structural justification of the occurrence of three different ionic clathrate hydrates derived from tetragonal structure-I in the (C(4)H(9))(4)NCl-H(2)O system has been found for the first time. A novel mode of hydrophilic inclusion of the halide anion with displacement of two hydrogen bonded host water molecules has been revealed. Structural data obtained are indicative of the possibility of location of tetrabutylammonium cations in combined cavities formed with participation of D-voids. PMID- 20735006 TI - Lidocaine oxidation by electrogenerated reactive oxygen species in the light of oxidative drug metabolism. AB - The study of oxidative drug metabolism by Cytochrome P450s (P450) is important in the earlier stages of drug development. For this purpose, automated analytical techniques are needed for fast and accurate estimation of oxidative drug metabolism. Previous studies have shown that electrochemistry in combination with mass spectrometry is a versatile analytical technique to generate drug metabolites that result from direct electron transfer. Here we show that electrochemical generation of reactive oxygen species (ROS), a process reminiscent of the catalytic cycle of P450, extends the applicability of electrochemistry in drug metabolism research. Oxidation products of lidocaine from one and two-compartment electrochemical cells, operated under various conditions were analyzed by LC-MS and metabolite structures were elucidated by collision-induced (LC-MS/MS), and thermally induced (APCI) fragmentation. Direct oxidation of lidocaine at the anode resulted in N-dealkylation, whereas reaction with H(2)O(2), generated at the cathode, produced the N-oxide, both known in vivo lidocaine metabolites. Catalytic activation of hydrogen peroxide, using the Fenton reaction, resulted in benzylic and aromatic hydroxylations thus covering all of the known in vivo phase-I metabolites of lidocaine. This study extends the applicability of electrochemistry combined with mass spectrometry as a valuable technique in assessing oxidative drug metabolism related to P450. PMID- 20735005 TI - Regulation of catch binding by allosteric transitions. AB - An allosteric model is used to describe changes in lifetimes of biological receptor-ligand bonds subjected to an external force. Force-induced transitions between the two states of the allosteric site lead to changes in the receptor conformation. The ligand bound to the receptor fluctuates between two different potentials formed by the two receptor conformations. The effect of the force on the receptor-ligand interaction potential is described by the Bell mechanism. The probability of detecting the ligand in the bound state is found to depend on the relaxation times of both ligand and allosteric sites. An analytic expression for the bond lifetime is derived as a function of force. The formal theoretical results are used to explain the anomalous force and time dependences of the integrin-fibronectin bond lifetimes measured by atomic force microscopy (Kong, F.; et al J. Cell Biol. 2009, 185, 1275-1284). The analytic expression and model parameters describe very well all anomalous dependences identified in the experiments. PMID- 20735008 TI - Determination of ultralow level 129I/127I in natural samples by separation of microgram carrier free iodine and accelerator mass spectrometry detection. AB - Separation of carrier free iodine from low iodine level samples and accurate measurement of ultralow level (129)I in micrograms of iodine target are essential but a bottleneck in geological dating of terrestrial system and tracer research using naturally produced (129)I. In this work, we present a carrier free method using coprecipitation of AgI with AgCl for preparing micrograms of iodine target, associated with combustion using a tube furnace for separating iodine from solid samples and anion exchange chromatography for preconcentrating iodine from a large volume of water. An accelerator mass spectrometry was used to measure ultralow level (129)I in micrograms of iodine target. The recovery of iodine in the entire separation procedure is higher than 80% and 65% for solid and water samples, respectively. One microgram iodine in the target (AgI-AgCl) can produce a stable (127)I signal for AMS measurement of (129)I/(127)I, and a detection limit of this method for (129)I is calculated to be 10(5) atoms. This will allow us to accurately determine (129)I in prenuclear geological samples of low iodine concentration with (129)I/(127)I of 10(-12), such as loess, soil, coral, rock, sediment, and groundwater. Some samples with low iodine content have been successfully analyzed, and the lowest value of the (129)I/(127)I ratio of 2 * 10( 11) was observed in 23.5 and 63.5 m loess samples collected in the Loess Plateau, China. The developed method sheds light on a wide application in earth science. PMID- 20735009 TI - Interfacial complexes between a protein and lipophilic ions at an oil-water interface. AB - The interaction between an intact protein and two lipophilic ions at an oil-water interface has been investigated using cyclic voltammetry, impedance based techniques and a newly developed method in which the biphasic oil-water system is analyzed by biphasic electrospray ionization mass spectrometry (BESI-MS), using a dual-channel electrospray emitter. It is found that the protein forms interfacial complexes with the lipophilic ions and that it specifically requires the presence of the oil-water interface to be formed under the experimental conditions. Furthermore, impedance based techniques and BESI-MS with a common ion to polarize the interface indicated that the Galvani potential difference across the oil water interface significantly influences the interfacial complexation degree. The ability to investigate protein-ligand complexes formed at polarized liquid-liquid interfaces is thus a new analytical method for assessing potential dependent interfacial complexation using a structure elucidating detection principle. PMID- 20735011 TI - Derivation of correlation functions to predict bond properties of phenyl-CH bonds based on vibrational and (1)H NMR spectroscopic quantities. AB - The study of electron density properties significantly contributes to the determination of important chemical relations. The experimental determination of the electron density distribution is limited to single crystals. However, equivalent information is often desired for molecules, which do not crystallize in a sufficient manner. Furthermore, it is of high impact to study changes in the electron density distribution (i.e., related reactivities) upon environmental variations. Consequently, here we investigate methods to derive electron density properties from spectroscopic data. In particular correlation functions are introduced, which are able to predict electron density properties in all five CH bonds of monosubstituted benzene derivatives at once. The prediction performance for electron densities and the corresponding Laplacians is lower as compared to previously introduced local functions [Presselt et al. J. Phys. Chem. A 2009, 113, 3210], but far less spectroscopic input data are needed. However, for ellipticities a higher prediction performance than this obtained for the previously derived local functions could be obtained despite the fact that less spectroscopic data were used. Thus, ellipticities are best predicted using (1)H NMR data for the para position of monosubstituted benzene derivatives. PMID- 20735010 TI - Ferrihydrite containing gel for chemical imaging of labile phosphate species in sediments and soils using diffusive gradients in thin films. AB - We report on a novel binding gel for phosphate, based on ferrihydrite, and its use in diffusive gradients in thin films (DGT) for measuring labile phosphate species in waters, sediments, and soils. An existing method of binding layer preparation was modified to overcome potential problems with deterioration of ferrihydrite due to conversion to goethite. The gel was characterized regarding its suitability for conventional DGT measurements as well as for measuring two dimensional distributions of P with high spatial resolution using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). The effects of pH, ionic strength and storage time of gels on phosphate binding were investigated and the kinetics of binding and the maximum binding capacity were determined. The gel is shown to have a considerably higher P capacity than the conventional ferrihydrite DGT binding layers. LA-ICPMS analysis of DGT standards with P concentrations ranging from 0.088 +/- 0.005 to 4.47 +/- 0.16 MUg cm(-2) resulted in reproducible calibration curves which could be described using a simple power function. We demonstrate that the new gel is well suited for analyzing small-scale changes of P concentrations in soils. Moreover, the gel can be used as an alternative to conventional DGT gels that incorporate powdered ferrihydrite, with improved characteristics for the determination of labile phosphate. PMID- 20735012 TI - Biocompatible silica nanoparticles-insulin conjugates for mesenchymal stem cell adipogenic differentiation. AB - There is increasing interest in developing bioconjugated carriers for the cellular delivery of bioactive molecules to stem cells, since they can allow modulation of stem cell differentiation. The present study reported biocompatible silica nanoparticle-insulin conjugates for rat mesenchymal stem cell (RMSC) adipogenic differentiation in vitro. A systematic study was first carried out on the biocompatibility of the SiNPs with RMSCs. The cell viability assay was performed to screen the SiNP concentration for creating little cytotoxicity on RMSCs. Furthermore, transmission electron microscopy (TEM) and adipogenesis and osteogenesis assays revealed that the pure SiNPs had no effect on cellular ultrastructures, adipogenic differentiation, and osteogenic differentiation. Under the optimized SiNP concentration with little cytotoxicity on RMSC and no effects on the RMSC phenotype, SiNP-insulin conjugates were prepared and used for RMSC adipogenic differentiation. Results showed that RMSCs had the ability to differentiate into adipocytes when cultured in the presence of insulin-conjugated SiNPs. This work demonstrated that the biological activity of insulin conjugated to the SiNPs was not affected and the SiNPs could be used as biocompatibile carriers of insulin for RMSC adipogenic differentiation, which would help to expand the new potential application of SiNPs in stem cell research. PMID- 20735013 TI - Fast preparation of printable highly conductive polymer nanocomposites by thermal decomposition of silver carboxylate and sintering of silver nanoparticles. AB - We show the fast preparation of printable highly conductive polymer nanocomposites for future low-cost electronics. Highly conductive polymer nanocomposites, consisting of an epoxy resin, silver flakes, and incorporated silver nanoparticles, have been prepared by fast sintering between silver flakes and the incorporated silver nanoparticles. The fast sintering is attributed to: 1) the thermal decomposition of silver carboxylate-which is present on the surface of the incorporated silver flakes-to form in situ highly reactive silver nanoparticles; 2) the surface activation of the incorporated silver nanoparticles by the removal of surface residues. As a result, polymer nanocomposites prepared at 230 degrees C for 5 min, at 260 degrees C for 10 min, and using a typical lead-free solder reflow process show electrical resistivities of 8.1*10(-5), 6.0*10(-6), and 6.3*10(-5) Omega cm, respectively. The correlation between the rheological properties of the adhesive paste and the noncontact printing process has been discussed. With the optimal rheological properties, the formulated highly viscous pastes (221 mPa s at 2500 s(-1)) can be non-contact-printed into dot arrays with a radius of 130 MUm. The noncontact printable polymer nanocomposites with superior electrical conductivity and fast processing are promising for the future of printed electronics. PMID- 20735014 TI - Role of the substituent effect over the squarate oxocarbonic ring: spectroscopy, crystal structure, and density functional theory calculations of 1,2 dianilinosquairane. AB - This work presents the crystal structure and the investigation under a supramolecular perspective of a squaric acid derivative obtained from the replacement of the hydroxyl groups by anilines. The squaraine obtained (1,2 dianilinesquaraine) crystallizes in the Pbcn space group, in a unit cell with a = 26.5911(8) A, b = 6.1445(10) A, and c = 7.5515(5) A. The bond lengths in the oxocarbon ring, squarate-N and C-O bonds present the character of double bonds. Also the difference between the longer and shorter C-C bond in the four-membered ring (DeltaCC) is 0.0667 A, showing a good degree of equalization of these bond lengths. The phenyl rings are slightly distorted in relation to the squarate ring, and the angle measured between the best plane fitted in each ring is 37.2(9) degrees . Each molecule is connected to the other through a hydrogen bond involving the N-H...O moieties, where the donor...acceptor distance is 2.826(1) A, forming ribbons in a unidimensional arrangement C(5)R22(10) along the b axis. These structures are mutually connected by pi-stacking interactions extending the supramolecular structure in a two-dimensional fashion. Besides, an interesting crossed structure can be easily identified in the formed sheets that are built through the C-H/pi interactions. DFT calculations at the B3LYP/6-311++G(d,p) level of theory show an approximately planar molecular structure for the isolated molecule. However, when a dimer model built from hydrogen bonds is considered, the optimized structure presents considerable torsion between the phenyl and squarate rings, as observed in the experimental data. The electronic spectrum shows a strong absorption band at 341 nm that is red-shifted compared to the squarate maximum absorption (290 nm), indicating a more effective electronic delocalization. The most characteristic vibrational modes of the oxocarbon species were used as spectroscopic probe to understand how the substituent groups affect the oxocarbon moiety and, consequently, the vibrational spectra. The analysis shows that the modes associated with the C-Cox bonds are the most affected. Also the character of the double bond of squarate-N and the single bond for the phenyl-N are easily identified. In a general form, the calculated vibrational modes of the dimer model were in better accordance with the experimental data, mainly when the mode has a contribution from the acceptor molecule in the intermolecular interaction. PMID- 20735015 TI - Phase separation and water channel formation in sulfonated block copolyimide. AB - We compared experimental and simulated data to investigate the phase separation and water channel formation of proton exchange membranes (PEMs) for fuel cell. Sulfonated block copolyimides (SPIs) were adopted as model polymers for experiments and simulations, and Nafion was used as a reference. Nafion and SPIs were observed to have different microscopic structures such as constituent atoms, backbone rigidity, and the locations of sulfonic acid groups, all of which significantly affect phenomenological properties at the macroscopic level such as density, water uptake, and proton conductivity. In particular, SPIs show much weaker microphase separation than Nafion, mainly due to the lower mobility of sulfonic acid groups and the existence of acceptable sites for hydrogen bonding even in hydrophobic segments, which impedes water channel formation for proton transport. As a result, the phase separation behavior and the resulting water channel formation are the major factors affecting macroscopic properties of PEMs such as water uptake and proton transport. PMID- 20735017 TI - Oxygen close-packed structure in amorphous indium zinc oxide thin films. AB - Amorphous indium zinc oxide (IZO) thin film structures of varying amounts of Zn content were investigated using X-ray diffraction measurements and molecular dynamics (MD) simulations. The characteristic amorphous structure having high oxygen coordination number and edge-shared polyhedra were confirmed using both techniques. Detailed analysis of the structural model revealed that the oxygen close-packed structure was almost realized in the nanometer range. It was also found that the number of Zn ions occupying the tetrahedral site of the oxygen close-packed structure increased with increasing ZnO content although In ions occupied the octahedral site. We conclude that the amorphous structure stability of the indium zinc oxide thin films is enhanced by the existence of Zn ions in the tetrahedral site, which block In ions in the octahedral site ordering similar to that in an In(2)O(3) crystal. PMID- 20735016 TI - Identification of SR1078, a synthetic agonist for the orphan nuclear receptors RORalpha and RORgamma. AB - The retinoic acid receptor-related receptors (RORs) are members of the nuclear receptor (NR) superfamily of transcription factors. Several NRs are still characterized as orphan receptors because ligands have not yet been identified for these proteins. Here, we describe the identification of a synthetic RORalpha/RORgamma ligand, SR1078. SR1078 modulates the conformation of RORgamma in a biochemical assay and activates RORalpha and RORgamma driven transcription. Furthermore, SR1078 stimulates expression of endogenous ROR target genes in HepG2 cells that express both RORalpha and RORgamma. Pharmacokinetic studies indicate that SR1078 displays reasonable exposure following injection into mice, and consistent with SR1078 functioning as a RORalpha/RORgamma agonist, expression of two ROR target genes, glucose-6-phosphatase and fibroblast growth factor 21, were stimulated in the liver. Thus, we have identified the first synthetic RORalpha/gamma agonist, and this compound can be utilized as a chemical tool to probe the function of these receptors both in vitro and in vivo. PMID- 20735018 TI - Iron thiobiurets: single-source precursors for iron sulfide thin films. AB - The iron(III) complexes of several 1,1,5,5-tetraalkyl-2-thiobiurets [Fe(SON(CN(i)Pr(2))(2))(3) (1), Fe(2)(MU-OMe)(2)(SON(CNEt(2))(2))(2) (2), Fe(SON(CNEt(2))(2))(3) (3), and Fe(SON(CNMe(2))(2))(3) (4)] have been synthesized, and the single-crystal X-ray structures of 1, 2, and 4 have been determined. The magnetic properties of complex 2 as a function of the temperature and field were studied. Thermogravimetric analysis of complexes 1-4 showed the decomposition in one major step to iron sulfide residues. All four complexes were used as single-source precursors for the deposition of iron sulfide thin films by aerosol-assisted chemical vapor deposition. Complex 1 gave hexagonal troilite FeS films with a small amount of tetragonal pyrrhotites Fe(1-x)S at 300 degrees C, whereas only troilite FeS was deposited at 350, 400, or 450 degrees C. Complexes 2 and 3 deposited a mixture of hexagonal troilite FeS and cubic pyrite FeS(2) films at all temperatures. Complex 4 deposited very thin films of FeS at all temperatures as troilite. Scanning electron microscopy images of the films deposited from all complexes showed that the morphology consisted of plates, granules, rods, and sheets like crystallites. The size and shapes of these crystallites were dependent on the growth temperature and the precursor used. This is the first time that iron(III) thiobiuret complexes have been used as single-source precursors for iron sulfide thin films. PMID- 20735019 TI - Electrical properties of polyelectrolyte layers adsorbed on colloidal particles at different ionic strength. AB - The investigation presents results on the low-frequency electrical polarization of beta-FeOOH particles with adsorbed layers from sodium salts of poly(4-styrene sulfonate), poly(acrylic acid), and carboxymethyl cellulose, obtained by electric light scattering. The adsorption is realized in aqueous NaCl solutions of different concentration, and the suspensions of the coated particles are then rinsed to low conductivity. Several electro-optical parameters are sensitive to the conformation of the adsorbed polyelectrolyte layer. The particle electrical polarizability increases drastically with the concentration of NaCl (correlating with significant increase of the adsorbed amount of polyelectrolyte), while their electrophoretic mobility remains practically unchanged. Two time scales are involved in the stepwise relaxation of the electrical polarizability. The faster process is attributed to movement of ions in the polymer layer, restricted by the coiled conformation to smaller distances. The contribution of the Debye atmosphere outside the polymer layer remains almost unchanged, which correlates with the low sensitivity of the electrophoretic mobility to the increasing amount of adsorbed polyelectrolyte. Abrupt increase in a narrow interval of salt concentrations is observed both for the low-frequency component of the particle polarization and for the hydrodynamic layer thickness, indicating changes in the surface electric state, most probably due to swelling of the adsorbed polymer layer. PMID- 20735020 TI - Synthesis and characterization of the M(II) (M = Ge, Sn, or Pb) phosphinidene dimers {M(MU-PAr')}2 (Ar' = C6H3-2,6-(C6H3-2,6-Pr(i)2)2). AB - Reaction of M{N(SiMe(3))(2)}(2) (M = Ge, Sn, or Pb) with the sterically encumbered primary phosphine Ar'PH(2) (2), Ar' = C(6)H(3)-2,6-(C(6)H(3)-2,6 Pr(i)(2)), at ca. 200 degrees C afforded the highly colored phosphinidene dimers {M(MU-PAr')}(2), M = Ge(3), Sn(4), or Pb(5), with disilylamine elimination. The compounds were characterized by single-crystal X-ray crystallography and heteronuclear NMR spectroscopy. The structures of 3, 4, and 5 featured similar M(2)P(2) ring cores, of which 4 and 5 have 50/50 P atom disorder, consistent with either a planar four-membered M(2)P(2) arrangement with anti aryl groups or with an M(2)P(2) ring folded along the M-M axis with syn aryl groups. A syn-folded structure was resolved for the Ge(2)P(2) ring in compound 3. The M-P distances resembled those in M(II) phosphido complexes and are consistent with single bonding. The coordination geometries at the phosphorus atoms are pyramidal. DFT calculations on the gas phase models {M(MU-PMe)}(2) (M = Ge, Sn, Pb) agreed with the syn (M-M folded) structural interpretation of the X-ray data. The synthesis of the bulky phosphine Ar'PH(2) 2 with the use of the aryl transfer agent Ar'MgBr(THF)(2) is also reported. This route afforded a significantly higher yield of product than that which was obtained using LiAr', which tends to result in aryl halide elimination and the observation of insoluble red phosphorus. PMID- 20735021 TI - Direct measurement of double-layer, van der Waals, and polymer depletion attraction forces between supported cationic bilayers. AB - The interactions of supported cationic surfactant bilayers and the effects of nonadsorbing cationic polyelectrolytes on these interactions were studied using the surface forces apparatus (SFA) technique. Bilayers of the cationic surfactant di(tallow ethyl ester) dimethyl ammonium chloride (DEEDMAC) were deposited on mica surfaces using the Langmuir-Blodgett technique, and the interactions between the bilayers were measured in various salt, nonionic polymer (PEG), and cationic polyelectrolyte solutions at different polymer molecular weights and concentrations. The forces between the bilayers in CaCl(2) solution are purely repulsive and follow the DLVO theory quantitatively down to bilayer separations of ~2 nm. Addition of nonadsorbing polymer or polyelectrolyte has a number of effects on the interactions including the induction of a depletion-attraction between the bilayers and screening of the double-layer repulsion due to the added ions in the solution from the polyelectrolyte. The experimental results are shown to agree well with standard theories of depletion attraction and double-layer screening associated with dissolved polyelectrolyte. We also observed significant time and rate effects on measuring the equilibrium bilayer-bilayer interactions possibly due to the unexpectedly long times (>1 min) associated with the charge regulation of the bilayer surfaces. Implications for the interactions and stability of vesicle dispersions, i.e., of free rather than supported bilayers, in polymer solutions are discussed. PMID- 20735022 TI - Lipoprotein complex of equine lysozyme with oleic acid (ELOA) interactions with the plasma membrane of live cells. AB - Recent evidence supports the idea that early aggregates, protein, and lipoprotein oligomers but not large aggregates like fibrils that are formed at late stages of the aggregation process are responsible for cytotoxicity. Oligomers can interact with the cellular plasma membrane affecting its structure and/or dynamics or may be taken up by the cells. In either case, disparate cascades of molecular interactions are activated in the attempt to counteract the disturbance induced by the oligomers. If unsuccessful, cell death follows. Here, we study the molecular and cellular mechanisms underlying PC12 cell death caused by ELOA oligomers. ELOA, a lipoprotein complex formed by equine lysozyme (EL) and oleic acid (OA), induces cell death in all tested cell lines, but the actual mechanism of its action is not known. We have used methods with single-molecule sensitivity, fluorescence correlation spectroscopy (FCS), fluorescence cross correlation spectroscopy (FCCS), and confocal laser scanning microscopy (CLSM) imaging by avalanche photodiodes (APD), so-called APD imaging, to study ELOA interactions with the plasma membrane in live PC12 cells. We detected ELOA accumulation in the cell surroundings, observed ELOA interactions with the plasma membrane, and local changes in plasma membrane lipid dynamics in the vicinity of ELOA complexes. These interactions resulted in plasma membrane rupture, followed by rapid influx and distribution of ELOA inside the already dead cell. In order to probe the ELOA-plasma membrane interaction sites at the molecular and atomic levels, the ELOA complexes were further studied by photochemically induced dynamic nuclear polarization (photo-CIDNP) spectroscopy, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). We observed a novel mechanism of oligomer toxicity-cell death induced by continuous disturbance of the plasma membrane, eventually causing permanent plasma membrane damage and identified the sites in ELOA that are potentially involved in the interactions with the plasma membrane. PMID- 20735023 TI - Silica mesostructures: control of pore size and surface area using a surfactant templated hydrothermal process. AB - The cooperative self-assembly of the silica precursor, tetraethyl ortho silicate (TEOS), with the surfactant molecule followed by the basic hydrolysis led to the formation of mesoporous silica with varying pore sizes. The pores are formed by the removal of the intermediate assemblies of the charged surfactant molecules. In the absence of formation of such assemblies of surfactants (example in the case of nonionic surfactants), the resulting mesostructures have very small pores, giving low surface area mesostructures. This study outlines the precise control of pore size in a wide size distribution (3.4-22 nm) by the systematic variation of the surfactant. The addition of polyethylene glycol (in situ) while carrying out the hydrolysis of TEOS results in the formation of large-sized cavities (~40 nm). Uniform spherical particles with pores (different from the cavities) as large as 22 nm and surface areas of ~1100 m(2)/g have been obtained by the combined effect of the hydrothermal conditions on the cetyl trimethyl ammonium bromide-templated synthesis. PMID- 20735024 TI - Probing strain-induced electronic structure change in graphene by Raman spectroscopy. AB - Two-phonon Raman scattering in graphitic materials provides a distinctive approach to probing the material's electronic structure through the spectroscopy of phonons. Here we report studies of Raman scattering of the two-dimensional mode of single-layer graphene under uniaxial stress and which implicates two types of modification of the low-energy electronic structure of graphene: a deformation of the Dirac cone and its displacement away from the K point. PMID- 20735025 TI - Immobilization of porphyrin derivatives with a defined distance and orientation onto a gold electrode using synthetic light-harvesting alpha-helix hydrophobic polypeptides. AB - Molecular assembly of Zn-porphyrin pigments on a gold electrode using synthetic 1alpha-helix hydrophobic polypeptides which have similar amino acid sequences to the hydrophobic core in the native photosynthetic light-harvesting (LH) 1-beta polypeptide from Rhodobacter sphaeroides has been achieved. This method is clearly successful in allowing assembly of porphyrins together with LH1 type functional complexes with a defined distance and orientation on the electrode. In this case, the photocurrent direction and the distance of electron transfer of pigments could be controlled by these synthetic LH1 model polypeptides. This method will be useful for the self-assembly of these pigment and protein complexes in order to study the energy transfer and electron transfer reactions between individual pigments in the supramolecular complexes on the electrode, as well as to provide insight into the effect of the distance and orientation of pigments and the effect of the structure of 1alpha-helix hydrophobic polypeptide on the energy transfer and electron transfer reactions. PMID- 20735026 TI - Dopamine adsorption on anatase TiO2(101): a photoemission and NEXAFS spectroscopy study. AB - The adsorption of dopamine onto an anatase TiO(2)(101) single crystal has been studied using photoemission and NEXAFS techniques. Photoemission results suggest that the dopamine molecule adsorbs on the surface in a bidentate geometry, resulting in the removal of band gap states in the TiO(2) valence band. Using the searchlight effect, carbon K-edge NEXAFS spectra indicate that the phenyl rings in the dopamine molecules are orientated normal to the surface. A combination of experimental and computational results indicates the appearance of new unoccupied states arising following adsorption. The possible role of these states in the charge-transfer mechanism of the dopamine-TiO(2) system is discussed. PMID- 20735027 TI - Insertion-coupling-cycloisomerization domino synthesis and cation-induced halochromic fluorescence of 2,4-diarylpyrano[2,3-b]indoles. AB - 2,4-Diarylpyrano[2,3-b]indoles are formed via a Pd-Cu-catalyzed insertion coupling-cycloisomerization domino reaction in moderate yields. Although the tricyclic systems are nonfluorescent in solution, protonation, quaternation, or complexation with metal ions induces intense green luminescence. Most strikingly, selective halochromic fluorescence of zinc and magnesium over calcium ions classify the title compounds as metal-selective luminescence sensors. PMID- 20735029 TI - Cobalt-catalyzed addition of azoles to alkynes. AB - A ternary catalytic system consisting of a cobalt salt, a diphosphine ligand, and a Grignard reagent promotes syn-addition of an azole C(2)-H bond across an unactivated internal alkyne with high chemo-, regio-, and stereoselectivities under mild conditions. Mechanistic experiments suggest that the reaction involves oxidative addition of the oxazolyl C-H bond to the cobalt center, alkyne insertion into the Co-H bond, and reductive elimination of the resulting diorganocobalt species. PMID- 20735028 TI - Intercluster compound between a tetrakis{triphenylphosphinegold(I)}oxonium cation and a keggin polyoxometalate (POM): formation during the course of carboxylate elimination of a monomeric triphenylphosphinegold(I) carboxylate in the presence of POMs. AB - The preparation and structural characterization of a novel intercluster compound, [{Au(PPh(3))}(4)(MU(4)-O)](3)[alpha-PW(12)O(40)](2).4EtOH (1), constructed between a tetrakis{triphenylphosphinegold(I)}oxonium cation and a saturated alpha Keggin polyoxometalate (POM) are described. The tetragold(I) cluster oxonium cation was formed during the course of carboxylate elimination of a monomeric phosphinegold(I) carboxylate complex, i.e., [Au((R,S)-pyrrld)(PPh(3))] [(R,S) Hpyrrld = (R,S)-2-pyrrolidone-5-carboxylic acid], in the presence of the free acid form of a Keggin POM, H(3)[alpha-PW(12)O(40)].7H(2)O. The liquid-liquid diffusion between the upper water/EtOH phase containing the Keggin POM and the lower CH(2)Cl(2) phase containing the monomeric gold(I) complex gave a pure crystalline sample of 1 in good yield (42.1%, 0.242 g scale). Complex 1 was formed by ionic interaction between the tetragold(I) cluster cation and the Keggin POM anion. As a matter of fact, the POM anion in 1 can be exchanged with the BF(4)(-) anion using an anion-exchange resin (Amberlyst A-27) in BF(4)(-) form. By using other Keggin POMs, such as H(4)[alpha-SiW(12)O(40)].10H(2)O and H(3)[alpha-PMo(12)O(40)].14H(2)O, the same tetragold(I) cluster cation was also formed, i.e., in the forms of [{Au(PPh(3))}(4)(MU(4)-O)](2)[alpha SiW(12)O(40)].2H(2)O (2) and [{Au(PPh(3))}(4)(MU(4)-O)](3)[alpha PMo(12)O(40)](2).3EtOH (3). Compounds 1-3, as dimethyl sulfoxide-soluble, EtOH- and Et(2)O-insoluble dark-yellowish white solids, were characterized by complete elemental analysis, thermogravimetric and differential thermal analyses, Fourier transform IR, X-ray crystallography, and solid-state (CPMAS (31)P and (29)Si) and solution ((31)P{(1)H} and (1)H) NMR spectroscopy. The molecular structures of 1 and 2 were successfully determined. The tetragold(I) cluster cation was composed of four PPh(3)Au(I) units bridged by a central MU(4)-oxygen atom in the geometry of a trigonal pyramid or distorted tetrahedron. PMID- 20735030 TI - Experimental and theoretical studies on the mechanism of photochemical hydrogen transfer from 2-aminobenzimidazole to npi* and pipi* aromatic ketones. AB - This work has examined the photoreactivity of benzophenone (3), 2 benzoylthiophene (4), 4-methoxybenzophenone (5), 4,4'-dimethoxybenzophenone (6), and 4-carboxybenzophenone (7) with 2-aminobenzimidazole (1). Laser flash photolysis (LFP) revealed quenching of the aromatic ketone triplets by 1, leading to formation of ketyl radicals plus aminyl radical 1-H*. The quenching rate constants obtained for 3 (npi* triplet) and 4 (pipi* triplet) were 6.2 * 10(9) and 3.9 * 10(9) M(-1) s(-1), respectively. The similarity between the two values suggests that the process is not a pure hydrogen abstraction but rather a charge transfer followed by proton transfer. This is in agreement with thermodynamic calculations, using the Rehm-Weller equation. In the case of 5 and 6, the transient absorption spectra showed distinct bands corresponding to both types of triplets (npi* and pipi*); their ratio was found to depend on solvent polarity. In the presence of 1, spectral changes were also consistent with formation of the aminyl/ketyl radical pairs. The rate constants for quenching of both types of triplets were very high, in the range 10(9)-10(10) M(-1) s(-1). When an electron acceptor substituent was attached to the aromatic ring, as in 7 (npi* triplet), the quenching rate constant was higher (8 * 10(9) M(-1) s(-1)), close to diffusion control. The reaction mechanism for hydrogen abstraction from 1 by triplet excited 3 or 4 was theoretically studied using density functional theory (DFT) methods. The results suggest formation of ground state molecular complexes, where one electron is transferred from the 2-aminobenzimidazole to the benzophenone or benzoylthiophene moieties upon excitation, giving radical ion pairs; subsequent proton transfer from the amino group to the carbonyl oxygen atoms leads to the neutral biradicals. A comparison between the relative energies and geometries of the species involved in the photochemical reactions indicates that all ketones follow a similar mechanism. PMID- 20735031 TI - Conductivity, viscosity, and dissolution enthalpy of LiNTF2 in ionic liquid BMINTF2. AB - The ionic conductivity, relative viscosity, and solution enthalpy of LiNTF(2) and NaNTF(2) solutions in ionic liquid BMINTF(2) have been measured. We observed that the conductivity decreased and the viscosity increased when the Li(+) and Na(+) salts were dissolved in BMINTF(2). We also observed that the dissolution is an exothermic process with a solution enthalpy of approximately -18.07 +/- 4.61 kJ/mol. The experimental results indicate that the Li(+) ion may associate with multiple NTF(2)(-) anions in the BMINTF(2) solution to form a solvated complex. PMID- 20735032 TI - Stabilization of kerosene/water emulsions using bioemulsifiers obtained by fermentation of hemicellulosic sugars with Lactobacillus pentosus. AB - The results of the present study show that Lactobacillus pentosus can produce extracellular bioemulsifiers by utilizing hemicellulosic sugars from grape marc as a source of carbon. The effectiveness of these bioemulsifiers (LPEM) was studied by preparing kerosene/water (K/W) emulsions in the presence and absence of these emulsifiers. Various parameters such as relative emulsion volume (EV), stabilizing capacity (ES), viscosity, and droplet size of K/W emulsions were measured. The EV values for K/W emulsions stabilized by concentrated LPEM were approximately 74.5% after 72 h of emulsion formation, with ES values of 97%. These values were higher than those obtained with dodecyl sodium sulfate as emulsifier (EV=62.3% and ES=87.7%). Additionally, K/W emulsions stabilized by LPEM produced polydisperse emulsions containing droplets of radius between 10 and 40 MUm, which were smaller than those obtained for K/W emulsions without LPEM (droplet radius=60-100 MUm). Moreover, the viscosity values of the K/W emulsions without and with LPEM were approximately 236 and 495 cP, respectively. PMID- 20735033 TI - Direct microscopic observation of forward osmosis membrane fouling. AB - This study describes the application of a noninvasive direct microscopic observation method for characterizing fouling of a forward osmosis (FO) membrane. The effect of the draw solution concentration, membrane orientation, and feed spacer on FO fouling was systematically investigated in a cross-flow setup using latex particles as model foulant in the feedwater. Higher draw solution (DS) concentrations (and thus increased flux levels) resulted in dramatic increase in the surface coverage by latex particles, suggesting that the critical flux concept might be applicable even for the osmotically driven FO process. Under identical draw solution concentrations, the active-layer-facing-the-feed-solution orientation (AL-FS) experienced significantly less fouling compared to the alternative orientation. This may be explained by the lower water flux in AL-FS, which is consistent with the critical flux concept. The use of a feed spacer not only dramatically enhanced the initial flux of the FO membrane, but also significantly improved the flux stability during FO fouling. Despite such beneficial effects of using the feed spacer, a significant amount of particle accumulation was found near the spacer filament, suggesting further opportunities for improved spacer design. To the best of the authors' knowledge, this is the first direct microscopic observation study on FO fouling. PMID- 20735034 TI - Elderberry (Sambucus nigra L.) wine: a product rich in health promoting compounds. AB - Color components, antioxidative potential, and total phenolic content were monitored in elderberry must and wine. Among individual phenolic compounds, quercetin and kaempferol compounds, phenolic acids, and anthocyanins were detected with high performance liquid chromatography coupled with mass spectrometry. Conventional enological parameters were measured in elderberry wine and compared to grape and other fruit wines. Elderberry wine has a moderate ethanol concentration, intense red coloration, and higher pH value compared to most red wines. Total phenolic content of elderberry must and wine ranged up to 2004.13 GAE L(-1). Antioxidative potential of elderberry wine was in the range of red wine, and a tight correlation was detected between total phenolic content and antioxidative potential of elderberry wine. Anthocyanins were the most abundant phenolics in elderberry wine in tight correlation with color hue, and their content significantly decreased with aging. Similarly, a decrease in total phenolic content and antioxidative potential was determined after storage. PMID- 20735035 TI - Comprehensive study of the evolution of gas-liquid partitioning of aroma compounds during wine alcoholic fermentation. AB - Calculating the gas-liquid partitioning of aromatic molecules during winemaking fermentation is essential to minimize the loss of aroma and to optimize the fermentation conditions. In this study, the effect of the main fermentation parameters on the partition coefficients (ki) of higher alcohols (2-methylpropan 1-ol and 3-methyl butan-1-ol) and esters (ethyl acetate, 3-methyl-1-butyl acetate, and 2-ethyl hexanoate) was assessed. The values of ki were first determined in synthetic media simulating must and wine. They varied considerably with both the hydrophobicity of the compound and the composition of the medium. Then, the effect of temperature on ki was quantified. The absence of any effect of gas composition was also established by replacing air with CO2. Finally, the impact of CO2 stripping was assessed by running specific fermentations in which the rate of CO2 production was kept constant by perfusion with assimilable nitrogen. These fermentations showed that in contrast to temperature and must composition, CO2 stripping did not change the gas-liquid partitioning of higher alcohols and esters. PMID- 20735036 TI - Membrane-aerated biofilm proton and oxygen flux during chemical toxin exposure. AB - Bioreactors containing sessile bacteria (biofilms) grown on hollow fiber membranes have been used for treatment of many wastestreams. Real time operational control of bioreactor performance requires detailed knowledge of the relationship between bulk liquid water quality and physiological transport at the biofilm-liquid interface. Although large data sets exist describing membrane aerated bioreactor effluent quality, very little real time data is available characterizing boundary layer transport under physiological conditions. A noninvasive, microsensor technique was used to quantify real time (~1.5 s) changes in oxygen and proton flux for mature Nitrosomonas europaea and Pseudomonas aeruginosa biofilms in membrane-aerated bioreactors following exposure to environmental toxins. Stress response was characterized during exposure to toxins with known mode of action (chlorocarbonyl cyanide phenyl hydrazone and potassium cyanide), and four environmental toxins (rotenone, 2,4 dinitrophenol, cadmium chloride, and pentachlorophenol). Exposure to sublethal concentrations of all environmental toxins caused significant increases in O(2) and/or H(+) flux (depending on the mode of action). These real time microscale signatures (i.e., fingerprints) of O(2) and H(+) flux can be coupled with bulk liquid analysis to improve our understanding of physiology in counter-diffusion biofilms found within membrane aerated bioreactors; leading to enhanced monitoring/modeling strategies for bioreactor control. PMID- 20735037 TI - Analysis of biliary excretion of icariin in rats. AB - Icariin is a bioactive herbal ingredient isolated from Epimedii Herba. This study evaluates the distribution of icariin in rats by microdialysis sampling and high performance liquid chromatography with ultraviolet detection (HPLC-UV). Microdialysis probes were simultaneously placed in the jugular vein, brain striatum, and bile duct of each anesthetized rat for sampling after the administration of icariin (dose=10 or 20 mg/kg) via the femoral vein. The role of P-glycoprotein (P-gp) on icariin distribution was assessed by pretreatment with cyclosporine (CsA, dose=20 mg/kg). This study is the first report of the biliary excretion of icarin in rats, defined as the blood-to-bile distribution (k value), calculated by dividing the area under the concentration-time curve (AUC) of icariin in bile by that in blood (k=AUCbile/AUCblood). The k values were 19.0+/ 5.9 and 18.8+/-3.8 at the doses of 10 and 20 mg/kg, respectively. The decreased biliary excretion of icariin due to pretreatment with CsA was evidenced by the reduced k values (18.8+/-3.8 vs 9.9+/-1.9, p=0.005). This work demonstrates that biliary excretion is the major elimination pathway for icariin disposition and that transporters, such as P-gp, might be related to icariin's biliary excretion. PMID- 20735039 TI - O((1)D) + N(2)O reaction: NO vibrational and rotational distributions. AB - The O((1)D) + N(2)O -> 2NO(X (2)Pi) reaction has been studied in a molecular beam experiment in which O(3) and N(2)O were coexpanded. The precursor O((1)D) was prepared by O(3) photodissociation at 266 nm, and the NO(X (2)Pi) molecules born from the reaction as the O((1)D) recoiled out of the beam were detected by 1+1 REMPI over the 220-246 nm probe laser wavelength range. The resulting spectrum was simulated to extract rotational and vibrational distributions of the NO(X (2)Pi) molecules. The product rotational distribution is found to be characterized by a constant rotational temperature of ~4500 K for all observed bands, v = 0-9. An inverted vibrational distribution is observed. A consistent explanation of this and previous experimental results is possible if there are two channels for the reaction, one producing a nearly statistical vibrational distribution for low O((1)D)-N(2)O relative velocity collisions and a second producing the inverted distribution observed here for high relative velocity collisions. The former might correspond to an insertion/complex-formation reaction, while the latter might correspond to a stripping reaction. Velocity relaxation of the O((1)D) is argued to compete strongly with reaction in most bulb studies, so that these studies see predominantly the nearly statistical distribution. In contrast, the beam experiments do not detect the part of the vibrational distribution produced in low relative velocity reactions because the O((1)D) is not relaxed from its initial velocity before it either reacts or leaves the beam. PMID- 20735040 TI - Effect of concentration and addition of ions on the adsorption of aerosol-OT to sapphire. AB - Aerosol-OT (sodium bis 2-ethylhexyl sulfosuccinate or NaAOT) adsorbs to hydrophilic sapphire solid surfaces. The structure of the formed bilayer has been determined over the concentration range 0.2-7.4 mM NaAOT. It was found that the hydrocarbon tails pack at maximum packing limit at very low concentrations, and that the thickness of the bilayer was concentration-independent. The adsorption was found to increase with concentration, with the surfactant molecules packing closer laterally. The area per molecule was found to change from 138 +/- 25 to 51 +/- 4 A(2) over the concentration range studied, with the thickness of the layer being constant at 33 +/- 2 A. Addition of small amounts of salt was found to increase the surface excess, with the bilayer being thinner with a slightly larger area per molecule. Addition of different salts of the same valency was found to have a very similar effect, as had the addition of NaOH and HCl. Hence, the effects of adding acid or base should be considered an effect of ionic strength rather than an effect of pH. Adsorption of NaAOT to the sapphire surface that carries an opposite charge to the anionic surfactant is similar in many respects to the adsorption reported previously for hydrophilic and hydrophobic silica surfaces. This suggests that the adsorption of NaAOT to a surface is driven primarily by NaAOT self-assembly rather than effects of electrostatic attraction to the interface. PMID- 20735038 TI - Emission factors of particulate matter and elemental carbon for crop residues and coals burned in typical household stoves in China. AB - Both particulate matter (PM) and black carbon (BC) impact climate change and human health. Uncertainties in emission inventories of PM and BC are partially due to large variation of measured emission factors (EFs) and lack of EFs from developing countries. Although there is a debate whether thermal-optically measured elemental carbon (EC) may be referred to as BC, EC is often treated as the same mass of BC. In this study, EFs of PM (EF(PM)) and EC (EF(EC)) for 9 crop residues and 5 coals were measured in actual rural cooking and coal stoves using the carbon mass balance method. The dependence of the EFs on fuel properties and combustion conditions was investigated. It was found that the mean EF(PM) were 8.19 +/- 4.27 and 3.17 +/- 4.67 g/kg and the mean EF(EC) were 1.38 +/- 0.70 and 0.23 +/- 0.36 g/kg for crop residues and coals, respectively. PM with size less than 10 MUm (PM(10)) from crop residues were dominated by particles of aerodynamic size ranging from 0.7 to 2.1 MUm, while the most abundant size ranges of PM(10) from coals were either from 0.7 to 2.1 MUm or less than 0.7 MUm. Of various fuel properties and combustion conditions tested, fuel moisture and modified combustion efficiency (MCE) were the most critical factors affecting EF(PM) and EF(EC) for crop residues. For coal combustion, EF(PM) were primarily affected by MCE and volatile matter, whereas EF(EC) were significantly influenced by ash content, volatile matter, heat value, and MCE. It was also found that EC emissions were significantly correlated with emissions of PM with size less than 0.4 MUm. PMID- 20735041 TI - Direct measurements of protein-stabilized gold nanoparticle interactions. AB - We report integrated video and total internal reflection microscopy measurements of protein stabilized 110 nm Au nanoparticles confined in 280 nm gaps in physiological media. Measured potential energy profiles display quantitative agreement with Brownian dynamic simulations that include hydrodynamic interactions and camera exposure time and noise effects. Our results demonstrate agreement between measured nonspecific van der Waals and adsorbed protein interactions with theoretical potentials. Confined, lateral nanoparticle diffusivity measurements also display excellent agreement with predictions. These findings provide a basis to interrogate specific biomacromolecular interactions in similar experimental configurations and to design future improved measurement methods. PMID- 20735043 TI - Water-collecting capability of radial-wettability gradient surfaces generated by controlled surface reactions. AB - In this work, we developed a controlled oxidation reaction of vinyl-terminated self-assembled monolayers (SAMs) to carboxylic acid-terminated ones to generate radially inward wettability gradient surfaces. The hydrophobicity was introduced on a silicon wafer by SAMs of 10-undecenyltrichlorosilane, and after the initial drop in oxidation, followed by the dilution-by-dropping method, radial wettability gradient surfaces having hydrophilic centers and hydrophobic exteriors were generated. This direct drop reaction on the SAMs did not require an elastomeric stamp to be fabricated, which allowed for facile tuning of the gradients in terms of sizes and shapes. The fabricated wettability gradient surfaces possessed a water-collecting capability toward the hydrophilic center, which was inactive on previous linear wettability gradient surfaces. PMID- 20735044 TI - Thermodynamic stability of neutral and anionic PFOS: a gas-phase, n-octanol, and water theoretical study. AB - The thermodynamic stability of the 89 isomers of the eight-carbon-atom compound perfluorooctane sulfonate (PFOS) in their neutral and anionic forms has been studied in the gas phase, n-octanol, and water using density functional theory (B3LYP/6-311+G(d,p)). The gas-phase calculations are compared with previous semiempirical and partial ab initio studies; the calculations in water and n octanol are reported for the first time. The results obtained indicate that the thermodynamic stability assessment of this family of persistent organic pollutants is independent of the environment and type of species (neutral or anionic) considered and that it is important to consider other PFOSs outside of the 83-89 set, which is the most frequently studied. PMID- 20735042 TI - Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl 1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform selective small molecule phospholipase D2 inhibitor. AB - Phospholipase D (PLD) catalyzes the conversion of phosphatidylcholine to the lipid second messenger phosphatidic acid. Two mammalian isoforms of PLD have been identified, PLD1 and PLD2, which share 53% sequence identity and are subject to different regulatory mechanisms. Inhibition of PLD enzymatic activity leads to increased cancer cell apoptosis, decreased cancer cell invasion, and decreased metastasis of cancer cells; therefore, the development of isoform-specific, PLD inhibitors is a novel approach for the treatment of cancer. Previously, we developed potent dual PLD1/PLD2, PLD1-specific (>1700-fold selective), and moderately PLD2-preferring (>10-fold preferring) inhibitors. Here, we describe a matrix library strategy that afforded the most potent (PLD2 IC(50) = 20 nM) and selective (75-fold selective versus PLD1) PLD2 inhibitor to date, N-(2-(1-(3 fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide (22a), with an acceptable DMPK profile. Thus, these new isoform-selective PLD inhibitors will enable researchers to dissect the signaling roles and therapeutic potential of individual PLD isoforms to an unprecedented degree. PMID- 20735045 TI - SECM investigations of immobilized porphyrins films. AB - Electronic properties of electrogenerated Zn-porphyrin layers linked by an electroactive linker and immobilized on a semitransparent ITO electrode were investigated by steady-state SECM in unbiased conditions in view of the numerous possible applications of such surface. This SECM strategy took advantage of the variations of the charge transfer kinetics of the organic redox couple (the mediator used in SECM) on ITO surface with the standard potential of the mediator. After preliminary characterization of nonmodified ITO, analysis of the SECM approach curves recorded with a series of redox mediators allows the characterizations of both film permeability and charge transport inside the organic film in conditions close to a "real optoelectronic device". Two types of porphyrin films were considered. In the first one, the film was produced by electropolymerization of a modified zinc-beta-octaethylporphyrin in which the bipyridinium pendant substituent is first introduced. The second type of film was prepared directly from an in situ electropolymerization method in which the Zn porphyrin is simply oxidized in the presence of 4,4'-bipyridine. Experiments show the occurrence of efficient charge transport inside both films after initial reduction of the electroactive linker. However, the first preparation method leads to films with stronger blocking character versus organic molecules and higher charge injection rates. PMID- 20735046 TI - Molecular dynamics simulations and elastic network analysis of protein kinase B (Akt/PKB) inactivation. AB - Akt (also called protein kinase B-PKB) is a key component of the phosphoinositide 3-kinase signaling pathway, which is responsible for cell proliferation and survival and is a novel target for antioncogenic indications. In its fully activated state, Akt is phosphorylated on the activation loop (A-loop) at residue Thr 309. We used molecular dynamics (MD) simulations and elastic network model normal-mode analysis (ENM-NMA) to study the initial stages of the active-inactive transition in the kinase catalytic domain. We first carried out MD simulations of the active phosphorylated Akt in complex with its ligands under different protonation states of His 196, the phosphothreonine-coordinating residue found in the alphaC helix. Analysis of trajectories suggested that the doubly protonated His 196 is most compatible with the crystallographic structure. Next we studied the dynamic processes involved in Akt inactivation: detachment of the ligands and A-loop dephosphorylation resulted in MD trajectories with increased mobility, particularly in the N-lobe and in the HJ-alphaG region of the C-lobe, and in stronger correlation and anticorrelation of motions. The first principal motions derived from the trajectories of phosphorylated and dephosphorylated apo structures were similar to each other but differed from the first principal motions derived from the complex trajectory. A rather large number of principal components obtained from MD trajectories and of ENM-NMA modes is required to describe the active-inactive conformational change of the kinase. The results are discussed in the context of related computational studies of kinase dynamics and kinase-specific inhibitor design. PMID- 20735047 TI - Investigation of copper speciation in pig slurry by a multitechnique approach. AB - It is now well-known that copper (Cu) can accumulate on the surface of soils upon which pig slurry has been applied. This is due to the high quantity of Cu in pig slurry resulting from its use as a growth promoter in animal feeds. The mobility and bioavailability of Cu from pig slurry spreading can be better predicted by determining the speciation of this element in addition to its total concentration. The aim of this study was to present a multitechnique approach to investigate Cu speciation in pig slurry. First, size fractionation and chemical characterization of each size fraction were performed to complement results obtained in raw samples. Micro X-ray fluorescence spectroscopy (MUXRF) highlighted the colocalization of Cu and sulfur (S). Finally, X-ray absorption near-edge structure spectroscopy (XANES) showed that Cu speciation in raw pig slurry and size fractions could be described by Cu(2)S and that its oxidation state is Cu(I). In addition, geochemical calculation demonstrated that chalcocite (Cu(2)S) was the major Cu species present under pig slurry lagoon physical chemical conditions. This Cu speciation in pig slurry may be the main reason for the observed Cu accumulation at the soil surface. PMID- 20735048 TI - Organic thin-film transistors: the passivation of the dielectric-pentacene interface by dipolar self-assembled monolayers. AB - In organic thin-film transistors (OTFTs), the conducting channel is located near the interface between the organic semiconductor and the oxide dielectric; this interface is crucial for transistor performance. Self-assembled monolayers (SAMs) on the interface reduce the negative influences of the oxide dielectric surface by decreasing the coupling of the carriers at the gate and the role of the active surface defects on transfer. In this paper, we show that SAMs carrying a dipole moment determine the OTFT performance by controlling the charge transfer between the oxide dielectric and the semiconductor. The charges introduced into the semiconductor by this transfer (i.e., residual carriers) lead to a threshold shift to positive values, as well as a decrease in the contact resistance and an increase in the apparent mobility. In this study, other effects of the SAMs, such as the gate potential shift in the channel or a direct reaction between semiconductor and SAM molecules, can be excluded as dominant processes. PMID- 20735049 TI - Rapid context-dependent ligand desolvation in molecular docking. AB - In structure-based screens for new ligands, a molecular docking algorithm must rapidly score many molecules in multiple configurations, accounting for both the ligand's interactions with receptor and its competing interactions with solvent. Here we explore a context-dependent ligand desolvation scoring term for molecular docking. We relate the Generalized-Born effective Born radii for every ligand atom to a fractional desolvation and then use this fraction to scale an atom-by atom decomposition of the full transfer free energy. The fractional desolvation is precomputed on a scoring grid by numerically integrating over the volume of receptor proximal to a ligand atom, weighted by distance. To test this method's performance, we dock ligands versus property-matched decoys over 40 DUD targets. Context-dependent desolvation better enriches ligands compared to both the raw full transfer free energy penalty and compared to ignoring desolvation altogether, though the improvement is modest. More compellingly, the new method improves docking performance across receptor types. Thus, whereas entirely ignoring desolvation works best for charged sites and overpenalizing with full desolvation works well for neutral sites, the physically more correct context dependent ligand desolvation is competitive across both types of targets. The method also reliably discriminates ligands from highly charged molecules, where ignoring desolvation performs poorly. Since this context-dependent ligand desolvation may be precalculated, it improves docking reliability with minimal cost to calculation time and may be readily incorporated into any physics-based docking program. PMID- 20735050 TI - Diazirine-modified gold nanoparticle: template for efficient photoinduced interfacial carbene insertion reactions. AB - Photolysis of a 3-aryl-3-(trifluoromethyl)diazirine-modified monolayer-protected gold nanoparticles (2-C(12)MPNs), with a core size of 1.8 +/- 0.3 nm, in the presence of model carbene trapping reagents leads to efficient, essentially quantitative, modification of the interface via carbene insertion reactions. The utility of carbene insertion reactions as a general approach for the modification of Au-MPNs to provide a breadth of new structures available was demonstrated using acetic acid, methanol, benzyl alcohol, phenol, benzylamine, methyl acrylate, and styrene (10a-g, respectively) as electrophilic carbene trapping agents to form the corresponding modified 3a-g-C(12)MPNs. The 1.8 +/- 0.3 nm gold nanoparticles bearing a diazirine group (2-C(12)MPNs) were synthesized using the ligand exchange reaction with the requisite 3-aryl-3 (trifluoromethyl)diazirinealkylthiol. The 2-C(12)MPNs and the resulting products of the reaction on the MPN (3a-g-C(12)MPN) were fully characterized by IR, (1)H NMR, and (19)F NMR spectroscopy and, when applicable, transmission electron microscopy (TEM). Verification for the 3a-g-C(12)MPNs was accomplished by comparison of the spectral data to those of obtained for the photoreactions of 3 (3-methoxyphenyl)-3-(trifluoromethyl)-3H-diazirine as a model with 10a-g. PMID- 20735051 TI - Resveratrol oligomers from Vatica albiramis. AB - Five new stilbenoids, vatalbinosides A-E (1-5), and 13 known compounds (6-18) were isolated from the stem of Vatica albiramis. The effects of these new compounds on interleukin-1beta-induced production of matrix metalloproteinase-1 (MMP-1) in human dermal fibroblasts were examined. Three resveratrol tetramers, ( )-hopeaphenol (6), vaticanol C (13), and stenophyllol C (14), were identified as strong inhibitors of MMP-1 production. PMID- 20735052 TI - Recent contributions from the Baylis-Hillman reaction to organic chemistry. PMID- 20735053 TI - Gigantic two-photon absorption cross sections and strong two-photon excited fluorescence in pyrene core dendrimers with fluorene/carbazole as dendrons and acetylene as linkages. AB - We report a series of stiff dendrimers (referred to as T1, T2, T3, and T4) that have both gigantic two-photon absorption (TPA) cross sections up to 25,000 GM and strong two-photon excited fluorescence (TPEF) with fluorescence quantum yield of ~0.5. The large TPA cross sections and high quantum yields of these dendrimers are directly related to their geometrical structures, where the polycyclic aromatic pyrene is chosen as the chromophoric core because of its planar and highly pi-conjugated structure, fluorene moieties as dendrons extend the conjugation length through the planar structure, and carbazole moieties are modified at three-, six-, and nine-positions as electron donor. All of these groups are linked with acetylene linkage for effective pi-electron delocalization, leading to large TPA cross section and high fluorescence quantum yield. The spectral properties of all dendrimers are investigated by one- and two photon excitations. Furthermore, steady-state fluorescence excitation anisotropy and quantum chemical calculation are also employed to determine the structure related mechanism of these dendrimers with gigantic TPA cross sections and high TPEF efficiency. We then show that the improvement of branched chains in the T series dendrimers enhances the light-harvesting ability. The core emission spectra, fluorescence quantum yield, and fluorescence lifetime are almost invariable by directly exciting the dendrons. These results will provide a guideline for the design of useful two-photon materials with structural motifs that can enhance the TPA cross-section and fluorescence quantum yield of a molecule without causing a red shift of the one- and two-photon excitation wavelengths for specific applications. PMID- 20735054 TI - Structure and order of phosphonic acid-based self-assembled monolayers on Si(100). AB - Organophosphonic acid self-assembled monolayers (SAMs) on oxide surfaces have recently seen increased use in electrical and biological sensor applications. The reliability and reproducibility of these sensors require good molecular organization in these SAMs. In this regard, packing, order, and alignment in the SAMs is important, as it influences the electron transport measurements. In this study, we examine the order of hydroxyl- and methyl-terminated phosphonate films deposited onto silicon oxide surfaces by the tethering by aggregation and growth method using complementary, state-of-art surface characterization tools. Near edge X-ray absorption fine structure (NEXAFS) spectroscopy and in situ sum frequency generation (SFG) spectroscopy are used to study the order of the phosphonate SAMs in vacuum and under aqueous conditions, respectively. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry results show that these samples form chemically intact monolayer phosphonate films. NEXAFS and SFG spectroscopy showed that molecular order exists in the octadecylphosphonic acid and 11-hydroxyundecylphosphonic acid SAMs. The chain tilt angles in these SAMs were approximately 37 degrees and 45 degrees , respectively. PMID- 20735055 TI - Precise, facile initial rate measurements. AB - Progress curve analysis has been used sparingly in studies of enzyme-catalyzed reactions due largely to the complexity of the integrated rate expressions used in data analysis. Using an experimental design that simplifies the analysis, the advantages and limitations of progress curve experiments are explored in a study of four different enzyme-catalyzed reactions. The approach involves relatively simple protocols, requires 20-25% of the materials, and provides 10- to 20-fold signal enhancements compared to analogous initial rate studies. Product inhibition, which complicates integrated rate analysis, was circumvented using cloned, purified enzymes that remove the products and draw the reaction forward. The resulting progress curves can be transformed into the equivalent of thousands of initial rate and [S] measurements and, due to the absence of product inhibition, are plotted in the familiar, linear double-reciprocal format. Allowing product to accumulate during a reaction produces a continuously changing substrate/product ratio that can be used as the basis for obtaining product inhibition constants and to distinguish among the three classical inhibition mechanisms. Algebraic models describing the double-reciprocal patterns obtained from such inhibition studies are presented. The virtual continuum of substrate concentrations that occurs during a progress curve experiment provides a nearly errorless set of relative concentrations that results in remarkably precise data; kinetic constant standard deviations are on the order of 0.5%. PMID- 20735056 TI - Double freezing of (NH(4))(2)SO(4)/H(2)O droplets below the eutectic point and the crystallization of (NH(4))(2)SO(4) to the ferroelectric phase. AB - This paper presents the differential scanning calorimetry (DSC) results obtained from measurements of single droplets of different subeutectic concentrations (<40 wt % (NH4)2SO4) and diameters of 1-1.5 mm. The measurements show that despite the fact that the freezing of the droplets takes place below the eutectic temperature of Te ~ 254.5 K, a phase separation into ice and a residual freeze-concentrated solution occurs. The residual solution is formed by the expulsion of NH4+ and SO42- ions from the ice lattice during the nucleation and growth of ice and may possess the eutectic concentration of 40 wt % (NH4)2SO4. On further cooling, the residual solution freezes to the eutectic solid mixture of ice/(NH4)2SO4 at a temperature that is either above or below the ferroelectric "Curie" temperature of Tc ~ 223 K. If the freezing of the residual solution takes place below the Tc, then (NH4)2SO4 crystallizes directly into the ferroelectric phase. PMID- 20735057 TI - From chemical risk assessment to environmental quality management: the challenge for soil protection. AB - The 40 years that have passed since the beginning of the 'environmental revolution' has seen a large increase in development of policies for the protection of environmental media and a recognition by the public of the importance of environmental quality. There has been a shift from policy in reaction to high profile events, then to control of releases to single environmental media, and to the present position of moving toward integrated management of all environmental media at present. This development has moved away from classical chemical risk assessment toward environmental holism, including recognition of the ecological value of these media. This work details how policy developments have taken place for air and water, with examples from the USA and EU, in order to compare this with policy development regarding soil. Soil, with quite different policy frameworks and distinct uses, understanding, and threats compared to other environmental media, is currently attracting attention regarding the need for its protection independent of use. Challenges for soil policy are identified and evaluated, and recommendations on how these challenges can be overcome are discussed with relevance to water and air protection policy. PMID- 20735058 TI - Triton X-100 as the "short-chain lipid" improves the magnetic alignment and stability of membrane proteins in phosphatidylcholine bilayers for oriented sample solid-state NMR spectroscopy. AB - A mixture of phospholipids and Triton X-100 in a molar ratio of 5:1 forms well aligned and stable bilayers that give superior solid-state NMR spectra of proteins. In a comparison, the oriented-sample (OS) solid-state NMR spectrum of Pf1 coat protein in aligned phospholipid bilayers displayed better resolution than the equivalent solution NMR spectrum of the same protein in micelles. Both samples and experimental parameters were fully optimized. PMID- 20735059 TI - Unconventional layer-by-layer assembly of graphene multilayer films for enzyme based glucose and maltose biosensing. AB - We have developed an unconventional method for the layer-by-layer (LbL) assembly of graphene multilayer films. Unconventional LbL assembly was achieved by the following two-step process. Graphene sheets were modified by pyrene-grafted poly(acrylic acid) (PAA) in aqueous solution, and then the modified graphene sheets were used for layer-by-layer alternating deposition with poly(ethyleneimine) (PEI). The graphene-multilayer-film-modified electrode shows enhanced electron transfer for the redox reactions of Fe(CN)(6)(3-) and excellent electrocatalytic activity of H(2)O(2). On the basis of this property, a bienzyme biosensing system for the detection of maltose was fabricated by successive LbL assembly of graphene, glucose oxidase (GOx), and glucoamylase (GA). LbL assembly of graphene combines the excellent electrochemical properties of graphene and the versatility of LbL assembly, showing great promise in highly efficient sensors and advanced biosensing systems. PMID- 20735060 TI - Aggregation control of hydrophilic maghemite (gamma-Fe2O3) nanoparticles by surface doping using cerium atoms. AB - The high-power ultrasonic irradiation of preformed magnetite (Fe(3)O(4)) nanoparticles in the presence of monoelectronic Ce-containing ceric ammonium nitrate [Ce(IV)(NH(4))(2)(NO(3))(6)] oxidant in MeCOMe afforded hydrophilic 50 nm sized colloidal, highly stable maghemite (gamma-Fe(2)O(3)) nanoparticles. An "inorganic" Ce atom doping of the NP surface has been proposed in order to rationalize the observed nanoparticle antiaggregation phenomenon. Quite importantly, this method did not require the use of any organic ligand and/or polymer for the passivation of the nanoparticle surface. PMID- 20735061 TI - Fabrication of highly conductive and transparent thin films from single-walled carbon nanotubes using a new non-ionic surfactant via spin coating. AB - Oligothiophene-terminated poly(ethylene glycol) was synthesized and used as a non ionic and amphiphilic surfactant for fabricating high-quality single-walled carbon nanotube (SWCNT) films by a simple spin coating method. The absence of charge repulsion between SWCNT/surfactant complexes successfully leads to formation of a dense network of SWCNTs on the substrate through a single deposition of spin coating. When the SWCNT film was treated with nitric acid and thionyl chloride after washed with dichloromethane and water, a high-performance SWCNT film with the sheet resistance of 59 ohm/sq and the transparency of 71% at 550 nm was successfully obtained. Since the SWCNT film exhibits a high value of sigma(dc)/sigma(ac) (~17) and excellent dimensional stability after releasing from the substrate, the film can be used as a transparent electrode in flexible optoelectronic devices. PMID- 20735062 TI - Photovoltaic charge generation in organic semiconductors based on long-range energy transfer. AB - For efficient charge generation in organic solar cells, photogenerated excitons must migrate to a donor/acceptor interface where they can be dissociated. This migration is traditionally presumed to be based on diffusion through the absorber material. Herein we study an alternative migration route--two-step exciton dissociation--whereby the exciton jumps from the donor to acceptor before charge creation takes place. We study this process in a series of multilayer donor/barrier/acceptor samples, where either poly(3-hexylthiophene) (P3HT) or copper phthalocyanine (CuPc) is the donor, fullerene (C60) is the acceptor, and N,N-diphenyl-N,N-bis(3-methylphenyl)-[1,1-bisphenyl]-4,4-diamine (TPD) acts as a barrier to energy transfer. By varying the thickness of the barrier layer, we find that energy transfer from P3HT to C60 proceeds over large distances (~50% probability of transfer across a 11 nm barrier), and that this process is consistent with long-range Forster resonance energy transfer (FRET). Finally, we demonstrate a fundamentally different architecture concept that utilizes the two step mechanism to enhance performance in a series of P3HT/CuPc/C60 devices. PMID- 20735063 TI - Giant thermoelectric effect from transmission supernodes. AB - We predict an enormous order-dependent quantum enhancement of thermoelectric effects in the vicinity of higher-order interferences in the transmission spectrum of a nanoscale junction. Single-molecule junctions based on 3,3' biphenyl and polyphenyl ether (PPE) are investigated in detail. The nonequilibrium thermodynamic efficiency and power output of a thermoelectric heat engine based on a 1,3-benzene junction are calculated using many-body theory and compared to the predictions of the figure-of-merit ZT. PMID- 20735064 TI - Synthesis of edge-closed graphene ribbons with enhanced conductivity. AB - Edge-closed and edge-opened graphene ribbons were synthesized on Pd nanowire templates using plasma-enhanced chemical vapor deposition (PECVD). After metal nanowire etching, the tubular shaped thin graphene layers were collapsed to edge closed graphene ribbon. In order to make edge-opened graphene ribbons, the graphene layers on the top part of the metal nanowire were selectively etched by O(2) plasma. The protected graphene layers at the bottom of nanowire are transformed to edge-opened graphene ribbon after nanowire etching. Because of defect-free edges, edge-closed graphene ribbon showed reduced D-band intensity compared to edge-opened graphene ribbons, and moreover, the conductivity of edge closed graphene ribbon was much higher than that of edge-opened graphene ribbon. PMID- 20735066 TI - Copper-catalyzed olefin aminoacetoxylation. AB - A new catalyst system for intramolecular olefin aminoacetoxylation is described. In contrast to previously reported palladium- and copper-catalyzed systems, the conditions outlined in this communication favor piperdine formation with terminal olefin substrates and induce cyclization with traditionally less reactive disubstituted olefins. PMID- 20735065 TI - Sesterterpenoids and other constituents of Salvia sahendica. AB - A new sesterterpene (1), a new norsesterterpene (3), and two new norditerpenes (4, 5) were isolated from the aerial parts of Salvia sahendica, together with 12 known compounds, comprising a sesterterpene, a sesquiterpene, a diterpene, two triterpenes, two steroidal compounds, and five flavonoids. The structures of the new compounds were established by spectroscopic data interpretation, and in the case of 4, its structure was confirmed by single-crystal X-ray analysis. PMID- 20735067 TI - Exciton fission and charge generation via triplet excitons in pentacene/C60 bilayers. AB - Organic photovoltaic devices are currently studied due to their potential suitability for flexible and large-area applications, though efficiencies are presently low. Here we study pentacene/C(60) bilayers using transient optical absorption spectroscopy; such structures exhibit anomalously high quantum efficiencies. We show that charge generation primarily occurs 2-10 ns after photoexcitation. This supports a model where charge is generated following the slow diffusion of triplet excitons to the heterojunction. These triplets are shown to be present from early times (<200 fs) and result from the fission of a spin-singlet exciton to form two spin-triplet excitons. These results elucidate exciton and charge generation dynamics in the pentacene/C(60) system and demonstrate that the tuning of the energetic levels of organic molecules to take advantages of singlet fission could lead to greatly enhanced photocurrent in future OPVs. PMID- 20735068 TI - X-ray crystal structures of [XeF][MF6] (M = As, Sb, Bi), [XeF][M2F11] (M = Sb, Bi) and estimated thermochemical data and predicted stabilities for noble-gas fluorocation salts using volume-based thermodynamics. AB - The crystal structures of the xenon(II) salts, [XeF][SbF(6)], [XeF][BiF(6)], and [XeF][Bi(2)F(11)], have been determined for the first time, and those of XeF(2), [XeF][AsF(6)], [XeF][Sb(2)F(11)], and [XeF(3)][Sb(2)F(11)] have been redetermined with greater precision at -173 degrees C. The Bi(2)F(11)(-) anion, which has a structure analogous to those of the As(2)F(11)(-) and Sb(2)F(11)(-) anions, has been structurally characterized by single crystal X-ray diffraction for the first time as its XeF(+) salt. The fluorine bridge between the bismuth atoms is asymmetric with Bi---F(b) bond lengths of 2.092(6) and 2.195(6) A and a Bi-- F(b)'---Bi bridge bond angle of 145.3(3) degrees . The XeF(+) cations interact with their anions by means of Xe---F(b)---M bridges. Consequently, the solid state Raman spectra of [XeF][MF(6)] (M = As, Sb, Bi) were modeled as the gas phase ion pairs and assigned with the aid of quantum-chemical calculations. Relationships among the terminal Xe-F(t) and bridge Xe---F(b) bond lengths and stretching frequencies and the gas-phase fluoride ion affinities of the parent Lewis acid that the anion is derived from are considered. The analogous krypton ion pairs, [KrF][MF(6)] (M = As, Sb, Bi) were also calculated and compared with their previously published X-ray crystal structures. The calculated cation-anion charge separations indicate that the [XeF][MF(6)] salts are more ionic than their krypton analogues and that XeF(2) is a stronger fluoride ion donor than KrF(2). The lattice energies, standard enthalpies, and free energies of formation for salts containing the NgF(+), Ng(2)F(3)(+), XeF(3)(+), XeF(5)(+), Xe(2)F(11)(+), and XeOF(3)(+) (Ng = Ar, Kr, Xe) cations were estimated using volume-based thermodynamics (VBT) based on crystallographic and estimated ion volumes. These estimated parameters were then used to predict the stabilities of noble-gas salts. VBT is used to examine and predict the stabilities of, inter alia, the salts [XeF(m)][Sb(n)F(5n+1)] and [XeF(m)][As(n)F(5n+1)] (m = 1, 3; n = 1, 2). VBT also confirms that XeF(+) salts are stable toward redox decomposition to Ng, F(2), and MF(5) (M = As, Sb), whereas the isolable krypton compounds and the unknown ArF(+) salts are predicted to be unstable by VBT with the ArF(+) salts being the least stable. PMID- 20735069 TI - Fabrication of free-standing, electrochemically active, and biocompatible graphene oxide-polyaniline and graphene-polyaniline hybrid papers. AB - In this work, we report a low-cost technique via simple rapid-mixture polymerization of aniline using graphene oxide (GO) and graphene papers as substrates, respectively, to fabricate free-standing, flexible GO-polyaniline (PANI) and graphene-PANI hybrid papers. The morphology and microstructure of the obtained papers were characterized by FESEM, FTIR, Raman, and XRD. As results, nanostructural PANI can be deposited on the surfaces of GO and graphene papers, forming thin, lightweight, and flexible paperlike hybrid papers. The hybrid papers display a remarkable combination of excellent electrochemical performances and biocompatibility, making the paperlike materials attractive for new kinds of applications in biosciences. PMID- 20735070 TI - Training, selection, and robust calibration of retention time models for targeted proteomics. AB - Accurate predictions of peptide retention times (RT) in liquid chromatography have many applications in mass spectrometry-based proteomics. Most notably such predictions are used to weed out incorrect peptide-spectrum matches, and to design targeted proteomics experiments. In this study, we describe a RT predictor, ELUDE, which can be employed in both applications. ELUDE's predictions are based on 60 features derived from the peptide's amino acid composition and optimally combined using kernel regression. When sufficient data is available, ELUDE derives a retention time index for the condition at hand making it fully portable to new chromatographic conditions. In cases when little training data is available, as often is the case in targeted proteomics experiments, ELUDE selects and calibrates a model from a library of pretrained predictors. Both model selection and calibration are carried out via robust statistical methods and thus ELUDE can handle situations where the calibration data contains erroneous data points. We benchmarked our method against two state-of-the-art predictors and showed that ELUDE outperforms these methods and tracked up to 34% more peptides in a theoretical SRM method creation experiment. ELUDE is freely available under Apache License from http://per-colator.com. PMID- 20735071 TI - Defining a stem length-dependent binding mechanism for the cocaine-binding aptamer. A combined NMR and calorimetry study. AB - We have used a combined approach of NMR spectroscopy and isothermal titration calorimetry (ITC) to determine the ligand-binding mechanism employed by a cocaine binding aptamer. We found that the length of the stem containing the 3' and 5' termini determines the nature of the binding mechanism. When this stem is six base pairs long, the secondary structure of the aptamer is fully folded in the free form and only putative tertiary interactions form with ligand binding. If this stem is shortened by three base pairs, the free form of the aptamer contains little secondary structure, and ligand binding triggers secondary structure formation and folding. This binding mechanism is supported by both NMR spectral changes and the ITC measured heat capacity of binding (DeltaC(p) degrees ). For the aptamer with the long stem the DeltaC(p) degrees value is -557 +/- 29 cal mol(-1) K(-1) and for the aptamer with the short stem the DeltaC(p) degrees value is -922 +/- 51 cal mol(-1) K(-1). Chemical shift perturbation data and the observation of intermolecular NOEs indicate that the three-way junction is the site of ligand binding. PMID- 20735072 TI - Metal monophosphonates M{(2-C5H4NO)CH2PO3}(H2O)2 (M = Co, Ni, Mn, Cd): synthesis, structure, and magnetism. AB - Four isostructural metal monophosphonates, M{(2-C(5)H(4)NO)CH(2)PO(3)}(H(2)O)(2) with M = Co (1), Ni (2), Mn (3), and Cd (4), were synthesized and structurally characterized. These compounds show a double-chain structure in which the M(2)(MU O)(2) dimers are connected by O-P-O bridges. The magnetic responses of 1-3 were investigated over a wide range of magnetic fields (up to 10 T) and temperatures (down to 50 mK). Except for 4, which is weakly diamagnetic from 2 K to room temperature, the dominant magnetic interactions are antiferromagnetic. Isothermal magnetic field sweeps at 50 mK provide signatures in the magnetic responses that are associated with antiferromagnetic to field-induced fully polarized (magnetically saturated) transitions. Analysis of the magnetic data indicates that 1 and 2 form magnetic dimer-like clusters with weak dimer-dimer interactions present. Contrastingly, the magnetic interactions present in 3 are significantly weaker, so a definitive description of the magnetism of this compound is elusive. PMID- 20735073 TI - Novel noncentrosymmetric zinc coordination polymer containing an unusual zinc carboxylate-sulfonate substructure with a (10,3)-d topology and its second harmonic-generation properties. AB - A novel 3D coordination polymer, Zn(2)(MU(2)-OH)(SIP)(DPP) (1), with mixed ligands of 5-sulfoisophthalate (SIP) and 1,3-di-4-pyridylpropane (DPP), has been hydrothermally synthesized and characterized. 1 contains an unusual 3D subnet with distorted (10,3)-d topology and left/right-handed helical channels. Second harmonic-generation (SHG) measurements revealed that the material has a strong SHG response (~2.5 times that of potassium dihydrogen phosphate (KDP)) and is phase-matchable. In addition, photoluminescent and thermogravimetric analysis were also performed on 1. PMID- 20735074 TI - InAs/GaSb heterostructure nanowires for tunnel field-effect transistors. AB - InAs/GaSb nanowire heterostructures with thin GaInAs inserts were grown by MOVPE and characterized by electrical measurements and transmission electron microscopy. Down-scaling of the insert thickness was limited because of an observed sensitivity of GaSb nanowire growth to the presence of In. By employing growth interrupts in between the InAs and GaInAs growth steps it was possible to reach an insert thickness down to 25 nm. Two-terminal devices show a diode behavior, where temperature-dependent measurements indicate a heterostructure barrier height of 0.5 eV, which is identified as the valence band offset between the InAs and GaSb. Three-terminal transistor structures with a top-gate positioned at the heterointerface show clear indications of band-to-band tunnelling. PMID- 20735075 TI - Robust high-kappa response in molecularly thin perovskite nanosheets. AB - Size-induced suppression of permittivity in perovskite thin films is a fundamental problem that has remained unresolved for decades. This size-effect issue becomes increasingly important due to the integration of perovskite nanofilms into high-kappa capacitors, as well as concerns that intrinsic size effects may limit their device performance. Here, we report a new approach to produce robust high-kappa nanodielectrics using perovskite nanosheet (Ca2Nb3O10), a new class of nanomaterials that is derived from layered compounds by exfoliation. By a solution-based bottom-up approach using perovskite nanosheets, we have successfully fabricated multilayer nanofilms directly on SrRuO3 or Pt substrates without any interfacial dead layers. These nanofilms exhibit high dielectric constant (>200), the largest value seen so far in perovskite films with a thickness down to 10 nm. Furthermore, the superior high-kappa properties are a size-effect-free characteristic with low leakage current density (<10(-7) A cm(-2)). Our work provides a key for understanding the size effect and also represents a step toward a bottom-up paradigm for future high-kappa devices. PMID- 20735076 TI - Palladium-catalyzed double carbonylation reactions of o-dihaloarenes with amines in phosphonium salt ionic liquids. AB - Palladium-catalyzed double carbonylation of o-dihaloarenes with amines in phosphonium salt ionic liquids proceeds efficiently to give the corresponding N substituted phthalimides. This process can tolerate a wide array of functional groups and affords products in excellent yields. The recyclability of the catalytic system was also investigated. PMID- 20735077 TI - 1,1-Dibromo-1-alkenes as valuable partners in the copper-catalyzed direct alkynylation of azoles. AB - The copper-catalyzed direct alkynylation of azoles with 1,1-dibromo-1-alkenes as electrophiles is described. These easily accessible substrates are a useful addition to the field of direct alkynylations in an efficient and functional group tolerant reaction to provide a straightforward entry to diverse alkynyl heterocycles. PMID- 20735078 TI - Unprecedented radical-radical reaction of a [2.2]paracyclophane derivative containing an imidazolyl radical moiety. AB - Pseudogem-DPIM-DPI[2.2]PC dimer (3), with a C-N bond between the [2.2]paracyclophane ([2.2]PC) moiety and the imidazole ring, was synthesized. This is the first crystallographic observation of a highly sterically constrained 1-ene-2,5-cyclohexadiene structure for a [2.2]PC derivative. Compound 3 shows a photochromic behavior, exhibiting a color change from pale yellow to green upon either UV or visible light irradiation, both in the solid state and in solution at room temperature. PMID- 20735079 TI - Alsmaphorazines A and B, novel indole alkaloids from Alstonia pneumatophora. AB - Two novel indole alkaloids, alsmaphorazines A and B, were isolated from the leaves of Alstonia pneumatophora (Apocynaceae), and their structures were determined on the basis of the 2D NMR and MS spectral analysis. These alkaloids possessed a new skeleton consisting of an 1,2-oxazinane and an isoxazolidine chromophore. The absolute configuration of alsmaphorazine B was determined by using CD spectral analysis. Alsmaphorazine A inhibited the NO production in the LPS-stimulated J774.1 cells dose-dependently without affecting the cell viability. PMID- 20735080 TI - Asymmetric hydrogenation of protected allylic amines. AB - A general method for the enantioselective hydrogenation of protected allylic amine derivatives is described. This procedure relies on the generation of a cationic ruthenium complex with the axially chiral ligand (-)-TMBTP. The utility is highlighted by the highly enantioselective hydrogenation of a diene substrate that can then be elaborated to prepare Telcagepant, a compound currently in Phase III clinical trials. The scope of the hydrogenation reaction was studied, and a variety of substituted allylic amine derivatives could be hydrogenated with enantiomeric ratios of 92:8 or higher. PMID- 20735081 TI - Enantioselective synthesis of cyclic sulfamidates by using chiral rhodium catalyzed asymmetric transfer hydrogenation. AB - Asymmetric transfer hydrogenation (ATH) of cyclic sulfamidate imines 4 and 9, using a HCO(2)H/Et(3)N mixture as the hydrogen source and well-defined chiral Rh catalysts (S,S)- or (R,R)-2, Cp*RhCl(TsDPEN), effectively produces the corresponding cyclic sulfamidates with excellent yields and enantioselectivities at room temperature within 0.5 h. ATH of 4,5-disubstituted imines 9, having preexisting stereogenic centers, is shown to take place with dynamic kinetic resolution. PMID- 20735082 TI - Periselectivity switch of acylketenes in cycloadditions with 1-azadienes: microwave-assisted diastereoselective domino three-component synthesis of alpha spiro-delta-lactams. AB - The microwave-assisted Wolff rearrangement of cyclic 2-diazo-1,3-diketones in the presence of primary amines and alpha,beta-unsaturated aldehydes provides a straightforward three-component stereoselective access to a variety of alpha spiro-delta-lactams following an imination/Wolff rearrangement/[2 + 4] cycloaddition domino sequence. With aniline derivatives, a complementary aza Wittig/Wolff rearrangement/[2 + 4] sequence was developed. These reactions feature an unprecedented reactivity of acylketenes as dienophiles in 6pi electrocyclic processes. PMID- 20735083 TI - Nonheme manganese-catalyzed asymmetric oxidation. A Lewis acid activation versus oxygen rebound mechanism: evidence for the "third oxidant". AB - The catalytic properties of a series of chiral nonheme aminopyridinylmanganese(II) complexes [LMn(II)(OTf)(2)] were investigated. The above complexes were found to efficiently catalyze enantioselective olefin oxidation to the corresponding epoxides with different oxidants (peroxycarboxylic acids, alkyl hydroperoxides, iodosylarenes, etc.) with high conversions and selectivities (up to 100%) and enantiomeric excesses (up to 79%). The effect of the ligand structure on the catalytic performance was probed. Epoxidation enantioselectivities were found to be strongly dependent on the structure of the oxidants (performic, peracetic, and m-chloroperbenzoic acids; tert-butyl and cumyl hydroperoxides; iodosylbenzene and iodosylmesitylene), thus bearing evidence that the terminal oxidant molecule is incorporated in the structure of the oxygen-transferring intermediates. High-valence electron-paramagnetic resonance-active manganese complexes [LMn(IV)?O](2+) and [LMn(IV)(MU O)(2)Mn(III)L](3+) were detected upon interaction of the starting catalyst with the oxidants. The high-valence complexes did not epoxidize styrene and could themselves only contribute to minor olefin oxidation sideways. However, the oxomanganese(IV) species were found to perform the Lewis acid activation of the acyl and alkyl hydroperoxides or iodosylarenes to form the new type of oxidant [oxomanganese(IV) complex with a terminal oxidant], with the latter accounting for the predominant enantioselective epoxidation pathway in the nonheme manganese catalyzed olefin epoxidations. PMID- 20735084 TI - Impact of Biopharmaceutics Classification System-based biowaivers. AB - The Biopharmaceutics Classification System (BCS) is employed to waive in vivo bioequivalence testing (i.e. provide "biowaivers") for new and generic drugs that are BCS class I. Granting biowaivers under systems such as the BCS eliminates unnecessary drug exposures to healthy subjects and provides economic relief, while maintaining the high public health standard for therapeutic equivalence. International scientific consensus suggests class III drugs are also eligible for biowaivers. The objective of this study was to estimate the economic impact of class I BCS-based biowaivers, along with the economic impact of a potential expansion to BCS class III. Methods consider the distribution of drugs across the four BCS classes, numbers of in vivo bioequivalence studies performed from a five year period, and effects of highly variable drugs (HVDs). Results indicate that 26% of all drugs are class I non-HVDs, 7% are class I HVDs, 27% are class III non HVDs, and 3% are class III HVDs. An estimated 66 to 76 million dollars can be saved each year in clinical study costs if all class I compounds were granted biowaivers. Between 21 and 24 million dollars of this savings is from HVDs. If BCS class III compounds were also granted waivers, an additional direct savings of 62 to 71 million dollars would be realized, with 9 to 10 million dollars coming from HVDs. PMID- 20735085 TI - BCRP at the blood-brain barrier: genomic regulation by 17beta-estradiol. AB - At the blood-brain barrier (BBB), the ABC transporter breast cancer resistance protein (BCRP) actively extrudes a variety of therapeutic drugs, including cytostatics, and diminishes their pharmacological efficacy in the brain. Consequently, new strategies to circumvent BCRP-mediated multidrug resistance in the CNS are required. One major approach to increase brain drug levels is to manipulate signaling mechanisms that control transporter expression and function. In the present study, we investigated the long-term effect of 17beta-estradiol on BCRP in an ex vivo model of isolated rat brain capillaries. BCRP function and protein expression were decreased after 6 h of incubation with nanomolar concentrations of 17beta-estradiol in capillaries from male and female rats. Concomitantly, levels of BCRP mRNA were also reduced by 17beta-estradiol suggesting that the transporter is down-regulated via a genomic pathway. Additionally, we identified the presence of both estrogen receptor (ER) subtypes alpha and beta at the rat BBB. Experiments using selective ER agonists and antagonists revealed that ER subtype beta is responsible for the hormone-induced reduction of BCRP function and protein expression. These findings were confirmed by the use of ERKO mice. Blocking the proteasome-dependent degradation by lactacystin reversed the 17beta-estradiol-mediated decrease of BCRP supposing that transcriptional down-regulation of the efflux transporter is paralleled by protein degradation. This study demonstrates that 17beta-estradiol induces the down-regulation of BCRP on transcriptional and translational levels via the activation of ERbeta in rat brain capillaries after 6 h. These results could help to improve brain targeting of BCRP substrates in the treatment of CNS diseases such as brain tumors and also contribute to an enlarged understanding of BCRP drug interactions at a chronic intake of phytoestrogens and oral contraceptives. PMID- 20735086 TI - A microscale platform for integrated cell-free expression and activity screening of cellulases. AB - Recent advances in production of cellulases by genetic engineering and isolation from natural microbial communities have necessitated the development of high throughput analytical technologies for cellulase expression and screening. We have developed a novel cost-effective microscale approach based on in vitro protein synthesis, which seamlessly integrates cellulase expression with activity screening without the need for any protein purification procedures. Our platform achieves the entire process of transcription, translation, and activity screening within 2-3 hours in microwell arrays compared with days needed for conventional cell-based cellulase expression, purification, and activity screening. Highly sensitive fluorescence-based detection permits activity screening in volumes as low as 2-3 MUL with minimal evaporation (even at temperatures as high as 95 degrees C) leading to two orders of magnitude reduction in reagent usage and cost. The platform was used for rapid expression and screening of beta glucosidases (BGs) and cellobiohydrolases (CBHs) isolated from thermophilic microorganisms. Furthermore, it was also used to determine optimum temperatures for BG and CBH activities and to study product inhibition of CBHs. The approach described here is well suited for first-pass screening of large libraries to identify cellulases with desired properties that can subsequently be produced on a large scale for detailed structural and functional characterization. PMID- 20735088 TI - Intestinal absorption mechanism of tebipenem pivoxil, a novel oral carbapenem: involvement of human OATP family in apical membrane transport. AB - Tebipenem pivoxil (TBPM-PI) is an oral carbapenem antibiotic for treating otolaryngologic and respiratory infections in pediatric patients. This agent is a prodrug to improve intestinal absorption of TBPM, an active form, and an absorption rate of TBPM-PI is higher than those of other prodrug-type beta-lactam antibiotics. In the present study, we hypothesized that a certain mechanism other than simple diffusion is involved in the process of improved intestinal absorption of TBPM-PI and examined the mechanism. TBPM-PI uptake by Caco-2 cells was decreased by ATP-depletion and lowering the temperature to 4 degrees C, suggesting the contribution of carrier-mediated transport mechanisms. This uptake was partially decreased by ACE inhibitors, and the reduction of the absorption by captopril was observed by in vivo study and in situ single-pass intestinal perfusion study in rat, supporting the contribution of influx transporters. Since some ACE inhibitors and beta-lactam antibiotics are reported to be substrates of PEPT and OATP families, we measured transporting activity of TBPM-PI by intestinally expressed transporters, PEPT1, OATP1A2, and OATP2B1. As a result, significant transport activities were observed by both OATP1A2 and OATP2B1 but not by PEPT1. Interestingly, pH dependence of TBPM-PI transports was different between OATP1A2 and OATP2B1, showing highest activity by OATP1A2 at pH 6.5, while OATP2B1-mediated uptake was higher at neutral and weak alkaline pH. OATP1A2 exhibited higher affinity for TBPM-PI (K(m) = 41.1 MUM) than OATP2B1 (K(m) > 1 mM) for this agent. These results suggested that TBPM-PI has high intestinal apical membrane permeability due to plural intestinal transport routes, including the uptake transporters such as OATP1A2 and OATP2B1 as well as simple diffusion. PMID- 20735087 TI - Direct evidence of conformational heterogeneity in human pancreatic glucokinase from high-resolution nuclear magnetic resonance. AB - High-resolution nuclear magnetic resonance is used to investigate the conformational dynamics of human glucokinase, a 52 kDa monomeric enzyme that displays kinetic cooperativity. (1)H-(15)N transverse relaxation optimized spectra of uniformly labeled glucokinase, recorded in the absence and presence of glucose, reveal significant cross-peak overlap and heterogeneous peak intensities that persist over a range of temperatures. (15)N-specific labeling of isoleucines and tryptophans, reporting on backbone and side chain dynamics, respectively, demonstrates that both unliganded and glucose-bound enzymes sample multiple conformations, although glucose stabilizes certain conformations. These results provide the first direct evidence of glucokinase conformational heterogeneity and hence shed light on the molecular basis of cooperativity. PMID- 20735089 TI - Immobilization of silanized DNA on glass: influence of the silane tether on the DNA hybridization. AB - Two trifunctional (trimethoxy and triethoxy) and one difunctional (methyldimethoxy) 3-mercaptopropyl-alkoxysilanes were covalently tethered to thiolated DNA oligonucleotides in solution. After deposition as microarrays onto glass, the immobilized DNA probes were tested for hybridization ability by a florescence-based method. The results demonstrate a large enhancement in the fluorescence signal when the functionality of the silane tether is reduced from three to two. An XPS analyses revealed that this is not due to a higher DNA surface density. FTIR spectra of the spin-coated silanes showed that the trifunctional silanes form branched and cyclic siloxane moieties, whereas the difunctional silane generates predominantly short straight siloxane chains. Therefore, the propensity of trifunctional silanes to form more complex networks leads to conformations of the bound DNA which are less favorable for the specific interaction with the complementary strand. The data implicate that further significant improvements in the DNA hybridization ability are possible by adroit choice of the silane system. PMID- 20735091 TI - Ionic liquid pretreatment of poplar wood at room temperature: swelling and incorporation of nanoparticles. AB - Lignocellulosic biomass offers economic and environmental advantages over corn starch for biofuels production. However, its fractionation currently requires energy-intensive pretreatments, due to the lignin chemical resistance and complex cell wall structure. Recently, ionic liquids have been used to dissolve biomass at high temperatures. In this study, thin sections of poplar wood were swollen by ionic liquid (1-ethyl-3-methylimidazolium acetate) pretreatment at room temperature. The samples contract when rinsed with deionized water. The controlled expansion and contraction of the wood structure can be used to incorporate enzymes and catalysts deep into the wood structure for improved pretreatments and accelerated cellulose hydrolysis. As a proof of concept, silver and gold nanoparticles of diameters ranging from 20 to 100 nm were incorporated at depths up to 4 mum. Confocal surface-enhanced Raman images at different depths show that a significant number of nanoparticles were incorporated into the pretreated sample, and they remained on the samples after rinsing. Quantitative X ray fluorescence microanalyses indicate that the majority of nanoparticle incorporation occurs after an ionic liquid pretreatment of less than 1 h. In addition to improved pretreatments, the incorporation of materials and chemicals into wood and paper products enables isotope tracing, development of new sensing, and imaging capabilities. PMID- 20735093 TI - Synthesis of Pt nanopetals on highly ordered silicon nanocones for enhanced methanol electrooxidation activity. AB - Platinum (Pt) nanopetals were electrodeposited on highly ordered silicon nanocones (SiNCs) and explored as the electrocatalyst for methanol oxidation reaction (MOR) for direct methanol fuel cells applications. Highly ordered SiNCs array fabricated using the porous anodic aluminum oxide as the template had a high surface area. Well-dispersed Pt nanopetals possessing high electrocatalytic surface area was synthesized by pulse-electrodeposition on the SiNCs. Pt nanopetals loaded on highly ordered SiNC support exhibited very good catalytic activity for MOR and a high tolerance against CO poisoning, as compared to Pt nanoflowers/flat Si, Pt nanoparticles/flat Si, and many previously reported works. The abundance of a large surface area for facile transport of methanol, SiO(2) sites in the vicinity of the SiNCs, as well as less contact area between the Pt nanopetals catalyst and SiNCs are suggested to be the major factors enhancing the electrocatalytic performance of the Pt nanopetal/SiNC electrode. Moreover, we believe this new nanostructure (Pt nanopetals/SiNCs) will enable many new advances in nanotechnology. PMID- 20735094 TI - Preparation of iron and gold silicide nanodomains on silicon (111) by the reaction of gold, iron-gold core-shell, and alloy nanoparticles with triethylsilane. AB - This study describes a strategy to use composite colloidal nanoparticles and triethylsilane as precursors to synthesize nanometer size structures on single crystal silicon substrate. The concept is demonstrated by depositing gold, iron gold alloy, and iron-gold core-shell nanoparticles on silicon (111). Upon heating, the nanoparticles form new crystalline phases on the Si (111) surface. Atomic force microscope (AFM) data show the collapse of the iron gold core-shell and alloy nanoparticles at temperatures 100-200 degrees C higher than gold nanoparticles, indicating the efficient tethering of iron containing nanoparticles on silicon (111). Both structural analysis and X-ray spectroscopy show that the iron-gold alloy and iron-gold core-shell nanoparticles successfully form the semiconducting beta-FeSi(2) phase at relatively low temperature. The stabilities of the silicide are assessed at elevated temperatures. Silicon successfully nucleates on the created nanostructures, which suggests strong catalytic activity towards producing further nanostructures on the surface. PMID- 20735095 TI - Rapid silica atomic layer deposition on large quantities of cohesive nanoparticles. AB - Conformal silica films were deposited on anatase titania nanoparticles using rapid silica atomic layer deposition (ALD) in a fluidized bed reactor. Alternating doses of tris(tert-pentoxy)silanol (TPS) and trimethylaluminum (TMA) precursor vapors were used at 175 degrees C. In situ mass spectroscopy verified the growth mechanism through a siloxane polymerization process. Transmission electron microscopy revealed highly conformal and uniform silica nanofilms on the surface of titania nanoparticles. A growth rate of approximately 1.8 nm/cycle was achieved for an underdosed and incomplete polymerization reaction. Primary nanoparticles were coated despite their strong tendency to form dynamic agglomerates during fluidization. Methylene blue oxidation tests indicated that the photoactivity of anatase titania particles was mitigated with the ALD films. PMID- 20735096 TI - Mechanistic insights into UV-induced electron transfer from PCBM to titanium oxide in inverted-type organic thin film solar cells using AC impedance spectroscopy. AB - An inverted organic bulk-heterojunction solar cell containing amorphous titanium oxide (TiOx) as an electron collection electrode with the structure ITO/TiO(x)/[6,6]-phenyl C(61) butyric acid methyl ester (PCBM): regioregular poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxylenethiophene):poly(4-styrene sulfonic acid)/Au (TiO(x) cell) was fabricated. Its complicated photovoltaic properties were investigated by photocurrent-voltage and alternating current impedance spectroscopy measurements. The TiO(x) cell required a significant amount of time (approximately 60 min) to reach its maximum power conversion efficiency (PCE) of 2.6%. To investigate the reason for this slow photoresponse, we investigated the influences of UV light and water molecules adsorbed on the TiO(x) layer. Surface treatment of the TiO(x) cell with water induced a rapid photoresponse and enhanced the performance, giving a PCE of 2.97%. However, the durability of the treated cell was considerably inferior that of the untreated cell because of UV-induced photodegradation. The cause of the rapid photoresponse of the treated cell was attributed to the formation of hydrogen bonds between adsorbed water molecules and carbonyl oxygen atoms in PCBM close to the TiO(x) surface. When the TiO(x) surface was positively charged by UV-induced holes, the carbonyl oxygen in PCBM close to the TiO(x) surface can quickly join to the TiO(x) surface, rapidly transporting photogenerated electrons from PCBM to TiO(x) in competition with the photocatalyzed degradation. The experimental results suggested that the slow photoresponse of the untreated TiO(x) cell was because the morphology of the photoactive organic layer changed gradually upon irradiation to improve the transport of photocarriers at the TiO(x)/PCBM:P3HT interface. PMID- 20735097 TI - Plasma amino acid coatings for a conformal growth of titania nanoparticles. AB - We report on the conformal synthesis of ultrathin films from the amino acid histidine on flat silicon substrates and 3D periodic polymer structures via plasma enhanced chemical vapor deposition. We demonstrate the efficient utilization of this functional amino acid nanocoating for the formation of individual titania nanoparticles with dimensions from 2 to 15 nm depending upon reduction conditions. The titania nanoparticles were grown directly on histidine functionalized planar and 3D polymer substrates by a wet-chemistry method that showed uniform surface coverage that reached approximately 75%. This approach demonstrates the potential for modifying the optical properties of periodic porous polymeric structures via direct conformal growth of titania nanoparticles. PMID- 20735099 TI - The effect of nonideal polar monolayers on molecular gated transistors. AB - Nonideal polar monolayers can induce a field-effect in molecular gated transistors. To quantify the magnitude of this phenomenon, we have calculated the effect of roughness and noncontinuity of such layers on the operation of hybrid silicon-on-insulator field-effect transistors. The results show that under most practical conditions, the nonideality of polar monolayers induces very small electric fields in the underlying transistor channel, and consequently a negligible gating effect. PMID- 20735100 TI - Multilayered nano-architecture of variable sized graphene nanosheets for enhanced supercapacitor electrode performance. AB - The diverse physical and chemical aspects of graphene nanosheets such as particle size surface area and edge chemistry were combined to fabricate a new supercapacitor electrode architecture consisting of a highly aligned network of large-sized nanosheets as a series of current collectors within a multilayer configuration of bulk electrode. Capillary driven self-assembly of monolayers of graphene nanosheets was employed to create a flexible, multilayer, free-standing film of highly hydrophobic nanosheets over large macroscopic areas. This nanoarchitecture exhibits a high-frequency capacitative response and a nearly rectangular cyclic voltammogram at 1000 mV/s scanning rate and possesses a rapid current response, small equivalent series resistance (ESR), and fast ionic diffusion for high-power electrical double-layer capacitor (EDLC) application. PMID- 20735101 TI - Building upon patterned organic monolayers produced via catalytic stamp lithography. AB - Soft lithographic sub-100 nm chemical patterning was demonstrated on organic monolayer surfaces using poly(dimethylsiloxane)-based stamps decorated with Pd nanostructures, structures termed "catalytic stamps". Chemically reactive azide or alkene functionalities were incorporated on oxide-capped silicon surfaces and utilized for patterning via Pd-catalyzed hydrogenation or Heck reactions. The catalytic stamps were soft lithographic stamps based on PDMS with embedded nanoscale palladium catalysts, prepared via block copolymer-based templating. Nanoscale chemical patterns were readily generated on the azide or alkene precursor surfaces simply by applying the Pd catalytic stamps and the reactive molecule, the molecular ink, to the surface, thanks to the highly localized catalytic transformations induced by the patterned, immobilized solid Pd catalysts. A series of successful postfunctionalization reactions on the resulting patterned surfaces further demonstrated the utility of this approach to construct novel designs of nanoarchitectures, with potentially unique and innovative properties. PMID- 20735103 TI - Cell migration at the interface of a dual chemical-mechanical gradient. AB - Cell migration plays a critical role in numerous physiological processes, such as wound healing, response to inflammation, and cancer metastasis. In recent years, accumulating evidence indicates that cell movement is regulated not only by chemical signals but also by mechanical stimuli. In this study, the primary goal is to identify whether a chemical or mechanical stimulus plays the decisive role in directing cell migration. Measuring the motility of cells when they are presented with a combination of chemical and mechanical cues will provide insight into the complex physiological phenomena that guide and direct migration. A novel polyacrylamide hydrogel was designed with an interfacial region where the chemical and mechanical properties varied in opposing directions. One side of the interface was stiff (high Young's modulus) with a low protein concentration, whereas the other side of the interface was compliant (low Young's modulus) with a high protein concentration. The chemical gradient was created by varying the collagen (type I) concentration and the mechanical gradient was introduced by changing the extent of cross-linking in the polymer. The length of the interface with opposing chemical-mechanical profiles was found to be approximately 100 mum. Our results demonstrate that when Balb/c 3T3 fibroblasts were presented with a choice, they either migrated preferentially toward the high-collagen-compliant (low Young's modulus) side of the interfacial region or remained on the high collagen region, suggesting a more dominant role for chemical stimuli in directing fibroblast locomotion. PMID- 20735106 TI - In situ controllable growth of Prussian blue nanocubes on reduced graphene oxide: facile synthesis and their application as enhanced nanoelectrocatalyst for H2O2 reduction. AB - As a single-atom-thick carbon material with high surface area and conductivity, graphene provides an ideal platform for designing composite nanomaterials for high-performance electrocatalytic or electrochemical devices. Herein, we demonstrated a facile strategy for controllably growing high-quality Prussian blue nanocubes on the surface of reduced graphene oxide (PBNCs/rGO), which represents a new type of graphene/transition metal complex heterostructure. The merit of this method is that the composite nanomaterials could be produced directly from GO in an in situ wet-chemical reaction, where the reduction of GO and the deposition of PBNCs occurred simultaneously. The obtained composite nanomaterials were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), Raman spectroscopy, and electrochemical techniques. It was found that uniform PBNCs with controlled size and good dispersion were directly grown on the surface of graphene nanosheets. Moreover, we also investigated the performance of PBNCs/rGO nanocomposites as amperometric sensor toward reduction of H(2)O(2). Such a sensor showed a rapid and highly sensitive response to H(2)O(2) with a low detection limit (45 nM), which might find promising applications in developing a new type of enzymeless biosensor. PMID- 20735105 TI - Magnetite nanoparticle-supported coordination polymer nanofibers: synthesis and catalytic application in Suzuki-Miyaura coupling. AB - Functional nanoscale coordination polymers are receiving growing scientific interest because of their potential applications in many domains. In this paper, we demonstrated that a nanofibrous networked metal-organic gel (G1-MNPs) was formed by simply mixing 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tris(N-(pyridin-3 ylmethyl)benzamide) (L) and Pd(COD)(NO(3))(2) in CHCl(3)-MeOH with a Pd/L molar ratio of 1:1 in the presence of magnetite nanoparticle (MNPs). The self-assembly behavior of nanofibers was not significantly effected by the introduction of magnetite nanoparticles. The xerogel of G1-MNPs was superparamagnetic and showed catalytic activity in Suzuki-Miyaura C-C coupling reactions. The Pd(II) xerogel could be magnetically isolated and recycled with a permanent magnet. It represents a novel strategy to introduce nanoparticles into functional coordination polymers for multifunctional materials. PMID- 20735107 TI - Large Seebeck coefficients of protonated titanate nanotubes for high-temperature thermoelectric conversion. AB - Titanate nanotubes Na(2-x)H(x)Ti(3)O(7) produced by alkali hydrothermally treated ground TiO(2) aerogels are investigated as possible materials for high temperature thermoelectric conversion by measuring their thermoelectric properties. Strikingly, the Seebeck coefficients increased sharply in the temperature range 745 to 1032 K, reaching a maximum of 302 muV/K. The electrical resistivity of the TNNTs ranged from 325 to 525 Omegam, which is lower than that of bulk TiO(2), and thermal conductivities at room temperature were also very low, ranging from 0.55 to 0.75 Wm(-1) K(-1). The hollow structure of the titanate nanotubes, with small, uniform diameters, is thought to be responsible for the ultralow thermal conductivity. The large thermoelectric power and ultralow thermal conductivity suggest that titanate nanotubes represent a new kind of p type oxide thermoelectric material. PMID- 20735109 TI - Facile fabrication of hierarchically structured silica coatings from hierarchically mesoporous silica nanoparticles and their excellent superhydrophilicity and superhydrophobicity. AB - Silica coatings with hierarchical structures were prepared on glass substrates via layer-by-layer assembly using hierarchically mesoporous silica nanoparticles as building block. These coatings demonstrated excellent superhydrophilic properties. After hydrophobic modification, the obtained coatings exhibited hydrophobic properties in the measurements of water contact angles by employing contact-mode and drip-mode, respectively. Water droplet of large volume (15 muL) had a smaller sliding angle than that of small volume (3 muL) when using the contact-mode due to the role of gravity despite the existence of large adhesive force between water droplet and the coating surface, while very small sliding angles were noted when using the drip-mode because of the existence of kinetic energy. The transmittance of fabricated coatings was enhanced and reduced, respectively, in the long and short wavelength ranges as compared with blank slide glass. PMID- 20735108 TI - Generation of nanoparticles of controlled size using ultrasonic piezoelectric oscillators in solution. AB - We demonstrate the operation of a device that can produce chitosan nanoparticles in a tunable size range from 50-300 nm with small size dispersion. A piezoelectric oscillator operated at megahertz frequencies is used to aerosolize a solution containing dissolved chitosan. The solvent is then evaporated from the aerosolized droplets in a heat pipe, leaving monodisperse nanoparticles to be collected. The nanoparticle size is controlled both by the concentration of the dissolved polymer and by the size of the aerosol droplets that are created. Our device can be used with any polymer or polymer/therapeutic combination that can be prepared in a homogeneous solution and vaporized. PMID- 20735111 TI - Surface properties of femtosecond laser ablated PMMA. AB - The effects of femtosecond laser ablation on the physical and chemical properties at the surface of poly methylmethacrylate (PMMA) were studied. Femtosecond laser microfabrication caused the initially wetting behavior of PMMA to become nonwetting, mainly because of the laser-induced surface porosity at the submicroscale. Static and dynamic contact angle measurements along with morphological characterization revealed that after the laser irradiation, the system lies in an intermediate regime between those theorized by Wenzel and Cassie-Baxter. Spectroscopic analysis did not evidence any significant variation in the chemical properties of the processed polymeric surfaces. PMID- 20735112 TI - Ag2O/TiO2 nanobelts heterostructure with enhanced ultraviolet and visible photocatalytic activity. AB - Ag(2)O/TiO(2) heterostructure with high photocatalytic activity both in ultraviolet and visible-light region was synthesized via a simple and practical coprecipitation method by using surface-modified TiO(2) nanobelts as substrate materials. The as-prepared heterostructure composite included Ag(2)O nanoparticles assembled uniformly on the rough surface of TiO(2) nanobelts. Comparing with pure TiO(2) nanobelts and Ag(2)O nanoparticles, the composite photocatalyst with a wide weight ratio between TiO(2) and Ag(2)O exhibited enhanced photocatalytic activity under ultraviolet and visible light irradiation in the decomposition of methyl orange (MO) aqueous solution. On the basis of the characterization by X-ray diffraction, photoluminescence and UV-vis diffuse reflectance spectroscopies, two mechanisms were proposed to account for the photocatalytic activity of Ag(2)O/TiO(2) nanobelts' heterostructure. PMID- 20735113 TI - Facile preparation of superhydrophobic biomimetic surface based on octadecyltrichlorosilane and silica nanoparticles. AB - The present paper describes the simple and low-cost process for the production of a superhydrophobic surface with micronano hierarchical structure from the chemisorptions of SiO(2) nanoparticles onto polymerized n-octadecylsilane. The process was carried out under ambient conditions without the use of expensive equipment. The as-prepared micronano-binary films exhibited a very high contact angle of 179.9 degrees and a low contact hysteresis of 2.5 degrees . On the basis of the results of the characterization techniques, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and contact angle (CA) measurements, a formation mechnism of the superhydrophobic micronano structure was proposed. Drop impact experiments on the modified-glass substrate showed that the as-prepared films possess a high-impalement threshold. PMID- 20735114 TI - Thermally cross-linked PNVP films as antifouling coatings for biomedical applications. AB - Protein repellent coatings are widely applied to biomedical devices in order to reduce the nonspecific adhesion of plasma proteins, which can lead to failure of the device. Poly(N-vinylpyrrolidone) (PNVP) is a neutral, hydrophilic polymer with outstanding antifouling properties often used in these applications. In this paper, we characterize for the first time a cross-linking mechanism that spontaneously occurs in PNVP films upon thermal annealing. The degree of cross linking of PNVP films and their solubility in water can be tailored by controlling the annealing, with no need for additional chemical treatment or irradiation. The physicochemical properties of the cross-linked films were investigated by X-ray photoelectron spectroscopy, infrared spectroscopy, neutron and X-ray reflectometry, ellipsometry, and atomic force microscopy, and a mechanism for the thermally induced cross-linking based on radical formation was proposed. The treated films are insoluble in water and robust upon immersion in harsh acid environment, and maintain the excellent protein-repellent properties of unmodified PNVP, as demonstrated by testing fibrinogen and immunoglobulin G adsorption with a quartz crystal microbalance. Thermal cross-linking of PNVP films could be exploited in a wide range of biotechnological applications to give antifouling properties to objects of any size, essentially making this an alternative to high-tech surface modification techniques. PMID- 20735115 TI - High-performance, flexible enzymatic glucose biosensor based on ZnO nanowires supported on a gold-coated polyester substrate. AB - The present work demonstrates the fabrication and performance of an enzymatic glucose biosensor based on ZnO nanowires (NWs) deposited on a Au-coated polyester (PET) substrate. Electrodeposition of ZnO NWs on the conducting PET substrate was carried out at 70 degrees C in an aqueous electrolyte consisting of zinc nitrate mixed with potassium chloride. Glucose oxidase (GOx) was subsequently immobilized on the as-synthesized ZnO NWs, and the electrocatalytic properties of GOx immobilized ZnO NWs were evaluated by amperometry. The resulting GOx/ZnO NWs/Au/PET bioelectrode exhibits excellent electrocatalytic performance with a high sensitivity of 19.5 muA mM(-1) cm(-2), a low Michaelis-Menten constant of 1.57 mM, and a fast response time of <5 s for the amperometric detection of glucose. The present study illustrates the feasibility of realizing light-weight, flexible, high-performance sensing devices using ZnO NWs. PMID- 20735117 TI - Tribochemical polymerization of adsorbed n-pentanol on SiO2 during rubbing: when does it occur and is it responsible for effective vapor phase lubrication? AB - The origin and role of tribochemical reaction products formed while sliding silicon oxide surfaces in the presence of adsorbed alcohol molecules in equilibrium with the vapor phase were studied. Wear and friction coefficient studies with varying contact loads and n-pentanol vapor environments were used to determine under what operating conditions the tribochemical reaction species was produced. Imaging time-of-flight secondary ion mass spectrometry and microinfrared spectroscopy found that hydrocarbon species with a molecular weight higher than the starting vapor molecules are produced when there is wear of the SiO(2) surface. When the n-pentanol vapor lubrication is effective and the silicon oxide surface does not wear, then the tribochemical polymerization products are negligible. These results imply that the tribochemical polymerization is associated with the substrate wear process occurring due to insufficient adsorbate supply or high mechanical load. The tribochemical reactions do not seem to be the primary lubrication mechanism for vapor phase lubrication of SiO(2) surfaces with alcohol, although they may lubricate the substrate momentarily upon failure of the alcohol vapor delivery to the sliding contact. PMID- 20735118 TI - Structure and RNA interactions of the plant MicroRNA processing-associated protein HYL1. AB - HYL1 is a double-stranded RNA binding protein involved in microRNA processing in plants. HYL1 enhances the efficiency and precision of the RNase III protein DCL1 and participates in microRNA strand selection. In this work, we dissect the contributions of the domains of HYL1 to the binding of RNA targets. We found that the first domain is the main contributor to RNA binding. Mapping of the interaction regions by nuclear magnetic resonance on the structure of HYL1 RNA binding domains showed that the difference in binding capabilities can be traced to sequence divergence in beta2-beta3 loop. The possible role of each domain is discussed in light of previous experimental data. PMID- 20735119 TI - Detection of volatile organic compounds using porphyrin derivatives. AB - Seven different porphyrin compounds have been investigated as colorimetric gas sensors for a wide range of volatile organic compounds. The porphyrins examined were the free base and Mg, Sn, Zn, Au, Co, and Mn derivatives of 5,10,15,20 tetrakis[3,4-bis(2-ethylhexyloxy)phenyl]-21H,23H-porphine. Chloroform solutions of these materials were prepared and changes in their absorption spectra induced by exposure to various organic compounds measured. The porphyrins that showed strong responses in solution were selected, and Langmuir-Blodgett films were prepared and exposed to the corresponding analytes. This was done to determine whether they are useful materials for solid state thin film colorimetric vapor sensors. Porphyrins that readily coordinate extra ligands are shown to be suitable materials for colorimetric volatile organic compound detectors. However, porphyrins that already have bound axial ligands when synthesized only show a sensor response to those analytes that can substitute these axial ligands. The Co porphyrin displays a considerably larger response than the other porphyrins investigated which is attributed to a switch between Co(II) and Co(III) resulting in a large spectral change. PMID- 20735116 TI - Proteomic investigation of epigenetics in neuropsychiatric disorders: a missing link between genetics and behavior? AB - Neuropsychiatric disorders affect a large segment of the human population and result in large costs to society. The majority of such disorders have unknown underlying causes. Recent evidence suggests an important role for epigenetic regulation in the emergence of neuropsychiatric disease. Epigenetics may provide a link between genetic and environmental factors and behavior. Epigenetic signaling involves changes on the structure of chromatin; such changes are often triggered and maintained by the post-translational modification of chromatin proteins and/or DNA. Recent proteomic technologies have enabled the study of epigenetic mechanisms in a high-throughput manner. This review will provide an overview of the major epigenetic pathways and modern techniques for their study, before focusing on experimental evidence supporting a strong role for epigenetics in selected psychiatric disorders such as depression, schizophrenia, and drug addiction. These results highlight a great need for the inclusion of the proteomic characterization of epigenetic mechanisms in the study of gene/disease associations in psychiatric disorders. PMID- 20735120 TI - Spectroscopic and modeling investigations of the gas phase chemistry and composition in microwave plasma activated B2H6/CH4/Ar/H2 mixtures. AB - A comprehensive study of microwave (MW) activated B2H6/CH4/Ar/H2 plasmas used for the chemical vapor deposition of B-doped diamond is reported. Absolute column densities of ground state B atoms, electronically excited H(n = 2) atoms, and BH, CH, and C2 radicals have been determined by cavity ring down spectroscopy, as functions of height (z) above a molybdenum substrate and of the plasma process conditions (B2H6, CH4, and Ar partial pressures; total pressure, p; and supplied MW power, P). Optical emission spectroscopy has also been used to explore variations in the relative densities of electronically excited H atoms, H2 molecules, and BH, CH, and C2 radicals, as functions of the same process conditions. These experimental data are complemented by extensive 2D(r, z) modeling of the plasma chemistry, which result in substantial refinements to the existing B/C/H/O thermochemistry and chemical kinetics. Comparison with the results of analogous experimental/modeling studies of B2H6/Ar/H2 and CH4/Ar/H2 plasmas in the same MW reactor show that: (i) trace B2H6 additions have negligible effect on a pre-established CH4/Ar/H2 plasma; (ii) the spatial extent of the B and BH concentration profiles in a B2H6/CH4/Ar/H2 plasma is smaller than in a hydrocarbon-free B2H6/Ar/H2 plasma operating at the same p, P, etc.; (iii) B/C coupling reactions (probably supplemented by reactions involving trace O2 present as air impurity in the process gas mixture) play an important role in determining the local BHx (x = 0-3) radical densities; and (iv) gas phase B atoms are the most likely source of the boron that incorporates into the growing B doped diamond film. PMID- 20735121 TI - Theoretical study on the structure and cation-anion interaction of amino acid cation based amino acid ionic liquid [Pro]+[NO3]-. AB - The proline cation based amino acid ionic liquid [Pro]+[NO3]- was systematically studied by density functional theory at the B3LYP/6-311++G** level. The stable geometries of the cation, anion, ion pair, as well as the ion-pair dimer [Pro]2+[NO3]2- with no imaginary frequencies were obtained and characterized. In the single [Pro]+[NO3]- unit, proton transfer from [Pro]+ to [NO3]- can be observed in some of the configurations and the corresponding proton-transferred products (neutral pairs) are strongly hydrogen bonded. While in the ion-pair dimer [Pro]2+[NO3]2-, proton transfer does not occur and the components are stabilized by ionic interaction and hydrogen bonding interaction jointly. The proton transfer reaction between the cation and the anion in the single ion-pair unit has been investigated, and the role that the proton transfer reaction may play in the physicochemical property change of the ionic liquids has also been discussed. The interactions in the single ion-pair unit [Pro]+[NO3]- and in the ion-pair dimer [Pro]2+[NO3]2- were both carefully studied. The hydrogen bonds (H bonds) between the various fragments were analyzed by the atoms in molecules theory and harmonic vibrational frequency. PMID- 20735124 TI - Energy transfer dynamics in metal-organic frameworks. AB - Isomorphous metal-organic frameworks (MOFs) based on {M[4,4'-(HO(2)C)(2) bpy](2)bpy}(2+) building blocks (where M = Ru or Os) were designed and synthesized to study the classic Ru to Os energy transfer process that has potential applications in light-harvesting with supramolecular assemblies. The crystalline nature of the MOFs allows precise determination of the distances between metal centers by X-ray diffraction, thereby facilitating the study of the Ru->Os energy transfer process. The mixed-metal MOFs with 0.3, 0.6, 1.4, and 2.6 mol % Os doping were also synthesized in order to study the energy transfer dynamics with a two-photon excitation at 850 nm. The Ru lifetime at 620 nm decreases from 171 ns in the pure Ru MOF to 29 ns in the sample with 2.6 mol % Os doping. In the mixed-metal samples, energy transfer was observed with an initial growth in Os emission corresponding with the rate of decay of the Ru excited state. These results demonstrate rapid, efficient energy migration and long distance transfer in isomorphous MOFs. PMID- 20735123 TI - Synthesis and characterization of an iron(IV) ketimide complex. AB - Addition of 4 equiv of LiN?C(t)Bu(2) to FeCl(2) in Et(2)O/THF results in the formation of [Li(THF)](2)[Fe(N?C(t)Bu(2))(4)] (1). Oxidation of 1 with 0.5 equiv of I(2) in Et(2)O/DME yields [Li(DME)][Fe(N?C(t)Bu(2))(4)] (2) in moderate yield. Both 1 and 2 are high spin and exhibit tetrahedral geometries in the solid state. Oxidation of 1 with 1 equiv of I(2) in Et(2)O yields Fe(N?C(t)Bu(2))(4) (3) in good yield. Surprisingly, complex 3 exhibits a diamagnetic ground state and a nearly square planar geometry about the Fe center. PMID- 20735122 TI - Transmembrane segment packing of the Na(+)/Ca(2+) exchanger investigated with chemical cross-linkers. AB - The Na(+)/Ca(2+) exchanger (NCX1) is a plasma membrane protein important in regulating Ca(2+) in cardiac myocytes. The topological model is comprised of nine transmembrane segments (TMSs). To gain insights into the TMS packing arrangement of NCX1, we performed cysteine cross-linking experiments. Pairs of amino acids in different TMSs were mutated to cysteine on the backbone of a cysteineless NCX1. The mutated exchangers were expressed in an insect cell line and treated with cysteine-specific chemical cross-linkers followed by SDS-PAGE to determine the proximity of the introduced cysteines. Previously, we showed that TMSs 2, 3, 7, and 8 are near one another and that residues in TMSs 1 and 2 are close to TMS 6. In this report, we use the same approach to provide evidence for the arrangement of the remaining three TMSs (4, 5, and 9). We present a computer-generated two dimensional model of transmembrane packing that minimizes the lengths of all cross-links. PMID- 20735125 TI - Controlled and chemoselective reduction of secondary amides. AB - This communication describes a metal-free methodology involving an efficient and controlled reduction of secondary amides to imines, aldehydes, and amines in good to excellent yields under ambient pressure and temperature. The process includes a chemoselective activation of a secondary amide with triflic anhydride in the presence of 2-fluoropyridine. The electrophilic activated amide can then be reduced to the corresponding iminium using triethylsilane, a cheap, rather inert, and commercially available reagent. Imines can be isolated after a basic workup or readily transformed to the aldehydes following an acidic workup. The amine moiety can be accessed via a sequential reductive amination by the addition of silane and Hantzsch ester hydride in a one-pot reaction. Moreover, this reduction tolerates various functional groups that are usually reactive under reductive conditions and is very selective to secondary amides. PMID- 20735126 TI - Synthesis and characterization of ERI-type UZM-12 zeolites and their methanol-to olefin performance. AB - A wide variety of different linear, diquaternary alkylammonium ions have been used as supplementary crystallization structure-directing agents (SDAs) in the synthesis of UZM-12, a high-silica version of zeolite erionite, via a charge density mismatch (CDM) approach. When tetraethylammonium is used as a CDM SDA, the crystallization of UZM-12 was found to be critically dependent not only on the type of alkali metal cations added as another crystallization SDA to the synthesis mixture, but also on the size of the groups on the diquaternary ammonium ion employed and the length of its central polymethylene chain that are closely related to the dimensions of cylindrical 23-hedral [4(12)6(5)8(6)] eri cages in this small-pore zeolite. (27)Al MQ MAS NMR measurements reveal a preferential location of Al on the high-multiplicity site over the lower multiplicity site of the UZM-12 framework. The catalytic results from the methanol-to-olefin reaction over a series of H-UZM-12 zeolites with similar acidic properties but different crystallite sizes (100-2500 nm in length) demonstrate that the nanocrystallinity (probably the <=100 nm range) may have a detrimental effect on the activity and stability for this reaction, probably due to the fast buildup of large coke molecules on the external surface of zeolite crystallites that inhibits the methanol diffusion to intrazeolitic acid sites, rendering them ultimately inaccessible for catalysis. PMID- 20735128 TI - Conformational control of thymine photodimerization in single-strand and duplex DNA containing locked nucleic acid TT steps. AB - The results of an integrated experimental and theoretical study of thymine thymine photodimerization in short single-strand and duplex DNA structures possessing a single locked nucleic acid TT step are reported. Control of ground state conformation by the locked nucleic acids results in a marked increase in both the quantum yield and the selectivity of photoproduct formation. PMID- 20735129 TI - A general and efficient cobalt(II)-based catalytic system for highly stereoselective cyclopropanation of alkenes with alpha-cyanodiazoacetates. AB - [Co(P1)], the cobalt(II) complex of the D(2)-symmetric chiral porphyrin 3,5 Di(t)Bu-ChenPhyrin, is an effective catalyst for catalyzing asymmetric olefin cyclopropanation with the acceptor/acceptor-type diazo reagent alpha cyanodiazoacetates. The [Co(P1)]-catalyzed reaction is versatile and suitable for both aromatic and aliphatic olefins with varied electronic properties, including electron-rich and -poor olefins. The Co(II)-based catalytic system can be operated in a one-time protocol under mild conditions, affording the desired cyclopropane products in high yields with both high diastereo- and enantioselectivity. The resulting enantiomerically enriched 1,1 cyclopropanenitrile esters provide convenient access to a number of densely functionalized chiral cyclopropane derivatives, including alpha-cyclopropyl-beta amino acids. PMID- 20735127 TI - Controlling a structural branch point in ergot alkaloid biosynthesis. AB - The ergot alkaloids are a diverse class of fungal-derived indole alkaloid natural products with potent pharmacological activities. The biosynthetic intermediate chanoclavine-I aldehyde 1 represents a branch point in ergot biosynthesis. Ergot alkaloids festuclavine 2 and agroclavine 3 derive from alternate enzymatic pathways originating from the common biosynthetic precursor chanoclavine-I aldehyde 1. Here we show that while the Old Yellow Enzyme homologue EasA from the ergot biosynthetic gene cluster of Aspergillus fumigatus acts on chanoclavine-I aldehyde 1 to yield festuclavine 2, EasA from Neotyphodium lolii, in contrast, produces agroclavine 3. Mutational analysis suggests a mechanistic rationale for the switch in activity that controls this critical branch point of ergot alkaloid biosynthesis. PMID- 20735130 TI - Influence of processing on the allergenic properties of pistachio nut assessed in vitro. AB - Pistachio (Pistacia vera) is a tree nut that has been reported to cause IgE mediated allergic reactions. This study was undertaken to investigate the distinctions between different cultivars of pistachio nut and the influence of different processing on the IgE-binding capacity of whole pistachio protein extracts. The influence of different processes on allergenicity was investigated using competitive inhibition ELISA and Western blotting assays. The Western blotting results of extracts from pistachio cultivars showed no marked difference among them. The IgE-binding capacity was significantly lower for the protein extract prepared from steam-roasted than from raw and dry-roasted pistachio nuts. The results of sensory evaluation analysis and hedonic rating proved no significant differences in color, taste, flavor, and overall quality of raw, roasted, and steam-roasted pistachio nut treatments. The most significant finding of the present study was the successful reduction of IgE-binding by pistachio extracts using steam-roast processing without any significant changes in sensory quality of product. PMID- 20735131 TI - Ascorbic acid is the only bioactive that is better preserved by high hydrostatic pressure than by thermal treatment of a vegetable beverage. AB - Variations in levels of antioxidant compounds (ascorbic acid, total phenolics, and total carotenoids), total antioxidant capacity, and color changes in a vegetable (tomato, green pepper, green celery, onion, carrot, lemon, and olive oil) beverage treated by high hydrostatic pressure (HHP) were evaluated in this work. The effects of HHP treatment, four different pressures (100, 200, 300, and 400 MPa) and four treatment times for each pressure (from 120 to 540 s) were compared with those of thermal treatment (90-98 degrees C for 15 and 21 s). High pressure treatment retained significantly more ascorbic acid in the vegetable beverage than thermal treatment. However, no significant changes in total phenolics were observed between HHP treated and thermally processed vegetable beverage and unprocessed beverage. Color changes (a*, b*, L, chroma, h degrees , and DeltaE) were less for pressurized beverage than thermally treated samples compared with unprocessed beverage. PMID- 20735132 TI - Pressure and temperature effects on degradation kinetics and storage stability of total anthocyanins in blueberry juice. AB - The degradation kinetics of total anthocyanins in blueberry (Vaccinium myrtillus) juice were studied during thermal processing by treatment at selected temperatures (60-121 degrees C) and combined high pressure-temperature processing (100-700 MPa, 40-121 degrees C). Anthocyanin stability was also studied for several of these treatments during storage at 4, 25, and 40 degrees C. Both pressure and temperature increased d, the degradation rate of total anthocyanins in blueberry juice, meaning that at constant temperature, anthocyanins were more rapidly degraded with increasing pressure. For example, 32% degradation of anthocyanins was observed after 20 min heating at 100 degrees C and atmospheric pressure, whereas at 100 degrees C and 600 MPa, approximately 50% of total anthocyanins were lost. Degradation of anthocyanins was significantly accelerated with increasing storage temperatures. Combined pressure temperature treatment of pasteurized juice led to a slightly faster degradation of total anthocyanins during storage compared to heat treatments at ambient pressure. Degradation of anthocyanins was best described by a 1.4th-order reaction at all conditions investigated. A mathematical model describing the degradation of blueberry anthocyanins in juice as a function of pressure, temperature, and treatment time is presented. PMID- 20735133 TI - Structural characterization and antioxidant activity evaluation of lignins from rice husk. AB - In recent years, lignin and extractives from herbaceous plants and crops are receiving increasing attention for their renewability and large annual biomass stock. It is worth noting that only a few studies deal with the chemical characterization of rice husk, a side product of one of the most important crops with regard to human nutrition. Thus, in this study lignin from rice husk was isolated and characterized. Two different extraction procedures were optimized and tested: acidolysis and alkaline enzymatic (AE). The different lignins isolated were fully characterized by means of gravimetric, chromatographic (GPC), and spectroscopic (31P NMR, 2D-HSQC-NMR) analyses with the aim to compare yields, sample purity, and chemical properties, recognized as key parameters for future development. Notwithstanding the extraction procedure, the results highlighted that rice husk lignin is mainly formed by guaiacyl and p-hydroxyphenyl units. The acidolytic approach showed an appreciable lignin recovery and high purity, whereas the AE lignin sample was found to be rich in residual polysaccharides and oxidized functionalities. Moreover, different rice husk extracts, along with acidolysis lignin and AE lignin specimens, were assayed for their antioxidant activity by means of a DPPH radical scavenging test. PMID- 20735134 TI - Tricyclic host for linear anions. AB - A tricyclic host for anions consisting of two tetraamide monocycles attached by two ethylene chains was designed and synthesized. Structural and binding results indicate that the receptor is selective for linear triatomic anions. Crystallographic data for two hydrated free bases, along with FHF(-), N(3)(-), and SO(4)(2-) complexes indicate that there are at least two preferred gross conformations for the host, one of which possesses pseudo-D(2) symmetry and the other pseudo-C(2h) symmetry. Both FHF(-) and N(3)(-) are encapsulated in the pseudo-D(2) symmetric complex, bridging the two tetraamido macrocyclic halves. The pseudo-C(2h) octahydrate structure shows an ice-like H-bonded (H(2)O)(6) array of water molecules embedded in the host cavity. The SO(4)(2-) structure has a nearly superimposable host conformation to the octahydrate but with the SO(4)(2 ) anions lying outside the host. Binding studies in DMSO-d(6) indicate selectivity for FHF(-), with lesser affinity for other inorganic anions. PMID- 20735136 TI - 4D Lorentz electron microscopy imaging: magnetic domain wall nucleation, reversal, and wave velocity. AB - Magnetization reversal is an important topic of research in the fields of both basic and applied ferromagnetism. For the study of magnetization reversal dynamics and magnetic domain wall (DW) motion in ferromagnetic thin films, imaging techniques are indispensable. Here, we report 4D imaging of DWs by the out-of-focus Fresnel method in Lorentz ultrafast electron microscopy (UEM), with in situ spatial and temporal resolutions. The temporal change in magnetization, as revealed by changes in image contrast, is clocked using an impulsive optical field to produce structural deformation of the specimen, thus modulating magnetic field components in the specimen plane. Directly visualized are DW nucleation and subsequent annihilation and oscillatory reappearance (periods of 32 and 45 ns) in nickel films on two different substrates. For the case of Ni films on a Ti/Si(3)N(4) substrate, under conditions of minimum residual external magnetic field, the oscillation is associated with a unique traveling wave train of periodic magnetization reversal. The velocity of DW propagation in this wave train is measured to be 172 m/s with a wavelength of 7.8 microm. The success of this study demonstrates the promise of Lorentz UEM for real-space imaging of spin switching, ferromagnetic resonance, and laser-induced demagnetization in ferromagnetic nanostructures. PMID- 20735135 TI - Modulating heme redox potential through protein-induced porphyrin distortion. AB - Hemoproteins are ubiquitous in biology and are commonly involved in critical processes such as electron transfer, oxidative phosphorylation, and signal transduction. Both the protein environment and the heme cofactor contribute to generate the range of chemical properties needed for these diverse functions. Using the heme nitric oxide/oxygen binding (H-NOX) protein from the thermophilic bacterium Thermoanaerobacter tengcongensis, we have shown that heme electronic properties can be modulated by porphyrin distortion within the same protein scaffold without changing the heme ligation state or heme environment. The degree of heme distortion was found to be directly correlated to the electron density at the heme iron, as evidenced by dramatic changes in the heme redox potential and pK(a) of the distal ligand ((-)OH vs H(2)O). Protein-induced porphyrin distortion represents a new strategy to rationally tune the electronic properties of protein bound porphyrins and could be used to engineer proteins with desired reactivity or functionality. PMID- 20735137 TI - Effects of thermal processing on the enzyme-linked immunosorbent assay (ELISA) detection of milk residues in a model food matrix. AB - Food products and ingredients are frequently tested for the presence of undeclared allergenic food residues (including milk) using commercial enzyme linked immunosorbent assays (ELISAs). However, little is understood about the efficacy of these kits with thermally processed foods. This study evaluated the performance of three milk ELISA kits with a model food processed by several methods. A model food (pastry dough squares) was spiked with nonfat dry milk at several concentrations. The pastry squares were processed by boiling (100 degrees C for 2 min), baking (190 degrees C for 30 min), frying (190 degrees C for 2 min), and retorting (121 degrees C for 20 min with 17 psi overpressure). Samples were analyzed with three commercial ELISA kits: Neogen Veratox Total Milk, ELISA Systems beta-lactoglobulin, and ELISA Systems casein. The detection of milk residues depended upon the type of processing applied to the food and the specific milk analyte targeted by the ELISA kit. Poor recoveries were obtained in all processed samples (2-10% of expected values) using the beta-lactoglobulin kit. Better recoveries were obtained in boiled samples (44 and 59%, respectively) using the total milk and casein kits. However, these kits performed poorly with baked (9 and 21%) and fried (7 and 18%) samples. Moderate recoveries were observed in retorted samples (23 and 28%). The decreased detection in processed samples is likely due to protein modifications, including aggregation and Maillard reactions, which affect the solubility and immunoreactivity of the antigens detected by the ELISA methods. The observed decreases in ELISA detection of milk are dramatic enough to affect risk-assessment decisions. However, a lower detection of milk residues does not necessarily indicate decreased allergenicity. These ELISA kits are not acceptable for all applications, and users should understand the strengths and limitations of each method. PMID- 20735138 TI - Evaluation of phenolic profile and antioxidant properties of Pardina lentil as affected by industrial dehydration. AB - This study presents the effects of soaking, cooking, and industrial dehydration treatments on phenolic profile and also on antioxidant properties in Pardina lentil. HPLC-PAC and HPLC-MS (ESI) analysis identified a total of 35 phenolic compounds in raw and processed lentil flours, corresponding to catechins and procyanidins (69% of the total of identified phenolic compounds), flavonols (17%), flavones, and flavanones (5%), and hydroxybenzoic and hydroxycinnamic compounds (5 and 4%, respectively). During the industrial process, catechins and procyanidins, flavonols, flavones, and flavanones decreased, while hydroxybenzoic compounds exhibited an important increase. In addition, raw lentils showed high values of the antioxidant activity (66.97 MUmol Trolox/g); although the thermal processing promotes decreased, the levels of antioxidant activity were still relevant. Thus, the significant occurrence of bioactive phenolic compounds along with the interesting antioxidant capacity of dehydrated lentil flours make them useful for daily inclusion in the human diet as ready-to-use for special meals to specific populations. PMID- 20735140 TI - Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues. AB - 6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively. PMID- 20735142 TI - Pd-catalyzed intermolecular ortho-C-H amidation of anilides by N nosyloxycarbamate. AB - A palladium-catalyzed ortho-C-H amidation of anilides by N-nosyloxycarbamates was developed for the synthesis of 2-aminoanilines. This reaction can be carried out under relatively mild conditions and exhibits excellent regioselectivity and functional group tolerance. The amidation reaction is probably initiated by rate limiting C-H cyclopalladation (k(H)/k(D) = 3.7) to form an arylpalladium complex, followed by nitrene functionalization. PMID- 20735144 TI - 4D shearforce-based constant-distance mode scanning electrochemical microscopy. AB - 4D shearforce-based constant-distance mode scanning electrochemical microscopy (4D SF/CD-SECM) is designed to assess SECM tip currents at several but constant distances to the sample topography at each point of the x,y-scanning grid. The distance dependent signal is achieved by a shearforce interaction between the in resonance vibrating SECM tip and the sample surface. A 4D SF/CD-SECM measuring cycle at each grid point involves a shearforce controlled SECM tip z-approach to a point of closest distance and subsequent stepwise tip retractions. At the point of closest approach and during the retraction steps, pairs of tip current (I) and position are acquired for various distances above the sample surface. Such a sequence provides x,y,I maps, that can be compiled and displayed for each selected data acquisition distance. Thus, multiple SECM images are obtained at known and constant distances above the sample topography. 4D SF/CD-SECM supports distance-controlled tip operation while continuous scanning of the SECM tip in the shear-force distance is avoided. In this way, constant-distance mode SECM imaging can be performed at user-defined, large tip-to-sample distances. The feasibility and the potential of the proposed 4D SF/CD-SECM imaging is demonstrated using on the one hand amperometric feedback mode imaging of a Pt band electrode array and on the other hand the visualization of the diffusion zone of a redox active species above a microelectrode in a generator/collector arrangement. PMID- 20735141 TI - Evolutionary selection of new breast cancer cell-targeting peptides and phages with the cell-targeting peptides fully displayed on the major coat and their effects on actin dynamics during cell internalization. AB - Filamentous phage as a bacteria-specific virus can be conjugated with an anticancer drug and has been proposed to serve as a carrier to deliver drugs to cancer cells for targeted therapy. However, how cell-targeting filamentous phage alone affects cancer cell biology is unclear. Phage libraries provide an inexhaustible reservoir of new ligands against tumor cells and tissues that have potential therapeutic and diagnostic applications in cancer treatment. Some of these identified ligands might stimulate various cell responses. Here we identified new cell internalizing peptides (and the phages with such peptides fused to each of ~3900 copies of their major coat protein) using landscape phage libraries and for the first time investigated the actin dynamics when selected phages are internalized into the SKBR-3 breast cancer cells. Our results show that phages harboring VSSTQDFP and DGSIPWST peptides could selectively internalize into the SKBR-3 breast cancer cells with high affinity, and also show rapid involvement of membrane ruffling and rearrangements of actin cytoskeleton during the phage entry. The actin dynamics was studied by using live cell and fluorescence imaging. The cell-targeting phages were found to enter breast cancer cells through energy dependent mechanism and phage entry interferes with actin dynamics, resulting in reorganization of actin filaments and increased membrane rufflings in SKBR-3 cells. These results suggest that, when phage enters epithelial cells, it triggers transient changes in the host cell actin cytoskeleton. This study also shows that using multivalent phage libraries considerably increases the repertoire of available cell-internalizing ligands with potential applications in targeted drug delivery, imaging, molecular monitoring and profiling of breast cancer cells. PMID- 20735145 TI - Preparation, size control, surface deposition, and catalytic reactivity of hydrophobic corrolazine nanoparticles in an aqueous environment. AB - Nanoparticles, each consisting of one of the three molecular corrolazine (Cz) compounds, H(3)(TBP(8)Cz), Mn(III)(TBP(8)Cz), and Fe(III)(TBP(8)Cz) (TBP(8)Cz = octakis(4-tert-butylphenyl)corrolazinato), were prepared via a facile mixed solvent technique. The corrolazine nanoparticles (MCz-NPs) were formed in H(2)O/THF (10:1) in the presence of a small amount of a polyethylene glycol derivative (TEG-ME) added as a stabilizer. This technique allows highly hydrophobic Czs to be "dissolved" in an aqueous environment as nanoparticles, which remain in solution for several months without visible precipitation. The MCz-NPs were characterized by UV-visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging, and shown to be spherical particles from 100-600 nm in diameter with low polydispersity indices (PDI = 0.003-0.261). Particle size is strongly dependent on Cz concentration. The H(3)Cz-NPs were adsorbed on to a modified self-assembled monolayer (SAM) surface and imaged by atomic force microscopy (AFM). Adsorption resulted in disassembly of the larger H(3)Cz-NPs to smaller H(3)Cz-NPs, whereby the resulting particle size can be controlled by the surface energy of the monolayer. The Fe(III)Cz-NPs were shown to be competent catalysts for the oxidation of cyclohexene with either PFIB or H(2)O(2) as external oxidant. The reactivity and product selectivity seen for Fe(III)Cz-NPs differs dramatically from that seen for the molecular species in organic solvents, suggesting that both the nanoparticle structure and the aqueous conditions may contribute to significant changes in the mechanism of action of the Fe(III)Cz catalyst. PMID- 20735147 TI - Racemization free protocol for the synthesis of N-tert-butanesulfinyl ketimines. AB - A general and robust racemization-free protocol for the synthesis of a variety of N-tert-butanesulfinyl ketimines is reported. Reaction progress was monitored by (1)H NMR using the nonperturbing internal standard diglyme, and ketimines were formed in good to high yields in either THF or CPME (cyclopentyl methyl ether) as solvent with heating to reflux. PMID- 20735148 TI - Structure and dynamics of alpha-aryl amide and ketone enolates: THF, PMDTA, TMTAN, HMPA, and crypt-solvated lithium enolates, and comparison with phosphazenium analogues. AB - A variety of multinuclear NMR techniques, in combination with X-ray diffraction methods, were used to probe the solution structure of alpha-aryl lithium enolates of bis(4-fluorobenzyl) ketone (1-H), phenyl 4-fluorobenzyl ketone (2-H), and N,N dimethyl 4-fluorophenylacetamide (3-H) in ethereal solvents and in the presence of cosolvent additives PMDTA, TMTAN, HMPA, and cryptand [2.1.1]. All three enolates were dimers in THF solution, and were converted to monomers by the triamine additives, PMDTA and TMTAN. The exchange of the triamine-solvated monomers with their ethereal-solvated dimer counterparts was probed by using dynamic NMR (DNMR). The cosolvent HMPA formed monomers along with minor amounts of lithiate species, (RO)(2)Li(-) and (RO)(3)Li(2-), which were also observed when cryptand [2.1.1] was used as a cosolvent, or when mixed lithium phosphazenium enolate solutions were prepared. Dynamic exchange of lithiate species was investigated by DNMR spectroscopy. The barrier to rotation of the conjugated 4-fluorophenyl ring of these diverse enolate structures was measured and found to be consistent with a resonance picture where lower aggregation states lead to increased delocalization of negative charge. The lithium enolate aggregates identified were compared to the "naked" alpha-4-fluorophenyl enolates generated with the phosphazene base P4. The barrier to aryl ring rotation was 2.7 kcal/mol higher for the phosphazenium enolate 3-Li.P4H compared to the dimer (3 Li)(2). Structural characterization of a phosphazenium enolate through X-ray crystallography was obtained for the first time. Additional aspects of the Schwesinger base P4 were investigated which included characterization of the solution exchange behavior of the protonated and unprotonated forms as well as determination of the solid state structure by X-ray diffraction. PMID- 20735149 TI - Computational study on the reactivity of tetrazines toward organometallic reagents. AB - The possible reaction pathways between methyllithium and disubstituted 1,2,4,5 tetrazines (bearing methyl, methylthio, phenyl, and 3,5-dimethylpyrazolyl groups) were investigated by means of the density functional theory B3LYP/6-31G* method. Solvation was modeled using the supermolecule approach, adding one tetrahydrofuran molecule to the complexes. Comparison of the calculated energies and structures for the alternate azaphilic and nucleophilic addition pathways showed that the azaphilic addition is kinetically favored over nucleophilic addition, while thermodynamically the nucleophilic addition is usually preferred. The coordination of the tetrazine molecule with methyllithium was found to play a crucial role in the process. These findings provide the first rationale for the experimentally observed unique reactivity of tetrazines toward polar organometallic reagents, suggesting the presence of a kinetically controlled process. PMID- 20735150 TI - Present and future of in vitro immunotoxicology in drug development. AB - The realization, that the immune system can be the target of many chemicals including environmental contaminants and drugs with potentially adverse effects on the host's health, has raised serious concerns within the public and the regulatory agencies. At present, assessment of immunotoxic effects relies on different animal models and several assays have been proposed to characterize immunosuppression and sensitization. The use of whole animals, however, presents many secondary issues, such as expense, ethical concerns, and eventual relevance to risk assessment for humans. Furthermore, due to the new policy on chemicals (REACH), in the European Union, in vitro methods will play a major role in the near future. In addition, there is still a lack of human cell-based immunotoxicity assays for predicting the toxicity of xenobiotics toward the immune system in a simple, fast, economical, and reliable way. Hypersensitivity and immunosuppression, for which animal models have been developed and validated, are considered the primary focus for developing in vitro methods in immunotoxicology. Nevertheless, in vitro assays, as well as in vivo models, to detect immunostimulation and autoimmunity are also needed. Even if no validated alternative in vitro tests to assess immunotoxicity exist, in the last decade, much progress has been made toward these assays. Such models can be, at least, used for the pre-screening and hazard identification of unintended immunosuppression and contact hypersensitivity of direct immunotoxicants. Following a brief introduction to immunotoxicology and to in vivo models use to assess immunotoxicity, this manuscript will review the state-of-the-art in the field of in vitro immunotoxicity. PMID- 20735151 TI - An alternative form and level of the human health ozone standard. AB - Controlled human laboratory studies have shown that there is a disproportionately greater pulmonary function response from higher hourly average ozone (O3) concentrations than from lower hourly average values and thus, a nonlinear relationship exists between O3 dose and pulmonary function (FEV1) response. The nonlinear dose-response relationship affects the efficacy of the current 8-h O3 standard to describe adequately the observed spirometric response to typical diurnal O3 exposure patterns. We have reanalyzed data from five controlled human response to O3 health laboratory experiments as reported by Hazucha et al. (1992), Adams (2003, 2006a, 2006b), and Schelegle et al. (2009). These investigators exposed subjects to multi-hour variable/stepwise O3 concentration profiles that mimicked typical diurnal patterns of ambient O3 concentrations. Our findings indicate a common response pattern across most of the studies that provides valuable information for the development of a lung function (FEV1)-based alternate form for the O3 standard. Based on our reanalysis of the realistic exposure profiles used in these experiments, we suggest that an alternative form of the human health standard, similar to the proposed secondary (i.e., vegetation) standard form, be considered. The suggested form is an adjusted 5-h cumulative concentration weighted O3 exposure index, which addresses both the delay associated with the onset of response (FEV1 decrement) and the nonlinearity of response (i.e., the greater effect of higher concentrations over the mid- and low-range values) on an hourly basis. PMID- 20735152 TI - Association between bowel symptoms, symptom severity, and quality of life in Swedish patients with fecal incontinence. AB - OBJECTIVES: The association between abdominal symptoms, disease severity of fecal incontinence (FI), and quality of life (QoL) is not yet clear. We hypothesized that it would become clearer by prospective diary data. We also aimed to compare QoL of FI patients with ulcerative colitis (UC) patients in relapse and remission. MATERIAL AND METHODS: Sixty-five consecutive female patients with FI recorded bowel symptoms prospectively on diary cards. QoL was evaluated with the disease specific short health scale questionnaire (SHS). Patients with UC in remission and relapse were used as a reference group regarding SHS. RESULTS: FI patients had median 3.5 leakage episodes/week. In all, 48% of bowel movements were associated with urgency. Urgency was correlated to decreased QoL according to SHS domains: symptoms (Rho = 0.54, p = 0.0002), function (Rho = 0.48, p = 0.0008), and disease related worry (Rho = 0.32, p = 0.027). Abdominal pain and bloating, reported by nearly half of patients, correlated to deceased QoL but not to number of leakages. QoL of patients with FI compared to UC in active phase (n = 35) was similar. FI patients had decreased QoL compared to UC in remission (n = 94) in all dimensions of SHS: symptoms (p < 0.0001), function (p < 0.0001), disease related worry (p < 0.0001), and general well being (p = 0.03). CONCLUSION: Urgency and irritable bowel syndrome (IBS)-like symptoms were associated with decreased QoL in FI. Therefore, IBS should be considered as an important confounding factor in FI QoL studies. QoL in patients with FI was considerably decreased, in a similar extent as in patients with UC in relapse. PMID- 20735153 TI - Immunogenicity of Mycobacterium avium subsp. paratuberculosis proteins in Crohn's disease patients. AB - The association between Mycobacterium avium subsp. paratuberculosis (MAP) and Crohn's disease (CD) is supported by several studies reporting the detection or isolation of MAP from human tissues, but a direct association is still debatable. OBJECTIVE: To evaluate the survival of MAP in human intestinal cells and to measure the presence of antibodies against two mycobacterial proteins necessary for the survival of the bacterium in the sera of CD patients. MATERIAL AND METHODS: Human-derived intestinal cells were infected with three isolates of MAP and the survival of the microorganism was determined. The presence of antibodies against protein tyrosine phosphatase A (PtpA) and protein kinase G (two proteins secreted within the host in the early stages of the invasion) in the sera of CD patients was evaluated. Sera of 20 CD patients and 20 controls were collected and the presence of the antibodies was assayed using enzyme-linked immunosorbent assay (ELISA). Secretion of the PtpA in vivo was visualized by immunostaining. RESULTS: MAP survived in intestinal cells, and immunostaining of PtpA showed that the protein was secreted within these cells. Wilcoxon rank sum test revealed that CD patient sera had significantly higher titer of antibodies specific for both of these antigens compared to controls. ELISA results for either protein were not statistically different between men and women. CONCLUSIONS: The presence of specific antibodies against mycobacterial proteins essential for establishing an infection in the host suggests that MAP can potentially be active in CD patients, and a serological test can be developed for early detection of MAP in CD patients. PMID- 20735154 TI - New prebiotics from rice bran ameliorate inflammation in murine colitis models through the modulation of intestinal homeostasis and the mucosal immune system. AB - BACKGROUND: Enzyme-treated rice fiber (ERF) is a recently developed prebiotic product made from rice bran by heat-resistant amylase, protease and hemicellulase treatment. Although the detailed mechanism of inflammatory bowel disease (IBD) is still unclear, the role of the resident luminal bacteria and its interaction on the mucosal barrier seem to be an important factor in the development of IBD and its chronicity. With the objective of manipulating the intestinal microbiota in IBD, this study was carried out to evaluate the effects of ERF on IBD with using experimental colitis models. METHODS: Three colitis models were used and they were induced by the oral administration of dextran sodium sulfate in male Sprague Dawley rats or BALB/c mice and transferring CD4+ CD45RB(high) T cells to female SCID mice, sequentially their CD4+ T cells were retransferred to new SCID mice. The evaluation included the measurement of body weight, spleen weight, colon length, histological examination, serum and mucosal cytokine (tumor necrosis factor-alpha (TNF-alpha), an interferon-gamma (IFN-gamma), interleukin-12 p70 (IL 12p70), IL-1beta, IL-6, IL-4) analysis, mucosal serotonin (5HT), and organic acid production and a microbiota analysis of the cecal contents. The characteristics of T cell surface markers including CD4, CD69, CD45RB of spleen and mesenteric lymph nodes (MLN) were also analyzed. In addition, the effects of ERF on the change in the induction of dendritic cells (DCs) were evaluated. RESULTS: The preventive effect of ERF on colitis was significantly superior to that of raw material rice bran or control group. An overexpression of inflammatory cytokine production was attenuated by ERF treatment, which was accompanied with a decrease in both the colonic mucosal damage and 5HT production. Furthermore, ERF significantly attenuated the T cell activation (CD4+CD69+) of spleen and MLN, and this characteristic was inherited by the retransferred mice. ERF significantly suppressed the growth of Clostiridium, and increased short-chain fatty acids (acetate, propionate and butyrate) content in colitis. The relatively hydrophilic fraction of ERF (ethanol-methanol soluble fraction) is therefore considered to have a potent ability to attenuate the induction of DCs. CONCLUSION: A new prebiotic, ERF, reduced inflammation by modulating the colonic environment and regulating immune cell differentiation. Although a more detailed study is required, this study showed the promising anti-inflammatory effects of an adjunctive prebiotic treatment for IBD. PMID- 20735155 TI - A national audit of temporal trends in endoscopic retrograde cholangiopancreatography in Norway. AB - OBJECTIVE: The introduction of non-invasive imaging for biliary-pancreatic diseases has changed the indications and volumes of endoscopic retrograde cholangiopancreatography (ERCP) over time. This study aimed to provide national figures on ERCP in Norway over the last decade. MATERIAL AND METHODS: Data from four national surveys on ERCP activity collected from 1998 to 2009 at the surgical and medical departments of all Norwegian hospitals were analyzed for variations in volumes among centers, regions, and specialties over time. RESULTS: A total of 42,260 procedures were reported (average 3842 procedures per year, range 3492-4632). The number of hospitals with ERCP decreased from 41 to 35 and the annual number of procedures decreased by 13% (from 4632 to 4036), but the number of ERCP endoscopists remained stable at ~100. The proportion of procedures performed by surgeons decreased from 40% to 32% (p < 0.001) during the first half of the study period; the number of gastrointestinal surgeons performing ERCP remained stable in the latter half (46% and 48% for 2004 and 2008, respectively). In 2004, 15 endoscopists signed up for a formal ERCP training program, including 8 (53%) surgeons. This number increased to 21 (48%) in 2008. A non-significant decrease in referrals (49% in 2002 vs. 35% in 2005) between various ERCP centers was reported. Regional variation in ERCP volumes leveled off during the study period. CONCLUSIONS: Though the number of both procedures and hospitals performing ERCP in Norway decreased, the proportion of low-volume and high-volume centers remained steady. The proportion of procedures by gastroenterological surgeons decreased significantly, yet roughly half of the endoscopists in ERCP training programs are surgeons. Regional variation in the ERCP numbers appears to have diminished. PMID- 20735156 TI - Dose-dependent modulation of apoptotic processes by fluoxetine in maturing neuronal cells: an in vitro study. AB - OBJECTIVES: Recent studies indicate that the selective serotonin reuptake inhibitor (SSRI) fluoxetine is not solely effective by the instant inhibition of the serotonin transporter (SERT) but also by its influence on mitotic and/or apoptotic processes. METHODS: To investigate the effects of the compound in vitro, we treated neurons from different brain areas with increasing concentrations of fluoxetine. Additionally, human embryonic kidney (HEK-293) cells and HEK-293 cells stably expressing the SERT were used. Cell viability was quantified by MTT-assay and apoptosis via fluorescence-activated cell-sorting analyses. Fluoxetine's effect on the gamma-aminobutyric acid (GABA) receptor was electrophysiologically investigated to test the hypothesis if a GABA-mimetic effect exists that might lead - additionally to the well-known N-methyl-D aspartate (NMDA)-antagonism - to increased apoptosis in immature neurons. RESULTS: In hippocampal, cortical, and both types of HEK-293 cells, viability decreased and apoptosis increased in a dose-dependent manner (0.5-75 MUM). In contrast, in mesencephalic and striatal cells the viability was unchanged or even slightly stimulated up to 20 MUM fluoxetine. An anti-apoptotic effect of concentrations below 10 MUM was observed in these cells. The GABA(A) receptor was directly activated by fluoxetine. CONCLUSIONS: We conclude that fluoxetine affects apoptotic processes independently from SERT expression. Since especially the combined GABA-mimetic and NMDA-antagonistic effects increase apoptosis in developing neuronal cells, whereas both effects are neuroprotective in adult neurons we hypothesise that these mechanisms explain the discrepancy of in vitro and in vivo studies. PMID- 20735157 TI - Psychiatric disorders in individuals with high-functioning autism and Asperger's disorder: similarities and differences. AB - OBJECTIVES: To investigate and compare the rate and type of psychiatric co morbidity in individuals with diagnosis of high functioning autism (HFA) and Asperger's disorder (AS). METHODS: This study includes 30 children and adolescents with diagnosis of HFA and 30 with diagnosis of AS. Diagnoses of HFA and AS were made using strict DSM-IV criteria. Psychiatric co-morbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL-T). RESULTS: The rate of comorbid psychiatric disorders was very high in both groups (93.3% in HFA and 100% in AS). The most common disorder in both groups was attention deficit hyperactivity disorder. There was no statistically significant difference between groups in the rate of associated psychiatric disorders, except for major depressive disorder (P = 0.029) and ADHD-combined type (P = 0.030). The AS group displayed greater comorbidity with depressive disorders and ADHD-CT. CONCLUSION: From a clinical perspective, it could be concluded that both disorders involve a high risk for developing psychiatric disorders, with AS patients at greater risk for depression. From a nosological perspective, the substantial similarities in terms of psychiatric comorbidity may support the idea that both disorders are on the same spectrum and differs in some aspects. PMID- 20735158 TI - Evidence of involvement of the human Par-4 (PAWR) gene in major depressive disorder. AB - QBJECTIVES: The aim of the study was to examine the associations between genetic variations in the human PAWR gene and major depressive disorder (MDD) as well as the response to antidepressant treatment. METHODS: Six-hundred and two patients with MDD and 543 controls were included in the study; among the MDD patients, 268 were followed-up for a further 8 weeks in order to assess their response to treatment with selective serotonin reuptake inhibitors (SSRIs). Six polymorphisms (rs17005769, rs4842318, rs7305141, rs2307223, rs8176874 and rs2307220) of the PAWR gene were investigated with regard to their association with MDD and antidepressant treatment efficacy. RESULTS: One polymorphism, rs8176874, was in genotypic (uncorrected P=0.005) and allelic (uncorrected P=0.0015) association with MDD. Several haplotypes spanning rs7305141-rs2307223-rs8176874 were also significantly associated with MDD after correction for multiple testing (corrected P<0.05). However, neither single-marker nor haplotype-based analyses suggested an association between the studied markers and SSRI treatment response. CONCLUSIONS: Genetic variations in the PAWR gene are related to susceptibility to MDD but not to SSRI treatment response. PMID- 20735159 TI - Prediction of HIV-1 protease inhibitory activity of 4-hydroxy-5,6-dihydropyran-2 ones: QSAR study. AB - Inhibition of human immunodeficiency virus 1 (HIV-1) protease is an important strategy for the treatment of HIV and acquired immune deficiency syndrome (AIDS). Therefore, HIV-1 protease inhibitory activity of dihydropyranone derivatives has been analyzed with different physico-chemical parameters. In the present work, QSAR studies were performed on a series of 4-hydroxy-5,6-dihydropyran-2-ones to explore the physico-chemical parameters responsible for their HIV-1 protease inhibitory activity. Physico-chemical parameters were calculated using WIN CAChe 6.1. Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The selected best QSAR model was having correlation coefficient (R) = 0.875 and cross-validated squared correlation coefficient (Q2) = 0.707. The developed significant QSAR model indicates that hydrophobicity of whole molecule and the substituent present at sixth position of dihydropyranones play an important role in the HIV-1 protease inhibitory activities of 4-hydroxy-5,6-dihydropyran-2-ones. PMID- 20735160 TI - Proteomic identification of human urinary biomarkers in diabetes mellitus type 2. AB - BACKGROUND: During the proteomic era, one of the most rapidly growing areas in biomedical research is biomarker discovery, particularly using proteomic technologies. The urinary proteome is known to be a valuable field of study and has become one of the most attractive subdisciplines in clinical proteomics for human diseases. We have described the levels of protein biomarkers specific to diabetes mellitus type 2 in the Pakistani population using proteomic technology. METHODS: One hundred type 2 diabetes patients with 50 age- and sex-matched normal healthy controls were recruited from Sheikh Zayed Hospital, Lahore, Pakistan. Urinary proteins were analyzed by two-dimensional liquid chromatography, using chromatofocusing in the first dimension and reverse-phase chromatography in the second, followed by mass spectrometric analysis. Levels of the proteins, which were found to vary in the diabetes type 2 patients compared to the controls, were then determined by enzyme-linked immunosorbent assay in all the samples. RESULTS: Levels of transthyretin, alpha-1-microglobulin/bikunin precursor, and haptoglobin precursor decreased by 30.8%, 55.2%, and 81.45%, whereas levels of albumin, zinc alpha2 glycoprotein, retinol binding protein 4, and E-cadherin increased by 486.5%, 29.23%, 100%, and 693%, respectively, in the diabetes patients compared to the controls. CONCLUSIONS: Variation in the levels of these identified protein biomarkers have been reported in other pathological states. Assessment of the levels of these biomarkers will be helpful not only in early diagnosis but also in prognosis of diabetes mellitus type 2. PMID- 20735161 TI - Immunosuppression or immunostimulation for aplastic anemia? A blast from the past. PMID- 20735162 TI - Defining the risks of mesenchymal stromal cell therapy. AB - Abstract We address the issue of the potential for malignant transformation of cultured mesenchymal stromal cells (MSC) commonly used in clinical cell-therapy protocols and describe the culture conditions under which tumorigenesis is likely to be an extremely uncommon event. PMID- 20735163 TI - An attempt to treat patients who have injured spinal cords with intralesional implantation of concentrated autologous bone marrow cells. AB - BACKGROUND AIMS: Spinal cord injury is common among young subjects involved in motor vehicle accidents. Mechanisms and attempts to reverse post-traumatic pathophysiologic consequences are still being investigated. Unfortunately no effective and well-established treatment modality has been developed so far. The regeneration capability of the human nervous system following an injury is highly limited. METHODS: The study involved four patients (two male, two female) who had suffered spinal cord injury as a result of various types of trauma. On neurologic examination, all the patients were determined to be in American Spinal Injury Association (ASIA) grade A. All patients were treated with decompression, stabilization and fusion for vertebral trauma anteriorly, as well as intralesional implantation of cellular bone marrow concentrates using a posterior approach 1 month after the first operation. The patients were then treated and followed-up in the physical rehabilitation clinic. RESULTS: At the end of the post-operative 1-year follow-up, two of the patients were classified as ASIA C while one was classified as ASIA B. One patient showed no neurologic change; none of the patients suffered from any complications or adverse effects as a result of intralesional application of bone marrow cells. CONCLUSIONS: The results of this experimental study show the potential contribution of intralesional implantation of bone marrow to neuronal regeneration in the injured spinal cord, with neuronal changes. In light of the results of this experimental study, the potential for regenerative treatment in injuries of the human spinal cord is no longer a speculation but an observation. PMID- 20735164 TI - Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells. AB - BACKGROUND AIMS: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-beta (TGF-beta), platelet-derived growth factor-BB (PDGF-BB), brain derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 * 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-beta, PDGF-BB, BDNF, GDNF and NGF. RESULTS: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors. PMID- 20735165 TI - Evaluation of mobilized peripheral stem cells according to CD34 and aldehyde dehydrogenase expression and effect of SSC(lo) ALDH(br) cells on hematopoietic recovery. AB - BACKGROUND AIMS: We evaluated hematopoietic stem cells according to CD34 expression and aldehyde dehydrogenase (ALDH) activity in peripheral blood and apheresis product samples from patients after mobilization with granulocyte colony-stimulating factor (G-CSF) alone or G-CSF after high-dose cyclophosphamide (4 g/m2) once daily, intravenously on day 1). We also investigated the relationship between the number of SSC(lo) CD45(dim) CD34(hi) cells, SSC(lo) ALDH(br) cells and engraftment. METHODS: Thirty patients (20 males and 10 females), who were candidates for autologous peripheral blood stem cell transplantation, were included in the study. Cyclophosphamide + G-CSF was used for 17 and G-CSF alone for 24 mobilizations. Primary diagnoses were multiple myeloma (n = 14), Hodgkin's lymphoma (n = 7), non-Hodgkin's lymphoma (n = 2), acute myloid leukemia (n = 2), chronic lymphocytic leukemia (n = 1) and germ cell testis tumor (n = 1). RESULTS: Numbers of SSC(lo) CD45(dim) CD34(hi) cells and SSC(lo) ALDH(br) cells were highly correlated in both peripheral blood and apheresis products (P < 0.001). We could not find a relationship between the transplanted SSC(lo) CD45(dim) CD34(hi) cell dose or SSC(lo) ALDH(br) cell dose and platelet or neutrophil recovery. The optimal thresholds for SSC(lo) CD45(dim) CD34(hi) cells were 5.40 * 106/kg for neutrophil recovery and 7.22 x 106/kg for platelet recovery. The optimal thresholds for SSC(lo) ALDH(br) cells were 6.53 x 106/kg for neutrophil recovery and 8.72 x 106/kg platelet recovery. CONCLUSIONS: According to our data, numbers of SSC(lo) ALDH(br) cells are in very good agreement with numbers of SSC(lo) CD45(dim) CD34(hi) cells and can be a predictor of stem cell mobilization. PMID- 20735166 TI - Stem cell-like properties of human umbilical cord lining epithelial cells and the potential for epidermal reconstitution. AB - BACKGROUND AIMS: Stem cells are particularly attractive for many cell-based therapeutic interventions because of their ability to self-renew and their capacity to differentiate into site-specific differentiating cells. Restoration of the integrity of epithelial continuity is an essential aspect of wound repair and tissue regeneration. We are currently looking at the potential of human umbilical cord lining cells as a source of epithelial stem cells with appropriate differentiation capacity for potential epidermal reconstitution. METHODS: We isolated human umbilical cord lining epithelial cells (CLEC) and characterized their phenotype from the perspective of proliferative potential, telomere length, expression of epidermal differentiation markers, as well as stem cell-specific markers, and clonogenicity. Their potential for epidermal reconstitution was investigated in an organotypic culture model. RESULTS: The results demonstrated that CLEC present a long telomere length and have a relatively high proliferative potential and passaging ability in culture. CLEC display some of the stem cell specific markers for epithelial as well as pluripotent stem cells, including CK19, p63, OCT-4, SSEA-4, TRA-1-60, SOX2 and Nanog. CLEC are capable of generating a fully stratified epithelium in organotypic culture. CONCLUSIONS: The potential of CLEC to be used in clinical applications for specialized epithelial reconstruction is still unexplored. The demonstration that CLEC have stem cell like properties and are capable of generating fully stratified epithelium provides support for their potential clinical application in epidermal reconstitution. PMID- 20735167 TI - Transplantation of human glial-restricted neural precursors into injured spinal cord promotes functional and sensory recovery without causing allodynia. AB - BACKGROUND AIMS: Traumatic injuries of the central nervous system cause damage and degeneration of specific cell populations with subsequent functional loss. Cell transplantation is a strategy to treat such injuries by replacing lost or damaged cell populations. Many kinds of cells are considered candidates for intraspinal transplantation. Human neural precursor cells (hNPC) derived from post-mortem fetal tissue are easy to isolate and expand, and are capable of producing large numbers of neuronal and glial cells. After transplantation into the nervous system, hNPC produce mature neural phenotypes and permit functional improvement in some models of neurodegenerative disease. In this study, we aimed to elucidate the therapeutic effect of different neuronal and glial progenitor populations of hNPC on locomotor and sensory functions of spinal cord-injured (SCI) rats. METHODS: Different populations of progenitor cells were obtained from hNPC by cell sorting and neural induction, resulting in cell cultures that were NCAM(+) A2B5(+), NCAM(+) A2B5(-) or A2B5(+) NG2(+). These different cell populations were then tested for efficacy in repair of the injured spinal cord by transplantation into rats with SCI. RESULTS: The A2B5(+) NG2(+) population of hNPC significantly improved locomotor and sensory (hindlimb) functional recovery of SCI rats. Importantly, no abnormal pain responses were observed in the forelimbs following transplantation. CONCLUSIONS: This treatment approach can improve functional recovery after SCI without causing allodynia. Further studies will be conducted to investigate the ability of A2B5(+) NG2(+) cells to survive, differentiate and integrate in the injured spinal cord. PMID- 20735168 TI - Expression of FLK1 and CD146 at day 7 following reperfused acute myocardial infarction. AB - OBJECTIVES: To investigate the expression of FLK1, CD146 and microvessel density of angiogenesis at the first week of reperfused acute myocardial infarction (AMI). METHODS: 16 of mini-swines (20 to 30 Kg) were randomly assigned to the sham-operated group and the AMI group. Pathologic myocardial tissue was collected at day 7 following reperfusion and detected by dual immunochemistry, real-time quantitative polymerase chain reaction and western blot. RESULTS: The infarcted area had higher FLK1 mRNA expression than the sham-operated area and the normal area (all P < 0.05), and the infarcted and marginal areas showed higher CD146 protein expression than the sham-operated area (all P < 0.05), but the microvessel density (CD31 positive expression of microvessels/HP) was not significantly different between the infarcted area and the sham-operated area (8.92 +/- 3.05 vs 6.43 +/- 1.54)(P > 0.05). CONCLUSION: FLK1 and CD146 expression significantly increase in the infarcted and marginal areas, and the microvessel density of angiogenesis in the infarcted area is similar to normal microvessel density of healthy heart tissue, suggesting that FLK1 and CD146 are possible associated with angiogenesis at day 7 following reperfused acute myocardial infarction. PMID- 20735169 TI - Improved motor function in dko mice by intravenous transplantation of bone marrow derived mesenchymal stromal cells. AB - BACKGROUND AIMS: We explored the potential therapeutic value of transplanting bone marrow (BM)-derived mesenchymal stromal cells (MSC) into utrophin/dystrophin deficient double knock-out (dko) mice, a murine model of Duchenne muscular dystrophy. METHODS: MSC from male rats were isolated and transplanted into female dko mice via the caudal vein. Behavior and locomotor function were later evaluated, along with the expression of dystrophin and utrophin in the sarcolemma of myofiber tissues. The presence of grafted cells was confirmed via polymerase chain reaction for the sex-determining region of the Y-chromosome. RESULTS: Locomotor activity improved significantly (P < 0.05) from 5 to 15 weeks after cell transplantation, as measured by traction, rotating rod and running wheel tests. We also found that the expression of dystrophin and utrophin increased significantly (P < 0.05) and progressively in the sarcolemma from 5 to 15 weeks after transplantation. The median lifespan of mice in the normal group (74.1 weeks) was significantly (P < 0.001) higher than those in the control (22.0 weeks) and transplantation (35.0 weeks) groups, and the median lifespan of mice in the transplantation group was significantly (P < 0.001) higher than that in the control group. CONCLUSIONS: Results of this study demonstrate that BM MSC have potential value in xenogeneic transplantation therapy for muscular dystrophy. PMID- 20735170 TI - Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model. AB - BACKGROUND AIMS: Tumor antigen-specific cytotoxic T lymphocytes (CTL) have been used in the treatment of human cancer, including leukemia. Several studies have established PR1 peptide, an HLA-A2.1-restricted peptide derived from proteinase 3 (P3), as a human leukemia-associated antigen. PR1-specific CTL elicited in vitro from healthy donors have been shown to lyse P3-expressing AML cells from patients. We investigated whether PR1-CTL can be adoptively transferred into NOD/SCID mice to eliminate human leukemia cells. METHODS: PR1-CTL were generated in bulk culture from peripheral blood mononuclear cells (PBMC) stimulated with autologous dendritic cells. Human acute myeloid leukemia (AML) patient samples were injected and engrafted in murine bone marrow at 2 weeks post-transfer. RESULTS: Following adoptive transfer, bone marrow aspirate from mice that received AML alone had 72-88% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 3-18% blasts in a hypocellular marrow. The PR1-CTL persisted in the bone marrow and liver and maintained a CD45RA-CD28+ effector phenotype. CONCLUSIONS: We found that adoptive transfer of PR1-CTL generated in vitro is associated with reduced AML cells in NOD/SCID mice. PR1-CTL can migrate to the sites of disease and maintain their capacity to kill the AML cells. The surface phenotype of PR1-CTL was consistent with their trafficking pattern in both vascular and end-organ tissues. PMID- 20735172 TI - Clustered cortical organization and the enhanced probability of intra-areal functional integration. AB - Similarly responsive neurons organize into submillimeter-sized clusters (domains) across many neocortical areas, notably in Areas V1 and V2 of primate visual cortex. While this clustered organization may arise from wiring minimization or from self-organizing development, it could potentially support important neural computation benefits. Here, we suggest that domain organization offers an efficient computational mechanism for intra-areal functional integration in certain cortical areas and hypothesize that domain proximity could support a higher-than-expected spatial correlation of their respective terminals yielding higher probabilities of integration of differing domain preferences. To investigate this hypothesis we devised a spatial model inspired by known parameters of V2 functional organization, where neighboring domains prefer either colored or oriented stimuli. Preference-selective joint probabilities were calculated for model terminal co-occurrence with configurations encompassing diverse domain proximity, shape, and projection. Compared to random distributions, paired neighboring domains (< or =1200 microm apart) yielded significantly enhanced coincidence of terminals converging from each domain. Using this reference data, a second larger-scale model indicated that V2 domain organization may accommodate relatively complete sets of intra-areal color/orientation integrations. Together, these data indicate that domain organization could support significant and efficient intra-areal integration of different preferences and suggest further experiments investigating prevalence and mechanisms of domain-mediated intra-areal integration. PMID- 20735171 TI - Tracing the source of an outbreak of methicillin-resistant Staphylococcus aureus in a tertiary-care oncology hospital by epidemiology and molecular methods. AB - This study describes the clinical and molecular characteristics of methicillin resistant Staphylococcus aureus (MRSA) isolates that emerged after an index case in a tertiary-care oncology hospital in Mexico City and identifies whether these isolates were related with the index case. All MRSA strains isolated from January 2006 until December 2007 were included. The clinical and demographic characteristics of patients were analyzed; molecular typing by pulsed-field gel electrophoresis was used to characterize the isolates. We included 44 MRSA isolates from 55 patients. Thirty-eight patients (86.4%) were classified with nosocomial infection and the remainder with healthcare-related infection. A single pulsed-field gel electrophoresis pattern (C) was identified with minor variations (two subtypes). The isolates analyzed were staphylococcal chromosome cassette mec type II (related with the New York-Japan strain). This case underscores the need to intensify strategies that identify and limit the spread of multiresistant pathogens imported by infected patients referred from other healthcare centers. PMID- 20735173 TI - The sex ratio of siblings of individuals with a history of developmental language disorder. AB - There is a well documented predominance of males diagnosed with neurodevelopmental disorders. The influence of sex steroids upon brain development has been suggested to mediate sex differences in developmental psychopathology, and has been epitomized in the 'extreme male brain theory'. The objective of this study was to extend previous studies dealing with the extreme male brain theory and to study the sex ratio (proportion of males) in the siblings of 469 individuals with a developmental language disorder (DLD) who were consecutively assessed in the same clinic during a period of 10 years. Among their 908 live-born siblings, 503 were males and 405 females. This yields a sex ratio of 0.554, which is significantly higher than the Danish live birth sex ratio of 0.514 over the same period (P = 0.02). Our findings are consistent with the hypothesis that male sex hormones may be implicated in the aetiology of DLD. PMID- 20735174 TI - Metallo-beta-lactamase expression confers an advantage to Pseudomonas aeruginosa isolates compared with other beta-lactam resistance mechanisms, favoring the prevalence of metallo-beta-lactamase producers in a clinical environment. AB - The Pseudomonas aeruginosa isolate TS-832035 was responsible for an outbreak that occurred in an Italian hospital between 1999 and 2002. It exhibited a high-level resistance to carbapenems due to the contemporary presence of two independent mechanisms: the production of a carbapenemase, coded by a bla(VIM-1) determinant carried by the chromosomal class 1 integron In70.2 (containing also the aacA4, aphA15, and aadA1 genes in its cassette array), and the lack of the OprD porin. We compared TS-832035 with a strictly related isolate, TS-103, whose resistance to carbapenems was due to the lack of the OprD porin only, as it did not carry In70.2. We evaluated their growth kinetics, in both separate cultures and competition assays, under permissive conditions. These experiments highlighted a significant in vitro fitness cost associated with the integron. On the contrary, none of the resistance determinants other than the bla(VIM-1) seemed to confer a real selective advantage to its host. Comparison of these results with the in vivo behavior, showing that the In70.2-carrying isolates largely prevailed over the In70.2-lacking ones, besides the detection of similar integrons in other Italian clinical isolates, evidenced the need to investigate accurately the causes of their large distribution, as possible soft spots could exist in the ability of their hosts to adapt to the hospital settings. PMID- 20735175 TI - Characterization of erythromycin-resistant porcine isolates of Campylobacter coli. AB - Erythromycin-resistant Campylobacter organisms were isolated from swine, and their resistance to the antibiotic was characterized. One hundred fourteen Campylobacter organisms were isolated from 572 swine intestinal samples. All isolates were identified as Campylobacter coli by sequence analysis of 16S rRNA gene and polymerase chain reactions with primers specific to hippuricase gene in Campylobacter jejuni and aspartokinase gene in C. coli. Minimal inhibitory concentrations (MICs) of erythromycin were determined by using the agar dilution method, and 80 isolates were found to be resistant to erythromycin (MIC >= 4 MUg/ml). Of these, 31 isolates had low-level resistance (MIC =4-16 MUg/ml), and 49 isolates had high-level resistance (HLR, MIC >= 32 MUg/ml). The HLR isolates carried a point mutation at position A2075 -> G in domain V of the 23S rRNA gene, whereas the low-level resistance isolates carried no mutation. These 49 HLR isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing to study their genetic diversity. Pulsed-field gel electrophoresis identified 16 distinct types with 50% genetic similarity as the cutoff. On the other hand, 28 different sequence types (STs), including 10 new STs, were identified with multilocus sequence typing. Forty-six of 49 erythromycin HLR isolates showed crossresistance to 6 macrolide derivatives. The correlation between the inhibitory activity of carbonyl cyanide m chlorophenylhydrazone and the existence of cmeB, which is responsible for efflux in HLR isolates, was found to be low. Erythromycin resistance was transferred from 38 of the 43 HLR isolates to susceptible C. coli by natural transformation, with a frequency of 1.217 x 10(-8)-4.618 x 10(-5) per recipient cell. All transformants were erythromycin resistant and had A2075 -> G mutation in at least one of three copies of the 23S rRNA gene. Results indicate that variable genotypes of HLR C. coli coexist in swine and high-level erythromycin resistance can be transferred to other strains. PMID- 20735176 TI - Molecular characteristics of methicillin-resistant Staphylococcus aureus blood isolates: clonal spread of staphylococcal cassette chromosome mec type IVA between the community and the hospital. AB - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is becoming increasingly common worldwide. The purpose of this study was to identify the prevalence and molecular characteristics of MRSA bloodstream isolates in hospitals. Clinical data from patients with MRSA bacteremia between 2003 and 2005 were collected. Isolates were classified as hospital-acquired (HA-MRSA), health care-associated (HCA-MRSA), or CA-MRSA according to the time of isolation and the risk factors for colonization. Available strains were tested for the presence of mecA, staphylococcal cassette chromosome mec (SCCmec), and by multilocus sequence test. Among 129 cases, 78 nonduplicated isolates were analyzed. The proportion of CA-MRSA, HCA-MRSA, and HA-MRSA was 2.6% (2), 23.1% (18), and 74.4% (58), respectively. According to multilocus sequence test and SCCmec, there were seven genotypes with sequence types (STs) and SCCmec types. The predominant genotype, ST5-MRSA-II, was found in 57.7% (45). All type IVA isolates was ST72 (9), and ST72-MRSA-IVA was identified in CA-MRSA (2, 100%), HCA-MRSA (1, 5.6%), and HA MRSA (6, 10.3%), respectively. In summary, CA-MRSA bacteremia was not common in our hospital during the period. PMID- 20735177 TI - Transcriptional regulation of energy metabolism in the liver. AB - Living organisms maintain energy homeostasis by constantly adjusting internal metabolic activities in response to nutritional states. Energy metabolism is regulated by the quality and quantity of the enzymes that catalyze metabolic reactions. Recruitment and regulation of enzymes responsible for transcriptional control, among others, play an important role in this process. Located downstream from intracellular signaling cascades, transcription factors receive information signals from multiple sources. Their primary function is to integrate and interpret this information in terms of transcriptional output. It was recently suggested that signal content is converted via post-transcriptional modifications of the transcription factors. Many studies have shown that multiple signaling pathways converge on single transcription factors. This review discusses the post translational modifications of transcription factors involved in the regulation of glucose metabolism, as well as the signaling networks in which they play a role. PMID- 20735178 TI - Binding patterns of peptide-containing liposomes in liver and spleen of developing mice: comparison with heparan sulfate immunoreactivity. AB - BACKGROUND: Liposomes incorporating peptide from the Plasmodium circumsporozoite protein (CSP) accumulate rapidly and selectively in adult mouse liver. PURPOSE: The development of the liposome-binding pattern in liver and spleen was studied in relationship to the development of extracellular matrix molecules. METHODS: Liposomes were administered to mice intravascularly or applied to the surface of liver and spleen slices in vitro. Slices were analyzed immunocytochemically. RESULTS: Liposomes were found along sinusoidal borders of liver, including the basolateral border of hepatocytes. The pattern was detected in the youngest animals studied (newborn). Intensity of heparan sulfate immunoreactivity increased until adult levels were reached at 20 days. Immunoreactivity for heparan sulfate proteoglycan, but not other proteoglycans, was detected in the youngest animals, and mimicked the pattern of liposome binding. The pattern of liposome binding in the spleen, concentrated in marginal zones, was similar to the pattern of heparan sulfate immunoreactivity, and also similar to the distribution of macrophage immunoreactivity. CONCLUSION: The postnatal development of liposome binding parallels the development of heparan sulfate immunoreactivity, supporting the suggestion that peptide-containing liposomes target liver by binding to heparan sulfate proteoglycans. Specific delivery of liposomes by targeting heparan sulfate proteoglycans is an effective strategy even at early time periods. PMID- 20735179 TI - The effects of 17-beta estradiol on enhancing proliferation of human bone marrow mesenchymal stromal cells in vitro. AB - Human bone marrow mesenchymal stromal cells (MSCs) with self-renewal and multiple differentiation potentials are considered a possible cell source for tissue engineering and regenerative medicine. However, the limited amount of MSCs in bone marrow and the loss of differentiation capacity following in vitro expansion restrict their practical application. Effective improvement of MSC proliferation is necessary for the clinical application of MSC-based tissue engineering. The effects of estrogen supplements on proliferation and characterizations of human MSCs were investigated at the present study. Supplements of 17-beta estradiol (E2) significantly increase the proliferation of human MSCs in vitro. The dose range of E2 to significantly increase MSC proliferation differs in the gender of MSC donor. E2 supplementation in cell proliferation maintains characterizations of MSCs, including cell surface markers, and osteogenic and adipogenic differentiation capacities. These data indicate that estrogen treatment can play an important role in improving human MSCs' expansion in vitro, which will effectively facilitate MSCs' function in the practical application of tissue engineering and regeneration. PMID- 20735180 TI - Microarray analysis of the effect of dexamethasone on murine cochlear explants. AB - CONCLUSIONS: The microarray analysis identified 39 genes up- or down-regulated by dexamethasone in the cultured tissue of mice cochlea. Of the eight genes most highly affected, several are suggested to have protective effects in the traumatized inner ear (Fkbp5, Glucocorticoid-induced leucine zipper (Gilz), glutathione peroxidase 3) and for others, a plausible mechanism of action can be offered (claudin 10, glutamate-ammonia ligase). The present data may support the use of dexamethasone to treat acute sensorineural hearing loss. It is warrantable to test these results in the in vivo cochlea. OBJECTIVES: To identify genes whose expression is markedly up- or down-regulated by dexamethasone in the cochlear tissue. METHODS: Murine cochlear tissue was cultured with or without dexamethasone for 48 h in vitro. The gene expression profiles were compared between the dexamethasone-treated and untreated cochlear tissue using a microarray that covers 33 696 transcripts (24 878 genes) of mice and quantitative real-time RT-PCR. RESULTS: The microarray analysis identified 39 genes that are up- or down-regulated by more than twofold in the presence of dexamethasone in the cochlear culture. Genes up- or down-regulated by at least threefold include Fkbp5, Gilz, glutathione peroxidase 3, claudin 10, glutamate-ammonia ligase, proteoglycan 1, integrin beta-like 1, and alpha subunit of glycoprotein hormone. PMID- 20735181 TI - Endoscopic endonasal surgery for recurrent cerebrospinal fluid rhinorrhea. AB - CONCLUSIONS: CT and MRI are helpful to detect the precise site of the fistula, which is crucial for carrying out the repair, and transnasal endoscopic surgery is an effective treatment for recurrent cerebrospinal fluid (CSF) rhinorrhea. OBJECTIVE: To discuss the cause and treatment of recurrent CSF rhinorrhea. METHODS: A retrospective study was undertaken to analyze the clinical characteristics of 32 patients with recurrent CSF rhinorrhea. After detailed examination and radiological evaluation by CT and MRI, all of them underwent transnasal endoscopic surgery. RESULTS: Six patients presented a leakage at the posterior wall of the frontal sinus, 12 at the ethmoid roof, and 14 at the sphenoid roof. Four cases with a defect in the frontal sinus and frontal recess were repaired with the DRAF III procedure, four cases with a defect in the sphenoid lateral recess were repaired through transpterygoid intervention and under an image-guided navigation system, while the others were operated by routine endoscopic sinus surgery. No recurrence was found during the follow-up for 14-60 months (mean 36.8) in 31 cases, and 1 case with recurrence recovered well after further surgery. PMID- 20735182 TI - Clinical efficacy of fat-graft myringoplasty for perforations of different sizes and locations. AB - CONCLUSION: Fat-graft myringoplasty (FGM) has a reliable tympanic closure rate for small to large perforations, but yields poor hearing improvement in the latter case. A topographic evaluation of FGM showed that the procedure resulted in a reliable perforation closure rate and audiologic outcome, regardless of perforation location. OBJECTIVES: This study assessed the utility of FGM in treating perforations of different sizes and locations. METHODS: This retrospective study involved 45 patients (46 ears) who underwent FGM at St Mary's Hospital (Seoul, Korea) between August 2007 and February 2010. RESULTS: The total perforation closure rate after FGM was 87% (40 cases), with no statistical difference among perforation size groups, even though the mean closure rates of the 10-20% and >30% perforation groups were lower than other groups. The difference in the closure rates of patients with anteriorly located perforations and those with perforations in other sites was not significant. The mean postoperative air-bone gap (ABG) was 14.3 (+/-7.5) dB. Mean postoperative ABG improved significantly after FGM; however, on a per-group basis, the >30% perforation group had the poorest results and the difference was statistically significant. The difference in mean postoperative ABGs of the two groups depending on the location of the perforation (anterior and other) was not significant. PMID- 20735183 TI - Intratympanic prednisolone therapy for sudden sensorineural hearing loss: A new protocol. AB - CONCLUSION: Intratympanic administration of prednisolone at a dose of 62.5 mg/ml performed every day for 3 consecutive days is more efficacious than the therapeutic approaches described so far in the literature. OBJECTIVES: The aim of the study was to evaluate the overall success rate, morbidity, and prognostic factors of a new protocol of intratympanic steroid administration as a means of primary therapy for idiopathic sensorineural hearing loss. METHODS: Overall, 34 patients presenting sudden unilateral sensorineural hearing loss of at least 30 dB over three frequencies that had developed within 72 h were treated once a day for 3 consecutive days with a single intratympanic injection of prednisone diluted in saline solution. RESULTS: Following intratympanic therapy with prednisone, 16 patients (47%) reported complete recovery of sudden sensorineural hearing loss, with a pure tone average that returned within 25 dB; 11 patients (32.3%) showed improvement in hearing of more than 30 dB; 4 patients presented improvement in pure-tone average between 10 and 30 dB. Only three patients failed to improve following intratympanic injection. PMID- 20735184 TI - Piezoelectric stapedotomy: the importance of a micropulse program. AB - CONCLUSIONS: We can consider the micropulse program as the best level of safety that should be used in all cases of piezoelectric stapedotomy. OBJECTIVES: The aim of this study was to describe the importance of a micropulse program in determining the success of piezoelectric stapedotomy. METHODS: A total of 112 patients (group A) affected by primary otosclerosis underwent piezoelectric stapedotomy for otosclerotic stapes fixation. A specific operative program was created to perforate the stapes footplate: this program makes it possible to perforate the footplate of the stapes with a predetermined and non-modifiable temporization. Before and 1 year after surgery, all the patients underwent the following instrumental examinations: pure-tone audiometry, tympanometry, transient-evoked otoacoustic emissions, distortion product otoacoustic emissions, and auditory brainstem response. Results were compared with those obtained from 30 patients who underwent piezoelectric stapedotomy without the specific operative program (group B). RESULTS: At 1 year after surgery, with regard to the pure-tone audiometry test, all patients had an air-bone gap (ABG) reduction: no worsening of the bone conduction and no postoperative sensorineural hearing loss were found. In group A, there was a closure of the ABG within 10 dB in all patients. PMID- 20735185 TI - Hearing rehabilitation in congenital aural atresia using the bone-anchored hearing aid: audiological and satisfaction results. AB - CONCLUSION: The BAHA (bone-anchored hearing aid) remains the most reliable method of auditory rehabilitation for patients with congenital aural atresia and improves hearing outcome and quality of life in these patients who are otherwise unable to benefit from traditional hearing aids. New techniques are being developed, such as fully implantable hearing devices, and will have to prove their efficacy and safety in this indication. OBJECTIVE: To evaluate the audiological results and patient satisfaction after rehabilitation of congenital aural atresia using the BAHA. METHODS: Sixteen patients suffering from bilateral congenital aural atresia were implanted with unilateral BAHA. Preoperative air- and bone-conduction thresholds and air-bone gap (ABG), preoperative sound reception threshold (SRT), postoperative aided thresholds, implantation complications, patient satisfaction, and the APHAB questionnaire were collected. RESULTS: After a mean follow-up period of 6.5 years, 15 patients were still using their device. Each patient had an average improvement of 33 +/- 7 dB. Closure of the ABG within 15 dB of the preoperative bone-conduction thresholds occurred in 10 patients. Adverse skin reactions appeared in 50% of patients over 6.5 years of follow-up. Eleven of the 12 patients used their BAHA for more than 8 h per day. PMID- 20735186 TI - Assessing mental representation of mastoidectomy by a computer-based drawing tool. AB - CONCLUSIONS: This simple computer-based drawing tool provides valid information on mental representation of mastoidectomy at its initial phase. OBJECTIVE: The aim of this study was to elaborate a simple computer-based drawing tool to assess the mental representation of mastoidectomy. METHODS: Twelve trainees in otology (five beginners, seven mid-level) and four otology experts participated in this prospective study. The image of a mastoid was displayed on a screen. All subjects reproduced the movements of mastoidectomy with a pen on a graphic tablet. Movements appeared as gray lines on the image. Surgeons were evaluated before and after a dissection course. The surface of mastoidectomy, perimeter, circularity, and the angle between traces and cavity edges were measured by Image J software. RESULTS: The total surface of mastoidectomy was higher in experts than in mid level and beginner trainees (respectively 99 +/- 6.5%, vs 57 +/- 1.5%, and 22 +/- 5.6%, p < 0.01 for experts vs beginners and p < 0.05 for experts vs mid-level, ANOVA and Bonferroni). Circularity was also higher in experts than in trainees. After training, total surface and circularity increased. The angle between traces and cavity edges was lower in experts than in trainees and was reduced after training. PMID- 20735187 TI - Predictors of stigmatizing attitudes towards people with mental disorders in a general population in Finland. AB - BACKGROUND: For planning effective and well-targeted initiatives to reduce stigma, we need to identify which factors are associated with stigmatizing of people with mental disorders. AIMS: This study examined how well a combination of variables predicts stigmatizing attitudes and discrimination in a general population. METHODS: A survey questionnaire was sent to 10,000 persons aged 15-80 years residing in western Finland. Attitudes were measured using a scale consisting of negative stereotypes about people with depression and stereotypical beliefs connected with mental problems, while discrimination was measured by a social distance scale. Predictors included demographic variables, mental health resources, personal experience of depression or psychological distress, knowing someone who suffers from mental health problems, and negative stereotypical beliefs. RESULTS: Although 86% of the population thought that depression is a real medical condition, the majority of respondents believed that people with depression are responsible for their illness. Social discrimination was significantly associated with respondents' age, gender, native language, sense of mastery, depression, stereotypical beliefs and familiarity with mental problems. CONCLUSIONS: The results suggest that the need to address stigma is higher among men, older people and those without familiarity with mental problems. When planning interventions to shape stereotypes, the need for change is highest among those with a low sense of life control and poor social networks. Direct interactions with persons who have mental problems may change the stereotypical beliefs and discriminative behaviour of those who do not have familiarity with mental problems. PMID- 20735188 TI - Attitudes to coercion at two Norwegian psychiatric units. AB - BACKGROUND: Many countries allow for the use of restraint and seclusion in emergencies with psychiatric inpatients. Authors have suggested that the attitudes of staff are of importance to the use of restraint and seclusion. AIM: To examine the attitudes to coercion at two Norwegian psychiatric units. In contrast to the idea that attitudes to coercion vary much within and between institutions, we hypothesized that staff's attitudes would be quite similar. METHODS: We distributed a questionnaire to staff at two psychiatric units in two Norwegian counties. Eight wards were included. The questionnaire contained fictitious case histories with one patient that was violent and one patient that was self-harming, and staff were asked to describe how they would intervene in each emergency. Emergency strategies were sorted according to degree of restrictiveness, from the highly restrictive (restraint, seclusion) to the unrestrictive (talking, offering medication). Data were analysed with regression analyses. RESULTS: There was only a limited degree of variance in how staff at the different units and various groups of staff responded. Staff were more likely to favour a highly restrictive intervention when the patients were physically violent. Male staff and unskilled staff were significantly more prone to choosing a highly restrictive intervention. CONCLUSIONS: Our hypothesis was confirmed, as there was a limited degree of variance in staff's responses with respect to degree of restrictiveness. The study supported the idea that a range of different interventions are used in emergency situations. PMID- 20735189 TI - Characteristics of high-risk HIV-positive IDUs in Vietnam: implications for future interventions. AB - The HIV epidemic in Vietnam is concentrated primarily among injecting drug users (IDUs). To prevent HIV-1 superinfection and to develop effective HIV prevention programs, data are needed to understand the characteristics of high-risk HIV positive IDUs. In 2003 , we conducted a community-based cross-sectional study among predominately male, out-of-treatment IDUs, aged 18?45, in the Bac Ninh Province, Vietnam. Among 299 male participants, 42.8% were HIV-positive, and among those, 96.9% did not know their status prior to the study. Furthermore, 32% were HIV-positive and had high HIV behavioral risk (having unprotected sex or having shared injecting equipment in the past 6 months). Injecting for ?3 years, younger age, and pooling money to buy drugs were independently associated with being at high risk for transmitting HIV. IDUs who purchased more than one syringe at a time were less likely to have high HIV behavioral risk. Structural interventions that increase syringe accessibility may be effective in reducing HIV risk behavior among HIV-positive IDUs. Study limitations are noted in the article. PMID- 20735190 TI - Early sexual experience and later onset of illegal drug use among African American students on HBCU campuses. AB - Few studies examine whether early sexual experience is associated with subsequent illegal drug use among adolescents. A sample of 7,372 African American students who had not used illegal drugs before the age of 14 were identified in the dataset of the 2001 Historically Black Colleges and Universities (HBCU) Substance Use Survey. Using self-reported ages of onset, discrete-time survival models estimated the hazard of illegal drug use onset after age 13 subsequent to first sexual intercourse. Early sex was modestly associated with subsequent illegal drug initiation, particularly among females. Drug use prevention services should be provided to youth engaged in early sexual activity. PMID- 20735191 TI - With God's help i can do it: crack users? Formal and informal recovery experiences in El Salvador. AB - Crack use has increased dramatically in El Salvador in the last few decades. As with other developing countries with sudden onsets of drug problems, El Salvador has few medical staff trained in addictions treatment. Little research has examined drug users? attempts to reduce or abstain from drug use in countries where government-regulated formal medical treatment for drug addiction is scarce. This paper uses qualitative and quantitative data gathered from active crack users to explore their formal and informal strategies to reduce or abstain from drugs, and compares these with components of informal and formal treatment in developed countries. PMID- 20735192 TI - Crossing a border for a low-cost, high-risk environment: smoking status and excessive drinking among young adults in Tijuana. AB - This study examines the drinking and smoking behavior of 2,311 college-age adults traveling from San Diego, California, to Tijuana, Mexico (December 2006 to December 2008). We describe this Border sample's drinking history and smoking status and estimate multivariate models of evening drinking participation and, conditional on drinking, blood alcohol concentration. Noting limitations, we present implications for identifying young adults at high risk for alcohol and tobacco use, particularly females, and lay the foundation for further research examining young adults? alcohol and tobacco use in reduced price scenarios. PMID- 20735193 TI - Family roles in homes with alcohol-dependent parents: an evidence-based review. AB - The behavioral health care field has seen attempts to understand the functioning of families in which a parent is dependent on alcohol as a set of roles into which the other family members fall. The most popular of these classifications taught in the United States includes five roles (enabler, hero, lost child, mascot, and scapegoat) that are used to conceptualize families and individuals in treatment and support group settings, as well as in popular self-help literature. Attempts to operationalize and measure these roles have, however, been fraught with difficulties. The resulting research base has seen conflicting evidence for the support of such roles, as well as little work on diverse families. The evidence against such well-defined family roles, the questions surrounding their development, and the difficulties of applying such constructs in real-life situations (with numerous confounding factors and unknown associated conditions) may indicate that their clinical utility does not win out over the problems inherent with this manner of classification. PMID- 20735194 TI - Discriminative validity of the Danish version of the Pediatric Evaluation of Disability Inventory (PEDI). AB - The Pediatric Evaluation of Disability Inventory (PEDI) assesses functional status in children with disabilities aged 0.5-7.5 years. The purpose of this study was to examine if the Danish version of the PEDI was able to discriminate between nondisabled children and children with cerebral palsy (CP) or juvenile idiopathic arthritis (JIA). Convenience sampling was used to select the clinical samples that consisted of 22 children with CP and 14 children with JIA aged 1.5 7.5 years. An additional sample, consisting of 224 nondisabled children aged 1.0 5.9 years, was obtained on the basis of random sampling. The PEDI was administered as a questionnaire completed by the parents. Results from receiver operating characteristics (ROC) analysis showed that in the case of discrimination between children with CP and nondisabled children, the sensitivity and specificity were 77.3 and 97.8%, respectively. In the discrimination between children with JIA and nondisabled children, the sensitivity and specificity were 99.8 and 81.7%, respectively. Study results indicate that the Danish version of the PEDI shows good discriminative validity. Further studies of the discriminative validity are recommended. PMID- 20735195 TI - Reported sensory processing of children with Down syndrome. AB - Investigators have identified delays and differences in cognitive, language, motor, and sensory development in children with Down syndrome (DS). The purpose of this study was to determine the parent-reported frequency of sensory processing issues in children with DS aged 3-10 years, and the parent-reported functional impact of those sensory issues. Parents completed the short sensory profile (SSP) and a parent questionnaire (PQ). SSP results revealed a total score definite difference rate of 49%. Highest rates of probable and definite difference were in the low energy/weak, underresponsive/seeks sensation, and auditory filtering subsections of the SSP. Themes were generated from responses on the PQ regarding the functional impact of sensory differences on occupational performance in their children with DS, and related strategies currently used by parents. Findings from the study provide information to parents and health care professionals regarding sensory processing patterns in children with DS, and provide foundational data for future research. PMID- 20735196 TI - Can I play? A concept analysis of participation in children with disabilities. AB - Participation is essential to children's development. Children with disabilities are at risk for restricted participation. Despite wide use of the word participation, the definition remains vague. The eight steps of analysis by Walker and Avant (2005) were used to guide the concept analysis. The uses and defining attributes of participation were identified and cases formulated within the context of children with disabilities and health care professions. In order to participate, a child with disabilities must take part in something or with someone, they must have a sense of inclusion, control over what they are taking part in, and be working toward obtaining a goal or enhanced quality of life. Through participation children acquire new skills, have increased physical, emotional and social well-being and enhanced quality of life. It is hoped that health care professionals can use this definition to address the shortcomings of existing programs and develop measures to assess the attributes of participation. PMID- 20735198 TI - A qualitative study of coping in mothers of children with an autism spectrum disorder. AB - A significant body of research exists that explores the stressors of raising a child with an autism spectrum disorder (ASD). There are fewer studies, however, that examine specific effective coping strategies of mothers of children with an ASD. This qualitative study explored mothers' perceptions of effective coping strategies for their parenting stressors. In-depth interviews were conducted with 11 mothers to inquire about their personal coping methods. Interviews were coded and emergent themes identified that included coping strategies such as "me time," planning, knowledge is power, sharing the load, lifting the restraints of labels, and recognizing the joys. The information from this study may benefit mothers of children with ASD and inform pediatric therapists providing services to children with ASD and their families. PMID- 20735199 TI - The role of occupational therapists and physical therapists in elementary school system early intervening services and response to intervention: a case report. AB - The Individuals with Disabilities Improvement Act and No Child Left Behind Act broadened the roles of occupational therapists (OTs) and physical therapists (PTs) to include therapist participation in early intervening services including response to intervention (RTI). This case report describes one school district's inclusion of OT and PT in the elementary school RTI program by identifying and implementing role responsibility and changing workloads for therapists. Therapist responsibilities included (a) administering a screening tool, (b) educating and supporting teachers and staff, (c) providing student resources and intervention strategies, and (d) referring students from RTI to special education and related services. Teachers responded positively using therapist-provided strategies and support. Limitations included an increased workload because of large numbers of students to screen and very few staff available for screening. Future research should include longitudinal studies that measure student responses to therapy intervention, teacher responses to collaboration, and the use of intervention strategies over time. PMID- 20735200 TI - A systematic review of common physiotherapy interventions in school-aged children with cerebral palsy. AB - This systematic review focused on the common conventional physiotherapy interventions used with children with cerebral palsy (CP), aged 4 to 18 years, and critically appraised the recent evidence of each of these interventions using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The search strategy yielded 34 articles after inclusion and exclusion criteria were applied. The investigated physiotherapy interventions included strength and functional training, weight-supported treadmill training (WBSTT), and neurodevelopmental treatment (NDT). A category of treatment dosage was also included. Strength training was the most studied intervention with significant improvements found in the strength of selected muscle groups using dynamometry, with fewer studies showing significant improvement in function. Functional training showed improvements in gross motor function, endurance, and temperospatial measures, such as gait speed and stride length. Nonsignificant trends of improvement on the Gross Motor Function Measure (GMFM) and gait velocity were found for WBSTT by a few studies with low levels of evidence (case series). Of three studies that evaluated NDT, one high-level evidence study, i.e., randomized controlled trial (RCT) found significant improvements on the GMFM. All studies reviewing treatment dosage had high levels of evidence (RCTs), yet found no significant differences for different intensities of treatment. These results indicate that the levels of evidence for physiotherapy interventions, particularly strengthening and to a lesser extent functional training, in school-aged children with CP has improved; however, further high-level evidence is needed for other interventions. PMID- 20735201 TI - Substance use, sexual identity, and health care provider use in men who have sex with men. AB - This article describes the association between substance use, sexual identity, and seeing a health care provider on a regular basis for 257 men who have sex with men (MSM). Data from in-person interviews were gathered from MSM who resided in Massachusetts between 2003 and 2007. A logistic regression analysis that controlled for demographic characteristics, health insurance status, HIV/AIDS status, drug use, and social support revealed that MSM who identified as heterosexual, compared with those who identified as gay or bisexual, were 60% less likely to access a health care provider on a regular basis. Further, the likelihood of seeing a provider regularly was 54% lower for MSM who had used illegal drugs in the past 30 days and 32% higher for MSM who had more social support. Study limitations and implications are discussed. PMID- 20735202 TI - Pharmacokinetics and tissue distribution studies of orally administered nanoparticles encapsulated ethionamide used as potential drug delivery system in management of multi-drug resistant tuberculosis. AB - Sustained release nanoformulations of second line anti-tubercular drugs can help in reducing their dosing frequency and improve patient's compliance in multi-drug resistant tuberculosis (MDR TB). The objective of the current study was to investigate the pharmacokinetics and tissues distribution of ethionamide encapsulated in poly (DL-lactide-co-glycolide) (PLGA) nanoparticles. The drug loaded nanoparticles were 286 +/- 26 nm in size with narrow size distribution, and zeta-potential was -13 +/- 2.5 mV. The drug encapsulation efficiency and loading capacity were 35.2 +/- 3.1%w/w and 38.6 +/- 2.3%w/w, respectively. Ethionamide-loaded nanoparticles were administered orally to mice at two different doses and the control group received free (unencapsulated) ethionamide. Ethionamide-loaded PLGA nanoparticles produced sustained release of ethionamide for 6 days in plasma against 6 h for free ethionamide. The Ethionamide was detected in organs (lung, liver, and spleen) for up to 5-7 days in the case of encapsulated ethionamide, whereas free ethionamide was cleared within 12 h. Ethionamide-loaded PLGA nanoparticles exhibited significant improvement in pharmacokinetic parameters, i.e. C(max), t(max), AUC0-infinity, AUMC0-infinity, and MRT of encapsulated ethionamide as compared with free ethionamide. Drug in nanoparticles also exhibited a dose proportional increase in the AUC0-infinity values. The pharmacodynamic parameters such as AUC0-24/MIC, C(max)/MIC, and Time > MIC were also improved. PLGA nanoparticles of ethionamide have great potential in reducing dosing frequency of ethionamide in treatment of MDR TB. PMID- 20735203 TI - Genotoxicity evaluation of amorphous silica nanoparticles of different sizes using the micronucleus and the plasmid lacZ gene mutation assay. AB - We investigated the potential of four well-characterized amorphous silica nanoparticles to induce chromosomal aberrations and gene mutations using two in vitro genotoxicity assays. Transmission electron microscopy (TEM) was used to verify the manufacturer's nominal size of 10, 30, 80 and 400 nm which showed actual sizes of 11, 34, 34 and 248 nm, respectively. The 80 (34) nm silica nanoparticles induced chromosomal aberrations in the micronucleus assay using 3T3 L1 mouse fibroblasts and the 30 (34) and 80 (34) nm silica nanoparticles induced gene mutations in mouse embryonic fibroblasts carrying the lacZ reporter gene. TEM imaging demonstrated that the majority of nanoparticles were localized in vacuoles and not in the nucleus of 3T3-L1 cells, indicating that the observed DNA damage was most likely a result of indirect mechanisms. Further studies are needed to reveal these mechanisms and to determine the biological relevance of the effects of these particular silica nanoparticles in vivo. PMID- 20735204 TI - Secondary transport of metal-citrate complexes: the CitMHS family. AB - Primary and secondary transport of citrate has been extensively studied in pathogenic and non-pathogenic bacteria. Primary transporters of citrate complexed with metal ions, particularly Fe, have also garnered attention, with the fec system of E. coli being a classic example. In contrast, little is known about secondary transporters of metal-citrate complexes. Recently, a family of proteins responsible for secondary metal-citrate transport in bacteria was discovered and designated as the CitMHS transporter family. Several members have been functionally characterized to date and serve as the foundation for understanding this family. Three subfamilies have been categorized, depending on the main metal ion transported. These subfamilies are the Mg(2+)-citrate transporter, the Ca(2+) citrate transporter, and the Fe(3+)-citrate transporter. Each subfamily is believed to be substrate-selective due to the metal-citrate complexes being abundantly present in their environment and/or the ability of the complex to be metabolized by the organism. The implication of this family in the pathogenic access to Fe, information about transcriptional control, putative structure, predicted family members, members characterized to date and potential use in bioremediation are discussed. PMID- 20735205 TI - Dosimetric effectiveness of targeted radionuclide therapy based on a pharmacokinetic landscape. AB - Assessment of targeted radionuclide therapy (TRT) agent effectiveness based on its pharmacokinetic (PK) properties could provide means to expedited agent development or its rejection. A broad PK model that predicts the relative effectiveness of TRT agents based on the relationship between their normal body (k(12), k(21)) and tumor (k(34), k(43)) PK parameters has been developed. A classic two-compartment open model decoupled from a tumor was used to represent the body. Analytically solved differential equations were used to develop a relationship that predicts TRT effectiveness. Various PK scenarios were created by pairing normal body PK parameters of 38 pharmaceuticals found in the literature with estimated tumor PK parameters. Each PK scenario resulted in a maximum permissible injected activity that limited the whole-body dose to 2 Gy and yielded a maximum delivered tumor dose. The model suggests that a k(34):k(43) ratio greater than 5 and a k(12):k(21) ratio less than 1 is effective at delivering doses that ensure sufficient solid tumor control. It was also shown that there is no direct relationship between tumor dose and acid dissociation constant (pK(a)), lipophilicity (log P), and fraction unbound (fu), which are important physicochemical properties. This study suggests that although effective TRT may be difficult to achieve for solid tumors, good TRT agents must have extremely desirable normal body PKs in conjunction with very high tumor retention. The developed PK TRT model could serve as a tool to compare the relative dosimetric effectiveness of existing TRT agents and novel TRT agents early in the developmental phase to potentially reject those that possess unfavorable PKs. PMID- 20735206 TI - Metalloporphyrin synergizes with ascorbic acid to inhibit cancer cell growth through fenton chemistry. AB - Ascorbic acid (AA) has been reported to inhibit tumor cell growth through the generation of extracellular hydrogen peroxide (H(2)O(2)). However, the clinical utility of AA has been limited by relatively low potency and in vivo efficacy. This study reports that the metalloporphyrin, Mn(III) tetrakis(N-methylpyridinium 2-yl)porphyrin(5+) (MnTMPyP), has a potent synergistic cytotoxic effect when combined with AA in a variety of cancer cell lines. In the presence of MnTMPyP, the concentration of AA required to inhibit cancer cell growth was markedly reduced. In vitro (cell-free) experiments demonstrated that AA alone enhanced the Fenton reaction that produces cytotoxic hydroxyl radical (HO(*)); however, this reaction was limited by the low rate by which AA generates H(2)O(2) (Fenton reaction substrate) from O(2). MnTMPyP catalyzed H(2)O(2) generation through the AA-facilitated Mn(II <--> III)TMPyP redox cycle and thereby markedly potentiated the Fenton reaction. Accordingly, MnTMPyP and AA resulted in increased cellular levels of H(2)O(2) and HO(*) in cancer cells, which mediate the synergistic cytotoxicity of this combined treatment. This effect was inhibited by cellular enzymes that metabolize H(2)O(2), such as catalase and glutathione peroxidase, suggesting that selective killing of cancer cells deficient in such enzymes can be achieved in vivo. PMID- 20735207 TI - Anticancer activity and molecular mechanism of resveratrol-bovine serum albumin nanoparticles on subcutaneously implanted human primary ovarian carcinoma cells in nude mice. AB - This study investigates the antitumor effects and functional mechanism of resveratrol-bovine serum albumin nanoparticles (RES-BSANP) on human primary ovarian carcinoma cells in nude mice. An implanted tumor model was established by injecting a suspension of the human primary ovarian cancer cell SKOV(3) into the subcutaneous tissue of nude mice. The tumor-bearing mice (n = 32) were randomly divided into 8 groups, which received intraperitoneal injections of normal saline (0.9%, 0.5 mL), BSA (1.5 mg/kg, 0.5 mL), or RES-BSANP or RES (200, 100, and 50 mg/kg, 0.5 mL), respectively, once a week for 4 weeks. The in vivo antitumor efficacy was evaluated by measurement of tumor volume, whereas morphological alterations were observed by transmission electron microscope (atomic force microscopy); TUNEL assays and immunoblotting for apoptotic and cell proliferation proteins were carried out to elucidate the possible mechanism. RES-BSANP was found to exhibit certain highly desirable characteristics such as innocuity, better dispersity, and water solubility; it affected the in vivo tissue/organ distribution of RES in a remarkable manner. The administration of RES-BSANP significantly retarded the growth of carcinomas in nude mice from the third week onwards, and the inhibition rate was markedly higher than in mice treated with RES (52.43% vs. 46.34%, p < 0.05), without causing weight loss (p > 0.05). Simultaneously, apoptotic and necrotic morphological characteristics were observed with electron microscopy in the tumor tissues of treated mice. TUNEL staining revealed that the tumors from RES-BSANP-treated mice exhibited a similar apoptotic index as RES control tumors. Western blot analysis of the protein expression profiles revealed that part of the mechanism may be mediated by triggering the release of cytochrome c from the intermembrane space and upregulating the expression of caspase-9 and caspase-3, suggesting that the mitochondrial apoptotic pathway was being activated. PMID- 20735208 TI - Rational approach to the synthesis, evaluation, and (68)ga labeling of a novel 4 anilinoquinoline epidermal growth factor receptor inhibitor as a new imaging agent that selectively targets the epidermal growth factor receptor tyrosine kinase. AB - Certain small-molecule inhibitors that target epidermal growth factor receptor (EGFR), such as Gefitinib, Erlotinib, and Lapatinib, provide a new approach for cancer treatment. In accordance with the pharmacophore model for inhibitor competition at EGFR-binding site, this study proposes a rationalized design for a novel 4-anilinoquinoline EGFR tyrosine kinase inhibitor, [6,7-dimethoxyethoxy] quinolin-4-yl]-(3-ethynylphenyl)-amine (YCU07). This is the first study to apply ring-closing metathesis toward synthesis of the quinoline nucleus for this 4 anilinoquinoline EGFR inhibitor. YCU07 expressed significant inhibitory activity for EGFR tyrosine kinase in A431 cells, as confirmed by an ABTS microwell peroxidase substrate system read colorimetrically at 405 nm. Injection of (68)Ga labeled glutamic acid polypeptide (GAP)-YCU07 conjugate in nude mice implanted with A431 was imaged by animal PET camera (LabPET8; Gamma Medica-Ideas) and computed tomography (eXplore Locus; GE Healthcare), to evaluate its biodistribution. (68)Ga-GAP-YCU accumulated in the receptor-positive tumors, with uptake values of 1.50% +/- 0.09% and 2.36% +/- 0.36% of injected activity per gram tissue at 30 and 90 minutes, respectively. PMID- 20735209 TI - A novel oncolytic adenovirus expressing Escherichia coli cytosine deaminase exhibits potent antitumor effect on human solid tumors. AB - PURPOSE: This study aims to generate a more potent oncolytic adenovirus, Ad.hTERT E1A/CMV-CD, which combines therapeutic gene and oncolytic effect. METHODS: A human telomerase reverse transcriptase (hTERT) gene promoter was used to regulate the expression of adenoviral immediate-early gene 1A (E1A) to induce selective replication of recombinant adenovirus in tumor cells. To further enhance antitumor effect, a cytomegalovirus (CMV) promoter-driven Escherichia coli cytosine deaminase (CD) gene expression cassette was further incorporated into E1 region and the antitumor effect of this novel adenovirus was evaluated in vitro and in vivo. RESULTS: Ad.hTERT-E1A/CMV-CD was capable to selectively replicate and lyse in various human tumor cell lines, including NCIH460, SW1990, and HeLa, while causing no damage to primary fibroblasts. The combined therapy of Ad.hTERT E1A/CMV-CD with prodrug 5-fluorocytosine (5-FC) elicited a greater killing effect on tumor cells than Ad.hTERT-E1A/CMV-CD alone, and it synergistically suppressed tumor growth in BALB/c nude mice bearing human lung tumor. CONCLUSIONS: As telomerase is reactivated in a broad spectrum of tumors and prodrug 5-FC is much safe than its metabolized 5-fluorouracil, a chemotherapeutic agent in the treatment of many malignancies, Ad.hTERT-E1A/CMV-CD in combination with 5-FC may be a potential strategy for the treatment of a wide range of solid tumors. PMID- 20735210 TI - Antitumor activity of theophylline in combination with Paclitaxel: a preclinical study on melanoma experimental lung metastasis. AB - Melanoma is one of the most aggressive forms of tumor, being responsible for about 80% of skin cancer deaths. Much effort is being directed at obtaining less toxic anticancer therapies, and the combination between low cytotoxic doses of chemotherapeutic drugs and natural differentiative compounds seems to be of particular importance. The present study was undertaken to examine the possible role of a combination therapy using paclitaxel (PTX) as chemotherapeutic molecule and theophylline (TH) as differentiative agent in the prevention of metastasis in B16-F10 melanoma-bearing C57BL6/N mice. In vitro proliferation studies demonstrated that TH enhanced the antiproliferative effect of PTX. In the in vivo experiments, a highly sensitive computerized image analysis method, performed on histological lung sections of mice injected with melanoma cells, was used to quantify the efficacy of the treatments. This study demonstrated that the simultaneous treatment of mice with TH and a low dose of PTX produced a similar anti-invasive effect than that caused by highly toxic PTX concentration. PMID- 20735212 TI - Ecstasy use and its correlates among young, low-income women. AB - We examined the association of illicit drug use with stress and sexual behaviors among 407 women, aged 18?31, who attended family-planning clinics in southeast Texas between June 2002 and May 2003 (n = 407). Paired comparisons of each of three types of drug users (of ecstasy, marijuana only, and other illicit drugs except ecstasy) with nonusers were assessed by logistic regressions. After controlling for demographics, both ecstasy users and marijuana-only users had a higher score on the stress scale than nonusers. All drug users were at higher risk of more lifetime sexual partners than those who had never used drugs, while those who had used ecstasy were more than twice as likely to have had prior sexually transmitted infections as those who had never used drugs. This study demonstrates that young, low-income women who use ecstasy experience higher levels of stress than nonusers. Stress level is correlated with drug use and participation in risky sexual behaviors. If stress is associated with drug use and risky sexual behavior, interventions designed to reduce substance use and risky sexual behavior in these women may need to also address factors that lead to increased stress. The study's limitations were noted. PMID- 20735213 TI - Quality of life, needs, and interest among cocaine users: differences by cocaine use intensity and lifetime severity of addiction to cocaine. AB - We examined the quality of life (QoL) of 149 patients who were recruited in 2005 at outpatient treatment centers for cocaine dependence in Spain. Important life areas and life areas with potential need and interest to change in order to improve the QoL were analyzed in terms of patients? cocaine use intensity within the previous six months and lifetime severity addiction to cocaine. The Spanish versions of the Drug User Quality of Life Scale and the Lifetime Severity Index for Cocaine were used to measure QoL, needs and interest, and severity addiction to cocaine. The data analysis employed t-tests, linear regression, Mann?Whitney U tests, multivariate regression, and chi-square tests. Tailoring treatment programs to address the life areas that are considered relevant to cocaine users considering their intensity of consumption and lifetime severity addiction to cocaine may improve retention and treatment outcomes. Further research needs to consider patients of different ethnic backgrounds and cultural contexts. The study's limitations are noted. PMID- 20735214 TI - Motives for illicit use of doping substances among athletes calling a national antidoping phone-help service: an exploratory study. AB - This study aimed to construct a hierarchy of motives linked to doping behaviors. Between 2000 and 2005, calls to a national antidoping phone-help service by 115 cyclists, 203 bodybuilders, and 40 footballers were analyzed. The results showed that the main motives were preserving health for cyclists, increasing muscular strength for bodybuilders, and personal recreation for footballers. However, in contrast to the literature, group influence was low and health preoccupations were high for cyclists; the influence of body image was relatively low for bodybuilders; and footballers cited muscular strength enhancement as a motive. The study's limitations are noted. The prevention campaigns therefore need to be specific. PMID- 20735215 TI - Crack, AIDS, and women in Sao Paulo, Brazil. AB - Brazil is currently experiencing a growing number of newly recorded cases of HIV infection among women, with transmission mainly occurring by sex. This increase may be associated with the development of sexually risky behavior among female crack users who, according to informal reports, prostitute themselves for drugs or for money to be used for buying drugs. Since epidemiologic studies have not yet addressed this phenomenon, the aim of this study was to investigate this in depth using a qualitative ethnographic approach. An intentional sample was utilized, composed of 75 female crack users in S?o Paulo, who were selected by specific criteria using the snowball strategy and key informants. Fourteen different chains of users were investigated, allowing us to include the largest possible number and variety of users. Each participant was submitted to a semi structured in-depth interview that was guided by a questionnaire. Verbal information was corroborated and extended using participative observation. These 14?45-year-old women, who had little schooling and no job connections, opted to sell their bodies as a strategy to obtain drugs and to satisfy their compulsive use of crack. The subjects engaged in up to nine acts of sexual intercourse per day, in unsafe locations and with multiple partners who were approached in a besieging way and selected using subjective criteria. These crack users generally exchanged sex under craving for ridiculously low prices and left the use of protection up to the client. Because the users used inadequate pipes to smoke crack, it was common for them to have lesions on their lips and mouths. Since they often provided oral sex, they exposed themselves to considerable risk for infection with STDs including HIV, because of the contact of their partners? semen with their open wounds. These women make up an important risk group with respect to the transmission of STDs including AIDS. PMID- 20735216 TI - Sexual intercourse experience and engagement in unprotected sex in adolescent MDMA users in Taiwan. AB - This study aimed to examine the multidimensional correlates of having sexual intercourse experience and engaging in unprotected sex among adolescent ecstasy (3,4-methylenedioxyamphetamine or MDMA) users in Taiwan. The rates of having sexual intercourse and engaging in unprotected sex in 200 adolescent ecstasy users were calculated. Individual, family, and peer correlates of sexual intercourse and engagement in unprotected sex were examined. The results found that 124 (62%) had had sexual intercourse and 79 (39.5%) had engaged in unprotected sex at least once. Adolescent ecstasy users who were female, had used ketamine, had parents with habitual alcoholic problems, and more actively interacted with their peers were more likely to have had sexual intercourse. Those who were higher in novelty seeking and more actively interacted with peers were more likely to have engaged in unprotected sex. Sexual intercourse and engaging in unprotected sex in adolescent ecstasy users were correlated to multidimensional factors; the findings could provide a basis for interventions of prevention and reduction of harm. PMID- 20735217 TI - Effects of motivational enhancement therapy on readiness to change MDMA and methamphetamine use behaviors in Taiwanese adolescents. AB - The aim of this study was to examine the effect of brief modified motivational enhancement therapy (MET) on readiness to change patterns of methylenedioxymethamphetamine (MDMA) and methamphetamine (MAMP) use behaviors in adolescents. A total of 94 adolescents who used MDMA or MAMP were consecutively recruited from a juvenile abstinence center; 46 received a three-session MET intervention (intervention group), and 48 received educational materials only and no MET intervention (control group). Analysis of covariance was performed to examine the effect of motivational interviewing on the readiness of change scores on the University of Rhode Island Change Assessment and on the scores of its subscales. By using the pretreatment scores as covariates, the intervention group demonstrated higher posttreatment scores of readiness to change and of the contemplation subscale on the University of Rhode Island Change Assessment than the control group. The results of this study support the finding that brief modified MET is effective in promoting readiness to change MAMP and MDMA use behaviors in adolescents who receive short-term treatment programs. PMID- 20735218 TI - Heroin use, dependence, and attitudes to treatment in non-treatment-seeking heroin users: a pilot study. AB - Much research examining heroin users utilizes treatment samples; non-treatment seeking heroin users are not well understood. It is unclear whether this group can avoid impaired control or negative sequelae commonly observed in treatment seeking populations. During 2000 and 2001, we recruited 69 non-treatment-seeking heroin users with no treatment history. Heroin use, management strategies, treatment attitudes, and risk behaviors were assessed; the DSM-IV checklist and severity of dependence scale were completed. Study limitations and implications for heroin use and its treatment are discussed. PMID- 20735219 TI - Nanotechnology contributions to the pharmacotherapy of pediatric HIV: a dual scientific and ethical challenge and a still pending agenda. PMID- 20735221 TI - Surface-modified PLGA-based nanoparticles that can efficiently associate and deliver virus-like particles. AB - AIM: To design and develop a new nanocarrier appropriately engineered for the adequate accommodation of a virus-like particle, the recombinant hepatitis B surface antigen (22 nm), and intended to be used for the transmucosal delivery of the associated antigen. The nanoparticles consisted of a core blend of poly(D,L lactide-co-glycolide) and poloxamer 188, and a hydrophilic shell of chitosan. RESULTS: By by conveniently adapting the nanoprecipitation technique, it was possible to associate a significant amount of active antigen (44%) to the nanocarrier. The resulting nanosystems had a size of around 200 nm and positive zeta potential attributed to the association of chitosan. The nanoparticles were able to deliver the associated antigen in a controlled manner for up to 14 days without compromising its activity, as determined by ELISA. Moreover, the antigenicity of the recombinant hepatitis B surface antigen was preserved for at least 14 days, when stored as an aqueous suspension, and for at least 3 months when converted in a freeze-dried powder. CONCLUSION: Poly(D,L,lactic-co-glycolic acid)-based nanoparticles represent a promising approach for the delivery of virus-like-particles. PMID- 20735222 TI - Amphiphilic curcumin conjugate-forming nanoparticles as anticancer prodrug and drug carriers: in vitro and in vivo effects. AB - Curcumin has been shown to have high cytotoxicity towards various cancer cell lines, but its water insolubility and instability make its bioavailability exceedingly low and, thus, it is generally inactive in in vivo anticancer tests. Here, we report an intracellular-labile amphiphilic surfactant-like curcumin prodrug--curcumin conjugated with two short oligo(ethylene glycol) (Curc-OEG) chains via beta-thioester bonds that are labile in the presence of intracellular glutathione and esterase. Curc-OEG formed stable nanoparticles in aqueous conditions and served two roles--as an anticancer prodrug and a drug carrier. As an anticancer prodrug, the formed nanoparticles had a high and fixed curcumin loading content of 25.3 wt%, and released active curcumin in the intracellular environment. Curc-OEG had high inhibition ability to several cancer cell lines due to apoptosis. Intravenously injected Curc-OEG significantly reduced the tumor weights and tumor numbers in the athymic mice xenografted with intraperitoneal SKOV-3 tumors and subcutaneous (mammary fat pad) MDA-MB-468 tumors. Preliminary systemic toxicity studies found that Curc-OEG did not cause acute and subchronic toxicities to mouse visceral organs at high doses. As drug carriers, Curc-OEG nanoparticles could carry other anticancer drugs, such as doxorubicin and camptothecin, and ship them into drug-resistant cells, greatly enhancing the cytotoxicity of the loaded drug. Thus, Curc-OEG is a promising prototype that merits further study for cancer therapy. PMID- 20735223 TI - Intracellular drug delivery by genetically engineered high-density lipoprotein nanoparticles. AB - AIM: Nascent high-density lipoprotein (HDL) capable of intracellularly delivering anticancer drugs was developed to potentiate antitumor activities. MATERIALS & METHODS: Apolipoprotein A-I, a major component protein of HDL, was genetically fused to TAT peptide, a protein transduction domain. Nascent HDL was prepared with this mutant and phospholipids. RESULTS & DISCUSSION: Intracellular delivery of doxorubicin (DXR) by TAT-fused HDL was confirmed by confocal microscopy. Treatment of cancer cells with TAT-fused HDL-DXR complex resulted in enhanced growth inhibition. Furthermore, TAT-fused HDL-DXR complex suppressed tumor growth in mice more efficiently than HDL-DXR complex. No bodyweight loss was observed for the TAT complex. These results clearly demonstrate the usefulness of TAT fusion to nascent HDL to potentiate the antitumor activity of DXR. CONCLUSION: The genetic fusion of apoA-I with biologically active peptides potentially enables a simple assembly of biocompatible and versatile drug carriers. PMID- 20735224 TI - Procoagulant properties of bare and highly PEGylated vinyl-modified silica nanoparticles. AB - AIMS: Undesired alterations of the blood clotting balance may follow the intravascular injection of nanotherapeutics/diagnostics. Here, we tested the procoagulant activity of synthetic amorphous silica (SAS) and organically modified silica (ORMOSIL) nanoparticles (NPs) and whether a high-density polyethylene glycol coating minimizes these effects. MATERIALS & METHODS: Hageman factor- and tissue factor-dependent activation of human blood/plasma coagulation, and binding to human monocytes, endothelial cells and platelets were quantified in vitro using naked and PEGylated ORMOSIL-NPs. Their effects were compared with those of SAS-NPs, present in many industrial products, and of poly(lactic-co glycolic acid)- and small unilamellar vesicles-NPs, already approved for use in humans. RESULTS: Both SAS-NPs and ORMOSIL-NPS presented a significant procoagulant activity. However, highly PEGylated ORMOSIL-NPs were particularly averse to the interaction with the soluble factors and cellular elements that may lead to intravascular blood coagulation. CONCLUSION: Stealth, highly PEGylated ORMOSIL-NPs with a poor procoagulant activity can be used as starting blocks to design hemocompatible nanomedical-devices. PMID- 20735225 TI - Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide. AB - BACKGROUND & AIMS: Gold nanoparticles (GNPs) have promising applications for drug delivery as well as for the diagnosis and treatment of several pathologies, such as those related to the CNS. However, GNPs are retained in a number of organs, such as the liver and spleen. Owing to their negative charge and/or processes of opsonization, GNPs are retained by the reticuloendothelial system, thereby decreasing their delivery to the brain. It is therefore crucial to modify the nanoparticle surface in order to increase its lipophilicity and reduce its negative charge, thus achieving enhanced delivery to the brain. RESULTS: In this article, we have shown that conjugation of 12 nm GNPs with the amphipathic peptide CLPFFD increases the in vivo penetration of these particles to the rat brain. The C(GNP)-LPFFD conjugates showed a smaller negative charge and a greater hydrophobic character than citrate-capped GNPs of the same size. We administered intraperitoneal injections of citrate GNPs and C(GNP)-LPFFD in rats, and determined the gold content in the tissues by neutron activation. Compared with citrate GNPs, the C(GNP)-LPFFD conjugate improved the delivery to the brain, increasing the concentration of gold by fourfold, while simultaneously reducing its retention by the spleen 1 and 2 h after injection. At 24 h, the conjugate was partially cleared from the brain, and mainly accumulated in the liver. The C(GNP) LPFFD did not alter the integrity of the blood-brain barrier, and had no effect on cell viability. PMID- 20735226 TI - Polymer-drug conjugates for novel molecular targets. AB - Polymer therapeutics can be already considered as a promising field in the human healthcare context. The discovery of the enhanced permeability and retention effect by Maeda, together with the modular model for the polymer-drug conjugate proposed by Ringsdorf, directed the early steps of polymer therapeutics towards cancer therapy. Orthodox anticancer drugs were preferentially chosen in the development of the first conjugates. The fast evolution of polymer chemistry and bioconjugation techniques, and a deeper understanding of cell biology has opened up exciting new challenges and opportunities. Four main directions have to be considered to develop this 'platform technology' further: the control of the synthetic process, the exhaustive characterization of the conjugate architectures, the conquest of combination therapy and the disclosure of new therapeutic targets. We illustrate in this article the exciting approaches offered by polymer-drug conjugates beyond classical cancer therapy, focusing on new, more effective and selective targets in cancer and in their use as treatments for other major human diseases. PMID- 20735227 TI - Cell interaction with nanopatterned surface of implants. AB - Metals such as titanium and alloys are commonly used for manufacturing orthopedic and dental implants because their surface properties provide a biocompatible interface with peri-implant tissues. Strategies for modifying the nature of this interface frequently involve changes to the surface at the nanometer level, thereby affecting protein adsorption, cell-substrate interactions and tissue development. Recent methods to control these biological interactions at the nanometer scale on the surface of implants are reviewed. Future strategies to control peri-implant tissue healing are also discussed. PMID- 20735228 TI - Introduction to the special focus issue: environmental toxicity of nanoparticles. Foreword. PMID- 20735229 TI - Chronic toxicity of double-walled carbon nanotubes to three marine organisms: influence of different dispersion methods. AB - AIM: Double-walled carbon nanotubes (DWNTs) are found in a variety of consumer products, but there are no ecotoxicity data of DWNTs into marine organisms. MATERIALS & METHODS: Chronic toxicity of DWNTs was investigated with the diatom Thalassiosira pseudonana, copepod Tigriopus japonicus and medaka Oryzias melastigma. DWNTs were dispersed using sonication (so-DWNTs) and stirring (st DWNTs) for comparison. RESULTS: The median aggregation size (0.89 microm(2)) of so-DWNTs was smaller than that of st-DWNTs (21.8 microm(2)). Exposure to DWNTs led to growth inhibition of T. pseudonana with EC(50)s of 1.86 and 22.7 mg/l for so- and st-DWNTs, respectively. Population growth of T. japonicus was reduced to 0.1 mg/l for so-DWNTs and 10 mg/l for st-DWNTs. Growth inhibition in O. melastigma was observed at 10 mg/l for so-DWNTs but not for st-DWNTs. CONCLUSION: Given that so-DWNTs are consistently significantly more toxic than st-DWNTs, dispersion method and size of aggregations should be considered in DWNT toxicity testing. PMID- 20735230 TI - Carbon nanotube ecotoxicity in amphibians: assessment of multiwalled carbon nanotubes and comparison with double-walled carbon nanotubes. AB - The potential impact of industrial multiwalled carbon nanotubes (MWNTs) was investigated under normalized laboratory conditions according to the International Standard micronucleus assay ISO 21427-1 for 12 days of half-static exposure to 0.1, 1, 10 and 50 mg/l of MWNTs in water. Three different end points were carried out for 12 days of exposure: mortality, growth inhibition and micronuclei induction in erythrocytes of the circulating blood of larvae. Raman spectroscopy analysis was used to study the presence of carbon nanotubes in the biological samples. Considering the high diversity of carbon nanotubes according to their different characteristics, MWNTs were analyzed in Xenopus larvae, comparatively to double-walled carbon nanotubes used in a previous study in similar conditions. Growth inhibition in larvae exposed to 50 mg/l of MWNTs was evidenced; however, no genetoxicity (micronucleus assay) was noticed, at any concentration. Carbon nanotube localization in the larvae leads to different possible hypothesis of mechanisms explaining toxicity in Xenopus. PMID- 20735231 TI - Silver nanoparticle exposure causes apoptotic response in the earthworm Lumbricus terrestris (Oligochaeta). AB - In terrestrial ecotoxicology there is a serious lack of data for potential hazards posed by engineered nanoparticles (ENPs). This is partly due to complex interactions between ENPs and the soil matrix, but also to the lack of suitable toxicological end points in organisms that are exposed to ENPs in a relevant manner. Earthworms are key organisms in terrestrial ecosystems, but so far only physiological end points of low sensitivity have been used in ecotoxicity studies with ENPs. We exposed the earthworm Lumbricus terrestris to silver nanoparticles and measured their impact on apoptosis in different tissues. Increased apoptotic activity was detected in a range of tissues both at acute and sublethal concentrations (down to 4 mg/kg soil). Comparing exposure in water and soil showed reduced bioavailability in soil reflected in the apoptotic response. Apoptosis appears to be a sensitive end point and potentially a powerful tool for quantifying environmental hazards of ENPs. PMID- 20735232 TI - Stability of nanoparticles in water. AB - Aqueous systems represent a likely carrier for manufactured nanoparticles upon their introduction into the natural environment. Their behavior in water, and in turn the risk that is posed by these materials to environmental and human communities, is a top concern. In terms of risk assessment, nanoparticle exposure to organisms is largely driven by their dispersion and behavior in aqueous systems, while their potential hazard, although not always well understood, is often related to their surface speciation. Both of these characteristics arise from the reactions that occur at the solid/liquid interface. The objective of this article is to establish the current state of the science with regard to the possible changes in surface properties and/or behavior of manufactured nanoparticles in different aqueous solutions of model and inorganic composition. The general reactions occurring at the nanoparticle/water interface, or between nanoparticles themselves, are first introduced. Following this, metal oxides, pure metals and carbon nanoparticles are considered on a case-by-case basis. PMID- 20735233 TI - Inorganic manufactured nanoparticles: how their physicochemical properties influence their biological effects in aqueous environments. AB - Among all environmental contaminants, those emerging from nanotechnologies constitute one of the most critical challenges for the coming years. The new properties of nanoparticles are at the heart of current scientific advances and the growing interest in harnessing them brings awareness of potential impacts that we cannot ignore. To date, scientists and industrialists have focused on the manufacture of nanomaterials more than on the assessment of the risks for humans and ecosystems. Few databases exist regarding the amounts released within ecosystems and no specific procedure of recycling has yet been established. However, nanoparticles cannot be considered as molecular pollutants or larger particles, and careful consideration is needed to establish a legal system that is specific. Their novel properties, surface energy and reactivity make it impossible to simply transfer our physicochemical, thermodynamic and toxicological knowledge from the micronscale to the nanoscale. This article highlights, nonexhaustively, the strong relationship existing between the unique properties of metallic and metal oxide nanoparticles and their biological effects on aquatic organisms. PMID- 20735234 TI - Considerations in evaluating the physicochemical properties and transformations of inorganic nanoparticles in water. AB - Nanomaterials and the technologies they enable are often presented as important innovations that will play a critical role in solving problems that range from energy, water and food supply to improved medical treatments. Ironically, many of the more 'media-genic' nanomaterial-enabled products making their way to consumers address considerably more humble objectives, such as making socks cleaner or reducing wrinkles. This very broad range of nanomaterial applications suggests an equally broad range of scenarios for nanomaterial use, incorporation into products and disposal, which characterizes the lifecycle of these novel materials. Nanomaterials introduced to environmental and physiological systems will most likely undergo significant transformations, complicating any effort to related underlying nanoparticle with observed effects. This article discusses several dimensions of nanoparticle reactivity and the potential for environmental transformation of the nanoparticle properties, in particular focusing on metallic nanoparticles. PMID- 20735236 TI - Pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV inhibitor after oral administration in rats. AB - The pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV (DPP IV) inhibitor, was studied in rats after oral administration for developing it as an antidiabetic agent. A liquid chromatography-tandem mass spectroscopy (LC MS/MS) method was developed to determine lipoyl vildagliptin in rat plasma. After an overnight fasting, rats were orally given lipoyl vildagliptin. Following a single oral dose of 25, 50, and 100 mg x kg(-1), T(max) values were from 1.25 to 1.84 h, CL/F values were around 100 l h(-1) kg(-1). In the dose range, C(max) values (63.9-296 MUg x l(-1)) and AUC(0-infinity)values (260-1214 MUg x h x l( 1)) were proportional to the doses. In conclusion, this LC-MS/MS method for the determination of lipoyl vildagliptin in rat plasma was selective and sensitive. In rats, lipoyl vildagliptin displayed linear pharmacokinetics after a single oral dose in the range of 25-100 mg x kg(-1). Lipoyl vildagliptin might have very high CL/F values and V(d)/F values, which indicated that the bioavailability of this drug might be low or lipoyl vildagliptin might distribute extensively or accumulate in tissues in view of its high liposolubility. PMID- 20735237 TI - Decoding the histone H4 lysine 20 methylation mark. AB - The molecular biology of histone H4 lysine 20 (H4K20) methylation, like many other post-translational modifications of histones, has been the subject of intensive interest in recent years. While there is an emerging consensus linking H4K20me1, H4K20me2, and H4K20me3 to transcription, repair, and constitutive heterochromatin, respectively, the specific details of these associations and the biological mechanisms by which the methylated histones are introduced and function are now the subject of active investigation. Although a large number of methylases capable of methylating H4K20 have been identified and characterized; there is no known demethylase of H4K20, though the search is ongoing. Additionally, many recent studies have been directed at understanding the role of methylated H4K20 and other histone modifications associated with different biological processes in the context of a combinatorial histone code. It seems likely that continued study of the methylation of H4K20 will yield extremely valuable insights concerning the regulation of histone modifications before and during cell division and the impact of these modifications on subsequent gene expression. PMID- 20735238 TI - Iatrogenic transmission of human T cell lymphotropic virus type 1 and hepatitis C virus through parenteral treatment and chemoprophylaxis of sleeping sickness in colonial Equatorial Africa. AB - BACKGROUND: The simultaneous emergence of human immunodeficiency virus (HIV)-1 group M and HIV-2 into human populations, circa 1921-1940, is attributed to urbanization and changes in sexual behavior. We hypothesized that the initial dissemination of HIV-1, before sexual transmission predominated, was facilitated by the administration, via reusable syringes and needles, of parenteral drugs against tropical diseases. As proxies for highly lethal HIV-1, we investigated risk factors for hepatitis C virus (HCV) and human T cell lymphotropic virus 1 (HTLV-1) infections, blood-borne viruses compatible with prolonged survival, in an area known in 1936-1950 as the most virulent focus of African trypanosomiasis. METHODS: Cross-sectional survey of individuals 55 years and older in Mbimou land and Nola, Central African Republic. Dried blood spots were used for HCV and HTLV 1 serologic testing and nucleic acid detection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were measured by logistic regression. RESULTS: The only risk factor for HCV genotype 4 infection was treatment of trypanosomiasis before 1951 (OR, 3.13; 95% CI, 1.38-7.09). HTLV-1 infection was associated with having received 2 injections of pentamidine for trypanosomiasis chemoprophylaxis (adjusted OR, 2.03; 95% CI, 1.01-4.06) and with transfusions (adjusted OR, 2.82; 95% CI, 1.04-7.67). From historical data, we predicted that 59% of Mbimous 65 years and older would report treatment for trypanosomiasis before 1951; only 11% did so. CONCLUSIONS: Treatment of trypanosomiasis before 1951 may have caused iatrogenic HCV transmission. Population-wide half-yearly intramuscular pentamidine for trypanosomiasis chemoprophylaxis in 1947-1953 may have caused iatrogenic HTLV-1 transmission. These and other interventions against tropical diseases could have iatrogenically transmitted SIV(cpz), jump-starting the HIV-1 epidemic. The excess mortality among patients with trypanosomiasis treated before 1951 supports this hypothesis. PMID- 20735239 TI - Undiagnosed active tuberculosis in HIV-infected patients commencing antiretroviral therapy. PMID- 20735240 TI - Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. AB - BACKGROUND: The World Health Organization (WHO) recommends cough as the trigger for tuberculosis screening in human immunodeficiency virus (HIV)-infected patients, with acid-fast bacillus (AFB) smear as the initial diagnostic test. Our objective was to assess the yield and cost of a more intensive tuberculosis screening in HIV-infected patients starting antiretroviral therapy (ART) in Durban, South Africa. METHODS: We prospectively enrolled adults, regardless of tuberculosis signs/symptoms, who were undergoing ART training from May 2007 to May 2008. After the symptom screen, patients expectorated sputum for AFB smear, tuberculosis polymerase chain reaction (PCR), and mycobacterial culture. Sensitivity and specificity of different symptoms and tests, alone and in combination, were compared with the reference standard of 6-week tuberculosis culture results. Program costs included personnel, materials, and cultures. RESULTS: Of 1035 subjects, 487 (59%) were female; median CD4 cell count was 100 cells/microL. A total of 210 subjects (20%) were receiving tuberculosis treatment and were excluded. Of the remaining 825 subjects, 158 (19%) had positive sputum cultures, of whom 14 (9%) had a positive AFB smear and 82 (52%) reported cough. The combination of cough, other symptoms, AFB smear, and chest radiograph had 93% sensitivity (95% confidence interval, 88%-97%) and 15% specificity (95% confidence interval, 13%-18%). The incremental cost of intensive screening including culture was $360 per additional tuberculosis case identified. CONCLUSIONS: Nearly 20% of patients starting ART in Durban, South Africa, had undiagnosed, culture-positive pulmonary tuberculosis. Despite WHO recommendations, neither cough nor AFB smear were adequately sensitive for screening. Tuberculosis sputum cultures should be performed before ART initiation, regardless of symptoms, in areas with a high prevalence of HIV and tuberculosis. PMID- 20735241 TI - An epidemic of hepatitis C virus infection while treating endemic infectious diseases in Equatorial Africa more than a half century ago: did it also jump start the AIDS pandemic? PMID- 20735243 TI - Social media and population-based care management. PMID- 20735242 TI - Risk factors for hepatitis C virus transmission in colonial Cameroon. AB - BACKGROUND: In southern Cameroon, where SIV(cpz), the source of human immunodeficiency virus 1 (HIV-1) group M, is prevalent among wild chimpanzees, approximately 50% of some human birth cohorts have been infected with hepatitis C virus (HCV) through unclear mechanisms. METHODS: To evaluate indirectly the hypothesis that medical interventions contributed to the early emergence of HIV 1, we conducted a cross-sectional study of 451 inhabitants of Ebolowa in southern Cameroon aged 60 years, using HCV as a marker of parenteral transmission of blood borne viruses. We administered a questionnaire and tested serum for antibodies against HCV. Viral gene sequences were obtained from HCV-positive sera. Molecular clock analyses provided an independent source of information on epidemic history. RESULTS: A total of 252 participants (56%) were HCV seropositive. HCV sequences were amplified and genotyped from 171 individuals. Independent risk factors for HCV seropositivity were older age, having received intravenous treatment against malaria, and having attended an ethnic school (women only), whereas having been circumcised by a traditional practitioner (men only) tended to be associated with HCV. In addition, transfusions were associated with HCV genotype 1 transmission. Molecular clock analyses of HCV genotypes 1, 2, and 4 revealed that each independently underwent exponential growth during the first half of the 20th century. CONCLUSIONS: Medical interventions (intravenous antimalarial drugs, transfusions) and to a lesser extent traditional practices (circumcision) were associated with the massive transmission of HCV among this population decades ago. This finding supports the hypothesis that medical interventions contributed to the transmission of blood-borne viruses, perhaps including SIV(cpz) and HIV-1, in the same region during the early 20th century. PMID- 20735244 TI - Is the United States ready to embrace concierge medicine? AB - Concierge medicine (also called retainer practices or consumer-focused care) represents a new approach to the delivery of primary care. This model involves more personalized attention and greater resources for individual patients, thus limiting the number of patients who can be served at each practice. All enrolled members must pay an annual membership fee or retainer. Given the short history and novelty of concierge medicine, this article explores the clinical, economic, marketing, ethical, and policy implications of this innovative approach to primary care. PMID- 20735245 TI - National estimates of enrollment in disease management programs in the United States: an analysis of the National Ambulatory Medical Care Survey data. AB - Disease management (DM) programs have demonstrated improvement in clinical and economic outcomes for patients with chronic conditions; however, the extent of utilization of these programs in the United States is not known. The rate of enrollment in DM programs was estimated using data from the National Ambulatory Medical Care Survey (NAMCS). Logistic regression analysis was used to identify predictors of enrollment in DM programs. The complex sampling design of the NAMCS was accounted in all analyses. The final study sample included 14,405 patient visits and indicated that only 21.3% of patients with at least 1 chronic condition utilize DM programs. Regression analysis demonstrated that patients who visit specialty physicians (excluding internal medicine) are more likely to be enrolled in a DM program than patients who visit general medicine/family practice physicians (P < 0.01). Patients with depression, diabetes, hyperlipidemia, or obesity were significantly more likely to be enrolled in a DM program than patients without these chronic conditions. Enrollment in a DM program was also affected by the total number of chronic conditions--patients with 2-4 chronic conditions were 1.29 times more likely to be enrolled in a DM program than patients with a single chronic condition (P = 0.026). In conclusion, although benefits of DM programs have been documented, their adoption rate remains extremely low. Additional studies are needed to identify other predictors and to tailor interventions to increase the adoption of such programs. PMID- 20735246 TI - Pharmacist counseling at the start of therapy: patient receptivity to offers of in-person and subsequent telephonic clinical support. AB - Patients who newly start prescription medications for chronic conditions are often in need of additional support related to both their condition and treatment. When patients initially fill their prescriptions, the offer of pharmacist counseling is considered standard practice from a professional and regulatory standpoint, but little is known about how well this offer actually satisfies patient needs. This was the focus of our study: Within a few weeks of newly starting medications, 100 patients were contacted telephonically by a nurse to engage them in a support program for their conditions. During those calls, the nurse used a brief questionnaire to determine each patient's recollection of the offer of local community pharmacist counseling at the time that they filled their prescription, and their current receptivity to immediate telephonic pharmacist support. Fifty-eight percent of patients did not recall being offered counseling at their local community pharmacy, and 11% declined the offer at that time, yielding 69% of patients who did not receive local pharmacist counseling when filling their initial prescription. An additional 12% (39% of patients counseled) were not satisfied with the information received. Among the 81% of surveyed patients who did not receive counseling or were dissatisfied with the counseling they did receive, 75% accepted the offer of telephonic support by a specialist pharmacist. Our findings suggest that many patients with chronic conditions have a need and a desire for pharmacist counseling about new medications that is unmet in the local community pharmacy setting. Telephonic pharmacist support can help address this need if offered within weeks of the new prescription. PMID- 20735247 TI - Acute care for the elderly: a literature review. AB - Traditionally, acute medical care has been insufficient to meet the complex care needs of frail older adults. The purpose of this study was to evaluate the effectiveness of Acute Care for the Elderly (ACE) units at improving hospitalization outcomes for adults older than 65 years of age. A review of the literature was performed, focusing on randomized controlled trials, clinical trials, reviews, and meta-analyses from 1990 to 2008. This review revealed ACE to be associated with positive global outcomes (eg, cost, length of stay, readmission rates, utilization, rehabilitation, cognition, function, patient/staff satisfaction). Furthermore, some studies may point to a decreased incidence of delirium and polypharmacy. Though larger studies with consistent operational definitions and replicative studies are needed, the literature presents compelling evidence that warrants further investigation of ACE as a valuable alternative paradigm of acute geriatric care. PMID- 20735248 TI - Virus silicification under simulated hot spring conditions. AB - Silicification of organisms in silica-depositing environments can impact both their ecology and their presence in the fossil record. Although microbes have been silicified under laboratory and environmental conditions, viruses have not. Bacteriophage T4 was successfully silicified under laboratory conditions that closely simulated those found in silica-depositing hot springs. Virus morphology was maintained, and a clear elemental signature of phosphorus was detected by energy-dispersive X-ray spectrophotometry (EDS). PMID- 20735249 TI - Astrobiological benefits of human space exploration. AB - An ambitious program of human space exploration, such as that envisaged in the Global Exploration Strategy and considered in the Augustine Commission report, will help advance the core aims of astrobiology in multiple ways. In particular, a human exploration program will confer significant benefits in the following areas: (i) the exploitation of the lunar geological record to elucidate conditions on early Earth; (ii) the detailed study of near-Earth objects for clues relating to the formation of the Solar System; (iii) the search for evidence of past or present life on Mars; (iv) the provision of a heavy-lift launch capacity that will facilitate exploration of the outer Solar System; and (v) the construction and maintenance of sophisticated space-based astronomical tools for the study of extrasolar planetary systems. In all these areas a human presence in space, and especially on planetary surfaces, will yield a net scientific benefit over what can plausibly be achieved by autonomous robotic systems. A number of policy implications follow from these conclusions, which are also briefly considered. PMID- 20735250 TI - Organics on Mars? AB - Organics are expected to exist on Mars based on meteorite infall, in situ production, and any possible biological sources. Yet they have not been detected on the martian surface; are they there, or are we not capable enough to detect them? The Viking gas chromatograph-mass spectrometer did not detect organics in the headspace of heated soil samples with a detection limit of parts per billion. This null result strongly influenced the interpretation of the reactivity seen in the Viking biology experiments and led to the conclusion that life was not present and, instead, that there was some chemical reactivity in the soil. The detection of perchlorates in the martian soil by instruments on the Phoenix lander and the reports of methane in the martian atmosphere suggest that it may be time to reconsider the question of organics. The high-temperature oxidizing properties of perchlorate will promote combustion of organics in pyrolytic experiments and may have affected the ability of both Phoenix's organic analysis experiment and the Viking mass spectrometer experiments to detect organics. So the question of organics on Mars remains open. A primary focus of the upcoming Mars Science Laboratory will be the detection and identification of organic molecules by means of thermal volatilization, followed by gas chromatography-mass spectrometry--as was done on Viking. However, to enhance organic detectability, some of the samples will be processed with liquid derivatization agents that will dissolve organics from the soil before pyrolysis, which may separate them from the soil perchlorates. Nonetheless, the problem of organics on Mars is not solved, and for future missions other organic detection techniques should therefore be considered as well. PMID- 20735251 TI - Adaptation of Bacillus subtilis cells to Archean-like UV climate: relevant hints of microbial evolution to remarkably increased radiation resistance. AB - In a precursory study for the space experiment ADAPT ("Molecular adaptation strategies of microorganisms to different space and planetary UV climate conditions"), cells of Bacillus subtilis 168 were continuously cultured for 700 generations under periodic polychromatic UV irradiation (200-400 nm) to model the suggested UV radiation environment on early Earth at the origin of the first microbial ecosystem during the Archean eon when Earth lacked a significant ozone layer. Populations that evolved under UV stress were about 3-fold more resistant than the ancestral and non-UV-evolved populations. UV-evolved cells were 7-fold more resistant to ionizing radiation than their non-UV-exposed evolved relatives and ancestor. In addition to the acquired increased UV resistance, further changes in microbial stress response to hydrogen peroxide, increased salinity, and desiccation were observed in UV-evolved cells. This indicates that UV sensitive ancestral cells are capable of adapting to periodically applied UV stress via the evolution of cells with an increased UV resistance level and further enhanced responses to other environmental stressors, which thereby allows them to survive and reproduce under extreme UV radiation as a selection pressure. PMID- 20735252 TI - Hygroscopic salts and the potential for life on Mars. AB - Hygroscopic salts have been detected in soils in the northern latitudes of Mars, and widespread chloride-bearing evaporitic deposits have been detected in the southern highlands. The deliquescence of hygroscopic minerals such as chloride salts could provide a local and transient source of liquid water that would be available for microorganisms on the surface. This is known to occur in the Atacama Desert, where massive halite evaporites have become a habitat for photosynthetic and heterotrophic microorganisms that take advantage of the deliquescence of the salt at certain relative humidity (RH) levels. We modeled the climate conditions (RH and temperature) in a region on Mars with chloride bearing evaporites, and modeled the evolution of the water activity (a(w)) of the deliquescence solutions of three possible chloride salts (sodium chloride, calcium chloride, and magnesium chloride) as a function of temperature. We also studied the water absorption properties of the same salts as a function of RH. Our climate model results show that the RH in the region with chloride-bearing deposits on Mars often reaches the deliquescence points of all three salts, and the temperature reaches levels above their eutectic points seasonally, in the course of a martian year. The a(w) of the deliquescence solutions increases with decreasing temperature due mainly to the precipitation of unstable phases, which removes ions from the solution. The deliquescence of sodium chloride results in transient solutions with a(w) compatible with growth of terrestrial microorganisms down to 252 K, whereas for calcium chloride and magnesium chloride it results in solutions with a(w) below the known limits for growth at all temperatures. However, taking the limits of a(w) used to define special regions on Mars, the deliquescence of calcium chloride deposits would allow for the propagation of terrestrial microorganisms at temperatures between 265 and 253 K, and for metabolic activity (no growth) at temperatures between 253 and 233 K. PMID- 20735253 TI - The use of surface-enhanced Raman scattering for detecting molecular evidence of life in rocks, sediments, and sedimentary deposits. AB - Raman spectroscopy is a versatile analytical technique capable of characterizing the composition of both inorganic and organic materials. Consequently, it is frequently suggested as a payload on many planetary landers. Only approximately 1 in every 10(6) photons are Raman scattered; therefore, the detection of trace quantities of an analyte dispersed in a sample matrix can be much harder to achieve. To overcome this, surface-enhanced Raman scattering (SERS) and surface enhanced resonance Raman scattering (SERRS) both provide greatly enhanced signals (enhancements between 10(5) and 10(9)) through the analyte's interaction with the locally generated surface plasmons, which occur at a "roughened" or nanostructured metallic surface (e.g., Cu, Au, and Ag). Both SERS and SERRS may therefore provide a viable technique for trace analysis of samples. In this paper, we describe the development of SERS assays for analyzing trace amounts of compounds present in the solvent extracts of sedimentary deposits. These assays were used to detect biological pigments present in an Arctic microoasis (a small locale of elevated biological productivity) and its detrital regolith, characterize the pigmentation of microbial mats around hydrothermal springs, and detect fossil organic matter in hydrothermal deposits. These field study examples demonstrate that SERS technology is sufficiently mature to be applied to many astrobiological analog studies on Earth. Many current and proposed imaging systems intended for remote deployment already posses the instrumental components needed for SERS. The addition of wet chemistry sample processing facilities to these instruments could yield field-deployable analytical instruments with a broadened analytical window for detecting organic compounds with a biological or geological origin. PMID- 20735254 TI - Dynamic temperature fields under Mars landing sites and implications for supporting microbial life. AB - While average temperatures on Mars may be too low to support terrestrial life forms or aqueous liquids, diurnal peak temperatures over most of the planet can be high enough to provide for both, down to a few centimeters beneath the surface for some fraction of the time. A thermal model was applied to the Viking 1, Viking 2, Pathfinder, Spirit, and Opportunity landing sites to demonstrate the dynamic temperature fields under the surface at these well-characterized locations. A benchmark temperature of 253 K was used as a lower limit for possible metabolic activity, which corresponds to the minimum found for specific terrestrial microorganisms. Aqueous solutions of salts known to exist on Mars can provide liquid solutions well below this temperature. Thermal modeling has shown that 253 K is reached beneath the surface at diurnal peak heating for at least some parts of the year at each of these landing sites. Within 40 degrees of the equator, 253 K beneath the surface should occur for at least some fraction of the year; and, within 20 degrees , it will be seen for most of the year. However, any life-form that requires this temperature to thrive must also endure daily excursions to far colder temperatures as well as periods of the year where 253 K is never reached at all. PMID- 20735255 TI - An experimental investigation of the evolution of chirality in a potential dynamic peptide system: N-terminal epimerization and degradation into diketopiperazine. AB - The APED model (activation-polymerization-epimerization-depolymerization) is a unique example of a chemical system that allows symmetry breaking through a dynamic process involving indirect network autocatalysis. In its simplest version, the autocatalytic behavior of this model partly relies on the reproduction of local chiral centers in dipeptides through an epimerization process, with a thermodynamic preference for homochiral chains. We studied the reactivity of di- and tripeptides, containing a N-terminal phenylglycine (Phg) residue, as model compounds for the experimental determination of the kinetic and thermodynamic parameters related to the N-terminal epimerization process. Although the N-terminal residue is prone to spontaneous epimerization, catalysis was required for the epimerization to reach the equilibrium state in reasonable time. Unexpectedly, the observed equilibrium diastereoisomeric excesses have shown a general tendency for more stable heterochiral peptides, especially strong in the case of dipeptides. In parallel to this process, a stereoselective peptide cleavage through diketopiperazine formation was observed. Contrary to the N terminal epimerization of peptides, the diketopiperazine formation did not need any catalyst, and heterochiral peptides were shown to be dynamically unstabilized, as they were cleaved faster than homochiral peptides. The validity of the extrapolation of these results to other residues and longer peptide chains is discussed, and some directions for future developments of the theoretical model are given. PMID- 20735256 TI - alpha-Fetoprotein gene delivery to the nasal epithelium of nonhuman primates by human parainfluenza viral vectors. AB - Over the last two decades, enormous effort has been focused on developing virus based gene delivery vectors to target the respiratory airway epithelium as a potential treatment for cystic fibrosis (CF) lung disease. However, amongst other problems, the efficiency of gene delivery to the differentiated airway epithelial cells of the lung has been too low for clinical benefit. Although not a target for CF therapy, the nasal epithelium exhibits cellular morphology and composition similar to that of the lower airways, thus representing an accessible and relevant tissue target for evaluating novel and improved gene delivery vectors. We previously reported that replication-competent human parainfluenza virus (PIV) based vectors efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to sufficient numbers of cultured CF airway epithelial cells to completely correct the bioelectric function of CF cells to normal levels, resulting in restoration of mucus transport. Here, using an in vitro model of rhesus airway epithelium, we demonstrate that PIV mediates efficient gene transfer in rhesus epithelium as in the human counterpart. Naive rhesus macaques were inoculated intranasally with a PIV vector expressing rhesus macaque alpha fetoprotein (rhAFP), and expression was monitored longitudinally. rhAFP was detected in nasal lavage fluid and in serum samples, indicating that PIV-mediated gene transfer was effective and that rhAFP was secreted into both mucosal and serosal compartments. Although expression was transient, lasting up to 10 days, it paralleled virus replication, suggesting that as PIV was cleared, rhAFP expression was lost. No adverse reactions or signs of discomfort were noted, and only mild, transient elevations of a small number of inflammatory cytokines were measured at the peak of virus replication. In summary, rhAFP proved suitable for monitoring in vivo gene delivery over time, and PIV vectors appear to be promising airway-specific gene transfer vehicles that warrant further development. PMID- 20735257 TI - Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells. AB - Neural stem cells (NSCs) have the potential to integrate seamlessly into the host tissues, and the development of potential stem cells resistant to stress injury is an elusive goal for efficient therapeutic application. Oxidative injury induces cellular and nuclear damages and the balanced regulation of reactive oxygen species is of critical significance for stem cell development, function, and survival. Agmatine, an endogenous primary amine and a novel neuromodulator synthesized from the decarboxylation of l-arginine catalyzed by arginine decarboxylase (ADC), has been reported to possess neuroprotective properties. In the present study, we determined whether the expression of ADC in NSCs can prevent the cells from oxidative injury. Retrovirus expressing human (ADC), (vhADC) was generated using a pLXSN vector. Cortical NSCs were infected with vhADC and subjected to H2O2 injury (200 MUM for 15 h). Reverse transcriptase polymerase chain reaction and immunocytochemical staining revealed that hADC mRNA and protein were highly expressed in the vhADC-infected NSCs (ADC-NSCs). High performance liquid chromatography (HPLC) analysis confirmed high concentration of agmatine in the ADC-NSCs, when exposed to H2O2 injury. Lactate dehydrogenase leakage and intracellular reactive oxygen species formation were about 2-fold reduced in ADC-NSCs when compared with control NSCs and NSCs infected with mock vector (P < 0.05). DNA fragmentation, chromatin condensation, and expression of apoptotic proteins such as p53, bax, and caspase-3 cleavage were significantly decreased in ADC-NSCs (P < 0.05), suggesting the prevention of apoptotic cell death following H2O2 injury. Our study demonstrates that overexpression of ADC is an effective novel approach to protect stem cells from oxidative damage. PMID- 20735259 TI - Allometric scaling of metabolism, growth, and activity in whole colonies of the seed-harvester ant Pogonomyrmex californicus. AB - The negative allometric scaling of metabolic rate with body size is among the most striking patterns in biology. We investigated whether this pattern extends to physically independent eusocial systems by measuring the metabolic rates of whole functioning colonies of the seed-harvester ant Pogonomyrmex californicus. These intraspecific scaling data were compared to the predictions of an additive model developed to estimate collective metabolic rates. Contrary to the prediction of the additive model, colony metabolic rate allometry resembled the pattern commonly observed interspecifically for individual organisms, scaling with colony mass(0.75). Among the same-aged colonies, net growth rate varied by up to sevenfold, with larger colonies exhibiting higher net growth efficiency than smaller colonies. Isolated worker groups exhibited isometric metabolic rate scaling, suggesting that the social environment of the colony is critical to regulating individual patterns of work output. Within the social environment, individual worker locomotor velocities exhibited power-law distributions that scaled with colony size so that larger colonies exhibited a greater disparity between active and inactive ants than did smaller colonies. These results demonstrate that behavioral organization within colonies may have a major influence on colony-level metabolism and in generating intraspecific variation in growth trajectories. PMID- 20735260 TI - Bighorn ewes transfer the costs of reproduction to their lambs. AB - Several studies of large mammals report no direct reproductive costs for females. Individual heterogeneity may hide fitness costs of reproduction, but mothers could also transfer some costs to their offspring. Using data on 442 lambs weaned by 146 bighorn sheep (Ovis canadensis) ewes at Ram Mountain, Alberta, we studied how reproductive effort varied with environmental and maternal conditions. During summer, lactating ewes should gain enough mass to survive the winter and to support their next gestation, while nursing their current lamb. We measured reproductive effort as summer mass gain by lambs corrected for maternal mass in June and maternal mass gain during summer. Females lowered their reproductive effort when population density increased and if they had weaned a lamb the previous year. A reduction in reproductive effort led to lower winter survival by lambs. Bighorn ewes have a conservative reproductive tactic and always favor their own body condition over that of their lambs. When resources are limited, ewes appear to transfer reproductive costs to their lambs, as expected from the much greater relative fitness consequences of a reduction in maternal than in offspring survival. PMID- 20735261 TI - Macroecology: does it ignore or can it encourage further ecological syntheses based on spatially local experimental manipulations? (American Society of Naturalists address). AB - Detailed natural history coupled to experimental ecology has provided a rich harvest of insights into how natural communities in all ecosystems function, insights that cannot be gleaned from macroecological analyses. That detail, generated by small-spatial-scale but often lengthy experiments, is essential to managing and even restoring ecosystems. My essay focuses primarily on the ecology of exposed rocky intertidal shores, but I believe the derived implications are generalizable to all ecosystems. A mainly experimental approach has tended to avoid a preoccupation with niches but instead has focused on the ecological roles exercised by particular species. Attention to roles has produced a growing appreciation for trophic cascades and their consequences, with obvious implications for the management of fisheries and the conservation significance of apex predators. Some studies are more phenomenological and others more reductionist in focus, but all provide pathways toward understanding abundance and body size variation or a miscellany of indirect effects. Microecology in all ecosystems should continue to prosper independently of a macroecological, predominately terrestrial perspective. PMID- 20735262 TI - Editorial. It is a serious responsibility to realize our limits when treating patients using new techniques. PMID- 20735258 TI - Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study. AB - BACKGROUND: Antiretroviral therapy is complicated by drug interactions and contraindications. Novel regimens are needed. METHODS: This open label study randomly assigned treatment-naive, human immunodeficiency virus (HIV)-infected subjects to receive tenofovir-emtricitabine with efavirenz (Arm I), with ritonavir-boosted atazanavir (Arm II), or with zidovudine/abacavir (Arm III). Pair-wise comparisons of differences in time-weighted mean change from baseline plasma HIV-RNA to week 48 formed the primary analysis. Treatment arms were noninferior if the upper limit of the 95% confidence interval (CI) was <0.5 log(10) copies/mL. Secondary objectives included virologic, immunologic and safety end points. RESULTS: The intention-to-treat population comprised 322 patients (Arm I, n = 114; Arm II, n = 105; and Arm III, n = 103). Noninferiority for the primary end point was established. Analysis for superiority showed that Arm III was significantly less potent than Arm I (-0.20 log(10) copies/mL; 95% CI, -0.39 to -0.01 log(10) copies/mL; P = .038). The proportions of patients on each of Arm I (95%) and Arm II (96%) with <200 copies/mL were not different (P = .75), but the percentage of patients in Arm III with <200 copies/mL (82%) was significantly lower (P = .005). CD4+ cell counts did not differ. Serious adverse events were more frequent in Arm III (n = 30) than in Arm I or Arm II (n = 15 for each; P = .062). CONCLUSIONS: A novel quadruple nucleo(t)side combination demonstrated significantly less suppression of HIV replication, compared with the suppression demonstrated by standard antiretroviral therapy regimens, although it did meet the predetermined formal definition of noninferiority. Secondary analyses indicated statistically inferior virologic and safety performance. Efavirenz and ritonavir-boosted atazanavir arms were equivalent in viral suppression and safety. PMID- 20735263 TI - Histomorphometric analysis and removal torque of small diameter implants with alternative surface treatments and different designs. AB - This study was designed to investigate the histomorphometric and biomechanical comparison of small-diameter implants with different designs. These implants can be placed surgically in narrow bone spaces, such as the lower incisor region, that have low occlusal loading. Specimens of screw-shaped pin implants were designed for the study. These specimen implants were divided into 6 groups: group 1, machined implants; group 2, resorbable blast media (RBM)-treated implants; group 3, machined implants with a long vertical groove; group 4, RBM-treated implants with a long vertical groove; group 5, RBM-treated implants with a vertical groove on the upper thread; and group 6, RBM-treated implants with a vertical groove on the lower trunk. The specimen implants were placed surgically on the medial side of the rabbit tibia. Animals were sacrificed 2, 4, and 8 weeks after surgery. The removal torque was measured and tissues were prepared for histologic and histomorphometric analysis. The bone-to-implant contact and the percentage of the bone area inside the threads were measured. RBM-treated implants with vertical groove groups showed significantly higher values of removal torque, bone-implant contact, and bone area rate than the ones of machined surface groups. PMID- 20735264 TI - Effect of platelet-rich plasma on peri-implant bone repair: a histologic study in dogs. AB - The present study evaluated the effect of platelet-rich plasma (PRP) on peri implant bone healing. A total of 9 mongrel dogs received 36 dental implants with sandblasted acid-etched surface in lower jaws in a split-mouth design: in the PRP group (n=18 implants) the implants were placed in association with PRP, and in the control group (n=18 implants) the implants were placed without PRP. Biopsies were obtained and prepared for histologic and histometric analysis after 15, 30, and 55 days of healing. The biopsies retrieved at 15 days showed delicate bone trabeculae formed by immature bone with presence of numerous osteoblasts for both groups. At 30 days the trabeculae presented reversal lines and evident lamellar disposition, where some thread spaces were filled by bone and dense connective tissue. At 55 days, bone healing was not altered in the control group, and histologic aspects were variable for the group treated with PRP. There was no significant difference between the groups for bone-to-implant contact (P>.05). PRP did not enhance bone formation around sandblasted acid-etched implants. PMID- 20735265 TI - A modified plastic shell technique for cement-retained implant restorations. AB - The best possible fit of prosthetic components should be the aim of the clinician. The technical report presented here describes the use of a modified plastic shell technique for modeling a cement-retained single-implant restoration. This approach will help to prevent potential errors caused by the wax modeling technique. PMID- 20735266 TI - Minimally invasive sinus augmentation. AB - Sinus lift surgery has become more common as patients choose dental implants for tooth replacement. The recent development of a graft material that stimulates osteogenesis coupled with the application of tissue engineering principles has allowed for refinement of this surgical modality. A simple nontraumatic subantral sinus lift microsurgery is presented. This sinus lift microsurgery resulted in a 97% implant success rate. PMID- 20735267 TI - A noninterventional study documenting use and success of implants with a new chemically modified titanium surface in daily dental practice. AB - A new chemically modified titanium surface, SLActive, has recently been developed. The results obtained in controlled clinical trials indicate that this implant can be safely used and that it offers predictable results. The goal of this noninterventional study was to verify that the success rates of implants used in daily dental practice are comparable to those reported in controlled clinical trials. This study was a prospective, noninterventional study using implants with a chemically modified surface according to the daily dental practice procedures applied by private practitioners. The choice of the implantation procedure and the loading protocol were the responsibility of the investigator and were chosen according to the patient's needs. Thirty clinical centers actively participated in this study, and 226 patients were treated, of which, 8 patients were lost to follow-up. Because of the noninterventional design of the study, the patients were not selected according to strictly defined inclusion/exclusion criteria. Thus, the study included individuals with risk factors such as smoking (24%), untreated gingivitis or periodontitis (9%), and bruxism (6%). The implants were equally distributed between mandible (46%) and maxilla (54%). A bone augmentation procedure was done in 31% of the cases. Early loading (functional loading between 48 hours and 3 months after implant insertion) was applied most frequently (48%), followed by the conventional loading protocol (3 to 6 months after implant placement, 34%). Immediate restoration and immediate loading were rare (7% and 2%, respectively). Of 276 implants inserted and documented, 5 implants failures were reported, all of which were associated with a sinus floor augmentation procedure. The survival rate was 98.2% at the 1-year follow-up visit. The results showed that implants with a chemically modified surface can be successfully restored with success rates similar to those reported in formal clinical trials under more controlled conditions. PMID- 20735268 TI - Survival rate of immediately vs delayed loaded implants: analysis of the current literature. AB - Immediate loading of oral implants has been reported as a beneficial treatment protocol in implant dentistry that increases the comfort of the patient. However, documentation in the literature is poor regarding the clinical outcome and the peri-implant bone response of immediately loaded implants compared with the conventional loading protocol placed in different bone qualities. The aim of this report was to present the role of bone quality in the survival rate of implants using conventional or immediate loading according to the literature. A literature search analysis was performed to demonstrate the survival rate of immediately loaded implants, as well as data from the histologic and histomorphometric evaluation in comparison with conventional loaded implants. This analysis showed high survival rates of immediately loaded implants along with osseointegration, with high percentages of bone-to-implant contacts based on histologic evaluation from human and animal studies of immediately and conventionally loaded implants. This study may provide histologic and clinical evidence of the immediate loading protocol for different bone qualities. PMID- 20735270 TI - Helicobacter pylori-induced loss of the inhibitor-of-apoptosis protein survivin is linked to gastritis and death of human gastric cells. AB - Helicobacter pylori infects the human stomach and modifies signaling pathways that affect gastric epithelial cell proliferation and viability. Chronic exposure to this pathogen contributes to the onset of gastric atrophy, an early event in the genesis of gastric cancer associated with H. pylori infection. Susceptibility to H. pylori-induced cell death ultimately depends on the presence of protective host cell factors. Although expression of the inhibitor-of-apoptosis protein survivin in adults is frequently linked to the development of cancer, evidence indicating that the protein is present in normal gastric mucosa is also available. Thus, we investigated in human gastric tissue samples and cell lines whether H. pylori infection is linked to loss of survivin and increased cell death. Our results show that infection with H. pylori decreased survivin protein levels in the mucosa of patients with gastritis. Furthermore, survivin down regulation correlated with apoptosis and loss of cell viability in gastrointestinal cells cocultured with different H. pylori strains. Finally, overexpression of survivin in human gastric cells was sufficient to reduce cell death after infection. Taken together, these findings implicate survivin as an important survival factor in the gastric mucosa of humans. PMID- 20735272 TI - The relationship of personal factors and subjective well-being to the use of assistive technology devices. AB - PURPOSE: To describe a measure and its performance specific to the relationship of personal factors and subjective well-being (SWB) to the use of assistive technology devices (ATDs). The primary hypothesis is that responses to a 33-item personal factors scale and a 12-item SWB scale are good indicators of an individual's predisposition for using, and subsequent match with, a given ATD. METHODS: Data analyses from a number of studies using the 33-item personal factors and the 12-item SWB scales of the Assistive Technology Device Predisposition Assessment with persons of various ages and types of disabilities. RESULTS: Regardless of type of disability or age of respondent, the ATD PA personal factors and the SWB scales identified important differences in predispositions to use an ATD as well as the subsequent quality of the match of person and device. CONCLUSIONS: A quantifiable relationship exists between the ATD PA's measure of personal factors and the SWB such that it is possible to characterise an individual's predisposition to use a particular ATD. Results also show that the scales are predictive of the quality of the ATD and user match at follow-up. Rehabilitation practitioners who use the ATD PA may achieve enhanced assistive technology service delivery outcomes by using this evidence-based measure. PMID- 20735271 TI - Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization. AB - BACKGROUND: The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). METHODS: This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. RESULTS: The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. CONCLUSION: RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050). PMID- 20735273 TI - Patients with more severe symptoms benefit the most from an intensive multimodal programme in patients with fibromyalgia. AB - PURPOSE: Patients with fibromyalgia (FM) experience symptoms over a long period of time impacting their quality of life (QoL). Patients are often treated in multimodal programmes that combine physical and cognitive treatment modalities. Purpose of this study was to identify prognostic factors of effectiveness of a multimodal programme. METHOD: A prospective study was performed with a group of 87 patients with FM who had participated in a multimodal programme. The Revised Illness Perception Questionnaire (IPQ) and the Fibromyalgia Impact Questionnaire (FIQ) were used. Criterion for clinically relevant improvement was a decline in total FIQ score of 12.5 points or more after the treatment programme. Investigated determinants of improvement of QoL were patient characteristics, illness perceptions (IP) and QoL at baseline. RESULTS: QoL of 34 patients with FM made a clinically relevant improvement after the programme. There was no difference in age, number of years with pain, number of years diagnosed or IP compared to the group that did not improve. The group of patients with an improved QoL after the programme reported severe impact on daily living, highest intensity of pain and most depression at baseline. CONCLUSIONS: Total FIQ score on QoL, intensity of pain, morning tiredness and depression can be used as prognostic factors to pre-select patients with FM for a multimodal treatment. IP were not adequate to predict treatment outcome. An intensive multimodal programme seemed most suitable for patients with severe symptoms and limitations. PMID- 20735274 TI - Living with acquired dysarthria: the speaker's perspective. AB - PURPOSE: To explore the speaker's experience of living with acquired chronic dysarthria. METHOD: Ten people with dysarthria and progressive neurological illness and one person with dysarthria following stroke were interviewed in depth about their experience of living with dysarthria. They covered a range of ages, time post-onset and dysarthria severity levels. Interviews were transcribed and analysed using Framework Method of Analysis. RESULTS: Acquired dysarthria can negatively impact on speakers' lives. Findings here suggest that the experience of living with dysarthria is highly individual. There were some common perspectives. Six key themes emerged from interviews: 'dysarthria as only part of the picture', 'communication has changed', 'people treat me differently', 'dysarthria resulting in negative emotions', 'barriers to communication' and 'life is different now. The impact of co-existing physical disability and the need to consider dysarthria in context was emphasised by all participants. CONCLUSION: Findings re-emphasise the need to consider the individual experience in clinical practice. The findings provide direction for assessment and intervention in the area. PMID- 20735275 TI - Impact on image quality and radiation exposure in coronary CT angiography: 100 kVp versus 120 kVp. AB - BACKGROUND: The risk of radiation-induced cancer has become a major concern with the increasing use of computed tomography (CT). PURPOSE: To compare image quality and radiation doses when decreasing X-ray tube peak kilovoltage (kVp) from 120 to 100 kVp in patients undergoing coronary CT angiography (CCTA). MATERIAL AND METHODS: Patients referred for evaluation of suspected coronary artery disease (CAD) underwent 64-channel detector CCTA using a tube voltage of either 120 kVp (n = 46) or 100 kVp (n = 82). The individual volume CT dose index (CTDI(vol)) and dose length product (DLP) were recorded and effective radiation dose was estimated on the basis of DLP. Subjective image quality was assessed by two radiologists on per-patient based consensus. Vascular density and image noise were quantified in the left main coronary artery (LMCA) and proximal ascending aorta (AA). Mean density in the adjacent perivascular tissue was also quantified. Contrast-to-noise ratio (CNR) was calculated. Corresponding invasive coronary angiography (ICA) was performed, which constituted the gold standard. RESULTS: Mean values in the 100/120 kVp cohorts regarding CNR in the LMCA were 12.7/16.0 (P<0.0001)) and in the AA 13.2/17.2 (P<0.0001), CTDI(vol) 34.4/57.4 mGy (a 40% reduction, P<0.0001), DLP 578/1125 mGy * cm (P<0.0001), and estimated effective dose 9.6/20.2 mSv (P<0.0001). There was no statistically significant difference in subjective image quality between the two cohorts. The sensitivity to detect significant coronary stenoses was 88% (120 kVp) and 84% (100 kVp) and the specificity was 71% (120 kVp) and 74% (100 kVp), respectively. CONCLUSION: By reduction of tube voltage from 120 to 100 kVp at CCTA, while keeping all other scanning parameters unchanged, the radiation dose to the patient can be almost halved while keeping the diagnostic image quality at a clinically acceptable level. PMID- 20735276 TI - Variations of the ulnar nerve in Guyon's canal: in vivo demonstration using ultrasound and 3 T MRI. AB - BACKGROUND: The clinical importance of Guyon's canal is emphasized due to the various branching patterns of the ulnar nerve. So far, the arborization pattern of the ulnar nerve in Guyon's canal has been investigated mostly by cadaveric studies. PURPOSE: To demonstrate anatomic variations of the ulnar nerve in Guyon's canal in vivo by using high definition ultrasound (US) and 3 T magnetic resonance imaging (MRI). MATERIAL AND METHODS: US imaging and 3 T MRI with an 8 channel coil was applied to 30 hands of 15 volunteers. The main trunk and the branched superficial and deep ulnar nerves, including neural bifurcation or trifurcation, were recognized on US and confirmed by 3 T MR images. The ulnar artery and vein and its branches were traced on color Doppler US and also visualized by MRI. The branching pattern of the ulnar nerve was determined from the inlet to the outlet of Guyon's canal. RESULTS: Of 30 hands, 21 (70%) revealed bifurcation and 9 (30%) had trifurcation branching pattern of the ulnar nerve. In 16 hands (54%), imaging demonstrated that a single nerve entered the canal and divided into two trunks, one superficial and one deep, then exited the canal. The bifurcation occurred predominantly just after entering the canal inlet. The typical trifurcation pattern indicated that a single trunk entered the canal and divided into two, then one of the two bifurcated, producing a trifurcated pattern with two superficial and one deep bundle. Of 15 participants, symmetrical branching of bilateral hands was identified in 4 cases (27%), whereas 11 (73%) had asymmetrical branching. CONCLUSION: US and 3 T MRI readily delineated the branching pattern of the ulnar nerve in Guyon's canal in vivo. Morphological understanding about this neural branching can be informative in presurgical planning and also in diagnosis. PMID- 20735277 TI - Diffusion tensor MRI of the kidney at 3.0 and 1.5 Tesla. AB - BACKGROUND: Diffusion tensor imaging (DTI) at 3 T provides information on the microstructure and pathophysiology of tissues that is not available from conventional imaging with an advantage of high signal to noise ratio (SNR). PURPOSE: To evaluate the feasibility of DTI of the normal kidney at 3.0 T compared to results obtained at 1.5 T. MATERIAL AND METHODS: DTI of the normal kidney of 15 healthy volunteers obtained with 3.0 and 1.5 T scanners using respiration-triggered acquisition was examined. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of both the renal cortex and the medulla and SNRs were measured (b-values 0 and 400 s/mm2, diffusion direction of 6). The image quality of FA and ADC maps was also compared subjectively. RESULTS: The FA values of the renal cortex were 0.15 +/- 0.03 at 3.0 T and 0.14+/- 0.03 at 1.5 T on average. This difference was not significant. The FA values of the renal medulla were 0.49 +/-0.04 at 3.0 T and 0.42 +/- 0.05 at 1.5 T. ADC values of the renal cortex were 2.46 x 10-3+/- 0.09 mm<2/s at 3.0 T and 2.20 x 10-3+/-0.11 mm2/s at 1.5 T. The ADC values of the renal medulla were 2.08 x 10-3 +/- 0.08 mm2/s at 3.0 T and 1.90 x 10-3+/- 0.11 mm2/s at 1.5 T. These FA and ADC values were consistent with previous publications. The difference was significant for the FA value of the medulla (P< 0.01) and ADC values in both cortex and medulla (P < 0.01). The subjective image quality of the FA map with the 3.0 T scanner was significantly superior to that with the 1.5 T scanner (P< 0.01), but not significant for the ADC map (P = 0.18). There was a significant difference in SNR between 3.0 T (48.8 +/- 6.6) and 1.5 T images (32.8 +/- 5.0). CONCLUSION: The feasibility of renal DTI with a 3.0 T magnet resulting in improved SNR was demonstrated. PMID- 20735278 TI - Application of breast MRI for prediction of lymph node metastases - systematic approach using 17 individual descriptors and a dedicated decision tree. AB - BACKGROUND: The presence of lymph node metastases (LNMs) is one of the most important prognostic factors in breast cancer. PURPOSE: To correlate a detailed catalog of 17 descriptors in breast MRI (bMRI) with the presence of LNMs and to identify useful combinations of such descriptors for the prediction of LNMs using a dedicated decision tree. MATERIAL AND METHODS: A standardized protocol and study design was applied in this IRB-approved study (T1-weighted FLASH; 0.1 mmol/kg body weight Gd-DTPA; T2-weighted TSE; histological verification after bMRI). Two experienced radiologists performed prospective evaluation of the previously acquired examination in consensus. In every lesion 17 previously published descriptors were assessed. Subgroups of primary breast cancers with (N+: 97) and without LNM were created (N-: 253). The prevalence and diagnostic accuracy of each descriptor were correlated with the presence of LNM (chi-square test; diagnostic odds ratio/DOR). To identify useful combinations of descriptors for the prediction of LNM a chi-squared automatic interaction detection (CHAID) decision tree was applied. RESULTS: Seven of 17 descriptors were significantly associated with LNMs. The most accurate were "Skin thickening" (P < 0.001; DOR 5.9) and "Internal enhancement" (P < 0.001; DOR 0.05), although displacements >3 mm were found more frequently when severe weight loss or tumor nodal shrinkage occurred. DISCUSSION: these results enable us to choose margins that guarantee with sufficient accuracy the coverage of PTVs and organs at risk sparing. Collected data confirmed the need for a strict check of patient position reproducibility in case of anatomical changes. PMID- 20735284 TI - Relative biological effectiveness of photon energies used in brachytherapy and intraoperative radiotherapy techniques for two breast cancer cell lines. AB - BACKGROUND: Partial breast irradiation (IORT or brachytherapy) differ from external radiation of whole breast in terms of irradiated volumes, fractionation, radiation energy and dose rate; all factors influencing the treatment outcome in a complex manner. Theoretically obtained RBE values comparing effects of radiation used in IORT and external therapy are published, but experimental studies are required to confirm these data. The aim of this study is to establish such RBE values for two breast cancer cell lines. MATERIALS AND METHODS: Colony formation of breast cancer cell lines (MCF-7 and T-47D) were studied after photon irradiation with qualities and dose rates used in IORT, brachytherapy and external radiation. RBE values from survival data were used to compare effects. RESULTS: Increasing the photon energy (dose rate 0.2 Gy/min) from 50 kV (Intrabeam) to 380 keV (192Ir source) and 6 MV (linear accelerator) yielded an increase in the cell survival, whereas increasing the dose rate to 6 Gy/min had minor effect. Average RBE values for 50 kV with 6 MV as reference radiation varied from about 1.4 (for doses < 5 Gy) to > 1.9 (for doses < 0.02 Gy) for MCF-7 cells and from about 1.4 to > 3.1 for T-47D cells for the same dose levels. Corresponding RBE values for 380 keV radiation were about 1.4 for MCF-7 cells and 1.3-2.3 for T-47D cells. CONCLUSION: RBE data for breast cancer cells exposed to radiation used in IORT, brachytherapy or external radiation differ among the cell lines tested. The values are in agreement with published theoretical and experimental work. PMID- 20735285 TI - Inter-aural attenuation with insert earphones. AB - The aim of the present study was to determine inter-aural attenuation (IA) values for pure tones and a broadband click obtained using an ER-3A insert earphone with a foam plug and with a customized hard acrylic earmould. Participants were 15 adults with a longstanding unilateral dead ear. IA was operationally defined as the difference between the good-ear and poorer-ear not-masked air conduction threshold. Minimum IA values for the foam earplug were 50 dB and 55 dB for pure tones and broadband click, respectively. Minimum IA values for the hard acrylic earmould were 45 dB and 50 dB for pure tones and broadband click, respectively. PMID- 20735286 TI - Transient myopic shift as the presenting symptom of systemic lupus erythematosus: a UBM study. AB - PURPOSE: To report ultrabiomicroscopy (UBM) evidence of choroid effusion as a cause of acute transient myopia in the onset of systemic lupus erythematosus. DESIGN: Observational case report. METHODS: A Caucasian 16-year-old girl was referred to the Hematology Department for progressive anemia, intermittent fever, and blurred vision. RESULTS: Systemic lupus erythematosus was confirmed by hematological investigations. UBM examination evidenced choroid effusion as the cause of a transient myopic shift. CONCLUSIONS: Early diagnosis, thanks to the performance of an ultrasound examination, enabled the timely institution of therapy and hence a rapid resolution of the symptoms. PMID- 20735287 TI - Clinical review: topical ophthalmic use of cyclosporin A. AB - Cyclosporine A (CsA) is an immunomodulatory agent that primarily inhibits the proliferation and action of T cells. Systemic CsA has been used successfully in solid organ transplantation and noninfectious uveitis. Topical CsA with various formulations has been used in the field of ocular surface diseases since early 1980s. An ophthalmic emulsion 0.05% (Restasis, Allergan, Irvine, CA), was approved by the United States Food and Drug Administration in 2003 to treat dry eye syndrome. This article aims to evaluate the peer-reviewed published scientific literature and to define well-established uses of CsA eyedrops in the field of ocular surface diseases. PMID- 20735288 TI - Cellular and tissue architecture of conjunctival membranes in epidemic keratoconjunctivitis. AB - PURPOSE: Conjunctival membranes are differentiated from pseudomembranes by bleeding on removal. The authors sought to study the cellular constituents and extracellular structure of formed conjunctival exudates in epidemic keratoconjunctivitis (EKC), and to determine whether these represent true conjunctival membranes. METHODS: Formed conjunctival exudates harvested from 2 patients with EKC were studied by immunohistochemistry. Adenoviral infection was evaluated by PCR. RESULTS: Each patient's tears were PCR positive for adenovirus, but not HSV-I. Both conjunctival specimens contained a fibrinous stroma richly populated with cells positive for CD4, CD8, CD20, CD68, myeloperoxidase, and fascin. Both specimens also contained cells positive for CD31 and Tie-2, and demonstrated expression of transforming growth factor-beta and vascular endothelial growth factor. CONCLUSIONS: Conjunctival exudates in EKC contain a range of leukocytes representing both innate and acquired immune responses, along with angiogenic factors and proliferating endothelial cells. Therefore, true conjunctival membranes can and do form in EKC. PMID- 20735289 TI - Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective, randomized pilot study. AB - PURPOSE: Comparison of pars plana vitrectomy (PPV) with immunomodulatory therapy (IMT) for patients with intermediate uveitis (IU). METHODS: A prospective, randomized pilot study was performed on patients with recalcitrant IU associated with degradation of visual acuity (VA) despite standard treatment. Outcome measures (VA, intraocular pressure, anterior chamber and vitreous cellular infiltrate) were collected. RESULTS: Sixteen patients (18 eyes) were randomized to the PPV IMT group. Nine of 11 eyes (82%) treated with PPV showed resolution of inflammation at follow-up, at 5.93 years. Four of 7 eyes (57%) given IMT had persistent inflammation requiring subsequent PPV. PPV patients showed greater improvement in Snellen line, IOP, and vitreous cell reduction. Three PPV patients had cystoid macular edema (CME) initially; all resolved postoperatively. CME improved in 2 of 3 eyes using IMT. CONCLUSIONS: A higher percentage of patients treated with PPV had improvement of uveitis compared to those given IMT. A multicentered clinical trial is needed to confirm and statistically validate these conclusions. PMID- 20735290 TI - A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors. AB - OBJECTIVES: Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, has been shown to increase platelet counts in adults with chronic immune thrombocytopenia and chronic hepatitis C. This multicenter phase 2 study assessed the efficacy and safety of eltrombopag in patients receiving first-line carboplatin/paclitaxel for the treatment of advanced solid tumors. RESEARCH DESIGN AND METHODS: Patients (N = 183) were randomized to placebo or eltrombopag 50 mg, 75 mg, or 100 mg given orally following chemotherapy on days 2 through 11 of each 21-day cycle, for at least two cycles. The primary endpoint was the difference in platelet count from day 1 in cycle 2 to the platelet nadir in cycle 2. CLINICAL TRIAL REGISTRY NUMBER: NCT00102726. RESULTS: Although the primary endpoint was not met, postnadir platelet counts increased during cycles 1 and 2 in all eltrombopag treatment groups compared with placebo. The most commonly reported adverse events across all study arms (including placebo) were nausea and alopecia and eltrombopag was generally well tolerated. CONCLUSIONS: This study provides preliminary information that eltrombopag does increase platelets in patients receiving chemotherapy for advanced solid tumors. Further investigation is needed to identify the optimal dose(s) and schedule of eltrombopag in patients receiving myelosuppressive chemotherapy. PMID- 20735292 TI - Fibrosing blepharo-conjunctivitis following pyogenic granuloma in ocular acne rosacea. AB - PURPOSE: To report a case of pyogenic granuloma associated with ocular acne rosacea. DESIGN: Case report. METHODS: Interventional case report. RESULTS: The patient developed an unusual lesion of the conjunctiva and limbus, histologically confirmed to be pyogenic granuloma. Excision of the lesion resulted in symblepharon formation, adhesions between lid margins, tarsal conjunctiva, and cornea, and reductions in visual acuity. The patient underwent surgical separation of the corneal lid adhesions with a mucosal autograft for the tarsal conjunctiva and an amniotic membrane graft for the cornea with good results. CONCLUSIONS: Ocular rosacea is a common condition but such excessive and unusual fibrotic healing responses following excision of pyogenic granulomas have not been previously reported. This case demonstrated significant morbidity and decreased visual acuity. However, early recognition and effective surgical management can lead to good visual outcomes. PMID- 20735291 TI - Non-clinical pharmacology, pharmacokinetics, and safety findings for the antihistamine bepotastine besilate. AB - SCOPE: The purpose of this review is to examine published non-clinical literature on the antihistamine bepotastine besilate, including pharmacokinetic and pharmacologic properties. METHODS: Standard literature searches using diverse databases were used to find articles on bepotastine besilate published between 1997 and 2009. Articles primarily described non-clinical data utilized for the development of an oral formulation of bepotastine besilate and were published in Japanese. No publications of non-clinical data for an ophthalmic formulation were found in the database searches. FINDINGS: Bepotastine besilate is a second generation antihistamine drug possessing selective histamine H(1) receptor antagonist activity. Bepotastine has negligible affinity for receptors associated with undesirable adverse effects, including histamine H(3), alpha(1)-, alpha(2)-, and beta-adrenergic, serotonin (5-HT(2)), muscarinic, and benzodiazepine receptors. Bepotastine possesses additional anti-allergic activity including stabilization of mast cell function, inhibition of eosinophilic infiltration, inhibition of IL-5 production, and inhibition of LTB(4) and LTD(4) activity. Bepotastine in vivo dose-dependently inhibited the acceleration of histamine induced vascular permeability and inhibited homologous passive cutaneous anaphylaxis in guinea pig studies. In mouse models of itching, oral bepotastine inhibited the frequency and duration of scratching behavior. Multiple in vivo animal toxicology studies have demonstrated bepotastine to be safe with no significant effects on respiratory, circulatory, central nervous, digestive, or urinary systems. The concentration of bepotastine after intravenous administration of bepotastine besilate (3 mg/kg) in rats was lower in the brain than in plasma, predicting reduced sedation effects compared to older antihistamines. CONCLUSION: Non-clinical in vitro and in vivo studies have demonstrated bepotastine is a histamine H(1) receptor antagonist with favorable pharmacokinetic, pharmacologic, safety, and antihistamine properties as well as operating on other pathways leading to allergic inflammation beyond those directly involving the histamine H(1) receptor. PMID- 20735293 TI - A case study examination of the impact of lawsuits on website accessibility. AB - PURPOSE: To evaluate the impact of lawsuits on the accessibility of company websites. METHOD: Convenience samples of websites for America Online (AOL), Southwest Airlines, Metropolitan Atlanta Rapid Transit Authority (MARTA), Priceline.com, and Claire's were evaluated for years surrounding their respective lawsuits. The results of each website were compared to a random control group of websites and to a reference website (of a similarly sized company that has not been sued and is in the same industry). Where possible, two archived instances of each website were collected per year. Accessibility was measured using the Web Accessibility Barrier (WAB) metric to evaluate the homepage and pages at level 1. Analysis of variance was computed on the common periods between each pairing of sued and reference websites. RESULTS: The case studies demonstrate mixed evidence that lawsuits work. In the cases of MARTA, Southwest and Priceline, there is supporting evidence that lawsuits have been successful. In the cases of AOL and Claire's, the evidence is weaker. CONCLUSION: This case study examination shows mixed evidence that lawsuits work to force companies to modify their websites to be more accessible to people with disabilities: three cases show evidence for the success and two show weaker supporting evidence. PMID- 20735294 TI - Patterns of uveitis in patients admitted to a University Hospital in Riyadh, Saudi Arabia. AB - PURPOSE: To analyze clinical patterns, causes, and systemic disease associations among patients with uveitis admitted to King Abdulaziz University Hospital. METHODS: The authors retrospectively reviewed the medical records of 351 patients (600 eyes). RESULTS: The study subjects consisted of 183 (52.1%) males and 168 (47.9%) females, with a mean age of 39.9 +/- 14.2 years at presentation. The most common anatomic diagnosis was panuveitis (68.6%), followed by posterior uveitis (12.7%), anterior uveitis (12.7%), and intermediate uveitis (6.0%). The most common identifiable specific diagnoses were presumed tuberculous uveitis (PTU) (28.2%), Vogt-Koyanagi-Harada (VKH) disease (19.4%), Behcet disease (BD) (12.5%), and toxoplasmosis (8.2%). After a mean follow-up period of 29.5 +/- 22.1 months, 63.5% of the eyes achieved visual acuity of 20/40 or better. Eyes from patients with PTU had the worst final visual outcome. CONCLUSIONS: The most common anatomic diagnosis was panuveitis. PTU, VKH disease, BD, and toxoplasmosis were the most frequent specific diagnoses. PMID- 20735295 TI - Intrathecal synthesis of immunoglobulins in patients with unexplained intermediate uveitis. AB - PURPOSE: To assess the value of lumbar punctures in adult patients with unexplained intermediate uveitis (IU). METHODS: Retrospective study of 17 patients with unexplained IU. All the patients underwent physical examination, complete laboratory tests, and cerebrospinal MRI. RESULTS: Out of the 12 patients who underwent a lumbar puncture, six had oligoclonal bands and/or increased IgG index. CONCLUSION: Intrathecal synthesis of immunoglobulins is not rare in patients with unexplained IU. A longer follow-up is mandatory to determine whether intrathecal immunoglobulins synthesis has a predictive value for subsequent progression to multiple sclerosis. PMID- 20735296 TI - Restoration of retinal architecture following systemic immunosuppression in birdshot chorioretinopathy. AB - PURPOSE: To describe restoration of retinal architecture following systemic immunosuppressive treatment in a patient with birdshot chorioretinopathy (BSCR). DESIGN: Case report. METHODS: A patient with BSCR and vitritis, reduced electroretinographic responses, and a constricted visual field was treated with prednisone and mycophenolate mofetil. RESULTS: Spectral domain optical coherence tomography (SD-OCT) at baseline demonstrated a disruption of retinal architecture. After 4 months of treatment retinal architecture, as visualized on SD-OCT, was restored to normal. CONCLUSIONS: Treatment of BSCR with systemic immunosuppression can result in restoration of disrupted retinal architecture. This structural improvement can be visualized and assessed using SD-OCT. PMID- 20735297 TI - Cystoid macular edema secondary to fluconazole toxicity. AB - Fluconazole is an antifungal commonly used to treat Coccidioides immitis, but this medication has a number of side effects including fatigue, rash, headache, dizziness, nausea, vomiting, diarrhea, and elevated liver enzymes. We are unaware of any cases of retinal toxicity related to fluconazole. In this case we present a 76 year old woman with longstanding Coccidioides treated with high dose fluconazole. She becomes symptomatic with fluconazole toxicity and subsequently develops bilateral cystoid macular edema. As her dose of fluconazole is decreased and she is transitioned to voriconazole the edema resolves and her visual acuity improves. This patient's clinical course illustrates retinal toxicity may present with high and prolonged doses of fluconazole. PMID- 20735298 TI - Pharmaceutical review articles: from good to great. PMID- 20735299 TI - Chitosan microspheres of aceclofenac: in vitro and in vivo evaluation. AB - The objective of this investigation was to achieve controlled drug release of Aceclofenac (ACE) microspheres and to minimize local side-effects in the gastrointestinal tract (GIT). Sustained release chitosan microspheres containing ACE were prepared using double-emulsion solvent evaporation method (O/W/O). Chitosan microspheres were prepared by varying drug to polymer ratio (1:3, 1:4, 1:5 and 1:6). Microspheres were characterized for morphology, swelling behavior, mucoadhesive properties, FTIR and DSC study, drug loading efficiency, in vitro release, release kinetics, and in vivo study was performed on rat model. ACE loaded microspheres were successfully prepared having production yield, 57-70% w/w. Drug encapsulation efficiency was ranging from 53-72% w/w, Scanning electron microscopy (SEM) revealed particle size of microspheres was between 39 and 55 mum. FTIR spectra and DSC thermograms demonstrated no interaction between drug and polymer. The in vitro release profiles of drug from chitosan microspheres showed sustained-release pattern of the drug in phosphate buffer, pH 6.8. In vitro release data showed correlation (r2 > 0.98), good fit with Higuchi/Korsmeyer-Peppas models, and exhibited Fickian diffusion. ACE microspheres demonstrated controlled delivery of aceclofenac and apparently, no G.I.T. erosion was noticed. PMID- 20735300 TI - Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets. AB - The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides (inulin 1.8 kDa, 4 kDa and 6.5 kDa). Solid dispersions with various drug loads were prepared by lyophilization. It was found that the drug solubility in aqueous PVP solutions was significantly increased indicating the presence of drug-carrier interaction while the drug solubility was not affected by the saccharides indicating absence of drug-carrier interaction. X-ray powder diffraction and modulated differential scanning calorimetry revealed that all solid dispersions were fully amorphous. Dissolution behavior of solid dispersion tablets based on either the PVPs or saccharides was governed by both dissolution of the carrier and drug load. It was shown that a fast drug dissolution of solid dispersions with a high drug load could be obtained with carrier that showed interaction with the drug. PMID- 20735301 TI - Formulation and stability study of chlorpheniramine maleate nasal gel. AB - Nasal administration has been of special interest in the last decade due to its feasibility and relative high bioavailability compared to the oral rout of administration. Our study aimed to develop a nasal gel formulation for an antihistaminic drug, Chlorpheniramine maleate (CPM), which suffers from poor oral bioavailability (25-45%) due to its first-pass metabolism in the liver. Different formulations of CPM nasal gels were prepared using different polymers in different concentrations, these gels were evaluated for their in vitro (physico chemical properties, release, permeability and stability) to select the best formulation which subject to in vivo tests including mucociliary clearance and bioavailability, both in comparison to the solution and commercial tablet Allergyl. PMID- 20735302 TI - Multidisciplinary management of childhood sarcoma: time to expand. PMID- 20735304 TI - Lapatinib and breast cancer: current indications and outlook for the future. AB - Lapatinib is an oral dual erbB 1/2 tyrosine kinase inhibitor that inhibits human EGF receptor 2 (HER2) and blocks the EGF receptor. Studies have shown that in patients with metastatic HER2-positive breast cancer that is resistant to trastuzumab, the addition of lapatinib to capecitabine improves progression-free survival and appears to lengthen overall survival. Furthermore, lapatinib has been studied in patients with involvement of the CNS and has been associated with stable disease and some responses. Its combination with letrozole provided an improvement in progression-free survival compared with single-agent letrozole in women with hormone receptor-positive, HER2-positive metastatic breast cancer. More recently, data suggested that the combination of lapatinib with trastuzumab significantly improves overall survival in women with metastatic breast cancer compared with single-agent lapatinib. Current indications in the USA for the use of lapatinib are for the treatment of metastatic HER2-positive breast cancer, both in combination with capecitabine in patients who have received taxane, anthracycline and traztuzumab, and in combination with letrozole for postmenopausal patients with hormone receptor- and HER2-overexpressing breast cancer. Common side effects of lapatinib include diarrhea and rash. Studies to date have found a less than 2% risk for cardiotoxicity, although most cardiac events that occurred during the studies were not attributed to lapatinib. It is important to consider that most of the patients in existing studies had already been treated with trastuzumab with no significant cardiotoxicity; therefore, future studies will show how trastuzumab-naive patients tolerate lapatinib. Ongoing research is evaluating the role of lapatinib in the adjuvant setting as a single agent or in combination with trastuzumab. PMID- 20735305 TI - American Radium Society 92nd Annual Meeting. AB - We provide a summary of the 92nd Annual Meeting of the American Radium Society (ARS), the oldest organization devoted to the study of cancer. This May 2010 meeting included a postgraduate course/contouring laboratory, seven scientific sessions, two keynote lectures, one Janeway lecture, four Panel presentations, one debate, one satellite symposium and 107 poster presentations--details of each of these activities are provided. All of these academic activities revolved around the major meeting theme of 'Improved Outcomes Through Judicious Applications of Advanced Technology'. PMID- 20735306 TI - Multigene assays and isolated tumor cells for early breast cancer treatment: time for bionetworks. AB - Despite advances with adjuvant endocrine treatment for hormone receptor-positive tumors and with trastuzumab for HER2-positive disease, overall, over 50% of women with early-stage breast cancer experience recurrence and die of the disease. Biomarkers for tailoring systemic adjuvant treatment to responder patients are needed. The multigene assays, 21-gene recurrence score (Oncotype DX [Genomic Health, CA, USA]) and 70-gene signature (MammaPrint [Agendia, CA, USA]), and the isolated tumor cells in sentinel lymph node(s) represent the latest advances for improving adjuvant chemotherapy decisions. This article evaluates how these new markers, added to current standard factors (age, tumor size, grade, hormone receptor status and HER2 status), could improve early breast cancer treatment decisions. Moreover, emerging evidence from the latest large-scale studies using next-generation DNA-sequencing technology reveals a high heterogeneity and complexity of breast cancer. This assessment now shapes a new research strategy towards completion of a breast cancer causal (driver) mutations catalog and understanding complex genetic interactions and signaling pathway networks. Despite multiple challenges, advances in cancer genomes and systems biology approaches promise the future development of robust biomarkers. PMID- 20735307 TI - Beyond triple-negative breast cancer: the need to define new subtypes. AB - Advances in the systemic treatment of early breast cancer have led to significant improvements in survival for patients with hormone receptor- and/or HER2-positive disease. In recent years, interest has focused on tumors that lack expression of the estrogen receptor, progesterone receptor and HER2, the so-called triple negative subgroup. As a group, triple-negative cancers have a relatively aggressive clinical course, with early development of visceral metastases and a poor long-term prognosis. These tumors, however, encompass a wide range of subtypes with varying prognosis, including a number of special types with a good prognosis (e.g., adenoid cystic carcinomas and secretory carcinoma). There is considerable overlap between triple-negative and basal-like tumors; however, microarray studies have demonstrated that the overlap between basal-like and triple-negative cancers is not complete. The similarities between sporadic triple negative cancers and tumors arising in BRCA1 mutation carriers and the fact that the majority of BRCA1 tumors display a triple-negative phenotype have led to studies demonstrating a potential loss of BRCA1 function in triple-negative cancers and offered potential therapeutic avenues for patients with these cancers. However, it should be noted that triple-negative breast cancers comprise a heterogeneous group of tumors. Understanding the molecular underpinning of distinct subgroups of these cancers is crucial for the identification of novel therapeutic targets and individualization of treatment for patients with triple negative disease. PMID- 20735308 TI - Prognostic factors for local recurrence following breast-conserving treatment in young women. AB - Breast cancer is a rare disease in young women. Its incidence has remained remarkably constant over the last decades, contrary to what has happened in older patients. Age is a major prognostic factor for local control after breast conserving treatments, which does not seem to be entirely explained by the poor prognostic features that are more commonly associated with breast cancers in young women. A better knowledge of the prognostic factors for local control, and, whenever possible, those pertaining specifically to the young age group, is key, not only to better select the patients who would benefit the most from a breast conserving approach but also to enhance the local control when this option has been elected. These prognostic factors can be related to the patient, the tumor and the treatment they receive. Finally, we will present a perspective of what the future could hold, both in terms of the selection of the patients and of a more customized therapeutic approach. PMID- 20735309 TI - Ipsilateral breast tumor recurrence after breast-conserving therapy. AB - In the modern era of breast-conserving therapy for early-stage breast cancer, ipsilateral breast tumor recurrence (IBTR) represents an increasingly common clinical dilemma. Two kinds of IBTRs have been described: true recurrences, which represent regrowth of uneradicated initial disease, and new primaries, which may be distinct from the index lesion in histology and location. Whether these two entities have different biologies and survival prognoses remains unclear. This article will examine contemporary clinical and pathologic methods to distinguish true recurrence from new primary tumors, focusing on available published data from prospective and retrospective studies. Current challenges and future avenues are discussed for developing a standardized, reproducible classification system for different types of IBTR that may be used in the clinical setting to prognosticate and individualize treatment for patients following in-breast recurrences. PMID- 20735310 TI - Early recurrence risk: aromatase inhibitors versus tamoxifen. AB - Aromatase inhibitors (AIs) are becoming the hormonal treatment of choice for postmenopausal women with early breast cancer. Large, well-controlled clinical studies have established the efficacy and safety of initial adjuvant therapy with letrozole or anastrozole versus the previous standard of 5 years of adjuvant tamoxifen and support using an AI (exemestane, anastrozole or letrozole) following tamoxifen for 2-3 years (early 'switch' treatment) or 5 years (extended adjuvant treatment). Reducing recurrence risk is a primary goal of adjuvant hormonal therapy. There is an early peak of recurrences 2 years after surgery; most are distant metastases rather than local or regional events. Therefore, treatment strategies such as initial therapy with AIs, which reduce early distant recurrence events, can be expected to improve long-term survival outcomes. Switching to an AI following 2-3 years of initial adjuvant tamoxifen is an effective option for patients unable to begin treatment with an AI. PMID- 20735311 TI - Simultaneous targeting of estrogen receptor and HER2 in breast cancer. AB - Approximately 50% of HER2-positive breast cancers express estrogen receptor (ER) and these tumors are characterized by short-lived responses to hormonal agents. Preclinical models have shown that dual targeting of ER and HER2 could reverse and delay the development of drug resistance. Two studies (TAnDEM & EGF3008) have recently been published addressing the combined use of an aromatase inhibitor (AI) and an anti-HER2-targeted agent. Both studies showed that the combined approach is associated with improvement in response rate and progression-free survival compared with an AI alone with an acceptable toxicity profile. These results would indeed extend the treatment options for patients with ER/HER2 positive metastatic breast cancer. In this article, we discuss how the improved understanding of the complex cross-talk between ER and HER2 has resulted in better clinical outcomes. We analyze clinical evidence regarding the combined use of AIs and anti-HER2-targeted agents. We also touch on possible mechanisms of resistance and ways to improve research in this field. PMID- 20735312 TI - Outcomes following adjuvant therapy for HER2-positive early breast cancer in the elderly. AB - A third of breast cancer diagnoses are made in women aged 70 years or over. Historically, older women have been regarded as presenting with tumors that are low grade and hormone sensitive and that are likely to have a good prognosis. However, in those older women whose tumors overexpress the HER2 oncogene, the prognosis is likely to be worse. Under these circumstances, due consideration should be given to adjuvant systemic therapy, including chemotherapy and targeted treatments, in order to minimize risks of disease recurrence. In this article we discuss the evidence base for the role of adjuvant systemic therapy in older women with HER2-positive early breast cancer. PMID- 20735313 TI - Intermeshing breast reconstruction and postmastectomy radiation. AB - In women with advanced breast cancer or those with early-stage cancer for whom there is a contraindication for breast-conserving therapy, mastectomy is the primary surgical treatment. This is often followed by breast reconstruction in either an immediate or delayed fashion. There is a great psychological and emotional benefit for the patient to have immediate reconstruction at the time of initial mastectomy. Recently, evidence has demonstrated that postmastectomy radiation therapy (PMRT) administered in conjunction with systemic therapy improves not only locoregional control but also survival. This has increased the number of women receiving PMRT and resulted in much debate in the literature regarding the timing of radiation therapy and the types of reconstructive options. In this article, the authors review the literature for controversies and currently accepted practices for intermeshing PMRT and breast reconstruction following mastectomy. We also summarize the key issues related to the integration of breast reconstruction with PMRT and detail the experience and complications arising from this integration. PMID- 20735314 TI - Selecting multimodal therapy for rhabdomyosarcoma. AB - Rhabdomyosarcoma is a typical tumor of childhood, characterized by a high grade of malignancy, local invasiveness and a marked propensity to metastasize, but also a generally good response to chemotherapy and radiotherapy. Multimodal therapy is essential to cure rhabdomyosarcoma patients, but different uses of surgery, radiotherapy and chemotherapy, and their intensity, need to be selected and modulated to different patient risk groups. This article attempts to give an account of the current treatment options, the open and debated issues and the potential novel strategies for the near future. PMID- 20735315 TI - Novel targeted therapies in the treatment of soft-tissue sarcomas. AB - Systemic therapy options for sarcomas historically have been limited once these tumors become resistant to traditional cytotoxic chemotherapy. Ongoing preclinical research into their biology and clinical trials based on rational biologic targeting have identified novel therapies. For example, the success of imatinib in gastrointestinal stromal tumor has led to the use of other tyrosine kinase inhibitors in other sarcoma subtypes. Other novel therapies include targeting of the mTOR pathway, and IGF-1 receptor. The heterogeneity of these tumors demands intelligently designed protocols in recognizing efficacy that may be restricted to certain histologic subtypes. This article will cover recent trials of new biologic agents in sarcomas that have exhibited promising activity. PMID- 20735316 TI - How can survival be improved in localized osteosarcoma? AB - Despite numerous chemotherapy trials and the introduction of novel agents, survival in localized osteosarcoma, which plateaued in the mid-1980s, has been recalcitrant to our best efforts. The authors considered that a review of previous and current strategies that target survival might provide a direction for research efforts. Here, the focus is placed mainly on the reappraisal of previous mass chemotherapy trials and prognostic factors, in the hope of contriving a strategy to overcome the current stasis. PMID- 20735317 TI - Animal models of osteosarcoma. AB - Appendicular osteosarcoma (OS) is a primary mesenchymal tumor arising from malignantly transformed osteoblasts. In people, OS is the most common nonhematopoietic, primary skeletal neoplasm diagnosed in adolescents and is the second leading cause of cancer-related fatalities within this age group. Despite aggressive therapeutic management, including limb-sparing surgeries and dose intense systemic chemotherapies, 30-40% of patients will experience progressive metastatic disease within 5 years of diagnosis. In order to reduce the fatality rate associated with recurrent or metastatic OS, a more thorough understanding of OS pathogenesis and biology is required. Towards this pursuit, comparative animal models of OS have been developed and are actively being studied to expand our fundamental understanding of OS. It is anticipated that specific animal models of OS, which most accurately recapitulate the natural disease process in people, will be most useful for advancing our understanding of OS biology, and will facilitate the discovery of disease pathogenesis and the identification of novel therapeutic strategies for managing this lethal metastatic bone sarcoma. PMID- 20735319 TI - Mineralization of hydrogels for bone regeneration. AB - Hydrogels are an important class of highly hydrated polymers that are widely investigated for potential use in soft tissue engineering. Generally, however, hydrogels lack the ability to mineralize, preventing the formation of chemical bonds with hard tissues such as bone. A recent trend in tissue engineering involves the development of hydrogels that possess the capacity to mineralize. The strategy that has attracted most interest has been the incorporation of inorganic phases such as calcium phosphate ceramics and bioglasses into hydrogel matrices. These inorganic particles act as nucleation sites that enable further mineralization, thus improving the mechanical properties of the composite material. A second route to create nucleation sites for calcification of hydrogels involves the use of features from the physiological mineralization process. Examples of these biomimetic mineralization strategies include (1) soaking of hydrogels in solutions that are saturated with respect to calcium phosphate, (2) incorporation of enzymes that catalyze deposition of bone mineral, and (3) incorporation of synthetic analogues to matrix vesicles that are the initial sites of biomineralization. Functionalization of the polymeric hydrogel backbone with negatively charged groups is a third mechanism to promote mineralization in otherwise inert hydrogels. This review summarizes the main strategies that have been developed in the past decade to calcify hydrogel matrices and render these hydrogels suitable for applications in bone regeneration. PMID- 20735320 TI - Group interactive structured treatment (GIST): a social competence intervention for individuals with brain injury. AB - BACKGROUND: Impairments in social competence are among the most prevalent sequelae of traumatic brain injury and present a major barrier to a person returning to a productive life. The recent increased incidence of TBI among military personnel and the subsequent difficulties these individuals face reintegrating into society accentuates the need for efficacious social competence treatment interventions for the TBI population. METHOD AND RESULTS: This paper outlines the theoretical model and clinical application of Group Interactive Structured Treatment (GIST) for Social Competence. GIST- Social Competence is a structured cognitive-behavioural group therapy model addressing the underlying cognitive, communicative and emotional impairments impeding social competence after TBI. A recent randomized control trial (RCT) funded by the National Institute on Disability and Rehabilitation Research demonstrated the efficacy of this programme. GIST integrates the principles of established cognitive behavioural therapy, group therapy and holistic neuro-rehabilitation in a manualized 13 week intervention combining a structured curriculum with a group therapy format. The structured cognitive-behavioural approach allows even those with significant underlying deficits (including self-awareness, memory, problem solving, etc.) to benefit from this intervention. CONCLUSION: The GIST model can be applied to other treatment areas in TBI rehabilitation. Clinical observations from application of GIST with military personnel are reviewed. PMID- 20735321 TI - Rib cartilage harvesting in rhinoplasty procedures based on CT radiological data. AB - CONCLUSION: In general, harvesting of costal cartilage from the seventh rib from the right side appears advisable for rhinoplasty procedures in male and female patients. The thickness of the soft tissue envelope anterior to the different ribs varies significantly, which demands an individual consideration in rhinoplasty procedures. OBJECTIVES: To clarify which of the sixth, seventh or eighth rib contains the maximum amount of cartilage and degree of calcification in relation to age, side, and gender. METHODS: Digital 2 mm slices of spiral diagnostic thorax CT scans were used to measure costal cartilage sizes in a retrospective study. A total of 60 male and 60 female patients with normal findings were collected and stratified by age (range 16-70 years). RESULTS: On both sides, the seventh rib was identified as the most cartilage-containing rib, independent of gender. The length of costal cartilage of the sixth and seventh rib was significantly related to age on both sides (p < 0.01). This finding did not reach statistical significance for the eighth rib, on either the right (p = 0.376) or the left side (p = 0.204). Calcification of the sixth and seventh rib, but not of the eighth rib, significantly increased with age. In general, calcification was not related to gender or one side. PMID- 20735322 TI - Preoperative combined 18-fluorodeoxyglucose positron emission tomography and computed tomography imaging in head and neck cancer: does it really improve initial N staging? AB - CONCLUSION: In our experience PET-CT cannot yet reliably predict the need for surgical neck dissection in patients with N0 neck. According to the results of PET-CT the neck dissection should be extended towards unusual lymph node areas. OBJECTIVE: To analyze the value of PET-CT for the initial N staging, comparing PET-CT data with histopathological results of the modified radical neck dissection. METHODS: Fifty patients with previously untreated head and neck squamous cell carcinoma were eligible for inclusion in this study. Modified radical unilateral or bilateral neck dissection was performed in all patients. PET-CT findings and histological findings were compared to determine their diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: In all, 105 levels had pathologically diagnosed metastases: PET-CT was positive in 87 levels and negative in 18 levels. Also, 399 levels had negative postoperative histology findings: PET-CT was positive in 24 levels and negative in 375 levels. The false-positive over-staged and the false-negative under-staged rates were 27% and 12%, respectively. PMID- 20735323 TI - Genetic relatedness and antifungal susceptibility profile of Candida albicans isolates from fungaemia patients. AB - A prospective study to assess fungaemia was conducted for 12 months at a Portuguese University Hospital. A total of 35 Candida albicans isolates obtained from 12 patients with fungaemia were compared by a multiplex PCR system using four microsatellite loci. Blood isolates were evaluated against concomitant isolates from urine, lower respiratory secretions and central venous catheters, as well as with successive isolates recovered from recurrent episodes of fungaemia. The data analyzed included the department of admission, underlying diseases and antifungal therapy. The susceptibility phenotypes of all isolates to amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin were determined according to the CLSI M27-A3 protocol. We observed a high degree of similarity between successive blood isolates and between blood and concomitant isolates from other sites of the same patient. This is suggestive of the recurrence of fungaemia and was due to the same strain, possibly as a result of the failure of antifungal therapy. The genetic similarity observed between some strains isolated from different patients suggested the likelihood that they were hospital acquired. Distinct patients were infected by the same strain at different time periods, and an increase in antifungal resistance was observed over time for some of these strains. Hospital-acquired exogenous nosocomial infections can be associated with higher risks of antifungal resistance and need to be closely monitored. Particular attention should also be given to endogenous non-blood Candida isolates which can be critical in high risk patients, as they often can become invasive in immunodeficient individuals. PMID- 20735324 TI - Potential applications of natural origin polymer-based systems in soft tissue regeneration. AB - Despite the many advances in tissue engineering approaches, scientists still face significant challenges in trying to repair and replace soft tissues. Nature inspired routes involving the creation of polymer-based systems of natural origins constitute an interesting alternative route to produce novel materials. The interest in these materials comes from the possibility of constructing multi component systems that can be manipulated by composition allowing one to mimic the tissue environment required for the cellular regeneration of soft tissues. For this purpose, factors such as the design, choice, and compatibility of the polymers are considered to be key factors for successful strategies in soft tissue regeneration. More recently, polysaccharide-protein based systems have being increasingly studied and proposed for the treatment of soft tissues. The characteristics, properties, and compatibility of the resulting materials investigated in the last 10 years, as well as commercially available matrices or those currently under investigation are the subject matter of this review. PMID- 20735325 TI - Diagnostic value of the rapid influenza antigen test for novel influenza A (H1N1). AB - We administered both the rapid antigen test and real-time reverse transcriptase polymerase chain reaction (RT-PCR) test to 2154 patients in order to assess the diagnostic value of the rapid antigen test during Korean pandemics of H1N1 2009. The overall sensitivity was 70.0%, specificity was 97.5%, positive predictive value was 97.4%, and negative predictive value was 71.2%. The sensitivity fell and the negative predictive value decreased as the RT-PCR positive rate increased. PMID- 20735326 TI - Legionnaires' disease and Pontiac fever after using a private outdoor whirlpool spa. AB - Pontiac fever and Legionnaires' disease are regarded as clinically and epidemiologically distinct diseases, caused by bacteria of the genus Legionella. Although several outbreaks of either Pontiac fever or Legionnaires' disease have been reported, they are rarely seen simultaneously. In this report we describe such a simultaneous outbreak of Pontiac fever and Legionnaires' disease that occurred in the Netherlands. In August 2009, 1 patient with Legionnaires' disease and 3 patients with Pontiac fever, all from a single family, were reported to the Municipal Health Service. All family members had been exposed to the private whirlpool spa in the garden of their home. A sampling investigation by the Legionella Source Identification Unit (LSIU) showed that a sample from the whirlpool spa, as well as a sample from the garden shower and 2 samples from a garden hose were positive for Legionella pneumophila serogroup 1, and genotyping results indicated the AFLP-type 004 Lyon (ST47) to be present in these samples. PMID- 20735327 TI - Skin and soft tissue infections caused by Staphylococcus lugdunensis: report of 20 cases. AB - Staphylococcus lugdunensis is an unusually virulent coagulase-negative Staphylococcus (CoNS). The aim of the present study was to investigate the clinical and microbiological characteristics of 20 cases of skin and soft tissue infections (SSTIs) due to S. lugdunensis that occurred in our area. The frequency of SSTIs due to this organism was 0.42%. The infection was secondary to trauma, surgery or skin disease in 15 patients (75%). Abscesses (7 cases), surgical wound infections (6 cases) and cellulitis (3 cases) were the most common clinical presentations. Breast, abdomen and lower limbs were the most frequent locations. Twelve infections were community-acquired (60%) and S. lugdunensis was the only pathogen isolated from 15 of the 20 specimens (75%). All patients were cured after therapy with antibiotics, associated or not with surgical drainage. The duration of antibiotic treatment ranged from 5 to 21 days. All isolates were susceptible to most of the antibiotics tested including oxacillin. In conclusion, S. lugdunensis is a CoNS that should be considered a potential pathogen when isolated from SSTIs, especially in patients with skin diseases or after trauma or surgery. S. lugdunensis can be underrated if microbiology laboratories do not routinely identify CoNS to the species level in these infections. PMID- 20735328 TI - Tuberculosis among children in Oslo, Norway, from 1998 to 2009. AB - We investigated all confirmed cases of tuberculosis (TB) among children (age < 16 y) in Oslo from 1998 to 2009. The overall incidence rate was 2.6 per 100,000 person-y. All 24 children diagnosed with TB were of non-Western origin, and the overall incidence rate in this group was 8.1 per 100,000 person-y. Among children of Somali origin, the incidence rate was 52.5 per 100,000 person-y. Pulmonary infiltrates (n = 7), hilar lymphadenopathy without infiltrates (n = 7) and lymph node TB in the neck (n = 5) were the most common clinical presentations. However, we also diagnosed TB meningitis, spondylitis, coxitis and pleuritis. None of the children were HIV-infected. Mycobacterium tuberculosis was cultivated in 19 out of 24 cases (79%). Of the 19 culture-positive cases, 13 had been tested with a polymerase chain reaction, of which 7 (54%) were positive. Isolates from 2 patients were resistant to isoniazid, 1 isolate was resistant to streptomycin, and 2 were resistant to both isoniazid and streptomycin. All children were treated according to a directly observed treatment short-course (DOTS) protocol. One child with TB meningitis died. Twenty-one patients finished treatment in Oslo, and all were cured without major sequelae or recurrence. TB among non Western immigrant children is still a challenge in Norway. PMID- 20735329 TI - Kikuchi-Fujimoto disease causing fever of unknown origin in a nine-year-old boy. AB - We describe a case of fever of unknown origin (FUO) in a 9-y-old boy finally diagnosed with Kikuchi-Fujimoto disease (KFD) and discuss the implications for the management of FUO in children. KFD should be considered in the differential diagnosis of patients presenting with FUO to prevent misdiagnosis and inappropriate treatment. PMID- 20735330 TI - Rickettsia felis infection in Sweden: report of two cases with subacute meningitis and review of the literature. AB - Two patients with headache and pleocytosis were diagnosed with Rickettsia felis infection using a polymerase chain reaction of cerebrospinal fluid and serological testing. Sequencing of the amplified products showed that they were 99-100% homologous to R. felis. These cases add to our knowledge of the clinical manifestations, as well as the geographical distribution, of this spotted fever agent. PMID- 20735331 TI - Pneumococcal serotype distribution in invasive paediatric disease in Southern Finland before the introduction of vaccine. AB - Vaccination with pneumococcal conjugate vaccines (PCV) has been started in many countries, resulting in a marked decrease in the incidence of invasive pneumococcal disease (IPD). After the decline, an increase in the incidence of IPD caused by non-vaccine serotypes has been observed. Finland has just decided to incorporate PCV into the national immunization programme, starting 1 September 2010. We describe the patients treated for IPD in one hospital in Finland before the use of PCV. Details of patients treated for IPD at the Children's Hospital, University of Helsinki between 2002 and 2007, were sought using the hospital discharge register and laboratory data. In total 118 cases of IPD were diagnosed in 113 children between 1 January 2002 and 31 December 2007. The yearly number of cases of IPD increased from 10 in 2002 to 26 in 2007. There were 5 deaths, all in patients with meningitis (5/19, 26%), and the total mortality was 4% (5/113). Seventy-five (77%) of the 97 pneumococcal isolates for which serotype was available were covered by the 7-valent PCV; 77% were also in the 10-valent PCV and 91% in the 13-valent PCV. Considering the serotype distribution of the pneumococcal isolates, a marked benefit is expected from including PCV in the vaccination programme. PMID- 20735332 TI - Molecular picture of community- and healthcare-associated methicillin-resistant Staphylococcus aureus circulating in a teaching hospital in Milan. AB - The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically changed over the past 10 y with the emergence of community associated MRSA (CA-MRSA). Recent studies have reported a frequent association of these strains with hospital outbreaks, and an incidence varying over time and by region. In order to evaluate the MRSA lineages circulating in our area of Italy, we performed a molecular characterization of CA-MRSA isolates prospectively collected from April 2006 to July 2007 at the San Paolo Hospital of Milan. We investigated the protein A-encoding gene (spa-typing), the staphylococcal chromosomal cassette SCCmec, the presence of Panton-Valentine leukocidin (PVL), and 3 adhesin genes. Twenty-five CA-MRSA isolates cultured from 25 patients were collected; an equal number of healthcare-associated (HA)-MRSA strains, from 25 patients hospitalized in various wards, were collected for comparison purposes. SCCmec type IV emerged as the most frequent genotype in both CA- and HA-MRSA. Seventeen different spa types were identified: t515 was the most common (36%), followed by t008 (20%). We detected 3 PVL-positive strains, only among the CA MRSA. On the whole, our local MRSA epidemiology appears to be heterogeneous, with a predominant t515 spa type, only recently considered to belong to clonal EMRSA 15. PMID- 20735333 TI - Resistance to tobramycin and colistin in isolates of Pseudomonas aeruginosa from chronically colonized patients with cystic fibrosis under antimicrobial treatment. AB - Tobramycin and colistin represent 2 standard antimicrobial agents in the treatment of cystic fibrosis (CF) patients who are chronically colonized with Pseudomonas aeruginosa. In this study, we determined the rate of resistance to tobramycin and colistin in 1844 isolates of P. aeruginosa obtained from 22 CF patients under alternate therapy with inhaled tobramycin and colistin. Resistance to tobramycin was observed in 27.5% of isolates. In contrast, all isolates were susceptible to colistin. Molecular typing of selected isolates suggested that only 1 clone occurred over time in each patient. To conclude, resistance to tobramycin in P. aeruginosa isolates from CF patients under antimicrobial therapy may occur while colistin resistance remains uncommon. PMID- 20735335 TI - Erwin frink smith-pioneer plant pathologist. PMID- 20735334 TI - Pylephlebitis: an overview of non-cirrhotic cases and factors related to outcome. AB - Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971-1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis. PMID- 20735336 TI - Extension plant pathology: challenges and opportunities. PMID- 20735337 TI - The changing role of extension plant pathologists. PMID- 20735338 TI - ePPR: a new strategy for the characterization of sensory cells from input/output data. AB - A central goal of systems neuroscience is to characterize the transformation of sensory input to spiking output in single neurons. This problem is complicated by the large dimensionality of the inputs. To cope with this problem, previous methods have estimated simplified versions of a generic linear-nonlinear (LN) model and required, in most cases, stimuli with constrained statistics. Here we develop the extended Projection Pursuit Regression (ePPR) algorithm that allows the estimation of all of the parameters, in space and time, of a generic LN model using arbitrary stimuli. We first prove that ePPR models can uniformly approximate, to an arbitrary degree of precision, any continuous function. To test this generality empirically, we use ePPR to recover the parameters of models of cortical cells that cannot be represented exactly with an ePPR model. Next we evaluate ePPR with physiological data from primary visual cortex, and show that it can characterize both simple and complex cells, from their responses to both natural and random stimuli. For both simulated and physiological data, we show that ePPR compares favorably to spike-triggered and information-theoretic techniques. To the best of our knowledge, this article contains the first demonstration of a method that allows the estimation of an LN model of visual cells, containing multiple spatio-temporal filters, from their responses to natural stimuli. PMID- 20735339 TI - Multilinear models of single cell responses in the medial nucleus of the trapezoid body. AB - The representation of acoustic stimuli in the brainstem forms the basis for higher auditory processing. While some characteristics of this representation (e.g. tuning curve) are widely accepted, it remains a challenge to predict the firing rate at high temporal resolution in response to complex stimuli. In this study we explore models for in vivo, single cell responses in the medial nucleus of the trapezoid body (MNTB) under complex sound stimulation. We estimate a family of models, the multilinear models, encompassing the classical spectrotemporal receptive field and allowing arbitrary input-nonlinearities and certain multiplicative interactions between sound energy and its short-term auditory context. We compare these to models of more traditional type, and also evaluate their performance under various stimulus representations. Using the context model, 75% of the explainable variance could be predicted based on a cochlear-like, gamma-tone stimulus representation. The presence of multiplicative contextual interactions strongly reduces certain inhibitory/suppressive regions of the linear kernels, suggesting an underlying nonlinear mechanism, e.g. cochlear or synaptic suppression, as the source of the suppression in MNTB neuronal responses. In conclusion, the context model provides a rich and still interpretable extension over many previous phenomenological models for modeling responses in the auditory brainstem at submillisecond resolution. PMID- 20735340 TI - MicroPET imaging of noxious thermal stimuli in the conscious rat brain. AB - Small animal positron emission tomography (microPET) has been utilized in the investigation of nociception. However, a possible drawback from previous studies is the reduced activation pattern due to the application of anesthesia. The purpose of the present study was to demonstrate a potential means of avoiding anesthesia during stimulation, as well as minimizing the confounding anesthetic effect. Sodium pentobarbital and ketamine were first evaluated to determine their effect on microPET images in the current study. [(18)F]-Fluorodeoxyglucose ((18)F FDG) was an appropriate radiotracer to reveal activated regions in rat brains. Pentobarbital anesthesia significantly reduced (18)F-FDG uptake in neural tissues, blurrier to lower contrast; therefore, ketamine was used to anesthetize animals during microPET. After the rats were anesthetized and secured in a laboratory-made stereotaxic frame, a simple, noninvasive stereotaxic technique was used to position their heads in the microPET scanner and to roughly conform the images in the stereotaxic atlas. For functional imaging, conscious rats were restrained in cages with minimal ambient noise; short repetitive thermal stimuli were applied to each rat's tail subsequently. The rats were adequately anesthetized with ketamine following 30 min of scanning without stimulation. An activation index (AI) was calculated from microPET data to quantify the local metabolic activity changes according to the normalized (18)F-FDG dosage. The average AI indicated a side-to-side difference for all innocuous stimulations in the thalamus. However, such side-to-side difference was only observed for noxious heat and cold stimulations in primary somatosensory cortex (SI), secondary somatosensory cortex (SII), and agranular insular cortex (AIC). The present study demonstrated the feasibility of the microPET technique to image metabolic functions of the conscious rat brain, offering better rationale and protocol designs for future pain studies. PMID- 20735341 TI - Infliximab-induced demyelination causes visual disturbance mistaken for recurrence of HLA-B27-related uveitis. AB - PURPOSE: To report a patient treated with infliximab for ankylosing spondylitis and HLA-B27 uveitis presenting with a scotoma in his left good eye due to infliximab-induced occipital demyelination mistaken for a uveitis recurrence. DESIGN: Case report. METHODS: Review of clinical features, visual field, and investigational procedures. RESULTS: Loss of visual function could not be explained by mere ophthalmic examination. Magnetic resonance imaging showed several demyelinating lesions, explaining the patient's symptoms and signs. Infiliximab was discontinued and the scotoma disappeared. CONCLUSION: This is the first report of infliximab-induced demyelination producing ocular symptoms and signs in a patient treated for uveitis. PMID- 20735342 TI - Effects of music therapy on psychological symptoms and heart rate variability in patients with dementia. A pilot study. AB - We assessed the effects of music therapy (MT) on behavioral and psychological symptoms (BPSD) in dementia associated with changes in physiological parameters, as heart rate (HR) and heart rate variability (HRV). Twenty subjects were randomly assigned to MT treatment or standard care; all patients underwent neuropsychological assessment and ECG Holter recordings before and after the 15 week treatment. The treatment included 30 MT sessions. Depression significantly decreased (p=0.021) in the MT group. PNN50 improved in 50% patients of the MT group, but in none of the control group (p=0.013). MT may improve symptoms of depression and increase HRV in demented patients. PMID- 20735343 TI - Honey, health and longevity. AB - Honey is a broad spectrum antimicrobial agent which can enhance wound healing. A beneficial effect in cancer has been shown in cell cultures and in animal studies and a number of further nutritional and physiological effects of relevance to health and function have been shown for honey. A representative sub-sample of 665 men within the Caerphilly Cohort kept a weighed dietary record for seven days. Risk factors for vascular and other diseases in 41 men who recorded eating honey suggest that these men were on the whole healthier than the 624 men who had not recorded honey consumption. All-cause mortality during 25 years of follow-up was considerably lower in the men who had consumed honey, the hazard ratio, adjusted for a number of possible confounding factors, being 0.44 (95% confidence limits 0.23, 0.86; P<0.017). Because of the small number of subjects and of deaths in this study, further data from other large cohorts will be required before any effect upon mortality and other health effects of honey consumption can be adequately evaluated. PMID- 20735344 TI - Amyloid beta (Abeta) protein- and amyloid precursor protein (APP)-immunoreactive structures in the brains of aged tree shrews. AB - BACKGROUND: Amyloid beta (Abeta) accumulates in the human brain in an age dependent manner during normal aging. However, Abeta accumulation has not been observed in rodents during normal aging. Tree shrews, the experimental animals studied here, are as small as rats but have a longer life span than rodents. METHODS: We investigated Abeta accumulations in the brains of young and aged tree shrews by amyloid histochemistry and immunohistochemistry using antibodies to Abeta-42, Abeta-40, Abeta-16 and amyloid precursor protein (APP). RESULTS: In the brain of young tree shrews, there were no Abeta- immunoreactive (-ir) and APP-ir profiles. In the brains of aged tree shrews, Abeta-42-ir neuronal profiles were observed in the cortex, subiculum, basal ganglia, mammillary body and hypothalamus, but there were only a few weak Congo red-positive amyloid deposits. Abeta-42-, Abeta-40-, Abeta-16- and APP-ir blood vessels were observed. CONCLUSIONS: An early stage of amyloid accumulation occurs in the brains of aged tree shrews, indicating that this animal may be a good model for studying the start of Abeta accumulation. PMID- 20735345 TI - Clearance of amyloid-beta peptide across the choroid plexus in Alzheimer's disease. AB - Aging and several neurodegenerative diseases bring about changes in the anatomy and physiology of the choroid plexus. The identification of specific membrane receptors that bind and internalize extracellular ligands has revolutionized the traditional roles of this tissue. Amyloid beta peptide (Abeta), the major constituent of the amyloid core of senile plaques in patients with Alzheimer's disease (AD) is known to contribute to disease neuropathology and progression. Recent emphasis on comorbidity of AD and a deficient clearance of Abeta across the blood-brain barrier and blood-cerebrospinal fluid barrier have highlighted the importance of brain Abeta clearance in AD. The megalin receptor has also been implicated in the pathogenesis of AD. Faulty Abeta clearance from the brain across the choroid plexus epithelium by megalin appears to mediate focal Abeta accumulation in AD. Patients with AD have reduced levels of megalin at the choroid plexus, which in turn seem to increase brain levels of Abeta through a decreased efflux of brain Abeta. Therapies that increase megalin expression at the choroid plexus could potentially control accumulation of brain Abeta. This review covers in depth the anatomy and function of the choroid plexus, focusing on the brain barrier at the choroid plexus, as it actively participates in Abeta clearance. In addition, we describe the role of the choroid plexus in brain functions, aging and AD, as well as the role of megalin in the process of Abeta clearance. Finally, we present current data on the use of choroid plexus cells to repair the damaged brain. PMID- 20735346 TI - Aging in bacteria, immortality or not-a critical review. AB - Bacteria were traditionally thought to have a symmetrical binary fission without a clear distinction between soma and germ-line, being thus considered as immortal biological entities. Yet it has been recently described that bacteria also undergo replicative aging (RA). That is, they exhibit finite replicative abilities under good conditions to growth. The apparently initial indistinguishability of sibling cells after cytokinesis is broken. After division, the daughter cell that inherits the "old" pole present in the "mother cell" progressively exhibits a decline in its proliferative capacity with increasing cell pole age. This is a clear hallmark and phenotypic manifestation of a bona fide RA phenomenon in toto. While the exact molecular mechanism(s) underlying to this lost of replicative potential are not yet fully understood, the "old pole cell" is considered as an aging parent that in a repeatedly manner is able to produce rejuvenated offspring which inherit a resetting of the biological clock. On the order hand, bacteria exhibit in addition to this "mandatory" RA the dubbed conditional senescence (CS). CS is defined as a decline in cellular viability observed in arrested-growing bacteria populations, a phenomenon apparently not related to RA under growing active conditions. To understand bacterial aging, it is necessary to put it within the sociality multicellularity framework. This is a new conceptual paradigm that expresses the natural reality of the bacterial world. From this more ecological perspective these bacterial aging phenomena probably should represent an insurance/bethedging anticipative survival strategy. This is underpinned in a self-generation of an appropriate level of populational phenotypic diversity. That is, bacterial aging could be considered a communitarian adaptive response to cope with different environmental stresses and threats. I have highlighted the necessity to construct an integrative conceptual framework to achieve a unified view of bacteria aging to answer this fundamental question: what are the reasons of bacterial aging? PMID- 20735347 TI - The relationship between age-related kidney dysfunction and Framingham risk score in healthy people in China. AB - BACKGROUND: Aging process reduces kidney function, glomerular filtration rate (GFR) and/or creatinine clearance rate (Ccr), and also significantly increases the risk level for cardiovascular diseases. The classical Framingham risk equation provides a method for predicting cardiovascular risk, but it does not include the kidney function indexes. In this study, we investigated the relationship between age-related kidney function and Framingham risk score (FRS) in healthy Chinese people, and validated to assess the risk factor by GFR/Ccr. METHODS: This community-based cross-sectional study recruited 505 healthy subjects (age from 35 to 93 yr.) with both gender is during September 2007 to June 2008 in Shenyang. Framingham risk equation was used to evaluate cardiovascular risk factors and generate FRS. GFR and Ccr were calculated with Cockcroft-Gault (CG) equation (GFR(CG)), abbreviated Modification of Diet in Renal Disease Study (MDRD) equation (GFR(MDRD1)) and modified MDRD equation (GFR(MDRD2)). All data were sorted according to FRS (low, moderate and high) risk levels, and five different age groups (<=44 yr; 45-54 yr; 55-64 yr; 65-74 yr and >=75 yr). The ANOVA, correlation, partial correlation between GFR/Ccr and FRS, as well as other risk factors were analyzed with SPSS16.0 statistical package. RESULTS: As the FRS level increased, GFR(CG), GFR(MDRD1), GFR(MDRD2) and Ccr decreased about 10 to 30% (low>moderate> high risk group, p<0.01). While the subjects were getting older, GFR(CG), GFR(MDRD1), GFR(MDRD2) and Ccr showed significant reduction (P<0.001). Ccr decreased about 50% from the young to oldest group (p<0.001). There was a significantly inverse correlation between FRS and GFR with Ccr having the Pearson correlation coefficient -0.586 (GFR(CG), P<0.001), - 0.449 (GFR(MDRD1) and GFR(MDRD2), P<0.001), -0.459 (Ccr, P<0.001). However, the relationship between FRS and Ccr was lost after controlling for age and other confounding variables. CONCLUSION: In healthy population, we found inverse correlations between Framingham risk score and GFR, Ccr and GFR were independently related to the FRS with similar correlation coefficient among three equations. With the increase of FRS, the GFR and Ccr decrease. Aging is the major factor of GFR and Ccr reduction in the healthy population. We suggest that GFR/Ccr could be used as risk indexes for cardiovascular diseases. PMID- 20735348 TI - Potentiality of oxygen-ozonetherapy to improve the health of aging people. AB - During the last century the lifespan of human beings has increased from about 49 to almost 80 years owing to the great advances of biomedical sciences. This fact has strongly stimulated the idea that it may be possible to prolong productive life for another twenty years but paradoxically the problem of both hyper- and hyponutrition severely jeopardizes this objective all over the world. Many causes of premature aging have been discussed in order to prevent it or find suitable medical treatment. So far only a moderate restriction of caloric intake that does not alter essential nutrients has proved capable of keeping animals and humans healthier for a prolonged time. This modality appears to activate critical longevity genes that can prolong survival: although this is a valuable line of research it will take considerable time to produce valid drugs to selectively activate these relevant genes. Meantime we propose to evaluate an easy and well accepted treatment based on a weekly quasi-total body exposure to oxygen-ozone inside a thermostatically controlled cabinet. The rational exposure to a minimal amount of ozone acting as a mild stressor induces a striking improvement of crucial metabolic activities capable of preserving a good health for several years. PMID- 20735349 TI - Younger for longer: insulin signalling, immunity and ageing. AB - Genes, the environment and stochastic factors such as lifestyle are major contributors to the universally shared phenomenon of ageing. It is now clear that these different inputs act through evolutionarily conserved pathways to regulate lifespan in a wide range of animals. Among several such pathways, the IIS [Insulin/IGF (Insulin -like growth factor)- like signalling] pathway, initially identified in the roundworm, Caenorhabditis elegans, is the most significant modulator of ageing. Consisting of a PI 3 kinase-signalling cascade downstream of a transmembrane insulin-like growth factor receptor, this pathway ultimately regulates the activity of a transcription factor with a huge repertoire of transcriptional outputs. The effect of this is that the IIS pathway co-ordinately controls several processes, including immunity and stress resistance,which in tandem seem to regulate longevity. Since both the function and molecular architecture of the IIS pathway is conserved from yeast to mammals, this coordinate regulation appears to be a general feature of the ageing processes in animals. Here we review the evolutionary conservation of the IIS pathway and discuss this in relation to recent findings on the molecular basis of ageing. We also reflect on the impact and significance of the evolutionary diversification of this pathway and propose a model for how such differences could explain both inter and intra-species differences in ageing. PMID- 20735350 TI - Pin1: a new genetic link between Alzheimer's disease, cancer and aging. AB - Epidemiologic data suggest that people who develop neurodegenerative diseases of aging have a decreased risk of cancer. This is intriguing, since there is growing evidence that neurodegeneration and carcinogenesis share a number of biological pathways, such as abnormal entry into the cell cycle. The unique enzyme Pin1 plays a key role in the pathogenesis of Alzheimer's disease and many human cancers. Pin1 acts on proteins after they have been phosphorylated at specific sites, causing them to twist between two completely distinct conformations. This conformational change profoundly affects protein activity and is a major method of cellular signaling and regulation. In the neuron, Pin1 promotes cellular health by restoring phosphorylated tau and amyloid precursor protein to a functional state. The loss of active Pin1 leads to the accumulation of abnormal tau and the overproduction of beta-amyloid, the cardinal features of Alzheimer's disease. Pin1 also regulates the cell cycle and is a necessary enzyme for cell division. Over-expression of Pin1 can promote oncogenesis through a number of signaling pathways. We hypothesize that Pin1 might help explain an inverse relationship between Alzheimer's disease and cancer. Pin1 deficiency in mice leads to an early-aging phenotype, suggesting that Pin1 activity is necessary for healthy aging and the prevention of age-related diseases. We review the role of Pin1 in cancer and neurodegeneration, discuss the relationship between Pin1 and aging, and explore its potential as a diagnostic and therapeutic target. PMID- 20735351 TI - Vascular endothelial growth factor (VEGF) in the pathogenesis of diabetic nephropathy of type 1 diabetes mellitus. AB - Diabetic nephropathy (DN) is a common complication of diabetes mellitus and is the primary cause of end-stage renal disease in the Western World. Vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of DN of type 1 diabetes mellitus. VEGF is the main angiogenic factor and a potent mitogen for endothelial cells. It is mainly produced in kidney by podocytes and exerts its biological activities by binding to its receptors (VEGFRs). Alternative splicing of a single VEGF gene produces various isoforms and two families with anti- and pro-angiogenic properties. In normal glomeruli, VEGF isoforms are in tight regulation and act in a paracrine and an autocrine manner preserving the integrity of glomerular filtration barrier. Many mediators in diabetic milieu induce the expression of VEGF and possibly the VEGFxxx isoform in animal models of type 1 diabetes, however, in human kidney with developed DN, VEGF expression seems to be lower or absent. Inhibition of VEGF in experimental DN ameliorates structural and functional changes and proposes possible therapeutic targets. Further studies are required before these treatments can be used in diabetic patients at early stages of DN. PMID- 20735352 TI - Targeting trypanothione metabolism in trypanosomatid human parasites. AB - The diseases caused by the trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are widely distributed throughout the world. Because of the toxic side-effects and the economically unviable cost of the currently used pharmaceutical treatments, the search for new drug targets continues. Since the antioxidant metabolism in these parasites relies on trypanothione [T(SH)(2)], a functional analog of glutathione, most of the pathway enzymes involved in its synthesis, utilization and reduction have been proposed as drug targets for therapeutic intervention. In the present review, the antioxidant metabolism and the phenotypic effects of inhibiting by genetic (RNA interference, knock-out) or chemical approaches, the T(SH)(2) and polyamine pathway enzymes in the parasites are analyzed. Although the genetic strategies are helpful in identifying essential genes for parasite survival/infectivity, they are less useful for drug-target validation. The effectiveness of targeting each pathway enzyme was evaluated by considering (i) the enzyme kinetic properties and antioxidant metabolite concentrations and (ii) the current knowledge and experimental approaches to the study of the control of fluxes and intermediary concentrations in metabolic pathways. The metabolic control analysis indicates that highly potent and specific inhibitors have to be designed for trypanothione reductase and the peroxide detoxification system, and hence other enzymes emerge (gamma-glutamylcysteine synthetase, trypanothione synthetase, ornithine decarboxylase, S-adenosylmethionine decarboxylase and polyamine transporters) as alternative more suitable and effective drug targets in the antioxidant metabolism of trypanosomatids. PMID- 20735353 TI - Prostanoid receptors as possible targets for anti-allergic drugs: recent advances in prostanoids on allergy and immunology. AB - Prostanoids, consisting of prostaglandins and thromboxane, are cyclooxygenase metabolites of arachidonic acid released in various pathophysiological conditions which exert a range of actions mediated through their respective receptors expressed on target cells. Although it has been difficult to analyze the physiological role of prostanoids, recent developments in both the disruption of the respective gene and receptor selective compounds have enabled us to investigate the physiological roles for each receptor. It has been demonstrated that each prostanoid receptor has multiple functions, and that their expression is regulated in a context-dependent manner that sometimes results in opposite, excitatory and inhibitory, outcomes. The balance of prostanoid production and receptor expression has been revealed to be important for homeostasis of the human body. Here, we review new findings on the roles of prostanoids in allergic and immune diseases, focusing on contact dermatitis, atopic dermatitis, asthma, rheumatoid arthritis, and encephalomyelitis, and also discuss the clinical potentials of receptor-selective drugs. PMID- 20735354 TI - Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. AB - Drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. It is a goal of drug development programs to design selective ligands that act on single disease targets to obtain highly effective and safe drugs with low side effects. Although this strategy was successful for many new therapies, there is a marked decline in the number of new drugs introduced into clinical practice over the past decades. One reason for this failure may be due to the fact that the pathogenesis of many diseases is rather multi-factorial in nature and not due to a single cause. Phytotherapy, whose therapeutic efficacy is based on the combined action of a mixture of constituents, offers new treatment opportunities. Because of their biological defence function, plant secondary metabolites act by targeting and disrupting the cell membrane, by binding and inhibiting specific proteins or they adhere to or intercalate into RNA or DNA. Phytotherapeutics may exhibit pharmacological effects by the synergistic or antagonistic interaction of many phytochemicals. Mechanistic reasons for interactions are bioavailability, interference with cellular transport processes, activation of pro-drugs or deactivation of active compounds to inactive metabolites, action of synergistic partners at different points of the same signalling cascade (multi-target effects) or inhibition of binding to target proteins. "-Omics" technologies and systems biology may facilitate unravelling synergistic effects of herbal mixtures. PMID- 20735355 TI - Golgi apparatus fragmentation as a mechanism responsible for uniform delivery of uroplakins to the apical plasma membrane of uroepithelial cells. AB - BACKGROUND INFORMATION: The GA (Golgi apparatus) has an essential role in membrane trafficking, determining the assembly and delivery of UPs (uroplakins) to the APM (apical plasma membrane) of superficial UCs (uroepithelial cells) of urinary bladder. UPs are synchronously and uniformly delivered from the GA to the APM by DFVs (discoidal- or fusiform-shaped vesicles); however, the mechanism of UP delivery is not known. We have used the culture model of UCs with the capacity to undergo terminal differentiation to study the process of uniform delivery of DFVs to the APM and to elucidate the mechanisms involved. RESULTS: By three dimensional localization using confocal microscopy of immunofluorescence-labelled GA-related markers [GM130 (cis-Golgi matrix protein of 130 kDa), GS15 (Golgi Snare 15 kDa), GS28 and giantin], uroepithelial differentiation-related markers (UPs), MTs (microtubules; alpha-tubulin) and intermediate filaments [CK7 (cytokeratin 7) and CK20], we found that in non-differentiated, UP-negative UCs the GA is mostly organized as a single ribbon-like structure close to the nucleus, whereas in differentiated, UP-positive UCs the GA is fragmented and spread almost through the entire cell. The FRAP (fluorescence recovery after photobleaching) experiments on the UCs transfected with GalT (trans-Golgi/TGN enzyme beta1,4-galactosyltransferase) fused to fluorescent protein showed that Golgi-resident enzyme cycles freely within ribbon-like GA but not within fragmented GA. By CLEM (correlative light-electron microscopy), we examined the GA fragments in cells expressing UPs. We found that GA fragments are fully functional and similar to the GA fragments that are formed after nocodazole treatment. Furthermore, we demonstrated that the reorganization of GA into a fragmented form is associated with the impairment of the MT organization in the basal, central and subapical cytoplasm and the accumulation of intermediate filaments in the apical cytoplasm that could affect the kinetics of MT star leading to the peripheral fragmentation of the GA in the differentiated UCs. CONCLUSIONS: The fragmentation of the GA and the subsequent spreading of GA to the cell periphery represent one of the key events that promote the uniform delivery of UPs over the entire APM of differentiating UCs and thus are of major importance in the final proper formation and maintenance of the blood-urine barrier. PMID- 20735356 TI - Cytoplasmic and nuclear localization of cadherin in honey bee (Apis mellifera L.) gonads. AB - Cadherins are crucial molecules mediating cell-cell interactions between somatic and germline cells in insect and mammalian male and female gonads. We analysed the presence and localization of cadherins in ovaries of honeybee queens and in testes of drones. Transcripts representing two classical cadherins, E-cadherin (shotgun) and N-cadherin, as well as three protocadherins (Starry night, Fat and Fat-like) were detected in gonads of both sexes. Pan-cadherin antibodies, which most probably detect a honeybee N-cadherin, were used in immunolocalization analyses. In the germarium of ovarioles, cadherin-IR (cadherin immunoreactivity) was evidenced as homogeneously distributed in the cytoplasm and as nuclear foci, in both germline and somatic cells. It was also detected in polyfusomes and ring canals. In testiolar tubules, cadherin-IR showed a cytoplasmic and nuclear distributon alike in ovaries. The unexpected nuclear localization and cytoplasmic distribution in ovaries and testes were corroborated by immunogold electron microscopy, which revealed cadherin aggregates associated with electron-dense nuclear structures. With respect to cadherin localization, the honeybee differs from Drosophila, the model for gametogenesis in insects, raising the question as to how differences among solitary and social species may be built into and generated from the general architecture of polytrophic meroistic ovaries. It also indicates the possibility of divergent roles for cadherin in the functional architecture of insect gonads, in general, especially in taxa with high reproductive output. PMID- 20735357 TI - Involvement of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 in EGF-induced angiogenesis. AB - Angiogenesis is a process during which endothelial cells divide and migrate to form new capillaries from the preexisting blood vessels. The present study was designed to investigate whether MAPKs (mitogen-activated protein kinases) play crucial roles in regulating EGF (epidermal growth factor)-induced endothelial cell angiogenesis. Our results showed that EGF stimulated HUVEC (human umbilical vein endothelial cells) proliferation in a concentration-dependent manner, of which the maximum effective concentration of EGF was 10 ng/ml. Western blot analysis showed that EGF at 10 ng/ml significantly induced the phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1 and 2) and p38 kinase at 5 min, while it induced the phosphorylation of JNK/SAPK (c-Jun N-terminal kinase/stress activated protein kinase) at 15 min. Further results showed that a JNK/SAPK inhibitor, SP600125, and a specific siRNA JNK/SAPK could both significantly inhibit EGF-induced tube formation in HUVEC cells, and an ERK1/2 inhibitor PD098059 could also block the tube formation in some content, while a p38 inhibitor SB203580 failed to do so. Furthermore, only SP600125 significantly inhibited EGF-induced HUVEC cell proliferation under no cytotoxic concentration, so did JNK/SAPK siRNA. In conclusion, JNK/SAPK and ERK1/2 signals therefore play critical roles in EGF-mediated HUVEC cell angiogenesis. PMID- 20735358 TI - The chaperone proteins HSP70, HSP40/DnaJ and GRP78/BiP suppress misfolding and formation of beta-sheet-containing aggregates by human amylin: a potential role for defective chaperone biology in Type 2 diabetes. AB - Misfolding of the islet beta-cell peptide hA (human amylin) into beta-sheet containing oligomers is linked to beta-cell apoptosis and the pathogenesis of T2DM (Type 2 diabetes mellitus). In the present study, we have investigated the possible effects on hA misfolding of the chaperones HSP (heat-shock protein) 70, GRP78/BiP (glucose-regulated protein of 78 kDa/immunoglobulin heavy-chain-binding protein) and HSP40/DnaJ. We demonstrate that hA underwent spontaneous time dependent beta-sheet formation and aggregation by thioflavin-T fluorescence in solution, whereas rA (rat amylin) did not. HSP70, GRP78/BiP and HSP40/DnaJ each independently suppressed hA misfolding. Maximal molar protein/hA ratios at which chaperone activity was detected were 1:200 (HSP70, HSP40/DnaJ and GRP78/BiP). By contrast, none of the chaperones modified the secondary structure of rA. hA, but not rA, was co-precipitated independently with HSP70 and GRP78/BiP by anti-amylin antibodies. As these effects occur at molar ratios consistent with chaperone binding to relatively rare misfolded hA species, we conclude that HSP70 and GRP78/BiP can detect and bind misfolded hA oligomers, thereby effectively protecting hA against bulk misfolding and irreversible aggregation. Defective beta-cell chaperone biology could contribute to hA misfolding and initiation of apoptosis in T2DM. PMID- 20735359 TI - Lipin proteins form homo- and hetero-oligomers. AB - Lipin family members (lipin 1, 2 and 3) are bi-functional proteins that dephosphorylate PA (phosphatidic acid) to produce DAG (diacylglycerol) and act in the nucleus to regulate gene expression. Although other components of the triacylglycerol synthesis pathway can form oligomeric complexes, it is unknown whether lipin proteins also exist as oligomers. In the present study, using various approaches, we revealed that lipin 1 formed stable homo-oligomers with itself and hetero-oligomers with lipin 2/3. Both the N- and C-terminal regions of lipin 1 mediate its oligomerization in a head-to-head/tail-to-tail manner. We also show that lipin 1 subcellular localization can be influenced through oligomerization, and the individual lipin 1 monomers in the oligomer function independently in catalysing dephosphorylation of PA. The present study provides evidence that lipin proteins function as oligomeric complexes and that the three mammalian lipin isoforms can form combinatorial units. PMID- 20735360 TI - Enhancement of the latent 3-isopropylmalate dehydrogenase activity of promiscuous homoisocitrate dehydrogenase by directed evolution. AB - HICDH (homoisocitrate dehydrogenase), which is involved in lysine biosynthesis through alpha-aminoadipate, is a paralogue of IPMDH [3-IPM (3-isopropylmalate) dehydrogenase], which is involved in leucine biosynthesis. TtHICDH (Thermus thermophilus HICDH) can recognize isocitrate, as well as homoisocitrate, as the substrate, and also shows IPMDH activity, although at a considerably decreased rate. In the present study, the promiscuous TtHICDH was evolved into an enzyme showing distinct IPMDH activity by directed evolution using a DNA-shuffling technique. Through five repeats of DNA shuffling/screening, variants that allowed Escherichia coli C600 (leuB-) to grow on a minimal medium in 2 days were obtained. One of the variants LR5-1, with eight amino acid replacements, was found to possess a 65-fold increased k(cat)/K(m) value for 3-IPM, compared with TtHICDH. Introduction of a single back-replacement H15Y change caused a further increase in the k(cat)/K(m) value and a partial recovery of the decreased thermotolerance of LR5-1. Site-directed mutagenesis revealed that most of the amino acid replacements found in LR5-1 effectively increased IPMDH activity; replacements around the substrate-binding site contributed to the improved recognition for 3-IPM, and other replacements at sites away from the substrate binding site enhanced the turnover number for the IPMDH reaction. The crystal structure of LR5-1 was determined at 2.4 A resolution and revealed that helix alpha4 was displaced in a manner suitable for recognition of the hydrophobic gamma-moiety of 3-IPM. On the basis of the crystal structure, possible reasons for enhancement of the turnover number are discussed. PMID- 20735361 TI - Identification of microRNAs expressed highly in pancreatic islet-like cell clusters differentiated from human embryonic stem cells. AB - Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, making it important to find a new alternative source of the islet beta cells to replace the damaged cells. hES (human embryonic stem) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into EBs (embryoid bodies) and then induced to generate the T3pi (pancreatic islet-like cell clusters derived from T3 cells), which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the T3pi were analysed and compared with those of undifferentiated hES T3 cells and differentiated EBs. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The T3pi showed very high expression of microRNAs, miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs and their target genes are very likely to play important regulatory roles in the development of pancreas and/or differentiation of islet cells, and they may be manipulated to increase the proportion of beta cells and insulin synthesis in the differentiated T3pi for cell therapy of type I diabetics. PMID- 20735362 TI - Physical activity positively predicts bone architecture and bone strength in adolescent males and females. AB - AIMS: Physical activity (PA) has positive effects on bone accrual and geometry in children during growth. However, we do not know how PA influences adaptations in bone architecture during growth. We evaluated the contribution of PA to bone density, architecture and strength in adolescents. METHODS: We used HR-pQCT (XtremeCT, Scanco Medical) to assess cross-sectional moments of inertia [Imin, Imax (mm4)], total bone density (Tt.Dn, mg HA/cm3), total bone area (Tt.Ar, mm2), cortical bone density (Ct.Dn, mg HA/cm3), cortical thickness (Ct.Th, MUm), trabecular bone density (Tb.Dn, mg HA/cm3), trabecular number (Tb.N, mm-1) and trabecular thickness (Tb.Th, MUm) at the distal tibia in 146 male and 132 female participants (15-20 years). We evaluated the contribution of impact loading PA (ImpactPA) and non-impact loading PA (NoimpactPA) on bone (p < 0.05). RESULTS: ImpactPA explained 10% of variance in Imin (p = 0.000), and 12% of variance in Imax (p = 0.000) in male participants. In male participants, ImpactPA explained 6% of variance in Tt.Ar (p = 0.003). In female participants, ImpactPA explained 4% of variance in Tt.Dn (p = 0.011), 5% of variance in Tb.Dn (p = 0.004) and 8% of variance in Tb.N (p = 0.001). CONCLUSION: Our findings suggest that ImpactPA is significantly associated with bone architecture and bone strength in adolescent males and females. PMID- 20735363 TI - Effects of short- and long-acting recombinant human growth hormone (PEG-rhGH) on left ventricular function in children with growth hormone deficiency. PMID- 20735364 TI - Addiction research centres and the nurturing of creativity The Norwegian Centre for Addiction Research (SERAF). AB - The Norwegian Centre for Addiction Research (SERAF) at the University of Oslo is a newly established, clinical addiction research centre. It is located at the Oslo University Hospital and has a major focus on opioid dependency, investigating Norwegian opioid maintenance treatment (OMT), with special interest in OMT during pregnancy, mortality, morbidity and criminality before, during and after OMT and alternatives to OMT, such as the use of naltrexone implants. The well-developed health registries of Norway are core assets that also allow the opportunity for other types of substance abuse research. This research includes health services, abuse of prescription drugs and drugs of abuse in connection with traffic. The centre also focuses upon comorbidity, investigating the usefulness and limitations of psychometric instruments, drug abuse in different psychiatric treatment settings and internet-based interventions for hazardous alcohol consumption. PMID- 20735365 TI - Prevalence of the metabolic syndrome in men and women with alcohol dependence: results from a cross-sectional study during behavioural treatment in a controlled environment. AB - AIMS: Prevalence of metabolic syndrome (MetS) in men and women who use alcohol has been inconsistent in the literature. The aim of this study is to compare the prevalence of MetS in patients with a diagnosis of alcohol dependence who are currently abstinent in a controlled environment, and in control subjects followed in primary care from a similar region in Northern Germany. DESIGN: Cross sectional study. SETTING: In-patient cognitive behavioural therapy. PARTICIPANTS: One hundred and ninety-seven men and women with alcohol dependence during behavioural treatment in a controlled environment were compared to 1158 subjects from primary care from a similar region in northern Germany. MEASUREMENTS: We used the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHBLI) criteria to determine the rate of MetS and each single criterion of MetS in both groups. FINDINGS: The prevalence of MetS was almost twice as high in men and women with alcohol dependence compared to control subjects (30.6% versus 17.0%). With respect to the single criteria, elevations were found for fasting glucose and blood pressure in both genders and for triglycerides in women only. High density lipoprotein (HDL)-cholesterol was higher in men and women with alcohol dependence. CONCLUSIONS: Our results demonstrate an increased rate of MetS, increased blood pressure and dysregulation of glucose and lipid metabolism in alcohol-dependent patients. Whether high HDL-cholesterol has cardioprotective effects in this context remain doubtful. PMID- 20735366 TI - Effectiveness of a mood management component as an adjunct to a telephone counselling smoking cessation intervention for smokers with a past major depression: a pragmatic randomized controlled trial. AB - AIMS: To assess whether the addition of a mood management component to telephone counselling produces higher abstinence rates in smokers with past major depression and helps to prevent recurrence of depressive symptoms. DESIGN: Pragmatic randomized controlled trial with two conditions, with follow-up at 6 and 12 months. The control intervention consisted of eight sessions of proactive telephone counselling. The mood management intervention was an integration of the control intervention with a mood management component. This component consisted of a self-help mood management manual, two more preparatory proactive telephone counselling sessions and supplementary homework assignments and advice. SETTING: Dutch national smoking cessation quitline. PARTICIPANTS: A total of 485 daily smokers with past major depression, according to the DSM-IV. MEASUREMENTS: The primary outcome measure was prolonged abstinence and secondary outcome measures were 7-day point prevalence abstinence and depressive symptoms. FINDINGS: The mood management intervention resulted in significantly higher prolonged abstinence rates at 6- and 12-month follow-up (30.5% and 23.9% in experimental condition, 22.3% and 14.0% in the control condition). The odds ratios were 1.60 (95% CI 1.06-2.42) and 1.96 (95% CI 1.22-3.14) for both follow-ups. The mood management intervention did not seem to prevent recurrence of depressive symptoms. CONCLUSIONS: Adding a mood management component to telephone counselling for smoking cessation in smokers with a past major depression increases cessation rates without necessarily reducing depressive symptoms. PMID- 20735367 TI - Mephedrone, new kid for the chop? AB - AIMS: Mephedrone (4-methylmethcathinone) is a novel synthetic stimulant drug that has recently become popular in the United Kingdom and elsewhere in Europe. It has a short history of human consumption and little is known about its prevalence and pattern of use. This study aimed to obtain preliminary data on its use and effects among dance drug users in the United Kingdom. DESIGN: Cross-sectional anonymous online survey of mephedrone recruited as part of larger study exploring patterns of drug use among those associated with the dance music scene. Setting UK-based dance music and clubbing website. PARTICIPANTS: A total of 947 ever users of mephedrone recruited as part of a wider study on dance drug use patterns. MEASUREMENTS: Assessment of demographics, ever and current drug use and patterns and selected effects following use of mephedrone. FINDINGS: A total of 947 (41.3%) of 2295 participants reported ever having used mephedrone. Mephedrone was the sixth most frequently used drug in the last month after tobacco, alcohol, cannabis, cocaine and 3,4-methylenedioxymethamphetamine (MDMA). Users were typically younger (P < 0.001) and male (P < 0.01); 15.1% reported using weekly or more frequently; 49.5% reported using between 0.5 and 1 g during a typical session; 69.5% reported that intranasal use was the most common route of use. Intranasal use was associated with increased abuse liability; 54.6% of those who have also used cocaine reported that the quality of the high obtained with mephedrone was better, with those using intranasally being significantly more likely than those who took the drug orally to report that mephedrone was more addictive (P < 0.02) and more risky (P < 0.02) than cocaine. Route of use was unrelated to any stimulant-related adverse effect apart from palpitations (P < 0.005). CONCLUSIONS: Mephedrone appears to be used primarily intranasally and to have comparable abuse potential to cocaine, with more than half those who use both reporting that mephedrone gives a better quality high. PMID- 20735368 TI - Should smokers be offered assistance with stopping? PMID- 20735369 TI - A comparison of four international surveys of tobacco dependence treatment provision: implications for monitoring the Framework Convention on Tobacco Control. AB - AIMS: Article 14 of the Framework Convention on Tobacco Control (FCTC) requires countries to implement systems to provide tobacco dependence treatment. We report on global efforts to monitor the implementation of Article 14, and compare the surveys used in this effort. DESIGN: Cross-sectional comparison of agreement (concordance and discordance) among the four main surveys used to monitor tobacco dependence treatment provision. SETTING: Four global surveys of tobacco treatment provision. PARTICIPANTS: The four surveys were Raw et al. (2009), the Framework Convention Alliance (FCA) Monitor, World Health Organization (WHO) MPOWER survey and the FCTC Party Reports. MEASUREMENTS: Concordance as measured by percentage providing the same answers, as well as kappa statistic of inter-rater agreement. FINDINGS: The four surveys used to monitor Article 14 implementation vary widely in countries sampled, questions asked, respondent characteristics and survey design. The four surveys generally show a moderate to high concordance (kappa > 0.60) with each other across most survey pairs and most domains, except for the MPOWER and FCTC Party governmental surveys (63% overall concordance, kappa =0.26). This concordance was lower than any other survey pair examined. Government respondents to the WHO MPOWER and FCTC Party Report surveys provided answers to the same question domains with relatively poorer concordance than those from surveys of non-governmental or mixed governmental/non-governmental sources. CONCLUSIONS: Current surveys of tobacco dependence treatment provision are in general agreement with each other except for the two official government surveys that rely on governmental respondents. We believe that this points to the continued need for independent non-governmental monitoring of FCTC protocol implementation. PMID- 20735370 TI - Identification of genetic determinants of IGF-1 levels and longevity among mouse inbred strains. AB - The IGF-1 signaling pathway plays an important role in regulating longevity. To identify the genetic loci and genes that regulate plasma IGF-1 levels, we intercrossed MRL/MpJ and SM/J, inbred mouse strains that differ in IGF-1 levels. Quantitative trait loci (QTL) analysis of IGF-1 levels of these F2 mice detected four QTL on chromosomes (Chrs) 9 (48 Mb), 10 (86 Mb), 15 (18 Mb), and 17 (85 Mb). Haplotype association mapping of IGF-1 levels in 28 domesticated inbred strains identified three suggestive loci in females on Chrs 2 (13 Mb), 10 (88 Mb), and 17 (28 Mb) and in four males on Chrs 1 (159 Mb), 3 (52 and 58 Mb), and 16 (74 Mb). Except for the QTL on Chr 9 and 16, all loci co-localized with IGF-1 QTL previously identified in other mouse crosses. The most significant locus was the QTL on Chr 10, which contains the Igf1 gene and which had a LOD score of 31.8. Haplotype analysis among 28 domesticated inbred strains revealed a major QTL on Chr 10 overlapping with the QTL identified in the F2 mice. This locus showed three major haplotypes; strains with haplotype 1 had significantly lower plasma IGF-1 and extended longevity (P < 0.05) than strains with haplotype 2 or 3. Bioinformatic analysis, combined with sequencing and expression studies, showed that Igf1 is the most likely QTL gene, but that other genes may also play a role in this strong QTL. PMID- 20735371 TI - Increased risk of esophageal varices, liver cancer, and death in patients with alcoholic liver disease. AB - BACKGROUND AND AIMS: During the last decades, a multitude of different treatments for chronic liver disease have been introduced. New surveillance programs have been established to detect esophageal varices and liver cancer. The aims of our study were to assess whether the prognosis for patients hospitalized with liver diseases between 1969 and 2006 had improved and to study the differences in mortality and complications between patients with alcoholic liver disease and nonalcoholic liver diseases. METHODS: We used the Swedish Hospital Discharge Register and Cause of Death Register at the National Board of Health and Welfare in Sweden between 1969 and 2006 to identify and follow-up a cohort of patients with liver disease according to the International Classification of Diseases-8, 9, and -10. RESULTS: There were 36,462 patients hospitalized with alcoholic and 95,842 with nonalcoholic liver diseases. The main finding was that patients hospitalized with alcoholic liver disease had an increased mortality risk, compared to patient with nonalcoholic liver disease, 1.89 (1.85 to 1.92). In addition, the patients with alcoholic liver disease had an increased risk for esophageal varices and liver cancer. There was a reduced risk for hospitalization with esophageal varices for patients with nonalcoholic liver disease up to 1998. CONCLUSIONS: We found that the prognosis for patients hospitalized with chronic liver diseases had not improved. Patients with alcoholic liver disease have an increased risk of complications, which suggest that the disease is more aggressive and are in need of closer follow-up than other chronic liver diseases. PMID- 20735372 TI - Late-life alcohol consumption and 20-year mortality. AB - BACKGROUND: Growing epidemiological evidence indicates that moderate alcohol consumption is associated with reduced total mortality among middle-aged and older adults. However, the salutary effect of moderate drinking may be overestimated owing to confounding factors. Abstainers may include former problem drinkers with existing health problems and may be atypical compared to drinkers in terms of sociodemographic and social-behavioral factors. The purpose of this study was to examine the association between alcohol consumption and all-cause mortality over 20 years among 1,824 older adults, controlling for a wide range of potential confounding factors associated with abstention. METHODS: The sample at baseline included 1,824 individuals between the ages of 55 and 65. The database at baseline included information on daily alcohol consumption, sociodemographic factors, former problem drinking status, health factors, and social-behavioral factors. Abstention was defined as abstaining from alcohol at baseline. Death across a 20-year follow-up period was confirmed primarily by death certificate. RESULTS: Controlling only for age and gender, compared to moderate drinkers, abstainers had a more than 2 times increased mortality risk, heavy drinkers had 70% increased risk, and light drinkers had 23% increased risk. A model controlling for former problem drinking status, existing health problems, and key sociodemographic and social-behavioral factors, as well as for age and gender, substantially reduced the mortality effect for abstainers compared to moderate drinkers. However, even after adjusting for all covariates, abstainers and heavy drinkers continued to show increased mortality risks of 51 and 45%, respectively, compared to moderate drinkers. CONCLUSIONS: Findings are consistent with an interpretation that the survival effect for moderate drinking compared to abstention among older adults reflects 2 processes. First, the effect of confounding factors associated with alcohol abstention is considerable. However, even after taking account of traditional and nontraditional covariates, moderate alcohol consumption continued to show a beneficial effect in predicting mortality risk. PMID- 20735373 TI - Reduced expression of circadian clock genes in male alcoholic patients. AB - BACKGROUND: There are clear interactions between chronic alcohol consumption and circadian rhythmicity that is regulated by several circadian clock genes. The altered expressions of these genes have been mainly described in animals. The mammalian master clock in the suprachiasmatic nuclei orchestrates the biological rhythms in peripheral tissues. As peripheral blood mononuclear cells (PBMCs) are the most accessible tissue clinically, we assessed the mRNA levels of these genes in patients with alcohol dependence (AD) undergoing alcohol-withdrawal (AW) treatment. METHODS: Twenty-two male patients fulfilled the DSM-IV diagnostic criteria of AD, and 12 comparison healthy control subjects were recruited. The patients with AD were further divided by the presence of delirium tremens (DTs), the most severe form of AW syndrome, into DT group and non-DT group. All the participants received blood withdrawal at 9 am, while the patients with AD had blood collection twice: on the next morning of admission (baseline) and on the seventh day. PBMCs were isolated from whole blood, and the mRNA expression profiles of hClock1, hBmal1, hPer1, hPer2, hCry1, and hCry2 were determined by quantitative real-time PCR. RESULTS: The baseline mRNA levels of the target circadian clock genes were markedly lower in patients with AD than in control subjects. After 1 week of alcohol detoxification, there were very limited restorations of discrete circadian gene expressions. DT group did not differ in the expression patterns of circadian clock genes from non-DT group. CONCLUSIONS: This is the first study demonstrating the overall lowering of circadian clock genes among patients with AD. The expression pattern is comparable between patients with and without DTs. Although preliminary with data at only one single time point, the observation of strikingly reduced mRNA levels supports the association between circadian clock gene dysregulation and chronic alcohol intake. PMID- 20735374 TI - Study of metamemory in patients with chronic alcoholism using a feeling-of knowing episodic memory task. AB - BACKGROUND: Alcoholism affects various cognitive processes, including components of memory. Metamemory, though of particular interest for patient treatment, has not yet been extensively investigated. METHODS: A feeling-of-knowing (FOK) measure of metamemory was administered to 28 alcoholic patients and 28 healthy controls during an episodic memory task including the learning of 20 pairs of items, followed by a 20-minute delayed recall and a recognition task. Prior to recognition, participants rated their ability to recognize each nonrecalled word among 4 items. This episodic FOK measure served to compare predictions of future recognition performance and actual recognition performance. Furthermore, a subjective measure of metamemory, the Metamemory In Adulthood (MIA) questionnaire, was completed by patients and controls. This assessment of alcoholic patients' metamemory profile was accompanied by an evaluation of episodic memory and executive functioning. RESULTS: FOK results revealed deficits in accuracy, with the alcoholic patients providing overestimations. There were also links between FOK inaccuracy, executive decline, and episodic memory impairment in patients. MIA results showed that although alcoholics did display memory difficulties, they did not differ from controls on questions about memory capacity. CONCLUSIONS: Chronic alcoholism affects both episodic memory and metamemory for novel information. Patients were relatively unaware of their memory deficits and believed that their memory was as good as that of the healthy controls. The monitoring measure (FOK) and the subjective measure of metamemory (MIA) showed that patients with chronic alcoholism overestimated their memory capacities. Episodic memory deficit and executive dysfunction would explain metamemory decline in this clinical population. PMID- 20735375 TI - Involvement of calmodulin kinase II in the action of sulphur mustard on the contraction of vascular smooth muscle. AB - Sulphur mustard (SM) is an alkylating agent whose mechanism is not fully understood. To investigate the early action of SM, we examined the effect of SM on contraction of vascular smooth muscles. Phenylephrine (PE)-induced contraction was reduced by SM, but only marginally by 70 mM KCl(-) . Additional reduction was induced by nifedipine in SM-treated arteries. In the absence of extracellular Ca(2+) , contraction of arteries by PE was reduced, which was fully recovered by addition of 2 mM Ca(2+) . However, recovery was attenuated by pre-treatment with SM. The effect of SM on contraction by PE was not influenced by pre- and post treatment with Phorbol 12, 13-dibutyrate. Calmodulin kinase II (CaMKII) was implicated as being responsible for the action of SM, because the contractile mechanisms of vascular smooth muscle via both Ca(2+) -calmodulin-myosin light chain kinase axis and protein kinase C-proline-rich tyrosine kinase axis were not related to the action of SM. Elevation of phosphorylated CaMKII level by Ionomycin or PE was attenuated by treatment of SM on western blot. CaMKII may be a candidate target molecule of SM in early stage contraction of vascular smooth muscle. PMID- 20735376 TI - Effect of 8-O-acetyl shanzhiside methylester increases angiogenesis and improves functional recovery after stroke. AB - We investigated whether 8-O-acetyl shanzhiside methylester (ND01) regulates angiogenesis and thereby improves functional outcome after stroke. Adult male rats were subjected to 1 hr of middle cerebral artery occlusion (MCAO) and reperfusion, and treated with or without different doses (5 and 10 mg/kg) of ND01, starting 24 hr after ischaemia and reperfusion (I/R) and by intravenous injection daily for 14 days. Neurological functional tests were performed and cerebral Evans blue extravasation was measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry and Western blot, respectively. The results indicated that ND01 significantly promoted angiogenesis in the ischaemic brain and improved functional outcome after stroke. ND01 also significantly increased vascularization compared with vehicle treatment. ND01 increased the expression of VEGF, Ang1, phosphorylation of Tie2 and Akt VEGF. The Ang1/Tie2 axis and Akt pathways appear to mediate ND01-induced angiogenesis. PMID- 20735377 TI - Modulation of early stress-related biomarkers in cytoplasm by the antioxidants silymarin and quercetin using a cellular model of acute arsenic poisoning. AB - Several pathologies (e.g. cancer and diabetes) are increased in arsenic-exposed populations, with oxidative stress being a major toxicological mechanism. Since the flavonoids silymarin (S) and quercetin (Q) are antioxidants and may protect cells, it would be valuable to develop a model which allows assessing the potential of xenobiotic against arsenic cytotoxicity in an efficient and rapid way. Thus, the oxidant production [e.g. reactive oxygen species and reactive nitrogen species (RNS)], the molecular parameters of biological response [e.g. plasma membrane composition, actin microfilaments and activated diphosphorilated c-Jun N-terminal kinase (JNK)] and cellular viability were determined in CHO-K1 cells treated with arsenite (As), S and Q. Arsenic caused loss of the cellular viability in a time-dependent manner. This effect was accompanied by a lipid hydroperoxide (LHP) formation, with no RNS induction or ganglioside content changes being found. Both flavonoids counteracted oxidative damage. Despite all treatments had unspecific responses on nitrite cellular release along the time, there was no relation between them and the cellular viability. Arsenic induced cytoplasmic microfilament rearrangement (tight perinuclear distribution with projections, stress fibres and pseudopodia) which was reversed by S. Also, activated JNK showed a similar distribution to actin. Contrarily, Q caused a dysmorphic granular pattern, thus behaving as a toxic agent. Summing up, toxic levels of arsenic disturb the redox homeostasis with LHP induction and early triggering of stress responses in cytoskeleton and cell signalling. Using the proposed model, only S showed to protect cells from arsenical cytotoxicity without own toxic properties. Thus, S might be considered for modulation of the human arsenic susceptibility. PMID- 20735378 TI - A predictive framework and review of the ecological impacts of exotic plant invasions on reptiles and amphibians. AB - The invasive spread of exotic plants in native vegetation can pose serious threats to native faunal assemblages. This is of particular concern for reptiles and amphibians because they form a significant component of the world's vertebrate fauna, play a pivotal role in ecosystem functioning and are often neglected in biodiversity research. A framework to predict how exotic plant invasion will affect reptile and amphibian assemblages is imperative for conservation, management and the identification of research priorities. Here, we present a new predictive framework that integrates three mechanistic models. These models are based on exotic plant invasion altering: (1) habitat structure; (2) herbivory and predator-prey interactions; (3) the reproductive success of reptile and amphibian species and assemblages. We present a series of testable predictions from these models that arise from the interplay over time among three exotic plant traits (growth form, area of coverage, taxonomic distinctiveness) and six traits of reptiles and amphibians (body size, lifespan, home range size, habitat specialisation, diet, reproductive strategy). A literature review provided robust empirical evidence of exotic plant impacts on reptiles and amphibians from each of the three model mechanisms. Evidence relating to the role of body size and diet was less clear-cut, indicating the need for further research. The literature provided limited empirical support for many of the other model predictions. This was not, however, because findings contradicted our model predictions but because research in this area is sparse. In particular, the small number of studies specifically examining the effects of exotic plants on amphibians highlights the pressing need for quantitative research in this area. There is enormous scope for detailed empirical investigation of interactions between exotic plants and reptile and amphibian species and assemblages. The framework presented here and further testing of predictions will provide a basis for informing and prioritising environmental management and exotic plant control efforts. PMID- 20735379 TI - Intrapartum risk factors for levator trauma. AB - OBJECTIVE: To determine intrapartum risk factors associated with levator trauma as identified by ultrasound imaging. DESIGN: A prospective observational study. SETTING: Antenatal clinic of a tertiary hospital between May 2005 and February 2008. POPULATION: Nulliparous women (n=488) in their first ongoing pregnancy. METHODS: An interview and four-dimensional translabial ultrasound was carried out between 36 and 38 weeks and again 3-4 months after delivery. Obstetric data were collected from the hospital database and/or participants' records. MAIN OUTCOME MEASURES: Levator macrotrauma ('avulsion') and microtrauma (irreversible overdistension). RESULTS: A total of 367 women (75%) returned for the postpartum assessment after normal vaginal delivery (n=187, 51%), vacuum (n=34, 9%), forceps (n=20, 5%) and caesarean section (n=126, 34%). Median follow up was 4.08 months (interquartile range 3.68-5.03 months). Levator avulsion was diagnosed in 32 (13%) of the women who delivered vaginally and in none of the caesarean section group regardless of indication. On multivariable regression forceps delivery was significantly associated with avulsion (P=0.01; OR 3.83; 95% CI 1.34-10.94). Using >20% peripartum increase in hiatal area on Valsalva as the cutoff, 28.5% of vaginally parous women were shown to have suffered irreversible overdistension. This was positively associated with the length of second stage (P=0.001; OR 1.01 per minute; 95% CI 1.0-1.02). Intrapartum epidural appeared to have a protective effect (P=0.03; OR 0.42; 95% CI 0.19-0.93). CONCLUSION: Levator trauma at the time of first delivery is associated with vaginal delivery, forceps and a longer second stage. Epidural pain relief may exert a protective effect. PMID- 20735380 TI - Long-term functional and morphological outcome after pyeloplasty for huge renal pelvis. AB - OBJECTIVE: * To evaluate the functional and morphological outcome after open pyeloplasty for ureteropelvic junction obstruction (UPJO) with huge renal pelvis. PATIENTS AND METHODS: * A retrospective review of all cases who underwent pyeloplasty for huge renal pelvis was conducted. * Records were evaluated with respect to age at presentation, preoperative imaging, surgical details and postoperative course. Patients were followed up regularly for both functional and morphological outcome. * Success was defined as both symptomatic relief and radiographic resolution of obstruction at last follow-up. RESULTS: * Between 1998 and 2008, 526 cases of primary UPJO underwent open dismembered pyeloplasty at our centre. * Of these patients, 41 (8%) had UPJO with huge renal pelvis. * No perioperative complications were encountered in the study group. Mean (range) follow-up was 34 (18-84) months and nine patients were lost to follow-up. The overall success rate was 91%. * Two patients underwent redo pyeloplasty, whereas secondary nephrectomy was necessary in one. * Improvement of hydronephrosis was evident in all patients, except in three patients who underwent secondary procedures. * However, persistent obstruction on diuretic renography was seen in most cases (65%). CONCLUSIONS: * Open pyeloplasty for huge pelvis UPJO is feasible with a high success rate. * Varying degrees of hydronephrosis and radiological obstruction after pyeloplasty are not uncommon. * Nephrectomy is rarely indicated in cases with severely deteriorated renal function. PMID- 20735381 TI - Detection of circulating tumour cells in peripheral blood of patients with advanced non-metastatic bladder cancer. AB - OBJECTIVE: * To prospectively detect and evaluate the biological significance of circulating tumour cells (CTC) in patients with bladder cancer, especially in those patients with non-metastatic, advanced bladder cancer (NMABC). PATIENTS AND METHODS: * Between July 2007 and January 2009, blood samples of 50 consecutive patients with localized bladder cancer and five patients with metastatic disease scheduled for cystectomy were prospectively investigated for CTC. Peripheral blood (7.5 ml) was drawn before cystectomy. * Detection of CTC was performed using the USA Food and Drug Administration-approved CellSearch(TM) system. Data were compared with the clinical and histopathological findings. RESULTS: * CTC were detected in 15 of 50 patients (30%) with non-metastatic disease and five of five patients with metastatic disease. The overall mean number of CTC was 33.7 (range: 1-372; median: 2). In non-metastatic patients, the mean number of CTC was 3.1 (range: 1-11; median: 1). Except for a univariate association between CTC with vessel infiltration (P= 0.047), all other common clinical and histopathological parameters did not reveal a significant correlation with CTC detection. * A median 1-year follow up was available for 53 patients (96.4%). Ten out of 19 preoperatively CTC-positive patients died as a result of cancer progression. * CTC-positive patients showed significantly worse overall (P = 0.001), progression-free (P < 0.001) and cancer specific survival (P < 0.001) compared to preoperatively CTC-negative patients. CONCLUSION: * This is the largest study demonstrating that detection of CTC in NMABC patients is feasible using the CellSearch(TM) system. Our findings suggest that the presence of CTC may be predictive for early systemic disease. PMID- 20735382 TI - Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma. AB - OBJECTIVE: * To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination. PATIENTS AND METHODS: * Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane-CD25 and intracytoplasmic-Foxp3 expression by flow cytometry. * Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25-depleted mononuclear cells (MNC) and CD25-depleted MNC cultured in the presence of purified CD25(+) Tregs. * Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models. RESULTS: * Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25(+) cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon-gamma production by CD25-depleted MNC, thus demonstrating that they are active Tregs. * Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL). CONCLUSION: * Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis. PMID- 20735383 TI - Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C. AB - OBJECTIVES: * To examine, using in vitro and in vivo models, the largely unexamined effect of mitomycin C (MMC), an effective intravesical treatment for superficial bladder cancer and carcinoma in situ, on expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2), which mediates many of the angiogenic properties of VEGF. * To measure, as a positive control, concentrations of the inhibitor of apoptosis, survivin, as an assessment of MMC effectiveness. * To measure MMC-induced changes in proliferation in the presence and absence of VEGF-A small interfering RNA (siRNA). MATERIALS AND METHODS: * After treatment with increasing MMC concentrations (5-200 ug/mL), we measured proliferation, as well as VEGF, survivin, VEGF receptor-1 (VEGFR-1) and VEGFR-2 concentrations in RT-4 and T-24 bladder cancer cells. * The effect of pre-treatment of VEGF siRNA and survivin siRNA on MMC-induced decreases in proliferation was measured. * Urinary VEGF concentrations and bladder and kidney concentrations of VEGF-A, VEGFR-1, VEGFR-2 and interleukin-6 (IL-6) mRNA were measured in rats intravesically instilled with saline or MMC (200 ug/mL). RESULTS: * Although MMC treatment inhibited cell proliferation and decreased survivin mRNA expression in T-24 and RT4 cells, MMC (12-50 ug/mL) increased VEGF-A mRNA and VEGFR-2 mRNA and protein expression. * Pre-treatment with VEGF-A siRNA or survivin siRNA before MMC treatment reduced proliferation more than MMC alone. * MMC-induced reductions in proliferation were reduced additively by pre-treatment with survivin siRNA, but were potentiated by pre-treatment with VEGF-A siRNA. * VEGFR-2 mRNA and protein concentrations and urinary VEGF concentrations were increased in bladders of rats instilled with MMC. CONCLUSIONS: * Intravesically instilled MMC increases urinary VEGF and bladder VEGFR-2 protein and mRNA in rats. * MMC increases VEGF mRNA and VEGFR-2 protein and mRNA concentrations in bladder cancer cells. Therefore, we speculate that MMC could increase the angiogenic potential of both cancer and normal cells. * In cancer cells this effect is largest at lower MMC concentrations. * Combining MMC with agents that reduce EGF concentrations could be of value in treatment of transitional cell carcinoma of the bladder (TCC). PMID- 20735384 TI - Expression of integrin proteins in non-muscle-invasive bladder cancer: significance of intravesical recurrence after transurethral resection. AB - OBJECTIVES: * To evaluate the expression of integrin proteins, a family of transmembrane heterodimers, in non-muscle-invasive bladder cancer (NMIBC). * To assess the significance of these proteins as prognostic indicators in patients undergoing transurethral resection (TUR). PATIENTS AND METHODS: * The present study comprised 161 patients diagnosed as having NMIBC after TUR. * Expression levels of six subunits of integrin proteins, including alpha2, alpha3, alpha5, alpha6, beta1 and beta4, were measured in TUR specimens by immunohistochemical staining. RESULTS: * Of the six proteins, expression levels of alpha2-, alpha3-, alpha6- and beta4-subunits were significantly associated with the incidence of intravesical recurrence. Univariate analysis identified expression levels of alpha3-, alpha6- and beta4-subunits as important predictors of intravesical recurrence, while tumour size, pathological T stage and concomitant carcinoma in situ (CIS) were also important. * Multivariate analysis showed that the expression level of the beta4 subunit, pathological T stage and concomitant CIS are independently related to intravesical recurrence. * There were significant differences in intravesical recurrence-free survival for patients who were positive for the three independent risk factors; intravesical recurrence occurred in 10 of 49 (20.4%) patients who were negative for all risk factors, 31 of 68 who were positive for one risk factor (45.6%), and 30 of 44 who were positive for two or three risk factors (68.2%). CONCLUSIONS: * Consideration of the expression levels of integrins, particularly those of the beta4 subunit, in TUR specimens, in addition to conventional variables, would contribute to accurate prediction of intravesical recurrence after TUR for NMIBC patients. PMID- 20735385 TI - Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate induced changes in rat urinary bladder. AB - What's known on the subject? and What does the study add? The mastocytosis in detrusor muscle and the leaky epithelium in interstitial cystitis were the most studied features. In this study the leaky epithelium was shown using the ruthenium red staining in electron microscopy and uroplakin distribution in light microscopy besides the mast cell concentration in detrusor muscle using tryptase immunohistochemistry. OBJECTIVE: * To study the effects of montelukast (ML), a leukotriene receptor antagonist which has been shown to be effective in inhibiting the action of cysteinyl-containing leukotrienes, on protamine sulphate (PS)-induced changes in rat urinary bladder. MATERIALS AND METHODS: * Wistar female rats were catheterized and intravesically infused with PBS (control group) or PS (PS group) dissolved in PBS twice in 24 h. * In the PS-applied and ML treated group (PS + ML group) after the 10 mg/kg PS instillation, ML was injected i.p. twice daily for 3 days. * The urinary bladder was investigated for general morphology under a light microscope. * Tryptase immunohistochemistry was used to observe mast cell distribution and activation. Uroplakin distribution was also identified with immunohistochemistry. RESULTS: * Alterations of glycosaminoglycan (GAG) and urothelial permeability were seen with ruthenium red (RR) staining techniques under a transmission electron microscope, and topographical changes of luminal urothelial structure were seen with a scanning electron microscope. * Biochemically malondialdehyde (MDA) and gluthatione (GSH) concentrations were analysed. In the PS group, there was degenerated urothelium with irregular uroplakin distribution, increased inflammatory cell infiltration, increased number of both granulated and activated mast cells, irregularity of GAG and penetration of RR into the intercellular spaces and dilated tight junctions. * In PS + ML group, there was relatively regular uroplakin distribution, a decrease in inflammatory cell infiltration, a decreased number of both activated and granulated mast cells in the mucosa, regular GAG and no penetration of RR into the intercellular areas, and regular tight junctions in most regions. * The significant decrease in MDA and the increased GSH concentrations in the PS + ML group was in accordance with the histological findings. CONCLUSION: * Montelukast appears to have a protective function in the bladder injury model via the anti inflammatory effects of this leukotriene receptor antagonist. PMID- 20735386 TI - Racial differences in prediction of time to prostate cancer diagnosis in a prospective screening cohort of high-risk men: effect of TMPRSS2 Met160Val. AB - INTRODUCTION: To evaluate the TMPRSS2-ERG gene polymorphism with respect to self identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high-risk men. PATIENTS AND METHODS: A total of 631 men aged between 35 and 69 years were studied. 'High-risk' was defined as >= one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations. Men with elevated prostate-specific antigen (PSA) concentrations or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis. Cox models were used to evaluate time to PCA diagnosis by genotype. RESULTS: Genotype distribution differed significantly by SIRE (CT/TT vs CC, P < 0.0001). Among 183 Caucasian men with at least one follow-up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (hazard ratio = 2.55, 95% CI = 1.14-5.70) after controlling for age and PSA. No association was seen among AA men by TMPRSS2 genotype. CONCLUSIONS: The T-allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2-ERG fusion, may be informative of time to PCA diagnosis for a subset of high-risk Caucasian men who are undergoing regular PCA screening. This variant, along with other genetic markers, warrant further study for personalizing PCA screening. PMID- 20735387 TI - Trends in the treatment of localized prostate cancer using supplemented cancer registry data. AB - OBJECTIVE: To conduct an analysis of localized prostate cancer treatment in the USA between 1998 and 2002. PATIENTS AND METHODS: Results from the National Cancer Institute's Patterns of Care study from 10 regional cancer registries in 1998 and 14 registries in 2002 were compared using univariate and multivariate statistical methods. RESULTS: Patients with localized prostate cancer in 2002 were younger, had lower prostate-specific antigen values, and higher Gleason scores compared with those diagnosed in 1998. Little change occurred in age-adjusted percentages of men who were treated with a radical prostatectomy (45-46%) or by external beam radiation (EBRT) alone (19-20%). The proportion receiving brachytherapy (BT), alone or with EBRT, increased from 14.9 to 17.7%, while the proportion receiving watchful waiting declined from 12.6 to 9.0%. Younger African-American men with intermediate/high-risk disease were less likely to receive any type of aggressive therapy in comparison with Non-Hispanic White men. Over 70% of men who were >= 75 years of age, with low-risk disease, were treated with EBRT or BT. CONCLUSIONS: Older men with low-risk disease might be overtreated with aggressive therapy, while younger intermediate/high-risk African-American men appear less likely to receive indicated aggressive therapy. PMID- 20735388 TI - Findings of fat-suppressed T2-weighted and diffusion-weighted magnetic resonance imaging in the diagnosis of non-palpable testes. AB - OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) findings, diagnostic accuracy and clinical usefulness of fat-suppressed T2-weighted and diffusion weighted imaging (DWI) in the management of non-palpable testes. PATIENTS AND METHODS: In all, 56 children (63 non-palpable testes) aged 8 months-11 years (mean 24.7 months) with non-palpable testes were enrolled. T1- and T2-weighted imaging, as well as fat-suppressed T2-weighted imaging and DWI were performed during MRI examination, and the imaging results were compared with surgical findings. RESULTS: In the 63 non-palpable testes, MRI identified 22% (14/63) as intra-abdominal, 20% (13/63) as intra-canalicular, 29% (18/63) as testicular nubbins, and 29% (18/63) as unidentifiable. Although it was difficult to confirm their presence in the abdominal cavity using T1- and T2-weighted imaging alone, additional assessment, including fat-suppressed T2-weighted imaging and DWI facilitated the detection of intra-abdominal testes more easily because they were imaged at a markedly higher signal intensity. The sensitivity, specificity and positive and negative predictive values for the MRI vs the operative findings were 100, 97.3, 96.3, and 100%, respectively. The overall prediction accuracy was 98.4%. CONCLUSION: Additional MRI assessments, fat-suppressed T2-weighted imaging and DWI are useful examinations to improve the preoperative diagnostic accuracy of non-palpable testes. PMID- 20735389 TI - Clinical significance of runt-related transcription factor 1 polymorphism in prostate cancer. AB - OBJECTIVE: To investigate the association of RUNX1 rs2253319 with clinicopathological characteristics of prostate cancer (PCa) and disease recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Taking advantage of the systematic stage and grade for each tumor in a cohort of 314 patients with localized PCa receiving RP, we evaluated the associations of RUNX1 rs2253319 with age at diagnosis, preoperative prostate-specific antigen (PSA) level, Gleason score, surgical margin, pathologic stage, status of lymph node metastasis, and PSA recurrence after RP. RESULTS: The minor allele, T, and the minor homozygote TT genotype of RUNX1 rs2253319 were significantly associated with a 1.49- to 2.76-fold higher risk for advanced pathologic stage and a 3.35- to 9.52-fold higher risk for lymph node metastasis. RUNX1 rs2253319 TT genotype was also associated with poorer PSA-free survival compared with the major homozygote CC genotype in Kaplan-Meier analysis (log-rank test, P= 0.038) and multivariate Cox proportional hazards model adjusting for age and PSA concentration (P= 0.045). CONCLUSION: RUNX1 rs2253319 is associated with adverse clinicopathological features and might be a prognostic factor for the recurrence of PSA in patients with PCa receiving RP. PMID- 20735391 TI - Novel ZEB1 expression in bladder tumorigenesis. AB - What's known on the subject? and What does the study add? Epithelial-mesenchymal transition (EMT) is involved in tumor progression where the underlying cellular changes associated with EMT have been identified in in vitro models and confirmed in a limited number of in vivo studies. ZEB1, which targets E-cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers. Regulation of ZEB1 expression has been shown to involve different microRNAs (miRNAs), identifying a potential role for miRNA in EMT. In the present study we have identified novel expression of ZEB1 in bladder tumours and shown a role for ZEB1 in enhanced migration and invasion potential in in vitro assays. Confirmation of ZEB1 expression in bladder tumours was shown in tissue microarrays (TMAs). OBJECTIVE: To evaluate ZEB1 expression in bladder tumorigenesis and define a possible role for this transcription factor in urothelial carcinomas of the bladder (UCBs). MATERIALS AND METHODS: Five hundred and fifty-eight samples were assembled in 10 tissue microarrays (TMAs; 263 non-muscle-invasive Ta/T1/Tis, 295 muscle-invasive T2-T4). All tumours were transitional cell carcinomas (TCCs) and processed for immunohistochemistry to assess nuclear ZEB1 expression. Expression levels of ZEB1 were modulated in bladder carcinoma cell lines CUBIII or UM-UC-3 after forced expression or shRNA knockdown, respectively. Protein expression levels were determined using western blot analysis and transfectants were assessed for migration and invasion potential in standard in vitro assays. RESULTS: Nuclear ZEB1 expression was recorded in 22.8% of non-muscle-invasive UCBs and 21.7% of muscle-invasive UCBs, including 24.1% grade I/II and 21.1% grade III tumours, and absent in normal bladder mucosa. No significant correlation was observed for tumour stage and grade, nodal involvement, vascular invasion, metastasis and overall or cancer-specific survival. The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively. Changes in ZEB1 expression were accompanied by altered microRNA (miRNA) expression underlying events linked to epithelial mesenchymal transition (EMT). CONCLUSION: The results in the present study showed novel expression of ZEB1 in bladder cancer in the absence of a link to clinical variables of change, including metastasis and survival. However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines. Modulation in expression of ZEB1 was closely linked to changes in the miR-200 family along with alternative known prognostic indicators of bladder tumour progression. PMID- 20735390 TI - The role of c-kit-positive interstitial cells in mediating phasic contractions of bladder strips from streptozotocin-induced diabetic rats. AB - OBJECTIVE: * To investigate the role of c-kit-positive interstitial cells (ICCs) in mediating muscarinic receptor-induced phasic contractions of isolated bladder strips from streptozotocin(STZ)-induced diabetic rats and to confirm the expression and location of ICCs in the rat bladder. MATERIALS AND METHODS: * Bladders were removed from STZ-induced diabetic rats at 1, 4 and 12 weeks after induction of diabetes and from age-matched controls. * To investigate the functional role of ICCs in mediating phasic contractions, bladder strips were isolated from control and diabetic rats and mounted in tissue baths. * Strips were stimulated with low concentrations of the muscarinic receptor agonist carbachol (CCH; 0.1 um) to induce phasic contractions and the effect of increasing concentrations (1-50 um) of imatinib (Glivec(r) or Gleevec(r), formerly STI571), a c-kit tyrosine kinase inhibitor, was then investigated. * For molecular studies, to detect expression of the c-kit tyrosine kinase receptor (c kit), total cellular RNA was extracted from rat bladders and reverse-transcribed to obtain complementary DNA (cDNA). * Reverse transcription-polymerase chain reaction (RT-PCR) was then performed using primers specific to the c-kit sequence and amplified products separated by agarose gel electrophoresis. * Amplified PCR products were excised from the gel, sequenced and compared with the known c-kit sequence to confirm their identity. * For immunohistochemical detection, whole mount preparations of control rat bladders were fixed in acetone and labelled using antibodies directed to the ICC marker c-kit. RESULTS: * In functional studies, CCH induced phasic contractions in bladder strips from control and diabetic rats. Bladder strips from 1-week diabetic rats showed CCH-induced phasic contractions, which were greater in amplitude, but had lower frequency, than the controls, whilst no such differences were apparent at later time points of diabetes. * Imatinib decreased the amplitude and the frequency of the CCH-induced phasic contractions in both control and diabetic tissues in a concentration dependent manner, although in diabetic tissues this effect was only seen at the higher concentrations of imatinib. RT-PCR of bladder cDNA yielded a single amplicon of 480 bp. * The sequence of this amplicon showed a 98% homology with the published c-kit sequence, thus confirming c-kit mRNA expression in both control and 1-week diabetic rat bladder. * Expression of c-kit protein was also detected in a network of cells on the edge of and between smooth muscle bundles of control rat bladders by positive immunoreactivity to c-kit specific antibodies. CONCLUSION: * These data show the presence of c-kit-positive ICCs in rat urinary bladder and their importance in mediating muscarinic receptor-induced phasic contractions of bladder strips from control and diabetic rats. The role of these ICCs does not seem to be significantly altered by the diabetic state. PMID- 20735392 TI - Epstein-Barr virus DNA load in tumour tissues correlates with poor differentiation status in non-muscle invasive urothelial carcinomas. AB - OBJECTIVE: To detect the correlation between the clinical staging, grading and genomic Epstein-Barr virus (EBV) viral numbers in tumour tissues of urothelial carcinoma patients. PATIENTS AND METHODS: From June 2004 to May 2008, 60 urothelial carcinoma patients (50 cases of bladder carcinoma and 10 of upper tract urothelial carcinoma (UTUC) were enrolled in the study. Eight patients who underwent transurethral resection of prostate for prostate hyperplasia and two patients receiving nephrectomy for non-function kidney were used as normal controls. The EBV viral copy numbers in genomic DNA were evaluated using a real time PCR-based study. The BamHI W region of the Namalwa cell line was constructed to the plasmid clone and was used as standard curve for absolute quantitative PCR (Q-PCR). RESULTS: Epstein-Barr virus DNA was detected in 56% (28/50) and 60% (6/10) of the bladder and UTUC patients, respectively. The EBV DNA could not be detected in the normal control group. By pooling the UTUC and bladder patients in stage Ta,T1, the high copy number in fixed genomic DNA amount (100 ng/20 uL) was correlated with the high grading in stage Ta,T1 urothelial carcinoma (P = 0.014). The overall grading was not statistically associated with EBV copy number (P = 0.25). Although the copy numbers between paired tumour and normal tissues were not statistically different (P= 0.169), there were more copies of EBV in the normal tissues adjacent to the tumours than in those free from urothelial carcinoma. There was no significant difference between recurrence of non-muscle invasive bladder cancer and the presence of EBV (P > 0.05). CONCLUSIONS: Epstein Barr virus DNA could be detected in the genome of the urothelial carcinoma specimens. The poor differentiation status was correlated with the high load of the EBV genome in non-muscle invasive urothelial carcinoma. However, recurrence free survival was not greater in EBV-positive patients than in EBV-negative patients. PMID- 20735393 TI - Late relapse (>2 years) on surveillance in stage I non-seminomatous germ cell tumours; predominant seminoma only histology. AB - OBJECTIVES: Surveillance is a standard management approach following orchidectomy for stage I non-seminomatous and mixed germ cell tumours. Patients who relapse following this approach are treated with cisplatin-based chemotherapy, with retroperitoneal lymph node dissection considered for patients with post chemotherapy residual masses. PATIENTS AND METHODS: We reviewed the clinicopathological data for all patients who relapse greater than 24 months after commencing our surveillance programme. RESULTS: Between 1989 and 2008, 453 patients with a median age of 30 years were entered into our surveillance program for stage I non-seminomatous germ cell tumours (NSGCTs) after orchidectomy alone. All primary tumour specimens contained NSGCT, with seminomatous elements identified in 168 cases (37%). One-hundred patients (22%) relapsed and the majority of relapses occurred within the first 2 years (76 <= 12 months, 15 >= 12 months <= 2 years). Nine patients relapsed after more than 2 years of surveillance. We found a high incidence of pure seminoma (56%) at sites of metastatic disease in this group. All late-relapsing patients were alive and disease free at a median follow up of 45 months from relapse. CONCLUSIONS: We recommend that late-relapsing patients with normal serum alpha fetoprotein levels undergo biopsy to define histologically the nature of recurrent disease. In those with pure seminoma retroperitoneal lymph node dissection for post chemotherapy residual masses can be avoided. PMID- 20735394 TI - A novel compensating mechanism for homozygous coagulation factor V deficiency suggested by enhanced activated partial thromboplastin time after reconstitution with normal factor V. PMID- 20735395 TI - Assessment of metabolic activity by PET-CT with F-18-FDG in patients with T-cell lymphoma. PMID- 20735396 TI - In vivo ribosomal RNA turnover is down-regulated in leukaemic cells in chronic lymphocytic leukaemia. PMID- 20735397 TI - Prospective study of a therapeutic regimen with all-trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia cooperative study. AB - In childhood acute promyelocytic leukaemia (APL), the efficacy of therapy combining cytarabine with all-trans retinoic acid (ATRA) and anthracyclines remains unclear in terms of long-term prognosis. Between August 1997 and March 2004, 58 children with APL (median age: 11 years) were enrolled into an acute myeloid leukaemia (AML) study (AML99-M3) and followed up for a median time of 86 months. The regimen included ATRA and anthracyclines combined with cytarabine in both induction and consolidation. In induction, two patients died of haemorrhage and four patients developed retinoic acid syndrome. Of 58 patients, 56 (96.6%) achieved complete remission, two of whom relapsed in the bone marrow after 15 and 19 months respectively. Sepsis was a major complication, with an incidence of 5.6 10.9% in the consolidation blocks, from which all but one of patients recovered. Consequently, 7-year overall and event-free survival rates were 93.1% and 91.4% respectively, and cumulative incidence of relapse plateaued at 3.6% after 2 years. Follow-up survey of 54 patients revealed no patients with late cardiotoxicity or secondary malignancy, except one with asymptomatic prolongation of QTc interval. This study suggests that the combination of cytarabine with ATRA and anthracycline-based therapy may have useful implications in the perspective of long-term prognosis and late adverse effects for childhood APL. PMID- 20735398 TI - Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). AB - To assess if immunochemotherapy influenced the prognostic value of IPI in elderly diffuse large B-cell lymphoma (DLBCL) patients, we evaluated the performance of the standard International Prognostic Index (IPI) and following modifications: age adjusted (AA)-IPI, revised (R)-IPI, and an elderly IPI with age cut-off 70 years (E-IPI) in patients > 60 years treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). In 267 patients, by IPI/AA-IPI 60% were high-intermediate, 53% high and 12% low risk. With R-IPI, 60% were poor risk and none very good risk. Using E-IPI, 45% were high intermediate/high risk and 27% low risk. No differences in outcome were seen in the low/low-intermediate groups with IPI/AA-IPI. For E-IPI, failure-free survival (FFS) and overall survival (OS) were significantly different for low/low intermediate groups. No differences were detected in the four indices with model fit/discrimination measures; however, E-IPI ranked highest. For elderly R-CHOP treated patients, distribution of IPI/AA-IPI skewed toward high/high-intermediate risk with no differences in FFS/OS between low/low-intermediate risk. In contrast, with E-IPI, more are classified as low risk with significant differences in FFS/OS for low-intermediate compared to low risk. The R-IPI does not identify a very good risk group, thus minimizing its utility in this population. The prognostic discrimination provided by the E-IPI for low and low intermediate elderly DLBCL patients needs validation by other datasets. PMID- 20735399 TI - Thrombopoietic effect of VPAC1 inhibition during megakaryopoiesis. AB - Megakaryocytes and platelets express the stimulatory G protein (Gs)-coupled VPAC1 receptor, for which the pituitary adenylyl cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are agonists. The neuropeptide PACAP and VPAC1 were previously found to negatively regulate megakaryopoiesis, and inhibition of their physiological pathway was found to have a thrombopoietic effect in conditions where megakaryopoiesis and thrombopoiesis were impaired, such as chemotherapy-induced thrombocytopenia and congenital thrombocytopenia. The present study explored the thrombopoietic effect of VPAC1 inhibition in a murine model of syngeneic bone marrow transplantation (BMT) and in passive immune thrombocytopenia. Treatment of donor mice with a neutralizing anti-VPAC1 antibody stimulated the initial, most critical recovery of the platelets in irradiated mice. In the passive immune thrombocytopenia model, we observed a thrombopoietic effect, resulting in a less severe platelet drop after induction of their removal in the spleen by an anti-platelet antibody. We concluded that inhibition of the physiological PACAP/VPAC1 pathway could stimulate in vivo megakaryopoiesis. This inhibition can be applied to attenuate thrombocytopenia in conditions where platelets are destroyed as the major pathogenetic mechanism, e.g. immune thrombocytopenia purpura, or need to be produced de novo, e.g. after irradiation and BMT. PMID- 20735400 TI - Advances in understanding the pulmonary infiltration in acute promyelocytic leukaemia. AB - In acute promyelocytic leukaemia (APL), differentiation therapy can be complicated by the development of a differentiation syndrome (DS). Pulmonary infiltration of differentiating leukaemic cells is a key event in the development of DS. Several mediators have been identified that may promote migration and extravasation of differentiating APL cells from the bloodstream into the tissue. Adhesion of APL cells to each other and to the endothelium is induced by upregulation of the expression of adhesion molecules and constitutively active beta2-integrins during differentiation therapy. The expression of chemokines and their receptors is significantly upregulated as well. Pulmonary chemokine production can trigger transendothelial migration of differentiating APL cells from the bloodstream into the underlying tissue (initiation phase of DS). Massive production of chemokines by infiltrated APL cells can further enhance transendothelial migration of differentiating APL cells, causing an uncontrollable hyperinflammatory reaction in the lung (aggravation phase), which is not efficiently switched-off by corticosteroids. PMID- 20735401 TI - Intravascular large B-cell lymphoma within a subcutaneous cavernous haemangioma. PMID- 20735402 TI - Phase I trial of bortezomib in combination with rituximab-HyperCVAD alternating with rituximab, methotrexate and cytarabine for untreated aggressive mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) outcomes have improved over the last two decades; however, late relapses occur. Bortezomib has shown single agent activity of 33% in relapsed MCL and has an additive/synergistic effect in vitro when combined with drugs currently used to treat MCL. We hypothesized that a combination of bortezomib with current intense non-transplant chemoimmunotherapy might prevent late relapses. The toxicity of bortezomib when combined with methotrexate and cytarabine is unknown. Patients aged 18-79 years with untreated aggressive MCL were treated with R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) alternating with rituximab-methotrexate/cytarabine (R M/A). Bortezomib was added to the R-Hyper-CVAD combination as a fixed dose of 1.3 mg/m(2) IV on days 2 and 5 and was added to the R-M/A regimen after rituximab, in increasing doses of 0.7, 1, and 1.3 mg/m(2) in cohorts of three patients. Twenty patients were assessed for toxicity of the regimen. The principal toxicity was haematological and did not differ from that observed with a similar regimen without the bortezomib. In particular, there was no pulmonary or neurological dose-limiting toxicity, showing that bortezomib can be safely combined with R HyperCVAD and R-M/A. PMID- 20735403 TI - Ranolazine selectively blocks persistent current evoked by epilepsy-associated Nanu1.1 mutations. AB - BACKGROUND AND PURPOSE: Mutations of SCN1A, the gene encoding the pore-forming subunit of the voltage-gated sodium channel Na(V) 1.1, have been associated with a spectrum of genetic epilepsies and a familial form of migraine. Several mutant Na(V) 1.1 channels exhibit increased persistent current due to incomplete inactivation and this biophysical defect may contribute to altered neuronal excitability in these disorders. Here, we investigated the ability of ranolazine to preferentially inhibit increased persistent current evoked by mutant Na(V) 1.1 channels. EXPERIMENTAL APPROACH: Human wild-type (WT) and mutant Na(V) 1.1 channels were expressed heterologously in human tsA201 cells and whole-cell patch clamp recording was used to assess tonic and use-dependent ranolazine block. KEY RESULTS: Ranolazine (30 uM) did not affect WT Na(V) 1.1 channel current density, activation or steady-state fast inactivation but did produce mild slowing of recovery from inactivation. Ranolazine blocked persistent current with 16-fold selectivity over tonic block of peak current and 3.6-fold selectivity over use dependent block of peak current. Similar selectivity was observed for ranolazine block of increased persistent current exhibited by Na(V) 1.1 channel mutations representing three distinct clinical syndromes, generalized epilepsy with febrile seizures plus (R1648H, T875M), severe myoclonic epilepsy of infancy (R1648C, F1661S) and familial hemiplegic migraine type 3 (L263V, Q1489K). In vitro application of achievable brain concentrations (1, 3 uM) to cells expressing R1648H channels was sufficient to suppress channel activation during slow voltage ramps, consistent with inhibition of persistent current. CONCLUSIONS AND IMPLICATIONS: Our findings support the feasibility of using selective suppression of increased persistent current as a potential new therapeutic strategy for familial neurological disorders associated with certain sodium channel mutations. PMID- 20735404 TI - Dual bronchodilatory and pulmonary anti-inflammatory activity of RO5024118, a novel agonist at vasoactive intestinal peptide VPAC2 receptors. AB - BACKGROUND AND PURPOSE: Vasoactive intestinal peptide is expressed in the respiratory tract and induces its effects via its receptors, VPAC(1) and VPAC(2). RO5024118 is a selective VPAC(2) receptor agonist derived via chemical modification of an earlier VPAC(2) agonist, RO0251553. In the present studies, we characterized the pharmacological activity of RO5024118. EXPERIMENTAL APPROACH: Stability of RO5024118 to human neutrophil elastase was assessed. Bronchodilatory activity of RO5024118 was investigated in guinea pig and human isolated airway smooth muscle preparations and in a guinea pig bronchoconstriction model. Pulmonary anti-inflammatory activity of RO5024118 was investigated in a lipopolysaccharide mouse model and in a porcine pancreatic elastase (PPE) rat model. KEY RESULTS: RO5024118 demonstrated increased stability to neutrophil elastase compared with RO0251553. In human and guinea pig isolated airway preparations, RO5024118 induced bronchodilatory effects comparable with RO0251553 and the long-acting beta-agonist salmeterol and was significantly more potent than native vasoactive intestinal peptide and the short-acting beta-agonist salbutamol. In 5-HT-induced bronchoconstriction in guinea pigs, RO5024118 exhibited inhibitory activity with similar efficacy as, and longer duration than, RO0251553. In a lipopolysaccharide-mouse model, RO5024118 inhibited neutrophil and CD8(+) cells and myeloperoxidase levels. In rats, intratracheal instillation of PPE induced airway neutrophilia that was resistant to dexamethasone. Pretreatment with RO5024118 significantly inhibited PPE-induced neutrophil accumulation. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that RO5024118 induces dual bronchodilatory and pulmonary anti-inflammatory activity and may be beneficial in treating airway obstructive and inflammatory diseases. LINKED ARTICLES: This article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2010.161.issue-6. PMID- 20735405 TI - Inhibition of monoacylglycerol lipase by troglitazone, N-arachidonoyl dopamine and the irreversible inhibitor JZL184: comparison of two different assays. AB - BACKGROUND AND PURPOSE: Drugs used clinically usually have a primary mechanism of action, but additional effects on other biological targets can contribute to their effects. A potentially useful additional target is the endocannabinoid metabolizing enzyme monoacylglycerol lipase (MGL). We have screened a range of drugs for inhibition of MGL and compared the observed potencies using different MGL enzyme assays. EXPERIMENTAL APPROACH: MGL activity was screened using recombinant human MGL (cell lysates and purified enzyme) with 4-nitrophenyl acetate (NPA) as substrate. 2-Oleolyglycerol metabolism by rat cerebellar cytosolic MGL and by recombinant MGL was also investigated. KEY RESULTS: Among the 96 compounds screened in the NPA assay, troglitazone, CP55,940, N arachidonoyl dopamine and AM404 inhibited NPA hydrolysis by the lysates with IC(50) values of 1.1, 4.9, 0.78 and 3.1uM, respectively. The potency for troglitazone is in the same range as its primary pharmacological activity, activation of peroxisome proliferator-activated receptor (PPAR) gamma. Among PPARgamma ligands, the potency order towards human MGL was troglitazone > ciglitazone > rosiglitazone > 15-deoxy-Delta(12,14) -prostaglandin J(2) ~ CAY 10415 > CAY 10514. In contrast to the time-dependent inhibitor JZL184, the potency of troglitazone was dependent upon the enzyme assay system used. Thus, troglitazone inhibited rat cytosolic 2-oleoylglycerol hydrolysis less potently (IC(50) 41uM) than hydrolysis of NPA by the human MGL lysates. CONCLUSIONS AND IMPLICATIONS: 'Hits' in screening programmes for MGL inhibitors should be assessed in different MGL assays. Troglitazone may be a useful lead for the design of novel, dual action MGL inhibitors/PPARgamma activators. PMID- 20735406 TI - The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice. AB - BACKGROUND AND PURPOSE: 20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20 Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. EXPERIMENTAL APPROACH: TS-011 (0.3 mg.kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. KEY RESULTS: The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS 011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. CONCLUSIONS AND IMPLICATIONS: These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. PMID- 20735407 TI - Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma. AB - BACKGROUND AND PURPOSE: Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma. EXPERIMENTAL APPROACH: Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease. KEY RESULTS: Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100ug.mL(-1) ) and thymic stromal lymphopoietin (TSLP; 20ng.mL(-1) ). Shikonin-treated BM-DCs were poor stimulators of CD4(+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL 13 and tumour necrosis factor (TNF)-alpha release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-alpha and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness. CONCLUSION AND IMPLICATIONS: Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases. PMID- 20735408 TI - Structural determinants in the second intracellular loop of the human cannabinoid CB1 receptor mediate selective coupling to G(s) and G(i). AB - BACKGROUND AND PURPOSE: The cannabinoid CB(1) receptor is primarily thought to be functionally coupled to the G(i) form of G proteins, through which it negatively regulates cAMP accumulation. Here, we investigated the dual coupling properties of CB(1) receptors and characterized the structural determinants that mediate selective coupling to G(s) and G(i). EXPERIMENTAL APPROACH: A cAMP-response element reporter gene system was employed to quantitatively analyze cAMP change. CB(1)/CB(2) receptor chimeras and site-directed mutagenesis combined with functional assays and computer modelling were used to determine the structural determinants mediating selective coupling to G(s) and G(i). KEY RESULTS: CB(1) receptors could couple to both G(s)-mediated cAMP accumulation and G(i)-induced activation of ERK1/2 and Ca(2+) mobilization, whereas CB(2) receptors selectively coupled to G(i) and inhibited cAMP production. Using CB(1)/CB(2) chimeric receptors, the second intracellular loop (ICL2) of the CB(1) receptor was identified as primarily responsible for mediating G(s) and G(i) coupling specificity. Furthermore, mutation of Leu-222 in ICL2 to either Ala or Pro switched G protein coupling from G(s) to G(i), while to Ile or Val led to balanced coupling of the mutant receptor with G(s) and G(i) . CONCLUSIONS AND IMPLICATIONS: The ICL2 of CB(1) receptors and in particular Leu-222, which resides within a highly conserved DRY(X)(5) PL motif, played a critical role in G(s) and G(i) protein coupling and specificity. Our studies provide new insight into the mechanisms governing the coupling of CB(1) receptors to G proteins and cannabinoid-induced tolerance. PMID- 20735409 TI - Are there functional beta3-adrenoceptors in the human heart? AB - beta3-Adrenoceptor mRNA is expressed in the human heart, but corresponding receptor protein has not yet consistently been demonstrated. Furthermore, their physiological role remains highly controversial. For example, in human atria these receptors apparently do not promote cAMP formation. Evidence presented in this issue of the BJP suggests that a previously reported beta3-adrenoceptor mediated stimulation of Ca(2+) channels at room temperature is absent at physiological temperatures, and that beta3-adrenoceptors have no effect on atrial contraction. Drugs classified as beta3-adrenoceptor agonists cause contraction in human atria but in most cases this involves beta1- and/or beta2-adrenoceptors. In contrast, in human ventricles beta3-adrenoceptor agonists can exhibit negative inotropic effects, potentially involving Pertussis toxin-sensitive G-proteins and activation of a NO synthase. However, firmer pharmacological evidence is required that these effects indeed occur via beta3-adrenoceptors. Whether the expected future use of beta3-adrenoceptor agonists in the treatment of urinary bladder dysfunction is associated with adverse events related to cardiac function remains to be determined from clinical studies. PMID- 20735411 TI - Dysregulation of epithelial Na+ absorption induced by inhibition of the kinases TORC1 and TORC2. AB - BACKGROUND AND PURPOSE: Although the serum and glucocorticoid-inducible protein kinase 1 (SGK1) appears to be involved in controlling epithelial Na(+) absorption, its role in this physiologically important ion transport process is undefined. As SGK1 activity is dependent upon target of rapamycin complex 2 (TORC2)-catalysed phosphorylation of SGK1-Ser(422) , we have explored the effects of inhibiting TORC2 and/or TORC1 upon the hormonal control of Na(+) absorption. EXPERIMENTAL APPROACH: Na(+) absorption was quantified electrometrically in mouse cortical collecting duct cells (mpkCCD) grown to confluence on permeable membranes. Kinase activities were assessed by monitoring endogenous protein phosphorylation, with or without TORC1/2 inhibitors (TORIN1 and PP242) and the TORC1 inhibitor: rapamycin. KEY RESULTS: Inhibition of TORC1/2 (TORIN1, PP242) suppressed basal SGK1 activity, prevented insulin- and dexamethasone-induced SGK1 activation, and caused modest (10-20%) inhibition of basal Na(+) absorption and substantial (~80%) inhibition of insulin/dexamethasone-induced Na(+) transport. Inhibition of TORC1 did not impair SGK1 activation or insulin-induced Na(+) transport, but did inhibit (~80%) dexamethasone-induced Na(+) absorption. Arginine vasopressin stimulated Na(+) absorption via a TORC1/2-independent mechanism. CONCLUSION AND IMPLICATIONS: Target of rapamycin complex 2, but not TORC1, is important to SGK1 activation. Signalling via phosphoinositide-3 kinase/TORC2/SGK1 can explain insulin-induced Na(+) absorption. TORC2, but not TORC1, is also involved in glucocorticoid-induced SGK1 activation but its role is permissive. Glucocorticoid-induced Na(+) transport displayed a requirement for TORC1 activity. Therefore, TORC1 and TORC2 contribute to the regulation of Na(+) absorption. Pharmacological manipulation of TORC1/2 signalling may provide novel therapies for Na(+)-sensitive hypertension. PMID- 20735410 TI - The GABAβ receptor as a target for antidepressant drug action. AB - Preclinical and clinical data suggest that a modification in GABA(B) receptor expression and function may contribute to the symptoms of major depression and the response to antidepressants. This includes laboratory animal experiments demonstrating that antidepressants modify brain GABA(B) receptor expression and function and that GABA(B) receptor antagonists display antidepressant potential in animal models of this condition. Clinical and post-mortem studies reveal changes in GABAergic transmission associated with depression as well as depression-related changes in GABA(B) subunit expression that are localized to the cortical depression network. Detailed in this review are the preclinical and clinical data implicating a role for the GABA(B) receptor system in mediating symptoms of this disorder and its possible involvement in the response to antidepressants. Particular emphasis is placed on clinical and post-mortem studies, including previously unpublished work demonstrating regionally-selective modifications in GABA(B) receptor subunit expression in brain samples obtained from depressed subjects. Together with the earlier preclinical studies, these new data point to a role for the GABA(B) system in major depression and support the antidepressant potential of GABA(B) receptor antagonists. PMID- 20735412 TI - Adenosine and inosine release during hypoxia in the isolated spinal cord of neonatal rats. AB - BACKGROUND AND PURPOSE: Adenosine and inosine accumulate extracellularly during hypoxia/ischaemia in the brain and may act as neuroprotectants. In spinal cord, there is pharmacological evidence for increases in extracellular adenosine during hypoxia, but no direct measurements of purine release. Furthermore, the efflux pathways and origin of extracellular purines are not defined. To characterize hypoxia-evoked purine accumulation, we examined the effect of acute hypoxia on the extracellular levels of adenosine and inosine in isolated spinal cords from rats. EXPERIMENTAL APPROACH: Extracellular adenosine and inosine concentrations were assayed in an in vitro preparation of the isolated spinal cord of the neonatal rat by HPLC. KEY RESULTS: The extracellular level of inosine was about 10-fold higher than that of adenosine. Acute hypoxia (10 min) caused a temperature-dependent increase in these two purines, which were inhibited by an increase in external Ca(2+), but not by several inhibitors of efflux pathways or metabolic enzymes of adenine nucleotides. Inhibitors of adenosine deaminase or the equilibrative nucleoside transporter (ENT) abolished the hypoxia-evoked increase in inosine but not adenosine. The inhibition of glial metabolism abolished the increase of both purines evoked by hypoxia but not by oxygen glucose deprivation, hypercapnia or an adenosine kinase inhibitor. CONCLUSIONS AND IMPLICATIONS: Our data suggest that hypoxia releases adenosine itself from intracellular sources. Inosine formed intracellularly may be released through ENTs. During hypoxia, astrocytes appear to play a key role in purine release from neonatal rat spinal cord. PMID- 20735413 TI - Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland. AB - BACKGROUND AND PURPOSE: To investigate the role of connexin 43 in the maintenance of spontaneous activity in prostate tissue from young and old guinea pigs. EXPERIMENTAL APPROACH: Conventional intracellular microelectrode and tension recording techniques, coupled with Western blot analysis and immunohistochemistry for connexin 43 (CX43) were used. The effects of three gap junction uncouplers, 18beta glycyrrhetinic acid (10 uM, 40 uM), carbenoxolone (10 uM, 50 uM) and octanol (0.5 mM, 1 mM), were studied in cells displaying slow wave activity and on spontaneously contracting tissue from prostate glands of young (2-5 months) and old (9-16 months) guinea pigs. KEY RESULTS: 18beta Glycyrrhetinic acid (40 uM), carbenoxolone (50 uM) or octanol (0.5 mM) abolished slow wave activity in prostate tissue from young and old guinea pigs and depolarized membrane potential by approximately 5 mV. These treatments also abolished all contractions in both sets of prostate tissue. These effects were reversed upon washout. Western blot analysis and CX43 immunohistochemistry showed that there was no age-related difference in the expression and distribution of CX43 in prostate tissues. CONCLUSION AND IMPLICATIONS: When gap junctional communication via CX43 was disrupted, spontaneous activity was abolished at a cellular and whole tissue level; CX43 is therefore essential for the maintenance of spontaneous slow wave activity and subsequent contractile activity in the guinea pig prostate gland. PMID- 20735415 TI - Therapeutic potential of targeting group III metabotropic glutamate receptors in the treatment of Parkinson's disease. AB - Current drugs used in the treatment of Parkinson's disease (PD), for example, L DOPA and dopamine agonists, are very effective at reversing the motor symptoms of the disease. However, they do little to combat the underlying degeneration of dopaminergic neurones in the substantia nigra pars compacta (SNc) and their long term use is associated with the appearance of adverse effects such as L-DOPA induced dyskinesia. Much emphasis has therefore been placed on finding alternative non-dopaminergic drugs that may circumvent some or all of these problems. Group III metabotropic glutamate (mGlu) receptors were first identified in the basal ganglia a decade ago. One or more of these receptors (mGlu4, mGlu7 or mGlu8) is found on pre-synaptic terminals of basal ganglia pathways whose overactivity is implicated not only in the generation of motor symptoms in PD, but also in driving the progressive SNc degeneration. The finding that drugs which activate group III mGlu receptors can inhibit transmission across these overactive synapses has lead to the proposal that group III mGlu receptors are promising targets for drug discovery in PD. This paper provides a comprehensive review of the role and target potential of group III mGlu receptors in the basal ganglia. Overwhelming evidence obtained from in vitro studies and animal models of PD supports group III mGlu receptors as potentially important drug targets for providing both symptom relief and neuroprotection in PD. PMID- 20735417 TI - GPR55-dependent and -independent ion signalling in response to lysophosphatidylinositol in endothelial cells. AB - BACKGROUND AND PURPOSE: The glycerol-based lysophospholipid lysophosphatidylinositol (LPI) is an endogenous agonist of the G-protein-coupled receptor 55 (GPR55) exhibiting cannabinoid receptor-like properties in endothelial cells. To estimate the contribution of GPR55 to the physiological effects of LPI, the GPR55-dependent and -independent electrical responses in this cell type were investigated. EXPERIMENTAL APPROACH: Applying small interference RNA-mediated knock-down and transient overexpression, GPR55-dependent and independent effects of LPI on cytosolic free Ca(2+) concentration, membrane potential and transmembrane ion currents were studied in EA.hy296 cells. KEY RESULTS: In a GPR55-dependent, GDPbetaS and U73122-sensitive manner, LPI induced rapid and transient intracellular Ca(2+) release that was associated with activation of charybdotoxin-sensitive, large conductance, Ca(2+)-activated, K(+) channels (BK(Ca)) and temporary membrane hyperpolarization. Following these initial electrical reactions, LPI elicited GPR55-independent long-lasting Na(+) loading and a non-selective inward current causing sustained membrane depolarization that depended on extracellular Ca(2+) and Na(+) and was partially inhibited by Ni(2+) and La(3+). This inward current was due to the activation of a voltage-independent non-selective cation current. The Ni(2+) and La(3+) insensitive depolarization with LPI was prevented by inhibition of the Na/K ATPase by ouabain. CONCLUSIONS AND IMPLICATIONS: LPI elicited a biphasic response in endothelial cells of which the immediate Ca(2+) signalling depends on GPR55 while the subsequent depolarization is due to Na(+) loading via non-selective cation channels and an inhibition of the Na/K-ATPase. Thus, LPI is a potent signalling molecule that affects endothelial functions by modulating several cellular electrical responses that are only partially linked to GPR55. PMID- 20735416 TI - New insights into the molecular mechanisms of general anaesthetics. AB - This paper provides new insights of how general anaesthetic research should be carried out in the future by an analysis of what we know, what we do not know and what we would like to know. I describe previous hypotheses on the mechanism of action of general anaesthetics (GAs) involving membranes and protein receptors. I provide the reasons why the GABA type A receptor, the NMDA receptor and the glycine receptor are strong candidates for the sites of action of GAs. I follow with a review on attempts to provide a mechanism of action, and how future research should be conducted with the help of physical and chemical methods. PMID- 20735414 TI - Aiming drug discovery at lysophosphatidic acid targets. AB - Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is the prototype member of a family of lipid mediators and second messengers. LPA and its naturally occurring analogues interact with G protein-coupled receptors on the cell surface and a nuclear hormone receptor within the cell. In addition, there are several enzymes that utilize LPA as a substrate or generate it as a product and are under its regulatory control. LPA is present in biological fluids, and attempts have been made to link changes in its concentration and molecular composition to specific disease conditions. Through their many targets, members of the LPA family regulate cell survival, apoptosis, motility, shape, differentiation, gene transcription, malignant transformation and more. The present review depicts arbitrary aspects of the physiological and pathophysiological actions of LPA and attempts to link them with select targets. Many of us are now convinced that therapies targeting LPA biosynthesis and signalling are feasible for the treatment of devastating human diseases such as cancer, fibrosis and degenerative conditions. However, successful targeting of the pathways associated with this pleiotropic lipid will depend on the future development of as yet undeveloped pharmacons. PMID- 20735418 TI - 2-Methoxystypandrone represses RANKL-mediated osteoclastogenesis by down regulating formation of TRAF6-TAK1 signalling complexes. AB - BACKGROUND AND PURPOSE: 2-Methoxystypandrone (2-MS) is a naphthoquinone isolated from Polygonum cuspidatum, a Chinese herb used to treat bone diseases. Here we have determined whether 2-MS antagonised osteoclast development and bone resorption. EXPERIMENTAL APPROACH: RAW264.7 cells were treated with receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) to induce differentiation into osteoclasts. RT-PCR and Western blot were used to analyse osteoclast-associated gene expression and signalling pathways. KEY RESULTS: The number of multinuclear osteoclasts, actin rings and resorption pit formation were markedly inhibited by 2-MS, targeting osteoclast differentiation at an early stage and without significant cytotoxicity. The anti-resorption effect of 2-MS was accompanied by decreasing dendritic cell-specific transmembrane protein and matrix metalloproteinase-9 (MMP-9) mRNA expression. RANKL-increased MMP-9 gelatinolytic activity was also attenuated by concurrent, but not by subsequent addition of 2-MS. 2-MS markedly inhibited not only the RANKL-triggered nuclear translocations of NF-kappaB, c-Fos and nuclear factor of activated T cells c1 (NFATc1), but also the subsequent NFATc1 induction. Degradation of IkappaB and phosphorylation of mitogen-activated protein kinases were also suppressed. RANKL facilitated the formation of signaling complexes of tumour necrosis factor receptor-associated factor 6 and transforming growth factor beta-activated kinase 1 (TRAF6-TAK1), important for osteoclastogenesis and formation of such signalling complexes was prevented by 2-MS. CONCLUSIONS AND IMPLICATIONS: The anti osteoclastogenic effects of 2-MS could reflect the block of RANKL-induced association of TRAF6-TAK1 complexes with consequent decrease of IkappaB-mediated NF-kappaB and mitogen-activated protein kinases-mediated c-Fos activation pathways and suppression of NFATc1 and other gene expression, essential for bone resorption. PMID- 20735420 TI - Insulin resistance in penile arteries from a rat model of metabolic syndrome. AB - BACKGROUND AND PURPOSE: Metabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vascular effects of insulin in penile arteries and whether these effects are impaired in a rat model of insulin resistance and metabolic syndrome. EXPERIMENTAL APPROACH: Penile arteries from obese Zucker rats (OZR) and their counterpart, lean Zucker rats (LZR), were mounted on microvascular myographs and the effects of insulin were assessed in the absence and presence of endothelium and of specific inhibitors of nitric oxide (NO) synthesis, phosphatidylinositol 3 kinase (PI3K) and mitogen-activated protein kinase (MAPK). Insulin-induced changes in intracellular Ca(2+) concentration [Ca(2+)](i) were also examined. KEY RESULTS OZR exhibited mild hyperglycaemia, hypercholesterolemia, hypertryglyceridemia and hyperinsulinemia. Insulin induced endothelium- and NO dependent relaxations in LZR that were impaired in OZR. Inhibition of PI3K reduced relaxation induced by insulin and by the beta-adrenoceptor agonist isoprenaline, mainly in arteries from LZR. Antagonism of endothelin 1 (ET-1) receptors did not alter insulin-induced relaxation in either LZR or OZR, but MAPK blockade increased the responses in OZR. Insulin decreased [Ca(2+)](i), a response impaired in OZR. CONCLUSIONS AND IMPLICATIONS: Insulin-induced relaxation was impaired in penile arteries of OZR due to altered NO release through the PI3K pathway and unmasking of a MAPK-mediated vasoconstriction. This vascular insulin resistance is likely to contribute to the endothelial dysfunction and erectile dysfunction associated with insulin resistant states. PMID- 20735419 TI - Inverse agonism of cannabinoid CB1 receptors potentiates LiCl-induced nausea in the conditioned gaping model in rats. AB - BACKGROUND AND PURPOSE: Cannabinoid CB(1) receptor antagonists/inverse agonists, potentiate toxin-induced nausea and vomiting in animal models. Here, we sought to determine if this potentiated nausea was mediated by inverse agonism or neutral antagonism of the CB(1) receptor, and if the potentiated nausea would be produced by intracerebroventricular (icv) administration of an inverse agonist. EXPERIMENTAL APPROACH: The conditioned gaping model of nausea in rats was used to compare the CB(1) receptor antagonist/inverse agonist, AM251, and the CB(1) receptor neutral antagonists, AM6527 (centrally and peripherally active) and AM6545 (peripherally active), in potentiating conditioned gaping produced by lithium chloride (LiCl) solution. The effect of icv (lateral ventricle and 4th ventricle) administration of AM251 on LiCl-induced gaping in this model was also evaluated. KEY RESULTS: At a dose that did not produce conditioned gaping on its own, systemically administered AM251 (1.25 mg.kg(-1)) potentiated LiCl-induced conditioned gaping and reduced sucrose palatability; however, even doses as high as 8 mg.kg(-1) of AM6545 and AM6527 neither potentiated LiCl-induced conditioned gaping nor reduced sucrose palatability. Infusions of AM251 into the lateral ventricles (1.25, 12.5 and 125 microg) or the 4th ventricle (2.5, 12.5 and 125 microg) did not potentiate LiCl-induced conditioned gaping reactions, but all doses attenuated saccharin palatability during the subsequent test. CONCLUSIONS AND IMPLICATIONS: Inverse agonism, but not neutral antagonism, of CB(1) receptors potentiated toxin-induced nausea. This effect may be peripherally mediated or may be mediated centrally by action on CB(1) receptors, located distal to the cerebral ventricles. PMID- 20735421 TI - Pentobarbital inhibition of human recombinant alpha1A P/Q-type voltage-gated calcium channels involves slow, open channel block. AB - BACKGROUND AND PURPOSE: Pre-synaptic neurotransmitter release is largely dependent on Ca(2+) entry through P/Q-type (Ca(V)2.1) voltage-gated Ca(2+) channels (PQCCs) at most mammalian, central, fast synapses. Barbiturates are clinical depressants and inhibit pre-synaptic Ca(2+) entry. PQCC barbiturate pharmacology is generally unclear, specifically in man. The pharmacology of the barbiturate pentobarbital (PB) in human recombinant alpha(1A) PQCCs has been characterized. EXPERIMENTAL APPROACH: PB effects on macroscopic Ca(2+)(I(Ca)) and Ba(2+)(I(Ba)) currents were studied using whole-cell patch clamp recording in HEK 293 cells heterologously expressing (alpha(1A))(human)(beta(2a)alpha(2)delta 1)(rabbit) PQCCs. KEY RESULTS: PB reversibly depressed peak current (I(peak)) and enhanced apparent inactivation (fractional current at 800 ms, r(800)) in a concentration-dependent fashion irrespective of charge carrier (50% inhibitory concentration: I(peak), 656 microM; r(800), 104 microM). Rate of mono-exponential I(Ba) decay was linearly dependent on PB concentration. PB reduced channel availability by deepening non-steady-state inactivation curves without altering voltage dependence, slowed recovery from activity-induced unavailable states and produced use-dependent block. PB (100 microM) induced use-dependent block during physiological, high frequency pulse trains and overall depressed PQCC activity by two-fold. CONCLUSION AND IMPLICATIONS: The results support a PB pharmacological mechanism involving a modulated receptor with preferential slow, bimolecular, open channel block (K(d)= 15 microM). Clinical PB concentrations (<200 microM) inhibit PQCC during high frequency activation that reduces computed neurotransmitter release by 16-fold and is comparable to the magnitude of Ca(2+) dependent facilitation, G-protein modulation and intrinsic inactivation that play critical roles in PQCC modulation underlying synaptic plasticity. The results are consistent with the hypothesis that PB inhibition of PQCCs contributes to central nervous system depression underlying anticonvulsant therapy and general anaesthesia. PMID- 20735422 TI - The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action. AB - BACKGROUND AND PURPOSE: Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. EXPERIMENTAL APPROACH: Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABA(A) receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective alpha(2)-adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam. RESULTS: Levetiracetam (10-200 mg.kg( 1); p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5-2 mg.kg(-1); i.p.), naloxone (1-3 mg.kg(-1); i.p.), methysergide (0.25-1 mg.kg(-1); i.p.) and yohimbine (1-3 mg.kg(-1); i.p.). CONCLUSIONS AND IMPLICATIONS: These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans. PMID- 20735423 TI - Effects of drug interactions on biotransformation and antiplatelet effect of clopidogrel in vitro. AB - BACKGROUND AND PURPOSE: The conversion of clopidogrel to its active metabolite, R 130964, is a two-step cytochrome P450 (CYP)-dependent process. The current investigations were performed to characterize in vitro the effects of different CYP inhibitors on the biotransformation and on the antiplatelet effect of clopidogrel. EXPERIMENTAL APPROACH: Clopidogrel biotransformation was studied using human liver microsomes (HLM) or specific CYPs and platelet aggregation using human platelets activated with ADP. KEY RESULTS: Experiments using HLM or specific CYPs (3A4, 2C19) revealed that at clopidogrel concentrations >10 microM, CYP3A4 was primarily responsible for clopidogrel biotransformation. At a clopidogrel concentration of 40 microM, ketoconazole showed the strongest inhibitory effect on clopidogrel biotransformation and clopidogrel-associated inhibition of platelet aggregation with IC(50) values of 0.03 +/- 0.07 microM and 0.55 +/- 0.06 microM respectively. Clarithromycin, another CYP3A4 inhibitor, impaired clopidogrel biotransformation and antiplatelet activity almost as effectively as ketoconazole. The CYP3A4 substrates atorvastatin and simvastatin both inhibited clopidogrel biotransformation and antiplatelet activity, less potently than ketoconazole. In contrast, pravastatin showed no inhibitory effect. As clopidogrel itself inhibited CYP2C19 at concentrations >10 microM, the CYP2C19 inhibitor lansozprazole affected clopidogrel biotransformation only at clopidogrel concentrations < or =10 microM. The carboxylate metabolite of clopidogrel was not a CYP substrate and did not affect platelet aggregation. CONCLUSIONS AND IMPLICATIONS: At clopidogrel concentrations >10 microM, CYP3A4 is mainly responsible for clopidogrel biotransformation, whereas CYP2C19 contributes only at clopidogrel concentrations < or =10 microM. CYP2C19 inhibition by clopidogrel at concentrations >10 microM may explain the conflicting results between in vitro and in vivo investigations regarding drug interactions with clopidogrel. PMID- 20735424 TI - F 15845, a new blocker of the persistent sodium current prevents consequences of hypoxia in rat femoral artery. AB - BACKGROUND AND PURPOSE: The persistent sodium current is involved in myocardial ischaemia and is selectively inhibited by the newly described 3-(R)-[3-(2 methoxyphenylthio-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5-benzoxathiepine bromhydrate (F 15845). Here, we describe the pharmacological profile of F 15845 against the effects of hypoxia in femoral arteries in vitro. EXPERIMENTAL APPROACH: Isometric tension measurement of rat isolated femoral arteries was used to characterize the protective effect of F 15845 against contraction of the vessels induced by veratrine (100 microg.mL(-1)) or hypoxia. KEY RESULTS: Rat femoral artery expressed the Na(v)1.5 channel isoform. When exposed to veratrine (100 microg.mL(-1)), vessels developed a rapid and strong contraction that was abolished by both absence of sodium and blockade of the Na(+)/Ca(++) exchanger by KB-R7943 (10 and 32 micromol.L(-1)) or treatment with F 15845. When used before veratrine exposure, the potency of F 15845 depended on the extracellular K(+) concentration (IC(50)= 11 and 0.77 micromol.L(-1) for 5 and 20 mmol.L(-1) KCl, respectively), whereas its potency was unaffected by extracellular K(+) concentration when given after veratrine. F 15845 did not affect either KCl (80 mmol.L(-1)) or phenylephrine-induced femoral artery contraction. Moreover, endothelium disruption did not affect the protective effect of F 15845 against veratrine-induced femoral artery contraction, suggesting a mechanism of action dependent on smooth muscle cells. Finally, F 15845 prevented in a concentration dependent manner rat femoral artery contraction induced by hypoxia. CONCLUSION AND IMPLICATIONS: F 15845, a selective blocker of the persistent sodium current prevented vascular contraction induced by hypoxic conditions. PMID- 20735425 TI - Induction of a novel cation current in cardiac ventricular myocytes by flufenamic acid and related drugs. AB - BACKGROUND AND PURPOSE: Interest in non-selective cation channels has increased recently following the discovery of transient receptor potential (TRP) proteins, which constitute many of these channels. EXPERIMENTAL APPROACH: We used the whole cell patch-clamp technique on isolated ventricular myocytes to investigate the effect of flufenamic acid (FFA) and related drugs on membrane ion currents. KEY RESULTS: With voltage-dependent and other ion channels inhibited, cells that were exposed to FFA, N-(p-amylcinnamoyl)anthranilic acid (ACA), ONO-RS-082 or niflumic acid (NFA) responded with an increase in currents. The induced current reversed at +38 mV, was unaffected by lowering extracellular Cl(-) concentration or by the removal of extracellular Ca(2+) and Mg(2+), and its inward but not outward component was suppressed in Na(+)-free extracellular conditions. The current was suppressed by Gd(3+) but was resistant to 2-aminoethoxydiphenyl borate (2-APB) and to amiloride. It could not be induced by the structurally related non fenamate anti-inflammatory drug diclofenac, nor by the phospholipase-A(2) inhibitors bromoenol lactone and bromophenacyl bromide. Muscarinic or alpha adrenoceptor activation or application of diacylglycerol failed to induce or modulate the current. CONCLUSIONS AND IMPLICATIONS: Flufenamic acid and related drugs activate a novel channel conductance, where Na(+) is likely to be the major charge carrier. The identity of the channel remains unclear, but it is unlikely to be due to Ca(2+)-activated (e.g. TRPM4/5), Mg(2+)-sensitive (e.g. TRPM7) or divalent cation-selective TRPs. PMID- 20735426 TI - Cis-isomerism and other chemical requirements of steroidal agonists and partial agonists acting at TRPM3 channels. AB - BACKGROUND AND PURPOSE: The transient receptor potential melastatin-3 (TRPM3) channel forms calcium-permeable, non-selective, cationic channels that are stimulated by pregnenolone sulphate (PregS). Here, we aimed to define chemical requirements of this acute steroid action and potentially reveal novel stimulators with physiological relevance. EXPERIMENTAL APPROACH: We used TRPM3 channels over-expressed in HEK 293 cells, with intracellular calcium measurement and whole-cell patch-clamp recording techniques. KEY RESULTS: The stimulation of TRPM3 channels was confined to PregS and closely related steroids and not mimicked by other major classes of steroids, including progesterone. Relatively potent stimulation of TRPM3-dependent calcium entry was observed. A sulphate group positioned at ring A was important for strong stimulation but more striking was the requirement for a cis (beta) configuration of the side group, revealing previously unrecognized stereo-selectivity and supporting existence of a specific binding site. A cis-oriented side group on ring A was not the only feature necessary for high activity because loss of the double bond in ring B reduced potency and loss of the acetyl group at ring D reduced efficacy and potency. Weak steroid stimulators of TRPM3 channels inhibited effects of PregS, suggesting partial agonism. In silico screening of chemical libraries for non-steroid modulators of TRPM3 channels revealed the importance of the steroid backbone for stimulatory effects. CONCLUSIONS AND IMPLICATIONS: Our data defined some of the chemical requirements for acute stimulation of TRPM3 channels by steroids, supporting the existence of a specific and unique steroid binding site. Epipregnanolone sulphate was identified as a novel TRPM3 channel stimulator. PMID- 20735427 TI - Advanced glycation end products (AGEs) activate mast cells. AB - BACKGROUND AND PURPOSE: Advanced glycation endproducts (AGEs) represent one of the many types of chemical modifications that occur with age in long-lived proteins. AGEs also accumulate in pathologies such as diabetes, cardiovascular diseases, neurodegeneration and cancer. Mast cells are major effectors of acute inflammatory responses that also contribute to the progression of chronic diseases. Here we investigated interactions between AGEs and mast cells. EXPERIMENTAL APPROACHES: Histamine secretion from AGEs-stimulated mast cells was measured. Involvement of a receptor for AGEs, RAGE, was assessed by PCR, immunostaining and use of inhibitors of RAGE. Production of reactive oxygen species (ROS) and cytokines was measured. KEY RESULTS: Advanced glycation endproducts dose-dependently induced mast cell exocytosis with maximal effects being obtained within 20 s. RAGE mRNA was detected and intact cells were immunostained by a specific anti-RAGE monoclonal antibody. AGEs-induced exocytosis was inhibited by an anti-RAGE antibody and by low molecular weight heparin, a known RAGE antagonist. RAGE expression levels were unaltered after 3 h treatment with AGEs. AGE-RAGE signalling in mast cells involves Pertussis toxin sensitive G(i)-proteins and intracellular Ca(2+) increases as pretreatment with Pertussis toxin, caffeine, 2-APB and BAPTA-AM inhibited AGE-induced exocytosis. AGEs also rapidly stimulated ROS production. After 6 h treatment with AGEs, the pattern of cytokine secretion was unaltered compared with controls. CONCLUSIONS AND IMPLICATIONS: Advanced glycation endproducts activated mast cells and may contribute to a vicious cycle involving generation of ROS, increased formation of AGEs, activation of RAGE and to the increased low-grade inflammation typical of chronic diseases. PMID- 20735428 TI - Histamine H1 receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory. AB - BACKGROUND AND PURPOSE: The histaminergic neurotransmitter system is currently under investigation as a target for drug treatment of cognitive deficits in clinical disorders. The therapeutic potential of new drugs may initially be screened using a model of histaminergic dysfunction, for example, as associated with the use of centrally active antihistamines. Of the selective second generation antihistamines, cetirizine has been found to have central nervous system effects. The aim of the present study was to determine whether cetirizine can be used as a tool to model cognitive deficits associated with histaminergic hypofunction. EXPERIMENTAL APPROACH: The study was conducted according to a three way, double-blind, cross-over design. Treatments were single oral doses of cetirizine 10 and 20 mg and placebo. Effects on cognition were assessed using tests of word learning, memory scanning, vigilance, divided attention, tracking and visual information processing speed. KEY RESULTS: Cetirizine 10 mg impaired tracking performance and both doses impaired memory scanning speed. None of the other measures indicated impaired performance. CONCLUSION AND IMPLICATIONS: Cetirizine affects information processing speed, but these effects were not sufficient to serve as a model for cognitive deficits in clinical disorders. PMID- 20735430 TI - Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal cancer. AB - No ideal serum markers for screening colorectal cancer (CRC) have been identified. The aim of this study was to determine the usefulness of endothelial cell-specific molecule-1 (ESM-1) as a serum marker for CRC. Illumina microarray was carried out to search CRC-related biomarkers. cDNA microarray detected that ESM-1 was one of the overexpressed genes in CRC. Overexpression of ESM-1 mRNA was confirmed in tissues of CRC by RT-PCR and real-time PCR. Immunohistochemical staining showed strong expression of ESM-1 in the cytoplasm of tumor cells. Overexpression of ESM-1 in human serum with CRC was found by Western blot analysis. For quantitative analysis of ESM-1 in serum, we determined the ESM-1 levels in serum specimens using an ELISA kit. We showed that the ESM-1 levels in the serum of patients with CRC were significantly elevated (70.1 +/- 29.7 pg/mL) compared to healthy subjects (29.7 +/- 14.9 pg/mL). The accuracy, sensitivity, and specificity of ESM-1 for CRC were 0.94, 99%, and 73%, respectively, by receiver operating characteristics curve analysis. The positive predictive value and negative predictive value were 63% and 95%, respectively. The likelihood ratios of a positive or negative test result were 73 and 0.27, respectively. When analyzed with a Cox regression model, a higher serum ESM-1 level (>=76.0 pg/mL) was correlated with poor prognosis. This study suggests that expression of ESM-1 is increased in tissue and serum of CRC patients and that ESM-1 can be used as a potential serum marker for the early detection of CRC. PMID- 20735429 TI - Protective effect of hydrogen sulphide against 6-OHDA-induced cell injury in SH SY5Y cells involves PKC/PI3K/Akt pathway. AB - BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S) is a novel neuromodulator. The present study aimed to investigate the protective effect of H(2)S against cell injury induced by 6-hydroxydopamine (6-OHDA), a selective dopaminergic neurotoxin often used to establish a model of Parkinson's disease for studying the underlying mechanisms of this condition. EXPERIMENTAL APPROACH: Cell viability in SH-SY5Y cells was measured using MTT assay. Western blot analysis and pharmacological manipulation were employed to study the signalling mechanisms. KEY RESULTS: Treatment of SH-SY5Y cells with 6-OHDA (50-200 microM) for 12 h decreased cell viability. Exogenous application of NaHS (an H(2)S donor, 100-1000 microM) or overexpression of cystathionine beta-synthase (a predominant enzyme to produce endogenous H(2)S in SH-SY5Y cells) protected cells against 6-OHDA-induced cell apoptosis and death. Furthermore, NaHS reversed 6-OHDA-induced loss of tyrosine hydroxylase. Western blot analysis showed that NaHS reversed the down regulation of PKCalpha, epsilon and Akt and the up-regulation of PKCdelta in 6 OHDA-treated cells. Blockade of PKCalpha with Go6976 (2 microM), PKCepsilon with EAVSLKPT (200 microM) or PI3K with LY294002 (20 microM) reduced the protective effects of H(2)S. However, inhibition of PKCdelta with rottlerin (5 microM) failed to affect 6-OHDA-induced cell injury. These data suggest that the protective effects of NaHS mainly resulted from activation of PKCalpha, epsilon and PI3K/Akt pathway. In addition, NaHS-induced Akt phosphorylation was significantly attenuated by Go6976 and EAVSLKPT, suggesting that the activation of Akt by NaHS is PKCalpha, epsilon-dependent. CONCLUSIONS AND IMPLICATIONS: H(2)S protects SH-SY5Y cells against 6-OHDA-induced cell injury by activating the PKCalpha, epsilon/PI3K/Akt pathway. PMID- 20735431 TI - Negative role of trihydrophobin 1 in breast cancer growth and migration. AB - Trihydrophobin 1 (TH1) is a member of the negative elongation factor complex, which is involved in transcriptional pausing. Although the negative elongation factor complex attenuates the estrogen receptor alpha-mediated transcription, little is known about the relationship between TH1 and tumor progression. Here, we report that the protein level of TH1 was negatively correlated with the aggressiveness of human breast cancer. Immunohistochemical analysis revealed that TH1 expression in clinical stage III-IV primary breast cancer tissues was statistically significantly lower than that in stage I-II breast tissues (P < 0.01), and especially inversely associated with lymph node metastasis (P < 0.001). Furthermore, we showed that overexpression of TH1 in MDA-MB-231 breast cancer cells inhibited, and knockdown of TH1 in MCF-7 cells enhanced, cell proliferation and migratory ability. Moreover, upregulation of TH1 in MDA-MB-231 cells resulted in the decrease of cyclin D1, beta-catenin, and ERK activity, and the increase of p21. In contrast, knockdown of TH1 in MCF-7 cells enhanced the expression of cyclin D1 and beta-catenin, increased the activity of ERK, and downregulated the expression of p21. Additionally, overexpression of TH1 in MDA MB-231 cells prevented. However, knockdown of TH1 in MCF-7 cells induced a number of molecular and cellular alterations associated with epithelial-mesenchymal transition. Taken together, our results suggest that TH1 might play an important role in regulation of proliferation and invasion in human breast cancer, and could be a potential target for human breast cancer treatment. PMID- 20735432 TI - Programmed cell death 4 enhances chemosensitivity of ovarian cancer cells by activating death receptor pathway in vitro and in vivo. AB - Chemoresistance is a major cause of treatment failure in ovarian cancer. Therefore, it is necessary to explore alternative therapeutic methods to overcome drug resistance for ovarian cancer treatment. We previously reported that programmed cell death 4 (PDCD4), a tumor suppressor, significantly suppresses the malignant phenotype of ovarian cancer cells and its lost or low expression in ovarian cancer is associated with unfavorable prognosis of patients. Here we show that PDCD4 improves the sensitivity of ovarian cancer cells to platinum-based chemotherapy. Overexpression of PDCD4 enhanced chemosensitivity in SKOV3 and CAOV3 cells with low levels of PDCD4, whereas knockdown of PDCD4 reduced chemosensitivity in OVCAR3 cells with high levels of PDCD4. Subsequently, the combination of enforced PDCD4 expression with cisplatin treatment significantly suppressed ovarian tumor growth in a xenograft animal model. The PDCD4 effect appears to be specific for cisplatin and carboplatin, not affecting cyclophosphamide, etoposide, or paclitaxel. Mechanistically, PDCD4 significantly increased cisplatin-induced cleavage of caspase-3 and caspase-8, but had only a slight impact on caspase-9 cleavage and the expression of Bax and Bcl-2 in vitro and in vivo. A specific caspase-8 inhibitor, Z-ITED-FMK, attenuated cisplatin induced apoptosis in PDCD4-overexpressing ovarian cancer cells. Taken together, our results indicate that PDCD4 enhances cisplatin-induced apoptosis by mainly activating the death receptor pathway, and PDCD4 gene transfer in combination with cisplatin therapy may break the resistance of ovarian cancer cells to chemotherapy. PMID- 20735433 TI - The side population, as a precursor of Hodgkin and Reed-Sternberg cells and a target for nuclear factor-kappaB inhibitors in Hodgkin's lymphoma. AB - Although disturbed cytokinesis of mononuclear Hodgkin (H) cells is thought to generate Reed-Sternberg (RS) cells, differentiation of Hodgkin's lymphoma (HL) cells is not fully understood. Recent studies indicate that cells found in a side population (SP) share characteristics of cancer stem cells. In this study we identified an SP in the HL cell lines, KMH2 and L428. This SP almost entirely consists of distinct small mononuclear cells, whereas the non-SP is a mixture of relatively large cells with H or RS cell-like morphology. Culture of the small mononuclear cells in the SP from KMH2 generated a non-SP. Single cell culture of the SP cells generated large cells with H or RS cell-like morphology. We found that CD30 overexpression and constitutive nuclear factor-kappaB (NF-kappaB) activity, both of which are characteristics of HL cells, are shared between the SP and non-SP cells for both KMH2 and L428. Inhibition of NF-kappaB induced apoptosis in both fractions, whereas the SP cells were resistant to a conventional chemotherapeutic agent doxorubicin. The results show that HL cell lines contain an SP, that is enriched for distinct small mononuclear cells and generates larger cells with H and RS cell-like morphology. The results also stress the significance of NF-kappaB inhibition for eradication of HL cells. PMID- 20735434 TI - let-7 and miR-17-92: small-sized major players in lung cancer development. AB - MicroRNA (miRNA)-encoding small non-coding RNA have been recognized as important regulators of a number of biological processes that inhibit the expression of hundreds of genes. Accumulating evidence also indicates the involvement of miRNA alterations in various types of human cancer, including lung cancer, which has long been the leading cause of cancer death in economically well-developed countries, including Japan. We previously found that downregulation of members of the tumor-suppressive let-7 miRNA family and overexpression of the oncogenic miR 17-92 miRNA cluster frequently occur in lung cancers, and molecular insight into how these miRNA alterations may contribute to tumor development has been rapidly accumulating. The present review summarizes recent advances in elucidation of the molecular functions of these miRNA in relation to their roles in the pathogenesis of lung cancer. Given the crucial roles of miRNA alterations, additional studies are expected to provide a better understanding of the underlying molecular mechanisms of disease development, as well as a foundation for novel strategies for cancer diagnosis and treatment of this devastating disease. PMID- 20735435 TI - Oxidative DNA damage and reporter gene mutation in the livers of gpt delta rats given non-genotoxic hepatocarcinogens with cytochrome P450-inducible potency. AB - Previous reports have proposed that reactive oxygen species resulting from induction of cytochrome P450 (CYP) isozymes might be involved in the modes of action of hepatocarcinogens with CYP-inducible potency. In the present study, we investigated 8-hydroxydeoxyguanosine (8-OHdG) levels, in vivo mutagenicity and glutathione S-transferase placental form (GST-P)-positive foci in the livers of gpt delta rats treated with piperonyl butoxide (PBO) or phenobarbital (PhB) for 4 and 13 weeks. Significant elevations in Cyp 1A1 and Cyp 1A2 mRNA levels after PBO treatment, and in Cyp 2B1 mRNA levels after PBO or PhB treatment, appeared together with remarkable hepatomegaly through the experimental period. Time dependent and statistically significant increases in 8-OHdG levels were observed in the PBO treatment group along with significant increases in proliferating cell nuclear antigen (PCNA)-positive hepatocytes at 4 weeks, while no increase in 8 OHdG levels was found in PhB-treated rats. No changes in mutant frequencies of gpt and red/gam (Spi(-)) genes in liver DNA from PBO- or PhB-treated rats were observed at 4 or 13 weeks. A 13-week exposure to either PBO or PhB did not affect the number and area of GST-P-positive hepatocytes. CYP 1A1 and 1A2 induction may be responsible for elevated levels of 8-OHdG in PBO-treated rats. However, neither GC:TA transversions nor deletion mutations, typically regarded as 8-OHdG related mutations, were observed in any of the treated rats. We conclude that reactive oxygen species, possibly produced through CYP catalytic pathways, likely induced genomic DNA damage but did not give rise to permanent gene mutation. PMID- 20735436 TI - Epigenetic alteration of the NF-kappaB-inducing kinase (NIK) gene is involved in enhanced NIK expression in basal-like breast cancer. AB - Basal-like breast cancers are triple-negative (estrogen receptor negative, progesterone receptor negative, erythroblastic leukemia viral oncogene homolog 2 (ERBB2) negative) tumors with an aggressive clinical behavior that lacks effective molecular targets for therapy. We reported previously that the basal like subtype cell lines display high constitutive nuclear factor (NF)-kappaB activation, whose inhibition in the basal-like subtypes suppressed their proliferation. Moreover, NF-kappaB-inducing kinase (NIK) is involved in the constitutive NF-kappaB activation. Here, we report that enhanced NIK expression, which is exclusively observed in the basal-like subtype rather than the luminal like subtype or non-tumorigenic mammary epithelial cells, is caused by epigenetic alteration of the NIK gene. The stability of NIK mRNA and transcriptional activity driven by the NIK promoter are similar in the basal-like and luminal like subtypes. However, histone H3 acetylation levels were up-regulated in the basal-like subtype. Furthermore, treatment of the luminal-like subtype with a histone deacetylase inhibitor, valproic acid, significantly increased NIK expression. Although DNA methylation of the NIK locus was not detected, NIK expression also increased when the luminal-like subtype was treated with 5 azacytidine, which inhibits histone H3-Lys-9 dimethylation in addition to DNA methylation. Taken together, these results suggest that the closed chromatin structure mediated by histone H3 methylation and deacetylation suppresses NIK expression in the luminal-like subtype, whereas disruption of these suppression mechanisms leads to enhanced NIK expression and the constitutive NF-kappaB activation in the basal-like subtype. Thus, NIK and genes induced by the NIK mediated constitutive NF-kappaB activation could be therapeutic targets of basal like breast cancer. PMID- 20735437 TI - Neisseria gonorrhoeae effectively blocks HIV-1 replication by eliciting a potent TLR9-dependent interferon-alpha response from plasmacytoid dendritic cells. AB - Clinical and epidemiological research provides evidence for a positive correlation between Neisseria gonorrhoeae infection and HIV transmission; however, mechanistic studies examining this relationship have yielded conflicting results. To explore this interaction, we exposed ex vivo cultured peripheral blood cells from acute HIV(+) individuals to N. gonorrhoeae. Unexpectedly, we observed a profound inhibition in HIV-1 replication in the ex vivo cultures, and this was recapitulated when peripheral blood mononuclear cells (PBMCs) from healthy donors were co-infected with HIV-1 and N. gonorrhoeae. Next, we established that gonococcal-infected PBMCs liberated a soluble factor that effectively blocked HIV-1 replication. Cytokine analyses and antibody blocking experiments revealed that the type I interferon, interferon-alpha (IFNalpha), was expressed upon exposure to N. gonorrhoeae and was responsible for the inhibition of HIV-1. Intracellular staining, TLR9-blocking and cell depletion-based studies demonstrated that the IFNalpha was elicited by plasmacytoid dendritic cells (pDCs) in a TLR9-dependent manner. The pDC response to N. gonorrhoeae was unexpected given pDCs more established role in innate defence against intracellular pathogens, suggesting this may be a bacterial immune evasion strategy. In the context of HIV, this overcomes the virus's otherwise effective avoidance of the interferon response and represents a previously unrecognized intersection between these two sexually transmitted pathogens. PMID- 20735438 TI - Age-related changes in biological characteristics of human alveolar osteoblasts. AB - OBJECTIVES: Age-related changes are common in many tissues and organs. However, cell-related causes in human alveolar bone remain unclear. This study has been carried out to explore the possibility that advancing age might change the biological characteristics of alveolar osteoblasts (AOBs) in women. MATERIALS AND METHODS: Alveolar osteoblasts from women donors (five women aged 33-38 years and five women aged 62-68 years) were cultured in vitro. The cells were serially passaged and maximal lifespan evaluated. Cell viability, ultramicrostructure and osteogenic differentiation ability were determined respectively, using MTT assay, transmission electron microscopy, alkaline phosphatase (ALP) activity assay and von Kossa staining assay. These parameters of the two groups of AOBs were evaluated. RESULTS: When compared with cells from young adult donors, AOBs from elderly women exhibited lower maximal lifespan (P < 0.05). Mean rate of population doubling was lower in elderly donor cells compared to those from young adult cells (P < 0.05). Organelles from AOBs of elderly donors were much fewer than those from young donors. MTT value of elderly donor cells was significantly lower than those of young adult donors from day 2 (P < 0.05). Relative ratio of ALP activity in elderly donor cells was significantly lower than those of the young womens' cells at 8, 12, 16 and 20 days (P < 0.05). Calcium nodules of young adult donors' specimens were significantly more numerous and larger than those from elderly donors. CONCLUSIONS: Comparison of biological characteristics of AOBs from young adult women with those from elderly women in vitro revealed differences in proliferative capacity and bone formation functions, which decreased with aging. These data indicate that aging may play an important role in pathogenesis of human AOBs loss. PMID- 20735439 TI - CD200R1 regulates the severity of arthritis but has minimal impact on the adaptive immune response. AB - CD200R1 is a member of the immunoglobulin supergene family that is thought to play an inhibitory role in immunity. Previous studies have established the anti arthritic effect of CD200Fc, an agonist of CD200R1. However, the physiological role played by CD200R1 in arthritis remains to be established. The aims of this study are to assess the contribution of endogenous CD200R1 in regulating the severity of arthritis and to determine its role in shaping the immune response to type II collagen within the context of collagen-induced arthritis, an animal model of rheumatoid arthritis. Arthritis was induced in DBA/1 mice by immunization with type II collagen and the kinetics of expression of CD200R1 and CD200 were monitored by quantitative reverse transcription-polymerase chain reaction. Next, a comparison was made between CD200R1(-/-) and wild-type mice in terms of the progression of collagen-induced arthritis, as well as the B and T cell responses to type II collagen. The expression of both CD200R1 and CD200 was increased after immunization and reached maximal levels at the height of the inflammatory response. In addition, the severity of arthritis was increased significantly in CD200R1(-/-) mice compared to wild-type mice. However, little or no differences were observed between CD200R1(-/-) and wild-type mice in terms of the T or B cell responses to type II collagen. It was concluded that the CD200R1/CD200 pathway is up-regulated in arthritis and plays a significant physiological role in regulating the severity of disease. In contrast, CD200R1 plays a minimal role in shaping the immune response to collagen in this model. PMID- 20735440 TI - Significant anti-tumour activity of adoptively transferred T cells elicited by intratumoral dendritic cell vaccine injection through enhancing the ratio of CD8(+) T cell/regulatory T cells in tumour. AB - We have shown that immunization with dendritic cells (DCs) pulsed with hepatitis B virus core antigen virus-like particles (HBc-VLP) packaging with cytosine guanine dinucleotide (CpG) (HBc-VLP/CpG) alone were able to delay melanoma growth but not able to eradicate the established tumour in mice. We tested whether, by modulating the vaccination approaches and injection times, the anti-tumour activity could be enhanced. We used a B16-HBc melanoma murine model not only to compare the efficacy of DC vaccine immunized via footpads, intravenously or via intratumoral injections in treating melanoma and priming tumour-specific immune responses, but also to observe how DC vaccination could improve the efficacy of adoptively transferred T cells to induce an enhanced anti-tumour immune response. Our results indicate that, although all vaccination approaches were able to protect mice from developing melanoma, only three intratumoral injections of DCs could induce a significant anti-tumour response. Furthermore, the combination of intratumoral DC vaccination and adoptive T cell transfer led to a more robust anti-tumour response than the use of each treatment individually by increasing CD8(+) T cells or the ratio of CD8(+) T cell/regulatory T cells in the tumour site. Moreover, the combination vaccination induced tumour-specific immune responses that led to tumour regression and protected surviving mice from tumour rechallenge, which is attributed to an increase in CD127-expressing and interferon-gamma-producing CD8(+) T cells. Taken together, these results indicate that repeated intratumoral DC vaccination not only induces expansion of antigen specific T cells against tumour-associated antigens in tumour sites, but also leads to elimination of pre-established tumours, supporting this combined approach as a potent strategy for DC-based cancer immunotherapy. PMID- 20735442 TI - Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. AB - BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio-facio cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild-type BRAF but is less strongly activating than the cancer associated p.V600E mutation. PMID- 20735441 TI - Transient immunosuppression: a bridge between infection and the atypical autoimmunity of Guillain-Barre syndrome? AB - Guillain-Barre syndrome (GBS) is an acute, usually monophasic, disorder of the peripheral nervous system that is assumed to be of immune-mediated pathogenesis. However, several clinical features and experimental findings of GBS are uncharacteristic for an immune-mediated disorder and set this condition apart from other disorders with a putative immune-mediated pathogenesis. These features include, among others, the monophasic nature of GBS, the lack of response to immunosuppressive (unlike immunomodulatory) therapy, the absence of a typical association with immunogenetic background and the inability to establish a valid and relevant animal model. We suggest a comprehensive hypothesis for the pathogenesis of GBS that is based on the assumption that the condition is due to a transient (or occasionally chronic) immune deficiency, as in most cases GBS follows an infection with pathogens known to induce immunosuppression. Such infections may be followed by breakdown of immune tolerance and induction of an immune attack on peripheral nerves. Mounting of the immune-mediated assault might be triggered either by the same infective pathogen or by secondary infection. Clearance of the infection and resumption of a normal immune response and tolerance eventually terminate the immune-mediated damage to the peripheral nerves and enable recovery. This hypothesis assumes that the entire sequence of events that culminates in GBS is due to transient exogenous factors and excludes a significant role for inherent host susceptibility, which explains the monophasic nature of the disorder. PMID- 20735443 TI - Validity in measuring breathing movements with the Respiratory Movement Measuring Instrument, RMMI. AB - BACKGROUND: The respiratory movement measuring instrument (RMMI) is a method for examining the differences in anteroposterior diameter of the body during breathing. OBJECTIVES: The aim of this study was to investigate the known group validity of the RMMI by comparing different body positions and breathing behaviours in healthy persons. METHOD: The respiratory motion of the rib cage and the abdomen was measured by the RMMI in 40 healthy subjects. The measurements were undertaken in the supine and sitting positions and during normal, abdominal and thoracic breathing. RESULTS: The proportion of rib cage motion was 36% in the supine and 52% in the sitting position (P<0.001). The proportion of rib cage motion in the supine position was 21% during abdominal breathing and 57% during thoracic breathing, both significantly different (P<0.001) in comparison to normal breathing. CONCLUSION: The RMMI showed a high degree of validity concerning distribution of motion between the rib cage and abdomen. PMID- 20735444 TI - Information-seeking and decision-making preferences among adult orthodontic patients: an elective health care model. AB - OBJECTIVES: When it comes to their own health care, adult patients traditionally demonstrate strong information-seeking desire but a somewhat lower desire to make their own treatment decisions in nonelective situations. Little is known about these desires in patients facing elective health care situations. We used the well-tested Autonomy Preferences Index (API) as a base to construct and test our elective Autonomy Preferences Index (eAPI) for both information-seeking and decision-making and analyzed demographic variables on both. METHODS: The eAPI was constructed to mirror the API but uses elective scenarios rather than the API's nonelective scenarios. It was validated using cognitive interviews to determine item intent and comprehension and by Cronbach's alpha. Both the API and eAPI were distributed to 188 active-treatment patients at the Division of Orthodontics, University of Minnesota. API and eAPI items were scored using a 1 (low) to 5 (high) Likert scale of desire. RESULTS: Mean information-seeking desire was universally high (>4, P < 0.001) for both API and eAPI instruments. Mean decision making (DM) desire was universally low to moderate: API-DM = 2.84 and eAPI-DM = 2.6. Decision-making preferences for nonelective items (API-DM) decreased as the condition severity presented in the vignettes increased: mild = 2.88, moderate = 2.67 and severe = 2.21. Conversely, elective decision-making preferences (eAPI DM) increased with increasing condition severity: mild = 2.51, moderate = 2.79 and severe = 3.18 (P < 0.001). CONCLUSIONS: Adult patients have universally high information-seeking preferences and moderate to low decision-making preferences regardless of the elective or nonelective nature of their condition. However, as vignette condition severity increases, patients facing nonelective scenarios display progressively less desire for decision-making, whereas patients facing elective scenarios show progressively more decision-making desire. PMID- 20735445 TI - Stressful negative life events and amalgam-related complaints. AB - OBJECTIVES: The role of stressful life events in the onset of self-reported amalgam-related complaints is unclear. The aim of this study was to examine the relationship between life events and amalgam-related complaints. METHOD: The participants were selected from a longitudinal population-based study. One-to-one matching of 337 participants with amalgam-related complaints to 337 participants without such complaints was performed. For 81 of the participants with amalgam related complaints and their matched controls, data was also available approximately 5 years before the onset of complaints, making longitudinal analysis possible. All participants completed questionnaires assessing the occurrence of 55 life events. RESULTS: The results showed that many participants with amalgam-related complaints experienced negative life events before and at the onset of amalgam-related complaints. They also reported more unexpected and uncontrollable events difficult to adjust to in comparison with controls. The groups did not differ on positive or neutral life events. Somatic illness or surgical operation was the most common life event. Death of a very close family member and a major change in financial situation were also commonly reported. CONCLUSIONS: This study indicates that adverse negative life events could play a vital role in understanding and explaining amalgam-related complaints. PMID- 20735446 TI - A prediction model for root caries in an elderly population. AB - OBJECTIVES: To identify factors associated with root caries development in a 12- month period, in an elderly Mexican population, so as to develop a prediction model for the occurrence of root caries. METHODS: A case-cohort study was carried out with 698 randomly selected beneficiaries of the Mexican Institute of Social Security (IMSS), residing in the southeast of Mexico City. Initially, base line (t0) data regarding sociodemographic variables, general health, general and oral healthy habits, salivary conditions, cariogenic microorganisms and oral health clinical indicators were collected. Twelve months from the date of the first clinical evaluation (t1), a new examination was carried out to determine the root caries increment. Variables that showed a significant association (P <= 0.05) with the root caries increment were included in the prediction model. RESULTS: Six hundred and ninety-eight elderly subjects were included in the cohort (t0), with 76.1% (n = 531) of the elderly patients followed up at 12 months (t1). Incidence of root caries was 21.7% (n = 115), a mean root caries increase of 0.4 (1.0) surfaces. The variables, DLBA limitations (Yes), smoking (Yes), mouthwash (No), Mutans streptococci (>=105 CFU/ml), healthy root surfaces (>=6) and Root Caries Index (>=8%), showed a statistically significant association (P < 0.05). This model showed a correct classification in 80.0% (n = 425) and an area under the Receiver Operating Characteristic curve of 0.75. CONCLUSIONS: This is a good prediction model for the 12 months root caries increment in this population of elderly Mexicans. PMID- 20735447 TI - Burnout and engagement in relation with job demands and resources among dental staff in Northern Ireland. AB - OBJECTIVES: To investigate the psychological health--in particular, levels of burnout and engagement, job demands, job resources, and general psychological distress--among dental staff in Northern Ireland. METHODS: Three hundred questionnaires were administered to all dental offices in the western part of Northern Ireland. The questionnaire consisted of 'Maslach Burnout Inventory (MBI)', 'Job Demands in Dentistry measure', 'Utrecht Work Engagement Scale (UWES)', 'Job Resources in dentistry measure', and 'General Health Questionnaire (GHQ)'. RESULTS: Overall response rate among all staff members was 45% (for general dental practitioners: 65%). Burnout mean scores were unfavourable when compared with MBI manual norm scores, 26% had scores in the 'high' categories of both emotional exhaustion (EE) and depersonalization (DP). This is an indication of severe burnout risk. Time pressure, financial worries, and difficult patients appeared to be the most prominent work demands (mean scores >3). All job demands' scales correlated significantly (P < 0.01) and positively with both EE and DP: 0.30 > r < 0.62. Mean scores for UWES, and all job resources' subscales were all well above each subscale's range midpoint. Treatment results appeared the most prominent work resource. GHQ mean score for all was 1.05 (SD = 0.51). No difference in mean score was found between dentists and other staff (F(1,123) = 1.08, NS). With 'case level' set at a score >3 as a cut-off point, 25% of the subjects have to be considered cases. CONCLUSION: Burnout is a serious threat for the dental team in this region of Northern Ireland, especially among general dental practitioners. One-quarter of the dentists were categorized as having a serious burnout risk. Dentists appeared to have most trouble with the work environment aspects: time pressure and financial worries. Furthermore, the proportion of those suffering from psychological distress was unusually high. In contrast to these findings, encouraging levels of engagement were identified. It is recommended that attention for burnout risk is given priority by dental associations. PMID- 20735448 TI - Parameters associated with active caries lesions assessed by two different visual scoring systems on occlusal surfaces of primary molars - a multilevel approach. AB - OBJECTIVE: The aim of this in vivo study was to evaluate the association between several parameters related to children and to their teeth, and the presence of active carious lesions assessed by two different visual indices on occlusal surfaces of primary molars. METHODS: Occlusal surfaces of 757 primary molars in 139 children (3-12 years old) were classified as sound, or having inactive or active carious lesions using the Nyvad criteria (NY) and the International Caries Detection and Assessment System (ICDAS-II) and a supplemental lesion activity assessment system (ICDAS-LAA). Several parameters related to the tooth and to the child were recorded. Associations between these parameters and the presence of active carious lesions on occlusal surfaces were evaluated using logistic multilevel analysis. RESULTS: Second primary molar teeth and children with high caries experience were more frequently with active occlusal carious lesions compared to sound and inactive occlusal carious lesions classified by both visual scoring systems. Teeth with a mature dental plaque on the occlusal surface and younger children had more active caries than inactive occlusal carious lesions (excluding sound teeth in the analysis). A previous visit to a dentist was related to a lower frequency of active occlusal carious lesions classified by NY only, and upper primary molars presented with higher numbers of active occlusal carious lesions classified by ICDAS-LAA. CONCLUSIONS: Presence of mature dental plaque and tooth type are tooth-related variables associated with active carious lesions on occlusal surfaces of primary teeth, as well as anterior caries experience and age are variables related to the child. PMID- 20735449 TI - Public awareness of oral cancer, of oral potentially malignant disorders and of their risk factors in some rural populations in Sri Lanka. AB - OBJECTIVE: The aim of this study was to investigate the level of public awareness of oral cancer, of oral potentially malignant disorders (OPMD) and of risk factors for developing these diseases in a province of Sri Lanka, a country with one of the highest incidences of these diseases in the world. METHODS: A cross sectional community-based survey was carried out in Sabaragamuwa province by interviewing 1029 subjects above 30 years of age, over a 1-year period from November 2006. RESULTS: The level of public awareness of oral cancer was 84%, but only 23% for OPMD. Awareness was especially poor in low socioeconomic groups. The majority of subjects were not aware of the symptoms of oral cancer and of OPMD. Thirty-two percent were unaware that chewing betel quid was a risk factor for these diseases, as were 65% for tobacco smoking and 81% for heavy consumption of alcohol. Overall, 76% were not aware of any of the dangers inherent in the frequent use of areca nut. The majority of smokers, betel quid chewers and alcohol consumers were not aware that their lifestyles were placing their long term health at serious risk. CONCLUSIONS: Knowledge of oral cancer, OPMD and their associated risk factors was poor among this population, indicating an urgent need to implement public health education and promotion strategies. PMID- 20735450 TI - Amphibian encounter rates on roads with different amounts of traffic and urbanization. AB - Although amphibians have relatively high rates of road mortality in urban areas, the conditions under which traffic threatens the survival of local amphibian populations remain unclear. In the Sandhills region of North Carolina (U.S.A.), we counted living and dead amphibians along two transects (total length 165 km) established on roads in areas with varying degrees of urbanization. We found 2665 individuals of 15 species, and amphibian encounter rates declined sharply as traffic and urban development increased. Regression-tree models indicated that 35 amphibians/100 km occurred on roads with <535 vehicles/day, whereas the encounter rate decreased to only 2 amphibians/100 km on roads with >2048 vehicles/day. Although mortality rate peaked at higher traffic levels (47% dead on roads with >5200 vehicles/day), the number of dead amphibians was highest at low levels of traffic. This suggests that areas where amphibian mortality is concentrated may actually contain the largest populations remaining on a given road transect. PMID- 20735451 TI - A regional perspective on the diversity and conservation of tropical Andean fishes. AB - The tropical Andes harbor an extraordinarily varied concentration of species in a landscape under increasing pressure from human activities. Conservation of the region's native plants and animals has received considerable international attention, but the focus has been on terrestrial biota. The conservation of freshwater fauna, particularly the conservation of fishes, has not been emphasized. Tropical Andean fishes are among the most understudied vertebrates in the world. We estimate that between 400 and 600 fish species inhabit the diverse aquatic environments in the region. Nearly 40% of these species are endemic. Tropical Andean fishes are vulnerable to ongoing environmental changes related to deforestation, water withdrawals, water pollution, species introductions, and hydropower development. Additionally, their distributions and population dynamics may be affected by hydrologic alterations and warmer water temperatures associated with projected climate change. Presently, at least three species are considered extinct, some populations are endangered, and some species are likely to decline or disappear. The long-term persistence of tropical Andean fishes will depend on greater consideration of freshwater systems in regional conservation initiatives. PMID- 20735452 TI - Using citizen science programs to identify host resistance in pest-invaded forests. AB - Threats to native forests from non-native insects and pathogens (pests) are generally addressed with methods such as quarantine, eradication, biological control, and development of resistant stock through hybridization and breeding. In conjunction with such efforts, it may be useful to have citizen scientists locate rare surviving trees that may be naturally pest resistant or tolerant. The degree of resistance of individual trees identified in this way can be tested under controlled conditions, and the most resistant individuals can be integrated into plant breeding programs aimed at developing pest-resistant native stock. Involving citizen scientists in programs aimed at identifying rare trees that survive colonization by pests provides a low-cost means of maximizing search efforts across wide geographic regions and may provide an effective supplement to existing management approaches. PMID- 20735453 TI - Effects of postfire salvage logging on deadwood-associated beetles. AB - In Canada and the United States pressure to recoup financial costs of wildfire by harvesting burned timber is increasing, despite insufficient understanding of the ecological consequences of postfire salvage logging. We compared the species richness and composition of deadwood-associated beetle assemblages among undisturbed, recently burned, logged, and salvage-logged, boreal, mixed-wood stands. Species richness was lowest in salvage-logged stands, largely due to a negative effect of harvesting on the occurrence of wood- and bark-boring species. In comparison with undisturbed stands, the combination of wildfire and logging in salvage-logged stands had a greater effect on species composition than either disturbance alone. Strong differences in species composition among stand treatments were linked to differences in quantity and quality (e.g., decay stage) of coarse woody debris. We found that the effects of wildfire and logging on deadwood-associated beetles were synergistic, such that the effects of postfire salvage logging could not be predicted reliably on the basis of data on either disturbance alone. Thus, increases in salvage logging of burned forests may have serious negative consequences for deadwood-associated beetles and their ecological functions in early postfire successional forests. PMID- 20735454 TI - Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas. AB - OBJECTIVE: Diagnosis of low grade non-Hodgkin B-cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service. METHODS: Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow-up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains. RESULTS: Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B-cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series. CONCLUSIONS: FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B-cell non-Hodgkin lymphomas. PMID- 20735455 TI - The normalisation of terror: the response of Israel's stock market to long periods of terrorism. AB - Man-made disasters such as acts of terrorism may affect a society's resiliency and sensitivity to prolonged physical and psychological stress. The Israeli Tel Aviv stock market TA-100 Index was used as an indicator of reactivity to suicide terror bombings. After accounting for factors such as world market changes and attack severity and intensity, the analysis reveals that although Israel's financial base remained sensitive to each act of terror across the entire period of the Second Intifada (2000-06), sustained psychological resilience was indicated with no apparent overall market shift. In other words, we saw a 'normalisation of terror' following an extended period of continued suicide bombings. The results suggest that investors responded to less transitory global market forces, indicating sustained resilience and long-term market confidence. Future studies directly measuring investor expectations and reactions to man-made disasters, such as terrorism, are warranted. PMID- 20735456 TI - Half full or half empty? Shelter after the Jogjakarta earthquake. AB - The international shelter response to the Jogjakarta earthquake in Indonesia in May 2006 is widely regarded as a success story, especially when compared with the response to the Indian Ocean tsunami 16 months earlier. This evaluation is largely in terms of the international aid system itself, which emphasises statistical measures of 'success' and internal coordination and efficiency. From the perspective of those closer to the ground, however, it was less successful, especially in terms of coordination and communication with and participation of local agencies and affected communities. This paper, by an aid worker resident in Jogjakarta and an anthropologist, examines the response from a perspective grounded both within and outside the aid system, local as well as global. It recognises the relative success of the response, but argues for an approach more grounded in local knowledge and responsive to local concerns, while also providing practical suggestions for improvement. PMID- 20735457 TI - Continuity, social change and Katrina. AB - For some time, disaster researchers have looked for social change and mostly found continuity. This paper argues that shifting the focus from investigating social change to documenting continuity may enhance the understanding and planning of post-disaster situations especially in industrialised societies like the United States. Drawing from qualitative data from post-Katrina New Orleans, it proposes using the concept of continuity as an analytical device both to identify the axes of continuity and evaluate the likelihood and possible dimensions of social change. The analysis of long-term recovery plans, along with field observations and interviews with evacuees, suggest that despite the well documented emergence of conflict in post-Katrina New Orleans, the likelihood of social change appears limited. PMID- 20735458 TI - Crime in post-Katrina Houston: the effects of moral panic on emergency planning. AB - This study used a mixed methods approach to estimate whether a moral panic occurred after Hurricane Katrina forced the evacuations of more than 250,000 people to Houston, Texas. The study viewed data from the Houston Police Department combined with a qualitative review of references of criminal activity in local print media. In total, over 8,500 lines of text were analysed to discern themes associated with media representations of the influence of evacuees on the city of Houston. There was little evidence of statistically significant increases in crime over the months following the evacuations. There was, however, evidence that evacuees, principally from New Orleans, were blamed for perceived increases in violent crime and lawlessness. There are also significant policy implications for state, local and federal governments. In particular, the policies of the Federal Emergency Management Agency were blamed for at least some of the perceived crime attributed to Katrina evacuees. PMID- 20735459 TI - Networking emergency teams in Jerusalem. AB - With the recent upsurge in terrorism, more and more attention is being directed at examining the effectiveness and efficiency of emergency teams. These teams tend to focus on their areas of expertise without necessarily communicating, cooperating or coordinating their operations. Research suggests that improved interpersonal communication and coordination enhances the overall work of each emergency team, and that their combined effort is far in excess of the sum of their individual endeavours. This paper outlines attempts made in Jerusalem to improve the performance of emergency teams and to help the helpers by holding training workshops, setting up a forum of co-workers and encouraging dialogue among various emergency teams in the city. A planned intervention programme was designed to enable informal networking between team leaders. The programme had an impact on team workers and resulted in a more coordinated and effective service delivery during emergencies. PMID- 20735460 TI - Land tenure, disasters and vulnerability. AB - Although often overlooked, land tenure is an important variable impacting on vulnerability to disaster. Vulnerability can occur either where land tenure is perceived to be insecure, or where insecure tenure results in the loss of land, especially when alternative livelihood and housing options are limited. Disasters often provide the catalyst for such loss. This paper avoids making generalisations about the security of particular types of tenure, but instead explores factors that mediate tenure security, particularly in the wake of a disaster. The paper identifies five mediating factors: (1) the local legal system; (2) government administrative authority; (3) the economy; (4) evidence of tenure, and; (5) custom and dominant social attitudes. It is shown that some mediating factors are more salient for particular types of tenure than others. The paper will highlight the importance of land tenure in any assessment of vulnerability, and conclude with suggestions for further research. PMID- 20735461 TI - 'You fix my community, you have fixed my life': the disruption and rebuilding of ontological security in New Orleans. AB - Using the concept of ontological security, this paper examines the physical and psychological loss of home and community following Hurricane Katrina. This qualitative longitudinal study includes 40 heads of households with school-age children who lived in New Orleans during Hurricane Katrina. Participants describe a breakdown in their social fabric at the individual and structural/community levels that contributes to a sense of community loss and social displacement, disrupting their ontological security--their notion of safety, routine and trust in a stable environment. Three interrelated reactions were common: 1) experiencing nostalgia for their old neighbourhoods specifically and New Orleans in general; 2) experiencing a sense of loss of people and things that represented a level of security or constancy; 3) initiation of a process for re-establishing ontological security whether or not they returned to New Orleans. The paper concludes that intangible losses have an important psychological effect on community redevelopment and recovery from trauma. PMID- 20735462 TI - How prepared is prepared enough? AB - Decisions about disaster preparedness are rarely informed by cost-benefit analyses. This paper presents an economic model to address the thorny question, 'how prepared is prepared enough?' Difficulties related to the use of cost benefit analysis in the field of disaster management concern the tension between the large number of high-probability events that can be handled by a single emergency response unit and the small number of low-probability events that must be handled by a large number of them. A further special feature of disaster management concerns the opportunity for cooperation between different emergency response units. To account for these issues, we introduce a portfolio approach. Our analysis shows that it would be useful to define disaster preparedness not in terms of capacities, but in terms of the frequency with which response capacity is expected to fall short. PMID- 20735463 TI - Signatures of range expansion and erosion in eastern North American trees. AB - Abundance and occupancy of populations at high- and low-latitude geographic range edges will be critically important in determining a species' response to climate change. Low abundance and occupancy at expanding (high latitude) edges of the range may limit a species capacity to migrate, and at trailing (low latitude) edges, may result in range erosion and regional extinction. We examined abundance occupancy distributions across the geographic ranges of 102 eastern North American trees and looked for signatures reflecting capacity to respond to climate change. We found that 62% of species display a signature consistent with higher climatic suitability in the northern latitudes of their range. However, our results suggest that the most common response is likely to involve range erosion in the south and limited range expansion in the north, possibly leading to an overall reduction in range size for many species. In particular, species with smaller ranges centred at lower latitudes may not have the capacity to successfully track the current rate of climate change. PMID- 20735464 TI - Positive diversity-stability relationships in forest herb populations during four decades of community assembly. AB - It is suggested that diversity destabilizes individual populations within communities; however, generalizations are problematic because effects of diversity can be confounded by variation attributable to community type, life history or successional stage. We examined these complexities using a 40-year record of reassembly in forest herb communities in two clearcut watersheds in the Andrews Long-term Ecological Research Site (Oregon, USA). Population stability was higher among forest than colonizing species and increased with successional stage. Thus, life history and successional stage may explain some of the variability in diversity-stability relationships found previously. However, population stability was positively related to diversity and this relationship held for different forest communities, for species with contrasting life histories, and for different successional stages. Positive relationships between diversity and population stability can arise if diversity has facilitative effects, or if stability is a precursor, rather than a response, to diversity. PMID- 20735465 TI - Metacommunity phylogenetics: separating the roles of environmental filters and historical biogeography. AB - Biogeographical, evolutionary and ecological processes interact to regulate patterns in metacommunities. However, as there are few quantitative methods for evaluating their joint effects, resolving this interaction is difficult. We develop a method that aims to evaluate the interaction between phylogenetic structure, historical biogeographic events and environmental filtering in driving species distributions in a large-scale metacommunity. Using freshwater zooplankton as a case study, we contrast the phylogenetic metacommunity structure of calanoid copepods and an ecologically similar but more vagile group, daphniids, in the northeastern US. We find that legacies of historical biogeographical events have strongly constrained calanoid distributions within this area, but that adaptation to different water chemistry and lake morphology drives the metacommunity structure of daphniids. Our findings show that biogeographic history and metacommunity processes jointly regulate community structure in these lakes and suggest that this also depends on factors that affect the colonization rate of different types of organisms. PMID- 20735466 TI - Living with secondary breast cancer: coping with an uncertain future with unmet needs. PMID- 20735467 TI - Uncertainty, lack of control and emotional functioning in women with metastatic breast cancer: a review and secondary analysis of the literature using the critical appraisal technique. AB - A diagnosis of metastatic (or secondary) breast cancer is frequently more distressing than the diagnosis of a primary tumour since it indicates that the cancer is no longer curable. Relatively little is known, however, about women's experiences of this condition in comparison with those diagnosed with primary breast cancer. This paper therefore reports findings from a secondary analysis of the published literature on the topic using tools from the critical appraisal skills programme to identify and analyse appropriate papers, and the constant comparative method as a means of identifying any overarching or dominant themes emerging from the literature. Uncertainty, lack of control and poor emotional functioning emerged as the main themes affecting women with metastatic breast cancer. These are discussed in relation to their antecedents in the original studies and their implications for nursing care. The themes demonstrate that living with metastatic (or secondary) breast cancer is a multifaceted experience that is influenced by a large number of factors, many of which are under researched in comparison with those affecting women diagnosed with primary disease. It is clear, however, that women affected by the condition need a great deal more support than they currently receive, and new services may be required to meet these needs. PMID- 20735468 TI - A survey of provision of breast care nursing for patients with metastatic breast cancer--implications for the role. AB - The role of the breast care nurse was developed in the UK and is now being adopted internationally. Although evidence is available to suggest that the role is beneficial in the care of women with primary breast cancer, it is emerging that women with metastatic breast cancer do not receive the same level of support. This study aimed to develop an understanding of the role of the breast care nurse in the provision of care for patients with metastatic breast cancer. A cross-sectional survey of 276 breast care nurses in the UK found that 91% of breast care nurses stated that they provided care for patients with metastatic disease and 81% provided ongoing information and support. However 57% of breast care nurses acknowledged that the provision of care for this population was inadequate and many reported feeling ill equipped to care for women with progressive disease. Care pathways for this patient group are unstructured and ill defined complicating the efforts of breast care nurses to identify and provide care for them. In conclusion, the current nursing service for women with metastatic breast cancer is inadequate but many breast care nurses are working to address this. PMID- 20735469 TI - Balance is the challenge--the impact of mitochondrial dynamics in Parkinson's disease. AB - Impaired mitochondrial function has been implicated in neurodegeneration in Parkinson's disease (PD) based on biochemical and pathoanatomical studies in brains of PD patients. This observation was further substantiated by the identification of exogenic toxins, i.e. complex I inhibitors that directly affect mitochondrial energy metabolism and cause Parkinsonism in humans and various animal models. Recently, insights into the underlying molecular signalling pathways leading to alterations in mitochondrial homeostasis were gained based on the functional characterization of mitoprotective genes identified in rare forms of inherited PD. Using in vitro and in vivo loss of function models of the Parkin, PINK1, DJ-1 and Omi/HtrA2 gene, the emerging field of mitochondrial dynamics in PD was established as being critical for the maintenance of mitochondrial function in neurons. This underscored the concept that mitochondria are highly dynamic organelles, which are tightly regulated to continuously adapt shape to functional and anatomical requirements during axonal transport, synaptic signalling, organelle degradation and cellular energy supply. The dissection of pathways involved in mitochondrial quality control clearly established the PINK1/Parkin-pathway in the clearance of dysfunctional mitochondria by autophagy and hints to a complex interplay between PD-associated proteins acting at the mitochondrial interface. The elucidation of this mitoprotective signalling network may help to define novel therapeutic targets for PD via molecular modelling of mitochondria and/or pharmacological modulation of mitochondrial dynamics. PMID- 20735470 TI - IL-18 gene polymorphism, cardiovascular mortality and coronary artery disease. AB - BACKGROUND: Interleukin 18(IL-18) is a pro-atherosclerotic cytokine. Elevated IL 18 levels and the genetic variation of the IL-18 have been previously linked with acute coronary events and cardiovascular mortality among patients with coronary artery disease (CAD). We studied the possible association between the IL-18 gene polymorphism and cardiovascular mortality during follow-up among Finnish patients who had undergone a clinical exercise stress test, in addition to the possible effect on the expression of angiography-verified CAD. MATERIALS AND METHODS: A total of 2152 patients of the Finnish Cardiovascular Study (cohort study) were followed up for 6.3years and cardiovascular mortality was recorded. Angiography was performed on 461 patients. Genotyping of five common single nucleotide polymorphisms (SNPs) of the IL-18 gene was performed using the 5'nuclease assay for allelic discrimination with the ABI Prism 7900HT Sequence Detection System. RESULTS: Among the study population, IL-18 gene polymorphism did not associate with cardiovascular mortality. According to adjusted binary regression analysis, the male carriers of one major haplotype (the only ones carrying the t allele of the +127 C/t SNP) had a lower occurrence rate for significant CAD defined as > 50% stenosis in at least one of the main branches of the coronary arteries (OR 0.495, 95% CI 0.862-0.284, P=0.041). No associations were observed among women. The sex-by-genotype interaction was significant (P=0.033). CONCLUSIONS: The IL-18 gene was not found to associate significantly with mortality. Among patients who had coronary angiography, one major haplotype of the IL-18 gene has a gender dependent different impact on the expression of CAD. PMID- 20735471 TI - Use of cardio-ankle vascular index in chronic dialysis patients. AB - BACKGROUND: Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality, particularly in patients with chronic kidney disease and end-stage renal disease (ESRD). The objective of this study was to determine the risk factors for de novo arterial stiffness in long-term dialysis patients. MATERIALS AND METHODS: A total of 59 dialysis patients without initial arterial stiffness were studied for 1 year. Cardio-ankle vascular index (CAVI) was measured and a CAVI value >= 9 at the end of 1 year was defined as de novo arterial stiffness. The initial baseline characteristics and laboratory parameters and final laboratory parameters after 1 year were analysed. RESULTS: Dialysis patients with de novo arterial stiffness were significantly older than dialysis patients without de novo arterial stiffness. Initial serum phosphorus and calcium * phosphorus product of dialysis patients with de novo arterial stiffness were significantly greater than those of dialysis patients without de novo arterial stiffness. The haematocrit of dialysis patients with de novo arterial stiffness was significantly lower than that of dialysis patients without de novo arterial stiffness. Multivariate logistic regression analysis showed that age and initial serum phosphorus were independent risk factors for de novo arterial stiffness in dialysis patients. CONCLUSION: After 1-year follow-up, de novo arterial stiffness in dialysis patients as determined by CAVI was significantly associated with age and initial serum phosphorus. PMID- 20735472 TI - Exogenous oxidative stress induces Ca2+ release in the yeast Saccharomyces cerevisiae. AB - The Ca(2+) -dependent response to oxidative stress caused by H(2)O(2) or tert butylhydroperoxide (tBOOH) was investigated in Saccharomyces cerevisiae cells expressing transgenic cytosolic aequorin, a Ca(2+) -dependent photoprotein. Both H(2)O(2) and tBOOH induced an immediate and short-duration cytosolic Ca(2+) increase that depended on the concentration of the stressors. Sublethal doses of H(2)O(2) induced Ca(2+) entry into the cytosol from both extracellular and vacuolar sources, whereas lethal H(2)O(2) shock mobilized predominantly the vacuolar Ca(2+). Sublethal and lethal tBOOH shocks induced mainly the influx of external Ca(2+), accompanied by a more modest vacuolar contribution. Ca(2+) transport across the plasma membrane did not necessarily involve the activity of the Cch1p/Mid1p channel, whereas the release of vacuolar Ca(2+) into the cytosol required the vacuolar channel Yvc1p. In mutants lacking the Ca(2+) transporters, H(2)O(2) or tBOOH sensitivity correlated with cytosolic Ca(2+) overload. Thus, it appears that under H(2)O(2)-induced or tBOOH-induced oxidative stress, Ca(2+) mediates the cytotoxic effect of the stressors and not the adaptation process. PMID- 20735473 TI - NtKTI1, a Kunitz trypsin inhibitor with antifungal activity from Nicotiana tabacum, plays an important role in tobacco's defense response. AB - A cDNA library from tobacco inoculated with Rhizoctonia solani was constructed, and several cDNA fragments were identified by differential hybridization screening. One cDNA clone that was dramatically repressed, NtKTI1, was confirmed as a member of the Kunitz plant proteinase inhibitor family. RT-PCR analysis revealed that NtKTI1 was constitutively expressed throughout the whole plant and preferentially expressed in the roots and stems. Furthermore, RT-PCR analysis showed that NtKTI1 expression was repressed after R. solani inoculation, mechanical wounding and salicylic acid treatment, but was unaffected by methyl jasmonate, abscisic acid and NaCl treatment. In vitro assays showed that NtKTI1 exerted prominent antifungal activity towards R. solani and moderate antifungal activity against Rhizopus nigricans and Phytophthora parasitica var. nicotianae. Bioassays of transgenic tobacco demonstrated that overexpression of NtKTI1 enhanced significantly the resistance of tobacco against R. solani, and the antisense lines exhibited higher susceptibility than control lines towards the phytopathogen. Taken together, these studies suggest that NtKTI1 may be a functional Kunitz trypsin inhibitor with antifungal activity against several important phytopathogens in the tobacco defense response. PMID- 20735474 TI - Hepatocyte nuclear factor-4alpha interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression. AB - Transthyretin is a negative acute phase protein whose serum level decreases during the acute phase response. Transthyretin gene expression in the liver is regulated at the transcriptional level, and is controlled by hepatocyte nuclear factor (HNF)-4alpha and other HNFs. The site-directed mutagenesis of HNF-4, HNF 1, HNF-3 and HNF-6 binding sites in the transthyretin proximal promoter dramatically decreases transthyretin promoter activity. Interestingly, the mutation of the HNF-4 binding site not only abolishes the response to HNF-4alpha, but also reduces significantly the response to other HNFs. However, mutation of the HNF-4 binding site merely affects the specific binding of HNF-4alpha, but not other HNFs, suggesting that an intact HNF-4 binding site not only provides a platform for specific interaction with HNF-4alpha, but also facilitates the interaction of HNF-4alpha with other HNFs. In a cytokine-induced acute phase response cell culture model, we observed a significant reduction in the binding of HNF-4alpha, HNF-1alpha, HNF-3beta and HNF-6alpha to the transthyretin promoter, which correlates with a decrease in transthyretin expression after injury. These findings provide new insights into the mechanism of the negative transcriptional regulation of the transthyretin gene after injury caused by a decrease in the binding of HNFs and a modulation in their coordinated interactions. PMID- 20735475 TI - Pulsed nitrogen supply induces dynamic changes in the amino acid composition and microcystin production of the harmful cyanobacterium Planktothrix agardhii. AB - Planktothrix agardhii is a widespread harmful cyanobacterium of eutrophic waters, and can produce the hepatotoxins [Asp(3)]microcystin-LR and [Asp(3)]microcystin RR. These two microcystin variants differ in their first variable amino acid position, which is occupied by either leucine (L) or arginine (R). Although microcystins are extensively investigated, little is known about the mechanisms that determine the production of different microcystin variants. We hypothesize that enhanced nitrogen availability will increase the intracellular content of the nitrogen-rich amino acid arginine, and thereby promote the production of the variant [Asp(3)]microcystin-RR. To test this hypothesis, we transferred P. agardhii strain 126/3 from nitrogen-replete to nitrogen-deficient conditions, and after 2 weeks of growth under nitrogen deficiency, we added a nitrogen pulse. We found a rapid increase in the cellular nitrogen to carbon ratio and the amino acids aspartic acid and arginine, indicative of cyanophycin synthesis. This was followed by a more gradual increase of the total amino acid content connected to balanced growth. As expected, the [Asp(3)]microcystin-RR variant increased strongly after the nitrogen pulse, while the [Asp(3)]microcystin-LR increased to a much lesser extent. We conclude that sudden nitrogen enrichment affects the amino acid composition of harmful cyanobacteria, which, in turn, affects the production and composition of their microcystins. PMID- 20735476 TI - Advancing the understanding of biogeography-diversity relationships of benthic microorganisms in the North Sea. AB - Knowledge on the spatial distribution of prokaryotic taxa is an essential basis to understand microbial diversity and the factors shaping its patterns. Large scale patterns of faunal distribution are thought to be influenced by physical environmental factors, whereas smaller scale spatial heterogeneity is maintained by species-specific life-history characteristics, the quantity and quality of food sources and local disturbances including both natural and man-induced events. However, it is still not clear which environmental parameters control the diversity and community structure of sedimentary microorganisms mediating important ecosystem processes. In this study, multiscale patterns were elucidated at seven stations in the Oyster Ground, North Sea (54 degrees 4'N/4 degrees E), 100 m to 11 km apart. These were related to biotic (e.g. multicellular organisms) and abiotic parameters (e.g. organic carbon content in the sediment) to establish the relationship between the distribution of both bacterial and archaeal communities and their environment. A relatively high variability was detected at all scales for bacterial and archaeal communities, both of which were controlled by different suites of biotic and abiotic environmental variables. The bacterial community consisted mainly of members belonging to the Gammaproteobacteria and the Fibrobacteres/Acidobacteria group. Members of the Deltaproteobacteria, Bacteroidetes and Actinobacteria also contributed to the bacterial community. Euryarchaeota formed the majority of archaeal phylotypes together with three phylotypes belonging to the Crenarchaeota. PMID- 20735477 TI - Frequent freeze-thaw cycles yield diminished yet resistant and responsive microbial communities in two temperate soils: a laboratory experiment. AB - Few studies have been conducted on adaptations of microbial communities to low and fluctuating temperatures using environmentally relevant conditions. In this study, six Himalayan and two temperate soils were selected as candidates for low temperature/freeze-thaw (FT)-adapted and susceptible soils, respectively. Redundancy analysis with forward selection was used to create a model of environmental parameters explaining variability in the initial microbial abundance and 4 degrees C activities. The best predictor was soil carbon, explaining more than 74% of data variability (P=0.002), despite significant differences in the soil characteristics and environmental history. We tested the hypothesis that the reproduced Himalayan FT fluctuations select physiologically similar communities in distinct soils. Microcosms were experimentally subjected to two separate 50 and 60 FT cycle (FTC) experiments. A significant decrease in abundance, 4 degrees C basal respiration and drastic rearrangements in community level physiological profiles (CLPP) were observed in microcosms with temperate soils until 40 FTC. CLPP remained distinct from those of the Himalayan soils. Minor changes were observed in the Himalayan soils, confirming that microbial populations with physiological traits consistent with the noncontinuous permafrost conditions reside in the Himalayan soils, whereas the surviving temperate soil microorganisms actively adjusted to novel environmental conditions. PMID- 20735478 TI - Stored-product insects carry antibiotic-resistant and potentially virulent enterococci. AB - A total of 154 enterococcal isolates from 95 stored-product insects collected from a feed mill, a grain storage silo, and a retail store were isolated and identified to the species level using PCR. Enterococcus casseliflavus represented 51% of the total isolates, followed by Enterococcus gallinarum (24%), Enterococcus faecium (14%), Enterococcus faecalis (7%), and Enterococcus hirae (5%). Many isolates were resistant to tetracycline (48%), followed by streptomycin (21%), erythromycin (14%), kanamycin (13%), ciprofloxacin (12%), ampicillin (4%), and chloramphenicol (<1%). Enterococci carried genes coding for virulence factors, including the gelatinase gene gelE (26% of isolates), an enterococcal surface protein gene esp (1%), and the cytolysin gene cylA (2%). An aggregation substance (asa1) gene was detected in six out of 10 E. faecalis isolates and five of these were positive for the aggregation substance. Enterococci were positive for hemolytic (57% of isolates) and gelatinolytic (23%) activity. The filter-mating assay showed that the tetracycline resistance gene, tetM, was transferable among E. faecalis by conjugation. These data demonstrated that stored-product insects can serve as potential vectors in disseminating antibiotic-resistant and potentially virulent enterococci. PMID- 20735479 TI - Knocking out salicylate biosynthesis genes in Mycobacterium smegmatis induces hypersensitivity to p-aminosalicylate (PAS). AB - Because of the emergence of strains of Mycobacterium tuberculosis resistant to first-line antituberculosis agents, one of the second-line drugs, p aminosalicylate (PAS), has regained importance in the treatment of tuberculosis. The mode of action of PAS, however, remains controversial as to whether it inhibits mycobactin or folate biosynthesis. To unravel this, we have studied the effect of PAS on wild-type Mycobacterium smegmatis and its mutants (gene knockouts of the salicylate pathway -trpE2, entC and entD). The wild type had no sensitivity to PAS (MIC>400 MUg mL(-1) ), whereas the mutants were hypersensitive, with 1 MUg mL(-1) inhibiting growth. The sulphonamides, trimethoprim and dapsone, had little effect on the growth of either the mutants or the wild type. In addition, PAS at 0.5 MUg mL(-1) increased the accumulation of salicylate with the wild type and mutants. These results support our hypothesis that PAS targets the conversion of salicylate to mycobactin, thus preventing iron acquisition from the host. PMID- 20735480 TI - The tolC locus affects the expression of sbmA through sigmaE activity increase. AB - The SbmA protein is involved in the transport of MccB17-, MccJ25-, bleomycin- and proline-rich peptides into the Escherichia coli cytoplasm. sbmA gene homologues were found in a variety of bacteria. However, the physiological role of this protein still remains unknown. Previously, we found that a combination of sbmA and tolC mutations in Tn10-carrying E. coli K-12 strains results in hypersusceptibility to tetracycline. In this work, we studied sbmA expression in a tolC mutant background and observed an increased expression throughout growth. We ruled out the global transcriptional regulator RpoS and the small RNA micF as intermediates in this regulation. The tolC mutation induced the expression of other well-characterized strong sigma(E) -dependent promoters in E. coli. We observed that the increase in sigma(E) activity led to a greater sbmA expression, conversely eliminating sigma(E) prevented expression of sbmA. We also observed that the sbmA upregulation in a tolC mutant context was abolished in an rpoE-null strain. These results suggest a sigma(E) -dependent positive regulation on sbmA by the tolC mutation. We hypothesize that this mechanism might be part of a compensatory cell envelope stress response. PMID- 20735481 TI - Exopolymeric substances (EPS) from Bacillus subtilis: polymers and genes encoding their synthesis. AB - Bacterial exopolymeric substances (EPS) are molecules released in response to the physiological stress encountered in the natural environment. EPS are structural components of the extracellular matrix in which cells are embedded during biofilm development. The chemical nature and functions of these EPS are dependent on the genetic expression of the cells within each biofilm. Although some bacterial matrices have been characterized, understanding of the function of the EPS is relatively limited, particularly within the Bacillus genus. Similar gaps of knowledge exist with respect to the chemical composition and specific roles of the macromolecules secreted by Bacillus subtilis in its natural environment. In this review, the different EPS from B. subtilis were classified into four main functional categories: structural (neutral polymers), sorptive (charged polymers), surface-active and active polymers. In addition, current information regarding the genetic expression, production and function of the main polymers secreted by B. subtilis strains, particularly those related to biofilm formation and its architecture, has been compiled. Further characterization of these EPS from B. subtilis remains a challenge. PMID- 20735483 TI - Deletion of the elongation factor 4 gene (lepA) in Streptomyces coelicolor enhances the production of the calcium-dependent antibiotic. AB - Elongation factor 4 is a widely distributed translational GTPase also known as LepA. Its physiological role is ambiguous, as only a few phenotypes resulting from lepA null mutations have been reported. Here, we report that a Streptomyces coelicolor lepA null mutant overproduces the calcium-dependent antibiotic (CDA). Our findings are the first that connect LepA (encoded by SCO2562) to antibiotic production. They lend additional evidence that perturbations in the quaternary structure and function of the ribosome can positively affect antibiotic production in Streptomyces bacteria. PMID- 20735484 TI - The unusual extended signal peptide region is not required for secretion and function of an Escherichia coli autotransporter. AB - The plasmid-encoded toxin, Pet, a prototypical member of the serine protease autotransporters of the Enterobacteriaceae, possesses an unusually long signal peptide, which can be divided into five regions termed N1 (charged), H1 (hydrophobic), N2, H2 and C (cleavage site) domains. The N1 and H1 regions correspond to a conserved N-terminal extension previously designated the extended signal peptide region (ESPR), while the N2, H2 and C regions resemble typical Sec dependent signal sequences and exhibit considerable sequence variability. We have shown previously that the ESPR directs Sec-dependent, post-translational translocation of Pet across the bacterial inner membrane. In this study, we demonstrate that the ESPR is not essential for the secretion or the function of Pet. PMID- 20735485 TI - In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore. AB - Neocarzinostatin (NCS) is an enediyne antibiotic produced by Streptomyces carzinostaticus. The NCS chromophore consists of an enediyne core, a sugar moiety, and a naphthoic acid (NA) moiety. The latter plays a key role in binding the NCS chromophore to its apoprotein to protect and stabilize the bioactive NCS chromophore. In this study, we expressed three genes: ncsB (naphthoic acid synthase), ncsB3 (P450 hydroxylase), and ncsB1 (O-methyltransferase), in Streptomyces lividans TK24. The three genes were sufficient to produce 2-hydroxy 7-methoxy-5-methyl-1-naphthoic acid. Production was analyzed and confirmed by LC MS and nuclear magnetic resonance. Here, we report the functional characterization of ncsB3 and thereby elucidate the complete biosynthetic pathway of NA moiety of the NCS chromophore. PMID- 20735486 TI - Lytic failure in cross-inoculation assays between phages and prokaryotes from three aquatic sites of contrasting salinity. AB - Little is known about the ability of phages to successfully colonize contrasting aquatic niches. We conducted experimental cross-infections between viruses and prokaryotes from three tropical sites of West Africa, with distinct salinities: a freshwater reservoir, a marine coastal station and a hypersaline lake. A cellular poison-based method (potassium cyanide) revealed that the addition of native viruses (regardless of the water type) consistently stimulated viral production. Conversely, in all incubations conducted with allochtonous (non-native) viruses, their overall production was not promoted, which suggests a lytic failure. Prokaryotic heterotrophic production increased in fresh and marine water supplemented with native viruses, but not in the hypersaline water. These results point to the role of the viral shunt in low-salinity environments, where the release of bioavailable lysis products might be of high nutritional value for the noninfected prokaryotes. In contrast, in hypersaline water where glycerol is a major carbon and energy source for the heterotrophic community, dissolved organic matter (DOM) of lytic origin may represent a less important DOM source for prokaryotes. Finally, our results suggest that cosmopolitan phages capable of moving between biomes are probably rare in aquatic habitats, supporting the common idea that most wild phages are relatively limited in their host range. PMID- 20735487 TI - Respiration-induced weathering patterns of two endolithically growing lichens. AB - The two endolithic lichen species Hymenelia prevostii and Hymenelia coerulea were investigated with regard to their thallus morphology and their effects on the surrounding substrate. The physiological processes responsible for the observed alterations of the rock were identified. Whereas the thallus surface of H. coerulea was level, H. prevostii formed small depressions that were deepest in the thallus center. In a cross-section, both species revealed an algal zone consisting of algal cavities parallel to the substrate surface and a fungal zone below. However, H. prevostii revealed significantly larger cavities with more than twice the cell number and a denser pattern of cavities than H. coerulea, resulting in a biomass per surface area being more than twice as large. Below H. prevostii the layer of macroscopically visibly altered rock material was about twice as deep and within this layer, the depletion of calcium and manganese was considerably higher. In simultaneous measurements of the oxygen uptake/oxygen release and pH shift, the isolated algal strains of both lichens revealed respiration-induced acidification of the medium in the dark. At higher light intensities, H. coerulea and to a lesser extent also H. prevostii alkalized the medium which may lessen the acidification effect somewhat under natural conditions. In a long-term growth experiment, the isolated algal strains of both lichens revealed acidification of the medium to a similar extent. Neither acidic lichen substances nor oxalic acid was identified. The significant differences between the weathering patterns of both species are based on the same respiration induced acidification mechanism, with H. prevostii having a greater effect due to its higher biomass per area. PMID- 20735488 TI - The influence of implant number and attachment type on maximum bite force of mandibular overdentures: a retrospective study. AB - AIM: Assessment of the influence of such factors as attachment type, number of implants, gender and age of patients on maximum bite force (MBF). MATERIAL AND METHODS: Sixty-two edentulous patients (32 females, 30 males; aged 64.03 +/- 10.07 years, range 42-90 years) with mandibular implant overdentures with various attachment types were included in the study and their MBFs were recorded. The results were evaluated statistically at a significance level of p < 0.05. RESULTS: The MBF in male patients was found to be statistically significantly (p < 0.05) higher than in female patients. No statistically significant differences (p > 0.05) were found with respect to age groups, attachment types and number of implants supporting the mandibular overdentures. CONCLUSION: Within the limitations of this study, it is concluded that independent of the number applied, dental implants increase MBF in edentulous patients. While males show higher bite force, patient age and attachment type seem not to play an important role. PMID- 20735489 TI - Evaluation of the flexural strength and elastic modulus of resins used for temporary restorations reinforced with particulate glass fibre. AB - OBJECTIVE: The flexural strength and the elastic modulus of acrylic resins, Dencor, Duralay and Trim Plus II, were evaluated with and without the addition of silanised glass fibre. MATERIALS AND METHODS: To evaluate the flexural strength and elastic modulus, 60 test specimens were fabricated with the addition of 10% ground silanised glass fibres for the experimental group, and 60 without the incorporation of fibres, for the control group, with 20 test specimens being made of each commercial brand of resin (Dencor, Duralay and Trim Plus II) for the control group and experimental group. After the test specimens had been completed, the flexural strength and elastic modulus tests were performed in a universal testing device, using the three-point bending test. For the specimens without fibres the One-Way Analysis of Variance and the complementary Tukey test were used, and for those with fibres it was not normal, so that the non parametric Mann-Whitney test was applied. RESULTS: For the flexural strength test, there was no statistical difference (p > 0.05) between each commercial brand of resin without fibres [Duralay 84.32(+/-8.54), Trim plus 85.39(+/-6.74), Dencor 96.70(+/-6.52)] and with fibres (Duralay 87.18, Trim plus 88.33, Dencor 98.10). However, for the elastic modulus, there was statistical difference (p > 0.01) between each commercial brand of resin without fibres [Duralay 2380.64 (+/ 168.60), Trim plus 2740.37(+/-311.74), Dencor 2595.42(+/-261.22)] and with fibres (Duralay 3750.42, Trim plus 3188.80, Dencor 3400.75). CONCLUSION: The result showed that the incorporation of fibre did not interfere in the flexural strength values, but it increased the values for the elastic modulus. PMID- 20735490 TI - Validation of the Brazilian versions of two inventories for measuring oral health related quality of life of edentulous subjects. AB - OBJECTIVES: To analyse the validity of the Brazilian versions of OHIP-EDENT and GOHAI as assessment tools of edentulous subjects' OHRQoL. BACKGROUND: Inventories for measuring oral health-related quality of life (OHRQoL) are important in clinical studies regarding oral rehabilitation. However, there is a need for comprehensive validation after translation into different cultural settings. MATERIALS AND METHODS: The sample comprised of 100 complete denture wearers (29 men, 71 women, mean age of 65.2 +/- 9.9 years). The associations between each OHRQoL inventory and other variables served as measurements of construct validity. Data analysis comprised the Spearman correlation test as well as multiple regression using the OHRQoL inventories as dependent variables and the other scales as determinants. RESULTS: Both OHRQoL inventories showed good correlation with denture satisfaction, whereas lower correlation coefficients were found among the inventories and the HAD subscales. Denture satisfaction alone explained 48% and 39% of the variance found for the OHIP-EDENT and GOHAI, respectively, as assessed by multiple regression. A smaller effect was found for OHIP-EDENT. CONCLUSION: Both OHIP-EDENT and GOHAI showed good construct validity for measurement of OHRQoL of edentulous subjects. PMID- 20735491 TI - Retire or not to retire - but will there be a pension? PMID- 20735492 TI - A study on oral rehabilitation in stroke patients: analysis of a group of 33 patients. AB - BACKGROUND: Stroke is the third leading cause of death in the world after cardiovascular disease and cancer. This study aimed to investigate the oro-dental status and removable denture conditions in stroke survivors. METHODS: At the Department of Vascular Disease of the Neurological Clinic of the Polyclinic Hospital of Bari, from January 2003 to May 2008, 189 consecutive patients were examined who had had a stroke, to select removable denture wearers. The oro dental examination was performed in a period between 12 and 60 months after the stroke and among these 189 patients, 60 were wearing a removable denture, but only 33 participated in our research. All the patients gave written informed consent. RESULTS: It was observed that in 42.4%, removable dentures needed to be remade, in 27.3%, they needed to be rebased and in 30.3%, they were adequate. CONCLUSION: The role of oral health providers is fundamental in order to maintain good oral health and to avoid oral diseases in stroke patients. They should, indeed, monitor these patients with a regular follow-up after 1 month and every 3 4 months. PMID- 20735493 TI - Parallel evolution of cytochrome b mediated bifenazate resistance in the citrus red mite Panonychus citri. AB - Bifenazate is a recently developed acaricide that is mainly used to control spider mites on a variety of crops. Although first thought to be a neurotoxin, genetic evidence obtained from bifenazate resistant Tetranychus urticae strains suggested an alternative mode of action as a Qo pocket inhibitor of the mitochondrial complex III. In this study, we reveal how bifenazate resistance in strains of Panonychus citri is maternally inherited and can confer cross resistance to the known Qo inhibitor acequinocyl. The mitochondrial genome of P. citri was sequenced and Qo pocket mutations were shown to be linked with the resistant trait. Parallel evolution of cytochrome b mediated bifenazate resistance corroborates the alternative mode of action and yet again illustrates that care should be taken when employing Qo inhibitors as crop protection compounds. PMID- 20735494 TI - Prevalence of accurate nursing documentation in patient records. AB - AIM: This paper is a report of a study conducted to describe the accuracy of nursing documentation in patient records in hospitals. Background. Accurate nursing documentation enables nurses to systematically review the nursing process and to evaluate the quality of care. Assessing nurses' reports in patient records can be helpful for improving the accuracy of nursing documentation. METHOD: In 2007-2008, we screened patient records (n = 341) from 35 wards in 10 hospitals in the Netherlands. The D-Catch instrument was used to quantify the accuracy of the (1) record structure, (2) admission data, (3) nursing diagnosis, (4) nursing interventions, (5) progress and outcome evaluations and (6) legibility of nursing reports. Items 2-5 were measured as a sum score of quantity criteria (1-4) and quality criteria (1-4), whereas Items 1 and 6 were measured on a 4-point Likert scale that addressed only quality criteria. FINDINGS: The domain 'accuracy of the interventions' had the lowest accuracy scores: 95% of the records revealed a scale score not higher than 5. However, the domain 'admission' had the highest scores: 80% of the records revealed a scale score over 5. CONCLUSION: Effective documentation systems that support nurses in linking diagnoses, interventions and progress and outcome evaluations could be helpful. To improve the accuracy of the documentation, further research is needed on what factors influence nursing documentation. Comparable outcomes from other studies indicate that applying our study findings to international contexts might support the development of universal criteria for accurate nursing documentation. PMID- 20735495 TI - School nurses' involvement, attitudes and training needs for mental health work: a UK-wide cross-sectional study. AB - AIM: The aim of this study was to identify school nurses' views concerning the mental health aspects of their role, training requirements and attitudes towards depression in young people. BACKGROUND: Mental health problems in children and young people have high prevalence worldwide; in the United Kingdom they affect nearly 12% of secondary school pupils. School nurses have a wide-ranging role, and identifying and managing mental health problems is an important part of their work. METHODS: A cross-sectional study was conducted using a postal questionnaire sent to a random sample of 700 school nurses throughout the United Kingdom in 2008. Questions concerned involvement in mental health work and training needs for this work. Attitudes were measured using the Depression Attitude Questionnaire. RESULTS: Questionnaires were returned by 258 (37%) nurses. Nearly half of respondents (46%) had not received any postregistration training in mental health, yet 93% agreed that this was an integral part of their job. Most (55%) noted that involvement with young people's psychological problems occupied more than a quarter of their work time. Staff attitudes were broadly similar to those of other primary care professionals, and indicated a rejection of stigmatizing views of depression and strong acknowledgement of the role of the school nurse in providing support. CONCLUSION: Working with young people who self harm, and recognizing and being better equipped to assist in managing depression and anxiety are key topics for staff development programmes. PMID- 20735496 TI - Illness representations predict health-related quality of life 6 months after hospital discharge in individuals with injury: a predictive survey. AB - AIM: This article is a report of a study investigating health-related quality of life and its predictors 6 months after hospital discharge in individuals who had experienced moderate to severe injury. BACKGROUND: Understanding the relationship between individuals' illness representations and health-related quality of life may provide the foundation for strategies to promote recovery after injury. METHODS: A longitudinal predictive a survey was undertaken. Questionnaires were administered while patients were in hospital, and telephone interviews were conducted 3 and 6 months after hospital discharge. Data were collected from August 2006 to February 2007. Demographic and clinical data were collected and the Chinese Illness Perception Questionnaire Revised (Trauma) and the Medical Outcomes Study Short Form 36, were used. Simultaneous multiple regressions were used to identify predictors of health-related quality of life. RESULTS: A total of 114 participants completed the 6-month survey. Demographic and clinical characteristics did not predict health-related quality of life. Predictors of 6 month Physical Summary Score were 3-month Physical Summary Score and two illness representation scales: Identity and Timeline (acute/chronic). Predictors of 6 month were 3-month Mental Summary Score, and three illness representation scales: Identity, Emotional representations and Timeline (acute/chronic). Independent variables accounted for 75.1% and 72.4% of the variance in Physical and Mental Summary Scores. CONCLUSION: Assessment of patients' illness representations may help clinicians to understand better how people who have sustained traumatic injury view their health and health-related quality of life and to help patients in their recovery process. PMID- 20735497 TI - Predicting incidence and asymptomatic rates for chlamydia in small domains. AB - AIM: This article is a report of a study of the use of predictive analysis using the Bayesian hierarchical model and small area estimation as an innovative methodology to address the challenges nurses face when managing fiscal and clinical resources in outpatient and inpatient settings. BACKGROUND: Nurses responsible for clinic management are confronted with the fiscal challenges in today's healthcare environment. Identifying those at risk for asymptomatic infections such as chlamydia and getting resources to that group has been a constant nursing care challenge for those in outpatient and inpatient clinics. METHODS: A secondary analysis of quantitative survey data was conducted in 2008, using predictive analysis with the Bayesian hierarchical model and small area estimation of statistics. DISCUSSION: The development of an innovative statistical procedure is an interesting and challenging opportunity. The opportunity to apply this innovative technique to an actual data set opens the possibility to replicating the technique and using it in other settings. If implemented and replicated, this innovative analysis can become a tool for managing limited fiscal and clinical resources. RESULTS: White, Hispanic and African American undergraduate students had slightly higher rates than the corresponding graduate students. The incidence rates were higher for White, Hispanic and African American undergraduate students than for graduate students. The incidence rates for African Americans were much higher than for the other identified racial groups, but very similar for graduate students and undergraduate students. CONCLUSION: Predictive analysis using the Bayesian hierarchal model and small area estimation can help nurses to project healthcare costs and services for underserved groups in healthcare clinics, with an improved empirical rationale. PMID- 20735498 TI - Research citation analysis of nursing academics in Canada: identifying success indicators. AB - AIM: This article is a report of a citation analysis of research publications by Canadian nursing academics. BACKGROUND: Citation analysis can yield objective criteria for assessing the value of published research and is becoming increasingly popular as an academic evaluation tool in universities around the world. Citation analysis is useful for examining the research performance of academic researchers and identifying leaders among them. METHODS: The journal publication records of 737 nursing academics at 33 Canadian universities and schools of nursing were subject to citation analysis using the Scopus database. Three primary types of analysis were performed for each individual: number of citations for each journal publication, summative citation count of all published papers and the Scopus h-index. Preliminary citation analysis was conducted from June to July 2009, with the final analysis performed on 2 October 2009 following e-mail verification of publication lists. RESULTS: The top 20 nursing academics for each of five citation categories are presented: the number of career citations for all publications, number of career citations for first-authored publications, most highly cited first-authored publications, the Scopus h-index for all publications and the Scopus h-index for first-authored publications. CONCLUSION: Citation analysis metrics are useful for evaluating the research performance of academic researchers in nursing. Institutions are encouraged to protect the research time of successful and promising nursing academics, and to dedicate funds to enhance the research programmes of underperforming academic nursing groups. PMID- 20735499 TI - Effects of perineal trauma on postpartum sexual function. AB - AIM: This article is a report of a study of the extent of postpartum sexual dysfunction associated with perineal trauma. BACKGROUND: Sexual health problems are common in the postpartum period but despite this it is a topic that lacks professional recognition. After delivery, many women experience reduced sexual desire and reduced vaginal lubrication, as well as weaker and shorter orgasms. METHODS: Women giving birth in the study hospital between 2005 and 2006 and meeting the inclusion criteria were studied, i.e. women at low-risk who expected vaginal delivery at over 38 weeks' gestation with a single foetus in the vertex position. One hundred and sixty-five women were invited for postpartum check-ups 3 months later and 55 attended. A detailed gynaecologic examination was carried out and the perineum was carefully inspected by the same physician. Questionnaires were administered and 20-minute face-to-face interviews were carried out to compare the women's sexual lives before pregnancy and after giving birth. FINDINGS: Compared to women with intact perineum, those who had both episiotomy and second degree perineal tears, had lower levels of libido, orgasm, and sexual satisfaction and more pain during intercourse. The presence of at least one sexual problem (reduced sexual desire, reduced vaginal arousal, reduced vaginal lubrication, reduced frequency of orgasm, dissatisfaction with sexual life and dyspareunia) was statistically significant more common after birth. CONCLUSION: Limiting perineal trauma during delivery is important for the resumption of sexual intercourse after childbirth. Routine episiotomy and fundal pressure should be avoided to prevent perineal trauma. PMID- 20735500 TI - Metacognitive Inventory for nursing students in Taiwan: instrument development and testing. AB - AIM: This paper is a report of the development and testing of an instrument that measures metacognitive abilities of nursing students. BACKGROUND: Metacognition refers to an individual's knowledge, awareness and command of thinking and learning strategies. Nursing students are challenged to think and learn in ways that will prepare them for practical work in a complex healthcare environment. Nursing educators have the responsibility to produce graduates who possess and use metacognitive skills to facilitate the solving of ill-structured problems using a variety of mental processes, such as reasoning, judgment and creativity. METHODS: In 2007, the Metacognitive Inventory for Nursing Students was developed, based on previous instruments, and administered to a sample of 802 senior nursing students in two nursing colleges and a university in Taiwan. Principal axis factor analysis and other statistical tests were performed to test the psychometric properties of the questionnaire. RESULTS: Preliminary analysis reduced the original 40 items to 28. Five factors were retained, accounting for 53.09% of the variance, and these five factors were identified as self monitoring, self-modification, self-awareness, effective learning and problem solving. The resultant Metacognitive Inventory achieved good internal consistency reliability, with a Cronbach's alpha coefficient of 0.94 and the coefficient for the five factors ranged from 0.73 to 0.90. CONCLUSION: Nurse educators in Taiwan could use the Metacognitive Inventory for Nursing Students to assess students and facilitate metacognitive skill development in classrooms and in practice settings. PMID- 20735501 TI - Motivation for entry, occupational commitment and intent to remain: a survey regarding Registered Nurse retention. AB - AIM: This paper is a report of a study of the relationships between Registered Nurses' motivation for entering the profession, occupational commitment and intent to remain with an employer until retirement. BACKGROUND: Identifying and supporting nurses who are strongly committed to their profession may be the single most influential intervention in combating the nursing shortage. An understanding of the characteristics these individuals possess could lead to a decline in the high attrition rates plaguing the profession. METHOD: Using a survey design, Registered Nurses enrolled at the school of nursing and/or employed at the associated university medical centre of a large, not-for-profit state university were polled in 2008. Logistic regression analysis was used to determine how the variables of motivation for entry and occupational commitment could indicate intent to remain. RESULTS: The strongest indicators of intent to remain were normative commitment and age, with a 70% average rate of correctly estimating retention. Exp(B) values for normative commitment (1.09) and age (1.07) indicated that for each one-point increase on the normative commitment scale or one-point increase in age, the odds of remaining with an employer until retirement increased by 1.1%. CONCLUSION: Transformational changes in healthcare environments and nursing schools must be made to encourage loyalty and obligation, the hallmarks of normative commitment. Retention strategies should accommodate mature nurses as well as promote normative commitment in younger nurses. PMID- 20735502 TI - Everyday ethics: ethical issues and stress in nursing practice. AB - AIM: This paper is a report of a study of the type, frequency, and level of stress of ethical issues encountered by nurses in their everyday practice. BACKGROUND: Everyday ethical issues in nursing practice attract little attention but can create stress for nurses. Nurses often feel uncomfortable in addressing the ethical issues they encounter in patient care. METHODS: A self-administered survey was sent in 2004 to 1000 nurses in four states in four different census regions of the United States of America. The adjusted response rate was 52%. Data were analysed using descriptive statistics, cross-tabulations and Pearson correlations. RESULTS: A total of 422 questionnaires were used in the analysis. The five most frequently occurring and most stressful ethical and patient care issues were protecting patients' rights; autonomy and informed consent to treatment; staffing patterns; advanced care planning; and surrogate decision making. Other common occurrences were unethical practices of healthcare professionals; breaches of patient confidentiality or right to privacy; and end of-life decision-making. Younger nurses and those with fewer years of experience encountered ethical issues more frequently and reported higher levels of stress. Nurses from different regions also experienced specific types of ethical problems more commonly. CONCLUSION: Nurses face daily ethical challenges in the provision of quality care. To retain nurses, targeted ethics-related interventions that address caring for an increasingly complex patient population are needed. PMID- 20735503 TI - Professional autonomy and job satisfaction: survey of critical care nurses in mainland Greece. AB - AIM: This paper is a report of a study conducted to describe Greek critical care nurses' views on professional autonomy and its relationship with job satisfaction and other work-related variables. BACKGROUND: Professional autonomy is generally considered a highly desirable nursing attribute and a major factor in nurse job satisfaction. In the critical care environment, a high level of accountability, responsibility and autonomy are required to optimize outcomes of critically unstable patients. METHOD: A questionnaire survey was conducted with a convenience sample of Greek critical care nurses (n = 431; response rate 70%) in 2007. Data were collected on professional autonomy, job satisfaction, role conflict and role ambiguity. RESULTS: Overall, nurses reported acting moderately autonomously. Younger nurses reported statistically significant lower levels of autonomy. Higher levels of autonomy were reported by female nurses. Multiple logistic regression revealed that appointment level, type of critical care unit and registration with a professional organization were independently associated with autonomy. A positive moderate association was found between reported autonomy, job satisfaction, role conflict and role ambiguity, but there was no relationship between job satisfaction and reported role conflict and role ambiguity. CONCLUSION: Further education, role enhancement and support are required for nurses working in critical care in Greece if they are to achieve the maximum potential of their professional role. Failure to address the perceptions of professional autonomy may have an impact on staff retention, because of job dissatisfaction. PMID- 20735504 TI - The science of intervention development for type 1 diabetes in childhood: systematic review. AB - AIM: This paper is a report of a review of the science of intervention development for type 1 diabetes in childhood and its implications for improving health outcomes in children, adolescents, and/or their families. BACKGROUND: Previous reviewers have identified insufficient evidence to support the application of effective interventions for type 1 diabetes in clinical practice. The need for quality randomized controlled trials to address shortcomings in previous study designs has been highlighted as a priority for future intervention research. However, there is also a need to consider the scientific development of interventions, which to date has received little attention. DATA SOURCE: A search for published randomized controlled trials over 5 years (2004-2008) was conducted in electronic databases (Medline, CINAHL, Cochrane Library, Psychinfo, ERIC). Reference lists of papers identified from electronic searches were examined for additional papers. METHODS: A systematic review was conducted. Studies were included if (i) an intervention for managing any aspect of type 1 diabetes was implemented, (ii) children, adolescents and/or their families were sampled, (iii) a randomized controlled trial, (iv) published in English. RESULTS: Fourteen randomized controlled trials were reviewed on education (n = 7), psychosocial (n = 5) and family therapy (n = 2) interventions. Compared to education interventions, family therapy and most psychosocial interventions were developed with greater scientific rigour, and demonstrated promising effects on more health outcomes measured. CONCLUSION: Interventions developed within clearly-defined scientific criteria offer potential for improving health outcomes in children and adolescents with type 1 diabetes and their families. Future reviews on interventions for type 1 diabetes in childhood need to include criteria for assessing the science of intervention development. PMID- 20735505 TI - Beyond incontinence: the stigma of other urinary symptoms. AB - AIM: This paper is a report of a study conducted to characterize the stigma of urinary frequency and urgency and differentiate it from the stigma of incontinence and to describe race/ethnic and gender differences in the experience of stigma among a diverse sample of individuals. BACKGROUND: Lower urinary tract symptoms, including frequency, urgency and incontinence, are susceptible to stigma, but previous stigma research has focused almost exclusively on incontinence. METHOD: The Boston Area Community Health Survey is a population based, random sample epidemiological survey of urologic symptoms (N = 5503). Qualitative data for this study came from in-depth interviews conducted between 2007 and 2008 with a random subsample of 151 black, white and Hispanic men and women with urinary symptoms. FINDINGS: Respondents reported stigma associated with frequency and urgency - not just incontinence. The stigma of frequency/urgency is rooted in social interruption, loss of control of the body, and speculation as to the nature of a non-specific 'problem'. Overall, the stigma of urinary symptoms hinged upon whether or not the problem was 'perceptible'. Men felt stigmatized for making frequent trips to the bathroom and feared being seen as impotent. Women feared having an unclean body or compromised social identity. Hispanic people in particular voiced a desire to keep their urinary symptoms a secret. CONCLUSION: The stigma of urinary symptoms goes beyond incontinence to include behaviours associated with frequency and urgency. Healthcare practitioners should assess for stigma sequelae (e.g. anxiety, depression) in individuals with frequency and urgency, and stress treatment options to circumvent stigmatization. PMID- 20735506 TI - Final-year nursing students' ability to assess, detect and act on clinical cues of deterioration in a simulated environment. AB - AIM: This is a report of a study investigating processes used by final-year nursing students to recognize and act on clinical cues of deterioration in a simulated environment. BACKGROUND: Initial decisions about patients who are deteriorating in medical and surgical wards are often made by newly qualified nurses and doctors, increasing the risk of clinical error. There has been an emphasis on the use of teams in simulation; however, signs of deterioration are missed by individual clinicians. METHODS: During July 2008, final-year undergraduate nursing students in Australia attended a simulation laboratory for 1.5 hours and completed a knowledge questionnaire and two (mannequin-based) scenarios simulating deteriorating patients with hypovolaemic and septic shock. Scenarios were video-recorded and reflective interviews conducted. Additionally, scenarios were stopped around the midpoint to ascertain students' level of Situation Awareness. RESULTS: Fifty-one students participated in the study, providing a total of 102 videoed scenarios and 51 interviews. Thematic analysis of video data and reflective interviews identified considerable differences in processes used by students to identify cues. Four aspects of cue recognition were evident: initial response, differential recognition of cues, accumulation of signs and diversionary activity. CONCLUSION: Nursing skills training should emphasize the importance of trends in identifying and acting on deterioration and the need for systematic assessment in stressful situations. Nursing curricula should focus on enhancing the ability to piece information together, including linking pathophysiology with patient assessment, and identify trends, rather than seeing observations as parallel to each other. PMID- 20735507 TI - Women's experiences of seeking reproductive health care in rural Ghana: challenges for maternal health service utilization. AB - AIM: This paper is a report of part of a larger study exploring rural Ghanaian women's experiences of seeking reproductive health care. The aim of this part of the study was to describe rural women's perspectives on their experiences in seeking reproductive care from professional nurses. BACKGROUND: Nurses' relationships with childbearing women have been linked to women's reproductive healthcare-seeking behaviour and service utilization. However, few researchers have studied women's perspectives on their relationships with nurses when seeking health care. In Ghana, the high rates of maternal mortality raise concerns about a number of factors, including nurses' relational practices. METHODS: Data were collected in 2007 with a convenience sample of 27 Ghanaian women via in-depth interviews, focus groups and participant observation. Women's ages ranged from 15 to 49 years. The translated and transcribed data were thematically analyzed. FINDINGS: Healthcare providers' relational practice influenced women's healthcare seeking behaviours. Major themes from women's stories were: (a) experiences of intimidation and being scolded, (b) experiences of limited choices, (c) receiving silent treatment, and experiences of lack of privacy. Women emphasized the importance of their relationships with nurses and the impact of these relationships on their healthcare-seeking. CONCLUSION: Nursing education in Ghana must place emphasis on basic relational practices. Structural changes to health clinics and routine nursing practices are necessary to create conditions for privacy to address women's health concerns. Women's perspectives must be considered for service improvement. Further research is needed to examine nurses' perspectives on relational care. PMID- 20735508 TI - Quality of life, dyspnea and ventricular function in patients with hypertension. AB - AIM: This paper is a report of an investigation of the relationship between health-related quality of life and left ventricular function among patients with hypertension who did not fulfil the criteria for heart failure. BACKGROUND: Heart failure is a common consequence of hypertension, with Doppler echocardiography being the gold-standard tool to evaluate left ventricular function, mainly hypertension-induced left ventricular damage. Echocardiographic data indicating poorer ventricular function have been related to lower levels of health-related quality of life in patients with systolic and/or diastolic heart failure. However, data are still lacking regarding the correlation between health-related quality of life and left ventricular function and structure in patients with hypertension who do not fulfil the criteria for heart failure. METHOD: Between September 2005 and February 2007, 98 patients with hypertension without systolic or diastolic heart failure were evaluated. Health-related quality of life was assessed using the Medical Outcomes Study Short Form-36. Left ventricular function was evaluated through Tissue Doppler echocardiography. RESULTS: Statistically significant but weak correlations (varying from r = -0.22 to 0.35) were observed between some of the Short Form-36 domains and echo data. To consider the potential effect of dyspnoea in this relationship, patients were split according to the presence or absence of the symptom. In the subgroup without dyspnoea, similar patterns of correlation were observed (varying from r = 0.26 to 0.32). In the subgroup with dyspnoea, however, more and stronger correlations were observed between echo data and health-related quality of life domains, varying from r = -0.40 to 0.50. CONCLUSION: Nurses should be aware of the relevance of evaluating the functional echocardiographic data of patients who not fulfil heart failure criteria, but who experience dyspnoea in order to implement appropriate action plans. PMID- 20735509 TI - Norovirus-binding proteins recovered from activated sludge micro-organisms with an affinity to a noroviral capsid peptide. AB - AIMS: Transmission routes of noroviruses, leading aetiological agents of acute gastroenteritis, are rarely verified when outbreaks occur. Because the destination of norovirus particles being firmly captured by micro-organisms could be totally different from that of those particles moving freely, micro-organisms with natural affinity ligands such as virus-binding proteins would affect the fate of viruses in environment, if such microbial affinity ligands exist. The aim of this study is to identify norovirus-binding proteins (NoVBPs) that are presumably working as natural ligands for norovirus particles in water environments. METHODS AND RESULTS: NoVBPs were recovered from activated sludge micro-organisms by an affinity chromatography technique in which a capsid peptide of norovirus genogroup II (GII) was immobilized. The recovered NoVBPs bind to norovirus-like particles (NoVLPs) of norovirus GII, and this adsorption was stronger than that to NoVLPs of norovirus genogroup I. The profile of two dimensional electrophoresis of NoVBPs showed that the recovered NoVBPs included at least seven spots of protein. The determination of N-terminal amino acid sequences of these NoVBPs revealed that hydrophobic interactions could contribute to the adsorption between NoVBPs and norovirus particles. CONCLUSIONS: NoVBPs conferring a high affinity to norovirus GII were successfully isolated from activated sludge micro-organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: NoVBPs could be natural viral ligands and play an important role in the NoV transmission. PMID- 20735510 TI - Temporal monitoring of the nor-1 (aflD) gene of Aspergillus flavus in relation to aflatoxin B1 production during storage of peanuts under different water activity levels. AB - AIMS: A relative quantification system (RQ-PCR) was used to monitor the correlations between the activity of the nor-1 (=aflD) gene of Aspergillus flavus using real-time PCR in relation to phenotypic aflatoxin B(1) (AFB(1) ) production and populations of A. flavus in stored peanuts at three water activity levels (a(w) , 0.95, 0.90 and 0.85) for 6 weeks. METHODS AND RESULTS: Real-time PCR was used to amplify the nor-1 gene (target gene), and benA56 (beta-tubulin gene) used as a control gene. Expression of three structural genes, nor-1 (=aflD), ver-1 (=aflM), and omtA (=aflP), and the regulatory gene aflR of the aflatoxin biosynthetic pathway were also assayed. There were significant differences between nor-1 gene expression at the three a(w) levels; higher expression at 0.90 a(w) in weeks 1-3, when compared to 0.95. In contrast, in the driest treatment (0.85 a(w) ) none or very low nor-1 expression occurred. The populations of A. flavus colony-forming units (CFUs g(-1) ) increased over time with the highest at 0.95 a(w) . Highest AFB(1) production was at 0.90 and 0.95 a(w) from weeks 3-6. A(w) had a significant effect on aflR transcription at 0.95 a(w) over the 6-week period, while at 0.90 a(w) , only in the last 2 weeks. CONCLUSIONS: Correlations between different factors showed that log AFB(1) * log CFUs, log AFB(1) * a(w) , and log CFUs * a(w) were statistically significant, while log CFUs * RQ-PCR and RQ-PCR * a(w) were not. The AflR gene may not have an important role in the regulation of nor-1 expression in food matrices (e.g. peanuts). SIGNIFICANCE AND IMPACT OF THE STUDY: Determination of correlations between nor-1 expression and aflatoxin production by A. flavus in raw peanuts under different a(w) levels could be helpful to predict potential risk of aflatoxin production during storage of this hygroscopic food product and minimize contamination with the AFB(1) . PMID- 20735511 TI - Borderline personality symptoms differentiate non-suicidal and suicidal self injury in ethnically diverse adolescent outpatients. AB - BACKGROUND: There is little research on how specific borderline personality disorder (BPD) symptoms relate to suicide attempts or suicide and non-suicidal self-injury (NSSI) within adolescent populations, which is important to know given the recent proposal of an NSSI disorder. Even less well known is whether specific BPD symptoms distinguish NSSI from suicide attempts or differentiate single from repeated acts of either suicide or NSSI. METHOD: Archival, de identified outpatient clinical charts from 441 ethnically diverse (4.3% Caucasian; 70.9% female) adolescents (mean age = 14.9, SD = 1.61) were reviewed. Data pertaining to NSSI, suicide attempt history, BPD symptoms, and psychiatric diagnoses were obtained from self-report measures and semi-structured interviews administered at intake. RESULTS: MANOVA and logistic regression analyses revealed significant differences across groups, with the BPD symptoms of 'confusion about self' and 'unstable interpersonal relationships' significantly predicting NSSI and NSSI+Suicide group status. The number of BPD criteria met plus high levels of confusion about self significantly predicted single vs. repeat self-harm group membership. CONCLUSIONS: Two BPD symptoms exhibit distinct relationships to NSSI and suicide attempts, but there is not strong variation in their relationship to BPD. Treatment addressing BPD symptoms may be useful to reducing both NSSI and suicide in ethnically diverse adolescents. PMID- 20735512 TI - Effects of chronic maltreatment and maltreatment timing on children's behavior and cognitive abilities. AB - BACKGROUND: Chronic maltreatment has been associated with the poorest developmental outcomes, but its effects may depend on the age when the maltreatment began, or be confounded by co-occurring psychosocial risk factors. METHOD: We used data from the National Survey of Child and Adolescent Well-Being (NSCAW) to identify four groups of children who varied in the timing, extent, and continuity of their maltreatment from birth to 9 years. Internalizing and externalizing problems, prosocial behavior, and IQ were assessed 21 months, on average, following the most recent maltreatment report. RESULTS: Children maltreated in multiple developmental periods had more externalizing and internalizing problems and lower IQ scores than children maltreated in only one developmental period. Chronically maltreated children had significantly more family risk factors than children maltreated in one developmental period and these accounted for maltreatment chronicity effects on externalizing and internalizing problems, but not IQ. The timing of maltreatment did not have a unique effect on cognitive or behavioral outcomes, although it did moderate the effect of maltreatment chronicity on prosocial behavior. CONCLUSION: There is a need for early intervention to prevent maltreatment from emerging and to provide more mental health and substance use services to caregivers involved with child welfare services. PMID- 20735513 TI - Contextual risk factors as predictors of disruptive behavior disorder trajectories in girls: the moderating effect of callous-unemotional features. AB - BACKGROUND: The presence of callous-unemotional (CU) features may delineate a severe and persistent form of conduct problems in children with unique developmental origins. Contextual risk factors such as poor parenting, delinquent peers, or neighborhood risk are believed to influence the development of conduct problems primarily in children with low levels of CU features. However, longitudinal studies examining the moderating effect of CU features on the relation between contextual risk factors and conduct problems trajectories in girls are rare. METHODS: Growth curve analysis was conducted using five annual measurements of oppositional defiant disorder/conduct disorder (ODD/CD) behaviors in a community sample of 1,233 girls aged 7-8 at study onset. The relation between contextual risk factors in multiple domains (i.e., family, peer, community) and trajectories of ODD/CD behaviors across time were examined for girls with differing levels of CU features. RESULTS: Growth curve analysis indicated that CU features were associated with chronically high levels of ODD/CD symptoms over time. Low levels of parental warmth were also associated with chronically high levels of ODD/CD, and this effect was particularly pronounced for girls with high CU features. Exposure to harsh parenting was associated with higher ODD/CD behaviors for girls in childhood regardless of their level of CU features, but this effect dissipated over time. CONCLUSIONS: Girls with elevated CU features who are exposed to low levels of parental warmth seem to exhibit particularly severe ODD/CD symptoms and should be targeted for intensive intervention in childhood. PMID- 20735514 TI - Early predictors of dyslexia in Chinese children: familial history of dyslexia, language delay, and cognitive profiles. AB - BACKGROUND: This work tested the rates at which Chinese children with either language delay or familial history of dyslexia at age 5 manifested dyslexia at age 7, identified which cognitive skills at age 5 best distinguished children with and without dyslexia at age 7, and examined how these early abilities predicted subsequent literacy skills. METHOD: Forty-seven at-risk children (21 who were initially language delayed and 26 with familial risk) and 47 control children matched on age, IQ, and mothers' education were tested on syllable awareness, tone detection, rapid automatized naming, visual skill, morphological awareness, and word reading at age 5 and subsequently tested for dyslexia on a standard Hong Kong measure at age 7. RESULTS: Of those with an early language delay, 62% subsequently manifested dyslexia; for those with familial risk, the rate of dyslexia was 50%. Those with dyslexia were best distinguished from those without dyslexia by the age-5 measures of morphological awareness, rapid automatized naming, and word reading itself; other measures did not distinguish the groups. In a combined regression analysis across all participants, morphological awareness uniquely explained word reading accuracy and rapid automatized naming uniquely explained timed word reading at age 7, with all other measures statistically controlled. Separate stepwise regression analyses by group indicated that visual skill uniquely explained subsequent literacy skills in the at-risk group only, whereas tone and syllable awareness were unique predictors of literacy skills in the control group only. CONCLUSIONS: Both early language delay and familial risk strongly overlap with subsequent dyslexia in Chinese children. Overall, rapid automatized naming and morphological awareness are relatively strong correlates of developmental dyslexia in Chinese; visual skill and phonological awareness may also be uniquely associated with subsequent literacy development in at-risk and typically developing children, respectively. PMID- 20735515 TI - Azithromycin as an adjunct to scaling and root planing in the treatment of Porphyromonas gingivalis-associated periodontitis: a pilot study. AB - OBJECTIVE: To evaluate the clinical and microbiological effects of systemic azithromycin as an adjunct to scaling and root planing (SRP) in the treatment of Porphyromonas gingivalis-associated chronic periodontitis. METHODS: Twenty-nine patients harbouring P. gingivalis were randomized into test and placebo groups. Test patients received SRP plus 500 mg of azithromycin per day (3 days), and control patients received SRP plus placebo. Clinical [plaque and bleeding indexes, probing pocket depth (PPD), clinical attachment level (CAL)] and microbiological data (four-sites pooled samples, processed by culture) were collected at baseline, and 1, 3 and 6 months, post-therapy. Clinical variables were compared by anova, and microbiological variables by chi-square, signed-rank and Wilcoxon tests. RESULTS: Fifteen test and 11 placebo patients completed the study. Mean PPD decreased 0.34 mm [95% confidence interval (CI) 0.19-0.49] in the placebo and 0.80 mm (CI 0.57-1.04) in the test group after 6 months. For mean CAL gain, the correspondent figures were 0.29 (CI 0.08-0.49) and 0.76 (CI 0.46-1.05), respectively. The frequency of detection of P. gingivalis decreased significantly (p0.01) in the test group after 1, 3 and 6 months. CONCLUSIONS: Within the limitations of this study, the adjunctive use of systemic azithromycin in the treatment of P. gingivalis periodontitis demonstrated significant clinical and microbiological benefits when compared with SRP plus placebo. PMID- 20735516 TI - Cutaneous perineural inflammation: a review. PMID- 20735517 TI - Morphology and phylogeny of two new pleurostomatid ciliates, Epiphyllum shenzhenense n. sp. and Loxophyllum spirellum n. sp. (Protozoa, Ciliophora) from a mangrove wetland, South China. AB - The morphology, infraciliature, and small subunit (SSU) rRNA gene sequences of two new pleurostomatid ciliates, Epiphyllum shenzhenense n. sp. and Loxophyllum spirellum n. sp., isolated from a mangrove wetland near Shenzhen, South China, were investigated. Epiphyllum shenzhenense n. sp. is morphologically characterized by leaf-shaped cell about 150 x 35 microm in vivo, usually with four contractile vacuoles, 20-29 right kineties and 10-26 left kineties, ca. four macronuclear nodules, and two types of extrusomes (i.e. short spindle-shaped and long bar-shaped). As a new species, L. spirellum n. sp. is distinguished from its congeners by its posterior dorsal margin twisted onto the left side, the distribution of extrusomes (evenly arranged along the oral slit, the posterior end, and clustered to 7-13 warts on dorsal margin), the subterminally positioned contractile vacuole, the number of kineties (8-10 on right side, 4-5 on left side), and its genetic distance from congeners. Phylogenetic trees based on the SSU rRNA gene sequence for both organisms were constructed, which indicate that Epiphyllum is a distinct genus and occupies a basal position in the Pleurostomatida clade; L. spirellum n. sp. falls well into the Loxophyllum clade, which has a close relationship with Litonotus and Spiroloxophyllum. PMID- 20735518 TI - In vivo reflectance confocal microscopy: automated diagnostic image analysis of melanocytic skin tumours. AB - BACKGROUND: In vivo reflectance confocal microscopy (RCM) has been shown to be a valuable imaging tool in the diagnosis of melanocytic skin tumours. However, diagnostic image analysis performed by automated systems is to date quite rare. OBJECTIVES: In this study, we investigated the applicability of an automated image analysis system using a machine learning algorithm on diagnostic discrimination of benign and malignant melanocytic skin tumours in RCM. METHODS: Overall, 16,269 RCM tumour images were evaluated. Image analysis was based on features of the wavelet transform. A learning set of 6147 images was used to establish a classification tree algorithm and an independent test set of 10, 122 images was applied to validate the tree model (grouping method 1). Additionally, randomly generated 'new' learning and test sets, tumour images only and different skin layers were evaluated (grouping method 2, 3 and 4). RESULTS: The classification tree analysis correctly classified 93.60% of the melanoma and 90.40% of the nevi images of the learning set. When the classification tree was applied to the independent test set 46.71 +/- 19.97% (range 7.81-83.87%) of the tumour images in benign melanocytic skin lesions were classified as 'malignant', in contrast to 55.68 +/- 14.58% (range 30.65-83.59%; t-test: P < 0.036) in malignant melanocytic skin lesions (grouping method 1). Further investigations could not improve the results significantly (grouping method 2, 3 and 4). CONCLUSIONS: The automated RCM image analysis procedure holds promise for further investigations. However, to date our system cannot be applied to routine skin tumour screening. PMID- 20735519 TI - Cutaneous metastasis of lung carcinoma: a retrospective study of 12 cases. AB - BACKGROUND: The skin is a rare site of metastasis of the internal malignancies. On the contrary, lung cancer is a common primary malignancy of skin metastasis. The latter is either synchronous with the primary lung tumour or can reveal it. OBJECTIVE: To analyse the clinical findings and the outcome of cutaneous metastasis in patients with primary lung cancer. METHODS: Retrospective study including 12 cases of cutaneous metastasis of lung cancer diagnosed in our institution during 6years. RESULTS: Our patients included three women and nine men with a median age of 59.83years. The cutaneous metastases were unique in seven cases. They revealed the primary tumour in two cases, were discovered synchronously with the primary tumour in six cases and after the primary tumour in four cases. They appeared in patients presenting multiple metastases in 10 cases. Clinical appearance consisted on a firm nodule, sometimes ulcerated with a diameter ranging from 0.5 to 5.5cm. The tumour was sited in the thorax, the back, the abdomen; or the upper or lower limbs. Pathological examination of bronchial biopsy revealed an adenocarcinoma in eight cases, a squamous cell carcinoma in two cases and a small cell carcinoma in two cases. In spite of lung cancer therapies, the patients with metastasis to other organs with a median follow-up time of 4months died. CONCLUSION: Cutaneous metastases of lung cancer are of poor prognosis. They are most of the time associated with an advanced neoplastic process with metastasis to other organs. Median survival after skin involvement does not exceed months. PMID- 20735521 TI - Origins of carbon sustaining the growth of whitefish Coregonus lavaretus early larval stages in Lake Annecy: insights from fatty-acid biomarkers. AB - The hypothesis that diatom carbon (C) produced during the spring peak supported spring zooplankton production and, ultimately, the growth of Coregonus lavaretus early larval stages from March to May 2006 in Lake Annecy, France, was tested using gut content analyses and fatty acid biomarkers. Gut content results showed that C. lavaretus larvae from stages 1 to 4 preferentially fed on copepods with Daphnia sp. only a minor proportion of larval diet. The levels of diatom-marker fatty acids (C16:1n-7 and C20:5n-3) were high in Daphnia sp., but lower in both copepods and C. lavaretus larvae from stages 0 to 4. These results indicated that the spring diatom biomass was actually grazed by Daphnia sp., but, contrary to what was expected, the spring bloom was not the only C source supporting copepods secondary production and, consequently, the growth of C. lavaretus early larval stages. In contrast, levels of terrestrial fatty acid marker (C24:0) were low in Daphnia sp. but high in copepods and C. lavaretus larvae, indicating a significant contribution of terrestrial carbon to copepods and, ultimately, to the growth of C. lavaretus early larval stages. PMID- 20735522 TI - Morphometric changes associated with the reproductive cycle and behaviour of the intertidal-nesting, male plainfin midshipman Porichthys notatus. AB - Morphometric changes in body condition, liver, sonic muscle and gonadal development associated with the annual reproductive cycle and behaviour of the intertidal-nesting male plainfin midshipman Porichthys notatus were investigated. Body condition of type I males rapidly increased during the pre-nesting (PN) period, peaked at the beginning of the summer nesting cycle and then gradually declined to lowest levels during the non-reproductive (NR) period. The gonado somatic index of type I males peaked during PN and then declined during the summer nesting cycle to lowest levels at the end of the nest cycle and during NR. Indices of sonic muscle and liver of type I males were lowest during NR, gradually increased during PN and then peaked during the summer nesting cycle. Results indicate that body condition and fecundity of type I males were positively correlated with body mass at the end of the nest cycle. These findings as they relate to the annual reproductive cycle and behaviour of the type I male P. notatus are discussed. PMID- 20735523 TI - Hyperplastic and hypertrophic growth of lateral muscle in blackspot seabream Pagellus bogaraveo from hatching to juvenile. AB - To understand better the growth mechanisms in the economically important fish Pagellus bogaraveo, in terms of muscle fibre hyperplasia v. hypertrophy, the lateral muscle of this fish was studied morphometrically from hatching to juvenile comparing rostral and caudal locations. Fish were sampled at 0, 5, 23, 40, 70, 100, 140 and 180 days. Fibre types were first identified by succinate dehydrogenase (SDH) and immunostaining with a polyclonal antibody against fish slow myosin (4-96). Morphometric variables were then measured in transverse body sections, at both post-opercular and post-anal locations, to estimate the following variables: total muscle area [A (muscle)], total fibre number [N (fibres)], fibre number per unit area of muscle [N(A)(fibres, muscle)] and cross sectional fibre area [a (fibres)] of the two main muscle fibre types (white and red). Overall, growth throughout the various stages resulted from increases both in the number and in the size of muscle fibres, paralleled by an expansion of the [A (muscle)]. Nonetheless, that increase was not significant between 0-5 days on one hand and 100-140 days, on the other hand. On the contrary, the [N(A)(fibres, muscle)] declined as the body length increased. Analysis of the muscle growth kinetics suggested that, within the important time frame studied, hyperplasia gave the main relative contribution to the increase of white muscle [A (white muscle)], whereas red muscle [A (red muscle)] mainly grew by hypertrophy, with both phenomena occurring at a faster pace posteriorly in the body. Finally, when comparing rostral and caudal locations, a greater [N (fibres)] and [A (muscle)] of the posterior white and red fibres were the consistent features. It was also observed that the proportion of the cross-sectional area of the myotomal muscle comprised of white muscle was greater in the anterior part of the fish. PMID- 20735524 TI - The electric organ discharges of the Petrocephalus species (Teleostei: Mormyridae) of the Upper Volta system. AB - In this study, a first comparative investigation of all four species of Petrocephalus (P. bovei, P. bane, P. soudanensis and P. cf. pallidomaculatus) present in the Upper Volta system and their electric organ discharges (EOD) was conducted. It was found that P. bovei was the most widespread (in terms of habitat use), but in several places P. bovei, P. soudanensis and P. cf. pallidomaculatus occurred syntopically. All species emitted a triphasic signal, and with very few exceptions, the Petrocephalus species of the Upper Volta system could clearly be identified on the basis of their EOD waveforms. The most obvious differences between species in EOD waveforms were in amplitude of the last phase, total duration and fast Fourier transformation (FFT) peak frequency. No sexual dimorphism was present in the EOD of any species although external dimorphism, i.e. an indentation at the base of the anal fin of mature males, was common. The EOD waveform diversity in the Upper Volta principally resembled that found in four sympatric Petrocephalus species from the Ogooue system (Gabon) and might play a role in species recognition and speciation processes. PMID- 20735525 TI - Effect of incubation temperature on muscle growth of barramundi Lates calcarifer at hatch and post-exogenous feeding. AB - Muscle morphology was investigated in newly hatched barramundi Lates calcarifer larvae incubated at set temperatures (26, 29 and 31 degrees C) prior to hatching. Three days after hatching (the start of exogenous feeding), larvae from the 26 and 31 degrees C treatments were each divided into two groups and reared at that temperature or transferred over the period of several hours to 29 degrees C (control temperature). Incubation temperature significantly affected muscle cellularity in the developing embryo, with larvae incubated at 26 degrees C (mean +/-s.e. 223.3 +/- 7.9) having on average 14.4% more inner muscle fibres than those incubated at 31 degrees C (195.2 +/- 8.8) and 4.8% more than those incubated at 29 degrees C (213.5 +/- 4.7). Conversely, inner muscle fibre cross sectional area significantly increased at the warm incubation temperature in L. calcarifer, so that the total cross-sectional muscle area was not different between treatment groups. The total cross-sectional area of superficial muscle fibres and the proportion of superficial to total fibre cross-sectional area in just hatched L. calcarifer were also affected by incubation temperature, with incubation at the cool temperature (26 degrees C) increasing both the total cross sectional area and proportion of superficial muscle fibres. By 9 days post-hatch, the aforementioned differences were no longer significant. Similarly, there was no difference in total superficial fibre cross-sectional area between any treatment groups of L. calcarifer, whereas incubation temperature still significantly affected the proportion of superficial to total muscle fibre cross sectional area. Larvae hatched and grown at 31 degrees C had a significantly reduced percentage of superficial muscle cross-sectional area (mean +/-s.e. 5.11 +/- 0.66%) compared with those incubated and grown at 29 degrees C (8.04 +/- 0.77%) and 26 degrees C (9.32 +/- 0.56%) and those incubated at 26 degrees C and transferred to 29 degrees C (7.52 +/- 0.53%), and incubated at 31 degrees C and transferred to 29 degrees C (6.28 +/- 0.69%). These results indicate that changes in muscle cellularity induced by raising or lowering the incubation temperature of L. calcarifer display varying degrees of persistence over developmental time. The significance of these findings to the culture of L. calcarifer is discussed. PMID- 20735526 TI - Cohesive social behaviour shortens the stress response: the effects of conspecifics on the stress response in lake sturgeon Acipenser fulvescens. AB - An examination was made of whether social interactions can have a beneficial effect through the attenuation of the stress response in a social species. In the first experiment, one larger (mean +/-s.e. 194.0 +/- 12.5 g) and seven smaller (32.0 +/- 2.6 g) juvenile lake sturgeon Acipenser fulvescens were placed in tanks to determine whether a classic dominance effect would be established based on body size (n = 6). Large fish did not establish a territory or aggressively interact with smaller fish, as there were no significant differences in nearest neighbour distances and an absence of aggressive behaviour (biting, chasing and pushing). In the second experiment, it was hypothesized that the presence of conspecifics would have a beneficial effect through an attenuation of the stress response. Fish in groups or isolation were stressed by a brief aerial exposure (30 s), and blood plasma was measured at regular time intervals (0, 20, 40, 60, 120 and 240 min) following the stressor via an implanted cannula (n = 9-11). The presence of conspecifics did not affect the peak cortisol response, however, the overall cortisol response was shorter in duration compared to fish in isolation. Furthermore, secondary stress variables (plasma ions and glucose) showed differences between fish in groups and isolation. The results of these experiments suggest that social interaction plays an important and beneficial role in regulating the stress response in cohesive social species such as A. fulvescens. PMID- 20735527 TI - Stable isotope evidence of ontogenetic changes in the diet of gizzard shad Dorosoma cepedianum. AB - Stable sulphur isotopic composition (delta(34)S) of gizzard shad Dorosoma cepedianum was used to investigate the seasonal and ontogenetic variation in the diet of young and adult fish. This study evaluated fish from a hypereutrophic lake that had recently undergone a 40% reduction of large (>300 mm total length, L(T)) D. cepedianum biomass as part of a biomanipulation experiment, which aimed at reducing internal nutrient loading. Dorosoma cepedianum delta(34)S values showed evidence of ontogenetic changes with young fish (<200 mm L(T)) depending more on benthic food sources than adults (>200 mm L(T)). The delta(34)S composition of the adult fish suggested an increasing importance of zooplankton in the diet, although benthic food sources remained part of the diet of all D. cepedianum collected in this study. The results indicated that benthic feeding is used by D. cepedianum of all sizes, suggesting that biomanipulation efforts may need to target all sizes of fish to realize benefits. PMID- 20735528 TI - Evolution of acoustic signals in Cyprinella: degree of similarity in sister species. AB - Signal structure and behavioural context were examined in two sister species, the Tallapoosa shiner Cyprinella gibbsi and the tricolor shiner Cyprinella trichroistia, with two more distantly related species, the Ocmulgee shiner Cyprinella callisema and the whitetail shiner Cyprinella galactura, in order to test the hypothesis that more closely related species would share components of signals not shared with more distant relatives, and to look at the degree of divergence. The species examined differed in number and type of signal components, contexts and frequency under which calls were produced. While all species produced pulses arranged into pulse bursts, C. gibbsi and C. trichroistia shared unique call types, chirps and rattles, and C. galactura and C. callisema both produced the knock call type. The sister species shared more components of their call repertoire with each other than with the more distantly related C. galactura and C. callisema and clustered together based on courtship call similarity. PMID- 20735529 TI - Thermal growth performance of juvenile brown trout Salmo trutta: no support for thermal adaptation hypotheses. AB - Using thermal growth data from eight populations of anadromous and lake-feeding brown trout Salmo trutta, hypotheses of adaptation to local optima and countergradient variation in growth were tested. The adaptation to local optima hypothesis suggests that natural selection can shift optimal performance temperatures to match the prevailing temperature in a new or changed thermal niche. In contradiction, the countergradient variation hypothesis suggests that populations from hostile environments perform better than conspecifics from benign environments at all temperatures. In this study, growth capacity varied between populations but there was no significant correlation between any of the estimated thermal performance parameters (e.g. lower and upper thermal growth limits, optimal temperature for growth and maximum growth capacity) and natural climatic conditions among populations. Hence, S. trutta growth response to temperature lends no support for either of the two suggested thermal adaptation hypotheses. Instead, growth capacity among populations tended to correlate positively with female size at maturity. PMID- 20735531 TI - Morphological variability of the Asiatic cyprinid, topmouth gudgeon Pseudorasbora parva, in its introduced European range. AB - To assess the spatial variability in external morphology of non-native populations of topmouth gudgeon Pseudorasbora parva within an ontogenetic context, triple regression analysis (distance-based measurements) was applied to data from eight European populations (two Slovak, four Romanian, one English and one French). The data from Slovakia were also subjected to geometrical analysis (co-ordinates-based measurements) to obtain a more complex picture of the species' overall morphology. Great phenotypic variability was observed, being expressed not only in the formation of different definite phenotypes but also in the manner by which the phenotypes are achieved. Thus, both the definite phenotype and the patterns of development in invasive P. parva may be highly influenced by environmental conditions. Such great morphological (phenotypic) variability is likely to be one of the attributes that make this species such a successful invader. PMID- 20735530 TI - The influence of light on the diel vertical migration of young-of-the-year burbot Lota lota in Lake Constance. AB - The diel vertical distribution of young-of-the-year (YOY) burbot Lota lota in the pelagic zone of Lake Constance was compared to light intensity at the surface and to the light intensity at their mean depth. Lota lota larvae inhabited the pelagic zone of Lake Constance from the beginning of May until the end of August. From early June, after the stratification of the water column, fish performed diel vertical migrations (DVM) between the hypolimnion and epilimnion. The amplitude of DVM increased constantly during the summer and reached 70 m by the end of August. Lota lota started their ascent to the surface after sunset and descended into the hypolimnion after sunrise. As the YOY fish grew from May to August, they experienced decreasing diel maximum light intensities: in May and early June L. lota spent the day at light intensities >40 W m(-2), but they never experienced light intensities >0.1 W m(-2) after the end of June. From this time, L. lota experienced the brightest light intensities during dusk and dawn, suggesting feeding opportunities at crepuscular hours. The present study implies, that YOY L. lota in the pelagic zone of Lake Constance increased their DVM amplitude during the summer to counteract a perceived predation risk related to body size and pigmentation. PMID- 20735532 TI - Reduced swimming abilities in fast-growing transgenic common carp Cyprinus carpio associated with their morphological variations. AB - Critical swimming speeds (U(crit)) and morphological characters were compared between the F(4) generation of GH-transgenic common carp Cyprinus carpio and the non-transgenic controls. Transgenic fish displayed a mean absolute U(crit) value 22.3% lower than the controls. Principal component analysis identified variations in body shape, with transgenic fish having significantly deeper head, longer caudal length of the dorsal region, longer standard length (L(S)) and shallower body and caudal region, and shorter caudal length of the ventral region. Swimming speeds were related to the combination of deeper body and caudal region, longer caudal length of the ventral region, shallower head depth, shorter caudal length of dorsal region and L(S). These findings suggest that morphological variations which are poorly suited to produce maximum thrust and minimum drag in GH transgenic C. carpio may be responsible for their lower swimming abilities in comparison with non-transgenic controls. PMID- 20735533 TI - Distribution, colour polymorphism and habitat use of the African killifish Nothobranchius furzeri, the vertebrate with the shortest life span. AB - Intensive collection in southern Mozambique across and outside the potential range of Nothobranchius furzeri, the species with the shortest recorded life span among vertebrates used as a model in ageing research, revealed that, contrary to previous data, it is a widespread species. It occurs in small freshwater pools south of the Save River and north of the Incomati River, including basins of the Limpopo, Changane, Chefu, Mazimechopes and Vaneteze Rivers. During collection in February 2008 (the second part of the rainy season), populations were strongly female biased (mean, 28% of males across 19 populations), and there was a spatial pattern in female bias among metapopulations. Populations varied in the proportion of male colour morphs. Fourteen populations were composed exclusively of the red male phenotype, three populations of the yellow male phenotype and 12 populations were mixed. Overall, the red phenotype was more common, but there was strong geographical variation in morph proportion, with yellow males more abundant at the periphery and red male dominance in the centre of the range of N. furzeri in the Limpopo basin. Nothobranchius furzeri was sympatric with Nothobranchius orthonotus (35% of investigated pools) and Nothobranchius rachovii (27% of sites). Analysis of habitat use of N. furzeri is presented; N. furzeri was associated with pools containing a soft muddy substratum and turbid water. PMID- 20735534 TI - Effects of competitor density and physical habitat structure on the competitive intensity of territorial white spotted charr Salvelinus leucomaenis. AB - This study compared the effects of interference competition in habitats of different complexity and in different densities. The influence of fish density and habitat structure was examined in manipulative experiments using young-of-the year white spotted charr Salvelinus leucomaenis as a model species. The difference of specific growth rate (G) range, an index of interference competitive intensity, was significantly smaller in the structurally complex treatments than structurally simple treatments, while there were no significant difference between high-density and low-density treatments. Thus, physical habitat structure was more effective for mitigating interference competition than manipulating competitor density. Although interference competition was not affected by competitor density, mean G were suppressed in the high-density treatments. This implied that exploitative competition may cause the decrease of G rather than interference competition does in the high-density treatments. Mean G were also suppressed in the structurally complex treatments. Chaotic flow pattern created by physical habitat structures may decrease G by reducing foraging success of experimental fish in the complex treatments. PMID- 20735535 TI - Effects of salinity and anatomical hook location on the mortality and physiological response of angled-and-released sand whiting Sillago ciliata. AB - Three experiments were done with sand whiting Sillago ciliata: the first two assessed the short-term mortality and physiological response of individuals after being mouth hooked and then subjected to rapid changes in salinity, while the third experiment investigated their longer-term fate after ingesting hooks (independent of salinity changes). In experiment one, 48 tanks containing a single S. ciliata were randomly assigned as either one of three treatments or a control. The fish in treatments one and two were exposed to salinity changes during their angling and subsequent release while those in treatment three were only subjected to angling and air exposure. Control fish remained untouched. Fish were then monitored for up to 6 days for mortalities before blood samples were taken to determine concentrations of plasma cortisol and glucose. Blood samples were also taken from five wild-caught fish to provide baseline estimates of the above variables. None of the treatment or control fish died over the 6 days, and there were no significant differences in blood cortisol or glucose between treatment, control and wild fish. In experiment two, 102 S. ciliata and 52 experimental tanks were used. The treatments were repeated as above, however, six individuals from each treatment and control group were removed and sampled for blood (and then glucose and cortisol) at 0, 24, 48 and 72 h post release. Some changes in behaviour due to the salinity changes occurred as well as a significant main effect of time for cortisol, with all fish having significantly elevated acute stress at the first sample time. In experiment three, 52 S. ciliata were placed into individual tanks. Twenty-six of these fish were allowed to ingest baited J-hooks, played for 60 s, removed from their tanks, and then released after their lines were cut (50 mm from their mouths). Control fish were not touched. All fish were then monitored over 21 days. Six of the treatment fish died (between 3 h and 14 days), while the remaining hooked fish resumed feeding within 5 days and 25% ejected their hooks (between 1 and 19 days). It was concluded that (1) salinity and mouth hooking had few independent or interactive effects on the mortality or physiological response of angled-and-released S. ciliata and (2) while hook ingestion caused some mortalities, the protracted physiological effects were limited, with all surviving fish resuming feeding and some eventually ejecting their hooks. PMID- 20735536 TI - Larval development of Argentine hake Merluccius hubbsi. AB - The ontogeny of the developmental stages of the hake Merluccius hubbsi is described. Fish larvae and post-transitional juveniles were collected in the Nor Patagonian area from 1989 to 2004. The opening of the mouth and the pigmentation of the eyes are coincident with yolk resorption, finishing the yolk-sac stage. This species presents pigmentation on the head, trunk and tail typical of gadiform larvae. Pectoral fin development is completed during the transformation stage. The post-transitional juvenile stage begins when the fin-ray complements are complete and squamation begins. The fins become fully formed in the following sequence: pelvic fins, first dorsal fin, second dorsal and anal fins together, caudal fin and pectoral fins. The caudal complex is totally developed in larvae of 22.0-23.0 mm standard lengths (L(S)) and all vertebral elements are first observed in larvae of 8.5 mm L(S). The rate of development of M. hubbsi observed in this study could be faster than the rates reported for other species of Merluccius by different authors. PMID- 20735537 TI - Skate Bathyraja spp. egg predation in the eastern Bering Sea. AB - Predation on skate eggs by snails was examined for three skate species at seven nursery sites in three regions (north, middle and south) of the eastern Bering Sea. Mean predation levels were 6.46% for the Alaska skate Bathyraja parmifera, 2.65% for the Aleutian skate Bathyraja aleutica and 22.25% for the Bering skate Bathyraja interrupta. Predation levels were significantly higher at the middle and north sites than the south sites for all species combined. Predation levels decreased with increasing egg-case densities at all nursery sites, and the highest predation levels occurred where egg-case densities were very low. Predated egg-case density increased with increasing snail densities across all nursery sites examined. The Oregon triton Fusitriton oregonensis was the most abundant snail species at all nursery sites and displayed ability to drill holes in the egg case of B. parmifera. Holes left by predatory snails in egg cases of B. parmifera were significantly larger, and of different shape at the middle site compared to the south site. Holes in B. parmifera were also significantly larger than those in egg cases of B. interrupta across all sites examined. Egg cases of B. aleutica possess surface spines that cover the egg case and may inhibit predation by snails at a greater rate than that of the B. parmifera and B. interrupta, which have a smoother egg-case surface. PMID- 20735538 TI - Sardine Sardinops sagax and anchovy Engraulis encrasicolus larvae avoid regions with low dissolved oxygen concentration in the northern Benguela Current system. AB - Larvae of sardine Sardinops sagax and anchovy Engraulis encrasicolus in the northern Benguela upwelling system were distributed predominantly in waters with dissolved oxygen concentrations >2.0 ml l(-1) and oxygen saturations >75%. PMID- 20735539 TI - Geographic variation in age, growth and size structure of Percilia irwini from south-central Chile. AB - Percilia irwini from the Andalien and Biobio River basins of south-central Chile exhibited a mean age of 1.4 years with a maximum age of 4 years. Size at age differed among river zones and males were 10% larger than females at all ages. Compared to other locations, populations of P. irwini inhabiting areas subject to industrial and domestic effluents exhibited smaller size structure. PMID- 20735540 TI - Long-term effects of passive integrated transponder (PIT) tagging on the kelp grouper Epinephelus bruneus. AB - The effects of passive integrated transponder (PIT) tagging on the growth and survival of kelp grouper Epinephelus bruneus was examined over 1 year. The overall average mass gain for the 1 year period of the abdominal cavity tagged group was higher than the dorsal muscle tagged group. No significant differences were found in overall specific growth rate and food conversion between control and treatment groups. PMID- 20735541 TI - Growth and mortality of European glass eel Anguilla anguilla marked with oxytetracycline and alizarin red. AB - The growth and mortality of European glass eel Anguilla anguilla 192 days after marking with oxytetracycline and alizarin red S were not significantly different between the two treatments and not different to the unmarked A. anguilla. PMID- 20735542 TI - Depth-dependent swimbladder compression in herring Clupea harengus observed using magnetic resonance imaging. AB - Changes in swimbladder morphology in an Atlantic herring Clupea harengus with pressure were examined by magnetic resonance imaging of a dead fish in a purpose built pressure chamber. Swimbladder volume changed with pressure according to Boyle's Law, but compression in the lateral aspect was greater than in the dorsal aspect. This uneven compression has a reduced effect on acoustic backscattering than symmetrical compression and would elicit less pronounced effects of depth on acoustic biomass estimates of C. harengus. PMID- 20735543 TI - Effects of external and surgically implanted dummy radio transmitters on mortality, swimming performance and physiological status of juvenile masu salmon Oncorhynchus masou. AB - The effects of external and surgically implanted radio transmitters on juvenile masu salmon Oncorhynchus masou were examined. External attachment of transmitters significantly decreased the survival of fish and caused a decreased critical swimming speed compared with surgical implantation. Although plasma cortisol, plasma glucose and haematocrit values did not differ significantly among groups, it appeared that the most suitable transmitter attachment method for juvenile O. masou may be surgical implantation. PMID- 20735544 TI - Variability in the growth rate of chub Leuciscus cephalus along a longitudinal river gradient. AB - An increase in individual growth rate of chub Leuciscus cephalus along a longitudinal river gradient of the Rhone River basin was observed and supported by significant differences between mean growth rates of successive river size groups. The potential implications of the results for studies on species traits variability along large-scale environmental gradients are discussed. PMID- 20735547 TI - Loss of shoaling preference for familiar individuals in captive-reared crimson spotted rainbowfish Melanotaenia duboulayi. AB - Captive-reared rainbowfish Melanotonia duboulayi showed no preference for familiar individuals in an experiment examining shoaling preferences. Fortnightly re-examination of the shoaling preferences of the captive-reared population showed that the lack of preference for familiar individuals did not alter over an 8 week period. The same experiment performed on laboratory-reared offspring raised in isolated groups for 8 months since hatching also showed no preference for shoals consisting of familiar individuals. In contrast, trials performed on a wild population of M. duboulayi found a strong preference for familiar shoalmates, a result that is consistent with previous studies. The lack of shoaling preferences in captive-reared populations is probably the result of relaxed selection and inbreeding in the captive environment. The consequences of captive breeding for fish social behaviour are discussed with particular reference to hatchery production. PMID- 20735548 TI - Density-dependent growth rate in an age-structured population: a field study on stream-dwelling brown trout Salmo trutta. AB - A field experiment during autumn, winter and spring was performed in a small stream on the west coast of Sweden, aiming to examine the direct and indirect consequences of density-dependent intercohort competition in brown trout Salmo trutta. Individual growth rate, recapture rate and site fidelity were used as response variables in the young-of-the-year (YOY) age class, experiencing two different treatments: presence or absence of yearlings and over-yearlings (age > or = 1+ year individuals). YOY individuals in stream sections with reduced density of age > or = 1+ year individuals grew significantly faster than individuals experiencing natural cohort structure. In the latter, growth rate was negatively correlated with density and biomass of age > or = 1+ year individuals, which may induce indirect effects on year-class strength through, for example, reduced fecundity and survival. Movement of YOY individuals and turnover rate (i.e. proportion of untagged individuals) were used to demonstrate potential effects of intercohort competition on site fidelity. While YOY movement was remarkably restricted (83% recaptured within 50 m from the release points), turnover rate was higher in sections with reduced density of age > or = 1+ year individuals, suggesting that reduced density of age > or = 1+ year individuals may have released favourable microhabitats. PMID- 20735549 TI - Variation in large-bodied fish-community structure and abundance in relation to water-management regime in a large regulated river. AB - Variation in life-history traits (growth, condition, mortality and recruitment) and relative abundance of 11 large-bodied fish species was investigated among three water-management regimes (unimpounded, run-of-the-river and winter reservoirs) in the large regulated Ottawa River, Canada. If waterpower management had an effect on fishes, then (1) would be expected community structuring among water-management regimes and (2) species with similar life-history traits should be affected in a similar manner. Large-bodied fish communities were assessed using two different standard index-netting techniques, one using trap nets and the other gillnets. Community structure could be discriminated based on species caught in nets using holographic neural networks (78.8% correct overall classification rate using trap nets and 76.0% using gillnets); therefore, water management regimes affected community structure in the Ottawa River. Littoral zone benthivores were significantly lower in abundance (P < 0.001) or absent in winter reservoirs, whereas the abundance of planktivores or species that were planktivorous at young ages were significantly greater than in unimpounded river reaches. Growth, condition and mortality did not vary among reach types except smallmouth bass Micropterus dolomieu were in better condition in winter reservoirs than unimpounded reaches. Lake sturgeon Acipenser fulvescens recruitment was impaired in run-of-the-river reaches, whereas recruitment for other species that spawn in fast water was not affected. PMID- 20735550 TI - Nuclear abnormalities of marine fish erythrocytes. AB - The aim of this study was to monitor erythrocyte nuclear abnormalities (NA) including micronuclei (MN) in cultured and wild sea bass Dicentrarchus labrax and wild mullet Mugil spp. Seasonal sampling was performed at seven locations along the eastern coast of the Adriatic Sea. The frequency of NA and MN was positively correlated to temperature (NA: P < 0.05, r = 0.11; MN P < 0.05, r = 0.10), and there was also a positive correlation between NA and MN frequency (P < 0.001, r = 0.43). The lowest NA and MN values for both fish species were recorded in spring, while the highest were recorded in autumn. Significantly higher frequency of NA was seen in D. labrax compared to Mugil spp., while MN frequency was low in both species and not significantly different. There was no significant difference in NA and MN frequency between cultured and wild D. labrax sampled in the same month, and there was no difference between wild Mugil spp. sampled near or far from fish farms. In view of sampling sites, the highest values were detected in fishes from the Limski Channel, the lowest from the Janjina location. PMID- 20735551 TI - Seasonal variability in growth of larval Japanese anchovy Engraulis japonicus driven by fluctuations in sea temperature in the Kii Channel, Japan. AB - Seasonal variability in the growth of larval Japanese anchovy Engraulis japonicus was examined through otolith microstructure analysis based on the samples collected from the northern side (inner area, IA) and the southern side (outer area, OA) of the Kii Channel from April 2006 to March 2007. Growth trajectories (otolith backcalculated mean standard length of 5 day intervals from 5 days after hatch to 24 days) as well as the most recent 5 day mean growth rate of larvae before capture (G(5)) differed among months. Growth trajectories showed the same pattern as G(5). In IA, mean +/-s.d.G(5) ranged from 0.31 +/- 0.04 mm day(-1) (January) to 0.73 +/- 0.06 mm day(-1) (October). In OA, mean +/-s.d.G(5) ranged from 0.36 +/- 0.05 mm day(-1) (January) to 0.79 +/- 0.11 mm day(-1) (August). G(5) values declined from November to January and then started to increase. In general, the seasonal patterns of growth were similar between IA and OA, and a clear seasonal pattern in growth was identified. When the relationships among larval growth rate, sea temperature, zooplankton density and larval density were examined, growth rate was positively related with sea temperature in both areas and not related with the other factors. The similar pattern in growth observed between IA and OA was probably due to the low spatial variability in sea temperature compared to its seasonal variability. PMID- 20735552 TI - Effects of food type on diel behaviours of common carp Cyprinus carpio in simulated aquaculture pond conditions. AB - In order to better understand behaviour patterns of common carp Cyprinus carpio in aquaculture ponds, their diel grazing, swimming, resting and schooling behaviours were observed in six 1 m(2) tanks under simulated pond conditions. Each tank was fertilized to stimulate natural food production before starting experiments, and then stocked with three C. carpio. Fish behaviours were compared among three treatments: (1) tanks with plankton only, (2) tanks with plankton and benthic macroinvertebrates and (3) tanks with plankton, benthic macroinvertebrates and artificial feed. Overall C. carpio grazed more frequently during daytime than at night and exhibited the reverse pattern for non-feeding swimming behaviour. A significant negative relationship (r(2) = 0.99, P < 0.01, n = 48) was observed between total per cent grazing time and total per cent swimming time. Fish dispersed to graze individually during daytime but schooled at night and did not display any agonistic behaviours. Diel variations in the vertical swimming behaviour of C. carpio were related to food types available. In tanks containing plankton only, fish grazed in the water column, whereas when benthic macroinvertebrates were present, they spent more time near the tank bottom. Resting behaviour was only seen in tanks with artificial feed and even then was rare (2-5% of total time). Results suggest that C. carpio growth and feed utilization efficiency in semi-intensive aquaculture systems could be optimized by using a combination of plankton, benthic macroinvertebrates and artificial feed, and feeding fish twice per day (at c. 0730 and c. 1630 hours). PMID- 20735553 TI - Investigation of first year biotic and abiotic influences on the recruitment of pike Esox lucius over 48 years in Windermere, UK. AB - Estimated pike Esox lucius recruitment varied by a factor of 16 for females from 1944 to 1991 and by a factor of 27 for males from 1943 to 1990 in Windermere, a temperate, mesotrophic U.K. lake. No significant stock-recruitment relationships were found, but analysis with general additive models (GAMs) revealed that early autumnal water temperature, strength and direction of the North Atlantic Oscillation displacement (corresponding to different climatic conditions in winter) and zooplankton abundance but above all, late summer water temperature were important explanatory variables over the entire time series. Female recruitment was also influenced by young-of-the-year winter temperature. There was no evidence that perch Perca fluviatilis year-class strength, lake level or the summer position of the Gulf Stream influenced recruitment. The fitted models explained up to c. 65% of the overall observed variation between years. PMID- 20735554 TI - Interspawning interval of wild female three-spined stickleback Gasterosteus aculeatus in Alaska. AB - The interspawning interval, or spawning frequency, of wild three-spined stickleback, Gasterosteus aculeatus, was estimated using histological examination of postovulatory follicles (POF). Females in Alaskan lakes appeared to have as much as a 48 h delay between ovulation and ovoposition, yet the POF method could still be used to estimate the interspawning interval. In two Alaskan lakes the interspawning interval was estimated to range from 2.2 to 7.8 days among individual female G. aculeatus. These estimates were consistent with the range (2.5 to 5 days) of previous estimates among individual females from laboratory observations of spawning G. aculeatus, as well as anecdotal accounts of spawning intervals reported from wild populations in Canada (5-10 days). The interspawning interval of females increased during the course of the spawning season in Alaska, showing that the majority of female spawning activity occurred during the earliest portion of the approximate 6-week reproductive season. The increased interspawning interval appears to be related to a previously reported decrease in body condition in reproductive females during the breeding season. Thus, female G. aculeatus may be unable to sustain the initial rate of reproduction as energy stores that support the rapid growth of vitellogenic oocytes are depleted. PMID- 20735555 TI - Dispersal and survival of stocked cyprinids in a small English river: comparison with wild fishes using a multi-method approach. AB - Mark-recapture and fixed-station passive integrated transponder (PIT) telemetry were used to compare movements, distribution and survival of stocked juvenile chub Leuciscus cephalus and roach Rutilus rutilus with those of wild conspecifics. Daily activity of wild fish activity was affected by a combination of river flow and temperature, whereas stocked fishes were not influenced by environmental factors. PIT telemetry recorded exploratory movements of stocked L. cephalus immediately after stocking, a substantial number of stocked fish moved both downstream and upstream during periods of elevated flow, and proportionally more stocked fish moved during the first 6 weeks after release than later on. Proportionally more stocked fish than wild fish moved through PIT antennae, stocked L. cephalus moved greater distances than wild L. cephalus and were more widely distributed than wild fish. Minimum estimates of survival after 5 months were 50.5% for stocked R. rutilus and 28.0% for stocked L. cephalus. Ultimately, stocked cyprinids appeared to be able to cope with elevated flows and most remained in the river section local to the stocking location. PMID- 20735556 TI - The effect of social environment during ontogeny on life history expression in the guppy Poecilia reticulata. AB - The effects of the social environment during development on life-history decisions and adult behaviour were assessed using male guppies Poecilia reticulata. Males raised with adults developed secondary sexual characteristics later than males raised either singly or with four of their siblings indicating social inhibition of maturation was evident in P. reticulata. There was no effect, however, of rearing environment on male behaviour. The results reveal that social environment during development can influence life-history decisions but is less important than immediate social context in determining male behavioural phenotype in P. reticulata. PMID- 20735557 TI - Assessment of reproductive potential in multiple-spawning fish with indeterminate fecundity: a case study of yellow sea bream Dentex hypselosomus in the East China Sea. AB - This study examined the spawning season, spawning frequency and batch fecundity of yellow sea bream Dentex hypselosomus in the East China Sea to reassess the previously reported reproductive characteristics of the species. Time-course sampling showed that this species had a diurnal ovarian maturation rhythm. Late tertiary yolk-stage oocytes appeared 2 days before spawning, starting the process of germinal vesicle movement and breakdown. On the day of spawning, ovulation and subsequent spawning occurred in the early morning (0400-0800 hours). Postovulatory follicles disappeared from the ovaries within c. 24 h of ovulation. Seasonal changes in the ovarian conditions indicated that this species spawned more or less throughout the year, with the peak ranging from spring to autumn. The compositions of the developing oocytes and degenerating postovulatory follicles in the ovaries suggested that most females spawned repeatedly over 2 to 3 consecutive days during the peak of the spawning season. Somatic body condition did not have a significant effect on batch fecundity, but there was a significant relationship between batch fecundity and fork length according to spawning status. Females spawning on consecutive days were more fecund than those spawning every other day. The findings show that this species has much greater reproductive potential than previously estimated. PMID- 20735558 TI - Latitudinal and altitudinal growth patterns of brown trout Salmo trutta at different spatial scales. AB - Spatial variation in growth of stream-dwelling brown trout Salmo trutta was explored in 13 populations using a long-term study (1993-2004) in the Bay of Biscay drainage, northern Spain. The high variability in fork length (L(F)) of S. trutta in the study area was similar to the body-size range found in the entire European distribution of the species. Mean L(F) at age varied: 0+ years, 57.4 100.7 mm; 1+ years, 111.6-176.0 mm; 2+ years, 155.6-248.4 mm and 3+ years, 194.3 290.9 mm. Average L(F) at age was higher in main courses and lower reaches compared with small tributaries and upper reaches. Annual specific growth rates (G(L)) were: 0+ to 1+ years, 0.634-0.825 mm mm(-1) year(-1); 1+ to 2+ years, 0.243-0.342 mm mm(-1) year(-1); 2+ to 3+ years, 0.166-0.222 mm mm(-1) year(-1), showing a great homogeneity. Regression models showed that water temperature and altitude were the major determinants of L(F) at age variability within the study area. A broader spatial analysis using available data from stream-dwelling S. trutta populations throughout Europe indicated a negative relationship between latitude and L(F) of individuals and a negative interaction between latitude and altitude. These findings support previous evidence of the pervasive role of water temperature on the L(F) of this species. Altitude appeared as the overall factor that includes the local variation of other variables, such as water temperature or food availability. At a larger scale, latitude was the factor that encompassed these environmental gradients and explained the differences in L(F) of S. trutta. In summary, L(F) at age in stream-dwelling S. trutta decreases with latitude in Europe, the converse of Bergmann's rule. PMID- 20735559 TI - Short-term dominance: stability and consequences for subsequent growth. AB - Dominance status was determined among groups of four fish by using individuals from eight brown trout Salmo trutta populations. Subsequent growth of the fish was later recorded in larger groups. Seven months after the first set of trials, an additional set of dominance trials was performed by using the same fish. Social status affected subsequent growth; individuals having the lowest ranks grew less when compared to the higher ranking fish. Furthermore, the short term dominance hierarchy was rather stable between the two trials. This was especially the case with the lowest ranking fish, which tended to remain in the lowest position also in the second trial. The results suggest that the short term dominance trials done among few conspecifics reflect relatively well not only the subordinates' relative but also absolute social status. PMID- 20735560 TI - Investigational piscivory of some juvenile Australian freshwater fishes by the introduced Mozambique tilapia Oreochromis mossambicus. AB - Experimental tanks were used to observe predatory effects in three different size classes of Mozambique tilapia Oreochromis mossambicus (one of the world's most widespread exotic species and generally regarded to be a herbivore or both herbivore and detritivore) when tested against 10 juvenile Australian freshwater fish species, and significant levels of predation against all were recorded. There was a general trend for larger O. mossambicus to kill more prey and this was also reflected in a separate series of experiments using juvenile barramundi Lates calcarifer over a range of size classes. Predatory effects by O. mossambicus broadly reflected the accepted models of predator-prey interactions, being that mortality (and survival) was closely related to relative body size and mouth gape limitation. Experimental evidence for piscivory in O. mossambicus was supported by field sampling that detected prey fish remains in 16% of all fish surveyed (n = 176). The recognition of active piscivory by O. mossambicus in laboratory and field situations is the first such evidence, and suggests a need to re-evaluate the nature of their effects in introduced environments. PMID- 20735561 TI - Lunar periodicity and the timing of river entry in Atlantic salmon Salmo salar. AB - Historical catch records of Atlantic salmon Salmo salar from three rivers discharging to the Baltic Sea in an area free from tides and from strong effects of the moon on illumination were analysed to investigate whether timing of S. salar river entry was associated with lunar cycles directly. Although a significant effect of lunar phase on river entry was detected, with more fish entering rivers around the full moon than other phases, the effect of the lunar cycle was very small compared with other sources of variation. Hence, the biological role of lunar cycle as a determinant of the timing of S. salar runs in the investigated populations was negligible, suggesting that lunar cycle per se does not play a role in the timing of S. salar river entry. PMID- 20735562 TI - Density-independent growth of floodplain river channel catfish Ictalurus punctatus. AB - This study investigated the relative influence of biotic and abiotic factors on the growth of channel catfish Ictalurus punctatus in seven Mississippi floodplain rivers. The results indicate that growth was density-independent, being defined largely by abiotic conditions. PMID- 20735563 TI - Colour morph of a probable queen angelfish Holacanthus ciliaris from Dry Tortugas, Florida. AB - An unusual colour morph of a probable Holacanthus ciliaris was observed in Dry Tortugas, Florida, which can possibly be explained by recessive homozygosity, however, further testing is necessary. This variation of H. ciliaris has previously only been described at St Paul's Rocks, Mid-Atlantic Ridge. PMID- 20735564 TI - The campaign to DNA barcode all fishes, FISH-BOL. AB - FISH-BOL, the Fish Barcode of Life campaign, is an international research collaboration that is assembling a standardized reference DNA sequence library for all fishes. Analysis is targeting a 648 base pair region of the mitochondrial cytochrome c oxidase I (COI) gene. More than 5000 species have already been DNA barcoded, with an average of five specimens per species, typically vouchers with authoritative identifications. The barcode sequence from any fish, fillet, fin, egg or larva can be matched against these reference sequences using BOLD; the Barcode of Life Data System (http://www.barcodinglife.org). The benefits of barcoding fishes include facilitating species identification, highlighting cases of range expansion for known species, flagging previously overlooked species and enabling identifications where traditional methods cannot be applied. Results thus far indicate that barcodes separate c. 98 and 93% of already described marine and freshwater fish species, respectively. Several specimens with divergent barcode sequences have been confirmed by integrative taxonomic analysis as new species. Past concerns in relation to the use of fish barcoding for species discrimination are discussed. These include hybridization, recent radiations, regional differentiation in barcode sequences and nuclear copies of the barcode region. However, current results indicate these issues are of little concern for the great majority of specimens. PMID- 20735565 TI - Distinguishing between two sympatric Acanthopagrus species from Dapeng Bay, Taiwan, using morphometric and genetic characters. AB - Morphometric and genetic data were used to compare two sympatric and morphologically similar species, Acanthopagrus berda and Acanthopagrus taiwanensis, in Dapeng Bay, South-western Taiwan. A principle component analysis of morphological data indicated a distinction between the two species, with pectoral fin length and eye diameter accounting for 32.27% of the variation. Interspecific sequence divergence, based on mtDNA cytochrome b (0.118 +/- 0.01), was larger than intraspecific divergences between haplotypes (0.007 for A. taiwanensis and 0.003 for A. berda). Individuals of the two species clustered into different groups in three phylogenetic trees with 100% bootstrap support. The mean observed heterozygosity for eight microsatellite loci was 0.471 +/- 0.202 for A. taiwanensis and 0.637 +/- 0.145 for A. berda. Nei's unbiased measure of interspecific genetic distance (D(S)) was 1.334. F(ST) (0.134) and R(ST) (0.404) values indicated significant differentiation between species. An unrooted neighbour-joining tree was constructed by allele-sharing distances and the factorial correspondence analysis split all specimens into two distinct clusters. The results of morphometric, mtDNA and microsatellite analyses indicated the presence of two species, A. taiwanensis and A. berda. PMID- 20735566 TI - Probing diversity in freshwater fishes from Mexico and Guatemala with DNA barcodes. AB - The freshwater fish fauna of Mexico and Guatemala is exceptionally diverse with >600 species, many endemic. In this study, patterns of sequence divergence were analysed in representatives of this fauna using cytochrome c oxidase subunit 1 (COI) DNA barcodes for 61 species in 36 genera. The average divergence among conspecific individuals was 0.45%, while congeneric taxa showed 5.1% divergence. Three species of Poblana, each occupying a different crater lake in the arid regions of Central Mexico, have had a controversial taxonomic history but are usually regarded as endemics to a single lake. They possess identical COI barcodes, suggesting a very recent history of isolation. Representatives of the Cichlidae, a complex and poorly understood family, were well discriminated by barcodes. Many species of Characidae seem to be young, with low divergence values (<2%), but nevertheless, clear barcode clusters were apparent in the Bramocharax Astyanax complex. The symbranchid, Opisthernon aenigmaticum, has been regarded as a single species ranging from Guatemala to Mexico, but it includes two deeply divergent barcode lineages, one a possible new endemic species. Aside from these special cases, the results confirm that DNA barcodes will be highly effective in discriminating freshwater fishes from Central America and that a comprehensive analysis will provide new important insights for understanding diversity of this fauna. PMID- 20735567 TI - Population structure in a common Caribbean coral-reef fish: implications for larval dispersal and early life-history traits. AB - Genetic population structure throughout the Caribbean Basin for one of the most common and widespread reef fish species, the bicolour damselfish Stegastes partitus was examined using microsatellite DNA markers. Spatial autocorrelation analysis showed a significant positive correlation between genetic and geographic distance (isolation by distance) over distances <1000 km, suggesting that populations are connected genetically but probably not demographically, i.e. over shorter time scales. A difference in spatial patterns of populations in the eastern v. the western Caribbean also raises the probability of an important role for meso-scale oceanographic features and landscape complexity within the same species. A comparison of S. partitus population structure and life-history traits with those of two other species of Caribbean reef fish studied earlier showed the findings to be concordant with a common hypothesis that shorter pelagic larval dispersal periods are associated with smaller larval dispersal scales. PMID- 20735568 TI - Rare and asymmetrical hybridization of the endemic Barbus carpathicus with its widespread congener Barbus barbus. AB - In endemic species that co-occur with widespread congeners, hybridization can lead to an influx of novel and beneficial genetic variation, but high rates of introgression may cause genetic swamping of the endemic species and have detrimental effects on its survival potential. This study examines hybridization between sympatric populations of the Carpathian barbel Barbus carpathicus, a recently discovered cryptic species with a restricted range, and the widespread common barbel Barbus barbus. Based on six diagnostic allozyme loci, a microsatellite locus and mtDNA, hybrids were found to be present at multiple localities within the Vistula River drainage (Baltic Sea) as well as in the Tisza River system of the Danube River drainage (Black Sea). However, the numbers of hybrids were very low; four individuals of 230 fish sampled from the Vistula drainage. Bayesian assessment of their nuclear genotypes suggested that two hybrids in the Vistula drainage and nine in the Tisza system were F1 generation, and one in the Vistula drainage and one in the Tisza system were backcrosses (BC) to B. barbus, while no F2 or BC to B. carpathicus were detected. No hybrid carried B. carpathicus mtDNA and cytonuclear linkage disequilibria showed significant positive associations between hybrid genotypes and B. barbus mtDNA, suggesting unidirectionality in the interspecific mating with a disproportionate contribution of B. barbus mothers. Despite geographically broad occurrence of hybrids, these data provide evidence of strong constraints on hybridization in the native breeding habitats and the lack of introgression towards B. carpathicus. PMID- 20735569 TI - Genetic structure of Melanotaenia australis at local and regional scales in the east Kimberley, Western Australia. AB - The Kimberley region of Western Australia possesses a poorly studied freshwater fish fauna with high endemism in an aquatic landscape subject to monsoonal floods and dry season isolation. In the first population genetic study of freshwater fish in this region, the authors tested the effects of geographic barriers on genetic structure at multiple spatial scales in east Kimberley populations of the western rainbowfish, Melanotaenia australis, the most widespread and abundant species in the region. Based on allozyme comparisons, hierarchical analysis of F(ST) revealed increasing genetic subdivision with spatial scale. Minimal genetic structure within creeklines demonstrated that wet season dispersal, rather than dry season isolation, determines genetic structure at small scales. At the scale of sub-catchments, a pattern of isolation by distance along creeklines was evident. Genetic subdivision between adjacent river systems was greater between rivers separated by a plateau than by lowlands. This implies greater connectivity of populations in lowland areas and may explain the greater similarity of the east Kimberly freshwater fish fauna with lowlands to the east than with the more rugged regions to the west. Similarly, greater connectivity between lowland populations may account for the on-average larger distribution of lowland Melanotaeniids. PMID- 20735570 TI - In vivo synthesis of meganuclease for generating transgenic zebrafish Danio rerio. AB - The authors show that co-injection at the one-cell stage of mRNA encoding a nuclear-targeted meganuclease I-SceI together with expression cassettes flanked by cognate restriction sites results in efficient stable transgenesis in zebrafish Danio rerio. PMID- 20735571 TI - A set of 37 microsatellite DNA markers for genetic diversity and structure analysis of Atlantic salmon Salmo salar populations. AB - Atlantic salmon Salmo salar microsatellite markers from a large database were analysed and selected with technical, economic and genetic criteria to provide an optimized set of polymorphic DNA markers for the analysis of the genetic diversity and the structure of anadromous Atlantic salmon populations. A set of 37 microsatellite markers was identified that are easy to use and provide a high level of differentiation power. PMID- 20735572 TI - Evidence for interspecific hybridization between native white-spotted charr Salvelinus leucomaenis and non-native brown trout Salmo trutta on Hokkaido Island, Japan. AB - Hybrids between native white-spotted charr Salvelinus leucomaenis and non-native brown trout Salmo trutta were identified in streams of Hokkaido, Japan, using both appearance and genetic characters. The DNA analyses indicated that the specimens were hybrids between female S. leucomaenis and male S. trutta. Occurrence of such hybrids implies increased mating opportunities between these species in wild streams. PMID- 20735573 TI - Rodlet cell biometry: interspecific and intraspecific variability. AB - Intraspecific and interspecific variability in rodlet cell size in various tissues of several species of freshwater and marine fish were documented. Differences were attributed mainly to fish species, although tissue type contributed significantly, providing evidence for the presence of rodlet cell morphotypes. PMID- 20735574 TI - Embryo developmental events and the egg case of the Aleutian skate Bathyraja aleutica (Gilbert) and the Alaska skate Bathyraja parmifera (Bean). AB - Embryo development events were correlated with egg-case changes for the Aleutian skate Bathyraja aleutica and the Alaska skate Bathyraja parmifera. Yolk absorption underwent two phases: that of steady absorption during early development and that of rapid yolk absorption during the final development stages. Total length (L(T)) for 50% of the pre-hatching embryos egg-case jelly disappearance was 92.04 mm (range 81-102 mm) and 99.36 mm (range 81-100 mm) for B. aleutica and B. parmifera, respectively, allowing the inner chamber to open to seawater flow. The tail filament underwent three phases of growth: rapid elongation during early development (<100 mm embryo L(T)), stasis of tail filament length during the remainder of embryo development and rapid absorption soon after hatching. Complete tail filament development coincided with the disappearance of egg-case jelly. Clasper buds first developed at embryos >70 mm L(T) for both species and the sex ratio was 1:1 well before hatching. Egg cases that were devoid of an ova or developing embryo were c. 5.0 and 6.5% of the egg cases examined for B. aleutica and B. parmifera, respectively. Measurements showed that egg cases containing only egg jelly were smaller in both width and length than those possessing an ova. Embryo stages were punctuated with distinct events that correlated with egg case changes controlling the internal environment of the developing embryo. PMID- 20735575 TI - Morphology-diet relationships in four killifishes (Teleostei, Cyprinodontidae, Orestias) from Lake Titicaca. AB - This study explores the relationship between morphology and diet in four Andean killifishes (Orestias) from Lake Titicaca that are known to differ in habitat use. Species that fed preferentially on amphipods (Orestias albus) or molluscs (Orestias luteus) separated in multivariate space from other species that feed on cladocera and algae (Orestias agassii and Orestias jussiei). Generally, specimens feeding on cladocera were characterized by a short, blunt nose with a small mouth; whereas, specimens feeding on amphipods exhibited a long snout with a large mouth. Specimens including molluscs in their diet tended to have a larger posterior part of the head and the larger opercles than others; while the occurrence of substratum in gut content was generally related to a short but deep head. The present analysis suggests that the littoral O. jussiei has an intermediate phenotype and diet between the pelagic (O. agassii) and benthic (O. albus and O. luteus) species. Results suggest that resource partitioning was occurring and that several morphological traits relate to characteristics of the diet, and it is inferred that the benthic, the pelagic and the littoral zones in the lake host different prey communities constituting distinct adaptive landscapes. PMID- 20735576 TI - Energy density of anchovy Engraulis encrasicolus in the Bay of Biscay. AB - The energy density (E(D)) of anchovy Engraulis encrasicolus in the Bay of Biscay was determined by direct calorimetry and its evolution with size, age and season was investigated. The water content and energy density varied seasonally following opposite trends. The E(D) g(-1) of wet mass (M(W)) was highest at the end of the feeding season (autumn: c. 8 kJ g(-1)M(W)) and lowest in late winter (c. 6 kJ g(-1)M(W)). In winter, the fish lost mass, which was partially replaced by water, and the energy density decreased. These variations in water content and organic matter content may have implications on the buoyancy of the fish. The water content was the major driver of the energy density variations for a M(W) basis. A significant linear relationship was established between E(D) g(-1) (y) and the per cent dry mass (M(D); x): y =-4.937 + 0.411x. In the light of the current literature, this relationship seemed to be not only species specific but also ecosystem specific. Calibration and validation of fish bioenergetics models require energy content measurements on fish samples collected at sea. The present study provides a first reference for the energetics of E. encrasicolus in the Bay of Biscay. PMID- 20735577 TI - Heart rate and ventilation in Antarctic fishes are largely determined by ecotype. AB - Extrinsic neural and humoral influences on heart rate (fH) and ventilation frequency (fV) were examined following varying periods of post-surgical recovery in eight related Antarctic fish species inhabiting an array of inshore niches. Resting fH after recovery from handling was lower than previous reports, and the novel measurement of routine fH in free-swimming Dissostichus mawsoni (6.14 beats min(-1), bpm) is the lowest recorded for any fish. The extent of cardio depressive cholinergic (vagal) tonus explained the large range of fH among species and varied with behavioural repertoire, being lower in the more active species, apart from Notothenia coriiceps. Adrenergic tonus was low compared with cholinergic tonus, with the exception of Trematomus newnesi. Hence, high cardiac cholinergic tonus may be a genotypic trait of the notothenioids that diverged with ecotype. Power spectral analysis showed that the vagal influence produced comparable spectra among species of similar morphology and ecotype. Removal of autonomic tonus resulted in a remarkably similar intrinsic fH between species. Simultaneous measurements of cardio-respiratory variables and oxygen consumption (M(O(2))) were made in the benthic Trematomus bernacchii and cryopelagic Pagothenia borchgrevinki. The slopes of the relationship between fH and M(O(2)) were similar. Trematomus bernacchii, however, had a higher M(O(2)) for a given fH than P. borchgrevinki, and P. borchgrevinki required a two-fold larger range in fH to reach a similar maximum M(O(2)), suggesting that there is a difference in cardiovascular fitness between the two species. Overall, the data suggest that cardio-respiratory control in Antarctic nototheniids is largely determined by activity levels associated with a given ecotype. PMID- 20735578 TI - Metabolic depression and spleen and liver enlargement in juvenile Arctic charr Salvelinus alpinus exposed to chronic parasite infection. AB - The present study on the connection between standard metabolic rate (R(S)) and chronic Diplostomum spp. infection resulted in a decrease in R(S), and an enlargement in spleen and liver sizes in the infected juvenile Arctic charr Salvelinus alpinus compared to control fish. As splenic enlargement observed in infected fish was not due to condition-related changes in the spleen, it could most probably be explained by increased leucocyte synthesis. The higher liver masses in infected S. alpinus may have been related to disorders in energetic function, which could have had major effects on biochemical regulation by the liver. The proposed metabolic syndrome with a possible reduction in insulin sensitivity in tissues results in ineffective glucose and lipid metabolism and thus it is suggested that chronic Diplostomum infection in S. alpinus might not impose direct energetic costs, but it may weaken the efficiency of energy metabolism and thus lead to lowered R(S). PMID- 20735579 TI - Metabolic rate, growth and aggressiveness in three Atlantic salmon Salmo salar populations. AB - Standard metabolic rate (R(S)), specific growth rate (G) and aggressiveness were investigated in three Finnish populations of Atlantic salmon Salmo salar (Neva, Saimaa and Teno), which were reared in identical hatchery conditions. The populations differed in their geographical origin and native habitat. There was a significant difference between populations in R(S): the southernmost Neva population had higher values in R(S) than the northernmost Teno population. No difference was found in G or aggressiveness between the populations. G was found to have a significant positive association with aggressiveness and R(S) among the three populations, however, these results were not statistically significant after correction for multiple tests. There was no significant association between R(S) and aggressiveness. Higher metabolic rate of the most southern population Neva is suggested to be an adaptation to the more abundant food sources of the southern stream. PMID- 20735580 TI - Effect of Flavobacterium columnare inoculation, antibiotic treatments and resident bacteria on rainbow trout Oncorhynchus mykiss eyed egg survival and external membrane structure. AB - This study was conducted to evaluate the potential pathogenicity of the bacterium Flavobacterium columnare on rainbow trout Oncorhynchus mykiss eyed eggs. Survival to hatching was unaffected by the inclusion in the incubation water of either 300 colony-forming units (CFU) ml(-1) or 3000 CFU ml(-1) of F. columnare at either 10 or 12 degrees C in either McConaughy or Shasta strain eyed eggs. Bacterial numbers, obtained via scanning electron microscopy or culture, and external membrane morphology were also not significantly different among eggs receiving different concentrations of F. columnare. Initial F. columnare burdens were significantly and positively correlated to the presence of biofilm on the egg external membrane, and biofilm was in turn significantly correlated with increased membrane degradation. The use of either streptomycin or tetracyclin antibiotics significantly reduced bacterial numbers on McConaughy strain eggs, and more eggs survived to hatch in those dishes treated with antibiotics. PMID- 20735581 TI - Oxygen consumption, ammonia excretion and protein use in response to thermal changes in juvenile Atlantic salmon Salmo salar. AB - Experiments were designed to examine the effects of various temperature challenges on oxygen consumption and ammonia excretion rates and protein utilization in juvenile Atlantic salmon Salmo salar. Fish acclimated to 15 degrees C were acutely and abruptly exposed to either 20 or 25 degrees C for a period of 3 h. To simulate a more environmentally relevant temperature challenge, a third group of fish was exposed to a gradual increase in temperature from 15 to 20 degrees C over a period of 3 h (c. 1.7 degrees C h(-1)). Oxygen consumption and ammonia excretion rates were monitored before, during and after the temperature shift. From the ammonia excretion and oxygen consumption rates, protein utilization rates were calculated. Acute temperature changes (15-20 degrees C or 15-25 degrees C) caused large and immediate increases in the oxygen consumption rates. When the temperature was gradually changed (i.e. 1.7 degrees C h(-1)), however, the rates of oxygen consumption and ammonia excretion were only marginally altered. When fish were exposed to warmer temperatures (i.e. 15-20 degrees C or 15-25 degrees C) protein use generally remained at pre-exposure (15 degrees C) levels. A rapid transfer back to 15 degrees C (20-15 degrees C or 25 15 degrees C) generally increased protein use in S. salar. These results indicate that both the magnitude and the rate of temperature change are important in describing the physiological response in juvenile salmonids. PMID- 20735582 TI - Hatch-period-dependent early growth and survival of Pacific herring Clupea pallasii in Miyako Bay, Japan. AB - Considerable interannual variation in the abundance of larval and juvenile Pacific herring Clupea pallasii was detected in Miyako Bay, on the Pacific coast of northern Japan; abundances were high in 2001 and 2003 and low in 2000 and 2002. Hatch dates and growth rates for larval and juvenile survivors were estimated through otolith analysis. Water temperature and food availability were monitored on the spawning and nursery grounds in the inner part of the bay. The number of spawning females caught in nets set around the spawning ground was recorded during each spawning season (January to May) in 2000-2003. No correlation was found between the number of spawning females and the abundance of larvae and juveniles on the spawning and nursery grounds. The hatch dates of surviving larvae and juveniles were concentrated at the end of the spawning season in 2001 and in the middle of the season in 2003. The larvae experienced relatively high prey concentrations during the first-feeding period in 2001 but low concentrations in 2003. Survival of larvae during the first-feeding period may be a function of prey concentration as well as water temperature. In 2003, low water temperature would reduce starvation mortality during the first-feeding period. In contrast, unfavourable feeding conditions with higher temperatures during the first-feeding period seemed to result in low larval survival in 2000 and 2002. The 2001 larvae grew faster than those in 2003 because of the late hatch dates and the higher ambient temperatures that resulted. Temperature might be a major factor controlling growth rates of C. pallasii larvae in Miyako Bay. PMID- 20735583 TI - Migratory timing, marine survival and growth of anadromous brown trout Salmo trutta in the River Imsa, Norway. AB - The aim of the paper was to study sea migration, growth and survival of brown trout Salmo trutta of the River Imsa, 1976-2005. The migratory S. trutta were individually tagged and fish leaving or entering the river were monitored daily in traps located near the river mouth. The mean annual duration of the sea sojourn was 6-9 months for first-time migrants moving to sea between January and June. It was 8-18 months for those migrating to sea between July and December. Veteran migrants stayed 12 months or less at sea and most returned to the river in August. Early ascending fish stayed the longest in fresh water because most returned to sea in April to May. The day number of 50% cumulative smolt descent correlated negatively with mean water temperature in February to March and the February North Atlantic Oscillation index (NAOI). Mean annual sea growth during the first 2 years after smolting was higher for S. trutta spending the winter at sea than those wintering in the River Imsa. First year's sea growth was lower for S. trutta descending in spring than autumn. For first-time migrants, it correlated negatively with the February NAOI of the smolt year. Sea survival was higher for spring than autumn descending first-time migratory S. trutta with a maximum in May (14.9%). Number of anadromous S. trutta returning to the river increased linearly with the size of the cohort moving to sea, with no evidence of density-dependent sea mortality. Sea survival of S. trutta smolts moving to sea between January and June correlated positively both with the annual number of Atlantic Salmo salar smolts, the specific growth rate at sea, and time of seaward migration in spring. This is the first study indicating how environmental factors at the time of seaward migration influence the sea survival of S. trutta. PMID- 20735584 TI - Habitat use and dispersal of post-smolt sea trout Salmo trutta in a Scottish sea loch system. AB - Post-smolt anadromous brown trout Salmo trutta, sea trout, from two Scottish west coast rivers, the Balgy and Shieldaig, flowing into adjacent sea lochs were tracked simultaneously using arrays of moored acoustic receivers to determine dispersal patterns and loss rates. Fish tended to stay close to their natal rivers for the first 14 day after entering the sea, during which time about half the fish were lost to the study. Although initially the overall pattern of dispersal was similar for individual fish from both rivers, towards the end of the study the groups had converged into one of the loch basins. There were also pronounced individual differences in habitat use with all those fish detected for >42 days exhibiting different patterns of habitat use. Loss rates were similar between the two rivers despite differences in the range of air-breathing predators to which the fish were initially exposed. These findings suggest that any management of predators or other mortality agents should be targeted towards mouths of rivers during and immediately following smolt emigration. PMID- 20735585 TI - The relationship of oocyte diameter and incubation temperature to incubation time in temperate freshwater fish species. AB - Based on the analysis of six egg variables and incubation temperature of 65 temperate freshwater fish species, the possible relationships between oocyte diameter, incubation time and incubation temperature were reassessed and compared to the results obtained from marine fishes. Most freshwater species have eggs (mean +/-s.d. 2.19 +/- 1.52 mm) larger than marine species, that are chiefly demersal and develop stuck to various substrata, such as plants or rocks. A strong negative relationship was found between incubation time (t, days) and incubation temperature (T, degrees C): t = 186.23e(-0.197T) (r(2)= 0.87). A strong dependence of incubation time on oocyte diameter (O, mm) and incubation temperature was also found and was defined as: log(10)t= 3.002 + 0.599 log(10)O - 1.91 log(10) (T + 2), which explained 92% of the variance of the data set. Five major groups of species were defined based on the principal component analysis (PCA) of four quantitative variables. There were two distinct groups of salmonids, displaying demersal and non-adhesive eggs with a long incubation time at low temperature, the eggs of which required a high number of degree-days. There was a large group of species possessing small, mostly demersal and adhesive eggs developing at high temperature during a short period of time, and requiring a low number of degree-days. Between these two extremes, there was a fourth group displaying intermediate values and a fifth group including three species with large, adhesive and demersal eggs incubating at high temperatures during a short period of time. The burbot Lota lota displayed an unusual combination of variables compared to the remaining species in the data set. PMID- 20735586 TI - Reversals in two dextral flounder species, Microstomus achne and Cleisthenes pinetorum (Pleuronectida; Teleostei), from Japan. AB - Reversals are described in Microstomus achne (three specimens) and Cleisthenes pinetorum (one specimen) collected from the Pacific coast of northern Japan, being the first published records of reversals in these genera. PMID- 20735587 TI - Behaviour and performance of juvenile shortnose sturgeon Acipenser brevirostrum at different water velocities. AB - Critical swimming speeds (mean +/-s.e.) for juvenile shortnose sturgeon Acipenser brevirostrum were 34.4 cm s(-1)+/- 1.7 (2.18 +/- 0.09 body lengths, BL s(-1)). Swimming challenges at 10, 20 and 30 cm s(-1) revealed that juvenile A. brevirostrum are relatively poor swimmers, and that the fish did not significantly modify their swimming behaviour, although they spent more time substratum skimming (i.e. contact with flume floor) at 30 cm s(-1) relative to 10 cm s(-1). When present, these behavioural responses are probably related to morphological features, such as flattened rostrum, large pectoral fins, flattened body shape and heterocercal tail, and may be important to reduce the costs of swimming. PMID- 20735588 TI - The 'egg sandwich': a method for linking spatially resolved salmonid hatching rates with habitat variables in stream ecosystems. AB - This paper describes the development of the 'egg sandwich', a system for assessing stream substratum quality by linking measurements of depth-specific salmonid egg hatching success and physico-chemical water variables from the same sites within the interstitial zone. PMID- 20735589 TI - Post-release and pre-spawning behaviour of simulated escaped adult rainbow trout Oncorhynhus mykiss in Lake Ovre Fryken, Sweden. AB - Using radio telemetry, the present study simulated the escape of 48 adult rainbow trout Oncorhynchus mykiss from a net-cage fish farm in the Lake Ovre Fryken, Sweden. The post-release dispersal of O. mykiss was fast, showed long-range dispersal behaviour, low winter survival and lacked the ability to find suitable spawning habitats. Thus, the present study suggested that reproducing for the first time may be an obstacle to the establishment of escaped farmed O. mykiss. PMID- 20735590 TI - Latitudinal variation in egg size and number in anadromous masu salmon Oncorhynchus masou. AB - Latitudinal variation in egg size and number in anadromous masu salmon Oncorhynchus masou was examined. Relatively greater variation in egg size occurred among rivers than among females within rivers or within females. Egg size was generally greater and egg number generally lower at more northerly latitudes. PMID- 20735591 TI - Deep-diving behaviour of a whale shark Rhincodon typus during long-distance movement in the western Indian Ocean. AB - A whale shark Rhincodon typus satellite tagged off the coast of Mozambique showed a highly directional movement across the Mozambique Channel and around the southern tip of Madagascar, a minimum distance of 1200 km in 87 days. Dives to depths well into the mesopelagic and bathypelagic zones (1286 m maximum depth) were recorded in a bathymetrically non-constraining habitat. The water temperature range recorded during the fish's movement was 3.4-29.9 degrees C. PMID- 20735592 TI - Electronic tags reveal behaviour of captured and discarded fish. AB - Internally implanted data storage tags (DST) recording hydrostatic pressure (depth) and temperature in Atlantic cod Gadus morhua were used to track the behaviour of nine individuals during fishing operations. Gadus morhua showed identifiable and characteristic behavioural responses to different capture processes. In a unique observation, one fish survived being discarded and upon return to the seabed exhibited a cessation of activity comparable to observations on stressed fish under laboratory conditions. PMID- 20735597 TI - The effect of nest aggregation on the reproductive behaviour of the peacock blenny Salaria pavo. AB - The effect of nest aggregation in courtship behaviour was tested experimentally in an ecologically constrained, sex-role reversed population of the peacock blenny Salaria pavo. Mixed sex groups of eight males and eight females were tested in experimental tanks, containing eight potential nests either aggregated or dispersed. In the aggregated treatment, males spent more time inside their nests and monopolized other potential nests, causing a female-biased operational sex ratio (OSR). In the aggregated treatment, females also expressed more courtship behaviour. The results in general support the prediction that the aggregation of nests promotes male monopolization of potential nests, resulting in fewer nest-holding males and therefore a female-biased OSR that leads to the reversal of sex roles. PMID- 20735598 TI - Conspicuous behaviour of Fundulus heteroclitus associated with high digenean metacercariae gill abundances. AB - Fundulus heteroclitus from six sites throughout the Hackensack Meadowlands District in northern NJ, U.S.A., were examined. Differences in behaviour (surfacing, conspicuousness and activity) were compared to gill infection intensity. Fish from populations infected with >1500 digenean metacercariae of Ascocotyle phagicola diminuta and Echinochasmus schwartzi, spent significantly more time at the water surface and exhibited significantly more conspicuous behaviour (e.g. jerking) than fish from less parasitized populations. This more conspicuous behaviour has the potential to increase trophic transmission of the parasite to its definitive wading-bird host. PMID- 20735596 TI - Caspases: evolutionary aspects of their functions in vertebrates. AB - Caspases (cysteine-dependent aspartyl-specific protease) belong to a family of cysteine proteases that mediate proteolytic events indispensable for biological phenomena such as cell death and inflammation. The first caspase was identified as an executioner of apoptotic cell death in the worm Caenorhabditis elegans. Additionally, a large number of caspases have been identified in various animals from sponges to vertebrates. Caspases are thought to play a pivotal role in apoptosis as an evolutionarily conserved function; however, the number of caspases that can be identified is distinct for each species. This indicates that species-specific functions or diversification of physiological roles has been cultivated through caspase evolution. Furthermore, recent studies suggest that caspases are also involved in inflammation and cellular differentiation in mammals. This review highlights vertebrate caspases in their universal and divergent functions and provides insight into the physiological roles of these molecules in animals. PMID- 20735599 TI - Rice protein-concentrate meal as a potential dietary ingredient in practical diets for blackspot seabream Pagellus bogaraveo: a histological and enzymatic investigation. AB - Field and laboratory studies were conducted to evaluate the intestinal responses to partial replacement of fish meal with rice protein concentrate (RPC) in practical diets for blackspot seabream Pagellus bogaraveo. Two experimental diets were formulated to be isoproteic and isoenergetic with an increasing level of RPC (20 and 35%, respectively) and were tested against a fish meal-based control diet (RPC0). The diets showed similar features for growth performances and both intestinal histology and digestive enzymes. This study confirmed that RPC does not induce intestinal mucosa alterations in this fish. The dietary RPC supplement caused a significant increase in trypsin activity, whereas lipase activity was reduced. PMID- 20735600 TI - Establishment of dominance relationships in gilthead sea bream Sparus aurata juveniles during feeding: effects on feeding behaviour, feed utilization and fish health. AB - In gilthead sea bream Sparus aurata held in groups of two, five or 10 fish, social hierarchies were observed. Subordinate S. aurata were characterized by elevation of basal levels of plasma cortisol, together with a reduced immunological potential. Subordinate fish also showed lower feed intake, feed utilization and lower growth. Fatty acid composition was also affected by social status, with a lower content of saturated acids, oleic and eicosapentaenoic, in muscle and liver of fish considered as subordinate. Results show that social hierarchy acts as a stressor in S.aurata. PMID- 20735601 TI - Population variables and life-history characteristics of the alligator pipefish Syngnathoides biaculeatus, in Papua New Guinea. AB - Population structure and life-history variables of the widely distributed alligator pipefish Syngnathoides biaculeatus were characterized in Bootless Bay, Papua New Guinea over the course of 11 months. There was little evidence of seasonality with four focal populations showing no significant change in abundance. Similarly, the sex ratio remained 1:1 for all but 1 month. Reproductive males carrying eggs (148-278 mm in total length, L(T)) were found in all months. Brood size was significantly, positively related to male L(T) for newly laid broods only. Maximum observed brood size was 351 and mean +/-s.d. brood size was 238 +/- 57 for newly laid broods. Juveniles and males showed no change in mean L(T) over the year while slightly smaller females were captured in November 2006 and September 2007. Males were significantly longer than females so von Bertalanffy growth coefficients were estimated separately for each sex: males L(infinity)= 285 mm, K = 0.82 year(-1) and females L(infinity)= 261 mm, K = 1.10 year(-1). These estimates suggest that this species grows rapidly and has a short life span. In the context of growing concern about overexploitation of syngnathids, a rapid growth rate combined with year round reproductive activity suggests that the tropical S. biaculeatus may be relatively resilient with regard to fishing pressure. PMID- 20735602 TI - Reproductive biology and implications for management of the orange-spotted grouper Epinephelus coioides in the southern Arabian Gulf. AB - The reproductive biology of Epinephelus coioides was determined from the examination of 1455 individuals collected between July 2005 and June 2007 in the southern Arabian Gulf. Histological preparations of gonads indicated that males were either derived from a juvenile phase or the transition of postspawning females, confirming a diandric protogynous sexual pattern. The spawning season was well defined, occurring once a year during April and early May. Peaks in spawning occurred after the full and new moons and was completed within a single lunar cycle. The presence of mature males over the entire size and age range and the absence of inactive mature females during the spawning season suggested that the population was not constrained by sperm limitation. While specimens undergoing sexual transition were only observed in size and age ranges of 335-685 mm total length (L(T)) and 5-6 years, patterns in the proportion of males in size and age classes suggested that sex change occurred at a relatively constant rate after female maturation up to the maximum size (1002 mm L(T)) and age (11 years). Relationships between reproductive output and capacity with size and age indicated that conventional regulations that equate the mean size at first capture to sexual maturation are unsuitable for the management of E. coioides. The maximum age, small size and young age at sexual maturation (L(min)= 320 mm L(T), 2 years, for females and 242 mm L(T), 1 year, for males) conflict with the general pattern for large epinepheline groupers and may be a direct result of the intensive demersal fishery in the southern Arabian Gulf. PMID- 20735603 TI - Seasonal changes in antioxidant defence system of liver and gills of Salmo trutta caspius, Salmo trutta labrax and Salmo trutta macrostigma. AB - Seasonal changes in antioxidant enzyme activities (superoxide dismutase, SOD, EC 1.15.1.1; catalase, CAT, EC 1.11.1.16; glutathione peroxidase, GPx, EC 1.11.1.9; glutathione reductase, GR, EC 1.6.4.2; glucose-6-phosphate dehydrogenase, G6PD, EC 1.1.1.49 and glutathione S-transferase, GST, EC 1.5.1.18) and lipid peroxidation (LPO) levels of livers and gills of female Caspian trout Salmo trutta caspius, Black Sea trout Salmo trutta labrax and mountain trout Salmo trutta macrostigma were investigated. SOD, CAT, GPx, G6PD and GST activities were higher in liver compared to gills of all sub-species; concomitantly, the GR activity was also higher in the livers of S. t. caspius and S. t. labrax, but the reverse was seen in S. t. macrostigma. LPO levels were higher in the gills compared to the liver of all sub-species. There was no general trend in the seasonal changes in the gill antioxidant enzyme (AE) activities or LPO levels. Higher AE activities, however, were found in the liver of each sub-species during autumn, and this coincided with an increase in the gonado-somatic index. PMID- 20735604 TI - Depth distribution and biological characteristics of the European eel Anguilla anguilla in Lough Ennell, Ireland. AB - Using a longline survey, a total of 196 European eels Anguilla anguilla were collected at different depths in Lough Ennell (maximum depth 30 m), central Ireland. The catch per unit of effort of A. anguilla that were caught from 1 to 25 m depths was lowest at 0.5-5.0 m and greatest at the deepest depth range (22.5 25.0 m). Sub-samples of A. anguilla from depths of <15 m showed little or no difference in size, sex ratio, age, growth rate, condition factor, length-mass relationship, gonado-somatic index, fin index or eye index with fish from depths of >15 m. All fish examined were female yellow-phase A. anguilla that had ages from 7 to 20 years (mean +/-s.d. = 10.3 +/- 2.9 years), with growth rates from 24.0-60.8 mm year(-1) (mean +/-s.d. = 40.7 +/- 8.5 mm year(-1)). Variations in the growth rates were greater in the shallow group than that of the deep group. This study suggested that deeper regions are important feeding habitats for A. anguilla and that fish in this lake were growing moderately fast compared to similar habitats and areas in the species' range. PMID- 20735605 TI - Exposure to low concentrations of dissolved ammonia promotes growth rate in walleye Sander vitreus. AB - The objective of the current study was to examine whether sublethal (moderate) levels of dissolved ammonia may be beneficial to growth in juvenile walleye Sander vitreus (recent evidence in juvenile rainbow trout Oncorhynchus mykiss has shown significant increases in protein synthesis in the presence of moderately elevated concentrations of dissolved ammonia). Moderately elevated dissolved ammonia concentrations between 100 and 300 micromol l(-1) suppressed routine aerobic metabolic activity by 20% during acute trials (2 h), while promoting specific growth rate (>50%) and elevating whole body soluble protein content by 20% in the early stages (14-42 days) in chronic ammonia exposure experiments. Juvenile S. vitreus held at ammonia concentrations between 107.6 +/- 5.5 and 225.5 +/- 4.7 micromol l(-1) (mean +/-s.e.) grew significantly faster than control fish and significantly reduced plasma cortisol levels (<3 microg dl(-1)). Results from this study suggest that chronic exposure to moderate amounts of dissolved ammonia significantly increase growth rates in juvenile S. vitreus by increasing nitrogen accessible for supplementary protein deposition leading to somatic development. PMID- 20735606 TI - Transgenerational marking of marine fish larvae: stable-isotope retention, physiological effects and health issues. AB - This study examined the toxicological and physiological responses of a commercially important coral-reef grouper, Plectropomus leopardus (Serranidae), to injection of enriched stable-isotope barium chloride (BaCl(2)) solution. Thirty adult P. leopardus were subject to one of two (138)BaCl(2) injection treatment groups (corresponding to dosage rates of 2 and 4 mg (138)Ba kg(-1) body mass), and a control group in which fish were injected with 0.9% sodium chloride (NaCl) solution. Fish from each group were sampled at post-injection intervals of 48 h and 1, 3, 5 and 8 weeks, at which time blood and tissue samples were removed from each fish. Residual concentrations of Ba and (138)Ba:(137)Ba ratios were measured in muscle, gonad, liver and bone tissues of each experimental fish. Elevated Ba concentrations were detected in all treatment fish tissue samples within 48 h post injection. Residual Ba concentrations decreased throughout the remainder of the 8 week experimental period in all tissues except bone. The BaCl(2) injection had no significant effects on measured whole blood variables or on the plasma concentrations of steroid hormones. Enriched Ba stable isotopes can therefore be used at low dosages to mark larvae of commercially important marine fishes, without adverse effects on the health of the fishes or on humans who may consume them. PMID- 20735607 TI - A comparison of gut evacuation models for larval mackerel (Scomber scombrus) using serial photography. AB - A novel technique is described, using serial photography of the gut contents of transparent living larval fishes, to generate individual gut evacuation time series. This technique was applied to Atlantic mackerel Scomber scombrus larvae to compare three widely used models of gut evacuation: linear, exponential and square-root. Regression r(2) for the exponential model exceeded those for the linear and square root models in 20 of 21 time series, strongly supporting the exponential model. At the initial gut fullness for each time series, total gut evacuation rates calculated with the exponential model averaged 2.2 and 1.3 times greater than those calculated with the linear and square-root models, respectively, and would produce correspondingly higher estimates of feeding rates for field-collected larvae with similar levels of gut fullness. The results highlight the importance of choosing the appropriate evacuation model in feeding studies, particularly those intended to examine short-term changes in larval fish feeding rates, a contributing factor to the highly variable yearly recruitment of many marine fish species. PMID- 20735608 TI - Temperature, selective mortality and early growth in the short-lived clupeid Spratelloides gracilis. AB - Six cohorts of the silver-stripe round herring Spratelloides gracilis, a fast growing and short-lived tropical clupeid, were collected as juveniles and then as adults during austral summers from November to February in 1998-1999 and 1999 2000, using light traps in the Dampier Archipelago, Western Australia. Otolith analysis allowed backcalculation of size and growth rate at age to examine the relative influences of selective mortality and water temperature on early growth. Negative size-selective mortality and growth-selective mortality between the juvenile and the adult stages was found only in the cohort that was the smallest and slowest growing in the period immediately following hatching. Selective mortality preferentially removed members of this cohort that were smaller from age 0 to 15 days, and slower growing from 0 to 10 days, resulting in an elevation of size at age to, or even above, that of cohorts that had not undergone this process. Size and growth rate at 5 day age intervals in the first 20 days after hatching differed among cohorts within and between summers and were strongly and positively correlated (r(2)= 0.61-0.83) with water temperature. PMID- 20735609 TI - Effect of initial size on daily growth and survival in freshwater Chondrostoma nasus larvae: a field survey. AB - Effects of initial size on the growth and survival of a freshwater fish, Chondrostoma nasus, were tested in a field survey, where individually tagged larvae were introduced into a potential nursery habitat. Characteristics of individual daily growth trajectories were utilized as a basis to explain growth, as well as survival patterns, in relation to ontogeny. Initial size only affected growth rates during the larval phase. Survival patterns could not be explained solely based on size-selective mortality processes because prey-predator interactions played a major role as well. This is confirmed by the Lande-Arnold selection model because directional, as well as stabilizing gradients, showed significant values. Thus, for the 0+ year freshwater fish, inherited size specific effects were a significant advantage for growth performance and survival in early ontogeny. As fish grew older, however, other effects such as compensatory growth and prey-predator interactions apparently gained in importance. PMID- 20735610 TI - Ionic regulation and Na(+)-K(+)-ATPase activity in gills and kidney of the freshwater stingray Paratrygon aiereba living in white and blackwaters in the Amazon Basin. AB - During low-water period, freshwater stingray Paratrygon aiereba collected in the whitewater (WW) of the River Amazon showed higher urea content, osmolality, Na(+) and Cl(-) concentrations in plasma and perivisceral fluid than those caught in blackwater (BW) of the River Negro. Gills and kidney Na(+)-K(+)-ATPase activities were significantly lower in WW than in BW fish. The high level of kidney Na(+) K(+)-ATPase activity in P. aiereba may minimize ion loss and generate diluted solute-free urine in ion-poor BW environment. PMID- 20735611 TI - 'Global worming': first record of an epidemic of Triaenophorus crassus in a population of Arctic charr Salvelinus umbla. AB - In May 2005, an epidemic of the cestode Triaenophorus crassus occurred in the Salvelinus umbla population of Lake Grundlsee, an oligotrophic Austrian Alpine Lake. Based on catches with a standardized multi-mesh gillnet survey 53% of S. umbla were infected with up to 17 cysts of T. crassus per fish. This is the first documented record of an epidemic of this tapeworm in S. umbla. PMID- 20735612 TI - Stunted growth of pikeperch Sander lucioperca in Lake Sahajarvi, Finland. AB - Growth of pikeperch Sander lucioperca in the eutrophic and clay-turbid Lake Sahajarvi, Southern Finland, was extremely slow in comparison with other lakes at similar latitudes. The most important food item in July was phantom midge larvae Chaoborus flavicans for all sizes of S. lucioperca (239-423 mm total length L(T)), while later, in August and September, the diet of S. lucioperca (149-407 mm L(T)) consisted of small (30-100 mm L(T)) perch Perca fluviatilis, ruffe Gymnocephalus cernuus and roach Rutilus rutilus. PMID- 20735616 TI - The outflow tract of the heart in fishes: anatomy, genes and evolution. AB - A large number of congenital heart defects associated with mortality in humans are those that affect the cardiac outflow tract, and this provides a strong imperative to understand its development during embryogenesis. While there is wide phylogenetic variation in adult vertebrate heart morphology, recent work has demonstrated evolutionary conservation in the early processes of cardiogenesis, including that of the outflow tract. This, along with the utility and high reproductive potential of fish species such as Danio rerio, Oryzias latipes etc., suggests that fishes may provide ideal comparative biological models to facilitate a better understanding of this poorly understood region of the heart. In this review, the authors present the current understanding of both phylogeny and ontogeny of the cardiac outflow tract in fishes and examine how new molecular studies are informing the phylogenetic relationships and evolutionary trajectories that have been proposed. The authors also attempt to address some of the issues of nomenclature that confuse this area of research. PMID- 20735617 TI - Low variation but strong population structure in mitochondrial control region of the plains topminnow, Fundulus sciadicus. AB - The plains topminnow Fundulus sciadicus is a freshwater killifish endemic to the Great Plains of North America. Rising concerns for future viability of this species have prompted recent changes in its conservation status. In this study, the results of a range-wide population genetic survey based on the sequence of entire mitochondrial control region (CR) are presented. A total of 181 fish were collected from 11 sites in Nebraska and 10 sites in Missouri spanning the distribution range of the species. Seven polymorphic sites were found in the 966 base pairs of the CR, and only nine unique haplotypes were detected among all fish. Phylogenetic analysis and statistical parsimony networks identified two distinct clades. The first included fish in the Osage, Gasconade and Spring River drainages in Missouri, while the second included individuals from Nebraska and the Lamine River in Missouri, although the Lamine River is much closer to the other Missouri sites than to the Nebraska sites. Pair-wise F(ST) and average population distances indicated that populations from most drainages are genetically distinct, as 93% of the total molecular variance was attributed to among-drainage effects. Four sites within the main distributions of this species and a highly disjunct site from the south-western portion of the range are suggested as potential targets for conservation. PMID- 20735618 TI - The name of the father: conflict between Louis and Alexander Agassiz and the Embiotoca surfperch radiation. AB - The surfperch genus Embiotoca currently comprises two species, Embiotoca jacksoni, the black surfperch, and Embiotoca lateralis, the striped surfperch. Originally, however, Louis Agassiz described a third species in the genus Embiotoca, the rainbow surfperch, Embiotoca caryi. This latter name was changed by Louis' son, Alexander, to Hypsurus caryi, a name that remains valid. In this study, new molecular data (3545 bp of DNA from four mitochondrial and two nuclear DNA regions) indicated that the rainbow surfperch should be retained within the genus Embiotoca, a result consistent with recent morphological data. Adaptive radiation combined with sexual selection resulting in rapid morphological changes in the rainbow surfperch may have contributed to the conflicting position of this species. PMID- 20735619 TI - Evolutionary dynamics of transferrin in Notropis. AB - This study reports on the development of comparative data for the transferrin (TF) gene in cyprinid fishes, focusing on the genus Notropis. While previous studies have suggested varied patterns of adaptation influencing the diversity at this gene locus both within and among species, sequence data for (TF) in Notropis exhibit limited evidence for selection. However, there are significant effects of sequence variation associated with Notropis lutipinnis, suggesting some form of diversifying selection acting among populations of this species. Overall, the gene performs well as a second locus for phylogenetic and biogeographic inference and may help improve description of the pattern and the process of diversification in Notropis. PMID- 20735620 TI - Evidence of two contrasting brown trout Salmo trutta populations spatially separated in the River Borne (France) and shift in management towards conservation of the native lineage. AB - A multidisciplinary study was made of brown trout Salmo trutta in the Borne River, a typical fast-flowing mountain stream in the Northern French Alps, in the geographical range of the Mediterranean lineages (ML). Information on (1) the proportion of stocked fluoro-marked fish in the angling harvest, (2) the introgression of introduced DNA microsatellite alleles into the native gene pool and (3) the demography of the population in situ in autumn revealed two contrasting populations separated by a physical barrier to upstream migration. A native S. trutta population (c. 10 000 adults) lives downstream of the barrier and is characterized by a large frequency of ML alleles (82-97%) and high densities (43-55 fish 100 m(-2)). This population is maintained predominantly by natural recruitment of juveniles (51-82%). In contrast, the upstream population is characterized by a large frequency of Atlantic lineage (AL) alleles (78-100%) and low densities (1-2 fish 100 m(-2)) and appears to be maintained by restocking (90-100%). The origins of these sharply contrasting populations appear to reflect isolation by an impassable barrier, catastrophic flooding, a downstream gradient in water quality, stocking and fishing pressure. The native downstream population has been resilient to large sudden floods and to intensive stockings of domesticated AL fish. The results of this study justify a shift in management towards conservation and rehabilitation of the native population. PMID- 20735621 TI - Temporal effective size estimates of a managed walleye Sander vitreus population and implications for genetic-based management. AB - The goal of this research was to use the long-term fishery data set and DNA from archived scales of walleye Sander vitreus in Escanaba Lake, WI, U.S.A., to improve the understanding of the underlying mechanism(s) influencing genetic diversity in naturally recruiting populations. The introduced population of S. vitreus in Escanaba Lake has a low mean effective population size (N(E)) between 124.6 and 185.5 despite a mean census size (N(C)) of 4659 (N(E)/N(C)c. 0.04), suggesting an accelerated rate of genetic drift between 1952 and 2002. These values are smaller than the median N(E) range of several studies suggesting typical N(E)/N(C) ratios of 0.11-0.16 in a wide range of taxa. N(E) increased steadily during the past two sampled decades (1992 and 2002) and was consistent with a lowering of the variance in S. vitreus reproductive success, possibly linked to a large, sustained exploitation (mean 28%) rate. Variance in reproductive success is one of the most important factors influencing N(E) in species, like S. vitreus, which have a potential for large fecundities and large juvenile mortalities (type III survivorship). The N(B) estimates across six sequential cohorts (age classes of S. vitreus, assayed from 1994 to 1999) was consistent with estimates of N(E) reported for 1992-2002. These results, coupled with in-depth census and exploitation data, show that the genetic characteristics of Escanaba Lake S. vitreus have changed substantially and that management activities, such as supplemental stocking and harvest practices, have profoundly influenced the genetic dynamics of S. vitreus in this lake. PMID- 20735622 TI - Shallow genetic and morphological divergence among seaperches in the South Pacific (family Scorpaenidae; genus Helicolenus). AB - The phylogenetic relationships among populations of seaperch, Helicolenus spp., in the south-west Pacific were examined with mtDNA markers. Parts of the cytochrome b gene [459 base pair (bp)] and the control region (448 bp) were sequenced in 58 specimens from the south-west Pacific and four specimens of Helicolenus lengerichi from Chile. Only one clade was recognized in New Zealand coastal waters, despite a wide range of colour morphs. This clade also occurred in the mid Tasman Sea on the Norfolk Ridge and around Tasmania and Victoria. A second sympatric clade was identified around Tasmania and Victoria and to the west of New Zealand. A third allopatric clade was identified to the north of New Zealand and in deep water on the Chatham Rise and a fourth clade on the Foundation Seamounts and the Louisville Ridge. Helicolenus lengerichi from Chile formed a fifth clade. Assuming a molecular clock, the clades were estimated to have diverged c. 0.7-2.6 million years ago. Only two clades, around Tasmania and Victoria, were separated using morphology, colour (in live) and dorsal-fin soft ray counts and were confirmed as Helicolenus percoides and Helicolenus barathri. Two characters, orbit diameter and colour variation, previously used to identify two species in New Zealand waters were unreliable characters for species discrimination. Principle component analyses of 11 morphological measures from 67 individuals did not delineate the clades. A canonical discriminant analysis was able to separate four of the five clades, but mean discriminate probabilities were low (77.6%), except for the five Chilean specimens of H. lengerichi (100%). PMID- 20735623 TI - Mixed parentage in Neolamprologus pulcher groups. AB - Genetic data collected on co-operatively breeding Neolamprologus pulcher groups from Lake Tanganyika revealed mixed parentage in 80% of the groups examined. A case (1/11) of shared maternity was detected where a subordinate female bred alongside the dominant female in a social group. Extra-pair paternity was assigned to other dominant males who held their own social groups, but subordinate males were not found to father young in any group (0/9). PMID- 20735624 TI - Complete mitochondrial control region sequences indicate a distinct variety of brown trout Salmo trutta in the Aral Sea. AB - Complete sequencing of the mtDNA control region (CR) from five specimens of brown trout Salmo trutta from the Amu Darya River identified two novel haplotypes belonging to the Danubian lineage. This finding supports the long-standing hypothesis that brown trout in the Aral Sea represent a distinct genetic stock and also illustrates the benefits that complete sequencing of the CR can provide for elucidating phylogeographic relationships. PMID- 20735625 TI - Implications of climate change for the fishes of the British Isles. AB - Recent climatic change has been recorded across the globe. Although environmental change is a characteristic feature of life on Earth and has played a major role in the evolution and global distribution of biodiversity, predicted future rates of climatic change, especially in temperature, are such that they will exceed any that has occurred over recent geological time. Climate change is considered as a key threat to biodiversity and to the structure and function of ecosystems that may already be subject to significant anthropogenic stress. The current understanding of climate change and its likely consequences for the fishes of Britain and Ireland and the surrounding seas are reviewed through a series of case studies detailing the likely response of several marine, diadromous and freshwater fishes to climate change. Changes in climate, and in particular, temperature have and will continue to affect fish at all levels of biological organization: cellular, individual, population, species, community and ecosystem, influencing physiological and ecological processes in a number of direct, indirect and complex ways. The response of fishes and of other aquatic taxa will vary according to their tolerances and life stage and are complex and difficult to predict. Fishes may respond directly to climate-change-related shifts in environmental processes or indirectly to other influences, such as community level interactions with other taxa. However, the ability to adapt to the predicted changes in climate will vary between species and between habitats and there will be winners and losers. In marine habitats, recent changes in fish community structure will continue as fishes shift their distributions relative to their temperature preferences. This may lead to the loss of some economically important cold-adapted species such as Gadus morhua and Clupea harengus from some areas around Britain and Ireland, and the establishment of some new, warm-adapted species. Increased temperatures are likely to favour cool-adapted (e.g. Perca fluviatilis) and warm-adapted freshwater fishes (e.g. roach Rutilus rutilus and other cyprinids) whose distribution and reproductive success may currently be constrained by temperature rather than by cold-adapted species (e.g. salmonids). Species that occur in Britain and Ireland that are at the edge of their distribution will be most affected, both negatively and positively. Populations of conservation importance (e.g.Salvelinus alpinus and Coregonus spp.) may decline irreversibly. However, changes in food-web dynamics and physiological adaptation, for example because of climate change, may obscure or alter predicted responses. The residual inertia in climate systems is such that even a complete cessation in emissions would still leave fishes exposed to continued climate change for at least half a century. Hence, regardless of the success or failure of programmes aimed at curbing climate change, major changes in fish communities can be expected over the next 50 years with a concomitant need to adapt management strategies accordingly. PMID- 20735626 TI - Seasonal stability and spatial variability of parasites in Brazilian sandperch Pinguipes brasilianus from the Northern Argentine Sea: evidence for stock discrimination. AB - The use of parasites as biological tags allowed the identification of two stocks of Brazilian sandperch Pinguipes brasilianus, in the Bonaerense region of the Argentine Sea. A total of 156 adult specimens of P. brasilianus were examined for parasites. Temporal variability in parasite burdens was assessed from fish caught seasonally in coastal waters of two zones, south Bonaerense (during autumn and winter) and north Bonaerense (during summer). Additional data from a previous study, comprising P. brasilianus caught during spring in these two zones, as well as in two populations from north Patagonian gulfs were used for comparative analyses of spatial variability. A total of 14 193 metazoan parasites belonging to 19 species were found. Comparisons of seasonal variability in pooled samples and within each locality showed that locality effects exceeded seasonal ones, suggesting the possible existence of two discrete stocks in the Bonaerense region. These findings were strongly supported by discriminant analyses and comparisons of prevalence and abundance between zones, after pooling seasonal samples within each zone. Further evidence of the discreteness of both stocks was assessed by inclusion of samples from Patagonian gulfs in the discriminant analysis, confirming that their differences were at a inter-population level. The parasite species that contributed most to the separation of the samples were generally those identified as biological markers in previous studies. Differing oceanographic conditions are discussed as potential causes of inter-population variation of parasite burdens. PMID- 20735627 TI - Biochemical composition of a dominant detritivorous fish Prochilodus lineatus along pollution gradients in the Parana-Rio de la Plata Basin. AB - The biochemical composition of muscle, liver and stomach contents of a detritivorous fish Prochilodus lineatus was analysed and compared to settling particles and sediments along pollution gradients over 1500 km of the Rio de la Plata Basin to evaluate the effects of anthropogenic discharges in a detritus food chain. The stomach contents of P. lineatus collected in the polluted Metropolitan Buenos Aires coast were enriched in proteins, carbohydrates and lipids, similar to settling particulates collected in the sewer area, and two to five times higher than underlying sediments, supporting the interpretation that P. lineatus feeds on unconsolidated organic flocs freshly decanted from mixed industrial and sewage outfalls. Fish from Buenos Aires had consistently higher standard length (L(S)) and mass (M(T)) slopes (b = 3.5), condition indexes (K = 3.01 +/- 0.47, mean +/-s.d.) and muscle fat content (fat = 23.8 +/- 13.8% wet mass, mean +/-s.d.) relative to northern fish (b = 2.7, K = 2.22 +/- 0.39, fat = 3.4 +/- 3.2% wet mass, respectively), suggesting that sewage-derived organic matter was an enriched diet, which allowed an enhanced body mass gain and fat accumulation compared to organic-poor vegetal detritus in the north Parana area. Buenos Aires fish also showed higher hepato-somatic indices (mean +/-s.d. I(H) 1.41 +/- 0.49 v. 0.70 +/- 0.32, respectively), which correlated with their two to three orders of magnitude higher hydrocarbon and polychlorinated biphenyl (PCB) loads, suggesting an enhanced detoxifying metabolism. The northward migration of fatty P. lineatus was evidenced by the presence of clear outliers in the L(S) and M(T) relationship, K and fat content along the Parana River. PMID- 20735628 TI - Salinity effects on behavioural response to hypoxia in the non-native Mayan cichlid Cichlasoma urophthalmus from Florida Everglades wetlands. AB - This study quantified the hypoxia tolerance of the Mayan cichlid Cichlasoma urophthalmus over a range of salinities. The species was very tolerant of hypoxia, using aquatic surface respiration (ASR) and buccal bubble holding when oxygen tensions dropped to <20 mmHg (c. 1.0 mg l(-1)) and 6 mmHg, respectively. Salinity had little effect on the hypoxia tolerance of C. urophthalmus, except that bubble holding was more frequent at the higher salinities tested. Levels of aggression were greatest at the highest salinity. The ASR thresholds of C. urophthalmus were similar to native centrarchid sunfishes from the Everglades, however, aggression levels for C. uropthalmus were markedly higher. PMID- 20735629 TI - Sibling-size variation in brown trout Salmo trutta in relation to egg size and stream size. AB - Sibling-size variation (SSV), estimated as the coefficient of variation of egg size, was investigated for 13 populations of brown trout Salmo trutta. SSV was negatively correlated with mean egg size both at the population and individual levels. After correction for the effect of mean egg size, SSV was also negatively correlated with stream size. These results provide new information about how salmonid SSV can vary at different ecological scales (individual, population and region). The results are discussed in light of competing theories for explaining SSV: (1) the passive effect hypothesis, stating that egg size variation follows passively from selection on egg size and (2) the bet-hedging hypothesis, stating that high SSV is adaptive in unpredictable environments. PMID- 20735630 TI - Factors influencing movement behaviour and home range size in ide Leuciscus idus. AB - Seventeen individuals of ide Leuciscus idus were radio-tracked weekly from September 2003 to September 2004 in the River Elbe, Czech Republic, to examine migration patterns and the influence of environmental factors on their diurnal behaviour. Of the 10 environmental factors measured, L. idus were significantly influenced by turbidity, which increased diurnal movement and the home range size of the species. The peak of longitudinal movement occurred in the spring, indicating pre-spawning migration. Migrating fish moved downstream and later returned upstream to the vicinity of their original locations, displaying a homing behaviour. PMID- 20735631 TI - Combined effects of chemical and visual information in eliciting antipredator behaviour in juvenile Atlantic salmon Salmo salar. AB - Under natural conditions, both young-of-the-year (YOY; 0+ year) and parr (1+ year) Atlantic salmon Salmo salar exhibited strong antipredator behaviour (e.g. increase in latency to resume foraging) following the exposure to damage-released chemical alarm cues relative to a stream water control. Subsequent exposure to a novel visual stimulus had contrasting results. Parr increased their reactive distance to the visual stimulus if they had been previously exposed to a chemical alarm cue, whereas YOY did not. On the other hand, both YOY and parr took significantly longer to resume foraging when exposed to a visual stimulus if they had been previously exposed to a chemical alarm cue than control groups. While YOY and parr differed in the type and intensity of antipredator responses to both chemical and visual stimuli, perhaps due to differential costs and benefits associated with age, both used the chemical and the visual information in a combined manner. PMID- 20735632 TI - Reproduction of the blue-spotted maskray Neotrygon kuhlii (Myliobatoidei: Dasyatidae) in south-east Queensland, Australia. AB - This study examined the reproduction and population structure of the blue-spotted maskray Neotrygon kuhlii within Moreton Bay, a subtropical embayment in south east Queensland, Australia. Mean sizes at maturity were 314 mm disc width (W(D)) in females (n = 140, 115-465 mm W(D)) and 294 mm W(D) in males (n = 123, 129-381 mm W(D)). Female N. kuhlii had a synchronous annual reproductive cycle, with one litter of one to three pups (mean +/-s.d. 1.67 +/- 0.71) produced per year. Mating behaviours were observed in October and November, and ovulation occurred early in the Austral summer, overlapping with the start of embryonic development. Gestation took c. 4 months with parturition occurring in late February and March. Size at birth was 115-170 mm W(D). The population showed a significant female bias, particularly in larger size classes. Tagging studies produced a total recapture rate of 16.1% and indicated that N. kuhlii were site resident for up to 1081 days. PMID- 20735633 TI - Thermally induced phenotypic plasticity of swimming performance in European sea bass Dicentrarchus labrax juveniles. AB - The vulnerability of embryonic and larval stages of European sea bass Dicentrarchus labrax to environmental temperature and the longer-term consequences for the early juveniles was demonstrated. This phenotypic plasticity was highlighted by subjecting D. labrax at 15.2 +/- 0.3 or 20.0 +/- 0.4 degrees C (mean +/-s.d.) up to metamorphosis and then at the same temperature (18.5 +/- 0.7 degrees C). After 4-6 weeks at the same temperature, the measurement of critical swimming speed at four exercise temperatures (15, 20, 25 and 28 degrees C) showed a significantly higher swimming capacity in the fish initially reared at 15 degrees C than for fish initially reared at 20 degrees C. This performance was correlated with significant differences in the phenotype of red muscle. Thermally induced phenotypic plasticity was clearly demonstrated as an important mechanism controlling swimming performance in early juveniles of D. labrax. PMID- 20735634 TI - Physiological, energetic and behavioural correlates of successful fishway passage of adult sockeye salmon Oncorhynchus nerka in the Seton River, British Columbia. AB - Electromyogram (EMG) radio telemetry was used in conjunction with physiological biopsy to relate prior physiological condition and subsequent swimming energetics and behaviours to passage success of 13 wild adult sockeye salmon Oncorhynchus nerka at a vertical-slot fishway on the Seton River, British Columbia. At the time of capture, plasma lactate, glucose and cortisol levels indicated that fish were not exhibiting unusually high levels of physiological stress. Very few differences existed between successful and unsuccessful fish in body size, initial plasma physiology and energy state and mean swim speed and energy use during passage. Generally, fish did not employ burst swimming during successful or failed attempts at passage, indicating that failure was probably not related to metabolic acidosis. Plasma Na(+) concentration was significantly lower in unsuccessful fish (P < 0.05), which is suggestive of a depressed ionic state or a possible stress component, although values in all fish were within an expected range for migrant adult O. nerka. Nevertheless, six of 13 fish failed to reascend the fishway and remained in the tailrace of the dam for more than a day on average before moving downstream and away from the dam. During this time, fish were observed actively seeking a means of passage, suggesting that there may have been other, undetermined causes of passage failure. PMID- 20735635 TI - Redistribution of the geographical ranges of the Iberian cyprinid genus Pseudochondrostoma based on a phylogenetic analysis: implications for the historical rearrangements of the north-western Iberian drainages. AB - A new distribution range is proposed for Pseudochondrostoma polylepis and Pseudochondrostoma duriense based on the phylogeny of two nuclear and one mitochondrial gene sequences, with implications on the geographic history of the north-western Iberian drainages. PMID- 20735636 TI - Over-summering behaviour of Atlantic salmon Salmo salar returning to rivers in the Cromarty Firth, north-east Scotland. AB - In 2005, a high percentage (50%) of Atlantic salmon Salmo salar fitted with acoustic transmitters, which entered rivers in the Cromarty Firth area of north east Scotland, dropped back to the estuary and ascended adjacent rivers after 33 80 days of freshwater residence. Fish residing in non-natal rivers generate mixed stock fisheries, and movements of fish between rivers could increase the risk of disease transmission between catchments. PMID- 20735639 TI - Aerobic scope for activity in age 0 year Atlantic cod Gadus morhua. AB - Key components of swimming metabolism: standard metabolism (R(s)), active metabolism (R(a)) and absolute aerobic scope for activity (R(a)-R(s)) were determined for small age 0 year Atlantic cod Gadus morhua. Gadus morhua juveniles grew from 0.50 to 2.89 g wet body mass (M(WB)) over the experimental period of 100 days, and growth rates (G) ranged from 1.4 to 2.9% day(-1), which decreased with increasing size. Metabolic rates were recorded by measuring changes in oxygen consumption over time at different activity levels using modified Brett type respirometers designed to accommodate the small size and short swimming endurance of small fishes. Power performance relationships were established between oxygen consumption and swimming speed measurements were repeated for individual fish as each fish grew. Mass-specific standard metabolic rates (RsMWB 1) were calculated from the power performance relationships by extrapolating to zero swimming speed and decreased from 7.00 to 5.77 micromol O(2) g(-1) h(-1), mass-specific active metabolic rates (RaMWB-1) were calculated from extrapolation to maximum swimming speed (U(max)) and decreased from 26.18 to 14.35 micromol O(2) g(-1) h(-1) and mass-specific absolute scope for activity was calculated as the difference between active and standard metabolism (RaMWB-1-RsMWB-1) and decreased from 26.18 to 14.35 micromol O(2) g(-1) h(-1) as M(WB) increased. Small fish with low R(s) had bigger aerobic scopes but, as expected, R(s) was higher in smaller fish than larger fish. The measurements and results from this study are unique as R(s), R(a) and absolute aerobic scopes have not been previously determined for small age 0 year G. morhua. PMID- 20735640 TI - Does predation risk influence habitat use by northern redbelly dace Phoxinus eos at different spatial scales? AB - This study investigated the relationship between spatial variations in predation risk and abundance of northern redbelly dace Phoxinus eos at both macroscale (littoral v. pelagic zones) and microscale (structured v. open water habitats in the littoral zone) of Canadian Shield lakes. Minnow traps were placed in both structured and open water habitats in the littoral zone of 13 Canadian Shield lakes, and estimates of the relative predation risk of P. eos in both the pelagic and the littoral zones were obtained from tethering experiments. Results showed that (1) the mean abundance of P. eos in the littoral zone was positively correlated with the relative predation risk in the pelagic zone, (2) P. eos preferentially used structured over open water habitats in the littoral zone and (3) this preference was not related to the relative predation risk in the littoral zone but decreased as the relative predation risk increased in the pelagic zone. At the lake level, these results support the hypothesis that P. eos enter the littoral zone to avoid pelagic piscivores. At the littoral zone level, the results do not necessarily contradict the widely accepted view that P. eos preferentially use structured over open habitats to reduce their predation risk, but suggest that flexibility in antipredator tactics (e.g. shelter use v. shoaling) could explain the spatial distribution of P. eos between structured and open water habitats. PMID- 20735641 TI - Pre-winter lipid stores in young-of-year Atlantic salmon along a north-south gradient. AB - The pre-winter lipid stores of young-of-the-year (YOY, age 0 year) Atlantic salmon Salmo salar were analysed along a north-south gradient from c. 71 to 58 degrees N, with winter conditions ranging from >200 days of ice cover to no ice. The rivers sampled in Northern Norway represent some of the most northerly S. salar rivers. There was an increase in lipid content with increasing latitude, and mean lipid content (size adjusted to common mass) for YOY in northern rivers were almost three times higher: 0.035 g compared to 0.013 g in southern rivers. The relationship was not sensitive to variation in sampling time or variation in YOY body size. The lipid stores, however, varied markedly between rivers and also between neighbouring rivers, indicating different strategies or opportunities for pre-winter lipid storage both at latitudinal and local scales. PMID- 20735642 TI - Stream-floodplain connectivity and fish assemblage diversity in the Champlain Valley, Vermont, U.S.A. AB - To evaluate the influence of main channel-floodplain connectivity on fish assemblage diversity in floodplains associated with streams and small rivers, fish assemblages and habitat characteristics were surveyed at 24 stream reaches in the Champlain Valley of Vermont, U.S.A. Fish assemblages differed markedly between the main channel and the floodplain. Fish assemblage diversity was greatest at reaches that exhibited high floodplain connectivity. Whereas certain species inhabited only main channels or floodplains, others utilized both main channel and floodplain habitats. Both floodplain fish alpha-diversity and gamma diversity of the entire stream corridor were positively correlated with connectivity between the main channel and its floodplain. Consistent with these results, species turnover (as measured by beta-diversity) was negatively correlated with floodplain connectivity. Floodplains with waterbodies characterized by a wide range of water depths and turbidity levels exhibited high fish diversity. The results suggest that by separating rivers from their floodplains, incision and subsequent channel widening will have detrimental effects on multiple aspects of fish assemblage diversity across the stream floodplain ecosystem. PMID- 20735643 TI - Evaluation of a new semi-natural incubation technique for Atlantic salmon Salmo salar fry. AB - The incubation environment had a significant effect on fork length (L(F)) and body mass (M) of Atlantic salmon Salmo salar fry at the time of emergence. Fry that were incubated in a new incubator design, that mimics the conditions in a natural redd (the Bamberger-Box), achieved significantly greater and attained a significantly higher M than those reared in conventional hatchery troughs for control. Fewer fry from the Bamberger-Boxes had visible deformities compared with those from the hatchery troughs. Results were consistent for five consecutive seasons using both wild and domesticated broodstock from genetically different origins. Survival from the eyed embryo stage in the Bamberger-Boxes and hatchery troughs was >93% during normal climatic conditions. Only larvae reared in Bamberger-Boxes, however, survived abnormally high water temperatures during one test season. The results demonstrate that the Bamberger-Box is an effective alternative to the conventional incubation technology. PMID- 20735644 TI - Habitat and behaviour of yellowfin tuna Thunnus albacares in the Gulf of Mexico determined using pop-up satellite archival tags. AB - This study presents the first data on movement, habitat use and behaviour for yellowfin tuna Thunnus albacares in the Atlantic Basin. Six individuals were tracked in the Gulf of Mexico using pop-up satellite archival tags. Records up to 80 days in length were obtained, providing information on depth and temperature preferences as well as horizontal movements. Thunnus albacares in the Gulf of Mexico showed a strong preference for the mixed layer and thermocline, consistent with findings for this species in other ocean basins. Fish showed a diel pattern in depth distribution, remaining in surface and mixed layer waters at night and diving to deeper waters during the day. The vertical extent of T. albacares habitat appeared to be temperature limited, with fish generally avoiding waters that were >6 degrees C cooler than surface waters. The vertical and thermal habitat usage of T. albacares differs from that of bigeye Thunnus obesus and bluefin Thunnus thynnus, Thunnus orientalis and Thunnus maccoyii tunas. These results are consistent with the results of earlier studies conducted on T. albacares in other oceans. PMID- 20735645 TI - Secondary sexual characters and sperm traits in coho salmon Oncorhynchus kisutch. AB - A study was undertaken to examine secondary sexual characters (spawning colouration and overall body size) in relation to sperm metrics in one alternative reproductive tactic of coho salmon Oncorhynchus kisutch: large hooknose males that spawn in dominance-based hierarchies. Males with less intense red spawning colouration had higher sperm velocities than males with darker red spawning colouration. There was no relationship between male body size and sperm metrics. These results suggest that within an alternative reproductive tactic, variation in sperm competition intensity may select for a trade-off between investment in sexual colouration and sperm quality. PMID- 20735646 TI - Dietary medicinal plant extracts improve growth, immune activity and survival of tilapia Oreochromis mossambicus. AB - The effects of supplementing diets with acetone extract (1% w/w) from four medicinal plants (Bermuda grass Cynodon dactylon, H(1), beal Aegle marmelos, H(2), winter cherry Withania somnifera, H(3) and ginger Zingiber officinale, H(4)) on growth, the non-specific immune response and ability to resist pathogen infection in tilapia Oreochromis mossambicus were assessed. In addition, the antimicrobial properties of the extract were assessed against Vibrio alginolyticus, Vibrioparahaemolyticus, Vibrio mimicus, Vibrio campbelli, Vibrio vulnificus, Vibrio harveyi and Photobacterium damselae. Oreochromis mossambicus were fed 5% of their body mass per day for 45 days, and those fed the experimental diets showed a greater increase in mass (111-139%) over the 45 days compared to those that received the control diet (98%). The specific growth rate of O. mossambicus fed the four diets was also significantly greater (1.66-1.93%) than control (1.52%) diet-fed fish. The blood plasma chemistry analysis revealed that protein, albumin, globulin, cholesterol, glucose and triglyceride levels of experimental fish were significantly higher than that of control fish. Packed cell volume of the blood samples of experimental diet-fed fish was also significantly higher (34.16-37.95%) than control fish (33.0%). Leucocrit value, phagocytic index and lysozyme activity were enhanced in fish fed the plant extract-supplemented diets. The acetone extract of the plants inhibited growth of Vibrio spp. and P. damselae with extracts from W. somnifera showing maximum growth inhibition. A challenge test with V. vulnificus showed 100% mortality in O. mossambicus fed the control diet by day 15, whereas the fish fed the experimental diets registered only 63-80% mortality at the end of challenge experiment (30 days). The cumulative mortality index for the control group was 12,000, which was equated to 1.0% mortality, and accordingly, the lowest mortality of 0.35% was registered in H(4)-diet-fed group. PMID- 20735647 TI - Experiments to test if allopatric Salvelinus alpinus are suitable year-round hosts of Gyrodactylus salaris (Monogenea). AB - There has been an increased focus on Salvelinus alpinus as a potential long-term host to Gyrodactylus salaris and, here, both susceptibility to G. salaris and ability to sustain a parasite population seasonally, was tested using fry and parr of S. alpinus from the River Skibotnelva, northern Norway. Fry were highly susceptible. Gyrodactylus salaris survived on allopatric S. alpinus parr during the 5 month-long winter when water temperatures were c. 1 degrees C. Salvelinus alpinus fry also maintained a pulse of G. salaris infection for over 155 days from early May until autumn. Gyrodactylus salaris are thus able to reproduce and survive on S. alpinus for long periods and at low water temperatures. In spring, newly hatched fry of S. alpinus may serve as an important host to maintain a G. salaris metapopulation within a river system. The results suggest that S. alpinus are adequate long-term hosts of G. salaris independent of the presence of the co occurring highly susceptible S. salar. PMID- 20735648 TI - Biochemical and stress responses of rohu Labeo rohita and mrigal Cirrhinus mrigala in relation to acclimation temperatures. AB - The biochemical and stress responses of two Indian major carps, rohu Labeo rohita and mrigal Cirrhinus mrigala were studied after acclimating them to four preset temperatures (26, 31, 33 and 36 degrees C) for 30 days. The blood glucose and liver glycogen levels showed an inverse trend in both the species and were significantly different in L. rohita at higher temperatures. The decrease in the liver glycogen level of C. mrigala, however, was not significant. Plasma cortisol levels increased significantly whereas the ascorbic acid content in the brain and kidney of both the species decreased significantly with increasing temperatures. Total lipid content in the liver of both the species decreased significantly with increasing acclimation temperatures. The phospholipid concentration decreased in L. rohita with increasing acclimation temperatures, and in C. mrigala the values decreased up to 33 degrees C and increased at 36 degrees C. In C. mrigala, the cholesterol level decreased up to 33 degrees C and then increased at 36 degrees C, but the absolute value was lower in comparison to L. rohita. The cholesterol levels, however, were not significantly different in L. rohita. Triglycerides and free fatty acids concentrations decreased significantly with increasing acclimation temperatures in both the species. The present study indicates species specific metabolic responses of L. rohita and C. mrigala to thermal acclimation. PMID- 20735649 TI - A west Balkanian freshwater gobiid fish, Knipowitschia mrakovcici sp. nov. (Teleostei: Gobiidae). AB - A west Balkanian freshwater gobiid fish, Mrakovcic's goby, Knipowitschia mrakovcici, from the River Krka catchment, Croatia, hitherto a nomen nudum, is given a formal description, and the affinities of K. mrakovcici with congeners having reduced squamation are discussed. PMID- 20735650 TI - Seasonal patterns of winter flounder Pseudopleuronectes americanus abundance and reproductive condition on the New York Bight continental shelf. AB - To resolve varied and sometimes conflicting accounts of spawning and habitat characteristics for winter flounder Pseudopleuronectes americanus, seasonal patterns in abundance and reproductive condition were investigated in the New York Bight, near the southern edge of their current reproductive range. Fish were collected from trawl surveys on the inner continental shelf from October 2006 to October 2007. Pseudopleuronectes americanus were most abundant during January and April surveys, were rarely collected in August, with intermediate abundances in June and October. Measurements of fish condition [hepato-somatic index (I(H)), condition factor (K) and the per cent dry mass of muscle tissue (%M(D))] and reproductive condition [gonado-somatic index (I(G))] were determined to evaluate seasonal changes in energy accumulation and depletion and reproduction. Males and females had similar patterns in body and reproductive condition, although the magnitude of change was greater for females. I(H) values were highest during spring and early summer, suggesting increased feeding following spawning. K and %M(D) increased through spring and summer then declined in the autumn and winter concurrent with gonadal development. Gonads began developing in the autumn, and in January, I(G) values approached spawning levels, with many spent individuals collected in spring. Within these general patterns, however, there was a large degree of variability among individuals, and a few mature non-reproductive ('skipped spawning') females were observed. In the period after spawning, increased energy intake, indicated by increased I(H), may influence reproductive output since this energy is gradually transferred to the muscle and used for gonadal development in the forthcoming year. The occurrence of ripening individuals on the inner continental shelf in January suggests that these fish either rapidly move into estuaries to spawn by February-March or they remain on the inner shelf to spawn, or some combination of these. Future studies should evaluate these possibilities, as both estuarine and inner shelf habitats are potentially affected by activities such as dredging, sand dredging and wind energy development. PMID- 20735651 TI - Tethering induces increased stress artifacts in social fish species. AB - Behaviour of juvenile mulloway Argyrosomus japonicus were investigated under laboratory conditions to determine the efficacy of estimating predation mortality using tethering. The occurrence and duration of stressed behaviour was evaluated for individual A. japonicus that were hooked but untethered, hooked and tethered and unhooked and untethered (free swimming), both in schools and in isolation. Tethered and hooked treatments showed a significantly higher incidence and duration of stressed behaviour over controls, but stressed behaviour was lower for hooked but untethered fish in the presence of a school. Artifacts associated with elevated stress may reduce the reliability of estimates of relative predation derived from tethering data for schooling fishes. PMID- 20735652 TI - Influence of sea temperature and initial marine feeding on survival of Atlantic salmon Salmo salar post-smolts from the Rivers Orkla and Hals, Norway. AB - The abundance of returning adult Atlantic salmon Salmo salar, in the River Orkla in mid-norway (1 sea-winter, SW, fish) and River Hals in north Norway (1-3 SW fish), was tested against the early marine feeding and the seawater temperature experienced by their corresponding year classes of post-smolts immediately after entry into the Trondheimsfjord (Orkla smolts, 22 years of data) and Altafjord (Hals smolts, 17 years of data). In both river-fjord systems, there was a significant positive correlation between the abundance of returning S. salar and the mean seawater temperature at the time of smolts descending to the sea. The number of 1SW fish reported caught in River Orkla was positively correlated to the proportion of fish larvae in the post-smolt stomachs in Trondheimsfjord. The abundance of returning S.salar was, however, neither correlated to forage ratio (R(F)) nor other prey groups in post-smolt stomachs in the two fjord systems. In the Altafjord, the post-smolts fed mainly on pelagic fish larva (70-98%) and had a stable R(F) (0.009-0.023) over the 6 years analysed. In the Trondheimsfjord, however, there was a higher variation in R(F) (0.003-0.036), and pelagic fish larvae were dominant prey in only two (50 and 91%) of the 8 years analysed. These 2 years also showed the highest return rates of S. salar in River Orkla. These results demonstrate that the thermal conditions experienced by post-smolts during their early sea migration may be crucial for the subsequent return rate of adults after 1-3 years at sea. Pelagic marine fish larvae seem to be the preferred initial prey for S. salar post-smolts. As the annual variation in abundance of fish larvae is related to seawater temperature, it is proposed that seawater temperature at sea entry and the subsequent abundance of returning adult S. salar may be indirectly linked through variation in annual availability of pelagic fish larvae or other suitable food items in the early post-smolt phase. PMID- 20735653 TI - Effects of putative stressors in public aquaria on locomotor activity, metabolic rate and cortisol levels in the Mozambique tilapia Oreochromis mossambicus. AB - Mozambique tilapia Oreochromis mossambicus were housed individually during 7 days in a continuous flow-trough respirometry system and daily exposed to one of three treatments: (1) a series of knocks on the side of the aquarium, (2) a series of photo-flashes and (3) control group. Exposure to photo-flashes did not change locomotor activity but decreased both night-time and daytime oxygen consumption throughout the experiment. Knocking induced a short-lived increase in locomotor activity and tended to increase oxygen consumption, but this latter effect was not significant. Night-time oxygen consumption was not affected by knocking exposure. Cortisol levels assayed from fish-holding water collected at the end of the experiment were significantly lower in subjects exposed to photo-flashes than in subjects exposed to knocks or controls. Males did not respond differently than females to the treatments in any of the measurements taken. In summary, the data reported here suggest that exposure to repetitive photo-flashes, but not knocking, suppressed normal energy metabolism and cortisol levels. These effects were present hours to a half day after exposure to the flashes. PMID- 20735654 TI - Behavioural thermoregulation by subyearling fall (autumn) Chinook salmon Oncorhynchus tshawytscha in a reservoir. AB - This study investigated behavioural thermoregulation by subyearling fall (autumn) Chinook salmon Oncorhynchus tshawytscha in a reservoir on the Snake River, Washington, U.S.A. During the summer, temperatures in the reservoir varied from 23 degrees C on the surface to 11 degrees C at 14 m depth. Subyearlings implanted with temperature-sensing radio transmitters were released at the surface at temperatures >20 degrees C during three blocks of time in summer 2004. Vertical profiles were taken to measure temperature and depth use as the fish moved downstream over an average of 5.6-7.2 h and 6.0-13.8 km. The majority of the subyearlings maintained average body temperatures that differed from average vertical profile temperatures during most of the time they were tracked. The mean proportion of the time subyearlings tracked within the 16-20 degrees C temperature range was larger than the proportion of time this range was available, which confirmed temperature selection opposed to random use. The subyearlings selected a depth and temperature combination that allowed them to increase their exposure to temperatures of 16-20 degrees C when temperatures <16 and >20 degrees C were available at lower and higher positions in the water column. A portion of the subyearlings that selected a temperature c. 17.0 degrees C during the day, moved into warmer water at night coincident with an increase in downstream movement rate. Though subyearlings used temperatures outside of the 16 20 degrees C range part of the time, behavioural thermoregulation probably reduced the effects of intermittent exposure to suboptimal temperatures. By doing so, it might enhance growth opportunity and life-history diversity in the population of subyearlings studied. PMID- 20735655 TI - Effects of river flows on growth of redbreast sunfish Lepomis auritus (Centrarchidae) in Georgia rivers. AB - Effects of river discharge on growth of redbreast sunfish Lepomis auritus were investigated in nine rivers in Georgia, U.S.A. Fish were aged and annular total length increments (L(Tinc)) estimated from measurements from sectioned sagittal otoliths using the generalized regression model that held for the effects of decreasing L(Tinc) from annual age (X): L(Tinc)=b(o)-b(1)(X) +/-b(i)(D), where b(o), b(1) and b(i) were the regression coefficients for the intercept and slopes and D, discharge, was either a single or multiple measurements of annular or seasonal flow volume or variation in flow volume. For eight of nine rivers, higher or greater variation in flows from April to June was associated with greater L. auritus growth; in the last river, higher flows from January to March were associated with greater fish growth. Across all rivers, L. auritus growth increments were 22, 45 and 36% greater in a wet year v. a dry year at ages 1, 2 and 3 years, respectively. Based on the results of this study, increasing water withdrawals by an additional 30% in five Georgia rivers would reduce the predicted number of L. auritus recruiting to 203 mm (angler preferred size) by 19 62%. PMID- 20735656 TI - How normal is abnormal? Discrimination between deformations and natural variation in gonad morphology of European whitefish Coregonus lavaretus. AB - The gonad morphology of whitefish Coregonus lavaretus collected in Lake Thun, Switzerland, and two neighbouring lakes was assessed in order to differentiate between 'normal' and 'abnormal' character states of gonad morphology, which had been previously described in C. lavaretus from Lake Thun (constrictions, asymmetries, aplasia, compartmentations, fusions and hermaphroditism). In total, 4668 fish were collected and analysed using two complementary sampling schemes: (1) monthly samples of catches by the commercial fishermen and (2) samples of ripe spawners of all known 33 spawning sites of the three lakes. Considerable variation in gonad morphology in C. lavaretus populations of all lakes was found. Notably, all deviation types were observed in fish of all three lakes. Asymmetries and constrictions were frequent in all three lakes and showed systematic differences in frequency between the two sampling strategies. This indicates that asymmetries and constrictions represent to a large extent natural variation in gonad morphology of C. lavaretus and are also prone to considerable measurement error. In contrast, aplasia, fusions, compartmentations and hermaphroditism occurred predominantly in one C. lavaretus form of Lake Thun and in particular in populations spawning at great depths. This suggests that these deviation types are probably reliable indicators for gonad deformations and supports the interpretation that Lake Thun harbours a unique case of deformed gonads in C. lavaretus of yet unknown origin. PMID- 20735657 TI - The Arabian scad Trachurus indicus, a new Indo-Pacific species in the Mediterranean Sea. AB - The Arabian scad Trachurus indicus is recorded for the first time from the Mediterranean Sea (Iskenderun Bay, Turkey). The presence of this Indo-Pacific fish in the Mediterranean Sea is probably because of migration from the Red Sea via the Suez Canal. PMID- 20735658 TI - Digestive enzymes of eight Amazonian teleosts with different feeding habits. AB - The levels of amylase, maltase, lipase and alkaline protease from eight fish species of the Amazon were analysed. The enzyme levels are not related to fish feeding habits, reflecting their ever-changing habitats and their opportunistic feeding behaviour. PMID- 20735659 TI - Magnetic particles associated with the lateral line of the European eel Anguilla anguilla. AB - Magnetization measurements of the European eel Anguilla anguilla demonstrated the presence of magnetic material concentrated in the region of the mandibular canals of the lateral line system. The data suggest that the material is magnetite, has a size suitable for magnetoreception and is of biogenic origin. The presence of magnetic particles in the lateral line system is discussed in relation to their possible role in allowing the fish to orientate with respect to the geomagnetic field during their extensive oceanic spawning migrations. PMID- 20735660 TI - Short-term cycling of skin colouration in the blackspotted rockskipper Entomacrodus striatus. AB - Physiological colour change was investigated in the blackspotted rockskipper Entomacrodus striatus in Moorea, French Polynesia. Fish colour cycled with significant autocorrelation over the 30 min observation period and was not affected by observation temperature (27 and 31 degrees C). Cycling depended most on dark and yellow pigments (as assayed by separation of colours via software), and therefore, it was hypothesized that short-term cycling was driven by melanophores and xanthophores. PMID- 20735661 TI - River discharge drives recruitment success of the European bitterling Rhodeus amarus in a regulated river in central Europe. AB - A 15 year data set revealed that the abundance of 0+ year Rhodeus amarus in a regulated river was negatively associated with mean river discharge, while mean standard length was positively related to the cumulative number of degree-days > or =10 degrees C. Results are discussed in the context of the recent invasion success of R. amarus. PMID- 20735662 TI - Development of a flatbed passive integrated transponder antenna grid for continuous monitoring of fishes in natural streams. AB - This paper describes a flatbed antenna grid designed for continuous remote monitoring of fish tagged with 23 mm passive integrated transponder (PIT) tags in a natural stream with extensive spatial coverage. A range of applications of the system is presented. PMID- 20735663 TI - Differences in thermal tolerance in coexisting sexual and asexual mollies (Poecilia, Poeciliidae, Teleostei). AB - This study reports significant differences between the gynogenetic Amazon molly Poecilia formosa and one of its sperm hosts, and the sexual sailfin molly Poecilia latipinna in the critical temperatures at which individual fishes lost motion control. Based on these measurements, it is suggested that cold snaps occurring in winter, but not summer temperatures, can significantly change population composition of these closely related fishes by inflicting higher mortality on P. formosa. PMID- 20735664 TI - The first record of a natural hybrid of the roach Rutilus rutilus and nase Chondrostoma nasus in the Danube River Basin, Czech Republic: morphological, karyological and molecular characteristics. AB - Morphological (meristic and morphometric traits), karyological and molecular (microsatellites, cytochrome b) analyses were performed to characterize a hybrid of the roach Rutilus rutilus and nase Chondrostoma nasus. Meristic and morphometric traits were different between hybrid and both parental species. The number of chromosomes found in hybrid specimen indicated that this individual represents the post-F(1) generation of hybrids and the microsatellite analysis of the hybrid showed the presence of variants typical for R. rutilus and C. nasus. PMID- 20735665 TI - First record of Chilomycterus reticulatus (Osteichthyes: Diodontidae) in the Mediterranean Sea. AB - The spotfin burrfish Chilomycterus reticulatus (405 mm standard length) is recorded for the first time on the shoreline of the Mediterranean Sea. The adult specimen was found dried on a beach near the south Sardinian Sea (S. Antioco's Island). Photographs and morphometrics of the specimen are given. PMID- 20735666 TI - Scalloped hammerhead shark Sphyrna lewini, utilizes deep-water, hypoxic zone in the Gulf of California. AB - A hammerhead shark Sphyrna lewini tracked for 74 days revealed an expansion of the range of vertical distribution for the species to include the extreme hypoxic environment of the oxygen minimum layer in the Gulf of California. PMID- 20735667 TI - Comments on 'Significance of developmental expression of amphioxus Branchiostoma belcheri and zebrafish Danio rerio Hsd17b10 in biological and medical research'. AB - The reported data on the developmental expression of Hsd17b10 gene in Danio rerio is crucial to the utilization of the D. rerio embryo as an animal model for human developmental disorders caused either by mutations on HSD17B10 (formerly HADH2) or by defective expression of the gene. Related diseases were summarized, and it was noticed that hyperinsulinaemic hypoglycaemia is not linked to HSD17B10. This inherited disease is actually caused by a deletion in the HADH gene on chromosome 4. Moreover, it was found by a revision of the reported phylogenetic tree that hydroxyacyl-CoA dehydrogenase II or rather hydroxysteroid (17beta) dehydrogenase 10 (HSD10) of amphioxus Branchiostoma belcheri-occupies a transition position from HSD10 orthologs of invertebrates to those of vertebrates. PMID- 20735668 TI - Myogenesis and molecules - insights from zebrafish Danio rerio. AB - Myogenesis is a fundamental process governing the formation of muscle in multicellular organisms. Recent studies in zebrafish Danio rerio have described the molecular events occurring during embryonic morphogenesis and have thus greatly clarified this process, helping to distinguish between the events that give rise to fast v. slow muscle. Coupled with the well-known Hedgehog signalling cascade and a wide variety of cellular processes during early development, the continual research on D. rerio slow muscle precursors has provided novel insights into their cellular behaviours in this organism. Similarly, analyses on fast muscle precursors have provided knowledge of the behaviour of a sub-set of epitheloid cells residing in the anterior domain of somites. Additionally, the findings by various groups on the roles of several molecules in somitic myogenesis have been clarified in the past year. In this study, the authors briefly review the current trends in the field of research of D. rerio trunk myogenesis. PMID- 20735669 TI - Morphological and mtDNA sequence studies on three crucian carps (Carassius: Cyprinidae) including a new stock from the Ob River system, Kazakhstan. AB - Three morphologically and genetically distinct forms of the genus Carassius were collected from the Ob River system, Kazakhstan, Central Asia; Carassius carassius, Carassius gibelio gibelio and an unknown stock tentatively referred to as Carassius gibelio sub-species M. The last mentioned had 33-41 gill rakers, being intermediate between the other two forms (23-27 in C. carassius and 44-49 in C. g. gibelio), and five scales in the upper transverse series, less than in the others. It also had a relatively larger erythrocyte suggesting triploidy and an mtDNA haplotype distinct from all other known crucian carps. Comparative mtDNA phylogenetic analysis suggested that C. gibelio gibelio in the Ob River system was introduced from China and the Amur River, the same possibly being true for European C. gibelio gibelio based on published haplotypes. C. gibelio sub-species M is thought to be more widely distributed in central Asia, probably extending as far west as European Russia. PMID- 20735670 TI - Exploring factors shaping population genetic structure of the freshwater fish Sinocyclocheilus grahami (Teleostei, Cyprinidae). AB - Phylogeographical analyses on Sinocyclocheilus grahami samples from seven localities within the Lake Dianchi Basin in China were conducted to explore the main factors shaping population structure within this species. Phylogenetic and network analyses revealed two major clades in 24 mtDNA haplotypes. One clade included three haplotypes exclusively from samples of the lower basin and another clade encompassed other haplotypes from samples of the upper basin. The estimated divergence time between the two clades predated the river capture event connecting the lower and upper lake basin and thus supported geographical isolation as the main factor shaping genetic divergence between these two clades. Furthermore, analysis of molecular variance and pair-wise Phi(ST) distances revealed significant genetic differentiation within the upper basin. Mantel tests clearly supported patterns of differentiation arose purely as a result of isolation by distance. These results further highlight the importance of geographical isolation in shaping differentiation within this species. PMID- 20735671 TI - A comparison of complete mitochondrial genomes of silver carp Hypophthalmichthys molitrix and bighead carp Hypophthalmichthys nobilis: implications for their taxonomic relationship and phylogeny. AB - Based upon morphological characters, Silver carp Hypophthalmichthys molitrix and bighead carp Hypophthalmichthys nobilis (or Aristichthys nobilis) have been classified into either the same genus or two distinct genera. Consequently, the taxonomic relationship of the two species at the generic level remains equivocal. This issue is addressed by sequencing complete mitochondrial genomes of H. molitrix and H. nobilis, comparing their mitogenome organization, structure and sequence similarity, and conducting a comprehensive phylogenetic analysis of cyprinid species. As with other cyprinid fishes, the mitogenomes of the two species were structurally conserved, containing 37 genes including 13 protein coding genes, two ribosomal RNA genes, 22 transfer RNA (tRNAs) genes and a putative control region (D-loop). Sequence similarity between the two mitogenomes varied in different genes or regions, being highest in the tRNA genes (98.8%), lowest in the control region (89.4%) and intermediate in the protein-coding genes (94.2%). Analyses of the sequence comparison and phylogeny using concatenated protein sequences support the view that the two species belong to the genus Hypophthalmichthys. Further studies using nuclear markers and involving more closely related species, and the systematic combination of traditional biology and molecular biology are needed in order to confirm this conclusion. PMID- 20735672 TI - No barriers to gene flow among sympatric polychromatic 'small' Telmatherina antoniae from Lake Matano, Indonesia. AB - Genetic divergence, assortative courtship and intermale aggression were assessed between sympatric colour morphs of the sailfin silverside Telmatherina antoniae, endemic to Lake Matano, Indonesia. Genetic analysis using microsatellite markers showed no barriers to gene flow among T. antoniae primary colour morphs (blue and yellow) within sampling sites, sympatric populations or at the lake-wide level. Low but significant genetic differentiation was found between yellow morphs and mixed (blue-yellow) morphs. Behavioural surveys indicated assortative courtship does occur along primary colour lines; however, intermale aggression among paired and intruding male morphs appeared equal with respect to male colour. These observations support the hypothesis that males view other males as threats to their courtship regardless of their colour. This study supports recent work suggesting that assortative mating is present in T. antoniae despite a lack of reproductive isolation among colour morphs. PMID- 20735673 TI - Microsatellite variability of wild and farmed populations of Sparus aurata. AB - The genetic diversity of Greek wild and farmed populations of Sparus aurata was investigated using seven microsatellite markers. Selective breeding programmes and founder effects have altered the composition of farmed populations leading to significant population differentiation between wild and cultured populations and lower allelic richness in farmed populations. PMID- 20735674 TI - Anguillid eels. PMID- 20735675 TI - Oceanic migration and spawning of anguillid eels. AB - Many aspects of the life histories of anguillid eels have been revealed in recent decades, but the spawning migrations of their silver eels in the open ocean still remains poorly understood. This paper overviews what is known about the migration and spawning of anguillid species in the ocean. The factors that determine exactly when anguillid eels will begin their migrations are not known, although environmental influences such as lunar cycle, rainfall and river discharge seem to affect their patterns of movement as they migrate towards the ocean. Once in the ocean on their way to the spawning area, silver eels probably migrate in the upper few hundred metres, while reproductive maturation continues. Although involvement of a magnetic sense or olfactory cues seems probable, how they navigate or what routes they take are still a matter of speculation. There are few landmarks in the open ocean to define their spawning areas, other than oceanographic or geological features such as oceanic fronts or seamounts in some cases. Spawning of silver eels in the ocean has never been observed, but artificially matured eels of several species have exhibited similar spawning behaviours in the laboratory. Recent collections of mature adults and newly spawned preleptocephali in the spawning area of the Japanese eel Anguilla japonica have shown that spawning occurs during new moon periods in the North Equatorial Current region near the West Mariana Ridge. These data, however, show that the latitude of the spawning events can change among months and years depending on oceanographic conditions. Changes in spawning location of this and other anguillid species may affect their larval transport and survival, and appear to have the potential to influence recruitment success. A greater understanding of the spawning migration and the choice of spawning locations by silver eels is needed to help conserve declining anguillid species. PMID- 20735676 TI - Sympatric spawning of Anguilla marmorata and Anguilla japonica in the western North Pacific Ocean. AB - Extensive collections were made of the larvae of the temperate Japanese eel Anguilla japonica and the tropical giant mottled eel Anguilla marmorata in an overlapping area of the North Equatorial Current region of the western North Pacific Ocean. Collections of 189 A. marmorata and > 2500 A. japonica larvae during nine surveys from 1991 to 2007 showed that these two anguillid eels have similar spawning areas just west of the southern West Mariana Ridge. In July to August 2006 and August 2007, morphologically and genetically identified A. marmorata preleptocephali were mainly collected between 14.5-15 degrees N and 142 142.5 degrees E, where A. japonica preleptocephali were also caught in some of the same net tows. Fewer A. marmorata preleptocephali, however, were collected (n = 31) compared to those of A. japonica (n = c. 165), and fewer small larvae of A. marmorata were collected per tow than A. japonica (n = 1-10 and 1-294, respectively), suggesting relatively smaller spawning aggregations of A. marmorata. The distribution of preleptocephali and small larvae was wider in longitude in A. marmorata (131- 143 degrees E) than in A. japonica (137-143 degrees E), while the latitudinal range was almost the same (12-17 degrees N). Although spawning by these two species overlaps both spatially and temporally, the tropical eels of the North Pacific population of A. marmorata probably have a much longer spawning season with fewer spawners, at least in summer, and recruit to a much wider latitudinal range of growth habitats. PMID- 20735677 TI - Clues to the location of the spawning area and larval migration characteristics of Anguilla mossambica as inferred from otolith microstructural analyses. AB - The spawning area location and the larval migration characteristics of Anguilla mossambica were studied through the examination of early life-history traits (ELHT) inferred from otolith microstructural analyses of 122 glass A. mossambica collected along the eastern coast of Madagascar, in the south-western Indian Ocean. Backcalculated hatching dates of leptocephali that recruited between November 2005 and February 2006 suggested that spawning was continuous from June to November 2005, although individual migration duration periods were variable. Larvae that exhibited the highest daily otolith growth rates had the shortest leptocephalus durations and total length (L(T)) at recruitment, possibly because they reached the competence to metamorphose more rapidly and to recruit to fresh waters. Migration durations and L(T) increased from north to south on the Malagasy eastern coast, supporting earlier suggestions that A. mossambica spawns north-east of Madagascar, west of the Mascarene Ridge in the Indian Ocean. PMID- 20735678 TI - The effects of seasonal and interannual variability of oceanic structure in the western Pacific North Equatorial Current on larval transport of the Japanese eel Anguilla japonica. AB - As the North Equatorial Current (NEC)-bifurcation is known to be related to El Nino-Southern Oscillation (ENSO) events, the influence of the position of the NEC bifurcation on transport success of the larval Japanese eel Anguilla japonica was investigated. Using a Lagrangian modelling approach, larval transport was simulated and the relative influence of El Nino and La Nina events and the NEC bifurcation position on the success of particle transport analysed. The number of particles transported from the NEC to the Kuroshio tended to be lowest during El Nino years, and differences between La Nina and regular years were small. The transport success observed in simulations showed some relationships to annual A. japonica glass eel recruitment to Tanegashima Island over 1993 to 2001, but not in 2002. The study shows that particle tracking simulations can be used to improve knowledge of the oceanic migration of A. japonica but further studies are required, including comparisons with the effects on larval survival of fluctuations in temperature and food availability. PMID- 20735679 TI - Estimates of the mortality and the duration of the trans-Atlantic migration of European eel Anguilla anguilla leptocephali using a particle tracking model. AB - Using Lagrangian simulations, based on circulation models over three different hydroclimatic periods in the last 45 years in the North Atlantic Ocean, the trans Atlantic migration of the European eel Anguilla anguilla leptocephali was simulated via the passive drift of particles released in the spawning area. Three different behaviours were modelled: drifting at fixed depth, undergoing a vertical migration or choosing the fastest currents. Simulations included mortality hypotheses to estimate a realistic mean migration duration and relative survival of A. anguilla larvae. The mean migration duration was estimated as 21 months and the mortality rate as 3.8 per year, i.e. < 0.2% of A. anguilla larvae may typically survive the trans-Atlantic migration. PMID- 20735680 TI - Influence of water temperature and feeding regime on otolith growth in Anguilla japonica glass eels and elvers: does otolith growth cease at low temperatures? AB - The influences of water temperature and feeding regime on otolith growth in Anguilla japonica glass eels and elvers were investigated using individuals reared at 5, 10, 15, 20, 25 and 30 degrees C and in fed or unfed conditions at salinity 32 after their otoliths were marked with alizarin complexone (ALC). To eliminate the difficulty of observing the edges of otoliths with optical (OM) or scanning electron (SEM) microscopes, three to 10 individuals were sampled from each tank at 10, 20 and 30 days during the experiment and reared for an additional 10 days at 25 degrees C after their otoliths were marked a second time. Otolith growth and the number of increments were measured using both OM and SEM. Most A. japonica commenced feeding after 10 days at 20-30 degrees C or after 20 days at 15 degrees C, but no feeding occurred at 5 and 10 degrees C. No otolith growth occurred at 5 and 10 degrees C except in two individuals with minimal increment deposition at 10 degrees C. Otolith growth was proportional to water temperature within 15-25 degrees C and not different between 25 and 30 degrees C. At 15, 25 and 30 degrees C, the mean otolith growth rate in fed conditions was higher than in unfed conditions. The number of increments per day was significantly different among water temperatures (0.00-0.01 day(-1) at 5 and 10 degrees C, 0.43-0.48 day(-1) at 15 degrees C and 0.94-1.07 day(-1) at 20-30 degrees C). These results indicated that otolith growth in A. japonica glass eels and elvers was affected by temperature and ceased at < or =10 degrees C under experimental conditions. Hence, future studies analysing the otoliths of wild caught A. japonica glass eels and elvers need to carefully consider the water temperatures potentially experienced by the juveniles in the wild. PMID- 20735681 TI - Differential effects of origin and salinity rearing conditions on growth of glass eels of the American eel Anguilla rostrata: implications for stocking programmes. AB - In this study, growth patterns were monitored in controlled fresh and brackish water (BW) conditions for 7 months during Anguilla rostrata glass eel and elver stages. Null hypotheses tested were that there is no significant difference in growth between glass eels (1) collected from two geographic regions typified by different sex ratios, (2) reared in fresh and BW and (3) due to origin x salinity interactions. It was found that young A. rostrata from Mira River (MR, Cape Breton, Nova Scotia, Canada, an area where both males and females occur) grew faster than those from Grande-Riviere-Blanche (Quebec, Canada, an area where population are highly skewed towards females; 99-100%). Anguilla rostrata from both origins also grew faster in BW, although there was a trend for origin x salinity interactions whereby this effect was more pronounced for fish from the MR. The results support the hypothesis that salinity can influence growth patterns, as possibly can quantitative genetic differences between A. rostrata glass eels from different origins. Possible explanations for these patterns and potential consequences for sex determination and translocation programmes are discussed. PMID- 20735682 TI - Inter and intra-estuary variability in ingress, condition and settlement of the American eel Anguilla rostrata: implications for estimating and understanding recruitment. AB - The objective of this study was to quantify spatial and temporal variability of anguillid glass eel ingress within and between adjacent watersheds in order to help illuminate the mechanisms moderating annual recruitment. Because single fixed locations are often used to assess annual recruitment, the intra-annual dynamics of ingress across multiple sites often remains unresolved. To address this question, plankton nets and eel collectors were deployed weekly to synoptically quantify early stage Anguilla rostrata abundance at 12 sites across two New Jersey estuaries over an ingress season. Numbers of early-stage glass eels collected at the inlet mouths were moderately variable within and between estuaries over time and showed evidence for weak lunar phase and water temperature correlations. The relative condition of glass eels, although highly variable, declined significantly over the ingress season and indicated a tendency for lower condition A. rostrata to colonize sites in the lower estuary. Accumulations of glass eels and early-stage elvers retrieved from collectors (one to >1500 A. rostrata per collector) at lower estuary sites were highly variable over time, producing only weak correlations between estuaries. By way of contrast, development into late-stage elvers, coupled with the large-scale colonization of up-river sites, was highly synchronized between and within estuaries and contingent on water temperatures reaching c. 10-12 degrees C. Averaged over the ingress season, abundance estimates were remarkably consistent between paired sites across estuaries, indicating a low degree of interestuary variability. Within an estuary, however, abundance estimates varied considerably depending on location. These results and methodology have important implications for the planning and interpretation of early-stage anguillid eel surveys as well as the understanding of the dynamic nature of ingress and the spatial scales over which recruitment varies. PMID- 20735683 TI - Anguilla rostrata glass eel migration and recruitment in the estuary and Gulf of St Lawrence. AB - This study describes catches of Anguilla rostrata glass eels and associated oceanographic conditions in the St Lawrence Estuary and Gulf. Ichthyoplankton survey data suggest that they enter the Gulf primarily in May, migrate at the surface at night, and disperse broadly once they have passed Cabot Strait. They arrive in estuaries beginning at about mid-June and through the month of July. Migration extends west up to Quebec City, in the freshwater zone of the St Lawrence Estuary, 1000 km west of Cabot Strait. Anguilla rostrata glass eels travel between Cabot Strait and receiving estuaries at a straight-line ground speed of c. 10-15 km day(-1). Catches of fish per unit effort in estuaries in the St Lawrence system are much lower than those reported for the Atlantic coast of Canada. Low abundance of A. rostrata glass eels in the St Lawrence system may be due to cold surface temperatures during the migration period which decrease swimming capacity, long distances from the spawning ground to Cabot Strait and from Cabot Strait to the destination waters (especially the St Lawrence River), complex circulation patterns, and hypoxic conditions in bottom waters of the Laurentian Channel and the St Lawrence Estuary. PMID- 20735684 TI - Environmental determinism of year-to-year recruitment variability of European eel Anguilla anguilla in a small coastal catchment, the Fremur River, north-west France. AB - The influence of environmental factors (mainly the river flow) on the year-to year variability of European eel Anguilla anguilla fluvial recruitment in a small coastal catchment, the Fremur River (north-west France) was examined. A comprehensive survey of catches from fixed traps at two weirs located at 4.5 km (Pont es Omnes Dam) and 6.0 km (Bois Joli Dam) above the river mouth was carried out between 1997 and 2004. Young pigmented elvers (mean +/-s.d. total length, 133.7 +/- 29.6 mm) were recruited in eel-passes from February to October, but the main runs followed a modal curve from April to September with a peak centred in May to June. Catches varied greatly between years, from 381 to 26 765 elvers. For each trap, a positive linear relationship between monthly mean river flow that preceded the maximal intensity of captures and annual total catches was observed. These relationships explained 73.1% (P < 0.01) and 89.0% (P < 0.001) of the year to-year variability of the recruitment observed in the Pont es Omnes and Bois Joli traps respectively. A significant increase in river flow at the beginning of the migration peak would thus trigger a greater proportion of A. anguilla settled in the estuary and in the downstream zone of the Fremur River to begin their freshwater colonization. The physicochemical roles of changes in river discharge in stimulating upstream migration are discussed. It is concluded that fluvial recruitment in the Fremur River is mainly determined by environmental factors. PMID- 20735685 TI - Swimming activity and behaviour of European Anguilla anguilla glass eels in response to photoperiod and flow reversal and the role of energy status. AB - To better understand migratory divergences among Anguilla anguilla glass eels, the behaviour of individuals caught at the time of their estuary entrance was studied through their response to a light:dark cycle and then to both water current reversal and light:dark cycle. In a first experiment, fish moving with the flow in response to dusk (M(+) fish) and fish that had not exhibited any movement (M(-) fish) were distinguished. Anguilla anguilla from these two groups were then individually marked and their response to water current reversal compared. M(+) individuals mainly exhibited negative rheotaxis with a tidal periodicity, whereas positive rheotaxis was mainly exhibited by M(-) individuals. Thus, M(+)A. anguilla glass eels showing negative rheotaxis appear to have the strongest propensity to migrate, the converse applies to M(-) ones showing positive rheotaxis. A small percentage of individuals (5%) were hyperactive, alternately swimming with and against the current with almost no resting phase. These fish lost c. 2 mg wet mass day(-1), whereas individuals which were almost inactive lost c. 1 mg day(-1). Wet and dry mass changes in relation to activity levels were compared with previous experiments and it was concluded that A. anguilla glass eel energy status might be involved in differences in migratory tendencies but other factors that might be important are discussed. It is proposed that any decrease in A. anguilla glass eel energy stores associated with global warming might lead to an increase in the proportion of sedentary individuals and thus be involved in the decrease in the recruitment to freshwater habitats. PMID- 20735686 TI - Recruitment of Anguilla spp. glass eels in the Waikato River, New Zealand. Evidence of declining migrations? AB - The timing of Anguilla spp. glass eel recruitment into the Waikato River, North Island, New Zealand, was studied over a 2 year period (2004-2005). While glass eels of both the shortfin eel Anguilla australis and the endemic longfin eel Anguilla dieffenbachii were caught, the former comprised >97% of the species composition. There was a positive correlation of glass eel migrations with spring tides, with peak migration periods typically occurring within a few hours of the peak of high tide, and between 2 and 4 days after the day of spring tide. Both water temperature and discharge had significant inverse relationships with glass eel catches, with temperature explaining >30% of the variance in catch periodicity. Comparison of catch data 30 years apart showed that main migration periods appear to occur several weeks earlier today than previously. Reduced catch per unit effort and duration of runs from recent years' sampling (compared with the 1970s) indicate that a reduction in recruitment may also have occurred during this period, something recorded in other temperate species of Anguilla. PMID- 20735687 TI - Genetic composition of Atlantic and Mediterranean recruits of European eel Anguilla anguilla based on EST-linked microsatellite loci. AB - Anguilla anguilla glass eels arriving at two Mediterranean and two Atlantic sites were tested for differences in genetic composition between regions using a total of 23 microsatellite loci developed from an expressed sequence tag (EST) library. Hierarchical analysis of molecular variance indicated a non-significant difference between regions (Mediterranean v. Atlantic), which contrasted with the significant differences observed between samples within regions. The existence of a single spawning site for all A. anguilla individuals and extensive migration loop with great opportunity for mixing of individuals might explain the homogeneity in genetic composition found between regions. The observation of a (small-scale) pattern of genetic patchiness among intra-annual samples (arrival waves) within geographic regions does not conflict with the lack of (large-scale) geographic sub-structuring found between the Mediterranean and Atlantic regions, but most likely is a consequence of the strong dependence of A. anguilla on oceanic conditions in the Sargasso Sea that might result in a limited parental contribution to each spawning event. The comparison of Atlantic and Mediterranean A. anguilla glass eel recruits based on EST-linked microsatellite loci provides evidence supporting the hypothesis of panmixia A. anguilla across Europe. PMID- 20735688 TI - Morphological and genetic seasonal dynamics of European eel Anguilla anguilla recruitment in southern France. AB - The fine scale morphological and genetic dynamics of successive waves of Anguilla anguilla glass eel recruitment was studied over a 2 year period at a southern European Mediterranean location (Camargue, France) with continuous recruitment. Using morphometric [total length (L(T)), mass (M), condition (K) and pigmentation stage] as well as genetic (allozyme) markers, the aim was to test for the existence of temporally separated spawning groups and explore the relation between genetic variability and morphological heterogeneity of recruits. The results showed that L(T), M and K varied over time, being highest from the end of summer to winter (peaking in December) and lowest in spring (lowest in April). The pigmentation stages within monthly samples were highly diverse with a heterogeneous seasonal pattern. Allozyme data showed high genetic variability values within samples, but low genetic differentiation among samples (F(ST) = 0.003, P < 0.05). Pairwise comparisons between samples indicated a positive correlation between genetic differentiation and difference in recruitment time (days), with a marked increase in genetic differentiation around 250 days between monthly recruitment samples. Furthermore, genetic diversity increased with the number of pigmentation stages per sample and was negatively correlated with the North Atlantic Oscillation (NAO) index during the putative year of trans-oceanic migration. No correlation, however, was found between the level of multilocus heterozygosity (MLH) and growth variables. A situation of genetic patchiness with fluctuating parental contribution can thus best explain the patterns observed, although the existence of two separate spawning periods cannot be excluded. More discriminatory and sensitive genetic markers, such as (neutral and adaptive) microsatellites, could probably provide additional insights into the most probable hypothesis explaining the population structure and recruitment heterogeneity of A. anguilla. PMID- 20735689 TI - Morphological and meristic evaluation of the population structure of Anguilla marmorata across its range. AB - The population structure of the giant mottled eel Anguilla marmorata was evaluated using statistical analysis of 21 morphological characters among 13 representative localities across the Indo-Pacific region and as far north as Japan. There were no clear differences in 15 proportional and six vertebral characters using principal component analysis. The total number of vertebrae (N(V)) of A. marmorata at these localities had the widest variation among the morphological and meristic characters examined. A statistical analysis of the N(V) of 1238 specimens from 14 localities that included previously published data found significant differences among Micronesia, French Polynesia and other localities, and between localities in the North Pacific and South Pacific regions. Few differences were detected between specimens from the Indian Ocean and the North Pacific or South Pacific regions. The differences in N(V) among some regions and the population genetic studies of this species indicate that there are at least four populations of A. marmorata (North Pacific, Micronesia, Indian Ocean and South Pacific), which appear to include metapopulation structures in the Indian Ocean and South Pacific. This population structure is consistent with the ocean current patterns in each region and the evolution of migration loops of each spawning population. PMID- 20735690 TI - Salinity-linked growth in anguillid eels and the paradox of temperate-zone catadromy. AB - Temperate-zone anguillid eels use both saline (marine or brackish) and fresh waters during their continental phase, but use of fresh waters is paradoxical because on average these fishes grow more rapidly in saline than in fresh waters. Based on data from anguillid eels whose habitat-residency histories had been determined by Sr:Ca otolithometry, superiority of growth rates in saline water is much greater in American eels Anguilla rostrata in north-eastern North America (mean saline:fresh growth rate ratio 2.07) than in European Anguilla anguilla, Japanese Anguilla japonica and shortfinned Anguilla australis eels (range of mean ratios 1.12-1.14). Data from A. rostrata in the Hudson Estuary, U.S.A., and Prince Edward Island, Canada, were used to test adaptive explanations of catadromous migrations. The hypothesis that lower mortality in fresh water offsets faster growth in saline water was not supported because loss (mortality + emigration ) rates did not vary between saline and fresh zones of the Hudson Estuary. Hypotheses that anguillid eels move to fresh water to escape from larger anguillid eels in saline water or to evaluate habitat quality were not supported by size and age distributions. Catadromy in temperate-zone anguillid eels increases the diversity of occupied habitats and therefore lowers fitness variance caused by environmental fluctuations. Catadromy in temperate-zone anguillid eels could be due to natural selection for maximum geometric mean fitness which is sensitive to fitness variance. Temperate-zone catadromy might also be maladaptive, at least in local areas, due to shifts over time in selective pressures or to inability of panmictic genetic systems to adapt to local conditions. PMID- 20735691 TI - Piscivory and trophic position of Anguilla anguilla in two lakes: importance of macrozoobenthos density. AB - The feeding habits of the European eel Anguilla anguilla (>300 mm total length, L(T)) were compared in two lakes of different environmental state: Lake Grosser Vatersee (LGV), Germany (clear water, mesotrophic and submerged macrophytes), and Lake Vallum (LV), Denmark (turbid, eutrophic and no submerged macrophytes). The density of macrozoobenthos was higher in LV (3500 individuals m(-2)) than in LGV (1500 individuals m(-2)). The abundance of small prey fishes (40-99 mm L(T)) was highest in LV. In LV, A. anguilla fed on macrozoobenthos, in particular, chironomid larvae. In LGV, A. anguilla used fishes as the main food component. Stable isotope analyses confirmed the stomach contents dietary results. The estimated mean +/-s.d. trophic positions of A. anguilla in LGV (3.7 +/- 0.2) was one level higher than those of fish in LV (2.7 +/- 0.2). Based on these results, it is concluded that piscivory among A. anguilla was generally controlled by the density of macrozoobenthos. Stable isotope analysis further indicated that A. anguilla may act as integrators between benthic and pelagic food webs when density of insect larvae is low. PMID- 20735692 TI - Effects of commercial fishing and predation by cormorants on the Anguilla anguilla stock of a shallow eutrophic lake. AB - Mortality of eels Anguilla anguilla in a large shallow lake in France due to predation by the cormorant Phalacrocorax carbo was found to be moderate when compared to fishery catches over a 9 year period. The results show that, contrary to previous extrapolations made at the pan-European scale, P. carbo predation in shallow lakes is not invariably a major contributor to A. anguilla mortality, even in the presence of large colonies. PMID- 20735693 TI - Route choices, migration speeds and daily migration activity of European silver eels Anguilla anguilla in the River Rhine, north-west Europe. AB - Downstream migration of Anguilla anguilla silver eels was studied in the Lower Rhine, Germany, and the Rhine Delta, The Netherlands, in 2004-2006. Fish (n = 457) released near Cologne with implanted transponders were tracked by remote telemetry at 12 fixed detection locations distributed along the different possible migration routes to the North Sea. Relatively more A. anguilla migrated via the Waal than the Nederrijn, as would be expected from the ratio of river discharges at the bifurcation point at Pannerden. Downstream migration from the release site to Rhine-Xanten, close to the German-Dutch border, generally occurred in the autumn of the year of release but migration speeds tended to be low and variable and unaffected by maturation status or river discharge rates. Detection frequencies were not significantly related to discharge peaks or lunar cycles, but there was a minor detection peak 1-6 h after sunset. Between 2004 and 2009, 43% of the 457 A. anguilla released were never detected and of the 260 detected entering the Netherlands, 83 (32%) were detected escaping to the sea, 78 (94%) via the Nieuwe Waterweg and three (4%) and two (2%) via the sluices in the Haringvlietdam and Afsluitdijk, respectively. Possible causes of non-detections are discussed and it is suggested that many A. anguilla temporarily ceased migration, but that fishing mortality could have been important during passage through the Dutch parts of the Rhine. Practical implications of the results for predicting emigration routes, timings and magnitudes and use in management initiatives to promote escapement of A. anguilla silver eels to the sea are critically discussed. PMID- 20735694 TI - Effects of the swimbladder parasite Anguillicola crassus on the migration of European silver eels Anguilla anguilla in the Baltic Sea. AB - In a mark-recapture study in 2006, migrating European Anguilla anguilla silver eels were caught, tagged and released in the Baltic Sea and recaptures in commercial pound nets examined for possible effects on migration of infection with the swimbladder parasite Anguillicola crassus. The overall recapture rate was 36%. The prevalence of infection was lowest at the northernmost sampling site. There were no significant differences between infected and uninfected A. anguilla in condition indices, body fat content and estimated migration speeds. Parasite infection intensity levels were significantly negatively correlated with times and distances covered between release and recapture, but did not correlate with migration speed. It appears that more heavily infected A. anguilla were relatively more vulnerable to recapture in pound nets. It is hypothesized that parasite-induced damage to the swimbladder inhibited vertical migrations and infected A. anguilla tended to migrate in shallower coastal waters, relatively close to the shore. PMID- 20735696 TI - Size selectivity of fyke nets for European eel Anguilla anguilla. AB - Size selectivity of fyke nets for European eels Anguilla anguilla was investigated by reviewing the results of published experimental studies. A general size selectivity model was then derived that can be easily incorporated into demographic models to simulate population dynamics, assess and monitor abundance and length structure of eel stocks and forecast the consequences of different management options. PMID- 20735695 TI - Development of a key using morphological characters to distinguish south-western Indian Ocean anguillid glass eels. AB - Two morphological characters were examined in 4099 anguillid glass eels sampled in four south-western Indian Ocean islands, and resulting identifications were tested using genetic analysis. Distance between the origin of the dorsal and anal fins as related to total length and tail and caudal fin pigmentation enabled formulation of a useful field identification key, which was able to discriminate 4036 glass eels of the regional species Anguilla bicolor bicolor, Anguilla marmorata and Anguilla mossambica, and excluded the occurrence of Anguilla nebulosa labiata in the sample. PMID- 20735697 TI - All that wheezes is not asthma--Alternative findings at autopsy. AB - A number of questions must be asked before asthma can be accepted as a valid diagnosis: were the episodes of shortness of breath investigated? Are there changes at autopsy in keeping with asthma? Did asthma either contribute to the terminal episode, cause death, or was it coincidental? Finally, is it possible that other conditions may have accounted for the clinical manifestations? A review of files at FSSA over a 10-year period from 1999 to 2008 identified six cases where shortness of breath and/or wheezing had been incorrectly attributed to asthma. Five were due to pulmonary thromboembolism and one to multiple injuries. In the latter case, an irreducible, left-sided diaphragmatic hernia was present. There was no morphological evidence of asthma in any case. Autopsy examination may, therefore, be crucial in revealing other conditions that may have caused or contributed to episodic breathlessness that may have been incorrectly attributed to asthma. PMID- 20735698 TI - Comparison of age estimation in Japanese and Scandinavian teeth using amino acid racemization. AB - Racemization method is currently considered to be one of the most accurate methods for age estimation. There are many factors that affect racemization reaction velocities. We investigated ethnic differences in the racemization reaction velocities between Japanese and Scandinavian teeth. After a heating experiment, the Arrhenius equation was used to obtain a rate constant (k). Both groups presented almost identical velocities, indicating that there was no difference in the tooth racemization reaction between the two groups. However, because 14 of the 18 Scandinavian teeth had multiple roots, it is possible that accurate racemization rates of the teeth themselves were not reflected in the results. These findings reconfirm that the type of tooth selected is extremely important when evaluating age by racemization. PMID- 20735699 TI - Sex determination using the second cervical vertebra--A test of the method. AB - Sex is one of the critical questions addressed when unidentified skeletal remains are discovered in forensic or archeological contexts. Continuous testing and re evaluation of existing techniques is essential to improve accuracy and precision. The Wescott (J Forensic Sci 2000;45(2):462-6) method of sex determination from dimensions of the second cervical vertebra was blind-tested on 153 adult individuals from the Spitalfields documented collection of human skeletal remains held at the Natural History Museum, London. Significant sex differences were determined for all dimensions measured (independent two-sample t-test, p<0.05 0.001). The discriminant functions developed by Wescott were shown to have an overall accuracy of classification of 76.99%. Using stepwise discriminant analysis, a discriminant function based on the Spitalfields data correctly classified sex in 83.3% of individuals and was able to classify males and females with equal accuracy. Additional discriminant functions are presented for use in instances where preservation of the second cervical vertebra is poor. PMID- 20735700 TI - Toolmark identification of a mattock to a clod of soil from a grave. AB - At a recent bushland gravesite that contained a deceased male, a clod of soil displaying a striated toolmark was collected during the excavation of the grave. This clod was preserved, and the mark was cast using MikrosilTM. Shovels and a mattock, which had been discarded by the suspects, were subsequently found at another location. A toolmark comparison identified the hoe end of the mattock head as having produced the striated toolmark. PMID- 20735701 TI - The effects of body mass on cremation weight. AB - Cremains have become increasingly frequent in forensic contexts, while higher body mass in the general population has simultaneously made cremation a more cost effective mortuary practice. This study analyzed the relationship between body mass and bone mass, as reflected through cremation weight. Antemortem data were recorded for samples used in the multi-regional data set. Each was rendered through commercial crematoriums and reweighed postincineration. Pearson's correlation demonstrates clear association between body mass and cremation weight (r=0.56; p<0.0001). However, multiple linear regression revealed sex and age variables also have a significant relationship (t=7.198; t=-2.5, respectively). Regressed in conjunction, body mass, sex, and age contribute approximately 67% of all variation observed in cremation weight (r=0.668). Analysis of covariance indicates significant regional variation in body and cremation weight. Explanations include bone modification resulting from increased loading stress, as well as glucose intolerance and altered metabolic pathways related to obesity. PMID- 20735702 TI - Discriminating Hodgdon Pyrodex((r)) and Triple Seven((r)) using gas chromatography-mass spectrometry. AB - Pyrodex((r)) and Triple Seven((r)) are black powder substitutes that often find use as fillers in improvised explosive devices, such as pipe bombs. These propellants have essentially the same overall appearance and oxidizers, but different fuels. For example, Pyrodex((r)) contains sulfur, sodium benzoate, and dicyandiamide (DCDA), whereas Triple Seven((r)) lacks sulfur but also contains 3 nitrobenzoic acid. In this method, intact particles and postblast solid residues were reacted with bis(trimethylsilyl)trifluoroacetamide + 1% trimethylchlorosilane in acetonitrile for 30 min at 60 degrees C. The resultant trimethylsilyl derivatives of the organic fuels were then analyzed by gas chromatography-mass spectrometry. Each derivative was clearly resolved from other components, and high-quality mass spectra were obtained. In addition, characteristic fragments resulting from loss of a methyl radical from the molecular ion (m/z 163 for sulfur, m/z 171 for DCDA, m/z 179 for benzoic acid, and m/z 224 for nitrobenzoic acid) were able to be monitored. PMID- 20735703 TI - Estimation of gestational age from tooth germs: Biometric study of DentaScan images. AB - The few available studies on fetal age estimation concern very small samples, and statistical analysis is sometimes inadequate. In this survey, we used germs of deciduous teeth to estimate fetal age. Forty-nine fetuses and 40 mandibles were scanned, and observations and measurements were made on DentaScan images. After checking their repeatability and reproducibility (analysis of variance), we defined thresholds using Fisher's linear discriminant analysis to calculate the probability that a fetus was over or below a predefined age threshold. The forensic threshold which is of particular interest in France is 22 weeks amenorrhea. Relationships between fetal age and deciduous germ measurements were then sought by multiple linear regression. The thresholds gave very good results: 91.84% of good probability for the threshold of 22 weeks amenorrhea with no chance of error. The most precise age evaluation obtained nevertheless gave a range of +/-4.6 weeks amenorrhea, so greater accuracy is still needed. PMID- 20735704 TI - The conviction of Dr. Crippen: new forensic findings in a century-old murder. AB - Dr. Hawley Crippen was accused and convicted of murdering his wife in London in 1910. Key to the conviction was microscopic analysis of remains found in the Crippen's coal cellar, which were identified as Cora Crippen based on a scar she was said to have. Dr. Crippen was hanged, always proclaiming his innocence. In this study, genealogical research was used to locate maternal relatives of Cora Crippen, and their mitochondrial haplotypes were determined. Next, one of the pathology slides of the scar was obtained, DNA was isolated, and the haplotype was determined. That process was then repeated. Finally, both DNA isolates were assayed for repetitive elements on autosomes and repetitive elements specific to the Y chromosome. Based on the genealogical and mitochondrial DNA research, the tissue on the pathology slide used to convict Dr. Crippen was not that of Cora Crippen. Moreover, that tissue was male in origin. PMID- 20735705 TI - Statistical evidence for the similarity of the human dentition. AB - Recent scrutiny of forensic science has focused on unreliability of expert witness testimony when based on statements of individuality. In bitemark analysis, assumptions regarding uniqueness of the dentition have been based on use of the product rule while ignoring correlation and nonuniformity of dental arrangement. To examine the effect of these factors, two separate sets of scanned dental models (n=172 and n=344) were measured and statistically tested to determine match rates. Results were compared to those of a prior study. Seven and 16 matches of the six anterior lower teeth were found in the respective data sets. Correlations and nonuniform distributions of tooth positions were observed. Simulation tests were performed to verify results. Results indicate that given experimental measurement parameters, statements of dental uniqueness with respect to bitemark analysis in an open population are unsupportable and that use of the product rule is inappropriate. PMID- 20735706 TI - Advanced framework for digital forensic technologies and procedures. AB - Recent trends in global networks are leading toward service-oriented architectures and sensor networks. On one hand of the spectrum, this means deployment of services from numerous providers to form new service composites, and on the other hand this means emergence of Internet of things. Both these kinds belong to a plethora of realms and can be deployed in many ways, which will pose serious problems in cases of abuse. Consequently, both trends increase the need for new approaches to digital forensics that would furnish admissible evidence for litigation. Because technology alone is clearly not sufficient, it has to be adequately supported by appropriate investigative procedures, which have yet become a subject of an international consensus. This paper therefore provides appropriate a holistic framework to foster an internationally agreed upon approach in digital forensics along with necessary improvements. It is based on a top-down approach, starting with legal, continuing with organizational, and ending with technical issues. More precisely, the paper presents a new architectural technological solution that addresses the core forensic principles at its roots. It deploys so-called leveled message authentication codes and digital signatures to provide data integrity in a way that significantly eases forensic investigations into attacked systems in their operational state. Further, using a top-down approach a conceptual framework for forensics readiness is given, which provides levels of abstraction and procedural guides embellished with a process model that allow investigators perform routine investigations, without becoming overwhelmed by low-level details. As low-level details should not be left out, the framework is further evaluated to include these details to allow organizations to configure their systems for proactive collection and preservation of potential digital evidence in a structured manner. The main reason behind this approach is to stimulate efforts on an internationally agreed "template legislation," similarly to model law in the area of electronic commerce, which would enable harmonized national implementations in the area of digital forensics. PMID- 20735707 TI - Contributions from forensic imaging to the investigation of upper cervical fractures. AB - Injuries to the upper cervical spine (UCS) are common in traumatic deaths and postmortem computed tomography (PMCT) may contribute to the forensic investigation. This study presents PMCT in comparison with autopsy in the examination of UCS injury. Thirteen consecutive cases with UCS fracture and / or cranio-cervical dislocation were examined with PMCT and autopsy, and the findings were correlated. Neither of the techniques identified all UCS injuries. Fractures of atlas and axis were best visualized with PMCT whereas cranio-cervical dislocation was better identified during autopsy. Serious injuries were present after both high- and low-energy trauma. Medico-legal autopsy in combination with PMCT produced a thorough evaluation of UCS injuries. By combining these procedures detailed investigations, including accident reconstruction and injury pattern analysis, can be performed. This study supports the routine application of PMCT, as a supplement to the medico-legal autopsy of deaths with UCS injuries. PMID- 20735708 TI - Using gas chromatography with ion mobility spectrometry to resolve explosive compounds in the presence of interferents. AB - Ion mobility spectrometry (IMS) is a valued field detection technology because of its speed and high sensitivity, but IMS cannot easily resolve analytes of interest within mixtures. Coupling gas chromatography (GC) to IMS adds a separation capability to resolve complex matrices. A GC-IONSCAN(r) operated in IMS and GC/ IMS modes was evaluated with combinations of five explosives and four interferents. In 100 explosive/interferent combinations, IMS yielded 21 false positives while GC/ IMS substantially reduced the occurrence of false positives to one. In addition, the results indicate that through redesign or modification of the preconcentrator there would be significant advantages to using GC/ IMS, such as enhancement of the linear dynamic range (LDR) in some situations. By balancing sensitivity with LDR, GC/ IMS could prove to be a very advantageous tool when addressing real world complex mixture situations. PMID- 20735709 TI - Isolated pharmacomechanical thrombectomy for the management of chronic DVT. AB - Thrombo-reduction in the setting of deep vein thrombosis (DVT) to prevent the postthrombotic syndrome has not been traditionally managed by interventional cardiologists. We report a case series of successful chronic DVT management with pharmacomechanical thrombectomy utilizing the Trellis device. PMID- 20735710 TI - Transcatheter closure of patent foramen ovale (PFO) in patients with paradoxical embolism: procedural and follow-up results after implantation of the Amplatzer(r) occluder device. AB - BACKGROUND: Prevalence of patent foramen ovale (PFO) with detectable right-to left shunt is higher in young adults with transient ischemic attack (TIA) and stroke compared to the general population. So far, published series included different occluder systems, various indications and regimens of postprocedural anticoagulation. In our experience, occluder systems may be associated with an increased prevalence of thrombus formation, which has also reported by other groups. The aim of the present study was to evaluate the follow-up results after implantation of the Amplatzer(r) occluder in patients with PFO using a consistent anticoagulation regimen. METHODS AND RESULTS: One-hundred and fourteen patients with PFO (60 men; age: 47 +/- 13 years) and >=1 thromboembolic event were included. Other causes for embolism were excluded. PFO-closure was successful in all patients. All patients were treated with aspirin (100 mg/day) and clopidogrel (75 mg/day) for 6 months. TEE was repeated at a mean of 10.3 months. Mean clinical follow-up period was 18 +/- 9 months. After a mean of 10 months, no patient had either a significant residual shunt nor a suspected thrombus formation on the occluder. During follow-up, 5 patients suffered from neurological events (1 stroke, 2 TIAs, 2 epileptic seizures), though complete closure of the PFO was documented by TEE. One patient suffered from bleeding complications (upper GI-bleeding). CONCLUSION: Percutaneous closure of PFO in symptomatic patients by Amplatzer(r) occluder represents an effective therapy with a low incidence of peri-interventional complications and recurrent thromboembolism. Thrombus formations on the occluder system were not detected in this cohort. PMID- 20735711 TI - Coronary stents and the uptake of new medical devices in the German system of inpatient reimbursement. AB - OBJECTIVES: This study aims to analyze mechanisms for facilitating the uptake of new medical devices in the German system of hospital reimbursement, focusing on the example of coronary stents, including (1) trends in their coding, (2) associated diagnosis-related group (DRG) payments, (3) their integration in the German DRG (G-DRG) system, and (4) their diffusion within the inpatient sector. METHODS: Published and gray literature provide the basis for analyzing the system of hospital reimbursement. Data on coronary stents were obtained from various regulatory and government bodies and examined in a longitudinal fashion. RESULTS: Although German Procedure Classification (Operationen- und Prozedurenschlussel; OPS) codes were created for a range of stent technologies between 2004 and 2009, the regular system of G-DRG reimbursement does not distinguish between different stents by means of unique DRGs. Instead, supplementary payments or extrabudgetary payments are used to ensure that newer technologies are reimbursed adequately. The limitations of extrabudgetary payments restrict the use of some devices to a small proportion of patients. Data on the diffusion of different stents show that factors other than the reimbursement regime likely also play a role in the frequency with which certain technologies are used. Bare metal stents currently account for most stent implantation procedures in Germany, followed by drug eluting stents. CONCLUSION: The current system of G-DRG reimbursement and of extrabudgetary payments ensures that even the most recently developed technologies can be used in the German inpatient sector. Nevertheless, certain technologies may not be reaching the broad patient population. PMID- 20735712 TI - Off-label use of drug-eluting versus bare metal stents: a lesion-specific systematic review of long-term outcomes. AB - OBJECTIVE: The purpose of this systematic review was to evaluate differences in lesion-specific outcomes with the "off-label" use of drug-eluting stents (DES) versus bare metal stents (BMS). METHODS: MEDLINE, PubMed, the Cochrane databases, and other Web were searched for studies evaluating off-label use of DES and BMS with the same characteristics. Of 1,258 abstracts or manuscripts reviewed, 112 studies were included (total N = 23,438). Studies were excluded if patients received both types of stent or no stent; lesion type was unknown; lesion specific outcomes for >=6 months were unavailable; or <25 patients were enrolled. RESULTS: Overall mortality at 6-12 months was approximately 3% for BMS and DES for off-label use. Increase in mortality was greater from 6-12 months to 2 years with BMS than with DES (3.3%-9.1%; 2.8%-4.1%); however, rates were similar at 3 years (BMS: 18.8%; DES:15.3%). Myocardial Infarction rates were similar for both types at 6-12 months (BMS: 6.5%; DES: 6.0%). Overall rates of stent thrombosis were 1.8% and 1.7% for BMS and DES, respectively. Similar or slightly lower rates of stent thrombosis were seen for most lesion types, except higher rates for small vessels for BMS (5.2%) and true bifurcation for DES (3.3%). Rates of target lesion revascularization (TLR) were 7.5% for BMS and 19.6% for DES at 6-12 months. At 2-years TLR remained lower than DES. When the combined group was compared to registry data alone, similar values were seen. CONCLUSIONS: Rates of mortality, myocardial infarction (MI), and stent thrombosis were similar in patients receiving BMS or DES, while TLR rates were lower in DES patients. PMID- 20735713 TI - Site-specific differences in latency intervals during biventricular pacing: impact on paced QRS morphology and echo-optimized V-V interval. AB - OBJECTIVE: To investigate differences in latency intervals during right ventricular (RV) pacing and left ventricular (LV) pacing from the (postero )lateral cardiac vein in cardiac resynchronization therapy (CRT) patients and their relationship to echo-optimized interventricular (V-V) intervals and paced QRS morphology. METHODS: We recorded digital 12-lead electrocardiograms in 40 CRT patients during RV, LV, and biventricular pacing at three output settings. Stimulus-to-earliest QRS deflection (latency) intervals were measured in all leads. Echocardiographic atrioventricular (AV) and V-V optimization was performed using aortic velocity time integrals. RESULTS: Latency intervals were longer during LV (34 +/- 17, 29 +/- 15, 28 +/- 15 ms) versus RV apical pacing (17 +/- 8, 15 +/- 8, 13 +/- 7 ms) for threshold, threshold *3, and maximal output, respectively (P < 0.001), and shortened with increased stimulus strength (P < 0.05). The echo-optimized V-V interval was 58 +/- 31 ms in five of 40 (12%) patients with LV latency >= 40 ms compared to 29 +/- 20 ms in 35 patients with LV latency < 40 ms (P < 0.01). During simultaneous biventricular pacing, four of five (80%) patients with LV latency >= 40 ms exhibited a left bundle branch block (LBBB) pattern in lead V(1) compared to three of 35 (9%) patients with LV latency < 40 ms (P < 0.01). After optimization, all five patients with LV latency >= 40 ms registered a dominant R wave in lead V(1) . CONCLUSIONS: LV pacing from the lateral cardiac vein is associated with longer latency intervals than endocardial RV pacing. LV latency causes delayed LV activation and requires V-V interval adjustment to improve hemodynamic response to CRT. Patients with LV latency >= 40 ms most often display an LBBB pattern in lead V(1) during simultaneous biventricular pacing, but a right bundle branch block after V-V interval optimization. PMID- 20735714 TI - Sleep disordered breathing and arrhythmia burden in pacemaker recipients. AB - BACKGROUND: Sleep disordered breathing (SDB), a common condition among patients with permanent pacemaker (PM), is associated with greater incidence of cardiac arrhythmias. Scarce availability of sleep laboratories and the high costs of nocturnal-attended polysomnography limit the routine screening of patients with PM for SDB. We investigated whether a novel PM that utilizes variations in transthoracic impedance to record the fluctuations in breathing pattern and minute ventilation could be used to screen patients for SDB. METHODS: Twenty patients who underwent dual-chamber PM implantation were studied. The Talent 3 DR PM (SORIN Group Italy S.r.l., Milan, Italy) calculates apnea-hypopnea index (AHI) by computing minute ventilation signal derived from transthoracic impedance measurements. Within a month after PM implantation, an in-home respiratory monitoring was performed to evaluate the accuracy of PM-derived AHI. Patients were followed for mean +/- standard deviation, 487 +/- 166 days. The PM was checked at each follow-up visit to retrieve the information about recurrent arrhythmias. RESULTS: Eleven patients were diagnosed with SDB by an in-home respiratory monitoring. An AHI derived from an in-home respiratory monitoring was similar to pacemaker-derived AHI (27 +/- 14 vs 16 +/- 13 events/hour, P = 0.15). The cumulative incidence of cardiac arrhythmias, including atrial fibrillation, extrasystolic beats, sustained and nonsustained ventricular tachycardia, and supraventricular tachycardia was similar in patients with and without SDB. CONCLUSION: SDB is highly prevalent in patients with permanent pacemaker. Screening for SDB with Talent 3 DR PM may facilitate diagnosis and treatment of SDB. PMID- 20735715 TI - Transvenous extraction performance of expanded polytetrafluoroethylene covered ICD leads in comparison to traditional ICD leads in humans. AB - BACKGROUND: In the Endotak Reliance G defibrillating leads (Guidant Corporation, St. Paul, MN, USA), coils are covered with expanded polytetrafluoroethylene (ePTFE) to prevent tissue ingrowth. The aim of the study was to evaluate transvenous extraction performance, outcomes, and fibrotic adherences rate of ePTFE defibrillating leads in comparison to traditional non-ePTFE cardiac defibrillator (ICD) leads. METHODS: Seventeen consecutive ICD recipients (ePTFE Group A, 16 men, mean age 66 +/- 12 years) with 17 Endotak Reliance G dual-coil ICD leads (mean implantation time 23 +/- 26 months) underwent a transvenous removal procedure. They were compared with two control groups, including 20 Sprint Quattro 6944 (non-ePTFE Group B; Medtronic Inc., Minneapolis, MN, USA) and 36 Riata 1570 ICD leads (non-ePTFE Group C; St. Jude Medical, St. Paul, USA). The indication for lead extraction was local infection in 35 patients (48%), sepsis in 24 patients (33%), and lead malfunction in 14 patients (19%). RESULTS: In all groups, all leads were successfully and completely removed without major complications. Overall manual traction was effective in six patients (8%) and more effective in the ePTFE Group (29%) compared to Group B (0%) and Group C (3%) (P = 0.001). Sixty-seven leads (92%) required mechanical dilatation by the venous entry site approach, with a shorter extraction time in the ePTFE Group (5 +/- 11 min) compared to Group B (21 +/- 22 min) and Group C (16 +/- 22 min) (P = 0.003). ePTFE leads showed a lower rate of fibrotic adherences at the superior vena cava level (P = 0.01) without statistically significant differences in the other sites. CONCLUSIONS: ePTFE-covered leads may be removed more easily and quickly than non-ePTFE leads, requiring less frequently mechanical dilatation. PMID- 20735716 TI - Twin souls, Brothers, and Muses. PMID- 20735717 TI - Water consumption beliefs and practices in a rural Latino community: implications for fluoridation. AB - OBJECTIVE: Adequate fluoride exposure is especially important for those experiencing disproportionately high prevalence of dental caries, such as rural Latino farm-workers and their children. Water is an important source of fluoride. This qualitative study examined water consumption beliefs and practices among Latino parents of young children in a rural community. METHODS: Focus groups and open-ended in-depth interviews explored parents beliefs about tap water, beverage preferences, and knowledge of fluoride. A questionnaire documented socio demographic characteristics and water consumption practices. Qualitative analysis revealed how water-related beliefs, social and cultural context, and local environment shaped participants' water consumption. RESULTS: The vast majority of participants (n = 46) avoided drinking unfiltered tap water based on perceptions that it had poor taste, smell, and color, bolstered by a historically justified and collectively transmitted belief that the public water supply is unsafe. Water quality reports are not accessible to many community residents, all of whom use commercially bottled or filtered water for domestic consumption. Most participants had little knowledge of fluoride beyond a general sense it was beneficial. While most participants expressed willingness to drink fluoridated water, many emphatically stated that they would do so only if it tasted, looked, and smelled better and was demonstrated to be safe. CONCLUSIONS: Perceptions about water quality and safety have important implications for adequate fluoride exposure. For vulnerable populations, technical reports of water safety have not only to be believed and trusted but matched or superseded by experience before meaningful change will occur in people's water consumption habits. PMID- 20735718 TI - Estimated dietary fluoride intake for New Zealanders. AB - OBJECTIVES: Existing fluoride concentration and consumption data were used to estimate fluoride intakes from the diet and toothpaste use, for New Zealand subpopulations, to identify any population groups at risk of high-fluoride intake. METHODS: For each sub-population, two separate dietary intake estimates were made--one based on a non-fluoridated water supply (fluoride concentration of 0.1 mg/L), and the other based on a water supply fluoridated to a concentration of 1.0 mg/L. Fluoride concentration data were taken from historical surveys, while food consumption data were taken from national 24-hour dietary recall surveys or from simulated diets. RESULTS: Mean and 95th percentile estimations of dietary fluoride intake were well below the upper level of intake (UL), whether intakes were calculated on the basis of a non-fluoridated or fluoridated water supply. The use of fluoride-containing toothpastes provides additional fluoride intake. For many of the population groups considered, mean fluoride intakes were below the adequate intake (AI) level for caries protection, even after inclusion of the fluoride contribution from toothpaste. Intake of fluoride was driven by consumption of dietary staples (bread, potatoes),beverages (particularly tea, soft drinks, and beer), and the fluoride status of drinking water. CONCLUSION: Estimates of fluoride intake from the diet and toothpaste did not identify any groups at risk of exceeding the UL, with the exception of infants (6-12 months) living in areas with fluoridated water supplies and using high-fluoride toothpaste. In contrast, much of the adult population may be receiving insufficient fluoride for optimum caries protection from these sources, as represented by the AI. PMID- 20735719 TI - Socioeconomic inequalities in the distribution of dental caries in Brazilian preschool children. AB - OBJECTIVES: This study assessed the inequality in caries distribution and the association between socioeconomic indicators and caries experience of preschool children in a city in Brazil. METHODS: A cross-sectional study in a multistage random sample of 455, 1-5-year-old children was conducted on National Children's Vaccination Day in Santa Maria, Brazil. Calibrated examiners evaluated the prevalence of dental caries and parents provided information about several socioeconomic indicators by means of a semistructured questionnaire. Data were analyzed using Poisson regression model. RESULTS: The caries prevalence was 23.5 percent and the means for the decayed, missing and filled primary teeth was 0.8. A high inequality in the caries distribution with Gini coefficient of 0.8 and Significant Caries Index of 2.8 was observed. The oldest children, non-white, with mothers having low level of education and from low household income had the highest prevalence of dental caries. CONCLUSION: Socioeconomic factors are strong predictors for the inequality in caries distribution in Brazilian preschool children. PMID- 20735720 TI - Platelet apoptosis by cold-induced glycoprotein Ibalpha clustering. AB - BACKGROUND: Cold-storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibalpha-distribution indicative of receptor clustering and initiates thromboxane A(2) -formation. GPIbalpha is associated with 14-3-3 proteins, which contribute to GPIbalpha-signaling and in nucleated cells take part in apoptosis regulation. OBJECTIVES AND METHODS: We investigated whether GPIbalpha-clustering induces platelet apoptosis through 14-3-3 proteins during cold (4 h 0 degrees C)-rewarming (1 h 37 degrees C). RESULTS: During cold rewarming, 14-3-3 proteins associate with GPIbalpha and dissociate from Bad inducing Bad-dephosphorylation and activation. This initiates pro-apoptosis changes in Bax/Bcl-x(L) and Bax-translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase-9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N-acetyl-D-glucosamine (GN), which blocks GPIbalpha-clustering, and by O-sialoglycoprotein endopeptidase, which removes extracellular GPIbalpha. CONCLUSIONS: Cold-rewarming triggers apoptosis through a GN-sensitive GPIbalpha change indicative of receptor clustering. Attempts to improve platelet transfusion by cold-storage should focus on prevention of the GPIbalpha-change. PMID- 20735721 TI - Mechanisms of factor VIIa-catalyzed activation of factor VIII. AB - BACKGROUND: Factor (F)VIIa, complexed with tissue factor (TF), is a primary trigger of blood coagulation, and has extremely restricted substrate specificity. The complex catalyzes limited proteolysis of FVIII, but these mechanisms are poorly understood. OBJECTIVES: In the present study, we investigated the precise mechanisms of FVIIa/TF-catalyzed FVIII activation. RESULTS: FVIII activity increased ~4-fold within 30 s in the presence of FVIIa/TF, and then decreased to initial levels within 20 min. FVIIa (0.1 nM), at concentrations present physiologically in plasma, activated FVIII in the presence of TF, and this activation was more rapid than that induced by thrombin. The heavy chain (HCh) of FVIII was proteolyzed at Arg(740) and Arg(372) more rapidly by FVIIa/TF than by thrombin, consistent with the enhanced activation of FVIII. Cleavage at Arg(336) was evident at ~1 min, whilst little cleavage of the light chain (LCh) was observed. Cleavage of the HCh by FVIIa/TF was governed by the presence of the LCh. FVIII bound to Glu-Gly-Arg-active-site-modified FVIIa (K(d), ~0.8 nM) with a higher affinity for the HCh than for the LCh (K(d), 5.9 and 18.9 nm). Binding to the A2 domain was particularly evident. Von Willebrand factor (VWF) modestly inhibited FVIIa/TF-catalyzed FVIII activation, in keeping with the concept that VWF could moderate FVIIa/TF-mediated reactions. CONCLUSIONS: The results demonstrated that this activation mechanism was distinct from those mediated by thrombin, and indicated that FVIIa/TF functions through a 'priming' mechanism for the activation of FVIII in the initiation phase of coagulation. PMID- 20735722 TI - Safety of outpatient treatment in acute pulmonary embolism. AB - INTRODUCTION: Data regarding outpatient treatment of pulmonary embolism (PE) is scarce. This study evaluates the safety of outpatient management of acute PE. METHODS: This is a retrospective cohort study of consecutive patients presenting at the Ottawa Hospital with acute PE diagnosed between 1 January 2007 and 31 December 2008. PE was defined as an arterial filling defect on CTPA or a high probability V/Q scan. Patients were managed as outpatients if they were hemodynamically stable, did not require supplemental oxygenation and did not have contraindications to low-molecular-weight heparin therapy. RESULTS: In this cohort of 473 patients with acute PE, 260 (55.0%) were treated as outpatients and 213 (45.0%) were admitted to the hospital. The majority of the patients were admitted because of severe comorbidities (45.5%) or hypoxia (22.1%). No outpatient died of fatal PE during the 3-month follow-up period. At the end of follow-up, the overall mortality was 5.0% (95% CI, 2.7-8.4%). The rates of recurrent venous thromboembolism (VTE) in outpatients were 0.4% (95% CI, 0.0 2.1%) and 3.8% (95% CI, 1.9-7.0%) within 14 days and 3 months, respectively. The rates of major bleeding episodes were 0% (95% CI, 0-1.4%) and 1.5% (95% CI, 0.4 3.9%) within 14 days and 3 months, respectively. Four (1.5%) outpatients were admitted to the hospital within 14 days. CONCLUSIONS: A majority of patients with acute PE can be managed as outpatients with a low risk of mortality, recurrent VTE and major bleeding episodes. PMID- 20735723 TI - Characterization of duplication breakpoints in the factor VIII gene. AB - BACKGROUND: Hemophilia A is caused by a wide spectrum of different mutations in the factor (F)VIII gene (F8), leading to deficiencies in coagulation FVIII activity and thus resulting in an inefficient blood clotting cascade. Large duplications comprising whole exons of F8 have been published for only a few cases so far. RESULTS: In the current study, we characterized the exact breakpoints for a total of 10 exon-spanning duplications of F8, including six novel duplications in seven unrelated patients. Seven breakpoints were located within long interspersed nuclear elements (LINEs), whereas short interspersed nuclear elements (SINEs) of the Alu-repeat type were observed at both breakpoint sites in four of the 10 duplications. At three breakpoints, microhomologies of 2 bp and 3 bp each could be identified. CONCLUSIONS: Duplication breakpoints in F8 were shown to be located in repetitive elements, especially SINEs or LINEs, but also in unique sequences. In addition, microhomologies, particular genomic features or sequence motifs, contribute to the duplication formation mechanisms. PMID- 20735724 TI - Major bleeding as a predictor of mortality in patients with venous thromboembolism: findings from the RIETE Registry. PMID- 20735725 TI - Risk of venous thrombosis in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A polymorphisms. AB - BACKGROUND: Pregnancy is associated with a 10-fold increased risk of venous thrombosis (VT), with different risk profiles for the antenatal and postnatal periods. The purpose of this study was to assess the risk of pregnancy-related VT associated with the factor (F)V Leiden and prothrombin gene G20210A polymorphisms. MATERIALS AND METHODS: The study comprised 377,155 women with 613,232 pregnancies at 18 Norwegian hospitals from 1 January 1990 to 31 December 2003. Of a total 559 cases with a validated first lifetime diagnosis of VT in pregnancy or within 14 weeks postpartum, and 1229 controls naive for VT, 313 cases and 353 controls donated biological material. RESULTS: The odds ratios for VT during pregnancy or puerperium were 5.0 [95% confidence interval (CI) 3.1-8.3] and 9.4 (95% CI 2.1-42.4) for heterozygous carriers of the FV Leiden and the prothrombin gene polymorphisms, respectively. All homozygous carriers of the FV Leiden polymorphism (n = 8) and the prothrombin polymorphism (n = 1) developed VT, indicating a very high risk of VT. We estimated that pregnancy-related VT occurred in 1.1/1000 non-carriers, in 5.4/1000 heterozygous carriers of the FV Leiden polymorphism, and in 9.4/1000 heterozygous carriers of the prothrombin polymorphism. To avoid one VT, the number of pregnant women needed to be screened for these two polymorphisms and the number needed to be given thromboprophylaxis were 2015 and 157, respectively. CONCLUSIONS: Although the relative risk for VT during pregnancy and after delivery was increased among carriers of the FV Leiden and the prothrombin polymorphisms, the overall probability for pregnancy-related VT was low. PMID- 20735726 TI - Plasminogen activator inhibitor type-1 is an independent marker of metabolic disorders in young adults born small for gestational age. AB - BACKGROUND: Metabolic syndrome (MS) has been associated with being born small for gestational age (SGA). In epidemiological studies plasminogen activator inhibitor type-1 (PAI-1) levels have been associated with MS. Few studies have examined this association in subjects born SGA. PATIENTS AND METHODS: Five hundred and fifty-seven SGA adults (birth weight < 10th percentile) were compared with 671 subjects with a birth weight between the 25th and 75th percentiles (control group). MS was defined using the World Health Organization (WHO) definition. Active PAI-1 was measured on citrated plasma with bio-immunoassay. RESULTS: MS was more prevalent in the SGA group (8.7%) than in the control group (5.5%; P = 0.03). In both groups, PAI-1 concentrations were significantly correlated with waist circumference, plasma triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR) and associated with male sex and MS. PAI-1 concentrations were significantly increased in the SGA group (12.2 +/- 21.2 vs. 10.0 +/- 13.5 IU mL-1, P = 0.03) and this remained after adjustment of metabolic variables (P = 0.009). PAI-1 concentrations above 4.9 IU mL-1 (= median of PAI-1 concentration in the control group) were present in 94% of the subjects with MS. Moreover, the adjusted odds ratio (OR) for having elevated PAI-1 was 1.48 (1.08; 1.95) in the SGA group in comparison with the control group (P = 0.005). CONCLUSIONS: PAI-1 plasma concentrations were significantly increased in SGA subjects independently of MS. These data suggest that elevation of PAI-1 concentrations might be an indication of an abnormal secretion at the level of the adipose tissue, endothelial cells or liver and implicated in metabolic disorders reported in SGA subjects. PMID- 20735727 TI - Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. AB - BACKGROUND: Warfarin, an antagonist of vitamin K, is an oral coumarin anticoagulant widely used to control and prevent thromboembolic disorders. Warfarin is clinically available as a racemic mixture of R- and S-warfarin. The S enantiomer has three to five times greater anticoagulation potency than its optical congener. Recently, vitamin K2 function has been proposed via the pregnane X receptor (PXR) in osteocytes. PXR acts as a xenobiotic sensor that controls expression of many genes involved in drug/xenobiotic metabolic clearance. OBJECTIVE: The aim was to examine whether enantiomers of warfarin stereoselectively interact with PXR to up-regulate main drug/xenobiotic metabolizing enzymes of the cytochrome P450 superfamily. METHODS: Interactions of warfarin enantiomers with PXR were tested by gene reporter assays and time resolved fluorescence resonance energy transfer technology (TR-FRET) ligand binding assay. Up-regulation of PXR-target gene mRNAs by warfarin enantiomers was studied using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in primary human hepatocytes. RESULTS: We found that R-warfarin interacts with the PXR nuclear receptor. Consistently, R-warfarin significantly induced CYP3A4 and CYP2C9 mRNAs in cultures of primary human hepatocytes or in LS174T intestinal cells. On the other hand, S-warfarin is a less potent inducer of PXR-target genes in human hepatocytes and activates PXR only at supraphysiological concentrations. In addition, we showed that racemic 10- and 4' hydroxywarfarins are also highly potent PXR ligands and inducers of CYP3A4 and CYP2C9 mRNA in human hepatocytes. CONCLUSION: We showed that R-warfarin can significantly up-regulate major drug-metabolizing enzymes CYP3A4 and CYP2C9 in the liver and thus may cause drug-drug interactions (DDI) with co-administered drugs. The results warrant reconsideration of racemic warfarin usage in clinics. PMID- 20735728 TI - Haplotype and genotype effects of the F7 gene on circulating factor VII, coagulation activation markers and incident coronary heart disease in UK men. AB - BACKGROUND: Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. METHODS: Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS-II). A second cohort, Whitehall II study (WH-II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. RESULTS: In NPHS-II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12-1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01-1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH-II, as was the association of H5 with higher CHD risk [pooled-estimate odds ratio (OR) 1.16 (1.00-1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD. CONCLUSION: tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not. PMID- 20735729 TI - Systematic review on the effect of glucocorticoid use on procoagulant, anti coagulant and fibrinolytic factors. AB - BACKGROUND: Whether glucocorticoid use contributes to a hypercoagulable state, and thereby enhances the thrombotic risk, is controversial. OBJECTIVE: We aimed to examine the effects of glucocorticoid use on coagulation and fibrinolysis. METHODS: MEDLINE and EMBASE databases were searched to identify published studies comparing glucocorticoid treatment with a glucocorticoid-free control situation. Subjects could be either patients or healthy volunteers. Two investigators independently performed study selection and data extraction. Results were expressed as standardized mean difference, if possible; data were pooled with a random-effects model. RESULTS: Of the 1967 identified publications, 36 papers were included. In healthy volunteers, a clear rise in factor (F)VII, VIII and XI activity was observed after glucocorticoid treatment, but these data alone provided insufficient evidence to support hypercoagulability. However, during active inflammation, glucocorticoids significantly increased levels of plasminogen activator inhibitor-1 (PAI-1), whereas levels of von Willebrand factor (VWF) and fibrinogen decreased. Peri-operative use of glucocorticoids inhibited the increase in tissue-type plasminogen activator induced by surgery. CONCLUSIONS: The present study showed differential effects of glucocorticoids depending on the clinical situation in which it is given, most likely as a result of their disease modifying properties. Clinical outcome studies are needed to adequately assess the risk-benefit of glucocorticoid use per population when thrombotic complication is the focus. PMID- 20735730 TI - Is baby-led weaning feasible? When do babies first reach out for and eat finger foods? AB - The baby-led weaning philosophy proposes that when solids are introduced, infants should be encouraged to self-feed with solid food, as opposed to spoon-feeding purees. We used data from the Gateshead Millennium Study (GMS) to define the range of ages at which infants reach out for and eat finger foods and related this to developmental status. GMS recruited infants shortly after birth and followed them prospectively using postal questionnaires. Of the 923 eligible children, 602 had data on when they first reached out for food, and 340 (56%) had done so before age 6 months, but 36 (6%) were still not reaching for food at age 8 months. Infants who had not reached out for food by 6 months were less likely to be walking unaided at age 1 year (85 out of 224, 38%) compared with those who did (155 out of 286, 54%; P < 0.001). For the 447 parents who completed a diary of the first five occasions when their child ate finger foods, the first finger food eaten was before age 6 months for 170 (40%) and before age 8 months for 383 (90%); foods offered were mainly bread, rusks or biscuits. Of the 604 with information at age 8 months about current intake, all but 58 (9.6%) were having some finger foods at least daily, but only 309 (51%) were having them more than once per day. Baby-led weaning is probably feasible for a majority of infants, but could lead to nutritional problems for infants who are relatively developmentally delayed. PMID- 20735731 TI - Energy intake misreporting among children and adolescents: a literature review. AB - While adults' energy intake misreporting is a well-documented phenomenon, relatively little is known about the nature and extent of misreporting among children and adolescents. Children's and adolescents' dietary reporting patterns are likely to be distinct because of their ongoing cognitive and social development. These developmental differences present unique challenges to aspects of dietary reporting, such as food knowledge, portion size estimation and response editing. This review of 28 articles describes energy intake misreporting among children and adolescents. Like adults, children and adolescents tended to underreport energy, with the largest biases observed with food records. Even when mean reported energy intake was close to its expected value, approximately half of all individuals were classified as misreporters, and overreporting appeared to be more common than it is among adults. Associations between numerous characteristics and misreporting were explored in the literature, with the most consistent findings for age and adiposity. Two predictors for adults, gender and social desirability, were not consistent factors among children and adolescents. The review concludes by highlighting knowledge gaps and recommendations for future research and practice. PMID- 20735732 TI - Household food insecurity is associated with depressive symptoms among low-income pregnant Latinas. AB - Latinas experience high rates of poverty, household food insecurity and prenatal depression. To date, only one USA study has examined the relationship between household food insecurity and prenatal depression, yet it focused primarily on non-Latina white and non-Latina black populations. Therefore, this study examined the independent association of household food insecurity with depressive symptoms among low-income pregnant Latinas. This cross-sectional study included 135 low income pregnant Latinas living in Hartford, Connecticut. Women were assessed at enrolment for household food security during pregnancy using an adapted and validated version of the US Household Food Security Survey Module. Prenatal depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale. A cut-off of >=21 was used to indicate elevated levels of prenatal depressive symptoms (EPDS). Multivariate backwards stepwise logistic regression was used to identify risk factors for EPDS. Almost one third of participants had EPDS. Women who were food insecure were more likely to experience EPDS compared to food secure women (OR = 2.59; 95% CI = 1.03-6.52). Being primiparous, experiencing heartburn and reporting poor/fair health during pregnancy, as well as having a history of depression were also independent risk factors for experiencing EPDS. Findings from this study suggest the importance of assessing household food insecurity when evaluating depression risk among pregnant Latinas. PMID- 20735733 TI - The power of genetic monitoring for studying demography, ecology and genetics of a reintroduced brown bear population. AB - Genetic monitoring has rarely been used for wildlife translocations despite the potential benefits this approach offers, compared to traditional field-based methods. We applied genetic monitoring to the reintroduced brown bear population in northern Italy. From 2002 to 2008, 2781 hair and faecal samples collected noninvasively plus 12 samples obtained from captured or dead bears were used to follow the demographic and geographical expansion and changes in genetic composition. Individual genotypes were used to reconstruct the wild pedigree and revealed that the population increased rapidly, from nine founders to >27 individuals in 2008 (lambda=1.17-1.19). Spatial mapping of bear samples indicated that most bears were distributed in the region surrounding the translocation site; however, individual bears were found up to 163 km away. Genetic diversity in the population was high, with expected heterozygosity of 0.74-0.79 and allelic richness of 4.55-5.41. However, multi-year genetic monitoring data showed that mortality rates were elevated, immigration did not occur, one dominant male sired all cubs born from 2002 to 2005, genetic diversity declined, relatedness increased, inbreeding occurred, and the effective population size was extremely small (Ne=3.03, ecological method). The comprehensive information collected through genetic monitoring is critical for implementing future conservation plans for the brown bear population in the Italian Alps. This study provides a model for other reintroduction programmes by demonstrating how genetic monitoring can be implemented to uncover aspects of the demography, ecology and genetics of small and reintroduced populations that will advance our understanding of the processes influencing their viability, evolution, and successful restoration. PMID- 20735734 TI - Colonization and/or mitochondrial selective sweeps across the North Atlantic intertidal assemblage revealed by multi-taxa approximate Bayesian computation. AB - Intertidal and subtidal communities of the western and eastern coasts of the North Atlantic Ocean were greatly affected by Pleistocene glaciations, with some taxa persisting on both coasts, and others recolonizing after being extirpated on one coast during the Last Glacial Maximum. In the original spirit of comparative phylogeography, we conducted a comparative analysis using mtDNA sequence data and a hierarchical approximate Bayesian computation (ABC) approach for testing these two scenarios across 12 intertidal and subtidal coastal invertebrates spanning the North Atlantic to determine the temporal dynamics of species membership of these two ephemeral communities. Conditioning on a low gene-flow model, our results suggested that a colonization or mitochondrial selective sweep history was predominant across all taxa, with only the bivalve mollusc Mytilus edulis showing a history of trans-Atlantic persistence. Conditioning on a high gene-flow model weakened the support for this assemblage-level demographic history. The predominance of a colonization-type history also highlights concerns about analyses based on single-locus data where genetic hitchhiking may be incorrectly inferred as colonization. In conclusion, driving factors in shifting species range distributions and membership of ephemeral coastal communities could be species-specific environmental tolerances, species interactions, and/or stochastic demographic extinction. Through a re-examination of a long-standing question of North Atlantic phylogeography, we highlight the flexibility and statistical honesty of using a model-based ABC approach. PMID- 20735735 TI - Genetic diversity and connectivity of deep-sea hydrothermal vent metapopulations. AB - Deep-sea hydrothermal vents provide ephemeral habitats for animal communities that depend on chemosynthetic primary production. Sporadic volcanic and tectonic events destroy local vent fields and create new ones. Ongoing dispersal and cycles of extirpation and colonization affect the levels and distribution of genetic diversity in vent metapopulations. Several species exhibit evidence for stepping-stone dispersal along relatively linear, oceanic, ridge axes. Other species exhibit very high rates of gene flow, although natural barriers associated with variation in depth, deep-ocean currents, and lateral offsets of ridge axes often subdivide populations. Various degrees of impedance to dispersal across such boundaries are products of species-specific life histories and behaviours. Though unrelated to the size of a species range, levels of genetic diversity appear to correspond with the number of active vent localities that a species occupies within its range. Pioneer species that rapidly colonize nascent vents tend to be less subdivided and more diverse genetically than species that are slow to establish colonies at vents. Understanding the diversity and connectivity of vent metapopulations provides essential information for designing deep-sea preserves in regions that are under consideration for submarine mining of precious metals. PMID- 20735736 TI - Low specificity and nested subset structure characterize mycorrhizal associations in five closely related species of the genus Orchis. AB - Most orchid species rely on mycorrhizae to complete their life cycle. Despite a growing body of literature identifying orchid mycorrhizal associations, the nature and specificity of the association between orchid species and mycorrhizal fungi remains largely an open question. Nonetheless, better insights into these obligate plant-fungus associations are indispensable for understanding the biology and conservation of orchid populations. To investigate orchid mycorrhizal associations in five species of the genus Orchis (O. anthropophora, O. mascula, O. militaris, O. purpurea, and O. simia), we developed internal transcribed spacer-based DNA arrays from extensive clone library sequence data sets, enabling rapid and simultaneous detection of a wide range of basidiomycetous mycorrhizal fungi. A low degree of specificity was observed, with two orchid species associating with nine different fungal partners. Phylogenetic analysis revealed that the majority of Orchis mycorrhizal fungi are members of the Tulasnellaceae, but in some plants, members of the Thelephoraceae, Cortinariaceae and Ceratobasidiaceae were also found. In all species except one (O. mascula), individual plants associated with more than one fungus simultaneously, and in some cases, associations with >=3 mycorrhizal fungi at the same time were identified. Nestedness analysis showed that orchid mycorrhizal associations were significantly nested, suggesting asymmetric specialization and a dense core of interactions created by symmetric interactions between generalist species. Our results add support to the growing literature that multiple associations may be common among orchids. Low specificity or preference for a widespread fungal symbiont may partly explain the wide distribution of the investigated species. PMID- 20735737 TI - Calculations of population differentiation based on GST and D: forget GST but not all of statistics! AB - G(ST)-values and its relatives (F(ST)) belong to the most used parameters to define genetic differences between populations. Originally, they were developed for allozymes with very low number of alleles. Using highly polymorphic microsatellite markers it was often puzzling that G(ST)-values were very low but statistically significant. In their papers, Jost (2008) and Hedrick (2005) explained that G(ST)-values do not show genetic differentiation, and Jost suggested calculating D-values instead. Theoretical mathematical considerations are often difficult to follow; therefore, we chose an applied approach comparing two artificial populations with different number of alleles at equal frequencies and known genetic divergence. Our results show that even for more than one allele per population G(ST)-values do not calculate population differentiation correctly; in contrast, D-values do reflect the genetic differentiation indicating that data based on G(ST)-values need to be re-evaluated. In our approach, statistical evaluations remained similar. We provide information about the impact of different sample sizes on D-values in relation to number of alleles and genetic divergence. PMID- 20735738 TI - Hybridization between distant lineages increases adaptive variation during a biological invasion: stickleback in Switzerland. AB - The three-spined stickleback is a widespread Holarctic species complex that radiated from the sea into freshwaters after the retreat of the Pleistocene ice sheets. In Switzerland, sticklebacks were absent with the exception of the far northwest, but different introduced populations have expanded to occupy a wide range of habitats since the late 19th century. A well-studied adaptive phenotypic trait in sticklebacks is the number of lateral plates. With few exceptions, freshwater and marine populations in Europe are fixed for either the low plated phenotype or the fully plated phenotype, respectively. Switzerland, in contrast, harbours in close proximity the full range of phenotypic variation known from across the continent. We addressed the phylogeographic origins of Swiss sticklebacks using mitochondrial partial cytochrome b and control region sequences. We found only five different haplotypes but these originated from three distinct European regions, fixed for different plate phenotypes. These lineages occur largely in isolation at opposite ends of Switzerland, but co-occur in a large central part. Across the country, we found a strong correlation between a microsatellite linked to the high plate ectodysplasin allele and the mitochondrial haplotype from a region where the fully plated phenotype is fixed. Phylogenomic and population genomic analysis of 481 polymorphic amplified fragment length polymorphism loci indicate genetic admixture in the central part of the country. The same part of the country also carries elevated within population phenotypic variation. We conclude that during the recent invasive range expansion of sticklebacks in Switzerland, adaptive and neutral between population genetic variation was converted into within-population variation, raising the possibility that hybridization between colonizing lineages contributed to the ecological success of sticklebacks in Switzerland. PMID- 20735739 TI - Evidence of recent and continuous speciation in a biodiversity hotspot: a population genetic approach in southern African gladioli (Gladiolus; Iridaceae). AB - There has been much debate over the origin of species diversity in biodiversity hotspots, particularly the rate of speciation over extinction and the geographic mode of speciation. Here, we looked at speciation with varying degrees of sympatry in a biodiversity hotspot, focusing on a distinct morphological clade in the Cape Floristic Region in southern Africa, the Gladiolus carinatus species complex (Iridaceae). We investigate the mechanisms involved in population and species differentiation through a combination of ecological and genomic approaches. We estimated spatial and phenological overlap, differences in floral morphology, genetic isolation and genomic selection. A genetic coalescent analysis estimated that the time of divergence between lineages followed the establishment of available habitat in the Cape littoral plain where these species currently overlap geographically. Marked shifts in flowering time and morphology, which act as barriers to gene flow, have developed to varying degrees over the last 0.3-1.4 million years. An amplified fragment length polymorphism genome scan revealed signatures of divergent and balancing selection, although half of the loci consistently behaved neutrally. Divergent species outliers (1%) and floral morph outliers (3%) represent a small proportion of the genome, but these loci produced clear genetic clusters of species and significant associations with floral traits. These results indicate that the G. carinatus complex represents a continuum of recent speciation. We provide further evidence for ecological adaptation in the face of gene flow. PMID- 20735740 TI - Comparative genome scan detects host-related divergent selection in the grasshopper Hesperotettix viridis. AB - In this study, we used a comparative genome scan to examine patterns of population differentiation with respect to host plant use in Hesperotettix viridis, a Nearctic oligophagous grasshopper locally specialized on various Asteraceae including Solidago, Gutierrezia, and Ericameria. We identified amplified fragment length polymorphism (AFLP) loci with significantly elevated F(ST) (outlier loci) in multiple different-host and same-host comparisons of populations while controlling for geographic distance. By comparing the number and identities of outlier loci in different-host vs. same-host comparisons, we found evidence of host plant-related divergent selection for some population comparisons (Solidago- vs. Gutierrezia-feeders), while other comparisons (Ericameria- vs. Gutierrezia-feeders) failed to demonstrate a strong role for host association in population differentiation. In comparisons of Solidago- vs. Gutierrezia-feeding populations, a relatively high number of outlier loci observed repeatedly in different-host comparisons (35% of all outliers and 2.7% of all 625 AFLP loci) indicated a significant role for host-related selection in contributing to overall genomic differentiation in this grasshopper. Mitochondrial DNA sequence data revealed a star-shaped phylogeny with no host- or geography-related structure, low nucleotide diversity, and high haplotype diversity, suggesting a recent population expansion. mtDNA data do not suggest a long period of isolation in separate glacial refugia but are instead more compatible with a single glacial refugium and more recent divergence in host use. Our study adds to research documenting heterogeneity in differentiation across the genome as a consequence of divergent natural selection, a phenomenon that may occur as part of the process of ecological speciation. PMID- 20735741 TI - The discordance of diversification: evolution in the tropical-montane frogs of the Eastern Arc Mountains of Tanzania. AB - Species with similar geographical distribution patterns are often assumed to have a shared biogeographical history, an assumption that can be tested with a combination of molecular, spatial, and environmental data. This study investigates three lineages of Hyperolius frogs with concordant ranges within the Eastern Afromontane Biodiversity Hotspot to determine whether allopatric populations of co-distributed lineages shared a parallel biogeographical response to their shared paleoclimatic histories. The roles of refugial distributions, isolation, and climate cycles in shaping their histories are examined through Hierarchical Approximate Bayesian Computation, comparative phylogeography, and comparisons of current and past geographical distributions using ecological niche models. Results from these analyses show these three lineages to have independent evolutionary histories, which current spatial configurations of sparsely available habitat (montane wetlands) have moulded into convergent geographical ranges. In spite of independent phylogeographical histories, diversification events are temporally concentrated, implying that past vicariant events were significant at the generic level. This mixture of apparently disparate histories is likely due to quantifiably different patterns of expansion and retreat among species in response to past climate cycles. Combining climate modelling and phylogeographical data can reveal unrecognized complexities in the evolution of co-distributed taxa. PMID- 20735742 TI - Chloroplast DNA-based studies in molecular ecology may be compromised by nuclear encoded plastid sequence. AB - Ongoing genetic transfer from mitochondria and plastids into the nucleus is a well-documented fact. While in metazoan molecular ecology the need for surveillance against pseudogene-mediated artefacts when analysing mtDNA sequences is commonly accepted, no comparable measurements have been established for plastid-based studies. We highlight the impact and management of nuclear mitochondrial insertions, argue that nuclear plastid sequences represent an underestimated but major factor in plant molecular ecology, and discuss potential avenues of remedy in chloroplast studies. PMID- 20735743 TI - Distinguishing between population bottleneck and population subdivision by a Bayesian model choice procedure. AB - Although most natural populations are genetically subdivided, they are often analysed as if they were panmictic units. In particular, signals of past demographic size changes are often inferred from genetic data by assuming that the analysed sample is drawn from a population without any internal subdivision. However, it has been shown that a bottleneck signal can result from the presence of some recent immigrants in a population. It thus appears important to contrast these two alternative scenarios in a model choice procedure to prevent wrong conclusions to be made. We use here an Approximate Bayesian Computation (ABC) approach to infer whether observed patterns of genetic diversity in a given sample are more compatible with it being drawn from a panmictic population having gone through some size change, or from one or several demes belonging to a recent finite island model. Simulations show that we can correctly identify samples drawn from a subdivided population in up to 95% of the cases for a wide range of parameters. We apply our model choice procedure to the case of the chimpanzee (Pan troglodytes) and find conclusive evidence that Western and Eastern chimpanzee samples are drawn from a spatially subdivided population. PMID- 20735744 TI - Origins and colonization history of pandemic Vibrio parahaemolyticus in South America. AB - The dynamics of dissemination of the environmental human pathogen Vibrio parahaemolyticus are uncertain. The O3:K6 clone was restricted to Asia until its detection along the Peruvian coasts and in northern Chile in 1997 in phase with the arrival of El Nino waters. A subsequent emergence of O3:K6 strains was detected in austral Chile in 2004. The origin of these 1997 and 2004 population radiations has not yet been conclusively determined. Multiple loci VNTR analysis using seven polymorphic loci was carried out with a number of representative strains from Asia, Peru and Chile to determine their genetic characteristics and population structure. Asian and Chilean subpopulations were the most genetically distant groups with an intermediate subpopulation in Peru. Population structure inferred from a minimum-spanning tree and Bayesian analysis divided the populations into two genetically distinct groups, consistent with the epidemic dynamics of the O3:K6 clone in South America. One group comprised strains from the original Asiatic population and strains arriving in Peru and Chile in 1997. The second group included the remaining Peruvian Strains and Chilean strains obtained from Puerto Montt in 2004. The analysis of the arrival of the O3:K6 clone at the Pacific coasts of South America has provided novel insights linking the origin of the invasion in 1997 to Asian populations and describing the successful establishment of the O3:K6 populations, first in Peru and subsequently in the South of Chile owing to a possible radiation of Peruvian populations. PMID- 20735745 TI - Synchrotron X-ray imaging for nondestructive monitoring of sap flow dynamics through xylem vessel elements in rice leaves. AB - A comprehensive understanding of the sap flow dynamics and xylem hydraulic properties is essential to unravel the functional features of water transport from roots to shoots in vascular plants. To evaluate quantitatively the safety and efficiency of this system, nondestructive methods to assess the interactions between sap ascent kinetics and xylem structure are required. In this study, synchrotron X-ray microscopy was employed to observe anatomical structures and sap flow dynamics in rice (Oryza sativa) xylem simultaneously. The phase-contrast imaging technique allowed nondestructive observation of the xylem structural characteristics and the air-water interfaces generated by dehydration-rehydration cycles in excised leaves. This X-ray microimaging method provided a unique tool to characterize the perforated end walls of vessel elements and to evaluate their influence on hydraulic resistance during the refilling of embolized vessels. The real-time monitoring of the axial and radial sap flow under various environmental conditions highlighted the important role of perforation plates. In summary, we report a new methodology to study the sap flow dynamics and xylem hydraulic properties with MUm spatial and ms temporal resolution using X-ray microscopy. The experimental procedure described herein provides a useful handle to understand key sap transport phenomena in xylem. PMID- 20735746 TI - Longitudinal treatment outcomes for geriatric patients with chronic non-cancer pain at an interdisciplinary pain rehabilitation program. AB - OBJECTIVE: This study examined depression, pain catastrophizing, psychosocial functioning, and physical and emotional health attributes for geriatric patients admitted to an interdisciplinary pain rehabilitation center compared with middle and younger age groups. DESIGN: Quasi-experimental time series. SETTING: Interdisciplinary pain rehabilitation center at a tertiary referral medical center. PATIENTS: In total, 411 patients with chronic non-cancer pain completed the pain rehabilitation program from October 2004 to April 2006. Patients were divided into three groups based on age: older (ages 60+; n = 78); middle-age (ages 40-59; n = 230) and younger (ages 18-39; n = 141). INTERVENTION: A 3-week outpatient interdisciplinary pain rehabilitation program based on a cognitive behavioral model that incorporates opioid withdrawal. OUTCOME MEASURES: The Multidimensional Pain Inventory (MPI), Short Form-36 Health Status Questionnaire (SF-36), Pain Catastrophizing Scale (PCS), and Center for Epidemiological Studies Depression Scale (CES-D) were administered at admission, discharge, and 6 months following treatment. The frequency of patients using opioids, nonsteroidal anti inflammatory drugs (NSAIDs), and benzodiazepines at each assessment point were compared. RESULTS: Older patients reported reduced depression, catastrophizing, pain severity, and pain interference (P < 0.001) at discharge and 6 months follow up. Older patients also reported increased perceived control, and physical and social functioning at discharge and follow-up (P < 0.001). Improvement in older patients was comparable in magnitude to that of middle-age patients on all variables, whereas younger patients exhibited greater improvement on four variables. Significant reductions in analgesic use were observed in all groups. CONCLUSION: Interdisciplinary pain rehabilitation incorporating opioid withdrawal can improve long-term psychological, social and physical functioning for geriatric chronic pain patients. PMID- 20735747 TI - Insulin is essential for the recovery from allodynia induced by complete Freund's adjuvant. AB - OBJECTIVE: To determine the effect of streptozotocin (STZ)-induced diabetes on the development and recovery of thermal and mechanical hyperalgesia associated with inflammation induced by subcutaneous injection of complete Freund's adjuvant (CFA). BACKGROUND: The response to nociceptive injury in diabetes differs from that seen in normal individuals in that diabetic patients have increased susceptibility to infections and recover slowly or incompletely from infections and tissue injury due to an abnormal inflammatory response. We have chosen to examine the effect of STZ-induced hypoinsulinemia on the hyperalgesia associated with the enhanced inflammatory state that is induced by the subcutaneous injection of CFA to delineate the potential role of insulin in the development of chronic pain. METHODS: STZ- and vehicle-treated Sprague-Dawley rats were tested using thermal and mechanical stimulation after subcutaneous injection of CFA. The behavioral response was compared with that similarly determined in non-diabetic controls and insulin-depleted rats that received insulin replacement. RESULTS: Recovery of the thermal hyperalgesic response to baseline levels occurred over a period of 9-14 days, but the allodynic response to mechanical stimulation persisted for the duration of the study in STZ-treated rats. Insulin replacement prevented the delay in recovery of mechanical allodynia, but had no obvious effect on nociception in uninflamed tissue. CONCLUSIONS: Normal insulin function is essential for recovery from mechanical allodynia associated with inflammation induced by CFA. Altered insulin metabolism may selectively influence fiber-type specific mechanisms related to mechanical allodynia associated with inflammation and wound healing. PMID- 20735748 TI - The moderating effect of obesity on cognitive-behavioral pain treatment outcomes. AB - OBJECTIVE: To assess the effects of body mass index on cognitive-behavioral pain treatment outcomes for chronic low back pain. DESIGN: Retrospective analyses of data from a clinical trial were performed, with body mass index used to divide patients into obese and non-obese groups for comparison. SETTING: VA medical center outpatient clinic. PATIENTS: Veterans (N = 74) receiving outpatient care through the VA. INTERVENTIONS: Delivery of a 10-week cognitive-behavioral pain treatment intervention. OUTCOME MEASURES: The Numerical Rating Scale (pain intensity), Roland Morris Disability Questionnaire (disability), Veteran's SF-36 (health-related quality of life), and Beck Depression Inventory (emotional functioning) were administered pre- and post-treatment. RESULTS: The study included 42 obese and 32 non-obese participants, most of whom were male (89%). The average body mass index was 32.44 kg/m2, with average pain intensity rated as 6.59 out of 10. There were no pre-treatment differences in outcome measures between the groups. Repeated measures ANOVAs revealed main effects of Time on all but one outcome (Mental Component score), indicating that the cognitive behavioral interventions were largely effective. However, Time-body mass index (BMI) group interactions revealed that non-obese participants showed greater improvement following treatment than did their obese counterparts on measures of disability (P < 0.05), physical aspects of quality of life (P < 0.01), and emotional functioning (P < 0.05). CONCLUSIONS: Standard cognitive-behavioral pain treatment did not yield comparable outcomes for obese and non-obese participants. Results suggest a potential moderating role of BMI in low back pain outcomes. Future work with other pain conditions, including examination of potential mechanisms through which BMI impacts treatment outcomes, is recommended. PMID- 20735749 TI - Psychiatric disorders and risk of transition to chronicity in men with first onset low back pain. AB - OBJECTIVE: To assess whether pre-existing psychiatric diagnoses increase the likelihood of transitioning from sub-acute to chronic back pain. DESIGN: Prospective cohort study. METHODS: Men (N = 140) experiencing a first onset of low back pain (LBP) were examined for lifetime psychiatric disorders approximately 8 weeks post pain-onset using the Diagnostic Interview Schedule (DIS-III-R), then re-evaluated at 6 months after pain onset to determine who did or did not progress to pain chronicity. OUTCOME MEASURE: Transition to chronic pain and disability was based on 6-month self-report measures of pain intensity and perceived disability. RESULTS: Men with a pre-pain lifetime diagnosis of major depressive disorder had 5 times greater risk of transitioning to chronic LBP (odds ratio [OR] = 4.99; 95% confidence interval [CI] 1.49-16.76). Increased risk was also associated with a pre-pain lifetime diagnosis of generalized anxiety (OR = 2.45; 95% CI 1.06-5.68), post-traumatic stress (OR = 3.23; 95% CI 1.11-9.44), and with current nicotine dependence (OR = 2.49; 95% CI 1.15-5.40). There were no statistically significant effects for abuse or dependence of alcohol or other psychoactive substances. DISCUSSION: Lifetime history of major depression or a major anxiety disorder may represent potential psychosocial "yellow flags" for the transition to chronicity in men with first-onset LBP. Screening for lifetime depressive or anxiety disorders may identify individuals at higher risk, who may benefit from referral for more intensive rehabilitation. PMID- 20735750 TI - Psychosocial correlates of chronic pain and depression in young adults: further evidence of the utility of the Profile of Chronic Pain: Screen (PCP: S) and the Profile of Chronic Pain: Extended Assessment (PCP: EA) battery. AB - OBJECTIVE: The goals of the present studies were 1) to determine the psychometric utility and norms of the Profile of Chronic Pain: Screen (PCP: S) in young adults (ages 17-24) with self-reported pain and 2) to compare non-, mildly-, and clinically-depressed young adults with chronic pain in their patterns of pain attitudes and pain beliefs as assessed by the Profile of Chronic Pain: Extended Assessment (PCP: EA) battery. METHODS: Participants in the first study included 2,475 male and female college students drawn from undergraduate introductory psychology classes in a large western (U.S.) university. Study 2 participants were 275 male and female introductory psychology students, screened for chronic pain and depression from a cohort of 1,266 students. RESULTS: Study 1 results confirmed the utility of the PCP: S as a screening tool for pain problems in young adults. Study 2 revealed that, although not differing in pain severity, clinically depressed participants differed from their nondepressed and mildly depressed peers in terms of enhanced catastrophizing tendencies and greater perceived disability. Both depressed groups scored lower on control beliefs than the nondepressed group. Moreover, the clinically depressed students reported the highest scores on pain-induced fear, differing from both the mildly depressed and the nondepressed. Finally, the three groups did not differ in their belief in a medical cure. CONCLUSIONS: Results suggest that depressed young persons with chronic pain demonstrate a pattern of negative attitudes and beliefs that could compromise their ability to flexibly adjust to changing life circumstances. PMID- 20735751 TI - Interlaminar versus transforaminal epidural steroid injections for the treatment of symptomatic lumbar spinal stenosis. AB - BACKGROUND: Lumbar spinal stenosis is a common condition that causes axial low back pain, radicular pain, and neurogenic claudication. Epidural steroid injections are commonly used for the treatment of radicular symptoms and neurogenic claudication associated with symptomatic lumbar spinal stenosis. No prior study has evaluated whether transforaminal or interlaminar epidural steroid injections produce better clinical outcomes. DESIGN: Retrospective case control study. METHODS: For each technique, 19 patients were retrospectively identified who received their first fluoroscopically guided epidural steroid injection for radicular and neurogenic claudication symptoms caused by lumbar spinal stenosis over a 12-month interval. All patients had corresponding MRI findings and had failed previous non-invasive therapies. Outcomes included the visual analog scale (VAS, 0-10 scale) immediately before the injection, immediately after the injection, and upon follow up at 4-6 weeks. Surgery rates and number of repeat injections over a 3 year period were also analyzed. The patient groups were matched for age and level of stenosis on MRI. RESULTS: There was no statistically significant difference between the two groups in pre injection to follow up VAS scores (P=0.919). The difference between number of repeat injections between the interlaminar and transforaminal groups was not statistically significant (0.91 mean 2.47 and 2.58, respectively). Both the interlaminar and transforaminal groups experienced statistically significant improvement in VAS scores from before the injection to after the injection, and on follow up. Low numbers underwent surgery (11% in the interlaminar group vs 15% in the transforaminal group, not significant, P=0.63). CONCLUSIONS: In the current study, neither transforaminal nor interlaminar steroid injections resulted in superior short term pain improvement or fewer long term surgical interventions or repeat injections when compared with each other. PMID- 20735752 TI - Analgesic discography: effect of adding a local anesthetic to routine lumbar provocation discography. AB - INTRODUCTION: There is a renewed interest in analgesic testing, influenced by several studies reporting robust surgical results when the diagnosis of discogenic pain is confirmed by relief of pain post-provocative discography after injecting local anesthetic into painful discs. OBJECTIVE: We anticipated and sought to confirm that injecting local anesthetic in intervertebral discs would provide convincing pain relief and that the degree of pain relief would help confirm or refute the findings of provocative discography. METHODS: There were 23 patients in the nonanalgesic group, and 47 patients in the analgesic group. The analgesic patient discs were injected with an equal volume of local anesthetic and nonionic contrast media. Lumbar discography was performed using an automated pressure-controlled provocative discographic (APCPD) technique. Subjects reported global subjective relief at 15 and 45 minutes after APCPD. Pre- and post procedure pain was rated using a numerical rating scale (NRS) using standardized pain provoking positions. In addition, we further compared the numbers of patients reporting a decrease in NRS scores (>=2) in standardized pain provoking positions. RESULTS: The addition of local anesthetic to APCPD did not affect the number of positive APCPD results that averaged ~30% positive discs in both groups. The addition of local anesthetic to contrast significantly reduced pain NRS scores by 2/10 or greater during forward flexion and sitting compared with patients whose discs were injected with contrast without local anesthetic. The average pain improvement using standardized pain provocation positions and average subjective relief were not, however, significantly different in the two groups. Only two patients reported overall pain relief equal or greater to 50%. CONCLUSIONS: Using an equal mixtures of injected local anesthetic and contrast during provocative discography in a cohort of patients did not provide significant overall subjective pain relief compared to using contrast alone in a comparative separate cohort. PMID- 20735753 TI - Botulinum toxin A (Botox) for treatment of proximal myofascial pain in complex regional pain syndrome: two cases. AB - OBJECTIVES: To describe development of myofascial pain syndrome (MFPS) with trigger points in the proximal muscles of the patients with complex regional pain syndrome (CRPS1) and improvement of distal symptoms of CRPS 1 after successful treatment of proximal MFPS. SETTING AND DESIGN: In our practice, we frequently encounter patients in whom a proximal myofascial pain syndrome develops ipsilateral to the distal limb of CRPS1 patients. We describe two such patients in detail with their treatment. PATIENT 1: A 48-year-old woman experienced severe allodynia, swelling and autonomic changes in the right hand after surgery for carpal tunnel syndrome. Over the succeeding months, she developed painful trigger points in the right trapezius and upper back muscles which was treated with administration of botulinum toxin A (BoNT-A) into the trigger points (20 unit/point). PATIENT 2: A 41-year-old woman following a traumatic forearm injury suffered from CRPS1 affecting the left hand and forearm. Proximal MFPS gradually developed on the same side over 12 months and was treated with administration of BoNT-A into the trapezius, splenius capitis, and rhomboid muscle trigger points. RESULTS: In both patients treatment with BoNT-A improved the proximal pain of MFPS and the distal symptoms of CRPS1. CONCLUSION: proximal MFPS develops ipsilateral to the distal painful limb in patients with CRPS1. Administration of BoNT-A into the affected proximal muscles may alleviate both MFPS and the distal allodynia, discoloration and, tissue swelling of CRPS. PMID- 20735754 TI - Allegations of medical malpractice in chronic opioid analgesic therapy possibly related to collaborative/split treatment and the P-450 enzyme system: forensic case report. AB - OBJECTIVES: The objectives of this forensic medicolegal case report were the following: 1) present details of a patient on chronic opioid analgesic therapy (COAT) where a disastrous outcome resulted in allegations of malpractice; 2) detail the plaintiff's and defendant's medical experts' opinions on this allegation; and 3) discuss issues potentially related to these allegations, i.e., split treatment and the P450 enzyme system. METHODS CASE REPORT RESULTS: Medicolegal issues surrounding these malpractice allegations are discussed. CONCLUSIONS: Split treatment can increase the difficulties in performing COAT. Clinicians should routinely consider the effects of all utilized drugs on the ability of the P450 enzyme system to metabolize/clear opioids. PMID- 20735756 TI - Increased serum-soluble interleukin-5 receptor alpha level precedes the development of eczema in children. AB - Interleukin-5 receptor alpha-subunit expression may be implicated in the development of allergic diseases. In a population-based birth cohort, we investigated the relationship between IL-5Ralpha and the development of allergic phenotypes in childhood, using soluble IL-5Ralpha (s-IL-5Ralpha) as a marker. Children (n = 510) were followed from birth and assessed at age 3, 5 and 8. Based on the onset and resolution of symptoms, we assigned children into the following wheeze and eczema phenotypes: never, transient, persistent, intermittent and late onset. Specific IgE to common allergens, s-IL-5Ralpha (ELISA) and urinary eosinophilic protein X (U-EPX) levels was measured at age 5. s-IL-5Ralpha was significantly higher among atopic compared to non-atopic children (pg/ml, geometric means [95% CI], 152.4 [126.0-184.5] vs. 103.4 [94.0-113.9], p < 0.0001). While we found no association between s-IL-5Ralpha and current eczema at age 5, there was a significant association between eczema phenotypes and s-IL 5Ralpha (multiple anova model adjusted for gender and atopy, F = 2.56, p = 0.04). After adjustment for multiple comparisons, we found that children with late-onset eczema had significantly higher s-IL-5Ralpha compared to those who have never had eczema (mean difference [95% CI], 2.41 [1.03-5.62], p = 0.04) and those with intermittent eczema (2.63 [1.08-6.41], p = 0.02), with no difference between children who have never had eczema and other eczema phenotypes. We found no such association for wheeze phenotypes. There was a weak correlation between s-IL 5Ralpha and U-EPX (r = 0.16, p < 0.0001). Increased serum s-IL-5Ralpha level at age 5 was associated with contemporaneous atopic sensitization and with subsequent development of eczema by age 8. PMID- 20735755 TI - Neurosteroids and self-reported pain in veterans who served in the U.S. Military after September 11, 2001. AB - OBJECTIVE: Nearly half of Operation Enduring Freedom/Operation Iraqi Freedom veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABA(A) receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans. DESIGN: We determined serum neurosteroid levels by gas chromatography/mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates. SETTING: Durham VA Medical Center. RESULTS: Allopregnanolone levels were inversely associated with low back pain (P=0.044) and chest pain (P=0.013), and DHEA levels were inversely associated with muscle soreness (P=0.024). DHEAS levels were positively associated with chest pain (P=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (P=0.002). CONCLUSIONS: Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders. PMID- 20735759 TI - An assessment of the association between childhood asthma and HLA DRB1*03 using extended haplotype analysis. AB - Ancestral haplotypes between human leukocyte antigen (HLA) class I and class II alleles are well-recognized in the literature. We previously published a positive association between the class II HLA allele DRB1*03 and the subsequent development of asthma in a retrospective cohort of 383 children. To refine this association, we investigated whether DRB1*03-specific haplotypes extending across the HLA are associated with asthma incidence. We found evidence of strong HLA DRB1*03-dependent linkage disequilibrium across the region, but no association between DRB1*03 ancestral haplotypes and childhood asthma. We did, however, observe a trend toward a positive association between HLA DRB1*03 and asthma by adding non-ancestral DRB1*03 positive haplotypes. Our results suggest that the role of the HLA DRB1*03 in asthma susceptibility is independent of ancestral haplotype-mediated linkage disequilibrium. PMID- 20735758 TI - Task requirements change signal strength of the primary somatosensory M50: Oddball vs. one-back tasks. AB - Studies on attention to tactile stimuli have produced conflicting results concerning the possibility and/or direction of modulation of early somatosensory evoked fields (SEFs). To evaluate sources of these conflicting results, the same subjects performed four different tasks in which the stimulation site, type, and intensity were kept constant. Twelve subjects performed an oddball-like tactile task, two different one-back tactile tasks, and a visual task, while two distal phalanges of the index and ring finger were stimulated. Task-dependent SEF modulations were found as early as 50 ms after stimulus onset (M50 component). Target/non-target ratios of M50 revealed enhanced values for the oddball-like tactile task, but decreased values for the tactile one-back task. This indicates that previously obtained conflicting results might be due to different central mechanisms induced by different task requirements. PMID- 20735757 TI - Distinct neural generators of sensory gating in schizophrenia. AB - Although malfunctioning of inhibitory processes is proposed as a pathophysiological mechanism in schizophrenia and has been studied extensively with the P50 gating paradigm, the brain regions involved in generating and suppressing the P50 remain unclear. The current investigation used EEG source analysis and the standard S1-S2 paradigm to clarify the neural structures associated with P50 gating in 16 schizophrenia patients and 14 healthy subjects. Based on prior research, the superior temporal gyrus, hippocampus, dorsolateral prefrontal cortex, thalamus, and their dipole moments were evaluated. In modeling the P50, a neural network involving all four brain regions provided the best goodness-of-fit across both groups. In healthy subjects, the P50 ratio score correlated positively with the hippocampal dipole moment ratio, whereas a significant association with the DLPFC dipole moment ratio was observed in schizophrenia patients. In each instance, the neural structure was found to account for unique variance in explaining the P50 ratio, along with some suggestion of DLPFC involvement in healthy subjects. PMID- 20735760 TI - Surgical blood order equation in femoral fracture surgery. AB - AIM: This study aimed at establishing the clinical utility of the surgical blood order equation (SBOE) in patients undergoing femoral fracture surgery. BACKGROUND: A blood ordering schedule defines the perioperative blood use in elective surgery. It lists the number of units of blood required for each procedure preoperatively. MATERIALS AND METHODS: A case-control study was performed among homogeneous groups of patients (n = 62 each) undergoing open reduction and internal fixation of femoral fractures. Correct prediction of blood use in the group of patients using the SBOE was compared to the group whose blood orders were made without any guideline. RESULTS: The surgical blood ordering equation was exactly correct in ordering blood for 46 (74.2%) of 62 patients (cases). The current unaided blood ordering method was exactly correct in ordering blood for 27 (43.5%) of 62 patients (controls). Use of the SBOE resulted in a significantly lower crossmatch-to-transfusion ratio compared to that of the current ordering system (1.5 vs 2.3) and saved the hospital transfusion laboratory 465 US$ of crossmatch and inventory management costs in this cohort of patients. CONCLUSION: The SBOE is a more accurate and cost-saving tool in predicting blood use. It should replace the current unaided method of ordering for perioperative blood in femoral fracture surgery at Mulago Hospital. However, its introduction to other hospitals should be preceded by more rigorous research to strengthen its external validity. PMID- 20735761 TI - Isolation of non-typhoidal Salmonella from a haematopoietic progenitor cell product. PMID- 20735762 TI - Treatment of severe neutropenic sepsis with granulocyte transfusion in the current era--experience from an adult haematology unit in Singapore. AB - OBJECTIVES: Granulocyte transfusion's (GT) efficacy among adult severe neutropenic sepsis (SNS) patients remains uncertain. We assessed GT's efficacy and its determinants among SNS patients in an adult haematology unit. The feasibility and safety of granulocyte donation (GD) and determinants of granulocyte yield were also evaluated. METHODS: Retrospective analysis of granulocyte donors and recipients from March 2008 to October 2009. RESULTS: Donors: Sixty GDs with a median WBC yield (WBCY) of 65.49 (31.30-131.72) * 10(9) were collected from 48 donors (9 repeat donors) using hydroxyethyl starch and intermittent flow centrifugation aphaeresis after receiving 8 mg dexamethasone and 300 mcg granulocyte colony-stimulating factor, with no serious adverse reactions (SAR). Six donations were urgently collected <3 h after pre-medication, the median WBCY of which was not significantly different from donations collected >12 h after pre-medication [59.18 (45.68-62.90) * 10(9) vs 67.45 (31.30-131.72) * 10(9) , P = 0.140]. Only pre-GD absolute neutrophil count (ANC) correlated with WBCY. PATIENTS: Fifteen patients (12 acute leukaemias, 1 severe AA, 1 myelodysplastic syndrome and 1 lymphoma) received median 3 (2-9) ABO/RhD-matched GTs over 2-24 (median 7) days at 3-61 (median 28) days from severe neutropenia (SN) onset without SAR. They received intensive chemotherapies (N = 9), allogeneic transplant (N = 3), autologous stem cell rescue (N = 1) or immunosuppressants (N = 2). Fourteen had bacterial (N = 1) infections, fungal (N = 3) infections or both (N = 10) and one had severe viral pneumonitis; 63.6 and 30.8% of bacterial and fungal infections responded, respectively. Median ANC increase (ANC(increase) ) was 1.26 (0-9.25) * 10(9) at 5-20 (median 11) h post GT. On multivariate analysis, each patient's median ANC(increase) only significantly correlated positively with median WBC dose/kg (P = 0.013). Five (33.3%) patients survived to discharge; the rest had infection-related mortality (IRM). IRM was significantly associated with inotropic requirement (P = 0.004), ventilatory requirement (P = 0.017) and persistent SN (P = 0.007). CONCLUSION: GD is safe and feasible with good WBCY obtainable using our protocol. The effect of shortening pre-medication interval on WBCY which may prevent delay in initiating GT is worth evaluating. GT most likely benefits SNS patients with prospects of neutrophil recovery before haemodynamic deterioration. Large randomised trials investigating the role and timing of GT among such patients are required. PMID- 20735763 TI - Perspectives of potential donors on cord blood and cord blood cryopreservation: a survey of highly educated, pregnant Korean women receiving active prenatal care. AB - BACKGROUND: The aim of the study was to investigate the knowledge of cord blood (CB) and attitudes toward CB banking among high-potential donors (i.e., well educated pregnant Koreans) because their voluntary donation is indispensable to the success of unrelated CB transplantation. STUDY DESIGN AND METHODS: Questionnaires examining perspectives on CB were distributed to and completed by 1001 women attending a maternity education program from April to October 2008; 863 women answered that they had heard of CB. We analyzed the 863 questionnaires to identify the sources of information, the plan for CB, the reasons for decisions, beliefs about the potential uses of CB, and knowledge about current therapeutic uses. RESULTS: Most subjects received information from promotional materials distributed by CB banks and the media; however, minimal information was obtained from obstetricians. More than 90% of women who planned to donate cited "altruism," and 75.0% of the "private preservation" group indicated that a desire to "safeguard for the future" was the reason for their decision. The probability of autologous CB transplantation (p = 0.001) and current usefulness were significantly overestimated in the private preservation group (p = 0.02). In addition, 56% of subjects underestimated the probability of identifying a matched CB in the public bank, and the overall rate of correct answers about current usefulness was 57.4%. CONCLUSIONS: A considerable portion of educated pregnant Korean women has more than minimal knowledge of CB, but the levels of knowledge regarding the potency of the public bank and the current usefulness and limitations of CB are generally low; in addition, obstetricians play insignificant roles in disseminating knowledge. Providing accurate and detailed information to pregnant women not only via brochures and the media and/or Internet but also by obstetricians would encourage CB donation. PMID- 20735764 TI - Thrombopoietin to replace megakaryocyte-derived growth factor: impact on stem and progenitor cells during ex vivo expansion of CD34+ cells mobilized in peripheral blood. AB - BACKGROUND: The first protocol of ex vivo expansion that enabled almost total abrogation of postmyeloablative chemotherapy neutropenia was based on a three cytokine cocktail (stem cell factor [SCF], granulocyte-colony-stimulating factor [G-CSF], pegylated-megakaryocyte growth and development factor [PEG-MGDF]) in a serum-free medium. Since the clinical-grade molecule MGDF is no longer available on the market, we evaluated its substitution by thrombopoietin (TPO). STUDY DESIGN AND METHODS: CD34+ cells of myeloma patients were expanded for 10 days in serum-free cultures with SCF, G-CSF, or MGDF (100 ng/mL) or with TPO (2.5, 10, 20, 50, and 100 ng/mL) instead of MGDF. Day 10 amplifications of total nucleated cells, CD34+ cells, committed progenitors (CFCs), the capacity of engraftment of NOD/SCID mice (SCID repopulating cells [SRCs]), and the immunophenotype of cells in expansion product (CD13, CD14, CD33, CD41, CD61) were analyzed. RESULTS: TPO in doses of 2.5 and 10 ng/mL exhibits an effect comparable to that of MGDF (100 ng/mL) on total, CD34+, and CFCs amplification. Compared to MGDF, TPO (starting at 10 ng/mL) enhances two- to threefold the percentage of megakaryocyte lineage cells (CD41+ and CD61+). Finally, TPO maintains or even enhances (depending on dose) SRC activity. CONCLUSIONS: The use of TPO instead of MGDF in our protocol is feasible without any negative effect on progenitor cell expansion. Furthermore, applied in dose of 10 or 100 ng/mL it could enhance both the stem cell activity and the percentage of megakaryocyte lineage cells in expansion product. PMID- 20735765 TI - Neonatal alloimmune neutropenia due to immunoglobulin G antibodies against human neutrophil antigen-5a. AB - BACKGROUND: Neonatal alloimmune-mediated neutropenia (NAIN) due to maternal alloantibodies directed against one of the human neutrophil antigens (HNAs) can cause severe infections. NAIN has been described as caused by antibodies against HNA-1a, -b, -c, -2a, -3a, or -4a, but not by antibodies against HNA-5a. RESULTS: Blood from a 3-week-old newborn and from his parents was sent to our laboratory because of suspicion of NAIN. Granulocyte-specific antibodies were present in the maternal antiserum and reactive with the paternal granulocytes. The specificity of the maternal alloantibodies was shown to be anti-HNA-5a by the monoclonal antibody immobilization of granulocyte antigens assay. The mother was genotyped HNA-5a negative, and the father was genotyped homozygous HNA-5a positive. CONCLUSION: We identified a first case of NAIN due to maternal alloantibodies against HNA-5a. PMID- 20735766 TI - Risk factors and outcome associated with hypomagnesemia in massive transfusion. AB - BACKGROUND: Electrolyte disturbances are common in patients with critical bleeding requiring massive transfusion. The risk factors and outcome associated with the occurrence of hypomagnesemia in massive transfusion remain uncertain. STUDY DESIGN AND METHODS: A cohort of 353 consecutive patients who required massive transfusion, defined as 10 or more units of allogeneic red blood cells or whole blood transfusion within 24 hours, between 2002 and 2008 in a quaternary health care center in Western Australia was considered. Logistic regression was used to identify risk factors and outcome associated with hypomagnesemia during massive transfusion (<0.7 mmol/L or 1.7 mg/dL). RESULTS: Of the 353 patients requiring massive transfusion during the study period, 298 patients (84%) had serum magnesium concentrations available for analysis. Hypomagnesemia was common (172 patients, 58%), and the mean magnesium concentration was 0.68 mmol/L (1.65 mg/dL; standard deviation, 0.15 mmol/L) in these patients. The risk factors for hypomagnesemia were hypocalcemia (odds ratio [OR], 1.67 per 0.1 mmol/L decrement; 95% confidence interval [CI], 1.36-2.01; p = 0.001) and hypofibrinogenemia (OR, 1.05 per 0.1 g/L decrement; 95% CI, 1.01-1.09; p = 0.009). The lowest serum magnesium concentrations were associated with the lowest ionized calcium concentrations (Spearman correlation coefficient, 0.377; p = 0.001). Both magnesium concentrations (OR, 0.91 per 0.1 mmol/L increment; 95% CI 0.31-2.69; p = 0.863) and the interaction term between magnesium and calcium concentrations were not associated with an increased risk of mortality after adjusting for other covariates. CONCLUSIONS: Hypomagnesemia was common and associated with hypocalcemia in massive transfusion, but serum magnesium concentrations had no independent effect or interactive effect with hypocalcemia on mortality of patients requiring massive transfusion. PMID- 20735767 TI - An unusual febrile nonhemolytic reaction occurred after transfusion in a thalassemia major patient with asymptomatic Plasmodium falciparum infection. AB - BACKGROUND: Febrile nonhemolytic transfusion reactions occur in 0.12% of transfusions, usually during transfusion or within 4 to 6 hours after transfusion and are not medically dangerous. CASE REPORT: A patient with thalassemia from Togo with asymptomatic malaria in which the infection became clinically manifest only after blood transfusion, mimicking a febrile nonhemolytic transfusion reaction, is presented. Thirty-two hours after transfusion of 2 O D- red blood cell (RBC) units, the patient (phenotype A(2) D+) developed fever and multiorgan failure and was admitted to the intensive care unit. Direct and indirect antiglobulin tests were negative on posttransfusion samples. Blood cultures and infectious diseases testing were negative. No malaria parasites were found at thick blood smear microscopic examination on Days 1 and 2 and the malaria rapid diagnostic test gave inconsistent results. Plasmodium total antibodies were detected in the serum at high levels. On Day 5, routine microscopic examination of blood smear revealed the presence of parasites in a very small number of RBCs. This finding was almost simultaneous to the availability of polymerase chain reaction testing results that were positive for P. falciparum. The sequential agglutination with anti-A antiserum allowed patient's and donors' RBCs to be separated and revealed that the parasitized cells were almost exclusively those of donors (14.4% vs. 0.029%). Malaria infection in implicated donors was excluded. CONCLUSION: In this patient with thalassemia with asymptomatic malaria, the infusion of two normal RBC units provided a favorable environment for a rapid parasite replication leading to a dramatic acute malaria attack. PMID- 20735768 TI - The effect of smoking on biliary complications following liver transplantation. AB - We sought to estimate the effect of smoking on the biliary complication rate following orthotopic liver transplantation. We retrospectively evaluated the records of liver transplant recipients at our center from July 1, 1999 to October 26, 2007. Using Cox proportional hazards models, we estimated the time to the earliest biliary complication (leak or stricture) based on smoking exposure, as active, former, or lifetime nonsmoker, adjusting for other clinical factors. Overall, 409 liver transplant recipients were evaluated. The overall biliary complication rate was 37.7% (n = 154). Biliary complications included 66 anastomotic leaks, 60 anastomotic strictures, and 28 nonanastomotic lesions. ERCP was the primary diagnostic modality (n = 112). 18.1% of liver transplant recipients were active smokers (n = 74) and 42.8% were former smokers (n = 175). Active smokers were at greatest risk for biliary complications on unadjusted analysis (P = 0.022). After multivariable adjustment, active smokers had a 92% higher rate of biliary complication rates compared with lifetime nonsmokers (HR 1.92, 95% CI 1.07-3.43), but no difference was noted in the rate of complication resolution. Smoking clearly portends a significant risk of biliary complications following liver transplantation. Smoking status should be clearly defined when evaluating transplant candidacy and in counseling patients with cirrhosis. PMID- 20735769 TI - Localized cowpox infection in a 5-month-old Rottweiler. AB - Cowpox virus (CPXV) infections are a sporadic cause of localized or disseminated skin disease in domestic animals and humans in Europe. Rodents are considered the primary reservoir host for CPXV. Cats can become infected by close contact with rodents and are the most important source of human infections. Recently, public awareness has also been drawn to CPXV infections by an outbreak of rat to human infections in central Europe. In dogs, CPXV infections are rare. Here we report a case of a 5-month-old Rottweiler with a focal nodule on the muzzle. The lesion was fully excised, and recovery was uneventful. The preliminary diagnosis of a CPXV infection was established by the characteristic inclusion bodies on histopathological examination. The diagnosis was confirmed by electron microscopy and polymerase chain reaction (PCR). Sequencing of the PCR product led to a 231 bp sequence of the orthopoxvirus HA gene that was identical to a CPXV strain previously isolated from a cat. This is the third documented case of a canine CPXV infection. PMID- 20735771 TI - The soybean root-specific protein kinase GmWNK1 regulates stress-responsive ABA signaling on the root system architecture. AB - In humans, members of the WNK protein kinase family are osmosensitive regulators of cell volume homeostasis and epithelial ion transport, and mutation of these proteins causes a rare inherited form of hypertension due to increased renal NaCl re-absorption. A related class of kinases was recently discovered in plants, but their functions are largely unknown. We have identified a root-specific WNK kinase homolog, GmWNK1, in soybean (Glycine max). GmWNK1 expression was detected in the root, specifically in root cells associated with lateral root formation, and was down-regulated by abscisic acid (ABA), as well as by mannitol, sucrose, polyethylene glycol and NaCl. In vitro and in vivo experiments showed that GmWNK1 interacts with another soybean protein, GmCYP707A1, which is a key ABA 8' hydroxylase that functions in ABA catabolism. Furthermore, 35S-GmWNK1 transgenic soybean plants had reduced lateral root number and length compared with wild type, suggesting a role of GmWNK1 in the regulation of root system architecture. We propose that GmWNK1 functions to fine-tune ABA-dependent ABA homeostasis, thereby mediating the regulation of the root system architecture by ABA and osmotic signals. The study has revealed a new function of a plant WNK1 gene from the important staple crop soybean, and has identified a new component of a regulatory pathway that is involved not only in ABA signaling, but also in the repression of lateral root formation by an ABA-dependent mechanism distinct from known ABA signaling pathways. PMID- 20735772 TI - Polypyrimidine tract-binding protein homologues from Arabidopsis underlie regulatory circuits based on alternative splicing and downstream control. AB - Alternative splicing (AS) of precursor mRNAs is a widespread phenomenon in plants; however, many questions, especially regarding its regulation and functional implications, remain to be elucidated. In vertebrates, polypyrimidine tract-binding proteins (PTBs) have been identified as key splicing factors influencing splice site selection and orchestrating coordinated splicing programmes during developmental processes. Here, we analysed three PTB homologues from Arabidopsis thaliana and provide evidence for their gene regulatory potential based on AS and a splicing-independent mechanism. Our data reveal that Arabidopsis PTB homologues are subject to extensive auto- and cross-regulation via AS-coupled nonsense-mediated decay, thereby establishing a basis for interlinking their expression. Furthermore, the multiple modes of action of Arabidopsis PTB homologues are reflected in their subcellular localization in the nucleus, cytosol and processing bodies. This work provides insight into the regulation of AS in plants and highlights the regulatory potential of the multifunctional plant PTB homologues, which might have important implications in diverse biological processes. PMID- 20735770 TI - A novel class of peptide pheromone precursors in ascomycetous fungi. AB - Recently, sexual development in the heterothallic ascomycete Trichoderma reesei (anamorph of Hypocrea jecorina) has been achieved and thus initiated attempts to elucidate regulation and determinants of this process. While the alpha-type pheromone of this fungus fits the consensus known from other fungi, the assumed a type peptide pheromone precursor shows remarkably unusual characteristics: it comprises three copies of the motif (LI)GC(TS)VM thus constituting a CAAX domain at the C-terminus and two Kex2-protease sites. This structure shares characteristics of both a- and alpha-type peptide pheromone precursors. Presence of hybrid-type peptide pheromone precursor 1 (hpp1) is essential for male fertility, thus indicating its functionality as a peptide pheromone precursor, while its phosphorylation site is not relevant for this process. However, sexual development in a female fertile background is not perturbed in the absence of hpp1, which rules out a higher order function in this process. Open reading frames encoding proteins with similar characteristics to HPP1 were also found in Fusarium spp., of which Fusarium solani still retains a putative a-factor-like protein, but so far in no other fungal genome available. We therefore propose the novel class of h-type (hybrid) peptide pheromone precursors with H. jecorina HPP1 as the first member of this class. PMID- 20735773 TI - A ubiquitin-10 promoter-based vector set for fluorescent protein tagging facilitates temporal stability and native protein distribution in transient and stable expression studies. AB - Fluorescent tagging of proteins and confocal imaging techniques have become methods of choice in analysing the distributions and dynamic characteristics of proteins at the subcellular level. In common use are a number of strategies for transient expression that greatly reduce the preparation time in advance of imaging, but their applications are limited in success outside a few tractable species and tissues. We previously developed a simple method to transiently express fluorescently-tagged proteins in Arabidopsis root epidermis and root hairs. We describe here a set of Gateway-compatable vectors with fluorescent tags incorporating the ubiqutin-10 gene promoter (P(UBQ10) ) of Arabidopsis that gives prolonged expression of the fluorescently-tagged proteins, both in tobacco and Arabidopsis tissues, after transient transformation, and is equally useful in generating stably transformed lines. As a proof of principle, we carried out transformations with fluorescent markers for the integral plasma membrane protein SYP121, a member of the SNARE family of vesicle-trafficking proteins, and for DHAR1, a cytosolic protein that facilitates the scavenging of reactive oxygen species. We also carried out transformations with SYP121 and its interacting partner, the KC1 K(+) channel, to demonstrate the utility of the methods in bimolecular fluorescence complementation (BiFC). Transient transformations of Arabidopsis using Agrobacterium co-cultivation methods yielded expression in all epidermal cells, including root hairs and guard cells. Comparative studies showed that the P(UBQ10) promoter gives similar levels of expression to that driven by the native SYP121 promoter, faithfully reproducing the characteristics of protein distributions at the subcellular level. Unlike the 35S-driven construct, expression under the P(UBQ10) promoter remained elevated for periods in excess of 2 weeks after transient transformation. This toolbox of vectors and fluorescent tags promises significant advantages for the study of membrane dynamics and cellular development, as well as events associated with environmental stimuli in guard cells and nutrient acquisition in roots. PMID- 20735774 TI - Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure. AB - BACKGROUND: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown. AIM: To examine whether paracetamol-induced acute liver failure increases long-term mortality. METHODS: We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984-2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not. RESULTS: We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02-2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure. CONCLUSIONS: Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself. PMID- 20735775 TI - Cell division in a minimal bacterium in the absence of ftsZ. AB - Mycoplasma genomes exhibit an impressively low amount of genes involved in cell division and some species even lack the ftsZ gene, which is found widespread in the microbial world and is considered essential for cell division by binary fission. We constructed a Mycoplasma genitalium ftsZ null mutant by gene replacement to investigate the role of this gene and the presence of alternative cell division mechanisms in this minimal bacterium. Our results demonstrate that ftsZ is non-essential for cell growth and reveal that, in the absence of the FtsZ protein, M. genitalium can manage feasible cell divisions and cytokinesis using the force generated by its motile machinery. This is an alternative mechanism, completely independent of the FtsZ protein, to perform cell division by binary fission in a microorganism. We also propose that the mycoplasma cytoskeleton, a complex network of proteins involved in many aspects of the biology of these microorganisms, may have taken over the function of many genes involved in cell division, allowing their loss in the regressive evolution of the streamlined mycoplasma genomes. PMID- 20735776 TI - A structural model of anti-anti-sigma inhibition by a two-component receiver domain: the PhyR stress response regulator. AB - PhyR is a hybrid stress regulator conserved in alpha-proteobacteria that contains an N-terminal sigma-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-sigma factor. PhyR thus functions as an anti-anti-sigma factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as sigma(T) and its anti-sigma factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 A resolution, which provides insight into the mechanism of anti-anti-sigma regulation. Direct intramolecular contact between the PhyR receiver and SL domains spans regions sigma2 and sigma4, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of alpha4-beta5-alpha5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions sigma2 and sigma4 in the SL domain to open about a flexible connector loop and bind anti-sigma factor. PMID- 20735777 TI - Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA. AB - Extracellular polysaccharides are important components of biofilms. In non-mucoid Pseudomonas aeruginosa strains, the Pel and Psl polysaccharides are major structural components of the biofilm matrix. In this study, we demonstrate that the alternative sigma-factor RpoS is a positive transcriptional regulator of psl gene expression. Furthermore, we show that psl mRNA has an extensive 5' untranslated region, to which the post-transcriptional regulator RsmA binds and represses psl translation. Our observations suggest that upon binding RsmA, the region spanning the ribosome binding site of psl mRNA folds into a secondary stem loop structure that blocks the Shine-Dalgarno sequence, preventing ribosome access and protein translation. This constitutes a novel mechanism for translational repression by this family of regulators. PMID- 20735778 TI - Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth. AB - The malaria parasite Plasmodium falciparum invades erythrocytes where it replicates to produce invasive merozoites, which eventually egress to repeat the cycle. Merozoite surface protein-1 (MSP1), a prime malaria vaccine candidate and one of the most abundant components of the merozoite surface, is implicated in the ligand-receptor interactions leading to invasion. MSP1 is extensively proteolytically modified, first just before egress and then during invasion. These primary and secondary processing events are mediated respectively, by two parasite subtilisin-like proteases, PfSUB1 and PfSUB2, but the function and biological importance of the processing is unknown. Here, we examine the regulation and significance of MSP1 processing. We show that primary processing is ordered, with the primary processing site closest to the C-terminal end of MSP1 being cleaved last, irrespective of polymorphisms throughout the rest of the molecule. Replacement of the secondary processing site, normally refractory to PfSUB1, with a PfSUB1-sensitive site, is deleterious to parasite growth. Our findings show that correct spatiotemporal regulation of MSP1 maturation is crucial for the function of the protein and for maintenance of the parasite asexual blood-stage life cycle. PMID- 20735779 TI - Purine restriction induces pronounced translational upregulation of the NT1 adenosine/pyrimidine nucleoside transporter in Leishmania major. AB - Leishmania and other parasitic protozoa are unable to synthesize purines de novo and are reliant upon purine nucleoside and nucleobase transporters to import preformed purines from their hosts. To study the roles of the four purine permeases NT1-NT4 in Leishmania major, null mutants in each transporter gene were prepared and the effect of each gene deletion on purine uptake was monitored. Deletion of the NT3 purine nucleobase transporter gene or both NT3 and the NT2 nucleoside transporter gene resulted in pronounced upregulation of adenosine and uridine uptake mediated by the NT1 permease and also induced up to a 200-fold enhancement in the level of the NT1 protein but not mRNA. A similar level of upregulation of NT1 was achieved in wild-type promastigotes that were transferred to medium deficient in purines. Pulse labelling and treatment of cells with the translation inhibitor cycloheximide revealed that control of NT1 expression occurs primarily at the level of translation and not protein turnover. These observations imply the existence of a translational control mechanism that enhances the ability of Leishmania parasites to import essential purines when they are present at limiting concentrations. PMID- 20735780 TI - Regulation of glutamate dehydrogenase expression in Pseudomonas putida results from its direct repression by NtrC under nitrogen-limiting conditions. AB - Nitrogen-regulated genes in enterobacteria are positively controlled by the transcriptional activator of sigma(N) -dependent promoters NtrC, either directly or indirectly, through the dual regulator Nac. Similar to enterobacteria, gdhA encoding glutamate dehydrogenase from Pseudomonas putida is one of the few genes that is induced by excess nitrogen. In P. putida, the binding of NtrC to the gdhA promoter region and in vitro transcription suggest that, unlike its enterobacterial homologue that is repressed by Nac, gdhA is directly repressed by NtrC. Footprinting analyses demonstrated that NtrC binds to four distinct sites in the gdhA promoter. NtrC dimers bind cooperatively, and those bound closer to the promoter interact with the dimers bound further upstream, thus producing a proposed repressor loop in the DNA. The formation of the higher-order complex and the repressor loop appears to be important for repression but not absolutely essential. Both the phosphorylated and the non-phosphorylated forms of NtrC efficiently repressed gdhA transcription in vitro and in vivo. Therefore, NtrC repression of gdhA under nitrogen-limiting conditions does not depend on the phosphorylation of the regulator; rather, it relies on an increase in the repressor concentration under these conditions. PMID- 20735781 TI - Temporal anatomy of an epigenetic switch in cell programming: the white-opaque transition of C. albicans. AB - The human pathogen Candida albicans undergoes a well-defined switch between two distinct cell types, named 'white' and 'opaque'. White and opaque cells differ in metabolic preferences, mating behaviours, cellular morphologies and host interactions. Each cell type is stable through many generations; switching between them is rare, stochastic and occurs without any known changes in the primary sequence of the genome; thus the switch is epigenetic. The white-opaque switch is regulated by a transcriptional circuit, composed of four regulators arranged in a series of interlocking feedback loops. To understand how switching occurs, we investigated the order of regulatory changes that occur during the switch from the opaque to the white cell type. Surprisingly, changes in key transcriptional regulators occur gradually, extending over several cell divisions with little cell-to-cell variation. Additional experiments, including perturbations to regulator concentrations, refine the signature of the commitment point. Transcriptome analysis reveals that opaque cells begin to globally resemble white cells well before they irreversibly commit to switching. We propose that these characteristics of the switching process permit C. albicans to 'test the waters' before making an all-or-none decision. PMID- 20735782 TI - Clinical trial: the microbiological and immunological effects of synbiotic consumption - a randomized double-blind placebo-controlled study in active Crohn's disease. AB - BACKGROUND: Crohn's disease is an inflammatory illness in which the immune response against gut microorganisms is believed to drive an abnormal immune response. Consequently, modification of mucosal bacterial communities, and the immune effects they elicit, might be used to modify the disease state. AIM: To investigate the effects of synbiotic consumption on disease processes in patients with Crohn's disease. METHODS: A randomized, double-blind placebo-controlled trial was conducted involving 35 patients with active Crohn's disease, using a synbiotic comprising Bifidobacterium longum and Synergy 1. Clinical status was scored and rectal biopsies were collected at the start, and at 3- and 6-month intervals. Transcription levels of immune markers and mucosal bacterial 16S rRNA gene copy numbers were quantified using real-time PCR. RESULTS: Significant improvements in clinical outcomes occurred with synbiotic consumption, with reductions in both Crohn's disease activity indices (P = 0.020) and histological scores (P = 0.018). The synbiotic had little effect on mucosal IL-18, INF-gamma and IL-1beta; however, significant reductions occurred in TNF-alpha expression in synbiotic patients at 3 months (P = 0.041), although not at 6 months. Mucosal bifidobacteria proliferated in synbiotic patients. CONCLUSION: Synbiotic consumption was effective in improving clinical symptoms in patients with active Crohn's disease. PMID- 20735783 TI - Dilated intercellular space in chronic laryngitis and gastro-oesophageal reflux disease: at baseline and post-lansoprazole therapy. AB - BACKGROUND: Dilation of intercellular spaces is reported to be an early morphological marker in gastro-oesophageal reflux. It remains unknown if this marker is useful in diagnosing reflux-related chronic laryngitis. AIM: To determine histopathology and electron microscopic changes in oesophageal and laryngeal epithelium in chronic laryngitis. METHODS: In this prospective blinded study, we enrolled 53 participants: 15 controls, 20 patients with GERD and 18 patients with chronic laryngitis. The latter two groups were subsequently treated with lansoprazole 30 mg bid for 12-weeks. Baseline and postacid suppressive therapy biopsies were obtained from distal oesophagus and laryngeal postcricoid areas. Biopsy specimens were evaluated for histopathology and dilated intercellular space changes. RESULTS: There was no significant increase in oesophageal or laryngeal epithelium intercellular spaces among GERD or laryngitis patients compared with controls at baseline or postacid suppressive therapy. Only patients with GERD had significantly (P = 0.03) higher proportion of moderate-to severe oesophageal spongiosis and basal cell hyperplasia, which normalized postacid suppressive therapy. CONCLUSIONS: There was no increase in the width of intercellular spaces in the oesophagus or larynx in GERD or chronic laryngitis at baseline or postacid suppressive therapy. Our findings question the uniform presence of dilated intercellular space in patients with GERD. PMID- 20735784 TI - The Mycoplasma genitalium MG352-encoded protein is a Holliday junction resolvase that has a non-functional orthologue in Mycoplasma pneumoniae. AB - Recombination between repeated DNA elements in the genomes of Mycoplasma species appears to lie at the basis of antigenic variation of several essential surface proteins. It is therefore imperative that the DNA recombinatorial pathways in mycoplasmas be unravelled. Here, we describe the proteins encoded by the Mycoplasma genitalium MG352 and Mycoplasma pneumoniae MPN528a genes (RecU(Mge) and RecU(Mpn) respectively), which share sequence similarity with RecU Holliday junction (HJ) resolvases. RecU(Mge) was found to: (i) bind HJ substrates and large double-stranded DNA molecules and (ii) cleave HJ substrates at the sequence 5'-(G) /(T) C?(C) /(T) T(A) /(G) G-3' in the presence of Mn(2+). Interestingly, RecU(Mpn) (from M. pneumoniae subtype 2 strains) did not possess obvious DNA binding or cleavage activities, which was found to be caused by the presence of a glutamic acid residue at position 67 of the protein, which is not conserved in RecU(Mge). Additionally, RecU(Mpn) appears not to be expressed by subtype 1 M. pneumoniae strains, as these possess a TAA translation termination codon at position 181-183 of MPN528a. We conclude that RecU(Mge) is a HJ resolvase that may play a central role in recombination in M. genitalium. PMID- 20735785 TI - Corneal volume measures for monitoring contact lens induced corneal swelling: a pilot study. AB - BACKGROUND: This study investigated the use of corneal volume to monitor the corneal swelling response induced by wearing high plus power contact lenses. METHODS: Twelve young non-contact lens wearers were recruited with one eye fitted with a soft contact lens (Polymacon material, 38.6 per cent water, Dk of 9 and 0.27 mm centre thickness) and the fellow eye served as control. The treated eye was patched for two hours leaving the control eye uncovered. Central corneal thickness (CCT) was measured with non-contact specular microscopy and corneal volumes (at three, five and 10 mm zones) were measured with a corneal topographer (Pentacam, Oculus Inc, Germany), before eye patching as well as immediately after and every 20 minutes for 100 minutes. RESULTS: Subjects had similar CCT and corneal volumes between the two eyes before treatment. The treatment eyes showed a mean corneal swelling of 8.1 per cent immediately after lens removal. Corneal volume was significantly increased at the three (mean swelling of 5.9 per cent), five (5.6 per cent) and 10 millimetre (3.3 per cent) zones. It took 20 minutes for the corneal volume at the 10 mm zone to return to baseline but required 60 minutes for the three and five millimetre zones to return to the baseline level. The central corneal thickness was still significantly thicker 80 minutes after patching. CONCLUSION: Corneal volume could be a useful parameter to monitor corneal change when an event affects the entire cornea. Corneal volume combined with central corneal thickness could give more comprehensive information to monitor central corneal swelling. PMID- 20735786 TI - Complications of cataract surgery. AB - Modern cataract surgery is safe in more than 95 per cent of patients. In the small number of cases where a serious complication occurs, the most common is an intra-operative posterior capsular rupture. This can lead to vitreous loss or a dropped nucleus and can increase the risk of post-operative cystoid macular oedema or retinal detachment. Post-operatively, posterior capsular opacification is the most common complication and can be readily treated with a YAG capsulotomy. The most devastating complication is endophthalmitis, the rate of which is now significantly decreased through the use of intracameral antibiotics. As a clinician, the most important step is to assess the patient pre-operatively to predict higher risk individuals and to counsel them appropriately. In these patients, various pre- or intra-operative management steps can be taken in addition to routine phacoemulsification to optimise their visual outcome. PMID- 20735787 TI - Surgical correction of astigmatism during cataract surgery. AB - High levels of corneal astigmatism are prevalent in a significant proportion of the population. During cataract surgery pre-existing astigmatism can be corrected using single or paired incisions on the steep axis of the cornea, using relaxing incisions or with the use of a toric intraocular lens. This review provides an overview of the conventional methods of astigmatic correction during cataract surgery and in particular, discusses the various types of toric lenses presently available and the techniques used in determining the correct axis for the placement of such lenses. Furthermore, the potential causes of rotation in toric lenses are identified, along with techniques for assessing and quantifying the amount of rotation and subsequent management options for addressing post operative rotation. PMID- 20735788 TI - Ocular preference following implantation of aspheric and spherical intraocular lenses; an intra-individual comparison. AB - PURPOSE: recently, intraocular lenses (IOLs) that possess an aspheric design, compensating for the spherical aberration (SA) of the cornea, have been developed. We designed this study to compare a group of patients who had undergone bilateral cataract surgery and had received one spherical IOL and one aspheric IOL, to assess their ocular preference. METHODS: patients were recruited from those who had undergone bilateral cataract surgery during the preceding six months (32 patients). Types of aspheric IOLs, which were used included: Tecnis ZA9003, AcrysofIQ SN60WF and Akreos Adapt AO. Contrast acuity was measured using a CSV-1000CVA instrument and spherical aberration (SA) was measured using a Zywave aberrometer. Patients also answered a brief questionnaire, designed to determine whether they could detect any difference between their spherical and aspheric IOLs and whether they had an ocular preference. RESULTS: no differences were found between spherical and aspheric IOLs in contrast acuity. Total ocular spherical aberration was greater among eyes with spherical IOLs compared with aspheric IOLs (t = 6.67; p < 0.0001). Patients' ocular preference was unrelated to the presence of an aspheric IOL or the amount of spherical aberration, but was associated with the level of ametropia and visual acuity. CONCLUSIONS: we were unable to find any impact on a patient's subjective visual quality from a reduction of spherical aberration by the presence of an aspheric IOL. Ocular preference was determined by level of visual acuity and degree of ametropia post operatively. PMID- 20735789 TI - Resolution of high myopia following herpes simplex keratitis. PMID- 20735790 TI - Prenatal undernutrition changes renovascular responses of nimesulide in rat kidneys. AB - Several studies in the Northeastern region of Brazil have demonstrated an association between hypertension in adult populations and prenatal and postnatal undernutrition. The central hypothesis we proposed was that hypertension could be favoured by programmed alterations in branches of the renal arachidonic pathway and consequently in counter-balancing the renin angiotensin system, especially during treatments with cyclooxygenase inhibitors. We assessed the influence of subchronic (21 days) and acute administration of nimesulide, a preferential cyclooxygenase-2 (COX-2) inhibitor, on mean blood pressure (MAP), renal blood flow (RBF), glomerular filtration rate (GFR) and urinary output (U(v)) in adult rats that were prenatally undernourished. Undernutrition per se led to the onset of mild hypertension in adult offspring, whereas subchronic nimesulide treatment increased MAP in control and elicited further augmentation in undernourished animals. The drug (i) decreased RBF and GFR in controls by 50%, whereas no effect was detected in the undernourished group, and (ii) increased U(v) by 25% in controls, an effect that was potentiated by 200% in programmed animals. In contrast, acute nimesulide administration decreased U(v) , with the hypertensive effect of the drug being potentiated during dehydration. These findings demonstrate that prenatal nutritional programming differentially modulates adult renovascular responses to nimesulide in the cortex and medulla, which may exacerbate the deleterious effects of COX-2 inhibition in the kidney. PMID- 20735791 TI - Short-term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia. AB - OBJECTIVES: To compare the efficacy and safety of silodosin and tamsulosin in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by a randomized crossover method. METHODS: BPH patients with the complaint of LUTS were included in this study, and were randomly divided into two groups: a silodosin-preceding group (4 weeks of twice daily administration of silodosin at 4 mg, followed by 4 weeks of once-daily administration of tamsulosin at 0.2 mg) or a tamsulosin-preceding group (4 weeks' administration of tamsulosin, followed by 4 weeks' administration of silodosin). No drug withdrawal period was provided when switching the drug. RESULTS: In the first treatment period, both drugs significantly improved the International Prostate Symptom Score total score, but the improvement by silodosin was significantly superior to that by tamsulosin. After crossover treatment, significant improvement was observed only with silodosin treatment. Moreover, intergroup comparison of changes revealed that silodosin showed significant improvement of straining and nocturia with first and crossover treatments, respectively, compared with tamsulosin. Silodosin also significantly improved quality of life (QOL) score in both treatment periods, while tamsulosin significantly improved QOL score only in the first treatment period. The most frequent adverse drug reaction was ejaculatory disorder with silodosin; however, the incidence of dizziness with silodosin was similar to that with tamsulosin. CONCLUSIONS: In BPH/LUTS patients, silodosin exhibits excellent efficacy in improving subjective symptoms in both initial and crossover treatment, and it appears to improve the QOL of patients. PMID- 20735792 TI - Wildlife diseases: from individuals to ecosystems. AB - 1. We review our ecological understanding of wildlife infectious diseases from the individual host to the ecosystem scale, highlighting where conceptual thinking lacks verification, discussing difficulties and challenges, and offering potential future research directions. 2. New molecular approaches hold potential to increase our understanding of parasite interactions within hosts. Also, advances in our knowledge of immune systems makes immunological parameters viable measures of parasite exposure, and useful tools for improving our understanding of causal mechanisms. 3. Studies of transmission dynamics have revealed the importance of heterogeneity in host behaviour and physiology, and of contact processes operating at different spatial and temporal scales. An important future challenge is to determine the key transmission mechanisms maintaining the persistence of different types of diseases in the wild. 4. Regulation of host populations is too complex to consider parasite effects in isolation from other factors. One solution is to seek a unified understanding of the conditions under which (and the ecological rules determining when) population scale impacts of parasites can occur. 5. Good evidence now shows that both direct effects of parasites, and trait mediated indirect effects, frequently mediate the success of invasive species and their impacts on recipient communities. A wider exploration of these effects is now needed. 6. At the ecosystem scale, research is needed to characterize the circumstances and conditions under which both fluxes in parasite biomass, and trait mediated effects, are significant in ecosystem processes, and to demonstrate that parasites do indeed increase 'ecosystem health'. 7. There is a general need for more empirical testing of predictions and subsequent development of theory in the classic research cycle. Experimental field studies, meta-analyses, the collection and analysis of long-term data sets, and data constrained modelling, will all be key to advancing our understanding. 8. Finally, we are only now beginning to understand the importance of cross-scale interactions associated with parasitism. Such interactions may offer key insights into bigger picture questions such as when and how different regulatory factors are important, when disease can cause species extinctions, and what characteristics are indicative of functionally resilient ecosystems. PMID- 20735794 TI - Tuning in to Kids: improving emotion socialization practices in parents of preschool children--findings from a community trial. AB - BACKGROUND: This study evaluated a new prevention and early intervention parenting program: Tuning in to Kids. The program aims to improve emotion socialization practices in parents of preschool children and is based on research evidence that parents' responses to, and coaching of, their children's emotions influence emotional and behavioral functioning in children. METHODS: Two hundred and sixteen primary caregiver parents of children aged 4.0-5.11 years were randomized into an intervention or waitlist control group. Parents in the intervention condition attended a 6-session group parenting program plus two booster sessions. Assessment occurred pre-intervention, post-intervention and at six-month follow-up. Questionnaires assessed parent emotion awareness and regulation, parent beliefs and practices of emotion socialization (emotion dismissing, emotion coaching, empathy) and child behavior (parent and teacher report). Observation of emotion socialization practices and child emotional knowledge was conducted pre-intervention and at follow-up with 161 parent-child dyads. RESULTS: Parents in the intervention condition reported significant improvements in their own emotion awareness and regulation, increases in emotion coaching, and decreases in emotionally dismissive beliefs and behaviors. There were increases in parents' observed use of emotion labels and discussion of causes and consequences of emotions with their children. Child emotional knowledge improved, and reductions in child behavior problems were reported by parents and teachers. CONCLUSIONS: This study provides support for the efficacy of a parenting intervention targeting parent emotion socialization practices that lead to improved child emotional knowledge and behavior. This preventative intervention targeting parents' own emotion awareness and regulation, as well as emotional communication in parent-child relationships, is a promising addition to available parenting programs. PMID- 20735795 TI - Enamel matrix derivative proteins for the treatment of proximal class II furcation involvements: a prospective 24-month randomized clinical trial. AB - OBJECTIVE: This study aimed to evaluate the response of proximal furcations treated with enamel matrix derivative proteins (EMD) in a 24-month follow-up. MATERIALS AND METHODS: Twelve patients presenting bilateral class II proximal furcation with vertical probing depth (PD) >=5 mm and bleeding on probing were selected. The furcations were assigned to: a control group (n=12), open flap debridement (OFD)+EDTA and a test group (n=12) - OFD+EDTA+EMD. The gingival margin position, PD, relative vertical and horizontal clinical attachment level (RVCAL and RHCAL), vertical and horizontal bone level (VBL and HBL) and furcation closure were evaluated before treatment and after 6, 12 and 24 months. RESULTS: After follow-up, no statistical difference could be seen between groups. At 24 months, the test group showed 1.9 +/- 1.6 mm PD reduction whereas the control group showed 1.0 +/- 1.3 mm PD reduction. RHCAL gains of the control and the test group were 0.7 +/- 1.3 and 1.4 +/- 0.9 mm, respectively. However, at 24 months, the test group only presented five remaining class II furcations versus 10 furcations in the control group (p<0.05). CONCLUSION: It could be concluded that EMD therapy promoted a reduction in the number of proximal furcations presenting a diagnosis of class II after 24 months of treatment compared with OFD therapy. PMID- 20735796 TI - Osteotome sinus floor elevation technique without grafting: a 5-year prospective study. AB - AIM: To evaluate the long-term stability of peri-implant bone formation following implant placement without grafting into resorbed posterior maxillae. MATERIALS AND METHODS: Twenty-five implants of 10 mm were placed in 17 patients to rehabilitate atrophic maxillae by means of an osteotome sinus floor elevation (OSFE) procedure without grafting. Mean residual bone height was 5.4+/-2.3mm. Bone levels were evaluated at 1, 3 and 5 years using periapical radiographs. RESULTS: All implants fulfilled survival criteria and gained peri-implant bone (mean increase 3.2+/-1.3mm). Implant protrusion into the sinus decreased from 4.9+/-1.9mm after surgery to 1.5+/-0.9mm after 5 years. Mean crestal bone loss amounting to 0.8+/-0.8mm stabilized over the 5-year observation interval. Twenty implants showed additional peri-implant bone gain following the 1-year control. CONCLUSIONS: Implant rehabilitation of atrophic maxillae may be greatly simplified using implants 10mm and the OSFE technique without grafting. Grafting material is not needed to gain at least 3mm of bone in the atrophic maxilla. The procedure appears predictable with favourable long-term results. PMID- 20735799 TI - Age-related changes in elastic properties and moisture content of lower labial mucosa. AB - The purpose of this study was to clarify age-related changes in the elastic properties and moisture content of the lower labial mucosa. Elastic properties and moisture content were also compared between the lower labial mucosa and skin. A total of 85 adults aged 20-82 took part in the study. Elastic properties (distensibility and elasticity) and moisture content of lower labial mucosa and skin were determined in each participant. Measurements for the oral mucosa were taken at the midline of the lower labial mucosa; for the skin, they were taken at the midpoint of the right anterior surface of the forearm. Pearson's correlation coefficient and the Mann-Whitney U test were used for the statistical analysis. A stepwise multiple linear regression analysis was also performed, with age as the dependent variable and sex, distensibility, elasticity and moisture content of the lower labial mucosa as independent variables. A negative correlation was found between age and distensibility of the lower labial mucosa. No correlation was observed between age and elasticity of the lower labial mucosa. A negative correlation was observed between age and moisture content of the lower labial mucosa. A significant difference was observed in moisture content between the 20- to 39-year-old group and the over 40-year-old group. Stepwise analysis identified distensibility and moisture content of the lower labial mucosa as predictive factors of age. The results indicate that distensibility and moisture content of the lower labial mucosa decrease with age. Moisture content in the over 40-year old group, in particular, was lower than in the 20- to -30-year-old group. PMID- 20735797 TI - Application of a sensitive, specific and controlled real-time PCR assay to surveillance indicates a low prevalence of viral haemorrhagic septicaemia virus (VHSV) in wild herring, Clupea harengus L., in Scottish waters. AB - Surveillance data on the distribution of viral haemorrhagic septicaemia virus (VHSV) in the North Sea (UK), targeting Atlantic herring in areas with previous virus detection, were obtained from research cruises conducted during 2005. The sensitive molecular approach of real-time RT-PCR (qRT-PCR) was applied alongside a newly developed endogenous positive control assay specific for herring (elongation factor 1alpha) to ensure integrity of template. Three hundred and five pools from 1937 individual herring were tested, and no evidence of VHSV in association with wild Atlantic herring was detected. Samples were obtained from Scottish waters where marine aquaculture is conducted. The results confirm that previous tissue culture studies have most likely not significantly underestimated the prevalence of carrier herring in this area. The significance of migratory species such as herring as a reservoir species for VHSV, with the potential to translocate virus genotypes between geographical areas, is discussed. PMID- 20735798 TI - Intrahippocampal corticosterone response in mice selectively bred for extremes in stress reactivity: a microdialysis study. AB - The hypothalamic-pituitary-adrenocortical (HPA) axis is one of the major stress hormone systems, and glucocorticoids (GCs) play a pivotal role in homeostatic processes throughout the body and brain. A dysregulation of the HPA axis, leading to an aberrant secretion of GCs, is associated with affective disorders such as major depression. In the present study, three mouse lines selectively bred for high (HR), intermediate (IR) or low (LR) stress reactivity were used to elucidate the temporal dynamics of intrahippocampal corticosterone (CORT) in response to a standardised stressor. In particular, we addressed the question of whether the distinct differences in HPA axis reactivity between the three mouse lines, as determined by plasma CORT measurements, are present in the central nervous system as well, and if the respective endophenotype is brought about by alterations in blood-brain barrier (BBB) functionality. We applied in vivo microdialysis in the hippocampus, demonstrating that the concentrations of CORT released from the adrenals in response to restraint stress are not only distinctly different in the plasma, but can also be found in the central nervous system, although the differences between the three mouse lines were attenuated, particularly between IR and LR animals. Additionally, a time lag of approximately 60 min was observed in all three lines regarding intrahippocampal peak concentrations of CORT after the onset of the stressor. Furthermore, we showed that the penetration and clearance of CORT in the hippocampal tissue was not affected by differences in BBB functionality because the multidrug resistance 1 P-glycoprotein (Mdr1 Pgp) was equally expressed in HR, IR and LR mice. Furthermore, we could exclude surgical damage of the BBB because peripherally-injected dexamethasone, which is a high affinity substrate for the Mdr1 Pgp and therefore restricted from entering the brain, could only be detected in the plasma and was virtually absent in the brain. PMID- 20735793 TI - Annual Research Review: Development of the cerebral cortex: implications for neurodevelopmental disorders. AB - The cerebral cortex has a central role in cognitive and emotional processing. As such, understanding the mechanisms that govern its development and function will be central to understanding the bases of severe neuropsychiatric disorders, particularly those that first appear in childhood. In this review, I highlight recent progress in elucidating genetic, molecular and cellular mechanisms that control cortical development. I discuss basic aspects of cortical developmental anatomy, and mechanisms that regulate cortical size and area formation, with an emphasis on the roles of fibroblast growth factor (Fgf) signaling and specific transcription factors. I then examine how specific types of cortical excitatory projection neurons are generated, and how their axons grow along stereotyped pathways to their targets. Next, I address how cortical inhibitory (GABAergic) neurons are generated, and point out the role of these cells in controlling cortical plasticity and critical periods. The paper concludes with an examination of four possible developmental mechanisms that could contribute to some forms of neurodevelopmental disorders, such as autism. PMID- 20735800 TI - Comparative immunogenicity of two vaccination schedules of a combined hepatitis A and B vaccine in healthy volunteers. AB - In 1996, a combined vaccine against both hepatitis A and B was licensed and commercialized and has been recommended for healthcare personnel in Belgium. This study compares the immunogenicity against hepatitis B virus (HBV) and safety of two vaccination schedules (0-1-12 months and 0-1-6 months) with this vaccine. This is a randomized, stratified and controlled study in healthy adult workers, who are not occupationally exposed to HBV. Seroconversion (>=1 IU/L) and seroprotection (>=10 IU/L) rates were compared using Fisher's exact test; geometric mean concentrations (GMCs) of anti-HBs were compared using one-way ANOVA. All statistical analyses were carried out with SPSS 11 on Apple Macintosh. A total of 399 subjects were enrolled in the study, and 356 were analysed according to the protocol. The rate of >=10 IU/L at 6 months was 70.6% in the group 0-1-12 and 79.9% in the group 0-1-6; this rate decreased to 55.9% at 12 months in the first group. Seroconversion and seroprotective rates against HBV measured at month 13 in group 0-1-12 (98.9% and 95.6%) and measured at month 7 in group 0-1-6 (99.4% and 97.1%) were not statistically significantly different. GMC of anti-HBs after the 0-1-12 schedule was more than two fold higher than after 0 1-6 schedule (P < 0.001). Reported side effects were comparable in both groups with a slight tendency to fewer side effects in the 0-1-12 group after the third dose. The results from our study show that the completed schedule 0-1-12 offers at least equal protective immunogenicity against HBV as the completed 0-1-6 schedule. People not receiving their third dose at 6 months can be given this dose up to 12 months after the first dose. The drawback of this flexibility, however, is the longer time period before the protection becomes effective. PMID- 20735801 TI - Emergence delirium and postoperative pain in children undergoing adenotonsillectomy: a comparison of propofol vs sevoflurane anesthesia. AB - BACKGROUND: Emergence delirium (ED) is a frequent postoperative complication in young children undergoing ENT procedures and it may be exacerbated by sevoflurane anesthesia whereas propofol maintenance has been suggested to decrease the incidence of ED. The aim of this randomized, prospective, double-blind study was to evaluate the effect of sevoflurane vs propofol anesthesia on the quality of recovery after adenotonsillectomy. METHODS: Forty-two patients were randomized to maintenance with either propofol or sevoflurane for adenotonsillectomy. At the conclusion of surgery, patients were extubated awake. ED and pain were assessed using the Pediatric Anesthesia Emergence Delirium (PAED) and the Children's Hospital of Eastern Ontario Scale (CHEOPS), respectively. Higher PAED scores (0 20) indicate greater severity of ED. Nursing and parental satisfaction, hospital length of stay, postoperative nausea and vomiting (PONV), anesthetic complications, and subsequent emergency room admissions were also assessed. RESULTS: Median PAED score was 14 in the propofol group and 17 in the sevoflurane group (NS). Propofol was associated with less pain medication required during recovery and a lower incidence of PONV (5.3% vs 36.8%, P < 0.05). Nursing and parental satisfaction as well as time spent in recovery room was similar for the two groups. CONCLUSION: Propofol anesthesia does not influence agitation after adenotonsillectomy, as measured by the PAED score. A PAED score of >= 10 was not useful in identifying patients with ED. However, propofol maintenance is associated with less need for pain medication in the recovery room and a lower incidence of PONV compared to sevoflurane anesthesia. PMID- 20735802 TI - Oral bioavailability of clonidine in children. AB - BACKGROUND: Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75-100% but is unknown in children. METHODS: Children (3-10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg.kg(-1) mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography-mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed-effects models. Current data were pooled with published time-concentration profiles from children (n = 49) administered intravenous clonidine to determine oral bioavailability. RESULTS: There were eight children studied (age 3-10 years, weight 10.5-36 kg). A two-compartment model with first-order absorption and elimination was used to describe time-concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70-kg person, were absorption half-life (Tabs), 0.45 (85.1; 0.221-0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002-0.316) h, Clearance (CL) 17.9 (30.3; 16-20.3) l.h(-1) per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1-165) l.h(-1) per 70 kg, central volume (V1) 81.2 (71.5; 60.7-105) l.70 kg(-1), peripheral volume of distribution (V2) 113 (33.9; 91-131) l.70 kg(-1). The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654). CONCLUSIONS: Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (T(max) 1.04 h, C(max) 0.77 mcg.l(-1)). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults. PMID- 20735803 TI - The relationship between intimate partner violence and children's asthma in 10 US states/territories. AB - Intimate partner violence (IPV) has been shown to negatively impact the health of both the adults who experience IPV and the children who are exposed to IPV. Although IPV experienced by women has been linked to children's asthma, this study is the first to examine this question among both women and men, and the first study in the United States to examine this question as part of a population based data set. In 2005, ten US states/territories administered an IPV module and a children's asthma module within the Behavioral Risk Factor Surveillance System (BRFSS). Lifetime IPV was assessed by four questions that asked about threatened, attempted, or completed physical violence, as well as unwanted sex, by a current or former intimate partner. The children's asthma module asked respondents to report whether a randomly selected child in their household had ever been diagnosed with asthma and whether the same child currently had asthma. Women who experienced lifetime IPV, in contrast to women who never experienced IPV, were significantly more likely to report that their children had ever had asthma and currently have asthma. Among men, significant differences were not found when comparing men who reported lifetime IPV to those that did not report lifetime IPV. The results highlight the importance of primary prevention of IPV, as reducing the occurrence of IPV could improve not only the long-term health of those who experience IPV but also the health of their children. PMID- 20735804 TI - A randomized, double-blind study comparing the efficacy of selenium sulfide shampoo 1% and ciclopirox shampoo 1% as adjunctive treatments for tinea capitis in children. AB - Our objective was to compare the efficacy of selenium sulfide shampoo 1% and ciclopirox shampoo 1% as adjunctive treatments for tinea capitis in children. Forty children aged 1-11 years with clinically diagnosed tinea capitis were randomized to receive selenium sulfide shampoo 1% or ciclopirox shampoo 1% twice a week as adjuncts to an 8-week course of ultramicronized griseofulvin dosed at 10-12 mg/kg/day. At weeks 2, 4, and 8, subjects returned to the clinic for evaluation and scalp cultures. Subjects then returned for follow-up visits 4 weeks after completing treatment. Overall, by 8 weeks, 30 of 33 (90.9%) treated children demonstrated mycological cure. Selenium sulfide shampoo 1% and ciclopirox shampoo 1% were equally effective as adjunctive treatments for tinea capitis in children in our study. PMID- 20735805 TI - Children treated for epileptic encephalopathies show improved glucose metabolism. AB - Epileptic neurological disorders in infants are often difficult to distinguish, and call for disparate treatments. Positron emission tomography (PET) using an [18F] fluoro-2-deoxyglucose (18FDG) tracer, is a powerful non-invasive technique successful in improving the diagnosis of a number of conditions. Interestingly, this technique has shown that cerebral glucose hypometabolism is present in children with epileptic encephalopathies (EE). Ten children with age-dependent EE were recruited and routine 18FDG PET images were evaluated for their ability to indicate cerebral glucose metabolism both before and after anti-epileptic treatment. We found that there is diffuse glucose hypometabolism in both hemispheres before treatment, indicating EE. Following treatment, the number of epileptic episodes significantly decreased (P < 0.05), while cerebral glucose metabolism improved. Our findings suggest that 18FDG PET can be utilized to monitor cerebral glucose metabolism as a measure of treatment progress in EE. PMID- 20735806 TI - Therapeutic strategies of meconium obstruction of the small bowel in very-low birthweight neonates. AB - BACKGROUND: Meconium obstruction without cystic fibrosis in low-birthweight neonates is a distinct clinical entity. We aimed to determine what therapeutic strategies work best in very-low-birthweight neonates with meconium obstruction of the small bowel under varied clinical conditions caused by the associated diseases of prematurity. METHODS: Medical records of very-low-birthweight neonates with meconium obstruction of the small bowel treated from 1998 to 2008 were retrospectively reviewed. Pre- and postnatal data, treatments, and clinical outcomes were assessed. RESULTS: Nine patients with perinatal complications were identified. Mean gestational age and birthweight were 26.9 weeks and 863 g, respectively. Abdominal distension developed from 1 to 7 days of life. Five patients were initially treated with Gastrografin enema, three of whom had successful outcomes. Two hemodynamically unstable patients failed to respond to Gastrografin treatment; they ultimately died of sepsis. The remaining four without Gastrografin treatment underwent enterostomy to resolve the obstructions with good results. CONCLUSIONS: Gastrografin and surgical treatments should be appropriately selected based on the underlying pathologies of meconium obstruction of the small bowel. Therapeutic Gastrografin enema is effective, safe and repeatable; however, it is not recommended for hemodynamically unstable patients. Surgical intervention is reserved for those who develop rapid abdominal distension that risks perforation. PMID- 20735807 TI - Prophylactic treatment for hypertension and seizure in a case of allogeneic hematopoietic stem cell transplantation after posterior reversible encephalopathy syndrome. AB - A six-yr-old boy developed PRES after induction chemotherapy for the relapse of acute lymphoblastic leukemia. Two months after PRES, he underwent BMT from an unrelated HLA-mismatched donor. There were many risk factors for PRES in the BMT including the long-term use of FK506 and methylprednisolone, grade III graft versus-host disease, thrombotic microangiopathy, and sepsis. Prophylactic treatment for hypertension with nicardipine in conjunction with close monitoring of the magnesium level and the use of valproic acid might be an effective management approach to prevent post-transplant PRES. PMID- 20735808 TI - Development and evaluation of fiber optic probe-based helium-neon low-level laser therapy system for tissue regeneration--an in vivo experimental study. AB - We report the design and development of an optical fiber probe-based Helium-Neon (He-Ne) low-level laser therapy system for tissue regeneration. Full thickness excision wounds on Swiss albino mice of diameter 15 mm were exposed to various laser doses of 1, 2, 3, 4, 6, 8 and 10 J cm(-2) of the system with appropriate controls, and 2 J cm(-2) showing optimum healing was selected. The treatment schedule for applying the selected laser dose was also standardized by irradiating the wounds at different postwounding times (0, 24 and 48 h). The tissue regeneration potential was evaluated by monitoring the progression of wound contraction and mean wound healing time along with the hydroxyproline and glucosamine estimation on wound ground tissues. The wounds exposed to 2 J cm(-2) immediately after wounding showed considerable contraction on days 5, 9, 12, 14, 16 and 19 of postirradiation compared with the controls and other treatment schedules, showing significant (P < 0.001) decrease in the healing time. A significant increase in hydroxyproline and glucosamine levels was observed for the 2 J cm(-2) irradiation group compared with the controls and other treatment groups. In conclusion, the wounds treated with 2 J cm(-2) immediately after the wounding show better healing compared with the controls. PMID- 20735809 TI - Revalidation and update of the TASH-Score: a scoring system to predict the probability for massive transfusion as a surrogate for life-threatening haemorrhage after severe injury. AB - BACKGROUND: The Trauma Associated Severe Haemorrhage (TASH)-Score has been recognized as an easy-to-calculate scoring system to predict the probability for massive transfusion (MT) as a surrogate for life-threatening haemorrhage after injury. Changes with respect to management and outcome of these patients over time prompted a revalidation and an update of the TASH-Score. METHODS: The performance of the TASH-Score developed from the 1993-2003 TR-DGU database (Trauma Registry Deutsche Gesellschaft fur Unfallchirurgie/German Trauma Society) was revalidated on 5834 datasets from the 2004-2007 TR-DGU database with respect to discrimination, precision and calibration. The performance of the TASH-Score applied onto the 2004-2007 TR-DGU database was compared to its initial performance, and the logistic function to calculate the probability for MT was modified for score adjustment. RESULTS/CONCLUSIONS: When the original TASH-Score was applied onto the 2004-2007 TR-DGU database, a slight increase in discrimination was observed while precision was considerably lower. The predicted rate for MT within the development dataset was 13.9% while the observed incidence was 14.1%. In contrast, the predicted rate for MT within the revalidation dataset was 11.7%, while the observed rate was 8.4%. The logistic function to calculate MT probability was modified, and the TASH-Score was again evaluated against the most recent TR-DGU 2004-2007 database. The high performance of the score was not only restored but enhanced reflected by an increased ROC/AUC of 0.905. The score can be calculated quickly upon arrival of the patient in the emergency department and may be supportive to correct coagulopathy, to activate logistics and for research. PMID- 20735810 TI - Limits of sequencing and phylogenetic analysis to assess B19V transmission by single-donor blood component. PMID- 20735811 TI - In vitro assessment of apheresis and pooled buffy coat platelet components suspended in plasma and SSP+ photochemically treated with amotosalen and UVA for pathogen inactivation (INTERCEPT Blood SystemTM). AB - BACKGROUND AND OBJECTIVES: INTERCEPT Blood SystemTM is a pathogen inactivation system for blood components. The initial approval required a platelet component to be suspended in a combination of plasma and Platelet additive Solution/PAS III. Improved platelet storage has been reported with Mg++ and K+ supplementation (PAS-IIIM). This study validated the use of INTERCEPTTM/PAS-IIIM for apheresis and pooled buffy-coat platelet components. MATERIALS AND METHODS: The platelet dose and pH throughout 5 days of storage met the European and French requirements for quality standards. RESULTS AND CONCLUSION: Additional metabolic and activation assessments of the treated platelets confirmed the previously reported superiority of PAS-IIIM over PAS-III, but extended it to the INTERCEPTTM process. PMID- 20735812 TI - Stabilizing mutations increase secretion of functional soluble TCR-Ig fusion proteins. AB - BACKGROUND: Whereas T cell receptors (TCRs) detect peptide/major histocompatibility complexes (pMHCs) with exquisite specificity, there are challenges regarding their expression and use as soluble detection molecules due to molecular instability. We have investigated strategies for the production of TCR-immunoglobulin (Ig) fusion proteins. Two different TCRs that are characteristic of a mouse model for idiotype (Id) dependent immune regulation were engineered. They are structurally unrelated with different variable (V), diversity (D) and joining (J) segments, but each share one V gene segment, either Valpha or Vbeta, with the well characterized murine TCR, 2C. RESULTS: Several TCR Ig formats were assessed. In one, the TCR V domains were fused to Ig constant (C) regions. In others, the complete extracellular part of the TCR was fused either to a complete Ig or an Ig Fc region. All molecules were initially poorly secreted from eukaryotic cells, but replacement of unfavourable amino acids in the V regions improved secretion, as did the introduction of a disulfide bridge between the TCR C domains and the removal of an unpaired cysteine. A screening strategy for selection of mutations that stabilize the actual fusion molecules was developed and used successfully. Molecules that included the complete heterodimeric TCR, with a stabilizing disulfide bridge, were correctly folded as they bound TCR-specific antibodies (Abs) and detected pMHC on cells after specific peptide loading. CONCLUSIONS: We show that fully functional TCR-Ig fusion proteins can be made in good yields following stabilizing engineering of TCR V and C region genes. This is important since TCR-Ig fusions will be important probes for the presence of specific pMHCs in vitro and in vivo. In the absence of further affinity maturation, the reagents will be very useful for the detection of kinetic stability of complexes of peptide and MHC. PMID- 20735813 TI - Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas. AB - BACKGROUND: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. METHODS: Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; RESULTS: Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders). Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups of samples: those discriminated by tumour location and, the most importantly, the group discriminated by their proliferative potential; CONCLUSIONS: Primary glioblastomas could be sub-classified according to the properties of their CD133+ cells. The molecular characterization of these potential stem cell populations could be critical to find new therapeutic targets and to develop an effective therapy for these tumours with very dismal prognosis. PMID- 20735814 TI - The effective fraction isolated from Radix Astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity. AB - BACKGROUND: Macrophage infiltration in adipose tissue together with the aberrant production of pro-inflammatory cytokines has been identified as the key link between obesity and its related metabolic disorders. This study aims to isolate bioactive ingredients from the traditional Chinese herb Radix Astragali (Huangqi) that alleviate obesity-induced metabolic damage through inhibiting inflammation. METHODS: Active fraction (Rx) that inhibits pro-inflammatory cytokine production was identified from Radix Astragali by repeated bioactivity-guided high throughput screening. Major constituents in Rx were identified by column chromatography followed by high-performance liquid chromatography (HPLC) and mass spectrometry. Anti-diabetic activity of Rx was evaluated in db/db mice. RESULTS: Treatment with Rx, which included calycosin-7-beta-D-glucoside (0.9%), ononin (1.2%), calycosin (4.53%) and formononetin (1.1%), significantly reduced the secretion of pro-inflammatory cytokines (TNF-alpha, IL-6 and MCP-1) in human THP 1 macrophages and lipopolysaccharide (LPS)-induced activation of NF-kappaB in mouse RAW-Blue macrophages in a dose-dependent manner. Chronic administration of Rx in db/db obese mice markedly decreased the levels of both fed and fasting glucose, reduced serum triglyceride, and also alleviated insulin resistance and glucose intolerance when compared to vehicle-treated controls. The mRNA expression levels of inflammatory cell markers CD68 and F4/80, and cytokines MCP 1, TNF-alpha and IL-6 were significantly reduced in epididymal adipose tissue while the alternatively activated macrophage marker arginase I was markedly increased in the Rx-treated mice. CONCLUSION: These findings suggest that suppression of the inflammation pathways in macrophages represents a valid strategy for high-throughput screening of lead compounds with anti-diabetic and insulin sensitizing properties, and further support the etiological role of inflammation in the pathogenesis of obesity-related metabolic disorders. PMID- 20735815 TI - Changes in water content and distribution in Quercus ilex leaves during progressive drought assessed by in vivo 1H magnetic resonance imaging. AB - BACKGROUND: Drought is a common stressor in many regions of the world and current climatic global circulation models predict further increases in warming and drought in the coming decades in several of these regions, such as the Mediterranean basin. The changes in leaf water content, distribution and dynamics in plant tissues under different soil water availabilities are not well known. In order to fill this gap, in the present report we describe our study withholding the irrigation of the seedlings of Quercus ilex, the dominant tree species in the evergreen forests of many areas of the Mediterranean Basin. We have monitored the gradual changes in water content in the different leaf areas, in vivo and non invasively, by 1H magnetic resonance imaging (MRI) using proton density weighted (rhow) images and spin-spin relaxation time (T2) maps. RESULTS: Rhow images showed that the distal leaf area lost water faster than the basal area and that after four weeks of similar losses, the water reduction was greater in leaf veins than in leaf parenchyma areas and also in distal than in basal leaf area. There was a similar tendency in all different areas and tissues, of increasing T2 values during the drought period. This indicates an increase in the dynamics of free water, suggesting a decrease of cell membranes permeability. CONCLUSIONS: The results indicate a non homogeneous leaf response to stress with a differentiated capacity to mobilize water between its different parts and tissues. This study shows that the MRI technique can be a useful tool to follow non-intrusively the in vivo water content changes in the different parts of the leaves during drought stress. It opens up new possibilities to better characterize the associated physiological changes and provides important information about the different responses of the different leaf areas what should be taken into account when conducting physiological and metabolic drought stress studies in different parts of the leaves during drought stress. PMID- 20735816 TI - Meeting report for mobile DNA 2010. AB - An international conference on mobile DNA was held 24-28 April 2010 in Montreal, Canada. Sponsored by the American Society for Microbiology, the conference's goal was to bring together researchers from around the world who study transposition in diverse organisms using multiple experimental approaches. The meeting drew over 190 attendees and most contributed through poster presentations, invited talks and short talks selected from poster abstracts. The talks were organized into eight scientific sessions, which ranged in topic from the evolutionary dynamics of mobile genetic elements to transposition reaction mechanisms. Here we present highlights from the platform sessions with a focus on talks presented by the invited speakers. PMID- 20735817 TI - Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2 mutated breast cancers. AB - BACKGROUND: Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. METHODS: To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1Delta/Delta;p53Delta/Delta, Brca2Delta/Delta;p53Delta/Delta and p53Delta/Delta mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. RESULTS: Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYC-associated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2 related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2Delta/Delta;p53Delta/Delta tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. CONCLUSIONS: The selection of the oncogenome during mouse and human breast tumor development is markedly different, apart from the MYC gain and RB1-associated loss. These differences should be kept in mind when using mouse models for preclinical studies. PMID- 20735818 TI - Effectiveness of alcohol-based hand disinfectants in a public administration: impact on health and work performance related to acute respiratory symptoms and diarrhoea. AB - BACKGROUND: The economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated. However, large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work, school and university each year. Hand disinfection is acknowledged as key element for infection control, but its effect in open, work place settings is unclear. METHODS: Our study involved a prospective, controlled, intervention-control group design to assess the epidemiological and economical impact of alcohol-based hand disinfectants use at work place. Volunteers in public administrations in the municipality of the city of Greifswald were randomized in two groups. Participants in the intervention group were provided with alcoholic hand disinfection, the control group was unchanged. Respiratory and gastrointestinal symptoms and days of work were recorded based on a monthly questionnaire over one year. On the whole, 1230 person months were evaluated. RESULTS: Hand disinfection reduced the number of episodes of illness for the majority of the registered symptoms. This effect became statistically significant for common cold (OR = 0.35 [0.17 - 0.71], p = 0.003), fever (OR = 0.38 [0.14-0.99], p = 0.035) and coughing (OR = 0.45 [0.22 - 0.91], p = 0.02). Participants in the intervention group reported less days ill for most symptoms assessed, e.g. colds (2.07 vs. 2.78%, p = 0.008), fever (0.25 vs. 0.31%, p = 0.037) and cough (1.85 vs. 2.00%, p = 0.024). For diarrhoea, the odds ratio for being absent became statistically significant too (0.11 (CI 0.01 - 0.93). CONCLUSION: Hand disinfection can easily be introduced and maintained outside clinical settings as part of the daily hand hygiene. Therefore it appears as an interesting, cost-efficient method within the scope of company health support programmes. TRIAL REGISTRATION NUMBER: ISRCTN96340690. PMID- 20735819 TI - Familial hemiplegic migraine Ca(v)2.1 channel mutation R192Q enhances ATP-gated P2X3 receptor activity of mouse sensory ganglion neurons mediating trigeminal pain. AB - BACKGROUND: The R192Q mutation of the CACNA1A gene, encoding for the alpha1 subunit of voltage-gated P/Q Ca2+ channels (Ca(v)2.1), is associated with familial hemiplegic migraine-1. We investigated whether this gain-of-function mutation changed the structure and function of trigeminal neuron P2X3 receptors that are thought to be important contributors to migraine pain. RESULTS: Using in vitro trigeminal sensory neurons of a mouse genetic model knockin for the CACNA1A R192Q mutation, we performed patch clamp recording and intracellular Ca2+ imaging that showed how these knockin ganglion neurons generated P2X3 receptor-mediated responses significantly larger than wt neurons. These enhanced effects were reversed by the Ca(v)2.1 blocker omega-agatoxin. We, thus, explored intracellular signalling dependent on kinases and phosphatases to understand the molecular regulation of P2X3 receptors of knockin neurons. In such cells we observed strong activation of CaMKII reversed by omega-agatoxin treatment. The CaMKII inhibitor KN-93 blocked CaMKII phosphorylation and the hyperesponsive P2X3 phenotype. Although no significant difference in membrane expression of knockin receptors was found, serine phosphorylation of knockin P2X3 receptors was constitutively decreased and restored by KN-93. No change in threonine or tyrosine phosphorylation was detected. Finally, pharmacological inhibitors of the phosphatase calcineurin normalized the enhanced P2X3 receptor responses of knockin neurons and increased their serine phosphorylation. CONCLUSIONS: The present results suggest that the CACNA1A mutation conferred a novel molecular phenotype to P2X3 receptors of trigeminal ganglion neurons via CaMKII-dependent activation of calcineurin that selectively impaired the serine phosphorylation state of such receptors, thus potentiating their effects in transducing trigeminal nociception. PMID- 20735822 TI - What are possible barriers and facilitators to implementation of a Participatory Ergonomics programme? AB - BACKGROUND: Low back pain (LBP) and neck pain (NP) are common among workers. Participatory Ergonomics (PE) is used as an implementation strategy to prevent these symptoms. By following the steps of PE, working groups composed and prioritised ergonomic measures, and developed an implementation plan. Working group members were responsible to implement the ergonomic measures in their departments. Little is known about factors that hamper (barriers) or enhance (facilitators) the implementation of ergonomic measures. This study aimed to identify and understand the possible barriers and facilitators that were perceived during implementation. METHODS: This study is embedded in a cluster randomised controlled trial that investigated the effectiveness of PE to prevent LBP and NP among workers. For the purpose of the current study, questionnaires were sent to 81 working group members. Their answers were used to make a first inventory of possible barriers and facilitators to implementation. Based on the questionnaire information, 15 semi-structured interviews were held to explore the barriers and facilitators in more detail. All interviews were audio taped, transcribed verbatim, and analysed according to a systematic approach. RESULTS: All possible barriers and facilitators were obtained from questionnaire data, indicating that the semi-structured interviews did not yield information about new factors. Various barriers and facilitators were experienced. The presence of implementation plans for ergonomic measures that were already approved by the management facilitated implementation before the working group meeting. In these cases, PE served as a strategy to improve the implementation of the approved measures. Furthermore, the findings showed that the composition of a working group (i.e., including decision makers and a worker who led the implementation process) was important. Moreover, stakeholder involvement and collaboration were reported to considerably improve implementation. CONCLUSIONS: This study showed that the working group as well as stakeholder involvement and collaboration were important facilitating factors. Moreover, PE was used as a strategy to improve the implementation of existing ergonomic measures. The results can be used to improve PE programmes, and thereby may contribute to the prevention of LBP and NP. TRIAL REGISTRATION NUMBER: ISRCTN27472278. PMID- 20735821 TI - Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease. AB - BACKGROUND: Current guidelines recommend dual anti-platelet therapy, aspirin and clopidogrel, for patients treated with drug-eluting stent for coronary heart disease. In a few small trials, addition of cilostazol on dual anti-platelet therapy (triple anti-platelet therapy) showed better late luminal loss. In the real-world unselected patients with coronary heart disease, however, the effect of cilostazol on platelet reactivity and ischemic vascular events after drug eluting stent implantation has not been tested. It is also controversial whether there is a significant interaction between lipophilic statin and clopidogrel. METHODS/DESIGN: CILON-T trial was a prospective, randomized, open-label, multi center, near-all-comer trial to demonstrate the superiority of triple anti platelet therapy to dual anti-platelet therapy in reducing 6 months' major adverse cardiovascular/cerebrovascular events, composite of cardiac death, nonfatal myocardial infarction, target lesion revascularization and ischemic stroke. It also tested whether triple anti-platelet therapy is superior to dual anti-platelet therapy in inhibiting platelet reactivity in patients receiving percutaneous coronary intervention with drug-eluting stent. Total 960 patients were randomized to receive either dual anti-platelet therapy or triple anti platelet therapy for 6 months and also, randomly stratified to either lipophilic statin (atorvastatin) or non-lipophilic statin (rosuvastatin) indefinitely. Secondary endpoints included all components of major adverse cardiovascular/cerebrovascular events, platelet reactivity as assessed by VerifyNow P2Y12 assay, effect of statin on major adverse cardiovascular/cerebrovascular events, bleeding complications, and albumin-to creatinine ratio to test the nephroprotective effect of cilostazol. Major adverse cardiovascular/cerebrovascular events will also be checked at 1, 2, and 3 years to test the 'legacy' effect of triple anti-platelet therapy that was prescribed for only 6 months after percutaneous coronary intervention. DISCUSSION: CILON-T trial will give powerful insight into whether triple anti-platelet therapy is superior to dual anti-platelet therapy in reducing ischemic events and platelet reactivity in the real-world unselected patients treated with drug-eluting stent for coronary heart disease. Also, it will verify the laboratory and clinical significance of drug interaction between lipophilic statin and clopidogrel. TRIAL REGISTRATION: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00776828). PMID- 20735820 TI - Biological functions of hCG and hCG-related molecules. AB - BACKGROUND: hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. RESULTS AND DISCUSSION: hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID- 20735823 TI - Process evaluation of a participatory ergonomics programme to prevent low back pain and neck pain among workers. AB - BACKGROUND: Both low back pain (LBP) and neck pain (NP) are major occupational health problems. In the workplace, participatory ergonomics (PE) is frequently used on musculoskeletal disorders. However, evidence on the effectiveness of PE to prevent LBP and NP obtained from randomised controlled trials (RCTs) is scarce. This study evaluates the process of the Stay@Work participatory ergonomics programme, including the perceived implementation of the prioritised ergonomic measures. METHODS: This cluster-RCT was conducted at the departments of four Dutch companies (a railway transportation company, an airline company, a steel company, and a university including its university medical hospital). Directly after the randomisation outcome, intervention departments formed a working group that followed the steps of PE during a six-hour working group meeting. Guided by an ergonomist, working groups identified and prioritised risk factors for LBP and NP, and composed and prioritised ergonomic measures. Within three months after the meeting, working groups had to implement the prioritised ergonomic measures at their department. Data on various process components (recruitment, reach, fidelity, satisfaction, and implementation components, i.e., dose delivered and dose received) were collected and analysed on two levels: department (i.e., working group members from intervention departments) and participant (i.e., workers from intervention departments). RESULTS: A total of 19 intervention departments (n = 10 with mental workloads, n = 1 with a light physical workload, n = 4 departments with physical and mental workloads, and n = 4 with heavy physical workloads) were recruited for participation, and the reach among working group members who participated was high (87%). Fidelity and satisfaction towards the PE programme rated by the working group members was good (7.3 or higher). The same was found for the Stay@Work ergocoach training (7.5 or higher). In total, 66 ergonomic measures were prioritised by the working groups. Altogether, 34% of all prioritised ergonomic measures were perceived as implemented (dose delivered), while the workers at the intervention departments perceived 26% as implemented (dose received). CONCLUSIONS: PE can be a successful method to develop and to prioritise ergonomic measures to prevent LBP and NP. Despite the positive rating of the PE programme the implementation of the prioritised ergonomic measures was lower than expected. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27472278. PMID- 20735824 TI - Exploring laccase-like multicopper oxidase genes from the ascomycete Trichoderma reesei: a functional, phylogenetic and evolutionary study. AB - BACKGROUND: The diversity and function of ligninolytic genes in soil-inhabiting ascomycetes has not yet been elucidated, despite their possible role in plant litter decay processes. Among ascomycetes, Trichoderma reesei is a model organism of cellulose and hemicellulose degradation, used for its unique secretion ability especially for cellulase production. T. reesei has only been reported as a cellulolytic and hemicellulolytic organism although genome annotation revealed 6 laccase-like multicopper oxidase (LMCO) genes. The purpose of this work was i) to validate the function of a candidate LMCO gene from T. reesei, and ii) to reconstruct LMCO phylogeny and perform evolutionary analysis testing for positive selection. RESULTS: After homologous overproduction of a candidate LMCO gene, extracellular laccase activity was detected when ABTS or SRG were used as substrates, and the recombinant protein was purified to homogeneity followed by biochemical characterization. The recombinant protein, called TrLAC1, has a molecular mass of 104 kDa. Optimal temperature and pH were respectively 40-45 degrees C and 4, by using ABTS as substrate. TrLAC1 showed broad pH stability range of 3 to 7. Temperature stability revealed that TrLAC1 is not a thermostable enzyme, which was also confirmed by unfolding studies monitored by circular dichroism. Evolutionary studies were performed to shed light on the LMCO family, and the phylogenetic tree was reconstructed using maximum-likelihood method. LMCO and classical laccases were clearly divided into two distinct groups. Finally, Darwinian selection was tested, and the results showed that positive selection drove the evolution of sequences leading to well-known laccases involved in ligninolysis. Positively-selected sites were observed that could be used as targets for mutagenesis and functional studies between classical laccases and LMCO from T. reesei. CONCLUSIONS: Homologous production and evolutionary studies of the first LMCO from the biomass-degrading fungus T. reesei gives new insights into the physicochemical parameters and biodiversity in this family. PMID- 20735825 TI - Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese. AB - BACKGROUND: Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population. METHODS: We genotyped three SNPs of the IL-10 promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade. RESULTS: No significant differences in allele frequency or genotype distribution were observed for any of the IL-10 SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, P = 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, P = 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, P = 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively). CONCLUSIONS: Our results identify that IL-10 promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression. PMID- 20735826 TI - Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling. AB - BACKGROUND: Nolz1 is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE), although its function is still unknown. RESULTS: Here we analyze the role of Nolz1 during LGE development. We show that Nolz1 expression is high in proliferating neural progenitor cells (NPCs) of the LGE subventricular zone. In addition, low levels of Nolz1 are detected in the mantle zone, as well as in the adult striatum. Similarly, Nolz1 is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of Nolz1 in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that Nolz1 over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, Nolz1 over-expression promotes the acquisition of a neuronal phenotype, since it increases the number of beta III tubulin (Tuj1)- and microtubule-associated protein (MAP)2-positive neurons, and inhibits astrocyte generation and/or differentiation. Retinoic acid (RA) is one of the most important morphogens involved in striatal neurogenesis, and regulates Nolz1 expression in different systems. Here we show that Nolz1 also responds to this morphogen in E12.5 LGE-derived cell cultures. However, Nolz1 expression is not regulated by RA in E14.5 LGE-derived cell cultures, nor is it affected during LGE development in mouse models that present decreased RA levels. Interestingly, we find that Gsx2, which is necessary for normal RA signaling during LGE development, is also required for Nolz1 expression, which is lost in Gsx2 knockout mice. These findings suggest that Nolz1 might act downstream of Gsx2 to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that Nolz1 induces the selective expression of the RA receptor (RAR)beta without altering RARalpha or RARgamma. In addition, Nozl1 over-expression increases RA signaling since it stimulates the RA response element. This RA signaling is essential for Nolz1-induced neurogenesis, which is impaired in a RA-free environment or in the presence of a RAR inverse agonist. It has been proposed that Drosophila Gsx2 and Nolz1 homologues could cooperate with the transcriptional co-repressors Groucho-TLE to regulate cell proliferation. In agreement with this view, we show that Nolz1 could act in collaboration with TLE 4, as they are expressed at the same time in NPC cultures and during mouse development. CONCLUSIONS: Nolz1 promotes RA signaling in the LGE, contributing to the striatal neurogenesis during development. PMID- 20735827 TI - Feasibility of a mental practice intervention in stroke patients in nursing homes; a process evaluation. AB - BACKGROUND: Within a multi-centre randomised controlled trial in three nursing homes, a process evaluation of a mental practice intervention was conducted. The main aims were to determine if the intervention was performed according to the framework and to describe the therapists' and participants' experiences with and opinions on the intervention. METHODS: The six week mental practice intervention was given by physiotherapists and occupational therapists in the rehabilitation teams and consisted of four phases: explanation of imagery, teaching patients how to use imagery, using imagery as part of therapy, and facilitating the patient in using it alone and for new tasks. It had a mandatory and an optional part. Data were collected by means of registration forms, pre structured patient files, patient logs and self-administered questionnaires. RESULTS: A total of 14 therapists and 18 patients with stroke in the sub acute phase of recovery were involved. Response rates differed per assessment (range 57-93%). Two patients dropped out of the study (total n = 16). The mandatory part of the intervention was given to 11 of 16 patients: 13 received the prescribed amount of mental practice and 12 practiced unguided outside of therapy. The facilitating techniques of the optional part of the framework were partly used. Therapists were moderately positive about the use of imagery in this specific sample. Although it was more difficult for some patients to generate images than others, all patients were positive about the intervention and reported perceived short term benefits from mental practice. CONCLUSIONS: The intervention was less feasible than we hoped. Implementing a complex therapy delivered by existing multi-professional teams to a vulnerable population with a complex pathology poses many challenges. PMID- 20735828 TI - Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats. AB - BACKGROUND: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone. METHODS: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin. RESULTS: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB4 and nitrites while bone marrow cells increased the release of TNF-alpha and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-alpha, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF- alpha by cultured BAL cells and bone marrow cells. CONCLUSIONS: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed. PMID- 20735829 TI - Expression of COX-1 and COX-2 in the endometrium of cyclic, pregnant and in a model of pseudopregnant rats and their regulation by sex steroids. AB - BACKGROUND: Cyclooxygenases (COXs) are the rate limiting enzymes in the process of prostaglandins (PGs) synthesis, which are critical regulators of a number of reproductive processes, including ovulation, implantation, decidualization and parturition. The aim of the present study was to investigate the expression and regulation of COX-1 and COX-2 and levels of prostaglandins during rat pregnancy, in a model of pseudopregnancy and estrous cycle. METHODS: Uteri were collected from the cyclic rats on each day of estrous cycle, after every two days for pregnant (days 2 to 22) and pseudopregnant rats (days 1 to 9). In vitro primary endometrial stromal cells were cultured in the presence of steroid hormones and their respective inhibitors for the possible modulation of COX-1 and COX-2. Endometrial protein extracts were used for western blot analysis and tissue sections were prepared for protein localization using immunofluorescence. Measurements of PGF2alpha and PGE2 metabolites in serum were performed by enzyme immunoassay (EIA). RESULTS: COX-1 expression was found to be elevated during implantation and parturition, however, the levels of COX-1 decreased during decidualization periods. COX-2 was detected during early pregnancy from day 2 to 5, increased during decidual regression, and was also expressed at the time of parturition. COX-2 protein expression was found to be increased at estrus phase in cyclic rats. Both enzymes were found to be modulated in the endometrium of pseudopregnant rats, suggesting that they are regulated by 17beta-estradiol and progesterone. A significant increase in PGE2 metabolite levels was observed on day 10, 12 and 14 of pregnancy. However, an increase in PGF2alpha metabolite levels was observed only on day 14. The concentration of both these metabolites changed during pseudopregnancy and maximum levels were observed at day 7. Significant increase in PGE2 metabolite was observed at proestrus phase, on the other hand, PGF2alpha metabolite was significantly increased at proestrus and metestrus phase. COX-2 protein was regulated by 17beta-estradiol in cultured endometrial stromal cells which was blocked in the presence of ICI-182,780. CONCLUSIONS: Taken together, these results suggest that COX-1 and COX-2 could be differentially regulated by steroid hormones and might be the key factors involved in embryo implantation, decidualization, decidua basalis regression and parturition in rats. PMID- 20735830 TI - Umbilical endosalpingiosis: a case report. AB - INTRODUCTION: Endosalpingiosis describes the ectopic growth of Fallopian tube epithelium. Pathology confirms the presence of a tube-like epithelium containing three types of cells: ciliated, columnar cells; non-ciliated, columnar secretory mucous cells; and intercalary cells.We report the case of a woman with umbilical endosalpingiosis and examine the nature and characteristics of cutaneous endosalpingiosis by reviewing and combining the other four cases existing in the international literature. CASE PRESENTATION: A 50-year-old Caucasian, Greek woman presented with a pale brown nodule in her umbilicus. The nodule was asymptomatic, with no cyclical discomfort or variation in size. Her personal medical, surgical and gynecologic history was uneventful. An excision within healthy margins was performed under local anesthesia. A cystic formation measuring 2.7*1.7*1 cm was removed. Histological examination confirmed umbilical endosalpingiosis. CONCLUSIONS: Umbilical endosalpingiosis is a very rare manifestation of the non neoplasmatic disorders of the Mullerian system. It appears with cyclic symptoms of pain and swelling of the umbilicus, but not always. The disease is diagnosed using pathologic findings and surgical excision is the definitive treatment. PMID- 20735831 TI - Awareness, knowledge and self-reported test rates regarding Hepatitis B in Turkish-Dutch: a survey. AB - BACKGROUND: Hepatitis B virus infection is an important health problem in the Turkish community in the Netherlands. To prevent transmission and progression of the disease in this community, increased screening is necessary. This study aimed to determine 1) the levels of awareness and knowledge regarding hepatitis B, comparing these in tested and non-tested Turkish-Dutch in Rotterdam; 2) the self reported hepatitis B test status in this population, and how this is related to demographic characteristics, knowledge and awareness. METHODS: We conducted a postal survey amongst first and second generation migrants, aged 16 - 40 years. RESULTS: The response rate was 30.2% (n = 355 respondents). Levels of awareness and knowledge regarding hepatitis B were low, as the majority of respondents (73%) never thought about the disease and 58% of the respondents scored 5 or less out of ten knowledge items. Weighted analysis of self-reports showed a test rate of 15%, and a vaccination rate of 3%. Regression analysis showed that having been tested for hepatitis B was related to being married and higher levels of awareness and knowledge. CONCLUSIONS: This study shows low levels of hepatitis B awareness and knowledge in the Turkish community in Rotterdam. Self-reported test rates are lower in people who are not currently married, and in those who have low levels of awareness and knowledge. Especially, knowledge about the consequences of hepatitis B, such as liver cancer, was lacking. Therefore, a health promotion intervention should foremost raise awareness, and increase knowledge on the seriousness of this disease. PMID- 20735832 TI - Tumour suppressor function of MDA-7/IL-24 in human breast cancer. AB - INTRODUCTION: Melanoma differentiation associated gene-7 (MDA-7), also known as interleukin (IL)-24, is a tumour suppressor gene associated with differentiation, growth and apoptosis. However, the mechanisms underlying its anti-neoplastic activity, tumour-specificity and efficacy across a spectrum of human cancers have yet to be fully elucidated. In this study, the biological impact of MDA-7 on the behavior of breast cancer (BC) cells is evaluated. Furthermore, mRNA expression of MDA-7 is assessed in a cohort of women with BC and correlated with established pathological parameters and clinical outcome. METHODS: The human BC cell line MDA MB-231 was used to evaluate the in-vitro impact of recombinant human (rh)-MDA-7 on cell growth and motility, using a growth assay, wounding assay and electric cell impedance sensing (ECIS). Localisation of MDA-7 in mammary tissues was assessed with standard immuno-histochemical methodology. BC tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription, MDA-7 transcript levels were determined using real-time quantitative PCR. Transcript levels were analyzed against tumour size, grade, oestrogen receptor (ER) status, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI) and clinical outcome over a 10 year follow-up period. RESULTS: Exposure to rh-MDA-7 significantly reduced wound closure rates for human BC cells in-vitro. The ECIS model demonstrated a significantly reduced motility and migration following rh MDA-7 treatment (p = 0.024). Exposure to rh-MDA-7 was only found to exert a marginal effect on growth. Immuno-histochemical staining of human breast tissues revealed substantially greater MDA-7 positivity in normal compared to cancer cells. Significantly lower MDA-7 transcript levels were identified in those predicted to have a poorer prognosis by the NPI (p = 0.049) and those with node positive tumours. Significantly lower expression was also noted in tumours from patients who died of BC compared to those who remained disease free (p = 0.035). Low levels of MDA-7 were significantly correlated with a shorter disease free survival (mean = 121.7 vs. 140.4 months, p = 0.0287) on Kaplan-Meier survival analysis. CONCLUSION: MDA-7 significantly inhibits the motility and migration of human BC cells in-vitro. MDA-7 expression is substantially reduced in malignant breast tissue and low transcript levels are significantly associated with unfavourable pathological parameters, including nodal positivity; and adverse clinical outcomes including poor prognosis and shorter disease free survival. MDA 7 offers utility as a prognostic marker and potential for future therapeutic strategies. PMID- 20735833 TI - Maxillary sinus textiloma: a case report. AB - INTRODUCTION: Textilomas have been reported in many locations. We report the first case of textiloma located in the maxillary sinus that mimicked a sinus cyst recurrence on computed tomography images. CASE PRESENTATION: A 60-year-old Caucasian man was referred for persistent infection of the right maxillary sinus. A maxillary sinus benign cyst had been removed three months before. Computed tomography showed a sinus opacity evoking a cyst recurrence. A new operation was planned to remove the cyst by a Caldwell-Luc approach. After excision of very thick fibrous tissue, a compress was discovered in the maxillary sinus. The patient did not present with any sinus infection after the operation. CONCLUSION: The surgeon should always take into account the possibility of textilomas in a patient with a history of sinus surgery. PMID- 20735835 TI - The relationship between water intake and foetal growth and preterm delivery in a prospective cohort study. AB - BACKGROUND: Interpretation of previous associations between water intake and adverse birth outcomes is challenging given that amount and type of water consumed can be non-specific markers of exposure or underlying behavioural characteristics. We examined the relationship between water intake measures and adverse birth outcomes in participants from three study sites in the United States. METHODS: Using a prospective cohort study, we examined daily intake of bottled, cold tap, total tap, and total water in relation to birth weight and risk of small-for-gestational-age (SGA) among term births and risk of preterm delivery. RESULTS: Based on water consumption data collected between 20-24 weeks of gestation, the adjusted mean birth weight was 27 (95% confidence interval [CI]: -34, 87), 39 (95% CI: -22, 99), and 50 (95% CI: -11, 110) grams higher for the upper three total water intake quartiles (> 51-78, > 78-114, and > 114 ounces/day) compared to the lowest quartile (<= 51 ounces/day). Adjusted birth weight results were similar for bottled water, cold tap water, and total tap water intake. An exposure-response gradient was not detected for either preterm delivery or SGA with increasing total water intake and total tap water intake, but adjusted relative risks for all three upper quartiles were below 1.0 (range: 0.6-0.9) for SGA. CONCLUSION: These data suggest that high water intake may be associated with higher mean birth weight following adjustment for confounding. PMID- 20735834 TI - Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial. AB - BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. METHODS: The study was designed as a prospective randomised, placebo-controlled, double blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >or=60%/Child-Pugh 0.5). All the correlations of the two subscales and the smoking- and health-related variables were statistically significant and in the expected directions although of small magnitudes, except daily cigarette consumption. CONCLUSIONS: The findings confirmed the satisfactory psychometric properties of all three Chinese versions of PSS. We recommend the use of PSS-10 for research which focuses on the two components of perceived stress, as it shows a higher reliability; and the use of PSS-4 if such partition is not essential and space for multiple measures is limited. PMID- 20735861 TI - TCMGIS-II based prediction of medicinal plant distribution for conservation planning: a case study of Rheum tanguticum. AB - BACKGROUND: Many medicinal plants are increasingly endangered due to overexploitation and habitat destruction. To provide reliable references for conservation planning and regional management, this study focuses on large-scale distribution prediction of Rheum tanguticum Maxim. ex Balf (Dahuang). METHODS: Native habitats were determined by specimen examination. An improved version of GIS-based program for the distribution prediction of traditional Chinese medicine (TCMGIS-II) was employed to integrate national geographic, climate and soil type databases of China. Grid-based distance analysis of climate factors was based on the Mikowski distance and the analysis of soil types was based on grade division. The database of resource survey was employed to assess the reliability of prediction result. RESULTS: A total of 660 counties of 17 provinces in China, covering a land area of 3.63 * 106 km2, shared similar ecological factors with those of native habitats appropriate for R. tanguticum growth. CONCLUSION: TCMGIS II modeling found the potential habitats of target medicinal plants for their conservation planning. This technology is useful in conservation planning and regional management of medicinal plant resources. PMID- 20735862 TI - Rationale of using different biological therapies in rheumatoid arthritis. AB - Due to ongoing developments of novel agents in the field of biological pharmacotherapy, there are now more arrows available in clinicians' quivers for the treatment of rheumatic conditions. As a consequence, however, clear treatment strategies have to be defined in order to guarantee a qualitatively high and individually stage-adapted, state-of-the-art regimen for affected patients. This review summarizes recent evidence regarding the rationale of using different biological therapies to treat rheumatoid arthritis, the most common inflammatory joint disorder after activated osteoarthritis, and draws an actual picture of a possible standardized therapeutic algorithm without claiming exclusive appropriateness. PMID- 20735864 TI - Clearing up the confusion: the results of two pilot studies of antipsychotics for ICU delirium. PMID- 20735863 TI - Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management. AB - Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in understanding and identifying the effector cells, the proinflammatory and profibrotic mediators, and the pathways involved in the pathogenesis of CTD-ILD. Serum biomarkers may provide new insights as risk factors for pulmonary fibrosis and as measures of disease progression. Despite these recent advances, the management of patients with CTD-ILD remains suboptimal. Further studies are therefore urgently needed to better understand these conditions, and to develop effective therapeutic interventions. PMID- 20735865 TI - A personal journey from the joint to the heart. AB - Predicting complications of diseases such as rheumatoid arthritis (RA) as well as the efficacy and toxicity of drugs used to treat the disease based on an understanding of genetic differences is leading to the development of highly individualized, personal medicine. The prevention of cardiovascular complications of RA has assumed greater importance as our ability to treat the underlying joint disease has improved and it may be possible to predict which patients with RA are at greatest risk of developing cardiovascular disease. PMID- 20735866 TI - Could the expression of CD86 and FcgammaRIIB on B cells be functionally related and involved in driving rheumatoid arthritis? AB - Aberrant immune responses play a pivotal role in the processes that cause inflammation and joint damage in patients with rheumatoid arthritis (RA). Polyclonal B cell activation and the production of autoantibodies are immunological hallmarks of the disease. However, controversy surrounds the pathogenicity of autoantibodies, mainly because not all patients are seropositive (10% of RA patients are seronegative), suggesting that they could be markers rather than makers of disease. Catalan and collaborators report that patients with RA display reduced expression of FcgammaRIIB on memory B cells and plasma cells, which inversely correlates with autoantibody levels. Considering that FcgammaRIIB stimulation down-regulates antibody production, this work strengthens the link between autoantibodies and pathogenicity. PMID- 20735867 TI - Lung reaeration after surfactant instillation--caused by surfactant or caused by instillation? PMID- 20735868 TI - [A man with exercise related shortness of breath]. AB - A 51-year old male was admitted to the hospital with complaints of fever, a productive cough and exercise-related shortness of breath. These complaints were caused by a pneumatocele, which was successfully treated with antibiotics. PMID- 20735869 TI - [Neonates with pseudohypoaldosteronism]. PMID- 20735870 TI - [Treatment of acute ischaemic stroke via the venous and arterial routes]. AB - Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is the standard therapy for acute ischaemic stroke in the first 4.5 hours after onset of neurological symptoms. The efficacy of IVT increases strongly the sooner it is initiated after onset of neurological symptoms. Intra-arterial thrombolysis (IAT) and mechanical thrombectomy are potentially valuable treatment options in patients with severe ischemic stroke caused by an occlusion in a proximal cerebral artery. Further research is needed to evaluate the safety and efficacy of IAT and mechanical thrombectomy a) compared with IVT within 4.5 hours of symptom onset, b) outside the time window for IVT, c) when there are contraindications for IVT, d) when IVT fails to achieve recanalisation and e) in patients with basilar artery thrombosis. The results of ongoing trials are required to make a decision on the exact indication for IAT and mechanical thrombectomy. These treatments should therefore only be given in specialised centres, preferably in a research setting. PMID- 20735871 TI - [IVF surrogacy after embryo transfer abroad. Dilemmas of pregnancy follow-up]. AB - A 43-year-old female, gravida 3, para 2, who was 9 weeks pregnant, presented herself as a surrogate mother for a 33-year-old couple at our outpatient clinic in Heerlen, the Netherlands, for pregnancy follow-up. As she had not passed the selection procedure in the Netherlands (VU University Medical Center, Amsterdam), IVF using the gametes of the prospective parents and embryo transfer was performed in Belgium. We discussed the management of possible problems and complications during pregnancy and delivery. After an uneventful pregnancy and delivery a healthy boy was taken home by the donor couple. In the Netherlands, high-tech surrogate motherhood under strict non-commercial conditions has been accepted by law since 1997. Since the inclusion criteria are very strict, some couples seem to find a way to have their wish fulfilled abroad. Uniformity of the IVF surrogacy legislation in Europe is necessary to discourage this practice. When this situation occurs nevertheless, it is important that doctors involved know how to handle the (often unknown) medical, ethical, legal, emotional and psychosocial aspects associated with high-tech IVF-surrogacy. PMID- 20735872 TI - [Severe metabolic acidosis as a result of 5-oxoproline in acetaminophen use]. AB - Acetaminophen overdose is a well known cause of liver function disorder and even hepatic failure. Less well known is that even a therapeutic dose of acetaminophen may lead to life-threatening problems. We describe an 84-year-old patient with severe metabolic acidosis and an increased anion gap secondary to 5-oxoproline elevation as a result of acetaminophen use. A systematic approach can help us to determine the cause of a high anion gap metabolic acidosis. In unexplained high anion gap acidosis clinicians should consider the possibility of 5-oxoproline accumulation in patients with risk factors such as acetaminophen use, female sex, malnutrition, infection, diminished liver function or renal failure. PMID- 20735873 TI - [Acute hepatitis, but not A, B, or C: consider E]. AB - OBJECTIVE: To determine the percentage of hepatitis E virus (HEV) infections in serum samples from patients with negative serology for hepatitis A, B and C and to find out what may be the harmful consequences of a missed diagnosis of acute HEV infection. DESIGN: Retrospective study. METHOD: Serum samples were selected from patients with infectious hepatitis who tested negative for hepatitis A, B and C virus. Serum samples that had elevated alanine aminotransferase (ALT; > 34 U/l) were included in this study. All samples were then tested for HEV using an enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Of patients with serological evidence of acute HEV, files were checked for the originally documented diagnosis at hospital discharge. RESULTS: In the period October 2007 September 2008, 139 serum samples met the inclusion criteria. In 23 serum samples the ELISA was positive (IgM positive and/or Ig total positive); in 16/23 serum samples immunoblot assay was also positive. The percentage of confirmed HEV infections was 11.5% (16/139). In only one patient was the originally documented diagnosis correct. Several patients underwent invasive diagnostic procedures and treatment as a result of an incorrect diagnosis. CONCLUSION: Hepatitis E serology should be a standard tool in the diagnostic workup of infectious hepatitis patients in the Netherlands. PMID- 20735874 TI - [Allow scalp cooling during adjuvant chemotherapy in patients with breast cancer; scalp metastases rarely occur]. AB - OBJECTIVE: To investigate the incidence of scalp metastases in high-risk breast cancer patients in order to assess whether caution is warranted with scalp cooling during adjuvant therapy. DESIGN: Observational study. METHODS: The incidence of scalp metastases and the disease course were studied in 885 very well evaluated high-risk breast cancer patients. These patients, who had at least four positive axillary lymph nodes, were treated in a randomised study with either classical chemotherapy, or the same chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (the so-called N4+ study). RESULTS: After a median follow up of 110 months, 403 of the 885 patients (46%) had relapsed or developed metastases. 25 patients (3%) had developed skin metastasis; 4 of these patients (0.5%) had developed hairy scalp metastasis. The scalp metastases always occurred at the same time as or later than metastases elsewhere. CONCLUSION: Scalp metastases occur with a very low frequency and not as the first sign of metastatic disease. It is therefore unlikely that scalp cooling (to prevent baldness) decreases the local working of chemotherapy to such an extent that the risk of scalp metastases increases. PMID- 20735875 TI - [Thomas Schwencke and Wolfgang Amadeus Mozart]. AB - Thomas Schwencke (1694-1767) was Professor of Anatomy and Surgery and Lecturer in Obstetrics at the Surgical School in The Hague, the Netherlands. In 1743 he published the very first textbook on haematology. Furthermore, he described his observations on the variolation of smallpox, and published the design of a new obstetric instrument. Schwencke was physician of the city of The Hague and also physician at the court of the princes van Nassau-Weilburg. In 1765 Princess Caroline of Nassau-Weilburg invited the young Wolfgang Amadeus Mozart to perform concerts. During his Dutch tour the young Mozart fell seriously ill, probably from typhoid fever. At the request of the court Mozart was seen for a second opinion and thereafter successfully treated by Schwencke. Mozart could continue his concert tour and Schwencke's reputation as Mozart's physician was established. PMID- 20735876 TI - [From a small-scale to a whole-system approach: the "Preoperative route" guideline]. AB - A 2007 report by the Dutch Health Care Inspectorate concluded that there were many deficiencies in the organization of preoperative care in the Netherlands, in particular a lack of coordination and poor patient information. A new national Guideline on Preoperative Care advises on how to best organize preoperative care, but purposely refrains from prescribing specific preoperative diagnostic workup strategies or prophylactic therapies. The author examines some factors that hamper coordination between the various hospital departments involved in the preoperative process. PMID- 20735877 TI - Lack of effects of tomato products on endothelial function in human subjects: results of a randomised, placebo-controlled cross-over study. AB - Epidemiological studies suggest that consumption of tomato products reduces the risk of CVD via antioxidant, hypocholesterolaemic and anti-inflammatory mechanisms. Although experimental data also describe beneficial effects on endothelial function, clinical data in human subjects are lacking. To test the hypothesis that tomato ingestion ameliorates endothelial function, we randomised healthy non-smoking postmenopausal women to consume a buttered roll with and without tomato puree (70 g) in a cross-over design. Endothelial-dependent flow mediated dilation (FMD) and endothelial-independent nitro-mediated dilation of the brachial artery were assessed with high-resolution ultrasound (13 MHz linear array transducer). Acute (24 h) and long-term (7 d) effects were examined after daily consumption of the described meal. Nineteen volunteers completed the protocol and provided technically suitable ultrasound measurement data. Plasma lycopene levels increased from 0.30 (sem 0.04) (baseline) to 0.42 (sem 0.04) and to 0.74 (sem 0.06) MUm after 24 h and 7 d, respectively, with tomato puree consumption. These data indicated an effective absorption of the tomato product. However, both acute and long-term tomato puree consumption had no effects on endothelium-dependent or -independent dilation of the brachial artery. In addition, we found no correlation between lycopene plasma levels and FMD. In conclusion, consumption of tomato products associated with a significant increase in plasma lycopene levels had no effects on endothelial function in healthy postmenopausal women. PMID- 20735878 TI - Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats. AB - EPA or fish oil supplementation has been suggested as treatments for the prevention of type 2 diabetes mellitus (T2DM) due to their lipid-lowering and potential insulin-sensitising effects. We investigated the effects of supplementation with EPA (1 g/kg body weight per d) or fish oil (3 g/kg body weight per d) on the age of onset of T2DM and circulating glucose, insulin, lipids, leptin and adiponectin in UC Davis (UCD)-T2DM rats. Animals were divided into three groups starting at 1 month of age: control, EPA and fish oil. All the animals were followed until diabetes onset or for up to 12 months of age. Monthly fasting blood samples were collected for the measurement of glucose, lipids, hormones and C-reactive protein (CRP). Neither EPA nor fish oil delayed the onset of T2DM or altered fasting plasma glucose, insulin, CRP, adiponectin or leptin concentrations. The groups did not differ in energy intake or body weight. Fish oil treatment lowered fasting plasma TAG concentrations by 39 (sd 7) % (P < 0.001) and EPA lowered fasting plasma NEFA concentrations by 23 (sd 5) % (P < 0.05) at 4 months of age compared with the control group. EPA and fish oil lowered fasting plasma cholesterol concentrations at 4 months of age by 19 (sd 4) and 22 (sd 4) % compared with the control group, respectively (both P < 0.01). In conclusion, EPA and fish oil supplementation lowers circulating lipid concentrations, but does not delay the onset of T2DM in UCD-T2DM rats. PMID- 20735880 TI - Therapeutic-like properties of a dopamine uptake inhibitor in animal models of amphetamine addiction. AB - N-substituted benztropine (BZT) analogs are molecules that display high affinity for the dopamine transporter (DAT), therapeutic-like effects in animal models of cocaine abuse, and psychopharmacological characteristics consistent with those of a substitute medication for cocaine addiction. Since amphetamine (Amph) and cocaine share mechanisms of action at the DAT, we evaluated the effectiveness of a BZT analog in animal models of Amph addiction. We tested in mice and rats the effects of the BZT derivative, 3alpha-[bis(4-fluorophenyl)methoxy]-tropane (AHN 1055), on Amph-induced conditioned place preference (CPP), locomotor activity, sensitization, self-administration and DeltaFosB accumulation in the nucleus accumbens (NAc). The results showed that AHN-1055 did not produce rewarding, stimulant, or sensitized locomotor effects in mice when administered alone but it readily blocked the rewarding, stimulant, and sensitizing effects of repeated Amph exposure. Furthermore, in mice undergoing conditioning in the CPP paradigm, the BZT analog prevented the accumulation of DeltaFosB protein induced in the NAc shell region by Amph treatment. Notably, treatment with AHN-1055 dose-dependently reduced Amph self-administration in rats with a steady history of voluntary Amph intake. These results provide a straightforward demonstration that a BZT derivative with binding affinity for DAT exhibits high efficacy in animal models of Amph abuse, suggesting that the novel generation of BZT analogs could have wider therapeutic applications in stimulant-spectrum disorders than those previously recognized. PMID- 20735881 TI - What have official classifications ever done for psychiatric genomics? Implications for DSM-V schizophrenia. PMID- 20735879 TI - Cognitive and neural correlates of depression-like behaviour in socially defeated mice: an animal model of depression with cognitive dysfunction. AB - Human depression is associated with cognitive deficits. It is critical to have valid animal models in order to investigate mechanisms and treatment strategies for these associated conditions. The goal of this study was to determine the association of cognitive dysfunction with depression-like behaviour in an animal model of depression and investigate the neural circuits underlying the behaviour. Mice that were exposed to social defeat for 14 d developed depression-like behaviour, i.e. anhedonia and social avoidance as indicated by reduced sucrose preference and decreased social interaction. The assessment of cognitive performance of defeated mice demonstrated impaired working memory in the T-maze continuous alternation task and enhanced fear memory in the contextual and cued fear-conditioning tests. In contrast, reference learning and memory in the Morris water maze test were intact in defeated mice. Neuronal activation following chronic social defeat was investigated by c-fosin-situ hybridization. Defeated mice exhibited preferential neural activity in the prefrontal cortex, cingulate cortex, hippocampal formation, septum, amygdala, and hypothalamic nuclei. Taken together, our results suggest that the chronic social defeat mouse model could serve as a valid animal model to study depression with cognitive impairments. The patterns of neuronal activation provide a neural basis for social defeat-induced changes in behaviour. PMID- 20735882 TI - Letter to the Editor: A rejoinder to Grool et al. (2010). PMID- 20735883 TI - Letter to the Editor: early intervention in psychosis: a response to McGorry et al. (2010). PMID- 20735884 TI - Concomitants of paranoia in the general population. AB - BACKGROUND: Paranoia is an unregarded but pervasive attribute of human populations. In this study we carried out the most comprehensive investigation so far of the demographic, economic, social and clinical correlates of self-reported paranoia in the general population. METHOD: Data weighted to be nationally representative were analysed from the Adult Psychiatric Morbidity Survey in England (APMS 2007; n=7281). RESULTS: The prevalence of paranoid thinking in the previous year ranged from 18.6% reporting that people were against them, to 1.8% reporting potential plots to cause them serious harm. At all levels, paranoia was associated with youth, lower intellectual functioning, being single, poverty, poor physical health, poor social functioning, less perceived social support, stress at work, less social cohesion, less calmness, less happiness, suicidal ideation, a great range of other psychiatric symptoms (including anxiety, worry, phobias, post-traumatic stress and insomnia), cannabis use, problem drinking and increased use of treatment and services. CONCLUSIONS: Overall, the results indicate that paranoia has the widest of implications for health, emotional well being, social functioning and social inclusion. Some of these concomitants may contribute to the emergence of paranoid thinking, while others may result from it. PMID- 20735885 TI - Social world interactions: how company connects to paranoia. AB - BACKGROUND: Experimental studies have indicated that social contact, even when it is neutral, triggers paranoid thinking in people who score high on clinical or subclinical paranoia. We investigated whether contextual variables are predictive of momentary increases in the intensity of paranoid thinking in a sample of participants ranging across a psychometric paranoia continuum. METHOD: The sample (n=154) consisted of 30 currently paranoid patients, 34 currently non-paranoid patients, 15 remitted psychotic patients, 38 high-schizotypy participants, and 37 control subjects. Based on their total score on Fenigstein's Paranoia Scale (PS), three groups with different degrees of paranoia were defined. The Experience Sampling Method (ESM), a structured diary technique, was used to assess momentary social context, perceived social threat and paranoia in daily life. RESULTS: There were differences in the effect of social company on momentary levels of paranoia and perceived social threat across the range of trait paranoia. The low and medium paranoia groups reported higher levels of perceived social threat when they were with less-familiar compared to familiar individuals. The medium paranoia group reported more paranoia in less-familiar company. The high paranoia group reported no difference in the perception of social threat or momentary paranoia between familiar and unfamiliar contacts. CONCLUSIONS: Paranoid thinking is context dependent in individuals with medium or at-risk levels of trait paranoia. Perceived social threat seems to be context dependent in the low paranoia group. However, at high levels of trait paranoia, momentary paranoia and momentary perceived social threat become autonomous and independent of social reality. PMID- 20735887 TI - Executive function in patients with obstructive sleep apnea treated with continuous positive airway pressure. AB - Obstructive sleep apnea (OSA) is characterized by disrupted breathing and hypoxemia during sleep, daytime sleepiness, and changes in cognition and mood. One important question is regarding the reversibility of cognitive deficits after treatment with continuous positive airway pressure (CPAP). Here, we report the outcomes of CPAP treatment as measured by tests of attention and executive function. Thirty-seven individuals with moderate to severe OSA and compliant on CPAP treatment were studied with working memory tasks, neuropsychological testing, and overnight polysomnographic sleep study and compared to 27 healthy controls. CPAP improved the respiratory disturbance index, minimum and mean oxygen saturation (SpO2), subjective sleep quality, and daytime sleepiness ratings compared to pre-treatment values. In terms of current neurocognitive function, treated individuals with OSA performed at a comparable level to controls on basic working memory storage functions but still showed a significant reduction on tests of working memory requiring the central executive. The OSA group also performed worse on neuropsychological measures of complex attention, executive function, and psychomotor speed. While CPAP is an effective treatment for OSA in terms of ameliorating breathing disruption and oxygen desaturation during sleep, as well as daytime sleepiness, some cognitive deficits may be more resistant to treatment. PMID- 20735886 TI - Preliminary evidence of motor impairment among polysubstance 3,4 methylenedioxymethamphetamine users with intact neuropsychological functioning. AB - Neuropsychological disturbances have been reported in association with use of the recreational drug "ecstasy," or 3,4-methylenedioxymethamphetamine (MDMA), but findings have been inconsistent. We performed comprehensive neuropsychological testing examining seven ability domains in 21 MDMA users (MDMA+) and 21 matched control participants (MDMA-). Among MDMA+ participants, median [interquartile range] lifetime MDMA use was 186 [111, 516] doses, with 120 [35-365] days of abstinence. There were no significant group differences in neuropsychological performance, with the exception of the motor speed/dexterity domain in which 43% of MDMA+ were impaired compared with 5% of MDMA- participants (p = .004). Motor impairment differences were not explained by use of other substances and were unrelated to length of abstinence or lifetime number of MDMA doses. Findings provide limited evidence for neuropsychological differences between MDMA+ and MDMA- participants with the exception of motor impairments observed in the MDMA+ group. However, replication of this finding in a larger sample is warranted. PMID- 20735888 TI - Confabulations are emotionally charged, but not always for the best. AB - There is disagreement regarding the underlying basis of confabulation and, in particular, whether emotional mechanisms influence the presence or the content of confabulations. In this study, we have examined the emotional content of confabulations and "true" memories given by 24 memory-disordered patients on two autobiographical memory tasks. Two judges made pleasant/neutral/unpleasant ratings. Although many of the "memories" were evaluated as "neutral", there was an enhanced level of statements rated as having affective content (either pleasant or unpleasant) amongst these patients' confabulations, compared with their "true" memories. This affective bias was present irrespective of whether patients had suffered focal pathology extending to the ventro-medial frontal cortex (VMFC) or other pathology. There was also a correlation between participants' self-evaluated mood-states and both true and false memories' affective content, suggestive of a mood congruency effect in both types of memory. In summary, there was an enhanced tendency to produce memories with affective content (pleasant and unpleasant) amongst confabulations (whether or not there was VMFC pathology). The affective content of both confabulations and true memories produced may relate, in part, to an individual's current mood state. PMID- 20735889 TI - The contribution of injury severity, executive and implicit functions to awareness of deficits after traumatic brain injury (TBI). AB - Deficits in self-awareness are commonly seen after Traumatic Brain Injury (TBI) and adversely affect rehabilitative efforts, independence and quality of life (Ponsford, 2004). Awareness models predict that executive and implicit functions are important cognitive components of awareness though the putative relationship between implicit and awareness processes has not been subject to empirical investigation (Crosson et al., 1989; Ownsworth, Clare, & Morris, 2006; Toglia & Kirk, 2000). Severity of injury, also thought to be a crucial determinant of awareness outcome post-insult, is under-explored in awareness studies (Sherer, Boake, Levin, Silver, Ringholz, & Walter, 1998). The present study measured the contribution of injury severity, IQ, mood state, executive and implicit functions to awareness in head-injured patients assigned to moderate/severe head-injured groups using several awareness, executive, and implicit measures. Severe injuries resulted in greater impairments across most awareness, executive and implicit measures compared with moderate injuries, although deficits were still seen in the moderate group. Hierarchical regression results showed that severity of injury, IQ, mood state, executive and implicit functions made significant unique contributions to selective aspects of awareness. Future models of awareness should account for both implicit and executive contributions to awareness and the possibility that both are vulnerable to disruption after neuropathology. PMID- 20735891 TI - The development and initial validation of the Chinese Significant Wish Fulfillment Scale. AB - BACKGROUND: This paper reports the development and validation of the Chinese Significant Wish Fulfillment Scale (CSWFS), a new multidimensional scale for assessing the perceived importance and level of fulfillment of wishes of older adults. METHODS: Three studies were involved. Study 1 developed a 26-item pool on wish fulfillment through in-depth interviews with 22 older adults. Study 2 reduced the pool to 23 items through validation with a new sample of 315 older adults and examined the internal reliability. Study 3 involved a confirmatory factor analysis (CFA) and examined the test-retest reliability and the convergent validity of the scale with the construct of regret. RESULTS: A five-factor structure model of 23 items was identified through exploratory factor analysis, which accounted for 51.67% of variance. As informed by the CFA in Study 3, a five factor 22-item model was the best fit. Internal reliability and test-retest reliability was found to be good. Convergent validity was examined through correlation with the construct of future regret. The correlation, though statistically significant, was small. CONCLUSION: CSWFS demonstrates good psychometric properties, but the construct might be slightly different from that of future regrets. Probably, CSWFS addresses a construct that is under-explored but is of importance to older adults and especially to the Chinese community. PMID- 20735890 TI - Mild traumatic brain injury and postconcussive symptoms in children and adolescents. AB - The vast majority of traumatic brain injuries (TBI) in children are of mild severity. Even if only a small proportion of children with mild TBI suffer negative outcomes, then mild TBI is a serious public health problem. This review summarizes the literature regarding the neurobehavioral outcomes associated with mild TBI in children and adolescents, focusing on the longstanding debate regarding postconcussive symptoms and attendant conceptual and methodological issues. The review also discusses future research directions, the long-term goal of which is to develop a comprehensive and integrated biopsychosocial model of outcomes that helps guide clinical management. PMID- 20735892 TI - The impact of young onset dementia on the family: a literature review. AB - BACKGROUND: The needs of younger people with dementia have become increasingly recognized in service development. However, little is known about the impact of a diagnosis of young onset dementia on people aged under 65 years and their families. This paper reviews the literature on the experiences of younger people with dementia and their families in the U.K., and outcomes for carers. METHODS: Twenty-six studies, encompassing a variety of themes concerning this population, were reviewed following a systematic literature search. RESULTS: Results are divided into the impact on the individual and the impact on the family, specifically carer outcomes and the impact on children. CONCLUSIONS: The studies reviewed reveal a number of negative outcomes for the individual and carers, and highlight the need for further research. PMID- 20735894 TI - Number of blastomeres and distribution of microvilli in cloned mouse embryos during compaction. AB - The events resulting in compaction have an important influence on the processes related to blastocyst formation. To analyse the quality of the embryos obtained by somatic cell nuclear transfer (SCNT) in aspects different from previous studies, not only the number of blastomeres of cloned embryos during the initiation of compaction, but also the distribution of microvilli in cloned, normal, parthenogenetic, and tetraploid embryos before and after compaction was preliminarily investigated in mouse. Our results showed that during compaction the number of blastomeres in SCNT embryos was fewer than that in intracytoplasmic sperm injection (ICSI) embryos and, before compaction, there was a uniform distribution of microvilli over the blastomere surface, but microvilli became restricted to an apical region after compaction in the four types of embryos. We also reported here that the time course of compaction in SCNT embryos was about 3 h delayed compared with that in ICSI embryos, while there was no significant difference between SCNT and ICSI embryos when developed to the 4-cell stage. We concluded that: (i) the cleavage of blastomeres in cloned embryos was slow at least before compaction; (ii) the distribution of microvilli in cloned, normal, parthenogenetic, and tetraploid embryos was coherent before and after compaction; and (iii) the initiation of compaction in SCNT embryos was delayed compared with that of ICSI embryos. PMID- 20735893 TI - Weight loss and incident dementia in elderly Yoruba Nigerians: a 10-year follow up study. AB - BACKGROUND: The relationship between weight and dementia risk has not been investigated in populations with relatively low body mass index (BMI) such as the Yoruba. This study set out to achieve this objective using a prospective observational design. METHODS: The setting was Idikan Ward in Ibadan City, Nigeria. The participants were all aged 65 years or older and were enrolled in the Indianapolis-Ibadan Dementia Project. Repeated cognitive assessments and clinical evaluations were conducted to identify participants with dementia or MCI during 10 years of follow-up (mean duration: 5.97 years). BMI measures, information on alcohol, smoking history, cancer, hypertension, diabetes, heart attack, stroke and depression were collected at each follow-up evaluation. Mixed effect models adjusted for covariates were used to examine the differences in BMI among participants who developed dementia or MCI and those who remained cognitively normal during the follow-up. RESULTS: This analysis included 1559 participants who had no dementia at their first BMI measurements. There were 136 subjects with incident dementia, 255 with MCI and 1168 with normal cognition by the end of the study. The mean BMI at baseline was higher for female participants (22.31; SD = 4.39) than for male (21.09; SD = 3.61, p < 0.001). A significantly greater decline in BMI was found in those with either incident dementia (p < 0.001) or incident MCI (p < 0.001) compared to normal subjects. CONCLUSION: Decline in BMI is associated with incident MCI and dementia in elderly Yoruba. This observation calls for close monitoring of weight loss in elderly individuals which may indicate future cognitive impairment for timely detection and tailored interventions. PMID- 20735895 TI - Ooplasm transfer and interspecies somatic cell nuclear transfer: heteroplasmy, pattern of mitochondrial migration and effect on embryo development. AB - Although interspecies somatic cell nuclear transfer (iSCNT) has potential applications in the conservation of exotic species, an in vitro developmental block has been observed in embryos produced by this approach. It has been suggested that mitochondrial mismatch between donor cell and recipient oocyte could cause embryonic developmental arrest. A series of experiments was conducted to investigate the effect of mixed mitochondrial populations (heteroplasmy) on early development of iSCNT-derived cloned embryos. The effect of combining the techniques of ooplasm transfer (OT) and somatic cell nuclear transfer (SCNT) was examined by monitoring in vitro embryonic development; the presence and pattern of migration of foreign mitochondria after OT was analysed by MitoTracker staining. In addition, the effect of transferring caprine ooplasm (iOT) into the bovine enucleated oocytes used in iSCNT was analysed. There was no significant effect of the sequence of events (OT-SCNT or SCNT-OT) on the number of fused, cleaved, blastocyst or hatched blastocyst stage embryos. MitoTracker Green staining of donor oocytes used for OT confirmed the introduction of foreign mitochondria. The distribution pattern of transferred mitochondria most commonly remained in a distinct cluster after 12, 74 and 144 h of in vitro culture. When goat ooplasm was injected into bovine enucleated oocytes (iSCNT), there was a reduction (p < 0.05) in fusion (52 vs. 82%) and subsequent cleavage rates (55 vs. 78%). The procedure of iOT prior to iSCNT had no effect in overcoming the 8- to 16-cell in vitro developmental block, and only parthenogenetic cow and goat controls reached the blastocyst (36 and 32%) and hatched blastocyst (25 and 12%) stages, respectively. This study indicates that when foreign mitochondria are introduced at the time of OT, these organelles tend to remain as distinct clusters without relocation after a few mitotic divisions. Although the bovine cytoplast appears capable of supporting mitotic divisions after iOT-iSCNT, heteroplasmy or mitochondrial incompatibilities may affect nuclear-ooplasmic events occurring at the time of genomic activation. PMID- 20735896 TI - Seroprevalence of Echinococcus granulosus infection in Croatian patients with cystic liver disease. AB - Cystic liver disease (CLD), presenting with solitary or multiple cysts in the liver, is a common diagnosis today, primarily due to the frequent application of modern radiological methods. There is a wide range of possible causes. CLD of infective origin is usually caused by an echinococcal species. During the past three decades a number of cystic echinococcosis (CE) control programmes have led to a significant decrease in the incidence of human hydatidosis in some endemic areas. The aim of this study was to determine the seroprevalence of E. granulosus infection in Croatian patients with CLD. A total of 540 serum samples from patients with hepatic cysts detected by imaging methods were screened for the presence of E. granulosus IgG antibodies using semiquantitative enzyme-linked immunosorbent assay. The Western blot technique was used as a confirmatory test for the CE diagnosis. The overall E. granulosus seroprevalence rate in patients with CLD was 3.9%. There was no significant difference in seroprevalence rate between male and female patients (P = 0.541). According to age groups, there was a significant difference in seropositivity among age groups (P = 0.002). The highest seroprevalence rate was detected in the youngest age group (up to 18 years), both in males and females (20% and 13%, respectively). This study indicates that CE still represents a public health problem in Croatia. Preventive measures should be used to control Echinococcus infections, including avoidance of contact with infected dogs, egg-contaminated soil or plants; control and treatment of dogs with antihelmintics; hand washing, improved sanitation and health education. PMID- 20735897 TI - Molecular and biochemical mining of heat-shock and 14-3-3 proteins in drug induced protoscolices of Echinococcus granulosus and the detection of a candidate gene for anthelmintic resistance. AB - Cystic echinococcosis (CE) caused by the larval stage of Echinococcus granulosus is a disease that affects both humans and animals. In humans the disease is treated by surgery with a supplementary option of chemotherapy with a benzimidazole compound. During the present study heat-shock protein 60 (HSP 60) was identified as one of the most frequently expressed biomolecules by E. granulosus after albendazole treatment. Data were correlated with 14-3-3 protein signature, and overexpression of this molecule after albendazole induction was an indicator of cell survival and signal transduction during in vitro maintenance of E. granulosus for up to 72 h. This observation was further correlated with a uniform expression pattern of a housekeeping gene (actin II). Out of three beta tubulin gene isoforms of E. granulosus, beta-tubulin gene isoform 2 showed a conserved point mutation indicative of benzimidazole resistance. PMID- 20735898 TI - Estimating the cost of smoking to the NHS in England and the impact of declining prevalence. AB - Smoking cost the National Health Service (NHS) in England in 1996 an estimated L1.4-L1.7 billion. In 1998, in Smoking Kills, the Government outlined an action plan for reducing smoking prevalence. This paper estimates 2006 costs and the impact of declining prevalence. Estimates are derived from costs, service use, and attributable proportions based on current and ex-smokers' prevalence and relative risk compared with never-smokers. Comparable 1996 costs were estimated by substituting 1996 prevalence. Smoking-attributable hospital admissions cost the NHS an estimated L1 billion in 2006, outpatient attendances cost L190 million, general practitioner (GP) consultations L530 million, practice nurse consultations L50 million and GP prescriptions L900 million; L2.7 billion in total. This represents 5% of adult hospital admission costs, 4% outpatients, 11% GP and 8% practice nurse consultations and 12% of prescription costs. Smoking accounted for 24% of respiratory disease hospital admission costs and 16% of cancer and cardiovascular disease costs (people aged >= 35 years). The 2006 cost is estimated to be 13% lower than if smoking had remained at 1996 levels. Smoking represents a substantial cost throughout the NHS. Significant savings are associated with a reduction in prevalence, but much of this stems from an earlier phase of the smoking epidemic. Securing future such savings requires further policies to reduce smoking prevalence. PMID- 20735899 TI - BJN impact factor increases by 25%. PMID- 20735900 TI - Expectant management--what is "limited life expectancy". PMID- 20735902 TI - Durability and retreatment rates of minimal invasive treatments of benign prostatic hyperplasia: a cross-analysis of the literature. AB - BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold standard of the treatment of benign prostatic hyperplasia (BPH). In recent years there has been a significant shift in the treatment of BPH and guidelines emphasize minimally invasive surgery as a new treatment option. Minimal invasive technologies (MITs), such as transurethral microwave thermotherapy (TUMT), laser ablations, transurethral needle ablation (TUNA) have emerged as an alternative to the TURP. OBJECTIVES: To assess the retreatment rates of the most commonly used minimal invasive techniques. SEARCH STRATEGY: Durability articles were selected by using defined search terms using PubMed as search engine. RESULTS: Comparing to the overall retreatment rates of MITs the results show that TUMT, holmium laser enucleation of the prostate (HoLEP) and contact laser vaporization (CLV) are among the treatments with the lowest retreatment rates. Studies show no significant differences in retreatment rates between TUMT and TURP. CONCLUSION: A review of the current literature, long term results and retreatment rates of MITs shows large variability in outcomes and retreatment rates. The true definition of a MIT remains unclear. High energy TUMT deserves reconsideration in clinical practices, due to low retreatment rates and the low need of anesthetics. PMID- 20735903 TI - Effect of modified suprapubic prostatectomy for benign prostatic hyperplasia on postoperative hemoglobin levels. AB - OBJECTIVES: Hemostasis during suprapubic prostatectomy for benign prostatic hyperplasia (BPH) is commonly affected by placing sutures at the 5 o'clock position and the 7 o'clock position of the bladder neck. However, the urethral arterial branches of the inferior vesical artery that supplies the prostate extend from the 1 o'clock to 5 o'clock position and from the 7 o'clock to 11 o'clock position of the bladder neck, with the largest branches located posteriorly. This study analyses the effect of a modified suprapubic prostatectomy technique, which covered the area from the 1 o'clock position to the 11 o'clock position, on postoperative blood hemoglobin levels, as a reflection of hemorrhage control. METHODS: This was a single-center, retrospective study of 47 patients who underwent suprapubic prostatectomy for BPH. Hemostatic sutures included the main areas of anatomic distribution of the urethral arterial branches of the inferior vesical artery. Preoperative and postoperative blood hemoglobin levels and perioperative complications were recorded. RESULTS: The mean decrease in blood hemoglobin was 1.06 mg/dL. Only three patients had clot retention, and these clots were easily flushed out. None of the patients required a blood transfusion. CONCLUSIONS: The modified suprapubic prostatectomy technique for BPH enhances hemostatic control and reduces the need for a blood transfusion. PMID- 20735904 TI - Association between erectile function and lower urinary tract symptoms in patients treated with permanent seed prostate brachytherapy. AB - PURPOSE: Among men who underwent permanent seed prostate brachytherapy, we aimed to: 1) investigate: whether development of lower urinary tract symptoms (LUTS) after permanent seed prostate brachytherapy was associated with suboptimal erectile function before brachytherapy, and 2) identify factors that are associated with normal erectile function before brachytherapy. METHODS AND MATERIALS: We analyzed data from 215 consecutive patients with low- or intermediate-risk prostate cancer who received permanent seed brachytherapy at our center. Erectile function at baseline (prior to brachytherapy) was assessed using the Mount Sinai Erectile Function Score (MSEFS). Urinary symptoms at baseline and at 1 month and 4 months after brachytherapy were measured using the International Prostate Symptom Score (IPSS) questionnaire. Multiple linear regression, and a multivariable mixed linear model were used to analyze differences in IPSS from baseline to 1 month and 4 months after brachytherapy. Multiple logistic regression was used to investigate factors associated with normal erectile function at baseline. RESULTS: A total of 124 patients had data available for baseline, and 1 month and 4 months after brachytherapy. Having normal erectile function (MSEFS of 3) versus suboptimal erectile function (MSEFS 0 to 2) was not associated with increases in IPSS from baseline to 1 month or 4 months after brachytherapy. Larger increases in IPSS were found in subjects who had smaller prostates (regression coefficient = -0.36) or higher seed radioactivity (regression coefficient = 0.33). Patients with higher baseline IPSS were less likely to have normal erectile function (MSEFS = 3) before brachytherapy (odds ratio = 0.88). CONCLUSION: Normal erectile function prior to brachytherapy was not associated with worse IPSS after brachytherapy. However, patients with a higher IPSS before brachytherapy also had worse erectile function before brachytherapy, which may point to a common pathway. PMID- 20735905 TI - Analysis of testosterone suppression in men receiving histrelin, a novel GnRH agonist for the treatment of prostate cancer. AB - BACKGROUND: Androgen deprivation therapy (ADT) is the standard care in men with advanced prostate cancer. Continuous testosterone suppression is essential to treatment efficacy. Recently a 1 year depot compound, histrelin, (VANTAS: Orion Pharmaceuticals, Finland; Endo Pharmaceuticals, USA), a gonadotropin-releasing hormone (GnRH) analog, was approved for hormone therapy of prostate cancer. In the present study the therapeutic efficacy of this compound was investigated, in addition to its impact on testosterone values and velocity as well as PSA. METHOD: One hundred thirty-one patients with histologically confirmed prostate cancer and normal testosterone levels were prospectively evaluated over 1 year. Androgen deprivation therapy was performed using a once yearly implant of the GnRH agonist histrelin. Testosterone and PSA levels, and histrelin serum profile were measured prospectively every month for 1 year. In addition, patients were stratified according to their PSA results and D'Amico risk profile. RESULTS: Testosterone suppression (testosterone < or = 50 ng/dL) was measured in all patients between weeks 4 and 52; 88% of patients had a continuous testosterone level under 20 ng/dL. The PSA level in the total population decreased significantly within the first 2 weeks compared with baseline, and after 52 weeks the median PSA level of the total population was 0.2 ng/mL. PSA responses were grouped into three typical therapeutic outcomes and correlated with the clinical risk distribution, and levels were lowered in all three risk groups. CONCLUSION: The GnRH agonist histrelin successfully suppressed testosterone over the entire study period. This effect was measured across a number of different clinical definitions of PSA response and clinical risk. The GnRH agonist therefore offers an effective therapy option in hormone treatment of prostate cancer. PMID- 20735906 TI - The effect of local compression and topical epinephrine on perioperative bleeding and degree of urinary extravasation on postoperative cystogram following radical retropubic prostatectomy. AB - OBJECTIVE: To evaluate the efficacy of local compression and topical epinephrine in controlling perioperative bleeding during open radical retropubic prostatectomy (ORRP) and its impact on the degree of urinary extravasation on initial postoperative cystogram. METHODS: Between September 2005 to March 2009, 476 men underwent ORRP performed by a single surgeon. Group 1 (n = 200) underwent ORRP between September 2005 and November 2006 without pelvic compression; Group 2 (n = 76) underwent ORRP between November 2006 and May 2007 and a dry laparotomy pad was positioned in the pelvis immediately prior to abdominal wound closure; Group 3 (n = 200) underwent ORRP between May 2007 and March 2009 with a epinephrine soaked laparotomy pad positioned in the pelvis prior to abdominal wound closure. Hematocrit values were obtained prior to anesthesia induction, upon arrival in the recovery room and at hospital discharge in order to estimate intraoperative and postoperative bleeding. The number of allogenic and autologous units transfused was recorded. The utility of compressing the pelvis with a pad was examined by comparing estimated postoperative bleeding between Group 1 versus Groups 2 and 3 and the hemostatic utility of soaking the pad in epinephrine was examined by comparing Group 2 versus 3. Systolic and diastolic blood pressure and pulse measurements were obtained at baseline and 5 and 10 minutes after introducing the epinephrine pad. The relationship between estimated blood loss and degree of extravasation on initial postoperative cystogram was investigated. RESULTS: Estimated intraoperative, postoperative and total blood loss (mean change in Hct) was 12.2, 2.3, 14.2, in Group 1, 10.0, 1.5, 11.1 in Group 2, and 10.8, 2.1, and 12.6 in Group 3. Estimated intraoperative and total blood loss was significantly less in the men treated with a compression pad (Groups 2 and 3) versus no pad (Group 1). There were no significant differences in number of patients transfused, the number of units transfused or the degree of extravasation on postoperative cystograms between Group 1 versus Group 2 and 3 or Group 2 versus 3. However, postoperative bleeding was significantly less in Group 2 compared to Group 3. Mean systolic and diastolic blood pressure and pulse values were unchanged from baseline after epinephrine use. CONCLUSIONS: Local compression of the pelvis with or without epinephrine prior to abdominal wound closure does not appear to have beneficial effects on reducing postoperative bleeding and decreasing the degree of urinary extravasation on cystogram following ORRP. While the use of topical epinephrine appears to be safe and relatively inexpensive, at the concentrations used in our study it does not appear to facilitate postoperative hemostasis. PMID- 20735907 TI - Lower urinary tract leiomyoma: is excision necessary? AB - INTRODUCTION/OBJECTIVES: Our objective was to review our experience with lower urinary tract leiomyomata to determine if presentation, exam and imaging allows for stratification of the treatment of this rare lesion. MATERIALS AND METHODS: A retrospective review of current practice was performed from the Mayo Clinic Rochester database identifying 13 female patients and 10 males from 1995-2008, focusing on the clinical presentation, cystoscopic findings, imaging and operative approaches. RESULTS: Symptomatic patients had larger lesions, were more likely to be females, or had midline periurethral or bladder neck lesions. Cystoscopic findings were uniformly described as submucosal polypoid lesions without surrounding erythema or mucosal involvement, a hallmark in the differential. There were no cases of rapid growth of these lesions. There were no recurrences after complete excision with follow up ranging in some cases for up to 4 years. CONCLUSIONS: Lower urinary tract urethral leiomyomata are benign lesions that can be clearly differentiated on the basis of modern imaging from malignant or other benign lesions. While these lesions can cause obstructive voiding symptoms, resection or excision is required only for relief of symptoms, and not for tissue confirmation. In comparison to the presentation of leiomyosarcoma, this benign mass presents with slowly progressive symptoms, is firm but with rounded contours on exam, mucosal ulceration is absent. Imaging confirms benign appearing, albeit, ectopic muscle tissue. Rare forms of metastatic uterine smooth muscle tumors are also easily differentiated from this lesion. Adoption of a conservative approach for the asymptomatic and benign appearing lesion appears prudent. PMID- 20735908 TI - Effects of combined behavioral intervention and tolterodine on patient-reported outcomes. AB - OBJECTIVE: To assess the effects of tolterodine extended release (ER) plus behavioral intervention on urgency and other patient-reported outcomes in subjects with overactive bladder (OAB) who were previously dissatisfied with antimuscarinic treatment. METHODS: In this 16-week, multicenter, open-label study, eligible adults (aged > or = 18 y) reported dissatisfaction with their most recent antimuscarinic OAB medication; > or = 8 micturitions and > or = 2 urgency episodes per 24 hours and > or = 1 UUI episode in 5 day bladder diaries; and OAB symptoms for > or = 3 months. Subjects received tolterodine ER plus a behavioral educational handout with verbal reinforcement of behavioral intervention content for 8 weeks. Those satisfied with treatment at week 8 continued with this therapy; those dissatisfied received tolterodine ER plus individualized behavioral intervention (pelvic floor muscle training, tailored behavioral techniques) for 8 weeks. Endpoints were changes from baseline in daytime and nocturnal micturition-related urgency episodes and frequency-urgency sum (a measure of urgency severity and frequency) reported in 5 day bladder diaries at weeks 4, 8, 12, and 16; Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), and Urgency Perception Scale (UPS) scores at weeks 8 and 16. RESULTS: Daytime and nocturnal urgency episodes and frequency-urgency sum were significantly reduced at all time points (all p < 0.0001). Significant improvements were also observed in PPBC, OAB-q Symptom Bother and Health-Related Quality of Life, and UPS scores at weeks 8 and 16 (all p < 0.0001). CONCLUSIONS: Patients with OAB who are dissatisfied with antimuscarinic therapy may experience improved treatment outcomes by adding a self-administered behavioral intervention to their drug regimen. PMID- 20735909 TI - High body mass index does not affect outcomes following robotic assisted laparoscopic prostatectomy. AB - INTRODUCTION: Given the anatomic constraints of obese patients, concern exists as to whether robotic assisted laparoscopic prostatectomy (RALP) is appropriate in patients with higher body mass index (BMI). We reviewed a large RALP database to determine if clinical outcomes are related to BMI. METHODS: The records of patients who underwent a RALP from 2003-2009 were reviewed. BMI stratifications were concordant with the Centers for Disease Control (CDC) standards: > or = 30, > or = 25 and < 30, and < 25 were classified as obese, overweight, and normal weight, respectively. Baseline, perioperative, histopathologic, and functional outcome data were collected. RESULTS: A total of 1420 patients were identified and BMI information was available for 1112 patients. Median BMI in the three strata was 23.5 (n = 270), 27.3 (n = 600), and 32.1 (n = 242). There were no significant differences in preoperative prostate specific antigen (PSA), clinical staging, and preoperative Gleason scores. Operating time was 6 minutes longer in the obese (p < 0.001) and prostate weight was 8 g greater (p < 0.001). Other perioperative factors were similar, including: EBL, pathologic stage and Gleason score and rates of positive surgical margins. The overall incidence of postoperative complications was similar between the three groups. Biochemical recurrence rates were similar among all patients, although there was a trend toward increased recurrence in the obese (p = 0.09). Recovery of erectile function and continence was similar regardless of BMI. CONCLUSIONS: RALP is an effective approach to prostatectomy in obese patients as perioperative and functional outcomes are almost identical across BMI strata. This supports the continued utilization of RALP in obese and overweight men. PMID- 20735911 TI - Orchitis in lupus/scleroderma overlap syndrome: a case report and literature review. AB - Testicular involvement in connective tissue diseases (CTD) is typically caused by medium vessel vasculitis as in polyarteritis nodosa. Systemic lupus erythrematosus (SLE) and systemic sclerosis cause small vessel vasculitis, which is an unusual cause of orchitis. We hereby report a case of orchitis in a 28-year old patient caused by vasculitis related to his lupus/scleroderma overlap CTD. He had an excellent response to steroids and azathioprine with complete resolution of his testicular and systemic symptoms. Our case highlights that although testicular involvement secondary to small vessel vasculitis in CTD is uncommon, it is still possible and should be evaluated. PMID- 20735910 TI - Experience with robotic assisted laparoscopic surgery in upper tract urolithiasis. AB - OBJECTIVE: Early results indicate that robot assisted laparoscopic surgery (RALS) may be useful in managing upper tract (UT) urolithiasis. We reviewed our experience of managing 50 cases of UT urolithiasis with or without reconstruction using RALS. MATERIALS AND METHODS: We performed a record review of 50 cases of RALS for UT urolithiasis performed in two institutions from July 2006 to June 2009. The RALS procedures included pyeloplasty with pyelolithotomy (29 cases), ureterolithotomy, tailoring and reimplantation for megaureters (5 cases), ureterolithotomy with ureteral stricture reconstruction (1 case), primary UT stone surgeries (8 cases), partial nephrectomy (1 case) and ablative surgeries (6 cases). Data pertaining to indications, operative details, and complications were analyzed. RESULTS: The average operating time was 105 min (86 min-135 min) for pyeloplasty with pyelolithotomy, 140 min (115 min-195 min) for ureterolithotomy, tailoring and ureteroneocystostomy and 106 min (88 min-174 min) for extended pyelolithotomy (5 cases). Mean blood loss was 77 mL (50 mL-250 mL). Stone clearance rate was 93.2%. One case of extended pyelolithotomy had hematuria requiring selective angioembolization. There was one conversion and no other major complication. CONCLUSIONS: RALS for UT urolithiasis is safe and efficacious. It is particularly useful when stone removal is combined with reconstruction. It is a reasonable alternative for treating a solitary partial staghorn or a large pelvic stone including those in pelvic/anomalous kidneys. RALS did not seem substantially better than pure laparoscopy for isolated ureterolithotomy and for nephrectomy for a nonfunctioning kidney. Its role in the treatment of large, multiple or complete staghorn calculi needs further investigation. PMID- 20735912 TI - Metanephric adenofibroma: robotic partial nephrectomy of a large Wilms' tumor variant. AB - PURPOSE: A case of the rare, benign, Wilms' tumor (WT) variant, metanephric adenofibroma (MAF), is presented. MATERIALS AND METHODS: The patient is a 21-year old female with an incidentally discovered enhancing renal mass. The diagnosis, workup and treatment are outlined. RESULTS: The 19 cm renal mass was ultimately resected via robot-assisted partial nephrectomy. Pathologic diagnosis at our institution was confirmed as a MAF by the National Wilms' Tumor Study Group (NWTSG). CONCLUSION: Difficult to differentiate from WT, it is imperative that MAF be recognized and appropriately diagnosed because unlike adult WT, the natural history of MAF is indolent and adjuvant chemo/radiation therapy is rarely necessary. This case reinforces the importance of review of potential WT variants by the NWTSG. PMID- 20735913 TI - Abstracts of the Mid-Atlantic Section of the American Urological Association 68th Annual Meeting. September 23 - 26, 2010. Farmington, Pennsylvania, USA. PMID- 20735914 TI - Office based urology trials. PMID- 20735915 TI - Open clinical uro-oncology trials in Canada. PMID- 20735916 TI - Recurrent Granulibacter bethesdensis infections and chronic granulomatous disease. AB - Chronic granulomatous disease (CGD) is characterized by frequent infections, most of which are curable. Granulibacter bethesdensis is an emerging pathogen in patients with CGD that causes fever and necrotizing lymphadenitis. However, unlike typical CGD organisms, this organism can cause relapse after clinical quiescence. To better define whether infections were newly acquired or recrudesced, we use comparative bacterial genomic hybridization to characterize 11 isolates obtained from 5 patients with CGD from North and Central America. Genomic typing showed that 3 patients had recurrent infection months to years after apparent clinical cure. Two patients were infected with the same strain as previously isolated, and 1 was infected with a genetically distinct strain. This organism is multidrug resistant, and therapy required surgery and combination antimicrobial drugs, including long-term ceftriaxone. G. bethesdensis causes necrotizing lymphadenitis in CGD, which may recur or relapse. PMID- 20735917 TI - Worldwide diversity of Klebsiella pneumoniae that produce beta-lactamase blaKPC-2 gene. AB - Klebsiella pneumoniaeisolates that produce carbapenemases (KPCs) are rapidly disseminating worldwide. To determine their genetic background, we investigated 16 blaKPC-2-harboring K. pneumoniae isolates from 5 countries. The isolates were multidrug resistant, possessed the blaKPC-2 gene, and differed by additional Beta lactamase content. They harbored a naturally chromosome-encoded bla gene (blaSHV 1 [12.5%], blaSHV-11 [68.7%], or blaOKP-AVB [18.8%]) and several acquired and plasmid-encoded genes (blaTEM-1 [81.3%], blaCTX-M-2 [31.3%], blaCTX-M-12 [12.5%], blaCTX-M-15 [18.7%], and blaOXA-9 [37.5%]). The blaKPC-2 gene was always associated with 1 of the Tn4401 isoforms (a, b, or c). Tn4401 was inserted on different-sized plasmids that belonged to different incompatibility groups. Several blaKPC-containing K. pneumoniae clones were found: 9 different pulsotypes with 1 major (sequence type 258) and 7 minor distinct allelic profiles. Different clones harboring different plasmids but having identical genetic structure, Tn4401, could be at the origin of the worldwide spread of this emerging resistance gene. PMID- 20735918 TI - Cercarial dermatitis transmitted by exotic marine snail. AB - Cercarial dermatitis (swimmer's itch) is caused by the penetration of human skin by cercariae of schistosome parasites that develop in and are released from snail hosts. Cercarial dermatitis is frequently acquired in freshwater habitats, and less commonly in marine or estuarine waters. To investigate reports of a dermatitis outbreak in San Francisco Bay, California, we surveyed local snails for schistosome infections during 2005-2008. We found schistosomes only in Haminoea japonica, an Asian snail first reported in San Francisco Bay in 1999. Genetic markers place this schistosome within a large clade of avian schistosomes, but do not match any species for which there are genetic data. It is the second known schistosome species to cause dermatitis in western North American coastal waters; these species are transmitted by exotic snails. Introduction of exotic hosts can support unexpected emergence of an unknown parasite with serious medical or veterinary implications. PMID- 20735919 TI - Influenza in refugees on the Thailand-Myanmar border, May-October 2009. AB - We describe the epidemiology of influenza virus infections in refugees in a camp in rural Southeast Asia during May-October 2009, the first 6 months after identification of pandemic (H1N1) 2009 in Thailand. Influenza A viruses were detected in 20% of patients who had influenza-like illness and in 23% of those who had clinical pneumonia. Seasonal influenza A (H1N1) was the predominant virus circulating during weeks 26-33 (June 25-August 29) and was subsequently replaced by the pandemic strain. A review of passive surveillance for acute respiratory infection did not show an increase in acute respiratory tract infection incidence associated with the arrival of pandemic (H1N1) 2009 in the camp. PMID- 20735921 TI - Legionellosis outbreak associated with asphalt paving machine, Spain, 2009. AB - From 1999 through 2005 in Alcoi, Spain, incidence of legionellosis was continually high. Over the next 4 years, incidence was lower, but an increase in July 2009 led health authorities to declare an epidemic outbreak. A molecular epidemiology investigation showed that the allelic profiles for all Legionella pneumophila samples from the 2009 outbreak patients were the same, thus pointing to a common genetic origin for their infections, and that they were identical to that of the organism that had caused the previous outbreaks. Spatial-temporal and sequence-based typing analyses indicated a milling machine used in street asphalt repaving and its water tank as the most likely sources. As opposed to other machines used for street cleaning, the responsible milling machine used water from a natural spring. When the operation of this machine was prohibited and cleaning measures were adopted, infections ceased. PMID- 20735920 TI - Cotton rats and house sparrows as hosts for North and South American strains of eastern equine encephalitis virus. AB - Eastern equine encephalitis virus (EEEV; family Togaviridae, genus Alphavirus) is an arbovirus that causes severe disease in humans in North America and in equids throughout the Americas. The enzootic transmission cycle of EEEV in North America involves passerine birds and the ornithophilic mosquito vector, Culiseta melanura, in freshwater swamp habitats. However, the ecology of EEEV in South America is not well understood. Culex (Melanoconion) spp. mosquitoes are considered the principal vectors in Central and South America; however, a primary vertebrate host for EEEV in South America has not yet been identified. Therefore, to further assess the reservoir host potential of wild rodents and wild birds, we compared the infection dynamics of North American and South American EEEV in cotton rats (Sigmodon hispidus) and house sparrows (Passer domesticus). Our findings suggested that each species has the potential to serve as amplification hosts for North and South America EEEVs. PMID- 20735922 TI - Comparison of pandemic (H1N1) 2009 and seasonal influenza, Western Australia, 2009. AB - We compared confirmed pandemic (H1N1) 2009 influenza and seasonal influenza diagnosed in Western Australia during the 2009 influenza season. From 3,178 eligible reports, 984 pandemic and 356 seasonal influenza patients were selected; 871 (88.5%) and 288 (80.9%) were interviewed, respectively. Patients in both groups reported a median of 6 of 11 symptoms; the difference between groups in the proportion reporting any given symptom was < or =10%. Fewer than half the patients in both groups had > or =1 underlying condition, and only diabetes was associated with pandemic (H1N1) 2009 influenza (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.5). A total of 129 (14.8%) persons with pandemic (H1N1) 2009 and 36 (12.5%) persons with seasonal influenza were hospitalized (p = 0.22). After controlling for age, we found that patient hospitalization was associated with pandemic (H1N1) 2009 influenza (OR 1.5; 95% CI 1.1-2.1). Contemporaneous pandemic and seasonal influenza infections were substantially similar in terms of patients' symptoms, risk factors, and proportion hospitalized. PMID- 20735923 TI - All-cause mortality during first wave of pandemic (H1N1) 2009, New South Wales, Australia, 2009. AB - In temperate countries, death rates increase in winter, but influenza epidemics often cause greater increases. The death rate time series that occurs without epidemic influenza can be called a seasonal baseline. Differentiating observed death rates from the seasonally oscillating baseline provides estimated influenza associated death rates. During 2003-2009 in New South Wales, Australia, we used a Serfling approach with robust regression to estimate age-specific weekly baseline all-cause death rates. Total differences between weekly observed and baseline rates during May-September provided annual estimates of influenza-associated death rates. In 2009, which included our first wave of pandemic (H1N1) 2009, the all-age death rate was 6.0 (95% confidence interval 3.1-8.9) per 100,000 persons lower than baseline. In persons ?80 years of age, it was 131.6 (95% confidence interval 126.2-137.1) per 100,000 lower. This estimate is consistent with a pandemic virus causing mild illness in most persons infected and sparing older persons. PMID- 20735925 TI - Trends in hospitalizations for peptic ulcer disease, United States, 1998-2005. AB - Infection with Helicobacter pylori increases the risk for peptic ulcer disease (PUD) and its complications. To determine whether hospitalization rates for PUD have declined since antimicrobial drugs to eradicate H. pylori became available, we examined 1998-2005 hospitalization records (using the Nationwide Inpatient Sample) in which the primary discharge diagnosis was PUD. Hospitalizations for which the diagnosis was H. pylori infection were also considered. The age adjusted hospitalization rate for PUD decreased 21% from 71.1/100,000 population (95% confidence interval [CI] 68.9-73.4) in 1998 to 56.5/100,000 in 2005 (95% CI 54.6-58.3). The hospitalization rate for PUD was highest for adults > or =65 years of age and was higher for men than for women. The age-adjusted rate was lowest for whites and declined for all racial/ethnic groups, except Hispanics. The age-adjusted H. pylori hospitalization rate also decreased. The decrease in PUD hospitalization rates suggests that the incidence of complications caused by H. pylori infection has declined. PMID- 20735924 TI - Determinants of multidrug-resistant tuberculosis clusters, California, USA, 2004 2007. AB - Laboratory and epidemiologic evidence suggests that pathogen-specific factors may affect multidrug-resistant (MDR) tuberculosis (TB) transmission and pathogenesis. To identify demographic and clinical characteristics of MDR TB case clustering and to estimate the effect of specific isoniazid resistance-conferring mutations and strain lineage on genotypic clustering, we conducted a population-based cohort study of all MDR TB cases reported in California from January 1, 2004, through December 31, 2007. Of 8,899 incident culture-positive cases for which drug susceptibility information was available, 141 (2%) were MDR. Of 123 (87%) strains with genotype data, 25 (20%) were aggregated in 8 clusters; 113 (92%) of all MDR TB cases and 21 (84%) of clustered MDR TB cases occurred among foreign born patients. In multivariate analysis, the katG S315T mutation (odds ratio 11.2, 95% confidence interval 2.2-Yen; p = 0.004), but not strain lineage, was independently associated with case clustering. PMID- 20735927 TI - Illicit drug use and risk for USA300 methicillin-resistant Staphylococcus aureus infections with bacteremia. AB - To assess the association of illicit drug use and USA300 methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, a multicenter study was conducted at 4 Veterans Affairs medical centers during 2004-2008. The study showed that users of illicit drugs were more likely to have USA300 MRSA bacteremia (in contrast to bacteremia caused by other S. aureus strains) than were patients who did not use illicit drugs (adjusted relative risk 3.0; 95% confidence interval 1.9-4.4). The association of illicit drug use with USA300 MRSA bacteremia decreased over time (p = 0.23 for trend). Notably, the proportion of patients with USA300 MRSA bacteremia who did not use illicit drugs increased over time. This finding suggests that this strain has spread from users of illicit drugs to other populations. PMID- 20735928 TI - Pneumococcal serotypes in children in 4 European countries. AB - After heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999-2002 (prevaccine) and 2005 2006 (postmarketing). Vaccine coverage increased to approximately 32%-48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3 4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9-16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends. PMID- 20735929 TI - Long-term health risks for children and young adults after infective gastroenteritis. AB - To quantify the risk and types of sequelae attributable to prior enteric infections, we undertook a population-based retrospective cohort study using linked administrative records. The risk for first-time hospitalization for sequelae was modeled by using Cox proportional regression analysis controlling for other health and sociodemographic factors. We identified a significant increase of 64% in the rate of first-time hospitalization for sequelae for persons with prior enteric infections: 52% for intragastrointestinal sequelae and 63% for extragastrointestinal sequelae compared with first-time hospitalization for those without prior infection. Extragastrointestinal sequelae occurred predominantly during the first 5 years after first-time enteric infection. In contrast, most intragastrointestinal sequelae occurred >10 years later. Infective gastroenteritis during childhood or adolescence increases the risk for first-time hospitalization for intragastrointestinal and extragastrointestinal disease over the 2 decades after first-time enteric infection, highlighting the importance of identifying ways of reducing the incidence of such infections. PMID- 20735930 TI - Typhoid fever and invasive nontyphoid salmonellosis, Malawi and South Africa. AB - To determine the prevalence of invasive nontyphoid salmonellosis and typhoid fever in Malawi and South Africa, we compared case frequency and patient age distribution. Invasive nontyphoid salmonellosis showed a clear bimodal age distribution; the infection developed in women at a younger age than in men. Case frequency for typhoid fever was lower than for salmonellosis. PMID- 20735931 TI - Novel hepatitis E virus genotype in Norway rats, Germany. AB - Human hepatitis E virus infections may be caused by zoonotic transmission of virus genotypes 3 and 4. To determine whether rodents are a reservoir, we analyzed the complete nucleotide sequence of a hepatitis E-like virus from 2 Norway rats in Germany. The sequence suggests a separate genotype for this hepatotropic virus. PMID- 20735932 TI - Increasing incidence of mucormycosis in University Hospital, Belgium. AB - To determine why incidence of mucormycosis infections was increasing in a large university hospital in Belgium, we examined case data from 2000-2009. We found the increase was not related to voriconazole use but most probably to an increase in high-risk patients, particularly those with underlying hematologic malignancies. PMID- 20735933 TI - Human herpesvirus 8 genotype E in patients with Kaposi sarcoma, Peru. AB - To determine human herpesvirus 8 (HHV-8) K1 genotypes in patients with Kaposi sarcoma (KS) from Peru, we characterized HHV-8 in 25 KS biopsy samples. Our findings of 8 A, 1 B, 14 C, and 2 E subtypes showed high HHV-8 diversity in these patients and association between E genotype and KS development. PMID- 20735934 TI - Rhinovirus outbreaks in long-term care facilities, Ontario, Canada. AB - Diagnostic difficulties may have led to underestimation of rhinovirus infections in long-term care facilities. Using surveillance data, we found that rhinovirus caused 59% (174/297) of respiratory outbreaks in these facilities during 6 months in 2009. Disease was sometimes severe. Molecular diagnostic testing can differentiate these outbreaks from other infections such as influenza. PMID- 20735935 TI - Tuberculosis acquired outside of households, rural Vietnam. AB - Using population-based data from rural Vietnam, we assessed tuberculosis (TB) transmission within and outside of households. Eighty-three percent of persons with recent household TB were infected by different strains of Mycobacterium tuberculosis than were their household members. This result argues against the effectiveness of active TB case finding among household members. PMID- 20735936 TI - Analysis of avian hepatitis E virus from chickens, China. AB - Avian hepatitis E virus (HEV) has been identified in chickens; however, only 4 complete or near-complete genomic sequences have been reported. We found that the near-complete genomic sequence of avian HEV in chickens from China shared the highest identity (98.3%) with avian HEV from Europe and belonged to avian HEV genotype 3. PMID- 20735938 TI - Co-infections with Plasmodium knowlesi and other malaria parasites, Myanmar. AB - To determine the frequency of co-infections with Plasmodium species in southern Myanmar, we investigated the prevalence of P. knowlesi. More than 20% of patients with malaria had P. knowlesi infection, which occurred predominantly as a co infection with either P. falciparum or P. vivax. PMID- 20735937 TI - Extensively drug-resistant tuberculosis, Pakistan. AB - Frequency of extensively drug-resistant tuberculosis in Pakistan increased from 1.5% in 2006 to 4.5% in 2009 (p<0.01). To understand the epidemiology, we genotyped selected strains by using spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats, and IS6110 restriction fragment length polymorphism analysis. PMID- 20735939 TI - Exposure of dentists to Mycobacterium tuberculosis, Ibadan, Nigeria. AB - To determine the prevalence of Mycobacterium tuberculosis infection among dental patients and to assess dentists' risk for exposure, we conducted a study among dental patients at a large tertiary hospital in Nigeria, a country where tuberculosis is endemic. Ten (13%) of 78 sputum samples obtained were positive for M. tuberculosis. PMID- 20735940 TI - KI and WU polyomaviruses and CD4+ cell counts in HIV-1-infected patients, Italy. AB - To investigate an association between KI and WU polyomavirus (KIPyV and WUPyV) infections and CD4+ cell counts, we tested HIV-1-positive patients and blood donors. No association was found between cell counts and virus infections in HIV 1-positive patients. Frequency of KIPyV infection was similar for both groups. WUPyV was more frequent in HIV-1-positive patients. PMID- 20735941 TI - Acute cervical lymphadenitis caused by Mycobacterium florentinum. PMID- 20735942 TI - Mobile messaging as surveillance tool during pandemic (H1N1) 2009, Mexico. PMID- 20735943 TI - Invasive Klebsiella pneumoniae infections, California, USA. PMID- 20735945 TI - Austrian syndrome associated with pandemic (H1N1) 2009 in child. PMID- 20735944 TI - Family outbreak of Shiga toxin-producing Escherichia coli O123:H-, France, 2009. PMID- 20735946 TI - Rickettsia sibirica mongolitimonae in traveler from Egypt. PMID- 20735947 TI - Increase in Neisseria meningitidis serogroup W135, Niger, 2010. PMID- 20735948 TI - Toscana virus infection in American traveler returning from Sicily, 2009. PMID- 20735949 TI - Hospital discharge data for Guillain-Barre syndrome and influenza A (H1N1) vaccine adverse events. PMID- 20735950 TI - Contact lens solution-associated Acanthamoeba and Fusarium keratitis. PMID- 20735951 TI - New infectious diseases and industrial food animal production. PMID- 20735952 TI - The soot that falls from chimneys. PMID- 20735953 TI - [Clinical significance of limited resection in lung cancer surgery.]. PMID- 20735954 TI - [Construction of the suppression subtractive cDNA libraries of human large cell lung cancer line L9981 before and after transfection with nm23-H1 gene.]. AB - BACKGROUND: It has been proven that nm23-H1 gene is an important metastaticsuppressed gene of lung cancer. In order to screen the differential expression genes related to nm23-H1 , we constructed the suppression subtractive cDNA libraries of human large cell lung cancer line L9981 transfected and untransfected with nm23-H1 gene by suppression subtractive hybridization (SSH) in this study, which lay a solid foundation for further screening and cloning metastatic-related genes of nm23-H1. METHODS: The forward and reverse suppression subtractive cDNA libraries were constructed in the human large cell lung cancer line L9981 before and after transfection with nm23-H1 gene (L9981 and L9981-nm23 H1) by SSH method. The positive clones were preliminarily screened by bluewhite colony, and precisely identified by PCR. RESULTS: The suppression subtractive cDNA libraries were successfully constructed in the human large cell lung cancer line L9981 transfected and untransfected with nm23-H1 gene (L9981-nm23-H1 and L9981). After the blue-white screening, about three hundred positive clones in the forward subtracted library and four hundred positive clones in the reverse subtracted library were obtained. Ramdom analysis of 96 clones in each library with colony PCR methods showed that 84 clones in the forward subtracted library and 83 clones in the reverse subtracted library contained (300-750) bp inserts. CONCLUSIONS: SSH is proved to be an efficient tool for differential expression gene cloning. The forward and reverse suppression subtractive cDNA libraries of human large cell lung cancer line L9981 transfected and untransfected with nm23 H1 gene (L9981-nm23-H1 and L9981) are successfully constructed by SSH and T/A cloning technology. The expression of nm23-H1 gene in the human large cell lung cancer cell lines may affect the differential expression of some metastatic related genes. PMID- 20735955 TI - [The expression of BAG-1 and its clinical significance in human lung cancer.]. AB - BACKGROUND: BAG-1 is a multifunctional anti-apoptotic protein that binds to a variety of cellular proteins and affects their functions. It has been proven that overexpression of BAG-1 was observed in a number of human maligancies and correlated with their prognosis. The aim of this study is to determine BAG-1 mRNA expression in human lung cancer tissues and its clinical significance. METHODS: The expression of BAG-1 was detected by real-time PCR in formalin-fixed, paraffin embedded human lung cancer tissues of 156 cases. RESULTS: (1) The median survival time (MST, 33.5 months) in BAG-1 low-expression group was significantly higher than that (20.5 months) in BAG-1 highexpression group (P <0.005); (2) The 3-year and 5-year survival rates (44.74%; 26.32%) in BAG-1 low-expression group were dramatically higher than that in BAG-1 high-expression group (32.5%; 21.25%)(P <0.05), respectively. The survival curves in BAG-1 low-expression group was also significantly better than that in BAG-1 high-expression group (P =0.045); (3) The further analysis indicated that the survical curves in BAG-1 low-expression group were much better than that in BAG-1 high-expression group in the lung cancer patient with TNM stage I, or with squamous cell cacrinoma, or without any metastasis, respectively (P <0.05). CONCLUSIONS: BAG-1 may be a biomarker for the prognosis of lung cancer patients, especially for the lung cancer patients with stage I or squamous cell carcinoma. PMID- 20735956 TI - [The killing effect of rmhTNF-alpha combined with gemcitabine on human lung adenocarcinoma cells A549.]. AB - BACKGROUND: At present clinical researches has proven that the chemotherapeutic effect on advanced non-small cell lung cancer (NSCLC) has gotten to plateau. Biotherapy combined with chemotherapy could improve curative effect on advanced NSCLC obviously. The project is aiming at exploring the killing effect and the mechanism of rmhTNF-alpha in combination with gemcitabine on human lung adenocarcinoma cell line A549. METHODS: CCK-8 was used to detect the inhibition ratio of rmhTNF-alpha and gemcitabine cell line A549; cell curve of growth was used to illustrate the influence of rmhTNF-alpha and gemcitabine on the proliferation of A549; FCM was used to detect the cell cycle and the apoptosis ratio of cell line A549 treated with either rmhTNF-alpha or gemcitabine or those combined. The change in cellular morphology and cell ultramicromorphology was observed by light microscope and transmission electron microscope respectively. RESULTS: The result of CCK-8 and cell curve of growth demonstrated that rmhTNF alpha not only inhibited the proliferation of A549, but also enhanced the killing effect of gemcitabine; FCM showed that rmhTNF-alpha promoted S cell cycle arrest and reduced proportion of G2/M cell arrest; also showed different apoptosis ratio was most significant in the group of rmhTNF-alpha combination with gemcitabine; the changes of morphology was observed obviously by light microscope and transmission electron microscope. CONCLUSIONS: rmhTNF-alpha enhances the the killing effect of gemcitabine on human lung adenocarcinoma cells A549 by inducing apoptosis and promoting cell cycle arrest. PMID- 20735957 TI - [The effect and mechanism of endothelin-1-induced intracellular free calcium in human lung adenocarcinoma cells SPC-A1.]. AB - BACKGROUND: Endothelin-1 (ET-1) is a potent mitogen involved in cell growth in human lung adenocarcinoma cells SPC-A1. The increase in intracellular free calcium ([Ca(2+)]i) plays a great role in this process. The aim of this study is to investigate the ET-1-induced [Ca(2+)]i responses in SPC-A1 cells and to explore its cellular mechanism. METHODS: [Ca(2+)]i was measured by Fura-2/AM fluorescent assay. Endothelin receptors antagonists, calcium channel blockers and intracellular signal transduction blockers were used to study the underlying mechanism of ET-1-induced [Ca(2+)]i responses in SPC-A1 cells. RESULTS: At the concentration of 1*10(-15) mol/L-1*10(-8) mol/L, ET-1 caused a dose-dependent increase of [Ca(2+)]i in SPC-A1 cells (P <0.05) in vitro . The ET-1-induced (1*10(-10) mol/L) increase of [Ca(2+)]i was blocked by BQ123 at 1*10(-7) mol/L (P <0.05), a highly selective endothelin receptor A (ETAR) antagonist, not by BQ788 at 10(-7) mol/L (P >0.05), a highly selective endothelin receptor B (ETBR) antagonist. Depletion of extracellular Ca(2+) with free Ca(2+) solution and 0.1mmol/L ethyleneglycol bis (2-aminoethyl ether) tetraacetic acid (EGTA) or blockade of voltage dependent calcium channel with nifedipine at 1*10(-6) mol/L significantly reduced the ET-1-induced increase of [Ca(2+)]i. The ET-1-induced (1*10(-10) mol/L) increase of [Ca(2+)]i was also significantly attenuated by U73122 at 1*10(-5) mol/L (P <0.05), a phospholipase C inhibitor, and by Ryanodine at 50*10(-6) mol/L. However, Staurosporine (2*10(-9) mol/L), a protein kinas C inhibitor, exerted no significant effect on the ET-1-induced (1*10(-10) mol/L) increase of [Ca(2+)]i. CONCLUSIONS: ET-1 elevates [Ca(2+)]i via activation of ETA receptor. Both phospholipase C/Ca(2+) pathway and Ca(2+) influx through voltage dependent Ca(2+) channel activate by ETAR contribute to this process. PMID- 20735958 TI - [Silencing effect study of Akt2-siRNA aimed at lung cancer cell NCI-H446.]. AB - BACKGROUND: Lung cancer is one of the most frequent malignant tumors and at the first place of mortality in today's world, It becomes more and more clear that the initiation and development of lung cancer is multistep processes involved in many genes. RNAi gets more and more attention in gene therapy because of its high efficiency and specificity. With RNAi technology, eukaryotic expression vectors aimed at AKT2 siRNA was designed and constructed, which is transfected into human small lung cancer cell line NCI-H446. The silencing effect was observed. METHODS: Using the known sequence of AKT2's mRNA (M95936), we designed two oligonucleotides that have short hairpin configuration and one oligonucleotide as control. DNA double strands was annealed, and cloned into vectorpGEM-T. Then, blue-white selection and T7/SP6 PCR was used to screen the positive clones, the target DNA and the express vector pRNAT-U6.2 were cut down by BamHI and XhoI restriction enzyme, and linked with each other; use PCR test to filtrate the positive clones and sequenced the target DNA, then transfected it into human small lung cancer cell line (NCI-H446), cultured and screened by G418, RT-PCR was used to detect the expression level of AKT2 mRNA in NCI-H446. RESULTS: validate the positive sequence by PCR and, transfect them to lung cancer cell line (NCI H446), AKT2-mRNA's expression was evidently declined. CONCLUSIONS: The expression vector pRNAT-U6.2-AKT2 was constructed successfully and the expression of Akt2 mRNA in small lung cancer cell line (NCI-H446) was obviously silenced after transfection. PMID- 20735959 TI - [Screening for proteins interacting with MCM7 in human lung cancer library using yeast two hybrid system.]. AB - BACKGROUND: MCM7 is a subunit of the MCM complex that plays a key role in DNA replication initiation. But little is known about its interaction proteins. In this study yeast two hybrid screening was used to identify the MCM7 interacting proteins. METHODS: Yeast expression vector containing human full length MCM7 pGBKT7 plasmid was constructed, and with a library of cDNAs from human lung cancer-pACT2 plasmid was transformed into yeast strain AH109, and was electively grew in X-a-gal auxotrophy medium SD/-Trp-Leu-His-Ade, and the blue colonies were picked up, the plasmid of the yeast colonies was extracted , and transformed into E. Coli to extract DNA and performed sequence analysis. RESULTS: Eleven proteins were identified which could specifically interact with MCM7 proteins, among these five were cytoskeleton proteins, six were enzymes, kinases and related receptors. CONCLUSIONS: The investigation provides functional clues for further exploration of MCM7 gene. PMID- 20735960 TI - [The proliferation promoting effects of MAG-2 on human lung cancer cell PLA801.]. AB - BACKGROUND: Both tumor proliferation and metastasis are multistep processes with many genes involved. A novel gene MAG-2, which may have close correlation with lung cancer metastasis, was identified in our lab through approach of suppression subtractive hybridization using lung cancer cell strains with same origin but different metastatic potential as models. The objective of our works presented here is to investigate the proliferation related effects of MAG-2 on human lung giant-cell line PLA801, and to explore the underlying molecular mechanism. METHODS: Sense and anti-sense expressing vector of MAG-2 were constructed and transfected into PLA801C and D cell respectively and the change of expressing levels of target gene in stable transfected cell strains was assayed by RT-PCR. The alteration in terms of proliferation and cytoplasm Ca(2+) of the stable transfected cell strains and vector controls were tested by the methods of MTT and Fluo-3-Am staining. The proteins levels of p53 and mRNA levels of PCNA of different cell strains were analyzed by Western blot and RT-PCR. RESULTS: The stable transfected cell strains of CMAG2+, DMAG2- and their vector controls Cvector and Dvector were obtained. The MAG-2 mRNA levels of CMAG2+ and DMPAG2- were 7 and 0.6 times higher or lower comparing those of vector controls. MAG-2 could increase the mRNA level of PCNA and down-regulated the p53 protein in PLA801C strain. In consistent with PCNA's mRNA elevating, the proportion of S phase cell in the mass was also increased. But the significant difference was not observed on MTT assay between CMAG2+ and its control, the reason might be due to the mutated p53, which had strong proliferation promoting effects, was also down regulated by MAG-2's over-expression in PLA801C, and the levels of cytoplasm calcium in CMAG2+ had 1.05 times more than that of vector control. As to the PLA801D strain, the decreased expression of MAG-2 result in lower level of cytoplasm calcium (0.64 time of control's) and the cell proliferation was also restrained by means of MTT assay. CONCLUSIONS: MAG-2 has taken part in the proliferation regulation of lung cancer cells PLA801, and the mechanism of its proliferation-related function maybe lie in its effects on cytoplasmic free calcium. PMID- 20735961 TI - [Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal mode.]. AB - BACKGROUND: Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. METHODS: Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4 benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H&E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. RESULTS: No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (Chi Square=8.12, P <0.01). Higher level of p53 expression in lung cancer tissues of group A was observed under microscope than that of group B, but the difference has no statistic significance (P >0.05). However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P <0.05). CONCLUSIONS: The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention. PMID- 20735962 TI - [Risk factors associated with atrial fibrillation in early period after operation of lung cancer.]. AB - BACKGROUND: Atrial fibrillation (AF) is a common complication after operation of lung cancer. Atrial fibrillation is often associated with longer hospital stay time and higher hospital cost, as well as increased postoperative mortality. The aim of this study is to explore the risk factors of atrial fibrillation (AF) in early period after operation of lung cancer and analyze its impact on short-term mortality, hospital stay time and hospitalization cost. METHODS: From January 2006 to December 2007, 416 consecutive lung cancer patients underwent operation in our hospital were chosen. Postoperative ECG (electrocardiography) was used to diagnose AF. The cases were divided into two groups: AF group and control group (Non-AF group). Statistic Chi-Square test was used to compare numeration data and Logistic regression was performed to find risk factors of postoperative AF. RESULTS: In the 416 lung cancer patients, 52 cases (12.5%) were with AF and most occurred in the 1 to 3 days after operation. Multivariate analysis showed that the patients with age older than 65, preoperative pulmonary infection, low preoperative FEV1%pre, Intrapericardia operation and postoperative hypoxemia are prone to occur AF after operation. In AF group, the hospital stay time was longer, the hospitalization cost was higher. No obvious difference was observed with short-term mortality between the two groups. CONCLUSIONS: The incidence of AF after operation with lung cancer is 12.5% (52/416). Patients with age older than 65, preoperative pulmonary infection, low FEV1%pre, intrapericardia operation and postoperative hypoxemia have a higher risk of AF following operation. Although postoperative AF has no obvious impact on short-term mortality, it is associated with longer impatient time and higher hospitalization cost. PMID- 20735963 TI - [Reduction of p120(ctn) isoforms is significantly associated with lymph node metastasis of lung cancer.]. AB - BACKGROUND: p120(ctn) plays an important role in cell adhesion and has a significant association with tumorigenesis. To investigate the expression of p120(ctn) (p120 cateinin) isoforms in lung squamous cell carcinomas and adenocarcinomas, and analyze the correlation between p120(ctn) and clinicopathological parameters. METHODS: The expression patterns of p120(ctn) in lung cancer tissues and the corresponding normal lung tissues were examined by reverse transcription-polymerase chain reaction (RT-PCR). Immunofluorescence, RT PCR, and Western blot were used to investigate the expression of p120(ctn) isoforms in lung cancer cell lines BE1 and LH7. RESULTS: Compared with corresponding normal lung tissues, lung cancer tissues have significantly lower levels of total mRNA, isoform1 and 3 mRNA (P <0.001, P <0.001, P =0.001). Furthermore, reduction of p120(ctn) isoform 1 mRNA is negatively associated whereas p120(ctn) isoform 3 is positively associated-with lymphatic metastasis (P =0.01, P =0.029). BE1 cells with 94% metastatic frequency has lower levels of p120(ctn) isoforms than LH7 cells with low metastatic potential. CONCLUSIONS: Reductions of p120(ctn) isoform 1 and 3 mRNA is a common phenomenon in lung cancer tissues and may play a role in metastasis progression of human lung cancer. PMID- 20735964 TI - [Research of loss of heterozygaity on chromosome 3p in non-small cell lung cancer.]. AB - BACKGROUND: It has been proven that allelic loss of chromosome region 3p occurs early and frequently in non-small-cell lung cancer, and numerous tumor suppressor genes at this locus may be targets of inactivation. The aim of this study is to investigate the relationship between loss of heterozygosity (LOH) of the allele genes on 3p and the diagnostic value of NSCLC. METHODS: A total of 32 NSCLC samples and 8 tissues of the pulmonary benign disease have been analyzed by fluorescent quantitative PCR. RESULTS: There were 25 of the 32 cases (78.125%) with NSCLC tumor had LOH on 3p . Among them, LOH detection was 14 cases (43.75%) at 3p 25, 18 cases (56.25%) at 3p14 and 18 cases (56.25%) at 3p 21.3, respectively, and was 18.75% (3p 25),31.25% (3p 14),50% (3p 21.3) in the nucleated cell in peripheral blood, respectively. The total detection was 20 cases (65.625%). LOH detection in the nucleated cells in peripheral blood was correlation with the tumor tissues and the combined detection is better than single ones. CONCLUSIONS: Our results showed that 3p LOH occur commonly in human NSCLC. The 3p LOH detection of the tumor tissue and the nucleated cell in peripheral blood is beneficial to the diagnosis of NSCLC. The combined LOH detection of 3 separate regions of 3p LOH is beneficial to increase the detection rate. PMID- 20735965 TI - [Expression of RhoC and its regulators RhoGDIbeta RhoGDIgamma and their clinical importance in lung squamous cell cancer and adenocarcinoma.]. AB - BACKGROUND: It has been proven that RhoC is known to be overexpressed in tumor. The activities of RhoC are negatively regulated by guanine nucleotide dissociation inhibitor beta,gamma(GDIbeta,gamma), but its role in cancer is quite limited. The purpose of the study is to investigate the expression of RhoC, RhoGDIbeta, RhoGDIgamma and analyze the correlation between RhoC and RhoGDIbeta RhoGDIgamma expression and clinic implication. METHODS: Western blot and RT-PCR were used to detect RhoC, RhoGDIbeta and RhoGDIgamma protein and mRNA, respectively in 40 lung cancer tissues. RESULTS: The expression levels of RhoC, RhoGDIbeta and RhoGDIgamma protein and mRNA were more remarkably higher in all tumor samples than those in the normal tissues. The expression levels of RhoC and RhoGDIgamma positively correlated with clinical TNM staging, lymph node metastasis (r =0.659, P <0.05)(r =0.597, P <0.05), and the expression levels of RhoGDIbeta negatively correlate with clinical TNM staging, lymph node metastasis (r =-0.621, P <0.05). CONCLUSIONS: RhoC, RhoGDIbeta and RhoGDIgamma are correlated with clinical TNM staging and may be correlated with lymph node metastasis of lung cancer. PMID- 20735966 TI - [The influence of anthracosis and p16(ink4a) gene abberant methylation to the oncogenesis and progression of small pulmonary adenocarcinoma.]. AB - BACKGROUND: Anthracosis is black dust matter deposition in the pulmonary parenchyma, which can cause bronchial deformity and destruction. Previously reported, anthracosis is closely correlated to the oncogenesis and progression of small pulmonary adenocarcinoma and p16(ink4a) gene aberrant methylation was closely associated with lung carcinogenesis. In this study, we want to characterize the influence of anthracosis and p16(ink4a) gene aberrant methylation on small adenocarcinoma. METHODS: DNA was bisulfite modified and then Methylation Specific PCR was used to detect p16(ink4a) gene aberrant methylation, and black dust matter was extracted from lung tissues, the absolute absorbance (A) detected by densitometry was defined as anthracotic index (AI). The histopathologic diagnosis was according to Noguchi's classification for small pulmonary adenocarcinoma. RESULTS: For heavy smokers, the mean AI was significantly higher than that of nonsmokers (P =0.005) and the frequency of p16(ink4a) gene aberrant methylation was also significantly higher than that of nonsmokers (P =0.023). The frequency of p16(ink4a) gene aberrant methylation of early stage small adenocarcinoma was lower than that of advanced and poor differentiated small adenocarcinoma, otherwise p16(ink4a) protein expression of early stage small adenocarcinoma was significantly higher than that of poor differentiated small adenocarcinoma (P =0.032). CONCLUSIONS: AI and p16(ink4a) gene aberrant methylation detection could be used as a combined potential biomarker of small adenocarcinoma. PMID- 20735967 TI - [The expression of Skp2 in human non-small cell lung cancer and its correlation with expression of p27 protein.]. AB - BACKGROUND: S-phase kinase-associated protein 2 (Skp2) is one of the positive regulators of the cell cycle that promote Ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in tumorigenesis. In this study, we investigated the expression of Skp2 in human nonsmall cell lung cancer (NSCLC) and its relationship with expression of p27 protein. METHODS: The expression of Skp2 and p27 protein were detected in 68 NSCLC, 17 normal bronchial epithelium by the tissue chip and immunohistochemistry technology. RESULTS: Skp2 was only expressed in NSCLC patients, there was closely relationship among Skp2 expression and histological subtype, cellular differentiation, sex and smoking; Otherwise, there was no relationship among skp2 expression and age or TNM stage. The expression of p27 protein was found in normal bronchial epithelial cells, and the expression was reduced in NSCLC. The expression of p27 was significantly reduced in patients with positive expression of Skp2. Expression of Skp2 was negatively correlated with expression of p27. CONCLUSIONS: The expression of Skp2 is up-regulated in NSCLC, and overexpression of Skp2 reduces the protein level of p27 through ubiquitin-dependent degradation, indicating Skp2 may play an important role in oncogenesis and development of NSCLC. PMID- 20735968 TI - [Effects of selenium and reduced glutathione on the proliferation and apoptosis of XWLC-05 cell.]. AB - BACKGROUND: Selenium is an essential micronutrient for mammals but toxic in large amounts. Most studies indicate that selenium has inhibitory effect on cancer. The aim of this study is to investigate the effects of selenium and reduced glutathione (GSH) combined application on the proliferation and apoptosis of human lung adenocarcinoma cell line XWLC-05. METHODS: XWLC-05 cells were respectively treated in vitro by four factors (sodium selenite, GSH, sodium selenite+GSH and blank control (RMPI-1640 +10% calf serum) in different concentrations for 24 h. Cell growth inhibition rates were determined by MTT assay, cytomorphology was observed under inverted phase contrast microscope and changes of cell cycle were detected by Flow Cytometry (FCM). RESULTS: Both selenium and GSH individual on the XWLC-05 cells were found to possess obvious growth inhibition effect on the XWLC-05 cells. Selenium and GSH combined application on the XWLC-05 cells had cooperative inhibition effect (P <0.01). The inhibition rate was increased in a dose-dependent relationship as selenium with concentrations between (0.5-4.0) mug/mL (P <0.01) whether it was selenium single factors or selenium and GSH combined effect. FCM results showed that some XWLC-05 cells were induced apoptosis and G1 phase cells were markedly increased and S, G2/M phase cells decreased in both selenium individual groups and selenium and GSH combined groups. CONCLUSIONS: Selenium and GSH combined application on XWLC 05 cells can enhance directly the cell growth inhibitory effect compared with selenium and GSH individual. The mechanism seems to inhibit the synthesis of RNA and protein and prevent cells from entering S phase. PMID- 20735969 TI - [Relationship between Glut-1, Glut-3 expression and fluorodeoxyglucose uptake in NSCLC and benign pulmonary lesion.]. AB - BACKGROUND: It has been known that facilitative glucose transporter (GLUT) is the main carrier which intervenes the glucose uptake of cell. The expression of Glut 1, Glut-3 has close relationship with the uptake of (18)Fluoro-2-deoxyglucose (FDG). The aim of this study is to discuss the relationship between expression of glucose transporter-1, 3 (Glut-1, Glut-3) and FDG uptake in NSCLC and benign pulmonary lesion. METHODS: Eighty-four NSCLC patients and twenty-four benign pulmonary lesion patients received PET/CT scan before operation. The expression of Glut-1, Glut-3 was detected by immunohistochemistry. The relationship among these factors was investigated. RESULTS: The range of average SUV (SUVave) of the eighty-four patients was 3.6-13.2, and the average value was 7.8+/-3.0. The range of average SUV (SUVave) of the twenty-four patients was 1.2-9.2, and the average value was 3.2+/-1.9. In NSCLC tissues, the average immunohistochemical staining intensity of Glut-1, Glut-3 was 4.4+/-1.3 and 2.6+/-1.9, respectively. In benign pulmonary lesion, the average immunohistochemical staining intensity of Glut-1, Glut-3 was 0.9+/-0.9 and 1.2+/-1.4, respectively. Both of the Glut-1 and the Glut 3 expression levels were significantly higher in NSCLC than those in benign pulmonary lesion (P <0.01). Glut-1 expression was positively correlated to SUVave (r =0.78, P <0.01) in NSCLC patients. Glut-3 expression was positively correlated to SUVave (r =0.45, P =0.03) in benign pulmonary lesion patients. CONCLUSIONS: The results show Glut-1 and Glut-3 express not only in NSCLC but also in benign pulmonary lesion. Glut-1 play an important role in FDG uptake in NSCLC. Glut-3 play an important role in FDG uptake in benign pulmonary lesion. PMID- 20735970 TI - [Effects of matrine on the growth inhibition, c-myc and hTERT protein expression in human adenocarcinoma lung cancer cell line A549.]. AB - BACKGROUND: It was reported that telomerase was associated with the oncogenesis and progression of cancer, and to be the common targets of cancer therapy. The mechanism of matrine on lung cancer in vitro is not clear. We studied the effect of matrine on growth of human lung adenocarcinoma A549 cells and the mechanism related with telomerase. METHODS: MTT was used for measuring A549 cells viability, Hoechst 33342-propidium iodide fluorescent staining for observing apoptotic cells, flow cytometry (FCM) for analyzing cell cycle and apoptosis, and immunocytochemistry for measuring the protein expressions of c-myc and hTERT in A549 cells. RESULTS: Matrine inhibited the proliferation of A549 cells with a time-dose-dependent manner (P <0.05). Hoechst 33342-propidium iodide staining showed apoptotic cells with chromatin condensation and fragmentation of nuclei. FCM analysis indicated elevating rate of cells in G0/G1 phase, lowering rate of that in S phase and the highering apoptotic rate. The levels of c-myc and hTERT protein expression in the matrine group was lower than that in the control group (P <0.05), and AOD of c-myc showed positive correlation with AOD of hTERT (r =0.633, P <0.01). CONCLUSIONS: The inhibitory effect of matrine on A549 cells may be related to the lower expression of c-myc and hTERT. PMID- 20735971 TI - [PML expression in lung carcinomas: analysis by RT-PCR in formalin-fixed and paraffin-embedded tissue.]. AB - BACKGROUND: Formalin-fixed and paraffin-embedded tissue (FPE) with long term follow-up and clinicopathological data are extensively available and easily accessible. They represent an extensive source of genetic materials and proteins to be investigated for clinical usage. We conducted the study to explore the possibility of extracting RNA from FPE of lung cancer, and checking up the transcription levels of the promyelocytic leukemia gene (PML) by RT-PCR. METHODS: five fresh frozen lung adenocarcinoma tissues and 40 FPEs of lung cancer were chosen; FPEs had been conserved for 60-85 months. All samples had been identified lacking expression of PML protein by immunohistochemical staining. The total RNA was extracted by using Trizol one-step method, and verified by testing OD value. RT-PCR was used to detect the transcription level of PML gene. RESULTS: The RNAs from both tissues had the OD value ranging from 1.7 to 2.1. RT-PCR results displayed that mRNA of PML (295 bps) and beta-actin (318 bps) was not absent in all cancer tissues. CONCLUSIONS: Trizol one-step method is easily accessible, and reliable for extracting RNA in fragments around 300 bases from FPEs. Loss of PML protein in lung cancer is not caused by downward adjustment of mRNA. PMID- 20735972 TI - [Experiences on the application of video-assisted mediastinoscopy for 40 patients with mediastinal lesions.]. AB - BACKGROUND: To evaluate the clinical experiences on the application of videoassisted mediastinoscopy for 40 patients with mediastinal lesions. METHODS: Forty patients underwent video-assisted mediastinoscopy through neck-way surgery, including 17 cases with sole mediastinal nodule or mass, of which the pathologic diagnosis was warranted; 18 cases diagnosed as lung cancer with enlarged mediastinal lymph nodes, of which the clinical stage needed to be clarified; and 5 cases of mediastinal mass with miscellaneous clinical conditions. The results of mediastinoscopy biopsy and pathological diagnosis were analyzed. RESULTS: Satisfied tissue for detailed examination was obtained for all of the 40 cases who underwent mediastinoscopy. The successful rate for biopsy was 100%. The final pathologic diagnosis were 11 cases of lymph node metastasis from lung cancer, 4 cases of lymph node metastasis from unknown site, 9 cases of sarcoidosis, 6 cases of lymph node reactive hyperplasia, 4 cases of tuberculosis, 2 cases of lymphoma, 2 cases of mediastinal cyst, 1 case of retrosternal thyroid, 1 case of inflammatory granuloma. Two cases of postoperative hemorrhage related to surgery were successfully treated. CONCLUSIONS: Video-assisted mediastinoscopy is safe and useful. It's essential for the diagnosis of sole mediastinal mass, a good method to clarify the pathologic stage of patients with lung cancer, and the only way to get the pathologic diagnosis for some special mediastinal disease. PMID- 20735973 TI - [A randomized clinical trial of combination of Aidi injection with Gemcitabine and Oxaliplatin regimen or Go regimen only in the treatment of advanced non-small cell lung cancer.]. PMID- 20735974 TI - [Early diagnosis strategy of peripheral lung carcinoma.]. PMID- 20735975 TI - [Research advances of microRNAs.]. PMID- 20735976 TI - [Recent progress of KSR-a MAPK scaffold of the Ras pathway.]. PMID- 20735977 TI - [The study progress of second-line chemotherapy of small cell lung cancer.]. PMID- 20735978 TI - [RNAi and non-small cell lung cancer.]. PMID- 20735979 TI - [Prognostic analysis of non-small lung cancer.]. PMID- 20735980 TI - [Combination of cryosurgery and argon plasma coagulation in rigid bronchoscope for treatment of main airway neoplasma.]. PMID- 20735981 TI - [A case report of lung adenocarcinoma with high level AFP.]. PMID- 20735982 TI - [A case of interstitial pneumonia caused by carmustine.]. PMID- 20735983 TI - The cleavage of N-cadherin is essential for chondrocyte differentiation. AB - The aggregation of chondroprogenitor mesenchymal cells into precartilage condensation represents one of the earliest events in chondrogenesis. N-cadherin is a key cell adhesion molecule implicated in chondrogenic differentiation. Recently, ADAM10-mediated cleavage of N-cadherin has been reported to play an important role in cell adhesion, migration, development and signaling. However, the significance of N-cadherin cleavage in chondrocyte differentiation has not been determined. In the present study, we found that the protein turnover of N cadherin is accelerated during the early phase of chondrogenic differentiation in ATDC5 cells. Therefore, we generated the subclones of ATDC5 cells overexpressing wild-type N-cadherin, and two types of subclones overexpressing a cleavage defective N-cadherin mutant, and examined the response of these cells to insulin stimulation. The ATDC5 cells overexpressing cleavage-defective mutants severely prevented the formation of cartilage aggregates, proteoglycan production and the induction of chondrocyte marker gene expression, such as type II collagen, aggrecan and type X collagen. These results suggested that the cleavage of N cadherin is essential for chondrocyte differentiation. PMID- 20735984 TI - MicroRNA-155 regulates angiotensin II type 1 receptor expression and phenotypic differentiation in vascular adventitial fibroblasts. AB - MicroRNAs (miRNAs), which are genomically encoded small RNAs, negatively regulate target gene expression at the post-transcriptional level. Our recent study indicated that microRNA-155 (miR-155) might be negatively correlated with blood pressure, and it has been suggested that miR-155-mediated target genes could be involved in the cardiovascular diseases. Bioinformatic analyses predict that angiotensin II type 1 receptor (AT(1)R) is a miR-155 target gene. The present study investigated the potential role of miR-155 in regulating AT(1)R expression and phenotypic differentiation in rat aortic adventitial fibroblasts (AFs). Luciferase assay demonstrated that miR-155 suppressed AT(1)R 3'-UTR reporter construct activity. miR-155 overexpression in AFs did not reduce target mRNA levels, but significantly reduced target protein expression. In addition, AFs transfected with pSUPER/miR-155 exhibited reduced Ang II-induced ERK1/2 activation. miR-155 overexpression in cells attenuated Ang II-induced alpha smooth muscle actin (alpha-SMA, produces myofibroblast) expression, but did not transform growth factor beta-1 (TGF-beta1). This study demonstrated that miR-155 could have an important role in regulating adventitial fibroblast differentiation and contribute to suppression of AT(1)R expression. PMID- 20735985 TI - Inactivation of Smad4 leads to impaired ocular development and cataract formation. AB - PURPOSE: Signaling by members of the TGFbeta superfamily of molecules is essential for embryonic development and homeostasis. Smad4, a key intracellular mediator in TGFbeta signaling, forms transcriptional activator complexes with Activin-, BMP-, and TGFbeta-restricted Smad proteins. However, the functional role of Smad4 in controlling different visual system compartments has not been fully investigated. METHODS: Using the Pax6 promoter-driven Cre transgenic, smad4 was conditionally inactivated in the lens, cornea and ectoderm of the eyelids. Standard histological and molecular analytical approaches were employed to reveal morphological and cellular changes. RESULTS: Inactivation of Smad4 in the lens led to microphthalmia and cataract formation in addition to the persistent adhesion of the retina to the lens and the iris to the cornea. Inactivation of Smad4 from the ectoderm of the eyelid and cornea caused disruption to eyelid fusion and proper development of the corneal epithelium and corneal stroma. CONCLUSIONS: Smad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina. PMID- 20735986 TI - Development of an efficient E. coli expression and purification system for a catalytically active, human Cullin3-RINGBox1 protein complex and elucidation of its quaternary structure with Keap1. AB - The Cullin3-based E3 ubiquitin ligase complex is thought to play an important role in the cellular response to oxidative stress and xenobiotic assault. While limited biochemical studies of the ligase's role in these complex signaling pathways are beginning to emerge, structural studies are lagging far behind due to the inability to acquire sufficient quantities of full-length, highly pure and active Cullin3. Here we describe the design and construction of an optimized expression and purification system for the full-length, human Cullin3-RINGBox 1 (Rbx1) protein complex from Escherichia coli. The dual-expression system is comprised of codon-optimized Cullin3 and Rbx1 genes co-expressed from a single pET-Duet-1 plasmid. Rapid purification of the Cullin3-Rbx1 complex is achieved in two steps via an affinity column followed by size-exclusion chromatography. Approximately 15mg of highly pure and active Cullin3-Rbx1 protein from 1L of E. coli culture can be achieved. Analysis of the quaternary structure of the Cullin3 Rbx1 and Cullin3-Rbx1-Keap1 complexes by size-exclusion chromatography and analytical ultracentrifugation indicates a 1:1 stoichiometry for the Cullin3-Rbx1 complex (MW=111kDa), and a 1:1:2 stoichiometry for the Cullin3-Rbx1-Keap1 complex (MW=280kDa). This latter complex has a novel quaternary structural organization for cullin E3 ligases, and it is fully active based on an in vitro Cullin3-Rbx1 Keap1-Nrf2 ubiquitination activity assay that was developed and optimized in this study. PMID- 20735987 TI - Antifungal properties and mode of action of psacotheasin, a novel knottin-type peptide derived from Psacothea hilaris. AB - Psacotheasin is a 34-mer knottin-type peptide that is derived from Psacothea hilaris larvae. In this study, the antifungal activity and mechanism(s) by which psacotheasin affects human fungal pathogens were investigated. Psacotheasin shows remarkable antifungal properties without hemolytic activity against human erythrocytes. To understand the antifungal mechanism(s) of psacotheasin in Candida albicans, flow cytometric analysis with DiBAC(4)(3) and PI was conducted. The results showed that psacotheasin depolarized and perturbed the plasma membrane of the C. albicans. Three-dimensional (3D)-flow cytometric contour-plot analysis, accompanied by decreased forward scatter (FS), which indicates cell size, confirmed that psacotheasin exerted antifungal effects via membrane permeabilization. The membrane studies, using a single GUV and FITC-dextran (FD) loaded liposomes, indicate that psacotheasin acts as a pore-forming peptide in the model membrane of C. albicans and the radius of pores were presumed to be anywhere from 2.3 to 3.3nm. Therefore, the current study suggests that the mechanism(s) of psacotheasin's antifungal properties function within the membrane. PMID- 20735988 TI - Differentiation of human neural progenitor cells regulated by Wnt-3a. AB - Wnt ligands play pivotal roles in the control of cell growth and differentiation during central nervous system development via the Wnt signaling pathway. In this study, we investigated the effects of Wnt-3a and beta-catenin on the differentiation of ReNcell VM human neural progenitor cells. After overexpression of Wnt-3a or mutant-stabilized beta-catenin in ReNcell VM cells, their effects on TCF-mediated transcription, Wnt target gene expression and differentiation into neuronal and glial cells were investigated. Our results show that activation of Wnt/beta-catenin signaling increases TCF-mediated transcription and the expression of the Wnt target genes Axin2, LEF1 and CyclinD1 in ReNcell VM cells. In contrast to mutant-stabilized beta-catenin, Wnt-3a increases neurogenesis during the differentiation of ReNcell VM cells. Thus, our data suggest that neurogenesis induced by Wnt-3a is independent of the transcriptional activity of Wnt/beta-catenin pathway in ReNcell VM cells. PMID- 20735989 TI - Epigenetic regulation of neonatal cardiomyocytes differentiation. AB - The relationship between DNA methylation, histone modifications and terminal differentiation in cardiomyocytes was investigated in this study. The upregulation of methylation-related proteins, including DNA methyltransferase (DNMT) 1, methyl-CpG binding domain proteins 1, 2 and 3, and the increase in global methylation during rat neonatal heart development were observed. Moreover, an increase in DNA synthesis and a delay in differentiation were found in 5 azacytidine (5-azaC)-treated cardiomyocytes. Increase in acetylation of H3-K9, H4 K5, H4-K8 and methylation of H3-K4 suggested a more accessible chromatin structure in 5-azaC-treated cells. Furthermore, methyl-CpG-binding protein 2 was found to be upregulated in differentiated cardiomyocytes. Overexpression of this protein resulted in an increase of global methylation levels. Therefore, we suggest that a hypermethylated genome and a more compact chromatin structure are formed during terminal differentiation of cardiomyocytes. PMID- 20735990 TI - (D-Ser2)Oxm[mPEG-PAL]: a novel chemically modified analogue of oxyntomodulin with antihyperglycaemic, insulinotropic and anorexigenic actions. AB - Oxyntomodulin (Oxm) is a hormone which has been shown to exhibit a range of potentially beneficial actions for alleviation of obesity-diabetes. However, exploitation of Oxm-based therapies has been severely restricted due to degradation by the enzyme dipeptidylpeptidase-IV (DPP-IV). Thus, the aim of this study was to assess the glucose-lowering, insulin-releasing and anorexigenic actions of chemically modified, enzyme-resistant analogues of Oxm. Oxm, (d Ser(2))Oxm and (d-Ser(2))Oxm[mPEG-PAL], were incubated with DPP-IV to assess enzyme stability and pancreatic beta-cells to evaluate insulin secretion. cAMP production was assessed using glucagon-like peptide-1 (GLP-1) and glucagon receptor transfected cells. In vivo effects of Oxm analogues on glucose homeostasis, insulin secretion, food intake and bodyweight were examined in obese diabetic (ob/ob) mice. (d-Ser(2))Oxm[mPEG-PAL] displayed enhanced DPP-IV resistance compared to (d-Ser(2))Oxm and Oxm. All peptides demonstrated similar in vitro cAMP and insulin-releasing actions, which was associated with dual action at GLP-1 and glucagon receptors. Acute administration of (d Ser(2))Oxm[mPEG-PAL] and (d-Ser(2))Oxm reduced plasma glucose and food intake, whilst plasma insulin levels were elevated. Once-daily administration of (d Ser(2))Oxm[mPEG-PAL] for 14 days to ob/ob mice decreased food intake, bodyweight, plasma glucose and increased plasma insulin. Furthermore, daily (d Ser(2))Oxm[mPEG-PAL] improved glucose tolerance, increased glucose-mediated insulin secretion, pancreatic insulin content, adiponectin and decreased both visfatin and triglyceride levels. The ability of enzyme-resistant (d Ser(2))Oxm[mPEG-PAL] to improve glucose homeostasis, insulin secretion, satiety, bodyweight and markers of fat metabolism suggests significant promise for Oxm based therapies for obesity-diabetes. PMID- 20735991 TI - Activation of ceramide synthase 6 by celecoxib leads to a selective induction of C16:0-ceramide. AB - Ceramides serve as bioactive molecules with important roles in cell proliferation and apoptosis. Ceramides (Cer) with different N-acyl side chains (C(14:0)-Cer C(26:0)-Cer) possess distinctive roles in cell signaling and are differentially expressed in HCT-116 colon cancer cells. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, exhibiting antiproliferative effects, activates the sphingolipid pathway. To elucidate the mechanism, HCT-116 cells were treated with 50MUM celecoxib leading to a significant increase of C(16:0)-Cer. Interestingly, 50MUM celecoxib resulted in a 2.8-fold increase of ceramide synthase (CerS) activity as measured by a cell-based activity assay. siRNA against several CerSs revealed that CerS6 was predominantly responsible for the increase of C(16:0)-Cer in HCT-116 cells. Moreover, the silencing of CerS6 partially protected HCT-116 cells from the toxic effects induced by celecoxib. Treatment of cells with celecoxib and fumonisin B1 (inhibitor of CerSs) or myriocin (inhibitor of l serine palmitoyl transferase) or desipramine (inhibitor of acid sphingomyelinase and acid ceramidase) revealed that the increase of C(16:0)-Cer results predominantly from activation of the salvage pathway. Using the nude mouse model we demonstrated that celecoxib induces also in vivo a significant increase of C(16:0)-Cer in stomach, small intestine and tumor tissue. In conclusion, celecoxib causes a specific increase of C(16:0)-Cer by activating CerS6 and the salvage pathway, which contribute to the toxic effects of celecoxib. PMID- 20735992 TI - Cyclosporine A attenuates hypoxic-ischemic brain injury in newborn rats. AB - Cyclosporine A (CsA) is neuroprotective in ischemic brain injuries of adult animals because it blocks the permeability transition of the mitochondrial membrane. In this study, we examined the neuroprotective effect of CsA on hypoxia ischemia (HI)-induced brain injury in newborn rats. Seven-day-old Sprague-Dawley rat pups were subjected to 2h of 8% oxygen following a unilateral carotid artery ligation. With a single dose of CsA treatment (20mg/kg, intraperitoneal) given immediately after HI, the HI-induced decrease in brain mitochondrial membrane potential measured with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl carbocyanine iodide (JC-1) and adenosine triphosphate levels, and increase in the brain lactate level, both apoptotic and necrotic cells measured with annexin V and propidium iodide (V-PI), and infarct area measured with 2,3,5 triphenyltetrazolium chloride (TTC) were significantly attenuated at 48 h, and the reduced brain volume also significantly improved 2 weeks following HI. In summary, Cyclosporine A, a mitochondrial permeability transition blocker, significantly attenuated hypoxia-ischemia-induced lowering of the mitochondrial membrane potential, cerebral energy status, increased apoptotic and necrotic cells, and the ensuing cerebral infarction in the immature brain. PMID- 20735993 TI - Postural control and attentional demand during adolescence. AB - In the present study we aimed to determine the attentional cost of postural control during adolescence by studying the influence of a cognitive task on concurrent postural control. 38 teenagers aged 12 to 17years and 13 young adults (mean age=26.1) stood barefoot on a force platform in a semi-tandem position. A dual-task paradigm consisted of performing a Stroop or a COUNTING BACKWARD task while simultaneously standing quietly on a firm or foam support surface. Different centre of pressure (CoP) measures were calculated (90% confidence ellipse area, mean velocity, root mean square on the antero-posterior (AP) and medio-lateral (ML) axes). The number and percentage of correct responses in the cognitive tasks were also recorded. Our results indicate (1) higher values of surface, ML mean velocity and ML RMS in the COUNTING BACKWARD task in adolescents aged 12 to 15 than in teenagers aged 16 to 17 and in adults, regardless of the complexity of the postural task and, (2) better cognitive performances in the Stroop than in the COUNTING BACKWARD task. The difference in the dual-task performance between the different age groups and particularly the existence of a turning point around 14-15years of age might be due to 1) difficulties in properly allocating attentional resources to two simultaneous tasks and/or, 2) the inability to manage increased cognitive requests because of a limited information processing capacity in adolescents aged 14-15years. PMID- 20735994 TI - Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein. AB - We hypothesized that one of the mechanisms underlying the protection of brain injury by therapeutic hypothermia is associated with preservation of neural stem cells. We investigated effects of moderate low temperature and the contribution of a cold-inducible molecule for the stemness of neural stem cells. The MEB5 mouse neural stem cell line was cultured in the presence or absence of EGF, and apoptosis, mRNA expression, and immunocytochemistry of the differentiation markers nestin and GFAP were evaluated at 37 or 32 degrees C. We investigated the contribution of the cold-inducible RNA binding protein (CIRP) on apoptosis and differentiation of MEB5 cells at 32 degrees C. EGF deprivation increased the number of apoptotic cells, decreased expression of nestin, and increased expression of GFAP. The moderate low temperature prevented apoptosis and decreases in expression of GFAP in MEB5 by EGF deprivation. The moderate low temperature significantly increased expression of CIRP. siRNA against CIRP significantly increased the apoptotic cell population of MEB5 cells via EGF deprivation at 32 degrees C. These findings suggest that moderate low temperature preserved stemness of neural stem cells and prevented cell apoptosis via the stimulation of CIRP, and one of the mechanisms of rescue of brain injury by the moderate hypothermia is associated with preservation of neural stem cells. PMID- 20735995 TI - Manganese induces the overexpression of alpha-synuclein in PC12 cells via ERK activation. AB - Manganese has been known to induce neurological disorders. In the present study, we determined the effect of manganese on the expression of alpha-synuclein in PC12 cells and its role in manganese-induced cytotoxicity. We also investigated the relationship between alpha-synuclein expression and the change of ERK1/2 MAPK activity. In our research, manganese exposure induced the overexpression of alpha synuclein, while siRNA knockdown of alpha-synuclein reversed manganese-induced cytotoxicity. Furthermore, manganese induced the activation of ERK1/2 MAPK. The MEK1 inhibitor PD98059, which inhibits the activation of ERK MAPK, attenuated the overexpression of alpha-synuclein and the cytotoxicity induced by manganese. In conclusion, our studies show that manganese may induce the overexpression of alpha-synuclein via ERK1/2 activation, which may play a role in manganese-induced cytotoxicity. PMID- 20735996 TI - A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. AB - Because children are becoming overweight, unhealthy, and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether higher- and lower-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, higher fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was also positively associated with performance on the relational but not the item memory task. Furthermore, bilateral hippocampal volume was found to mediate the relationship between fitness level (VO(2) max) and relational memory. No relationship between aerobic fitness, nucleus accumbens volume, and memory was reported, which strengthens the hypothesized specific effect of fitness on the hippocampus. The findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain. PMID- 20735997 TI - Glutamatergic lateral parabrachial neurons innervate orexin-containing hypothalamic neurons in the rat. AB - We performed this study to understand the anatomical substrates of parabrachial nucleus (PBN) modulation of orexin (ORX)-containing neurons in the hypothalamus. After biotinylated dextranamine (BDA) injection into the lateral PBN and immunostaining of ORX-containing neurons in the rat, the prominent overlap of the distribution field of the BDA-labeled fibers and that of the ORX-immunoreactive (ir) neurons was found in the lateralmost part of the dorsomedial nucleus and adjacent dorsal perifornical area (this overlapping field was referred to as "suprafornical area" in the present study), and the labeled axon terminals made asymmetrical synaptic contacts with somata and dendrites of the ORX-ir neurons. We further revealed that almost all the "suprafornical area"-projecting lateral PBN neurons were positive for vesicular glutamate transporter 2 mRNA and very few of them were positive for glutamic acid decarboxylase 67 mRNA. The present data suggest that ORX-containing neurons in the "suprafornical area" may be under the excitatory influence of the glutamatergic lateral PBN neurons probably for the regulation of arousal and waking. PMID- 20735998 TI - Association between serotonin transporter polymorphisms and problem behavior in adult males with intellectual disabilities. AB - Research on aggression over the past two decades has focused on gene-environment interaction models to explain the relative contribution of each to this behavioral phenotype in various clinical populations. Recent investigations suggest a link between aggression in people with intellectual disabilities the functionality of the serotonin transporter. The aims in this study were to examine the possible association of the STin2 and/or the 5-HTTLPR serotonin transporter polymorphisms in adult males with and without intellectual disabilities, and to examine the association of these polymorphisms with aggression in people with intellectual disabilities. DNA samples and behavioral records were obtained from adult males with intellectual disabilities, distinguished only by the presence or absence of aggression. No association was found between either transporter polymorphism for aggression. However, the long 5 HTTLPR allele, and not the short allele or the heterozygous state, was associated with the severity of aggression. The association with aggression appears to be genetically complex, suggesting there may be other genes, interactions between genes, and/or environmental relations occasioning aggression in people with intellectual disabilities. PMID- 20735999 TI - Placebo analgesia as a case of a cognitive style driven by prior expectation. AB - Placebo analgesia has been shown to be driven by expectations of treatment effects. We suggest that the expectation of treatment creates uncertainty about the sensory information of pain. We tested the hypothesis that in placebo responders uncertainty generated by expectations generalizes to other cognitive processes by recruiting participants for a placebo study who had previously taken part in a visual cue-picture decision making perceptual task. The task investigated how participants utilised prior cues against discrepant and uncertain sensory information. Participants were selected based on their degree of acquiescence in the cue-picture task. The placebo experiment was split into three blocks of pre-treatment, treatment and post-treatment. Participants were told that they may or may not receive an anaesthetic cream on one arm. However, all participants received inactive cream paired with non-painful stimuli during the treatment block. Electroencephalography (EEG) was used to measure pain evoked potentials to laser heat to determine if the behavioural misperception of pain translated into a physiological response. Regression models showed that both behavioural and physiological placebo responses could be predicted by participants' scores of acquiescence in the cue-picture decision making task. Placebo analgesia seems to be influenced by a cognitive style that assimilates responses to expectations increasing the chances of error when detecting discrepant sensory information. PMID- 20736000 TI - Association of brain-derived neurotrophic factor (Val66Met) genetic polymorphism with methamphetamine dependence in a Malaysian population. AB - Methamphetamine is a highly addictive psychostimulant that has surged in popularity worldwide in the last decade. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is widely expressed in the adult mammalian brain and plays an important role in the long-term survival, differentiation, and outgrowth of neurons. Previous studies suggested that the BDNF gene may be involved in the mechanisms underlying substance dependence. This study investigated the association of the BDNF gene Val66Met polymorphism with methamphetamine dependence and with psychosis in a Malaysian population with different ethnicities. The BDNF Val66Met polymorphism was genotyped by PCR-RFLP in 186 male methamphetamine-dependent subjects and in 154 male controls of four different ethnicities, namely, Malay, Chinese, Kadazan-Dusun, and Bajau. Our results showed that the distribution of the BDNF Val66Met genotype in Chinese subjects with methamphetamine dependence (OR=2.6, p=0.015) and methamphetamine psychosis (OR=0.2, p = 0.034) were significant compared with controls. The frequency of the 66Val allele in methamphetamine-dependent subjects was higher than that in the control group, suggesting that the 66Val carriers are more susceptible to methamphetamine dependence. However, 66Val allele frequency in other ethnicities was not significantly different from the controls. The results of the study also showed that in the Chinese methamphetamine-dependent subjects, there was a difference in allele frequency when comparing those who developed psychosis and those who did not. Our findings suggest that the BDNF Val66Met polymorphism may contribute to methamphetamine dependence and psychosis in the Chinese population but not in other Malaysian ethnicities. PMID- 20736001 TI - The value of apelin-36 and brain natriuretic peptide measurements in patients with first ST-elevation myocardial infarction. AB - BACKGROUND: We aimed to assess apelin-novel endogenous ligand for the angiotensin like 1 receptor in patients with ST-elevation myocardial infarction (STEMI) and to compare its value with B-type natriuretic peptide (BNP). METHODS: In 78 consecutive patients with first STEMI treated with primary PCI, plasma apelin-36 (RIA) and BNP (MEIA) concentrations were measured twice: on admission and on the fifth day of hospitalization. Left ventricle ejection fraction (LVEF) was assessed on admission and composite endpoint (CEP)-after 1 year follow-up. RESULTS: During the 5-day interval median plasma BNP level significantly increased and median plasma apelin concentration significantly decreased. BNP, but not apelin, correlated with low LVEF (<50%). In ROC analysis only BNP measurements were diagnostic for low LVEF. In ANOVA test, in patients with CEP, a significant decrease in apelin (but not BNP) concentrations measured in 5-day interval was found. ROC analysis identified only second BNP measurement as significant to estimate adverse outcome 0.627 in the prediction of CEP (95% confidence interval=0.507-0.736). CONCLUSION: Following STEMI there is a decrease of plasma apelin-36 concentration and an increase of plasma BNP concentration. BNP is better, than apelin diagnostic value for the detection of impaired LVEF. Both BNP and apelin have prognostic value, although both needs further evaluation. PMID- 20736002 TI - Acute presentation of dizziness in vitamin B12 deficient old patient of cardiac disease: a case report. AB - BACKGROUND: Neuropsychiatric and hematological manifestations of vitamin B12 deficiency are well known. The present report highlights the biochemical basis for the impaired synthesis of DNA and neurological disorders associated with vitamin B12 deficiency. METHODS: We present a case of an old patient who developed acute ataxia, dizziness and imbalance 2 days after pacemaker implantation in a cardiac care unit. RESULTS: On evaluation, the patient was found to have low vitamin B12 levels (121 pmol/l) with raised plasma homocysteine levels (28 MUmol/l) and methylmalonic acid levels (17 MUmol/l). Neurological examination revealed signs and symptoms of peripheral neuropathy. CT scan of the brain was found to be normal. The usual hematological presentation was absent in this case. The patient responded dramatically to parenteral vitamin B12 supplementation. CONCLUSION: Though frequent, the vitamin B12 deficiency often goes unnoticed in elderly population. So, with this report we emphasize that deficiency of serum vitamin B12 levels should be suspected and evaluated in elderly patients presenting with neuropsychiatric symptoms. PMID- 20736003 TI - Inhibition of phosphatidylinositol 3-kinase promotes tumor cell resistance to chemotherapeutic agents via a mechanism involving delay in cell cycle progression. AB - Approaches to overcome chemoresistance in cancer cells have involved targeting specific signaling pathways such as the phosphatidylinositol 3-kinase (PI3K) pathway, a stress response pathway known to be involved in the regulation of cell survival, apoptosis and growth. The present study determined the effect of PI3K inhibition on the clonogenic survival of human cancer cells following exposure to various chemotherapeutic agents. Treatment with the PI3K inhibitors LY294002 or Compound 15e resulted in increased survival of MDA-MB-231 breast carcinoma cells after exposure to doxorubicin, etoposide, 5-fluorouracil, and vincristine. Increased survival following PI3K inhibition was also observed in DU-145 prostate, HCT-116 colon and A-549 lung carcinoma cell lines exposed to doxorubicin. Increased cell survival mediated by LY294002 was correlated with a decrease in cell proliferation, which was linked to an increase in the proportion of cells in the G(1) phase of the cell cycle. Inhibition of PI3K signaling also resulted in higher levels of the cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1); and knockdown of p27(kip1) with siRNA attenuated resistance to doxorubicin in cells treated with LY294002. Incubation in the presence of LY294002 after exposure to doxorubicin resulted in decreased cell survival. These findings provide evidence that PI3K inhibition leads to chemoresistance in human cancer cells by causing a delay in cell cycle; however, the timing of PI3K inhibition (either before or after exposure to anti-cancer agents) may be a critical determinant of chemosensitivity. PMID- 20736004 TI - Telomerase protects adult rodent olfactory ensheathing glia from early senescence. AB - Adult olfactory bulb ensheathing glia (OB-OEG) promote the repair of acute, subacute, and chronic spinal cord injuries and autologous transplantation is a feasible approach. There are interspecies differences between adult rodent and primate OB-OEG related to their longevity in culture. Whereas primate OB-OEG exhibit a relatively long life span, under the same culture conditions rodent OB OEG divide just three to four times, are sensitive to oxidative stress and become senescent after the third week in vitro. Telomerase is a "physiological key regulator" of the life span of normal somatic cells and also has extratelomeric functions such as increased resistance to oxidative stress. To elucidate whether telomerase has a role in the senescence of rodent OB-OEG, we have introduced the catalytic subunit of telomerase mTERT into cultures of these cells by retroviral infection. Native and modified adult rat OB-OEG behaved as telomerase-competent cells as they divided while expressing mTERT but entered senescence once the gene switched off. After ectopic expression of mTERT, OB-OEG resumed division at a nonsenescent rate, expressed p75 and other OEG markers, and exhibited the morphology of nonsenescent OB-OEG. The nonsenescent period of mTERT-OEG lasted 9weeks and then ectopic mTERT switched off and cells entered senescence again. Our results suggest a role of telomerase in early senescence of adult rodent OB OEG cultures and a protection from oxidative damage. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. PMID- 20736005 TI - Phenotypes and peripheral mechanisms underlying inflammatory pain-related behaviors induced by BmK I, a modulator of sodium channels. AB - The integrated mechanisms of dynamic signaling of sodium channels involved in clinical pain are still not yet clear. In this study, a new rat inflammatory pain model was developed by using the unilateral intraplantar injection of BmK I, a receptor site 3-specific modulator of sodium channels from the venom of scorpion Buthus martensi Karsch (BmK). It was found that BmK I could induce several kinds of inflammatory pain-related behaviors including spontaneous pain companied with unique episodic paroxysms, primary thermal hypersensitivity, and mirror-image mechanical hypersensitivity with different time course of development, which could be suppressed by morphine, indomethacin, or bupivacaine to a different extent. The dramatic attenuation by pretreatment with resiniferatoxin (RTX), an ultrapotent analog of capsaicin, on BmK I-induced pain-related behaviors, paw edema, and spinal L4-L5 c-Fos expression demonstrated that capsaicin-sensitive primary afferent neurons played important roles in pain induced by BmK I. Furthermore, the electrophysiological recordings showed that BmK I persistently increased whole-cell and tetrodotoxin-resistant (TTX-R) peak sodium currents and significantly delayed the inactivation phase of whole-cell sodium currents but could not enhance capsaicin-evoked inward currents, in acute isolated small dorsal root ganglion neurons of rat. The results strongly suggested that the dynamic modulation of BmK I on sodium channels located in peripheral primary afferent neurons, especially in capsaicin-sensitive neurons, mediated pain sensation. Thus, BmK I may be a valuable pharmacological tool to understand the sodium channel-involved pain mechanisms. PMID- 20736006 TI - Characterization of brain lesions in a mouse model of progressive multiple sclerosis. AB - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by damage to the neuronal myelin sheath, which results in different levels of muscle paralysis that can lead to neuronal death. In most MS mouse models, the neurologic damage mostly affects the spinal cord with limited damage to the brain, which cannot be monitored by magnetic resonance imaging (MRI) as used for humans. We show that immunization of non-obese diabetic (NOD) mice with myelin oligodendrocyte glycoprotein peptide 35-55 leads to the development of relapsing-remitting stages, evident from days 20 to 70, which then develops into a chronic progressive stage. This cycle is similar to MS stages found in humans. Brain MRI gadolinium-enhanced T1-weighted image analysis showed an increased blood-brain barrier permeability in brain gray and white matter specific to the corpus callosum, fimbria, and internal capsule as found in humans. MRI fractional anisotropy analysis showed demyelination and axonal damage in identical regions. Immunohistologic analysis supported the MRI data. No evidence of brain lesions was found in a common model of MS using C57BL/6 mice. We suggest that an increase in astrocyte toxicity in experimental autoimmune encephalomyelitis-induced NOD mice may be linked to brain lesion development. We suggest using NOD mice as a suitable model for studying MS using MRI methods toward future diagnostic and drug development. PMID- 20736007 TI - Fasciola gigantica: production and characterization of a monoclonal antibody against recombinant cathepsin B3. AB - A number of monoclonal antibodies (MoAbs) against a recombinant cathepsin B3 (rCatB3) of Fasciola gigantica were produced in BALB/c mice. Reactivity and specificity of these MoAbs were assessed by indirect ELISA and immunoblotting techniques. Six stable clones, namely 1C4, 1E9, 2E5, 2F9, 5B4, 5D7 were obtained. All MoAbs reacted with rCatB3 at molecular weight (MW) 37 kDa as well as the glycosylated peptide at 55-75 kDa and with the native CatB3 at MW 37 kDa in WB extracts of metacercariae (Met) and newly excysted juveniles (NEJ). It was found to be IgG(1) and lambda light chain isotypes. Immunolocalization of CatB3 in metacercariae, NEJ, 4-week-old juvenile and adult F. gigantica performed by immunoperoxidase technique by using these MoAbs as probes indicated that CatB3 was present in high concentration in the caecal epithelium and caecal lumen of the Met and NEJ, but not in the 4-week-old juvenile and adult fluke. The MoAbs show no cross-reactions with antigens of other parasites including Gigantocotyl explanatum, Eurytrema pancreaticum, Paramphistomum cervi, Schistosoma spindale, S. mansoni, Haemonchus placei and Setaria labiato-papillosa. Thus, it is possible that these MoAbs could be a good candidate for immunodiagnosis of fasciolosis. PMID- 20736008 TI - Plasmodium falciparum: Solanum nudum SN-1 steroid antiplasmodial activity when combined with antimalarial drugs. AB - The effect of 16 alpha-acetoxy-26-hydroxycholest-4-ene-3,22-dione (SN-1) isolated from Solanum nudum Dunal (a Solanaceae traditionally used for treating fever in Colombia) on Plasmodium falciparum erythrocyte stages and its in vitro antiplasmodial activity when combined with the following conventional drugs was studied: chloroquine (CQ), amodiaquine (AQ), desethylamodiaquine (desethyl-AQ), quinine (QN), artemisinin (AR), atovaquone (ATV) and quinine (QN). It was found that SN-1 targeted trophozoites and had a synergistic effect when combined with CQ and QN; however, it had an antagonist effect when used with the other combinations. PMID- 20736009 TI - Toxoplasma gondii: infection natural congenital in cattle and an experimental inoculation of gestating cows with oocysts. AB - Two studies, of a natural infection and an experimental infection, were performed in order to study congenital transmission of Toxoplasma gondii in cattle. In the first study, 50 fetuses were harvested from gestating cows that were eutanasied at a municipal slaughterhouse in Jaboticabal, Sao Paulo state, Brazil. In the second study, 11 gestating cows were divided into four groups for inoculation with T. gondii: GI consisted of three cows inoculated with 1.0 * 10(5) oocysts during their first trimester of gestation; GII consisted of three cows inoculated with 1.0 * 10(5) oocysts during their second trimester of gestation; GIII consisted of three cows inoculated with 1.0 * 10(5) oocysts during their last trimester of gestation; and GIV consisted of two control cows, one during its first and the other during its second trimester of gestation. In both studies, the presence of T. gondii was confirmed both indirectly by immunofluorescence assay (IFAT). In the natural infection experiment, 18% (9/50) of the gestating cows were confirmed to have specific antibodies (IFAT--1:64) against T. gondii. The bioassay was able to diagnose the presence of T. gondii in the tissue samples from three calves. In the second experiment, the nine cows from groups I, II and III presented with specific antibodies (IFAT) against T. gondii. In contrast, T. gondii could not be detected by IFAT, histopathological examination or the bioassay in any of the nine calves born to cows experimentally infected with T. gondii oocysts. Based on the results from both studies, we conclude that congenital infection of T. gondii in cattle, while infrequent, does occur naturally. The pathogenicity of the strain of T. gondii may influence the likelihood of this route of transmission. PMID- 20736010 TI - BDNF stimulates Ca2+ oscillation frequency in melanotrope cells of Xenopus laevis: contribution of IP3-receptor-mediated release of intracellular Ca2+ to gene expression. AB - Pituitary melanotrope cells of the amphibian Xenopus laevis are neuroendocrine cells regulating the animal's skin color adaptation through secretion of alpha melanophore-stimulating hormone (alpha-MSH). To fulfill this function optimally, the melanotrope cell undergoes plastic changes in structure and secretory activity in response to changed background light conditions. Xenopus melanotrope cells display Ca(2+) oscillations that are thought to drive alpha-MSH secretion and gene expression. They also produce brain-derived neurotrophic factor (BDNF), which stimulates in an autocrine way the biosynthesis of the alpha-MSH precursor, pro-opiomelanocortin (POMC). We have used this physiological adaptation mechanism as a model to investigate the role of BDNF in the regulation of Ca(2+) kinetics and Ca(2+)-dependent gene expression. By dynamic video imaging of isolated cultured melanotropes we demonstrated that BDNF caused a dose-dependent increase in Ca(2+) oscillation frequency up to 64.7+/-2.3% of control level. BDNF also induced a transient Ca(2+) peak in Ca(2+)-free medium, which was absent when calcium stores were blocked by thapsigargin and 2-aminoethoxydiphenyl borate, indicating that BDNF stimulates acute release of Ca(2+) from IP(3)-sensitive intracellular Ca(2+) stores. Moreover, we show that thapsigargin inhibits the expression of BDNF transcript IV (by 61.1+/-28.8%) but does not affect POMC transcript. We conclude that BDNF mobilizes Ca(2+) from IP(3)-sensitive intracellular Ca(2+) stores and propose the possibility that the resulting Ca(2+) oscillations selectively stimulate expression of the BDNF gene. PMID- 20736011 TI - Thyroid hormone mediates otolith growth and development during flatfish metamorphosis. AB - Flatfish begin life as bilaterally symmetrical larvae that swim up-right, then abruptly metamorphose into asymmetrically shaped juveniles with lateralized swimming postures. Flatfish metamorphosis is mediated entirely by thyroid hormone (TH). Changes in flatfish swim posture are thought to be regulated via vestibular remodeling, although the influence of TH on teleost inner ear development remains unclear. This study addresses the role of TH on the development of the three otolith end-organs (sacculus, utricle, and lagena) during southern flounder (Paralichthys lethostigma) metamorphosis. Compared with pre-metamorphosis, growth rates of the sacculus and utricle otoliths increase dramatically during metamorphosis in a manner that is uncoupled from general somatic growth. Treatment of P. lethostigma larvae with methimazol (a pharmacological inhibitor of endogenous TH production) inhibits growth of the sacculus and utricle, whereas treatment with TH dramatically accelerates their growth. In contrast with the sacculus and utricle otoliths that begin to form and mineralize during embryogenesis, a non-mineralized lagena otolith is first visible 10-12 days after hatching. The lagena grows during pre- and pro-metamorphosis, then abruptly mineralizes during metamorphic climax. Mineralization of the lagena, but not growth, can be induced with TH treatment, whereas treatment with methimazol completely inhibits lagena mineralization without inhibiting its growth. These findings suggest that during southern flounder metamorphosis TH exerts differential effects on growth and development among the three types of otolith. PMID- 20736012 TI - Assessment of luteinizing hormone and prolactin immunoactivity in Asian and African elephant urine using assays validated for serum. AB - Analysis of serum hormones is useful for timing artificial insemination (Luteinizing hormone) and diagnosing pregnancy (prolactin) in elephants. However, these tests require blood collection, which is not tolerated by all animals, and is impractical for field studies. Thus, developing a means to obtain these measures noninvasively could improve species management. Matched urine and serum was collected from Asian and African elephants daily throughout the follicular phase and after administration of a GnRH analogue for LH determination, and in pregnant and nonpregnant females for prolactin analyses using immunoassays validated for elephant serum. Despite identifying robust increases in circulating hormone concentrations, no concomitant changes in urinary LH or prolactin immunoactivity was detected. Concentration of samples by centrifugal filtration or ethanol precipitation did not increase the ability to measure biologically relevant changes in endogenous urinary LH or prolactin immunoactivity. Sample matrix interference was ruled out following sufficient recovery of exogenous LH or prolactin added to samples, except for samples concentrated >35-fold where some interference was suspected. These results suggest that elephants either do not excrete native LH or prolactin in urine, or concentrations are too low to be measured accurately by standard immunoassay techniques that are valid for serum analyses. Thus, it does not appear feasible or economically viable to use these noninvasive tests for ovulation detection or for pregnancy diagnosis in elephants. PMID- 20736013 TI - Long-term obesity levels in female OLETF rats following time-specific post weaning food restriction. AB - Obesity and the metabolic syndrome represent serious health threats affecting increasing numbers of individuals, with females being more affected than males and with growing incidence among children and adolescents. In the present study, we used the OLETF rat model of early-onset obesity to examine the influence of different timing of food restriction on long-term obesity levels in females. Food restriction took place at different time windows: from weaning until postnatal day (PND) 45 (early); from weaning until PND90 (chronic); or from PND45 until PND70 (late). Follow-up continued until PND90. During and after the termination of the diet-restriction period, we focused on peripheral adiposity-related measures such as fat pad weight (brown, retroperitoneal and inguinal); inguinal adipocyte size and number; and leptin, oxytocin and glucose levels. We also examined body weight, feeding efficiency, spontaneous intake after release from diet-restriction, and plasma creatinine levels and estrous cycle characteristics as a result of the chronic diet. The results suggest that while food restriction produced significant weight and adiposity loss, OLETF females presented poor weight loss retention after the early and late short-term diets. The estrous cycle structure and time of first estrous of the OLETF rats were normalized by chronic food restriction. Females responded to early food restriction in a different manner than males did in previous studies, further emphasizing the importance of sex-appropriate approaches in the investigation and treatment of the pathologies related to obesity and the metabolic syndrome. PMID- 20736014 TI - Estradiol lowers intracranial self-stimulation thresholds and enhances cocaine facilitation of intracranial self-stimulation in rats. AB - Women initiate cocaine use at a younger age and have more complications (e.g., higher rates of major or minor depression) related to cocaine use than men. It has been proposed that estrogens play an important role in these sex differences. The addictive potential of psychoactive drugs can be measured in rats via a rewarding intracranial self-stimulation (ICSS) procedure. The rate-independent method of ICSS allows researchers to assess the "pure" rewarding effect of cocaine without influence of nonspecific motor reactions. The present study aimed to estimate effects of estradiol and a combination of estradiol and cocaine on ICSS in ovariectomized female rats. 17-beta-estradiol (5MUg/animal/day, 2 days) produced a long-lasting gradual lowering of the thresholds for ICSS. The ability of estradiol to decrease thresholds for ICSS has never been shown previously. Combination of 17-beta-estradiol and cocaine (5.0mg/kg, 5 days) produced a greater effect on ICSS thresholds than the effect of either compound alone. No tolerance or sensitization to cocaine developed during the study. Present findings suggest estradiol increases sensitivity of the brain reward system in rats, which may have an important implication in understanding sex differences in cocaine effects. PMID- 20736015 TI - Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats. AB - Prenatal alcohol exposure (PAE) alters adult neurogenesis and the neurogenic response to stress in male rats. As the effects of stress on neurogenesis are sexually dimorphic, the present study investigated the effects of PAE on adult hippocampal neurogenesis under both nonstressed and stressed conditions in female rats. Pregnant females were assigned to one of three prenatal treatments: (1) alcohol (PAE)-liquid alcohol (ethanol) diet ad libitum (36% ethanol-derived calories); (2) pair-fed-isocaloric liquid diet, with maltose-dextrin substituted for ethanol, in the amount consumed by a PAE partner (g/kg body wt/day of gestation); and (3) control-lab chow ad libitum. Female offspring were assigned to either nonstressed (undisturbed) or stressed (repeated restraint stress for 9 days) conditions. On day 10, all rats were injected with bromodeoxyuridine (BrdU) and perfused either 24 hours (cell proliferation) or 3 weeks (cell survival) later. We found that PAE did not significantly alter cell proliferation or survival, whereas females from the pair-fed condition exhibited elevated levels of cell survival compared to control females. Importantly, however, the proportion of both new neurons and new glial cells in the hippocampal dentate gyrus was reduced in PAE compared to control females. Exposure to stress did not alter neurogenesis in any of the prenatal treatment groups. In summary, compared to females from the control condition, prenatal dietary restriction enhanced the survival of new neurons, whereas PAE altered the differentiation of newly produced cells in the adult dentate gyrus. Alterations in hippocampal neurogenesis following PAE may contribute to learning and memory deficits seen in individuals with fetal alcohol spectrum disorders. PMID- 20736016 TI - The neogregarine protozoan Farinocystis sp. reduces longevity and fecundity in the West Indian sweet potato weevil, Euscepes postfasciatus (Fairmaire). AB - The number of West Indian sweet potato weevils, Euscepes postfasciatus, being mass-reared in a facility for use in sterile insect technique (SIT) eradication programs has undergone a drastic reduction. A neogregarine protozoan pathogen Farinocystis sp. (an undescribed species) was detected in vivo in the mass-reared E. postfasciatus. We investigated the effects of this disease on the longevity and fecundity of host weevils and the incubation time of the disease in the host body under mass-rearing conditions. Our results demonstrated that infection by this Farinocystis sp. decreased both longevity and fecundity in E. postfasciatus. In particular, the pathogen severely limited the production of progeny by infected females compared to healthy females. Therefore, we consider this protozoan infection to be the major cause of the decreased E. postfasciatus production in the mass-rearing facility. PMID- 20736018 TI - Diagnostic yield of upper endoscopy in treated GERD patients. PMID- 20736017 TI - HIV protease inhibitors elicit volume-sensitive Cl- current in cardiac myocytes via mitochondrial ROS. AB - HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl(-) current (I(Cl,swell)) is activated by ROS, we tested whether HIV PI stimulate I(Cl,swell) in ventricular myocytes. Ritonavir and lopinavir elicited outwardly rectifying Cl(-) currents under isosmotic conditions that were abolished by the selective I(Cl,swell) blocker DCPIB. In contrast, amprenavir, nelfinavir, and raltegravir, an integrase inhibitor, did not modulate I(Cl,swell) acutely. Ritonavir also reduced action potential duration, but amprenavir did not. I(Cl,swell) activation was attributed to ROS because ebselen, an H(2)O(2) scavenger, suppressed ritonavir- and lopinavir-induced I(Cl,swell). Major ROS sources in cardiomyocytes are sarcolemmal NADPH oxidase and mitochondria. The specific NADPH oxidase inhibitor apocynin failed to block ritonavir- or lopinavir-induced currents, although it blocks I(Cl,swell) elicited by osmotic swelling or stretch. In contrast, rotenone, a mitochondrial e(-) transport inhibitor, suppressed both ritonavir- and lopinavir-induced I(Cl,swell). ROS production was measured in HL-1 cardiomyocytes with C-H(2)DCFDA-AM and mitochondrial membrane potential (DeltaPsi(m)) with JC-1. Flow cytometry confirmed that ritonavir and lopinavir but not amprenavir, nelfinavir, or raltegravir augmented ROS production, and HIV PI-induced ROS production was suppressed by rotenone but not NADPH oxidase blockade. Moreover, ritonavir, but not amprenavir, depolarized DeltaPsi(m). These data suggest ritonavir and lopinavir activated I(Cl,swell) via mitochondrial ROS production that was independent of NADPH oxidase. ROS-dependent modulation of I(Cl,swell) and other ion channels by HIV PI may contribute to some of their actions in heart and perhaps other tissues. PMID- 20736020 TI - Rifaximin in hepatic encephalopathy: is an ounce of prevention worth a pretty penny? PMID- 20736022 TI - To drain or not to drain: that is the question. PMID- 20736023 TI - Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1. AB - AIMS: the multifunctional potential of neferine derived from the embryo of Nelumbo nucifera seeds for the age-related neurodegenerative disorders, in vivo anti-amnesic activities and in vitro cholinesterases (ChEs)- and beta-site APP cleaving enzyme 1 (BACE1)-inhibitory activities, as well as anti-inflammatory and antioxidant activities were investigated. MAIN METHODS: in vivo anti-amnesic activities were performed via the passive avoidance, Y-maze, and Morris water maze tasks in a scopolamine-induced amnesia model. The cell-free antioxidant capacities were evaluated by in vitro scavenging activities against 1,1-diphenyl 2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals, and peroxynitrite (ONOO(-)), as well as inhibitory activities against nitric oxide (NO), superoxide anion (O(2)(-)), lipid peroxidation, and ONOO(-)-mediated tyrosine nitration. The intracellular antioxidant capacities were also determined via inhibitory activities of lipopolysaccharide (LPS)-induced NO generation and NF-kappaB activation in RAW 264.7 cells. KEY FINDINGS: neferine showed significant improvement in cognitive impairment in scopolamine-induced amnesia animal models and moderate inhibitory activities in ChEs and BACE1 assays. In addition, it exhibited notable scavenging activities against DPPH, ABTS, NO, and O(2)(-) radicals, as well as ONOO(-). Neferine also demonstrated remarkable inhibitory activity against lipid peroxidation and protein nitration in cell-free antioxidant assays and moderate inhibitory activity of NO generation with exceptional suppression of NF-kappaB activation in cell-based assays. SIGNIFICANCE: the results demonstrate that the anti-amnesic effect of neferine may be mediated via antioxidant and anti inflammatory capacities, as well as inhibition of ChEs and BACE1. PMID- 20736024 TI - Flecainide inhibits the stimulatory effect of veratridine on the response of airway mechanoreceptors to maintained inflations in rats. AB - AIMS: the purpose of the present study was to investigate (a) whether maintained inflations result in the inhibition of slowly adapting pulmonary stretch receptor (SAR) discharge to elicit an abrupt change in receptor activity and (b) whether pretreatment with veratridine, a Na(+) channel opener, and/or flecainide, a Na(+) channel blocker, alters the responses of SAR properties to maintained inflations. MAIN METHODS: we measured the properties of SAR activity during maintained inflations at different pressures in 31 anesthetized, artificially ventilated rats with unilateral vagotomy. KEY FINDINGS: During maintained inflations (approximately 5, 10 and 15 cmH(2)O) for about 5s, the procedures did not produce the induction of inhibition of either 16 low-threshold SARs (firing during both inflation and deflation) or 15 high-threshold SARs (firing during inflation only). In these preparations, the excitatory responses of SARs to maintained inflations at three different pressures were markedly enhanced after administration of veratridine (50 MUg/kg), but under such conditions, the inhibition of SAR discharges was not observed. In the same SAR preparations, after flecainide treatment (9 mg/kg) sufficient for the blockade of veratridine (50 MUg/kg)-induced SAR stimulation, maintained inflations at higher pressures (10 and 15 cmH(2)O) greatly inhibited SAR discharges. Under these conditions, the inhibition of SAR discharges was not observed during maintained inflations at 5 cmH(2)O. SIGNIFICANCE: These results suggest that neither low-threshold SARs nor high-threshold SARs in the rat lung are deactivated during maintained inflations at higher pressures. PMID- 20736026 TI - Adaptation modulates the electrophysiological substrates of perceived facial distortion: support for opponent coding. AB - In two experiments we determined the electrophysiological substrates of figural aftereffects in face adaptation using compressed and expanded faces. In Experiment 1, subjects viewed a series of compressed and expanded faces. Results demonstrated that distortion systematically modulated the peak amplitude of the P250 event-related potential (ERP) component. As the amount of perceived distortion in a face increased, the peak amplitude of the P250 component decreased, regardless of whether the physical distortion was compressive or expansive. This provided an ERP metric of the degree of perceived distortion. In Experiment 2, we examined the effects of adaptation on the P250 amplitude by introducing an adapting stimulus that affected the subject's perception of the distorted test faces as measured through normality judgments. The set of test faces was held constant and the adapting stimulus was systematically varied across experimental days. Adapting to a compressed face made a less compressed test face appear more normal and an expanded test face more distorted as measured by normality ratings. We found that the adaptation conditions that increased the perceived distortion of the distorted test faces also decreased the amplitude of the P250. Likewise, adaptation conditions that decreased the perceived distortion of the distorted test faces also increased the amplitude of the P250. The results demonstrate that perceptual adaptation to compressed or expanded faces affected not only the behavioral normality judgments but also the electrophysiological correlates of face processing in the window of 190-260 ms after stimulus onset. PMID- 20736025 TI - Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma. AB - Transcriptional silencing of tumor suppressor genes and other cancer-related genes induced by promoter CpG island hypermethylation is an important epigenetic mechanism of hepatocarcinogenesis. Previous studies have established methylation profiles of hepatocellular carcinomas (HCCs) and demonstrated that methylation of several candidate genes in resected tissues may be associated with time to recurrence. The goals of our study were to test whether specific promoter methylation and mRNA levels of candidate genes, as well as global changes in DNA methylation, can be linked with time to recurrence and clinicopathological variables in a homogenous study group of HCC patients. Forty-three tumorous and 45 non-tumorous liver tissue samples from the surgical margin were obtained from HCV-positive, HBV-negative HCC patients who underwent tumor resection surgery and who were monitored for tumor recurrence thereafter (median follow-up time: 16 months (range, 0-79 months)). Methylation-specific PCR was used to assess the promoter methylation status of P16(INK4a), SOCS-1, RASSF1A, APC, GSTP1, RIZ1, and MGMT genes, while the level of LINE-1 methylation was used as marker of global DNA methylation levels. Methylation frequencies in P16(INK4a), RASSF1A, APC, GSTP1, and RIZ1 genes were significantly greater in tumorous versus non-tumorous tissues. Methylation of RIZ1 in non-tumorous tissues was significantly associated with time to recurrence. Additionally, genomic DNA was significantly more hypomethylated in tumorous tissues, and this change was associated with shorter recurrence, but not with clinicopathological features. In conclusion, this study supports the role of aberrant methylation in the pathobiology of HCV-positive HCCs. The finding that RIZ1 methylation and increased levels of LINE-1 hypomethylation in non-tumorous tissues are associated with time to recurrence underscores the importance of assessing the epigenetic state of the liver remnant. PMID- 20736027 TI - The visual magnocellular pathway in Chinese-speaking children with developmental dyslexia. AB - Previous research into the cognitive processes involved in reading Chinese and developmental dyslexia in Chinese, revealed that the single most important factor appears to be orthographic processing skills rather than phonological skills. Also some studies have indicated that even in alphabetic languages some dyslexic individuals reveal deficits in orthographic processing skills, which are linked to a deficit in the visual magnocellular pathway. The current study therefore employed a visual psychophysical experiment together with visual and auditory event-related potential (ERP) experiments eliciting mismatch negativity (MMN) to investigate the link between visual magnocellular functional abnormalities and developmental dyslexia in Chinese. The performance levels of Chinese children with developmental dyslexia (DD) from the behavioural and electrophysiological experiments were compared to those of the chronological age-matched (CA) children and those of the reading level matched (RL) younger children. Both the behavioural and electrophysiological results suggest that the orthographic processing skills were compromised in the Chinese developmental dyslexics, which in turn is linked to a deficit in the visual magnocellular system. PMID- 20736028 TI - Auditory-tactile speech perception in congenitally blind and sighted adults. AB - The present study investigated whether manual tactile information from a speaker's face modulates the intelligibility of speech when audio-tactile perception is compared with audio-only perception. Since more elaborated auditory and tactile skills have been reported in the blind, two groups of congenitally blind and sighted adults were compared. Participants performed a forced-choice syllable decision task across three conditions: audio-only and congruent/incongruent audio-tactile conditions. For the auditory modality, the syllables were embedded or not in noise while, for the tactile modality, participants felt in synchrony a mouthed syllable by placing a hand on the face of a talker. In the absence of acoustic noise, syllables were almost perfectly recognized in all conditions. On the contrary, with syllables embedded with acoustic noise, more correct responses were reported in case of congruent mouthing compared to no mouthing, and in case of no mouthing compared to incongruent mouthing. Interestingly, no perceptual differences were observed between blind and sighted adults. These findings demonstrate that manual tactile information relevant to recovering speech gestures modulates auditory speech perception in case of degraded acoustic information and that audio-tactile interactions occur similarly in blind and sighted untrained listeners. PMID- 20736029 TI - Plant-pollinator population dynamics. AB - We formulate and analyze a multi-generation population dynamics model for pollinators' mutualism with plants. The centerpiece of our model is an analytical expression for population-level plant-pollinator interactions extrapolated from a model of individual-level flowers and bees interactions. We also show that this analytical expression can be productively approximated by the Beddington DeAngelis formula-a function used to model trophic interactions in mathematical ecology. PMID- 20736030 TI - Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells. AB - Poly(amidoamine) (PAMAM) dendrimer nanoparticles have been demonstrated to elicit a well defined cytotoxicological response from mammalian cell lines, the response increasing systematically with dendrimer generation and number of surface amino groups. In this work, using generation G4, G5, and G6 dendrimers, this systematic response is furthermore demonstrated for the generation of reactive oxygen species, lysosomal activity, and the onset of apoptosis and levels of DNA damage. The results are consistent with a pathway of localisation of PAMAM dendrimers in the mitochondria leading to ROS production causing oxidative stress, apoptosis and DNA damage. ROS production is co-located in the mitochondria, and both generated levels and timescales are systematically generation dependent (G40.05) increase in enamel wear with toothpaste concentration. The mean dentine wear was in the range 0.28-27.63MUm and the dentine wear increased significantly (p<0.05) with toothpaste concentration, with Toothpaste B giving more wear than Toothpaste A. Analysis with published in vivo data showed that 50% of dentine wear occurs in the first 20s of brushing and that the wear approaches a plateau value with brushing time as the toothpaste concentration is reduced. CONCLUSIONS: Enamel wear increases only slightly with toothpaste concentration whereas dentine wear increases with toothpaste concentration. PMID- 20736045 TI - Inner retinal circadian clocks and non-visual photoreceptors: novel players in the circadian system. AB - Daily and annual changes in ambient illumination serve as specific stimuli that associate light with time and regulate the physiology of the organism through the eye. The eye acts as a dual sense organ linking light and vision, and detecting light that provides specific stimuli for non-classical photoreceptors located in the inner retina. These photoreceptors convey information to the master circadian pacemaker, the hypothalamic suprachiasmatic nuclei (SCN). Responsible for sensing the light that regulates several non-visual functions (i.e. behavior, pupil reflex, sleep, and pineal melatonin production), the retina plays a key role in the temporal symphony orchestra playing the musical score of life: it is intrinsically rhythmic in its physiological and metabolic activities. We discuss here recent evidence in support of the hypothesis that retinal oscillators distributed over different cell populations may act as clocks, inducing changes in the visual and circadian system according to the time of the day. Significant progress has recently been made in identifying photoreceptors/photopigments localized in retinal ganglion cells (RGCs) that set circadian rhythms and modulate non-visual functions. Autonomous retinal and brain oscillators could have a more complex organization than previously recognized, involving a network of "RGC clock/SCN clock cross-talk". The convergence of oscillatory and photoreceptive capacities of retinal cells could deeply impact on the circadian system, which in turn may be severely impaired in different retinal pathologies. The aim of this review is to discuss the state of the art on inner retinal cell involvement in the light and temporal regulation of health and disease. PMID- 20736046 TI - Functional and topological aspects of pH-dependent regulation of electron and proton transport in chloroplasts in silico. AB - In this work, we summarize results of computer simulation of electron and proton transport processes coupled to ATP synthesis in chloroplasts performed within the frames of a mathematical model developed as a system of differential equations for concentrations of electron carriers and hydrogen ion inside and outside the granal and stromal thylakoids. The model takes into account topological peculiarities and lateral heterogeneity of the chloroplast lamellar system. This allowed us to analyze the influence of restricted diffusion of protons inside small compartments of a chloroplast (e.g., in the narrow inter-thylakoid gap) on electron transport processes. The model adequately describes two modes of pH dependent feedback control of electron transport associated with: (i) the acidification of the thylakoid lumen, which causes the slowing down of plastoquinol oxidation and stimulates an increase in dissipation of excess energy in PS2, and (ii) the alkalization of stroma, inducing the activation of the BBC (Bassham-Benson-Calvin) cycle and intensified consumption of ATP and NADPH. The influence of ATP on electron transport is mediated by modulation of the thylakoid membrane conductivity to protons through the ATP synthase complexes. We also analyze the contribution of alternative electron transport pathways to the maintenance of optimal balance between the energy donating and energy consuming stages of the light-induced photosynthetic processes. PMID- 20736047 TI - Nitric oxide synthase (NOS) in the trigeminal vascular system and other brain structures related to pain in rats. AB - Nitric oxide (NO) is considered to be a key mediator in the pathophysiology of migraine but the localisation of NO synthesizing enzymes (NOS) throughout the pain pathways involved in migraine has not yet been fully investigated. We have used quantitative real-time PCR and Western blotting to measure the respective levels of mRNA and protein for nNOS and eNOS in peripheral and central tissues involved in migraine pain: dura mater, pial arteries, trigeminal ganglion (TG) trigeminal nucleus caudalis (TNC), periaqueductal grey (PAG), thalamus, hypothalamus, cortex, pituitary gland, hippocampus and cerebellum. iNOS was excluded from the present study because it was not induced. In the trigeminal vascular system we found the highest expression of nNOS mRNA in pial arteries. However, protein expression of nNOS was maximum in TNC. Among other brain structures, nNOS mRNA and protein expression was remarkably higher in the cerebellum than in any other tissues. Regarding eNOS in the trigeminovascular system, the highest mRNA expression was found in pial arteries. In the other brain structures, eNOS mRNA expression was similar but with lowest mRNA concentration in the pituitary gland and the highest concentration in cortex. The same pattern of expression was also observed with the eNOS protein. In conclusion, we found both nNOS and eNOS located to areas relevant to migraine supporting the involvement of NO in migraine mechanisms. PMID- 20736048 TI - Systemic but not local administration of retinoic acid reduces early transcript levels of pro-inflammatory cytokines after experimental spinal cord injury. AB - Early rises of pro-inflammatory cytokines play a key role in tissue damage and has detrimental consequences for functional outcome after spinal cord injury (SCI). All-trans retinoic acid (RA) has been shown to be a therapeutic agent reducing cytokine expression in vitro, but its use may be limited due to adverse side effects associated with systemic delivery. Local delivery of RA may circumvent adverse side effects, but may simultaneously reduce the therapeutic benefits of the therapy. Here, we investigated whether local or systemic RA treatment differentially affected pro-inflammatory cytokine expression early after rat SCI. Pro-inflammatory cytokines IL-1beta, IL-6 and TNFalpha were investigated at 6h after moderate contusion injury of the thoracic (T9) spinal cord, when mRNA levels are known to peak. Rats were either treated with intrathecal RA (0, 2.5, 10, or 100ng) or received an intraperitoneal injection of RA (15mg/kg bodyweight). Surprisingly intrathecal RA up to amounts of 100ng did not attenuate SCI-induced increases in gene-expression of pro-inflammatory cytokines. In contrast, intraperitoneal RA rendered a 60%, 35% and 58% reduction of IL-1beta, IL-6 and TNFalpha mRNA levels, respectively. Although local doses higher than 100ng RA may reduce pro-inflammatory cytokine gene-expression, such doses precipitate and possibly increase risks of adverse side effects. We conclude that in contrast to systemic delivery, intrathecal administration of RA up to doses of 100ng is ineffective in reducing early pro-inflammatory cytokine gene-expression. Future studies are required to investigate the effects of single intraperitoneal RA treatment on long-term SCI outcome. PMID- 20736049 TI - Expression patterns of estrogen receptors in the central auditory system change in prepubertal and aged mice. AB - Estrogens are important in the development, maintenance and physiology of the CNS. Several studies have shown their effects on the processing of hearing in both males and females, and these effects, in part, are thought to result from regulation of the transcription of genes via their classical estrogen receptor (ER) pathway. In order to understand the spatiotemporal changes that occur with age, we have studied the expression of ERs in the central auditory pathway in prepubertal and aged CBA mice with immunohistochemistry. In prepubertal mice a clear dichotomy was noted between the expression of ERalpha and ERbeta. ERbeta positive neurons were found in the metencephalon whereas the majority of ERalpha was found in mesencephalon, diencephalon or the telencephalon. In the aged animals a different pattern of ER expression was found in terms of location and overall intensity. These age-induced changes in the expression pattern were generally not uniform, suggesting that region-specific mechanisms regulate the ERs' age-related expression. Neither the prepubertal nor the aged animals showed sex differences in any auditory structure. Our results demonstrate different age dependent spatial and temporal changes in the pattern of expression of ERalpha and ERbeta, suggesting that each ER type may be involved in distinct roles across the central auditory pathway in different periods of maturation. PMID- 20736050 TI - Orbitofrontal dopaminergic dysfunction causes age-related impairment of reversal learning in rats. AB - Reversal learning is a domain that involves cognitive flexibility and is defined as the ability to rapidly alter established patterns of behavior when confronted with changing circumstances. This function depends critically on the orbitofrontal cortex (OFC) in the prefrontal cortical (PFC) structure, which is among the most sensitive to the influences of aging, and impaired reversal learning is a common functional disturbance of aged brain. The present study was designed to clarify the precisely neurochemical basis of this impaired learning in rats. For this purpose, we first examined reversal learning in young (3-month old) and aged (24-month-old) rats using a T-maze discrimination task. The ability of aged rats to learn initially a reward rule for a T-maze discrimination task was almost equal to that of young rats, suggesting that simple discrimination ability was normal in aged rats. However, the ability to learn a reversed rule in a subsequent task was markedly impaired in aged rats. In addition, aged rats had reduced dopaminergic transmission concomitant with attenuated tyrosine hydroxylase (TH) activity in the OFC. Moreover, age-related impairment of reversal learning was improved by an intra-OFC infusion of 30 ng, but not 10 ng, of the D1 receptor agonist SKF 81297. Increasing dose of SKF 81297 to 100 ng also improved the impairment, but this effect was weaker than that of 30 ng, indicating that the SKF 81297 response was an inverted "U" pattern. The maximum SKF 81297 response (30 ng) was abolished by the D1 receptor antagonist SCH 23390. Thus, age-related impairment of reversal learning was due to a D1 receptor mediated hypodopaminergic mechanism in the OFC. This finding provides direct evidence showing the involvement of OFC dopaminergic dysfunction in the development of cognitive inflexibility during the normal aging process. PMID- 20736051 TI - Specific disruption of astrocytic Ca2+ signaling pathway in vivo by adeno associated viral transduction. AB - Astrocytes are the predominant glial-cell type in the CNS and they are known to play an active role in modulating neuronal function. Since many of the same molecules including G-protein coupled receptors (GPCRs) are expressed in both neurons and astrocytes, in vivo pharmacological manipulations to target astrocytes lack specificity. In this study, we investigated the effect of Pleckstrin Homology (PH) domain of Phospholipase C (PLC)-like protein p130 (p130PH) on Ca(2+) signaling in astrocytes in vivo. We used the serotype 2/5 recombinant adeno-associated virus (rAAV2/5) vectors to introduce p130PH fused with a tagged protein monomer red fluorescent protein at the N-terminal (i.e., transgene mRFP-p130PH). In order to selectively disrupt the Ca(2+) signaling pathway in astrocytes, the transgene was driven by a novel astrocyte-specific promoter gfaABC(1)D. Our results show that mRFP-p130PH is exclusively expressed in astrocytes with a high efficiency and a stable expression level. In vivo imaging using two-photon microscopy demonstrated reduced Ca(2+) signal in transduced astrocytes in response to ATP stimulation. As Ca(2+) signaling is a characteristic form of cellular excitability in astrocytes that can mediate chemical transmitter release and contribute to neuronal excitotoxicity, the current study provides an in vivo approach to better understand Ca(2+)-dependent gliotransmission and its involvement in glia-related diseases. PMID- 20736052 TI - P2X2 purinoreceptor protein in hypothalamic neurons associated with the regulation of food intake. AB - Purines such as ATP act as extracellular messengers through specific purinergic receptors. Three different classes of purinergic receptors have been identified and termed P1, P2X and P2Y. The purinergic receptor subunit P2X2 is a ligand gated ion channel that is widely expressed by neurons in the central nervous system. The aim of this study was to study the cellular localization and to identify the chemical phenotypes of ionotropic P2X2 receptor (P2X2R)-containing neurons in the rat mediobasal hypothalamus by immunohistochemistry using three different P2X2R antisera, with special reference to neurons that influence food intake and body weight. P2X2R immunoreactivity was mainly observed in cell bodies and neural extensions located in the ventromedial part of the hypothalamic arcuate nucleus, a subregion of the nucleus with a weak blood-brain barrier (BBB). At the subcellular level, P2X2R immunoreactivity was located to the periphery of individual cells, likely representing the plasma membrane. Many P2X2R-immunoreactive cell bodies in the arcuate nucleus contained the orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP), and the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). In contrast, P2X2R immunoreactive cell bodies of the arcuate nucles only occasionally contained the anorexigenic peptides alpha-melanocyte-stimulating hormone (alpha-MSH) or cocaine and amphetamine-regulated transcript (CART), or the opioid peptide dynorphin (DYN). There was no evidence for colocalization of P2X2R with somatostatin or neuronal nitric oxide synthase (nNOS) in neurons of the arcuate nucleus. In the parvocellular part of the paraventricular nucleus, P2X2R was demonstrated in some corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and CART-containing neurons. In some cell bodies of the lateral hypothalamic area P2X2R was colocalized with DYN. The presence of P2X2R immunoreactivity in primarily orexigenic NPY/AgRP/GABA-containing neurons of the arcuate nucleus suggests that extracellular ATP has a regulatory action on this neuronal population located in a strategic position of the brain. PMID- 20736053 TI - Mu and delta opioid receptors on nociceptors attenuate mechanical hyperalgesia in rat. AB - Sensitization to mechanical stimuli is important in most pain syndromes. We evaluated the populations of nociceptors mediating mechanical hyperalgesia and those mediating mu-opioid receptor (MOR) and delta-opioid receptor (DOR) agonist induced inhibition of hyperalgesia, in the rat. We found that: (1) intradermal injection of both the endogenous ligand for the Ret receptor, glia-derived growth factor (GDNF), and the ligand for the tropomyosin receptor kinase A (TrkA) receptor, nerve growth factor (NGF)-which are present on distinct populations of nociceptors-both produce mechanical hyperalgesia; (2) DOR agonist 4-[(R)-[(2S,5R) 4-allyl-2,5-dimethylpiperazin-1-yl](3-methoxyphenyl)methyl]-N,N-diethylbenzamide (SNC) but not MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) inhibit GDNF-induced hyperalgesia; (3) both DAMGO and SNC inhibit NGF hyperalgesia, even in rats pretreated with isolectin B4 (IB4)-saporin, a toxin that destroys IB4 binding neurons; (4) co-administration of low doses of DAMGO and SNC produce enhanced analgesia, and; (5) repeated administration of DAMGO produces cross tolerance to the analgesic effect of SNC. These findings demonstrate that, most nociceptors have a role in mechanical hyperalgesia, only the DOR agonist inhibits GDNF hyperalgesia, and MOR and DOR are co-localized on a functionally important population of TrkA-positive nociceptors. PMID- 20736054 TI - An aqueous extract of Poncirus fructus activates the prokinetic activity of 5-HT receptor subtype 4 without hERG interaction. AB - AIM OF THE STUDY: Poncirus fructus (PF)--also known as the dried, immature fruit of Poncirus trifoliata (L.) Raf. (Rutaceae)--is a natural substance that has long been used for various gastrointestinal disorders in eastern Asia. An aqueous extract of PF (PF-W) has particularly potent gastroprokinetic effects, but its molecular mechanism was not well understood. Identification of the underlying prokinetic mechanism of PF-W was pursued in the present study. MATERIALS AND METHODS: Changes in in vitro cAMP levels and in vivo intestinal transit rate (ITR) caused by PF-W were measured after pretreatment with GR125487, an antagonist for serotonin receptor subtype 4 (5-HT4R). An [(3)H] astemizole binding assay and electrophysiology experiments were performed to determine if PF W has any interaction with the human ether-a-go-go related gene (hERG) potassium channel. RESULTS: PF-W induced an increase in intracellular cAMP in 5-HT4R expressing HEK293T cells, indicating that PF-W does activate 5-HT4R. Moreover, pretreatment with GR125487 successfully blocked the increase, suggesting that the response was 5-HT4R-specific. More importantly, pretreatment of GR125487 in rats inhibited the elevation of ITR by PF-W, indicating that the prokinetic effect of PF-W was indeed exerted via 5-HT4R. On the other hand, both [(3)H]-astemizole binding assay and electrophysiological experiments revealed that PF-W did not interfere at all with the hERG channel. CONCLUSION: It was found that PF-W exerts its prokinetic activity through a 5-HT4R-mediated pathway, with no interaction with hERG channels. Therefore, PF-W is a good candidate that might be developed as a prokinetic agent with fewer expected cardiac side effects. PMID- 20736055 TI - Antihypertensive and neuroprotective activities of rhynchophylline: the role of rhynchophylline in neurotransmission and ion channel activity. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria species (Gouteng in Chinese) have been used as ethnopharmacological medicines to treat ailments of the cardiovascular and central nervous systems. As the main alkaloid constituent of Uncaria species, rhynchophylline has drawn extensive attention in recent years for its antihypertensive and neuroprotective activities, and its pharmacological effects are related to ethnopharmacological medicine properties of Uncaria species. AIM OF THE REVIEW: This review examined the pharmacological studies and mechanisms of rhynchophylline, with an emphasis on cardiovascular and central nervous system diseases linked to the ethnopharmacological uses of Uncaria species. METHODS: We conducted both an electronic search and a library search of in vivo and in vitro studies. The terms and keywords for the search included rhynchophylline, Uncaria species, Gouteng, pharmacological effects, and mechanism. We focused on the papers, including ours, with studies on all related pharmacological effects and mechanisms of rhynchophylline. RESULTS: Rhynchophylline was the main constituent of several components identified from Uncaria species. Rhynchophylline mainly acts on cardiovascular and central nervous system diseases, including hypertension, bradycardia, arrhythmia, sedation, vascular dementia, epileptic seizures, drug addiction, and cerebral ischemia. Rhynchophylline also has effects on anticoagulation, inhibits vascular smooth muscle cell proliferation, and has been shown to be anti-endotoxemic. The active mechanisms are related to modulation of calcium and potassium ion channels, protection of neural and neuroglial cells, and regulation of central neurotransmitter transport and metabolism. More studies are necessary to verify the pharmacological activities and determine the exact mechanisms of rhynchophylline activity. CONCLUSIONS: Rhynchophylline treatment of cardiovascular and central nervous system diseases has a strong linkage with traditional concepts and uses of Uncaria species in ethnopharmacological medicine, such as treatment for lightheadedness, convulsions, numbness, and hypertension. As a candidate drug for several cardiovascular and central nervous system diseases, rhynchophylline will attract scientists to pursue the potential pharmacological effects and mechanisms with new technologies. Relatively few clinically relevant studies of rhynchophylline have been conducted. Thus, more in vivo validations and investigations of antihypertensive and neuroprotective mechanisms of rhynchophylline are necessary. PMID- 20736056 TI - Daily muscle activity and quiescence in non-frail, pre-frail, and frail older women. AB - Reduced muscle mass and strength are likely fundamental components of frailty. The purpose of this study was to measure daily muscle activity and quiescence in non-frail, pre-frail, and frail older women using portable electromyography (EMG). Thirty-three community-dwelling older Greek women were categorized as non frail (n=10, 74+/-4years), pre-frail (n=11, 75+/-4years), and frail (n=12, 81+/ 6years) based upon the frailty phenotype. Surface EMG over a 9-hour typical day was recorded from the biceps brachii, triceps brachii, vastus lateralis, and biceps femoris of the dominant side. Burst and gap analysis was used to quantify muscle activity and quiescence. The total duration of the muscles that were active (~2.5h) and quiescent (~4h) did not differ across frailty groups. However, the number of bursts was 28% fewer and the mean burst duration was 26% longer in frail women compared with the non-frail women. In addition, muscle activity was greater in the arm muscles than the thigh muscles across all groups (e.g. ~60% greater burst percentage). Burst number and duration indicate that muscle activity differs across stages of frailty in older women and is greater in the upper compared with lower limbs. PMID- 20736057 TI - Carboxymethyl chitin-glucan (CM-CG) protects human HepG2 and HeLa cells against oxidative DNA lesions and stimulates DNA repair of lesions induced by alkylating agents. AB - A large number of functional foods, including those that contain beta-d-glucans, have been shown to prevent human DNA against genotoxic effects and associated development of cancer and other chronic diseases. In this paper, carboxymethyl chitin-glucan (CM-CG) isolated from Aspergillus niger was investigated from two standpoints: (1) DNA-protective effects against oxidative DNA damage induced by H(2)O(2) and alkylating DNA damage induced by MMS and MNNG, and (2) a potential effect on rejoining of MMS- and MNNG-induced single strand DNA breaks. The results obtained by the comet assay in human cells cultured in vitro showed that CM-CG reduced significantly the level of oxidative DNA lesions induced by H(2)O(2) but did not change the level of alkylating DNA lesions induced by MMS or MNNG. On the other side, the efficiency of DNA-rejoining of single strand DNA breaks induced by MMS and MNNG was significantly higher in HepG2 cells pre treated with CM-CG. The antioxidative activity of carboxymethyl chitin-glucan was confirmed by the DPPH assay. PMID- 20736058 TI - Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line. AB - Pesticides have been suspected to act as endocrine disruptive compounds (EDCs) through several mechanisms of action, however data are still needed for a number of currently used pesticides. In the present study, 30 environmental pesticides selected from different chemical classes (azole, carbamate, dicarboximide, organochlorine, organophosphorus, oxadiazole, phenylureas, pyrazole, pyrimidine, pyrethroid and sulfonylureas) were tested for their ability to alter in vitro the transcriptional activity of the androgen receptor in the MDA-kb2 reporter cell line. The responsiveness of the system was checked by using a panel of reference ligands of androgen and glucocorticoid receptors. When tested alone at concentrations up to 10 MUM, none of the studied pesticides were able to induce the reporter gene after a 18 h exposure. Conversely, co-exposure experiments with 0.1 nM dihydrotestosterone (DHT) allowed identifying 15 active pesticides with IC(50) ranging from 0.2 MUM for vinclozolin to 12 MUM for fenarimol. Fipronil and bupirimate were here newly described for their AR antagonistic activity. PMID- 20736059 TI - Chemoresistance testing of human ovarian cancer cells and its in vitro model. AB - Ovarian carcinoma represents the most common cause of death from gynecological malignancies in Europe and North America, being the third most frequent and the first as to the mortality. The standard chemotherapeutical regimen for ovarian cancer involves the administration of platinum derivate (carboplatin, cisplatin), in advanced stage is platinum derivate combined with paclitaxel. Introducing chemoresistance testing of ovarian tumour cells may help to choose optimal chemotherapeutic drug and customize the individual chemotherapeutical regimens in patients. One of approaches of individualization of chemotherapy is in vitro chemosensitivity testing. In our study, we evaluated the cytotoxic effects of selected chemotherapeutics in cells isolated from ovarian tumours and ascites of individual patients. Panel of chemotherapeutics used in the study included cisplatin, paclitaxel, carboplatin, topotecan, gemcitabine and etoposide and their effects on cell viability were determined by the MTT assay. In the total number of 32 clinical samples of tumour and ascites cells, the highest sensitivity showed cells to topotecan, sensitivity to cisplatin was higher than to carboplatin and paclitaxel used in clinical practice showed most often only the marginal reactivity. Resistance to carboplatin and most of the time to gemcitabine and etoposide was commonly present. When the same test on cells that have been frozen for several weeks was repeated it was found that in 20 cases chemosensitivity increased while in 18 cases decreased. In remaining cases there was no change in reactivity to cytostatics. Moreover, chemosensitivity of cells isolated from solid tumour and ascites from the same patient did not show any significant difference with exaption of paclitaxel. PMID- 20736060 TI - Genome-wide analysis of expression modes and DNA methylation status at sense antisense transcript loci in mouse. AB - The functionality of sense-antisense transcripts (SATs), although widespread throughout the mammalian genome, is largely unknown. Here, we analyzed the SATs expression and its associated promoter DNA methylation status by surveying 12 tissues of mice to gain insights into the relationship between expression and DNA methylation of SATs. We have found that sense and antisense expression positively correlate in most tissues. However, in some SATs with tissue-specific expression, the expression level of a transcript from a CpG island-bearing promoter is low when the promoter DNA methylation is present. In these circumstances, the expression level of its opposite-strand transcript, especially when it is poly(A) negative was coincidentally higher. These observations suggest that, albeit the general tendency of sense-antisense simultaneous expression, some antisense transcripts have coordinated expression with its counterpart sense gene promoter methylation. This cross-strand relationship is not a privilege of imprinted genes but seems to occur widely in SATs. PMID- 20736061 TI - Cytoprotective effects of vitamin E homologues against glutamate-induced cell death in immature primary cortical neuron cultures: Tocopherols and tocotrienols exert similar effects by antioxidant function. AB - Glutamate plays a critical role in pathological cell death within the nervous system. Vitamin E is known to protect cells from glutamate cytotoxicity, either by direct antioxidant action or by indirect nonantioxidant action. Further, alpha tocotrienol (alpha-T3) has been reported to be more effective against glutamate induced cytotoxicity than alpha-tocopherol (alpha-T). To shed more light on the function of vitamin E against glutamate toxicity, the protective effects of eight vitamin E homologues and related compounds, 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2-carboxy-2,5,7,8-pentamethyl-6-chromanol (Trolox), against glutamate induced cytotoxicity on immature primary cortical neurons were examined using different protocols. Glutamate induced the depletion of glutathione and generation of reactive oxygen species and lipid hydroperoxides, leading to cell death. alpha-, beta-, gamma-, and delta-T and -T3; PMC; and Trolox all exerted cytoprotective effects against glutamate-induced cytotoxicity, and a longer preincubation time increased both the cellular content and the cytoprotective effects of T more significantly than those of T3, the effect of preincubation being relatively small for T3 and PMC. The protective effect of Trolox was less potent than that of PMC. The cytoprotective effects of alpha-T and alpha-T3 corresponded to their intracellular content. Further, lipid peroxidation products were measured after reduction with triphenylphosphine followed by saponification with potassium hydroxide. It was found that glutamate treatment increased the formation of hydroxyeicosatetraenoic acid, hydroxyoctadecadienoic acid, and 8 F(2)-isoprostane 2alpha, which was suppressed by alpha-T. This study shows that vitamin E protects cells from glutamate-induced toxicity primarily by direct antioxidant action and that the apparent higher capacity of T3 compared to T is ascribed to the faster uptake of T3 compared to T into the cells. It is suggested that, considering the bioavailability, alpha-T should be more effective than alpha-T3 against glutamate toxicity in vivo. PMID- 20736062 TI - SOD1 and MitoTEMPO partially prevent mitochondrial permeability transition pore opening, necrosis, and mitochondrial apoptosis after ATP depletion recovery. AB - Generation of excessive reactive oxygen species (ROS) leads to mitochondrial dysfunction, apoptosis, and necrosis in renal ischemia-reperfusion (IR) injury. Previously we showed that lentiviral vector-mediated overexpression of superoxide dismutase-1 (SOD1) in proximal tubular epithelial cells (LLC-PK(1)) reduced cytotoxicity in an in vitro model of IR injury. Here, we examined the effects of SOD1 overexpression on mitochondrial signaling after ATP depletion-recovery (ATP DR). To examine the role of mitochondrial ROS, a subset of cells was treated with the mitochondrial antioxidant MitoTEMPO. ATP-DR-mediated increase in mitochondrial calcium, loss of mitochondrial membrane potential, and increase in mitochondrial permeability transition pore (MPTP) were attenuated by SOD1 and MitoTEMPO (P<0.01). SOD1 prevented ATP-DR-induced mitochondrial Bax translocation, although the release of proapoptotic proteins from mitochondria was not prevented by SOD1 alone and required the presence of both SOD1 and MitoTEMPO. SOD1 suppressed the increase in c-jun phosphorylation, suggesting that JNK signaling regulates Bax translocation to mitochondria via ROS. ATP-DR mediated changes in MPTP and mitochondrial signaling increased necrosis and apoptosis, both of which were partially attenuated by SOD1 and MitoTEMPO. These studies show that SOD1 and MitoTEMPO preserve mitochondrial integrity and attenuate ATP-DR-mediated necrosis and apoptosis. PMID- 20736063 TI - An experimental model for studying the biomechanics of embryonic tendon: Evidence that the development of mechanical properties depends on the actinomyosin machinery. AB - Tendons attach muscles to bone and thereby transmit tensile forces during joint movement. However, a detailed understanding of the mechanisms that establish the mechanical properties of tendon has remained elusive because of the practical difficulties of studying tissue mechanics in vivo. Here we have performed a study of tendon-like constructs made by culturing embryonic tendon cells in fixed length fibrin gels. The constructs display mechanical properties (toe-linear-fail stress-strain curve, stiffness, ultimate tensile strength, and failure strain) as well as collagen fibril volume fraction and extracellular matrix (ECM)/cell ratio that are statistically similar to those of embryonic chick metatarsal tendons. The development of mechanical properties during time in culture was abolished when the constructs were treated separately with Triton X-100 (to solubilise membranes), cytochalasin (to disassemble the actin cytoskeleton) and blebbistatin (a small molecule inhibitor of non-muscle myosin II). Importantly, these treatments had no effect on the mechanical properties of the constructs that existed prior to treatment. Live-cell imaging and (14)C-proline metabolic labeling showed that blebbistatin inhibited the contraction of the constructs without affecting cell viability, procollagen synthesis, or conversion of procollagen to collagen. In conclusion, the mechanical properties per se of the tendon constructs are attributable to the ECM generated by the cells but the improvement of mechanical properties during time in culture was dependent on non muscle myosin II-derived forces. PMID- 20736064 TI - Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor beta3. AB - Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon like tissue in 7days mediated by transforming growth factor (TGF) beta3. MSCs cultured in fixed-length fibrin gels spontaneously synthesized narrow-diameter collagen fibrils and exhibited fibripositors (actin-rich, collagen fibril containing plasma membrane protrusions) identical to those that occur in embryonic tendon. In contrast, BM-MNCs did not synthesize tendon-like tissue under these conditions. We performed real-time PCR analysis of MSCs and BM-MNCs. MSCs upregulated genes encoding type I collagen, TGFbeta3, and Smad2 at the time of maximum contraction of the tendon-like tissue (7days). Western blot analysis showed phosphorylation of Smad2 at maximum contraction. The TGFbeta inhibitor SB 431542, blocked the phosphorylation of Smad2 and stopped the formation of tendon like tissue. Quantitative PCR showed that BM-MNCs expressed very low levels of TGFbeta3 compared to MSCs. Therefore we added exogenous TGFbeta3 protein to BM MNCs in fibrin gels, which resulted in phosphorylation of Smad2, synthesis of collagen fibrils, the appearance of fibripositors at the plasma membrane, and the formation of tendon-like tissue. In conclusion, MSCs that self-generate TGFbeta signaling or the addition of TGFbeta3 protein to BM-MNCs in fixed-length fibrin gels spontaneously make embryonic tendon-like tissue in vitro within 7days. PMID- 20736065 TI - Selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 as a potential treatment for breast cancer. AB - Human 3beta-hydroxysteroid dehydrogenase/isomerase type 1 (3beta-HSD1) is a critical enzyme in the conversion of DHEA to estradiol in breast tumors and may be a target enzyme for inhibition in the treatment of breast cancer in postmenopausal women. Human 3beta-HSD2 participates in the production of cortisol and aldosterone in the human adrenal gland in this population. In our recombinant human breast tumor MCF-7 Tet-off cells that express either 3beta-HSD1 or 3beta HSD2, trilostane and epostane inhibit the DHEA-induced proliferation of MCF-7 3beta-HSD1 cells with 12-16-fold lower IC(50) values compared to the MCF-7 3beta HSD2 cells. Trilostane and epostane also competitively inhibit purified human 3beta-HSD1 with 12-16-fold lower K(i) values compared to the noncompetitive K(i) values measured for human 3beta-HSD2. Using our structural model of 3beta-HSD1, trilostane was docked in the active site of 3beta-HSD1, and Arg195 in 3beta-HSD1 or Pro195 in 3beta-HSD2 was identified as a potentially critical residue. The R195P-1 mutant of 3beta-HSD1 and the P195R-2 mutant of 3beta-HSD2 were created, expressed and purified. Kinetic analyses of enzyme inhibition suggest that the high-affinity, competitive inhibition of 3beta-HSD1 by trilostane may be related to the presence of Arg195 in 3beta-HSD1 versus Pro195 in 3beta-HSD2. In addition, His156 in 3beta-HSD1 may play a role in the higher affinity of 3beta-HSD1 for substrates and inhibitors compared to 3beta-HSD2 containing Try156. Structural modeling of the 3beta-HSD1 dimer identified a possible interaction between His156 on one subunit and Gln105 on the other. Kinetic analyses of the H156Y-1, Q105M-1 and Q105M-2 support subunit interactions that contribute to the higher affinity of 3beta-HSD1 for the inhibitor, epostane, compared to 3beta-HSD2. Article from the Special issue on Targeted Inhibitors. PMID- 20736066 TI - Nicotinamide improves motor deficits and upregulates PGC-1alpha and BDNF gene expression in a mouse model of Huntington's disease. AB - Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine (polyQ) repeat in exon-1 in the Huntingtin gene (HTT). This results in misfolding and accumulation of the huntingtin (htt) protein, forming nuclear and cytoplasmic inclusions. HD is associated with dysregulation of gene expression as well as mitochondrial dysfunction. We hypothesized that by improving transcriptional regulation of genes necessary for energy metabolism, the HD motor phenotype would also improve. We therefore examined the protective effects of nicotinamide (NAM), a well characterized water-soluble B vitamin that is an inhibitor of sirtuin1/class III NAD(+)-dependent histone deacetylase (HDAC). In this study, both mini-osmotic pumps and drinking water deliveries were tested at 250 mg NAM/kg/day, using the B6.HDR6/1 transgenic mouse model. Results were similar for both modes of delivery, and there was no evidence of toxicity. We found that NAM treatment increased mRNA levels of brain-derived neurotrophic factor (BDNF), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha), the master regulator of mitochondrial biogenesis. Protein levels of BDNF were also significantly increased. In addition, NAM treatment increased PGC-1alpha activation in HD mice, pointing to a possible mode of action as a therapeutic. Critically, NAM treatment was able to improve motor deficits associated with the HD phenotype, tested as time courses of open field, rotarod, and balance beam activities. These improvements were substantial, despite the fact that NAM did not appear to reduce htt aggregation, or to prevent late-stage weight loss. Our study therefore concludes that NAM or similar drugs may be beneficial in clinical treatment of the motor dysfunctions of HD, while additional therapeutic approaches must be added to combat the aggregation phenotype and overall physiological decline. PMID- 20736067 TI - L-DOPA-induced dyskinesia in hemiparkinsonian rats is associated with up regulation of adenylyl cyclase type V/VI and increased GABA release in the substantia nigra reticulata. AB - L-DOPA treatment induces abnormal involuntary movements (AIMs) in Parkinson's patients and experimental animals. We examined the relationship between the development of AIMs (dyskinesia) and changes in [(3)H]-GABA release and cAMP signaling in striatonigral terminals of rats with unilateral 6-OHDA lesions. Analysis of AIMs scores in hemiparkinsonian rats treated with L-DOPA for 20 days was fitted by the sum of two Gaussian distributions showing the presence of two populations: one with mild and the other with severe dyskinesia. cAMP signaling was evaluated in the two populations by determining changes in cAMP formation, Galpha(olf) and adenylyl cyclase type V/VI levels. In animals that were not treated with L-DOPA, all the parameters were significantly increased in the denervated side. In the animals that had mild dyskinesia, L-DOPA treatment normalized these parameters. In contrast, in the animals in which l-DOPA treatment induced severe dyskinesia all the parameters, except for Galpha(olf) levels, were significantly higher in the denervated side. Similarly, D1 stimulated [(3)H]-GABA release was not elevated in L-DOPA-treated animals with mild dyskinesia but was increased in animals with severe dyskinesia. Changes in Galpha(olf) and adenylyl cyclase type V/VI levels in the striatum paralleled the response in the SNr. The linkage between the changes in [(3)H]-GABA release and cAMP activity was further evaluated with the selective adenylyl cyclase V/VI antagonist NKY80. This inhibitor blocked the increases of both [(3)H]-GABA release and cAMP production. These results indicate that increased expression of adenylyl cyclase V/VI is a major determinant of increased GABAergic transmission in the substantia nigra pars reticulata of animals in which L-DOPA induces severe dyskinesia. PMID- 20736068 TI - Effect of IPTG amount on apo- and holo- forms of glycerophosphate oxidase expressed in Escherichia coli. AB - Escherichia coli has proved to be a successful host for the expression of many heterologous proteins, and much efforts have been made toward improving recombinant protein expression including the usage of strong promoters and co expression with chaperones. But little attention was paid on the relation between expression level and function of the target protein. Glycerophosphate oxidase (GPO) is a protein with FAD cofactor (without free cysteine and disulfide bonds).It was observed that the specific activity of GPO dramatically decreased with the increase of inducer IPTG. In addition, the stability of it decreased correspondingly. The structural difference of samples expressed under varying IPTG was investigated using size-exclusion and reverse-phase high performance liquid chromatography, together with CD spectrum. It was found that the conformation of peptide and organization of subunits were not affected. The loss of specific activity and stability were correlated to incomplete attachment of FAD onto GPO. These results revealed that synthesis speed should be controlled either by reduction of IPTG amount or using weak promoters in the production of GPO. PMID- 20736069 TI - Spatial attention influences trial-by-trial relationships between response time and functional connectivity in the visual cortex. AB - Variations of response time (RT) in selective attention tasks are often associated with variations of activity and functional connectivity in sensory cortices that process relevant stimuli. Here, we investigated whether such relationships are influenced by spatial attention. To investigate this hypothesis, we asked fourteen healthy adults to perform a covert spatial attention task, which made use of bilateral stimulus displays, while we recorded their brain activity using functional magnetic resonance imaging (fMRI). As expected, activity in the middle occipital gyrus increased when spatial attention was directed to the contralateral (versus the ipsilateral) visual field. Surprisingly, variations of RT were not associated with variations in the magnitude of this attentional enhancement. As predicted, however, they were linked to opposing variations of functional connectivity between middle occipital regions contralateral (but not ispilateral) to the attended visual field and the left fusiform gyrus, which is thought to figure prominently in the perceptual processing of visually presented letters. These findings suggest that trial-by trial variations of RT reflect, at least partially, trial-by-trial variations in the extent to which spatial attention enhances functional connectivity between sensory regions that process relevant stimuli. PMID- 20736070 TI - Emotional conflict in interpersonal interactions. AB - Facial displays of emotions can help to infer the mental states of other individuals. However, the expectations we generate on the basis of people's emotions can mismatch their actual behaviour in certain circumstances, which generates conflict. In the present study, we explored the neural mechanisms of emotional conflict during interpersonal interactions. Participants had to accept or reject economic offers made by several partners who displayed emotional expressions. On every trial, a cue informed participants of whether they could trust the emotion of their partner or not. Trustworthy (low-conflict) partners with happy facial expressions were cooperative and those with angry expressions did not cooperate. Untrustworthy (high-conflict) partners, on the other hand, cooperated when their expression was angry and did not cooperate when they displayed a happy emotion. Behavioural responses were faster for trustworthy than for untrustworty partners. High-conflict partners activated the anterior cingulate and the anterior insula. In turn, trustworthy partners were associated with activations in the left precuneus. Our results suggest that the emotion displayed by another person affects our decision-making in social contexts. When emotional expressions are linked to their natural consequences, they engage ToM processes. In contrast, untrustworthy emotional expressions engage conflict related brain regions. PMID- 20736071 TI - High-resolution imaging of the fusiform face area (FFA) using multivariate non linear classifiers shows diagnosticity for non-face categories. AB - Does the "fusiform face area" (FFA) code only for faces? This question continues to elude the neuroimaging field due to at least two kinds of problems: first, the relatively low spatial resolution of fMRI in which the FFA was defined and second, the potential bias inherent in prevailing statistical methods for analyzing the actual diagnosticity of cortical tissue. Using high-resolution (1 mm * 1 mm * 1 mm) imaging data of the fusiform face area (FFA) from 4 subjects who had categorized images as 'animal', 'car', 'face', or 'sculpture', we used multivariate linear and non-linear classifiers to decode the resultant voxel patterns. Prior to identifying the appropriate classifier we performed exploratory analysis to determine the nature of the distributions over classes and the voxel intensity pattern structure between classes. The FFA was visualized using non-metric multidimensional scaling revealing "string-like" sequences of voxels, which appeared in small non-contiguous clusters of categories, intertwined with other categories. Since this analysis suggested that feature space was highly non-linear, we trained various statistical classifiers on the class-conditional distributions (labelled) and separated the four categories with 100% reliability (over replications) and generalized to out-of-sample cases with high significance (up to 50%; p<.000001, chance=25%). The increased noise inherent in high-resolution neuroimaging data relative to standard resolution resisted any further gains in category performance above ~60% (with FACE category often having the highest bias per category) even coupled with various feature extraction/selection methods. A sensitivity/diagnosticity analysis for each classifier per voxel showed: (1) reliable (with S.E.<3%) sensitivity present throughout the FFA for all 4 categories, and (2) showed multi-selectivity; that is, many voxels were selective for more than one category with some high diagnosticity but at submaximal intensity. This work is clearly consistent with the characterization of the FFA as a distributed, object-heterogeneous similarity structure and bolsters the view that the FFA response to "FACE" stimuli in standard resolution may be primarily due to a linear bias, which has resulted from an averaging artefact. PMID- 20736072 TI - Comparisons of the genetic structure of Squalius populations (Teleostei, Cyprinidae) from rivers with contrasting histories, drainage areas and climatic conditions based on two molecular markers. AB - The genetic structure of Squalius populations from Portuguese Atlantic- and Mediterranean-type streams (assigned to six distinct morphoclimatic regions) was compared using sequences of the cytb and beta-actin genes. The drainage area was significantly correlated to all the genetic diversity indices, pointing to the need to control for this effect in comparing populations with different histories and paleoecologies. A significant correlation was also found between genetic diversity and the morphoclimatic regions to which the rivers were assigned, with the highest diversity in warmer, lower latitude, Mediterranean-type streams. This relationship was not due to idiosyncratic characteristics of the clades compared. When the drainage area and phylogenetic effects were removed, the southern Mediterranean streams harboured significantly more genetic diversity even when compared with much larger northern streams. It is argued that these results are likely caused both by the metapopulation structure of the Mediterranean streams and by the severe reduction or local extinction of populations in the northern rivers during glaciations. PMID- 20736073 TI - A neotropical polymorphic damselfly shows poor congruence between genetic and traditional morphological characters in Odonata. AB - The Neotropical damselfly genus Polythore consists of nineteen described morphospecies. We used the COI barcode locus (799 bp), male genitalia, wing venation, and geometrical pattern variation to clarify specific status in four Polythore procera populations in the Andean foothills of Colombia. Morphological data corroborates that all populations are P. procera, but molecular data suggests two well-supported reciprocal monophyletic clades. A high genetic divergence (~ 3%) was observed between them, and different degrees of gene flow were estimated by MDIV among populations. Our results support a recent (1.4 mya) possible speciation with morphological stasis where unknown reproductive mechanisms may be involved. PMID- 20736074 TI - Evidence that spatial memory deficits following bilateral vestibular deafferentation in rats are probably permanent. AB - Previous studies of rats with bilateral vestibular deafferentation (BVD) have demonstrated spatial memory deficits, suggesting adverse effects on the hippocampus. However, the longest post-operative time interval that has been studied was approx. 5-7 months post-surgery. In this study, we investigated whether rats exhibited spatial memory deficits at 14 months following BVD and whether these deficits could be exacerbated by administration of cannabinoid (CB) drugs. Twenty-eight adult rats were divided into four groups: (1) sham surgery+vehicle; (2) sham surgery+the CB1/CB(2) receptor agonist WIN55,212-2 ('WIN'); (3) BVD+vehicle; and (4) BVD+WIN. WIN (1.0 or 2.0 mg/kg/day) or vehicle, was administered (s.c.) on days 1-10 and 11-20 (respectively), 30 min before the rats performed in a foraging task. On day 21, the CB receptor inverse agonist, AM251 (3.0 mg/kg, s.c.), was administered before WIN or vehicle. To our surprise, BVD animals were impaired in using the visual cues during the probe test in light. In the dark trials, when visual cues were unavailable, BVD animals were unable to use self-movement cues in homing. However, WIN at 2 mg/kg, significantly improved BVD animals' homing time and number of errors in the dark through strategies other than the improvement in using self-movement cues. Furthermore, AM251 significantly improved heading angle in vehicle-treated animals and the first home choice in WIN-treated animals. These results suggest that at 14 months post-BVD, the animals are not only impaired in path integration, but also piloting and that the spatial memory deficits may be permanent. The involvement of the cannabinoid system is more complicated than expected. PMID- 20736075 TI - Changes in fMRI BOLD response to increasing and decreasing task difficulty during auditory perception of temporal order. AB - We have discovered changes in brain activation during difficult and easy milliseconds timing. Structures engaged in difficult and easier auditory temporal order judgment were identified in 17 young healthy listeners presented with paired-white-noises of different durations. Within each pair, a short (10 ms) and a long (50 ms) noise was separated by a silent gap of 10, 60 or 160 ms, corresponding to three levels of task difficulty, i.e. difficult, moderate and easy conditions, respectively. A block design paradigm was applied. In temporal order judgment task subjects were required to define the order of noises within each pair, i.e. short-long or long-short. In the control task they only detected the presentation of the stimulus pair. A multiple regression with 'task difficulty' as a regressor ('difficult', 'moderate', 'easy') showed dynamic changes in neural activity. Increasing activations accompanying increased task difficulty were found in both bilateral inferior parietal lobuli and inferior frontal gyri, thus, in classic regions related to attentional and working memory processes. Conversely, decreased task difficulty was accompanied by increasing involvement of more specific timing areas, namely bilateral medial frontal gyri and left cerebellum. These findings strongly suggest engagement of different neural networks in difficult or easier timing and indicate a framework for understanding timing representation in the brain. PMID- 20736076 TI - Distinct patterns of Fos immunoreactivity in striatum and hippocampus induced by different kinds of novelty in mice. AB - In this study the immediate-early gene Fos was used to investigate the response to different novel stimuli in a wide array of brain regions including the hippocampus, the rhinal cortex, the frontal cortex and different components of the striatal complex. Independent groups of CD-1 mice were exposed to three different novelty conditions: (1) novel environment (empty open field); (2) complex novel environment (i.e. open field containing objects); and (3) identity based detection of novel objects. We observed that a complex novel environment and a knowledge-based novelty modulated Fos levels in both the dorsal and the ventral components of the striatum, while Fos immunoreactivity in the medial temporal lobe was only increased after exposure to novel environments, regardless of their complexity. Finally, we observed a strong increase of Fos levels in the prefrontal cortex in all the three novel conditions examined, indicating a major involvement of this structure in novelty assessment. Overall the present study demonstrates that distinct brain regions are recruited in different kinds of novelty and emphasizes the role of the striatal complex in processing complex novel information. PMID- 20736077 TI - Early CMV viremia is associated with impaired viral control following nonmyeloablative hematopoietic cell transplantation with a total lymphoid irradiation and antithymocyte globulin preparative regimen. AB - The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naive donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control. PMID- 20736080 TI - Mycophenolic acid inhibits natural killer cell proliferation and cytotoxic function: a possible disadvantage of including mycophenolate mofetil in the graft versus-host disease prophylaxis regimen. AB - To determine how immunosuppressant agents used for graft-versus-host disease (GVHD) prophylaxis affect natural killer (NK) cells, we examined the effects of cyclosporine (CSP), tacrolimus (TAC), mycophenolic acid (MPA, an active form of mycophenolate mofetil), and methotrexate (MTX) on the proliferation and cytotoxicity of NK cells. The proliferation of NK cells from healthy individuals in the presence of interleukin (IL)-2 and IL-15 was suppressed to 51% +/- 16% of that of the controls with CSP, to 31% +/- 19% with TAC, to 14% +/- 6% with MPA, and to 87% +/- 18% with MTX. Both CSP and TAC increased the proportion of CD16( )CD56(bright) cells, a NK cell subset capable of secreting high amount of cytokines, and also enhanced NKp30 expression, whereas MPA markedly decreased the proportion of CD16(-)CD56(bright) cells and reduced the expression of all activating NK cell receptors, including NKG2D, NKp30, NKp44, and NKp46. MPA also reduced the cytotoxicity against K562 cells from 61% +/- 15% to 17% +/- 7% and that against Daudi cells from 44% +/- 4% to 4% +/- 4%, whereas the other 3 drugs did not diminish these cytotoxicities. The inhibition of NK cell proliferation and cytotoxicity against leukemic cell lines by MPA was partially abolished by the inclusion of guanosine in the culture. Similar to the effect of MPA on T cells, MPA inhibited the down-regulation of p27 on NK cells induced by the incubation of NK cells in the presence of IL-2. These results suggest that MPA is a potent inhibitor of NK cells, and that its inclusion in the GVHD prophylaxis regimen might diminish the graft-versus-leukemia effect of NK cells. PMID- 20736078 TI - Evaluating the impact of antithymocyte globulin on lung function at 1 year after allogeneic stem cell transplantation. AB - The use of antithymocyte globulin (ATG) in hematopoietic stem cell transplantation (HSCT) conditioning regimens has reduced the incidence of graft versus-host disease, particularly in its chronic form. The impact of this approach on the prevention of lung dysfunction has not been well characterized, however. We performed a retrospective analysis of pulmonary function in patients who underwent HSCT after conditioning with oral busulfan followed by either cyclophosphamide or fludarabine with or without the addition of ATG. A total of 393 patients were included; 75 patients received ATG, and 318 did not. No differences between the 2 groups were seen in the mean percentage of the predicted values for forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), total lung capacity, and lung CO diffusing capacity at 80 days or 1 year after transplantation. However, the mean value of FEV(1)/FVC ratio at 1 year was higher in the patients who received ATG. The difference in mean change in pulmonary function parameters from baseline to 1 year post-HSCT was statistically nonsignificant for all parameters except FEV(1)/FVC ratio, which demonstrated less decline in the ATG group. The risk of developing severe airflow obstruction or a restrictive pattern was similar in the 2 treatment groups at 1 year post-HSCT. Incorporation of ATG into the HSCT conditioning regimen provided protection against a decline in FEV(1)/FVC ratio but did not decrease the risk of other pulmonary events that we evaluated within the first year after HSCT. Further evaluations in larger numbers of patients are needed to better clarify the role of ATG in the development of delayed pulmonary complications. PMID- 20736079 TI - Fludarabine-based conditioning chemotherapy for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia. AB - Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naive, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m(2)/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 * 10(8)/kg (range, 0.60-6.7 * 10(8)/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade >=II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naive patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner. PMID- 20736081 TI - Evidence for the cytotoxic effects of Mycobacterium tuberculosis phospholipase C towards macrophages. AB - Phospholipase Cs (PLCs) contribute importantly to the virulence and pathogenicity of several bacteria. It has been reported in previous studies that mutations in the four predicted plc genes of Mycobacterium tuberculosis inhibit the growth of these bacteria during the late phase of infection in mice. These enzymes have not yet been fully characterised, mainly because they are not easy to produce in large quantities. With a view to elucidating the role of all Mycobacterium tuberculosis phospholipase Cs (PLC-A, PLC-B, PLC-C and PLC-D), a large amount of active, soluble recombinant PLCs, were expressed and purified using Mycobacterium smegmatis as expression system. These enzymes showed different pH activity profiles. PLC-C was found to be the most active of the four recombinant PLCs under acidic conditions. All the enzymes tested induced cytotoxic effects on mouse macrophage RAW 264.7 cell lines, via direct or indirect enzymatic hydrolysis of cell membrane phospholipids. These results open new prospects for characterising biochemical and structural features of Mycobacterium tuberculosis PLCs, which might lead to the identification of novel anti-tuberculosis drug targets. All mycobacterial phospholipase Cs can now be studied in order to determine their role in the virulence and pathogenicity of bacteria of this kind. PMID- 20736082 TI - The complexity of HDL. AB - Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with coronary artery disease risk in large epidemiologic studies. This rule, however, has many exceptions in individual patients, and evidence suggests that other facets of high-density lipoprotein particle biology not captured by measuring HDL-C levels are responsible for HDL's effects in vivo. This article reviews the evidence for the protective nature of HDL, current evidence from animal and human studies regarding HDL-based therapies, the major steps in HDL particle formation and metabolism, alterations leading to dysfunctional HDL in diabetes and inflammatory states, and potential alternatives to HDL-C to measure HDL function and predict its protective value clinically. PMID- 20736084 TI - Enzymological studies on the biosynthesis of N-acylethanolamines. AB - Ethanolamides of different long-chain fatty acids constitute a class of endogenous lipid molecules generally called N-acylethanolamines (NAEs). They contain N-arachidonoylethanolamine (anandamide), N-palmitoylethanolamine, and N oleoylethanolamine, which receive considerable attention because of their actions as an endogenous cannabinoid receptor ligand (endocannabinoid), an anti inflammatory substance, and an appetite-suppressing substance, respectively. Identification of their biosynthetic routes in animal tissues and molecular characterization of the enzymes involved are essential for better understanding of physiological importance of NAEs as well as development of enzyme inhibitors as possible therapeutic drugs. In the classical "transacylation-phosphodiesterase pathway", NAEs are formed from glycerophospholipids via N acylphosphatidylethanolamine (NAPE), an unusual derivative of phosphatidylethanolamine with a third acyl chain attached to the amino group, by sequential catalyses by Ca(2+)-dependent N-acyltransferase and NAPE-hydrolyzing phospholipase D. However, recent studies reveal that NAE-generating pathways are more complex than presumed before. In this review article, we will focus on recent findings regarding mammalian enzymes that are involved or might be involved in the biosynthesis of NAEs. PMID- 20736083 TI - Repercussion of a deficiency in mitochondrial beta-oxidation on the carbon flux of short-chain fatty acids to the peroxisomal beta-oxidation cycle in Aspergillus nidulans. AB - The fungus Aspergillus nidulans contains both a mitochondrial and peroxisomal beta-oxidation pathway. This work was aimed at studying the influence of mutations in the foxA gene, encoding a peroxisomal multifunctional protein, or in the scdA/echA genes, encoding a mitochondrial short-chain dehydrogenase and an enoyl-CoA hydratase, respectively, on the carbon flux to the peroxisomal beta oxidation pathway. A. nidulans transformed with a peroxisomal polyhydroxyalkanoate (PHA) synthase produced PHA from the polymerization of 3 hydroxyacyl-CoA intermediates derived from the peroxisomal beta-oxidation of external fatty acids. PHA produced from erucic acid or heptadecanoic acid contained a broad spectrum of monomers, ranging from 5 to 14 carbons, revealing that the peroxisomal beta-oxidation cycle can handle both long and short-chain intermediates. While the ?foxA mutant grown on erucic acid or oleic acid synthesized 10-fold less PHA compared to wild type, the same mutant grown on octanoic acid or heptanoic acid produced 3- to 6-fold more PHA. Thus, while FoxA has an important contribution to the degradation of long-chain fatty acids, the flux of short-chain fatty acids to peroxisomal beta-oxidation is actually enhanced in its absence. While no change in PHA was observed in the ?scdA?echA mutant grown on erucic acid or oleic acid compared to wild type, there was a 2- to 4-fold increased synthesis of PHA in ?scdA?echA cells grown in octanoic acid or heptanoic acid. These results reveal that a compensatory mechanism exists in A. nidulans that increases the flux of short-chain fatty acids towards the peroxisomal beta-oxidation cycle when the mitochondrial beta-oxidation pathway is defective. PMID- 20736085 TI - stac1 and stac2 genes define discrete and distinct subsets of dorsal root ganglia neurons. AB - Deciphering the precise in vivo function of a particular neuronal subpopulation is one of the most challenging issues in neurobiology. Dorsal root ganglia (DRG) neurons represent a powerful model system to address this fundamental question. These neurons display many morphological, anatomical and few molecular characteristics. With the aim of expanding the molecular description of the primary sensory neurons, we used Affimetrix microarrays to compare global gene expression profiles of DRG of wild type and trkA(trkC/trkC) knock-in mice at birth and identified several hundred potential markers of nociceptive neurons and few markers of proprioceptive neurons. Here, we describe the identification of two members of a family of putative adapter proteins STAC1 and STAC2. We found STAC1 and STAC2 being expressed in a mutually exclusive fashion in adult DRG neurons. STAC1 mainly marks peptidergic nociceptive neurons while STAC2 is expressed in a subset of nonpeptidergic nociceptors, in all trkB+ neurons and in a subpopulation of proprioceptive neurons. Our expression data demonstrate that STAC proteins identify four categories of primary sensory neurons; one class of peptidergic neurons, a subset of nonpeptidergic neurons, all TrkB+neurons and a subset of proprioceptive neurons. Genetic marking of STACs-expressing sensory neurons will lend significant advance into our understanding of DRG neuronal functional diversity. PMID- 20736087 TI - Mechanisms for acute oxygen sensing in the carotid body. AB - Hypoxic chemotransduction in the carotid body requires release of excitatory transmitters from type I cells that activate afferent sensory neurones. Transmitter release is dependent on voltage-gated Ca2+ entry which is evoked by membrane depolarization. This excitatory response to hypoxia is initiated by inhibition of specific O2 sensitive K+ channels, of which several types have been reported. Here, we discuss mechanisms which have been put forward to account for hypoxic inhibition of type I cell K+ channels. Whilst evidence indicates that one O2 sensitive K+ channel, BKCa, may be regulated by gasotransmitters (CO and H2S) in an O2-dependent manner, other studies now indicate that activation of AMP activated protein kinase (AMPK) accounts for inhibition of both BKCa and 'leak' O2 sensitive K+ channels, and perhaps also other O2 sensitive K+ channels reported in different species. We propose that type I cell AMPK activation occurs as a result of inhibition of mitochondrial oxidative phosphorylation, and does not require increased production of reactive oxygen species. Thus, AMPK activation provides the basis for unifying the 'membrane' and 'mitochondrial' hypotheses, previously regarded as disparate, to account for hypoxic chemotransduction. PMID- 20736088 TI - Sympathetic overactivity coupled with active expiration in rats submitted to chronic intermittent hypoxia. AB - It is well known that the respiration modulates sympathetic outflow in basal conditions. Recordings of sympathetic nerve activity demonstrated that central respiratory activity produces rhythmical oscillations in sympathetic discharge that appear mainly during inspiratory phase. This led us to hypothesize that changes in the mechanisms regulating the central entrainment between respiratory and sympathetic activities may contribute to sympathetic overactivity and hypertension. This issue was addressed using rats submitted to chronic intermittent hypoxia (CIH), in which we evaluated whether or not the sympathetic overactivity and hypertension observed in these animals were linked to changes in respiratory pattern. We verified that under baseline conditions, CIH rats exhibited a reduction in post-inspiratory activity of vagus nerve and an enhanced late-expiratory activity in abdominal motor nerve. As a consequence of this altered expiratory pattern, we observed that CIH rats showed an additional burst in sympathetic activity phase-locked with the enhanced late-E expiratory activity. These findings pointed out that the entrainment between pontine medullary expiratory and sympathetic neurons of CIH rats is strengthened, indicating for the first time in this experimental model that changes in the coupling of respiratory and sympathetic activities may contribute to hypertension. Subsequent studies performed in other models of hypertension also demonstrated similar changes, supporting the concept that alterations in central mechanisms of respiratory-sympathetic coupling is a novel and important mechanism to be considered in the pathogenesis of hypertension. PMID- 20736086 TI - Expression patterns of astrocyte elevated gene-1 (AEG-1) during development of the mouse embryo. AB - Expression of astrocyte elevated gene-1 (AEG-1) is elevated in multiple human cancers including brain tumors, neuroblastomas, melanomas, breast cancers, non small cell lung cancers, liver cancers, prostate cancers, and esophageal cancers. This gene plays crucial roles in tumor cell growth, invasion, angiogenesis and progression to metastasis. In addition, over-expression of AEG-1 protects primary and transformed cells from apoptosis-inducing signals by activating PI3K-Akt signaling pathways. These results suggest that AEG-1 is intimately involved in tumorigenesis and may serve as a potential therapeutic target for various human cancers. However, the normal physiological functions of AEG-1 require clarification. We presently analyzed the expression pattern of AEG-1 during mouse development. AEG-1 was expressed in mid-to-hindbrain, fronto-nasal processes, limbs, and pharyngeal arches in the early developmental period from E8.5 to E9.5. In addition, at stages of E12.5-E18.5 AEG-1 was localized in the brain, and olfactory and skeletal systems suggesting a role in neurogenesis, as well as in skin, including hair follicles, and in the liver, which are organ sites in which AEG-1 has been implicated in tumor development and progression. AEG-1 co localized with Ki-67, indicating a role in cell proliferation, as previously revealed in tumorigenesis. Taken together, these results suggest that AEG-1 may play a prominent role during normal mouse development in the context of cell proliferation as well as differentiation, and that temporal regulation of AEG-1 expression may be required during specific stages and in specific tissues during development. PMID- 20736089 TI - Exploring the positional importance of aromatic residues and lysine in the interactions of peptides with the Plasmodium falciparum Hsp70-1. AB - Plasmodium falciparum harbors an essential relict plastid called the apicoplast that is involved in several important biosynthetic processes. Over 500 nuclear encoded proteins are imported into the organelle that is now recognized as an important therapeutic target. These proteins contain an N-terminal transit peptide sequence essential for apicoplast targeting during which the P. falciparum Hsp70-1 plays an important role. In the present study, we have focused on the in vitro interactions of PfHsp70-1 with synthetic peptides endowed with transit peptide like features. The peptides exhibit higher affinity for PfHsp70-1 in the presence of ADP compared to ATP. The results highlight the positional importance of selected residues in the designed peptides for affinity. They suggest that better peptide affinity for the protein requires a Lys at second position, retention of aromatic residue at the last position, and absence of acidic residues at any position in the transit peptides. Overall, the present work is the first in vitro fluorescence-based study of PfHsp70-1 with peptides possessing transit peptide-like features. PMID- 20736090 TI - Progress in tracing the evolutionary paths of cytochrome P450. AB - The state of cytochrome P450 sequence accumulation in different phyla is summarized. 12,456 P450s are currently named, with about 6000 more that are known, but not yet named. As the number of genomes sequenced moves from a few dozen to an inevitable few thousand, issues of nomenclature are discussed. Orthology will be the guiding principle for naming across related genomes such as vertebrates. Even if 1000 vertebrate genomes are sequenced there will still be only 19 CYP families in vertebrates. The variable clusters of genes in families CYP2, CYP3 and CYP4 may pose challenges for naming as 1:1 orthologs do not necessarily exist. The value of synteny across genomes is emphasized as a tool for deep time evolutionary studies of P450s in animals. There is evidence that macrosynteny may be useful in tracing the origin of animal CYP clans. The concept of saturation of sequence space is described and used to estimate how complete our knowledge is of P450s in different phyla. The special niche of filamentous fungal P450s acting in secondary metabolite gene clusters is discussed. From one quarter to one third of P450s in these fungi may be dedicated to these roles. PMID- 20736091 TI - A bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. AB - Although a major effect of bisphosphonates on bone is inhibition of resorption resulting from their ability to interfere with osteoclast function, these agents also prevent osteoblast and osteocyte apoptosis in vitro and in vivo. However, the contribution of the latter property to the overall beneficial effects of the drugs on bone remains unknown. We compared herein the action on glucocorticoid induced bone disease of the classical bisphosphonate alendronate with that of IG9402, a bisphosphonate analog that preserves osteoblast and osteocyte viability but does not induce osteoclast apoptosis in vitro. The bisphosphonates were injected daily (2.3 MUmol/kg) to 5-month-old Swiss Webster mice (6-11 per group), starting 3 days before implantation of pellets releasing the glucocorticoid prednisolone (2.1 mg/kg/day). IG9402 did not affect levels of circulating C telopeptide or osteocalcin, markers of resorption and formation, respectively, nor did it decrease mRNA levels of osteocalcin or collagen 1a1 in bone. On the other hand, alendronate decreased all these parameters. Moreover, IG9402 did not reduce cancellous mineralizing surface, mineral apposition rate, or bone formation rate, whereas alendronate induced a decrease in each of these bone formation measures. These findings demonstrate that, in contrast to alendronate, IG9402 does not inhibit bone turnover. Both alendronate and IG9402, on the other hand, activated survival kinase signaling in vivo, as evidenced by induction of ERK phosphorylation in bone. Furthermore, both bisphosphonates prevented the increase in osteoblast and osteocyte apoptosis as well as the decrease in vertebral bone mass and strength induced by glucocorticoids. We conclude that a bisphosphonate that does not affect osteoclasts prevents osteoblast and osteocyte apoptosis and the loss of bone strength induced by glucocorticoids in mice. PMID- 20736092 TI - Collagen mutation causes changes of the microdamage morphology in bone of an OI mouse model. AB - Previous studies have postulated that ultrastructural changes may alter the pattern and capacity of microdamage accumulation in bone. Using an osteogenesis imperfecta (OI) mouse model, this study was performed to investigate the correlation of collagen mutation with the microdamage morphology and the associated brittleness of bone. In this study, femurs from mild OI and wild type mice were fatigued under four-point bending to create microdamage in the specimens. Then, the microdamage morphology of these specimens was examined using the bulk-staining technique with basic fuchsin. Similar with the results of previous studies, it was observed that linear microcracks were formed more easily in compression, whereas diffuse damage was induced more readily in tension for both wild-type and mild-type mice. However, less diffuse damage was found in the tensile side of mild OI mouse femurs (collagen mutation) compared with those of wild type mice, showing that the microdamage morphology is correlated to the brittleness of bone. The results of this study provide direct evidence that supports the prediction made by the previous numerical simulation studies, suggesting that microdamage morphology in bone is significantly correlated with the integrity of the collagen phase. PMID- 20736093 TI - Collagen gene polymorphisms influence fracture risk and bone mass acquisition during childhood and adolescent growth. AB - Fractures are common in childhood with incidence maximal during puberty, around the time of peak height velocity. The relationships between single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2, bone mass acquisition, and childhood fractures are unclear. We recruited 394 children and adolescents aged 4 to 16 years into a noninterventional case control study. All had suffered an episode of trauma leading to hospital presentation; 205 had sustained a fracture. We determined the frequency of COL1A1 Sp1 and COL1A2 PvuII SNPs. Lumbar spine dual energy X-ray absorptiometry (DXA) measurements were compared between fracture and control groups according to genotype. Subgroup analyses were performed according to sex, pubertal status, and site of injury. We found that the COL1A2 'PP' genotype approximately halved the odds of fracture in the study group as a whole (OR=0.45 [95% CI=0.24-0.82], p=0.01). In particular, possession of the same genotype by subjects who had not yet progressed beyond midpuberty was associated with reduced odds of fracture (OR=0.38 [95% CI=0.19-0.79], p=0.01) and significantly increased lumbar spine bone mineral content (p=0.03) and areal bone mineral density (p=0.007). The COL1A1 Sp1 binding site 's' allele was associated with a trebling of the odds of fracture in prepubertal children (OR=3.1 [95% CI=1.43-6.61], p=0.004), but there was no association with any DXA measures. This is the first paediatric study to our knowledge that shows an association of the COL1A2 PvuII restriction site 'PP' genotype with a reduced risk of fracture and of the COL1A1 Sp1 binding site 's' allele with an increased risk. The association of these variants with fracture risk is greatest during periods of predominantly appendicular bone growth. PMID- 20736094 TI - Effects of three different preservation methods on the mechanical properties of human and bovine cortical bone. AB - BACKGROUND AND PURPOSE: In the development of new strategies for fracture fixation, new methods have to be tested biomechanically under in vitro conditions before clinical trials can be performed. The gold standard for laboratory evaluations is fresh-frozen specimen. As the availability of fresh-frozen specimens is limited and since their use bears infectious risks, specimens treated with various chemical embalming fluids are also used. These preservation methods may alter the mechanical properties of the specimens used. Therefore, the aims of the present study were to determine the effects of three different preservation methods (formalin fixation (FO), Thiel-fixation (TH), and alcohol glycerine fixation (AG)) on the elastic and postyield mechanical properties of cortical bone and to compare these properties to those of fresh-frozen (FF) specimens. MATERIALS AND METHODS: Cylindrical cortical specimens (diameter 3mm, length 60 mm) were obtained from human femurs (n=48) and bovine tibiae (n=40). Before specimen immersion in different fixation fluids, bone mineral density (BMD) as well as the initial Young's modulus was determined. The Young's modulus was determined in a nondestructive bending test, and measurements were repeated after 6 months of immersion in fixative solution. Subsequent to the nondestructive test, a destructive 3-point bending test was conducted to assess the postyield and fracture properties. RESULTS: The BMD as well as the initial Young's modulus showed no significant differences between the four test groups. After 6 months in fixative solution, the Young's modulus was significantly lowered in human Thiel specimens and only showed minor changes in formalin- and alcohol-glycerine-treated specimens. The plastic energy absorption of human and bovine specimens was altered significantly. Formalin as well as alcohol-glycerine fixation yielded a significant decrease in plastic energy absorption, whereas Thiel fixation significantly increased the plastic energy absorption. DISCUSSION/CONCLUSION: Because of the significantly altered plastic mechanical properties of cortical bone, the use fresh-frozen bone specimens is recommended in biomechanical studies investigating failure loads of orthopaedic implants. The use of embalmed specimens should be restricted to pilot tests. PMID- 20736095 TI - A gain-of-function I(K-ATP) mutation and its role in sudden cardiac death associated with J-wave syndromes. PMID- 20736096 TI - Regulatory T cell immunotherapy for transplantation tolerance: step into clinic. AB - Recent studies in animal models have demonstrated that adoptive transfer of antigen-specific CD4+CD25+ regulatory T cells (Tregs) can prevent or even cure autoimmune diseases, and appear to induce transplantation tolerance. Thus, adoptive cell therapy using ex vivo induced and expanded patient-specific CD4+CD25+Tregs has emerged as a promising individualized medicine for the treatment of inflammatory disease. Here we discuss our current efforts on the pursuit of regulatory T cell therapy for the induction of transplantation tolerance. PMID- 20736097 TI - Light pollution in the sea. PMID- 20736098 TI - Relationship between differential retention of Escherichia coli and Enterococcus faecalis and variations in enzyme activity in the scallop Patinopecten yessoensis. AB - Uptake of Escherichia coli and Enterococcus faecalis and variations of trypsin amylase activity acid phosphatase and superoxide dismutase in tissue of the scallop Patinopecten yessoensis were detected. The results showed that P. yessoensis accumulated E. faecalis in larger numbers and more rapidly than E. coli, both with the highest concentration in the digestive tract and lowest in hemolymph. Compared to E. coli, all scallops exposed to E. faecalis showed significantly higher trypsin and AMS activity. SOD activity in hemocytes and ACP activity in hemolymph was significantly higher in the treatments with 5 log(10)CFU/ml E. coli than with E. faecalis. But no significant differences in ACP activity of P. yessoensis exposed to a 3 log(10)CFU/ml inoculum of both bacteria were recorded. In conclusion, the mass retention of gut microflora in P. yessoensis is positively correlated with digestive enzymes activity and negatively correlated with ACP activity in the hemocyte. PMID- 20736099 TI - Acute and chronic conditions of the ear, nose, throat and related head and neck structures. PMID- 20736100 TI - Evaluation and management of the patient with "sinus". AB - The patient with "sinus" is common. However, an accurate diagnosis for a patient's sinus complaints may be elusive. The diagnostic uncertainty with these patients is a result of nonspecific symptoms, subtle or absent physical examination findings, and limited diagnostic testing options. Rhinitis should be distinguished from sinusitis. In acute illness, viral upper respiratory tract infection should be distinguished from acute bacterial sinusitis. For patients with chronic sinus symptoms, objective evidence of paranasal sinus inflammation should be confirmed before labeling the patient with chronic sinusitis. PMID- 20736101 TI - The patient with allergies. AB - Allergic disease affects a sizeable percentage of the general population, has a significant impact on patient quality of life, and exerts a significant financial burden on society. Atopic symptoms from inhalant allergens are among the most frequent complaints in outpatient medical visits. Key history and physical examination findings help to distinguish allergic rhinitis from other forms of chronic rhinosinusitis. Diagnostic testing may not be necessary unless immunotherapy is contemplated. PMID- 20736102 TI - Evaluating and managing the patient with nosebleeds. AB - Epistaxis is a common clinical problem often seen by primary care physicians. This can be caused by multiple factors, each of which should be explored to treat the epistaxis and prevent recurrences. In this article, etiologies and methods of evaluation for the patient with epistaxis are discussed. Treatment strategies are outlined in a stepwise fashion, as are recommendations for situations requiring referral to an otolaryngologist. PMID- 20736103 TI - The patient with "postnasal drip". AB - Postnasal drip (PND) is a common clinical complaint, yet its physiologic basis and appropriate treatment have been inadequately addressed in the medical literature. PND may be caused by a variety of conditions involving the nose and throat. Often, the symptom is not caused by actual secretions draining from the nose into the pharynx. In many instances, no definitive cause can be identified. Empiric treatment for PND symptoms should be guided by associated symptoms that suggest either a sinonasal cause or gastroesophageal reflux. Rarely, PND may be a symptom of a serious process such as a mass lesion in the pharynx or a malignancy and thus referral to an otolaryngologist is appropriate if symptoms are persistent, unexplainable, or associated with warning signs of malignancy. PMID- 20736104 TI - The patient with sore throat. AB - Sore throat is a common medical complaint seen by the emergency practitioner, internist, pediatrician, and otolaryngologist. The differential for sore throat is vast. However, with a directed history this can often be narrowed down to 2 to 3 possible diagnoses. By paying particular attention to the associated symptoms and duration of symptoms, common self-limited etiologies like viral pharyngitis and nonstreptococcal tonsillitis can be distinguished from those that require more investigation, such as supraglottitis and tonsillar cancer. A sore throat is most commonly caused by an infectious, inflammatory, or neoplastic etiologic factor. PMID- 20736105 TI - Diagnostic evaluation and management of hoarseness. AB - Hoarseness is a common symptom that can result from a wide spectrum of underlying causes ranging from the common cold to a malignancy. A framework for diagnostic evaluation is presented based on categorizing the myriad of causes by how they interfere with the voice production mechanism. Triaging of cases by necessity or urgency of laryngoscopy is assisted by forming a global index of suspicion based on targeted history taking. Laryngoscopy is required in most cases to obtain a diagnosis for the hoarseness. Treatments commonly prescribed for hoarseness are critically examined in this article. To listen to audio clips of patients with different types of hoarseness, please visit our website, www.medical.theclinics.com. PMID- 20736106 TI - Otalgia. AB - Otalgia, pain in the ear, can be a consequence of otologic disease (primary or otogenic otalgia), or can arise from pathologic processes and structures other than the ear (secondary or referred otalgia). In children, ear disease is far and away the most common cause of otalgia, but in adults, secondary or referred otalgia is more common. Otalgia can be the only presenting symptom of several serious conditions, and its etiology should be fully explored. Unfortunately, its workup is complex and no simple algorithm exists. This article outlines the common causes, presentation, and treatment options for primary and secondary otalgia. PMID- 20736107 TI - Hearing loss. AB - Hearing loss is one of the most common sensory impairments and affects almost 10% of the adult population. The percentage of adults with hearing loss markedly increases with advancing age. The differential diagnosis for patients presenting with hearing loss is extensive, but can often be narrowed with a directed hearing history and physical examination. The severity of the hearing loss may warrant additional diagnostic studies, including audiometry, and possible imaging in selected cases. Hearing aids, assistive listening devices, middle ear surgery, and cochlear implantation are potential therapeutic options available to patients depending on the type and severity of the hearing loss. PMID- 20736108 TI - The dizzy patient. AB - The dizzy patient often presents a challenge to the physician. The history is the most important component of the evaluation of the dizzy patient and often allows the cause of the dizziness to be categorized as peripheral or central. Peripheral causes include benign paroxysmal positional vertigo, Meniere's disease, and vestibular neuritis. Central causes include migraine-associated dizziness, postconcussion syndromes, cerebrovascular disease, and multiple sclerosis. Treatment depends on the cause of the dizziness and may include dietary modifications, diuretics, vestibular suppressants, vestibular rehabilitation, or surgical intervention. PMID- 20736109 TI - The patient with a thyroid nodule. AB - Nodular thyroid disease is common in the United States and throughout the world. Although most thyroid nodules are benign in nature, certain clinical, radiographic, and cytologic features are associated with an increased risk of malignancy. A clear understanding of these risk factors assists in the decision making process when evaluating a patient with a thyroid nodule. It is this process that ultimately determines whether or not a patient is referred for surgery. This article provides a framework for clinicians to risk-stratify and appropriately manage patients with thyroid nodules. PMID- 20736110 TI - Evaluating the adult patient with a neck mass. AB - The objective of this article is to provide the internist with general considerations when confronted with an adult patient presenting with a neck mass. A thorough gathering of historical information and a complete physical examination are crucial in developing a differential diagnosis for these patients. Specifically, the location of the mass, its time of onset, and duration are important because of the high likelihood of neoplastic processes in patients older than 40 years. The young adult patient has an increased incidence of inflammatory, congenital, and traumatic processes as causes of their neck mass, but again, neoplasms are not out of the realm of possibility. Judicious use of imaging studies, namely computed tomography scanning with contrast, is a valuable adjunct to the physical examination. Other than infectious etiology, referral to an otolaryngologist is frequently warranted to obtain a definitive diagnosis for the development of an appropriate treatment plan, which is predominantly surgical. PMID- 20736111 TI - Head and neck cancer. AB - Early detection of upper aerodigestive tract cancer improves prognosis. The primary care physician plays an important role in early detection of these cancers. Most upper aerodigestive tract cancers are squamous cell carcinomas that are linked to tobacco, alcohol, or human papillomavirus exposure. These cancers produce nonspecific symptoms; thus, any persistent oral cavity lesion or neck mass or other unexplainable ear, nose, and throat symptoms should prompt an evaluation for malignancy. Although overall survival has not improved, nonsurgical treatment approaches have led to higher rates of organ preservation and rehabilitation after treatment has improved the quality of life of survivors. PMID- 20736112 TI - Snoring and obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) may be associated with myriad clinical consequences such as increased risk of systemic hypertension, coronary vascular disease, congestive heart failure, cerebrovascular disease, glucose intolerance, impotence, obesity, pulmonary hypertension, gastroesophageal reflux, and impaired concentration. Nonetheless, OSA remains undiagnosed in 82% of men and 93% of women with the condition. Early identification and treatment of OSA provides significant relief for individuals, prevents complications of OSA, and reduces overall health care costs. Better understanding of the pathogenesis, risk factors, diagnosis, and treatment of OSA has the potential to improve early recognition of OSA and prevention of adverse effects on the individual and society. PMID- 20736113 TI - Quantifying exposure risk: surgical masks and respirators. AB - BACKGROUND: The interaction between the source of respiratory infectious aerosols and the receiver has not been investigated. Using a bench model, we measured the effects of filtration and deflection achieved with surgical masks and N95 respirators. METHODS: We constructed a chamber designed to produce radiolabeled wet aerosols simulating contaminated particles exhaled during tidal breathing (source). Particles within the chamber were exposed to either 6 or 0 air exchanges/hr. Aerosols were defined by cascade impaction. Source aerosols were exhaled via a ventilated mannequin head suitable for mask protection. A similar ventilated head within the chamber assessed recipient exposure (receiver). A filter within the receiver quantified exposure. Two types of masks, an N95 respirator and surgical mask, were tested. Data were presented as percent of nebulized particles on the receiver filter (exposure) and simulated workplace protection factor (sWPF). RESULTS: In the presence of chamber air exchange, applying a mask on the source (primarily deflection) resulted in significant reduction in exposure to the receiver (sWPF170-320). Masks on receiver (filtration) did not significantly reduce exposure from that of no masks (sWPF1.37-2.21), except with a Vaseline seal (sWPF118). With 0 air exchanges/hr, only Vaseline seal was effective in reducing exposure (sWPF 16-101). CONCLUSION: In a ventilated space, deflection of exhaled particles with a mask worn at the source achieved far greater levels of protection than any mask on the receiver. Mask filtration at source or receiver did not play a significant role in reducing exposure. PMID- 20736114 TI - Secular trends of candidemia in a tertiary care hospital. AB - BACKGROUND: Candidemias account for 8% to 15% of hospital-acquired bloodstream infections. They have been associated with previous exposure to antimicrobials and are considered high-morbidity infections with high treatment costs. This study characterizes candidemias in a tertiary care hospital and assesses their incidence rates, clinical and microbiological features, and use of antifungals. METHODS: We assessed hospital-acquired candidemias in the period from January 1997 to July 2007 in a high-complexity private hospital. RESULTS: There were 151 cases of candidemia in 147 patients. The incidence rate was 0.74 episodes/1000 admissions. The mean age of the patients was 60 years (standard deviation +/- 24.9), and the mean length of hospital stay before the blood culture identified candidemia was 40.9 days (standard deviation +/- 86.3). The in-hospital mortality rate was 44.2%. C albicans was isolated in 44% (n = 67) of the cases, and no difference in mortality rates was found between species (Candida albicans vs C non-albicans, P = .6). The average use of antifungals in the period was 104.0 defined daily dose/1000 patient-days. CONCLUSION: We found a high mortality rate associated to candidemia events and an increasingly important role of Candida non albicans. New approaches to health care-related infection control and to defining prophylactic and preemptive therapies should change this scenario in the future. PMID- 20736115 TI - Do as I say, not as I do: handwashing compliance of infectious diseases experts during influenza pandemic. PMID- 20736116 TI - Calling it 'multidose' doesn't make it so: inappropriate sharing and contamination of parenteral medication vials. PMID- 20736117 TI - Is gastrointestinal endoscopy a risk factor for Clostridium difficile associated diarrhea? PMID- 20736118 TI - Exposure to blood and body fluid among medical students in Korea. PMID- 20736119 TI - Microbial contamination in surgical instruments: a comment. PMID- 20736120 TI - Distinctive clinical features of bilateral Duane retraction syndrome. AB - PURPOSE: To compare the clinical characteristics of unilateral and bilateral forms of Duane retraction syndrome. METHODS: A retrospective chart review of patients with Duane syndrome over a 10-year span was performed. All participants underwent a complete medical and ophthalmologic examination at the time of diagnosis. Data collected included the following: sex, age at first visit, form (unilateral/bilateral), side, type, ocular duction and version, abnormal head position, best-corrected visual acuity, refractive errors, presence of strabismus, binocular function, and associated congenital anomalies. RESULTS: Of 94 patients identified, 17% were bilaterally affected. Of the bilateral patients, 12% had familial antecedents; 87.5% had the same type in both eyes with 75% bilateral type 1. Patients with bilateral Duane syndrome had significantly different visual acuity (mean, 0.1214 logMar vs 0.0035; p = 0.045), abnormal head position (56.25% vs 89%; p = 0.04), A or V patterns (69% vs 27.6%; p = 0.003), and associated congenital anomalies (50% vs 14%; p = 0.003) than patients with unilateral disease. There was also a suggestion of higher rates of ametropia, global vertical dysfunction, and abnormal stereoacuity in bilateral Duane syndrome that were not statistically significant. CONCLUSIONS: Patients with bilateral Duane syndrome had lower visual acuity, a lower incidence of abnormal head posture, and a higher incidence of A or V patterns and associated congenital anomalies. Bilateral Duane retraction syndrome seems to involve multiple instances of deinnervation and fibrosis, resulting in horizontal and vertical oculomotor deficits and functional impairments. PMID- 20736121 TI - Long-term results of the surgical management of intermittent exotropia. AB - PURPOSE: To examine long-term surgical success rates (>10 years) for patients with intermittent exotropia and the risk factors for failure of surgery in these patients. METHODS: An attempt was made to contact all patients who underwent surgical treatment for intermittent exotropia between the years of 1970 to 1998 with a minimum postoperative follow-up of 10 years. Each patient underwent a detailed sensory and motor examination, including measurements of near and distance stereoacuity, cover testing, and ocular rotations. Patients were classified as achieving an excellent, fair, or poor outcome on the basis of motor and sensory outcomes. Risk factor analysis was performed to evaluate associations with a poor outcome and reoperations. RESULTS: Of 197 patients identified, 50 were reevaluated. When combined motor/sensory criteria for surgical success were used, we found that 38% of patients achieved an excellent outcome, whereas 34% and 28% achieved a fair or poor outcome, respectively. When only the motor criteria were used, we found that 64% had an excellent outcome, whereas the remaining patients achieved either a fair (18%) or a poor (18%) outcome. During the follow-up period, 60% of patients required at least one reoperation. Multivariate risk factor analysis determined that anisometropia (p = 0.03) was associated with a poor outcome, whereas postoperative undercorrection (p = 0.04) and lateral incomitance (p = 0.06) were associated with reoperations. CONCLUSIONS: Long-term surgical results in intermittent exotropia are less encouraging when sensory status is added to the evaluation. Patients with anisometropia, lateral incomitance, and immediate postoperative undercorrection are at increased risk for poor outcomes and to require reoperations. PMID- 20736122 TI - The effect of optical correction on refractive development in children with accommodative esotropia. AB - PURPOSE: To compare the effects of partial or full hyperopic optical correction on refractive development in children with accommodative esotropia. METHODS: Children with accommodative esotropia and hyperopia >3 D were enrolled in this prospective, nonrandomized study. All children underwent an ophthalmologic examination, including refraction, keratometry, and axial length. Subjects were divided into either full- or partial-correction groups according to their tolerance of the full hyperopic correction. Routine follow-up examinations were performed for at least 3 years. The main outcome measure was cycloplegic spherical equivalent at the end of the study period. RESULTS: A total of 120 children were enrolled. The mean cycloplegic spherical equivalent, corneal radius, and axial length were significantly (p < 0.05) different between the first and last visits in both groups. However, when all the measurements were adjusted for the age difference between groups, only the difference in axial length between the first and last visits was statistically significant (p < 0.05). Partial or full optical correction in age-adjusted cohorts with accommodative esotropia did not result in a significant change in refraction, keratometry, or axial length between the first and last visits. CONCLUSIONS: Partial or full optical correction of hyperopia had similar effects on refractive development of the eye in children with accommodative esotropia. Treatment of accommodative esotropia in children older than age 5 did not appear to impair refractive development. PMID- 20736123 TI - Concentration-dependent bupivacaine myotoxicity in rabbit extraocular muscle. AB - PURPOSE: Bupivacaine myotoxicity to the extraocular muscles, from retrobulbar or peribulbar anesthesia, has been reported after cataract surgery and other intraocular procedures. However, there are no data on the concentration dependence of bupivacaine in causing extraocular muscle toxicity. METHODS: Six aged rabbits received different concentrations of bupivacaine (0.75% and lower) in 3 extraocular muscles, namely, superior rectus, inferior rectus, and inferior oblique muscles of each rabbit's eye. The animals were euthanized at 5 days or 1 month after the injections. Hematoxylin and eosin- and Masson trichrome-stained sections were obtained from the involved extraocular muscles after paraffin embedding. RESULTS: Five days after the initial injection, the 0.75% bupivacaine injected extraocular muscles showed extensive myonecrosis and degeneration with early-stage regenerating muscle fibers. However, muscle tissue injected with half concentration bupivacaine (0.38%) showed scattered and significantly fewer areas of mild muscle fiber degeneration with regeneration. There were no areas of muscle tissue degeneration observed in any muscle injected with quarter concentration bupivacaine (0.19%). At 1 month, however, only 0.75% bupivacaine injected muscles displayed areas of regenerated muscle fiber cells with foci of scar formation. There was no visible scar formation in muscles injected with any bupivacaine concentration lower than 0.75%, or with saline, at 1 month after injection. CONCLUSIONS: Extraocular muscle injection with full-strength bupivacaine (0.75%) can cause myonecrosis and degeneration acutely, with regeneration appearing by 5 days, followed by some late-stage scar formation. However, no long-term effects were observed with bupivacaine concentrations of 0.38% or 0.19%. PMID- 20736124 TI - Clinicopathologic review of pediatric enucleations during the last 50 years. AB - PURPOSE: To evaluate diagnoses leading to enucleations in the pediatric age group over time. METHODS: All pathology reports of enucleation specimens at the University of California-San Francisco eye pathology laboratory from children (ages 0 to 18 years) from 1960 to 2008 were reviewed. The main outcome measures were the frequency of pediatric enucleation specimens in each diagnostic category as compared with total pathological laboratory volume over time, and the age and gender distribution of histopathological diagnostic categories over time. RESULTS: Specimens of 746 eyes from 729 pediatric patients were analyzed. Pediatric enucleated eyes constituted 2.7% of all specimens received at the pathology laboratory. The overall frequency of pediatric enucleation specimens did not change over time. Retinoblastoma specimens increased by a factor of 2.9 over time (p < 0.0001). The increase in retinoblastoma was offset by a decrease in nonretinoblastoma enucleations, which decreased by a factor of 3.8 between the 1960s and 2000s (p < 0.0001), driven by a decrease in enucleations caused by trauma (p < 0.0001). Beginning in the 1980s, pediatric enucleations caused by nonrhegmatogenous retinal detachment, nematode and non-nematode endophthalmitis, and congenital glaucoma decreased significantly. Retinoblastoma was the most common diagnosis overall (45%), in girls (60%), and in ages <5 years (78%). Trauma was the second most common diagnosis (32%) and the most common in boys (42%) and in children ages 6-12 (58%) and 13-18 (72%) years. CONCLUSIONS: A decrease in pediatric nonretinoblastoma enucleations was observed over time, possibly attributable to better diagnostic capabilities, surgical techniques, and public health interventions. The increase in retinoblastoma enucleations over time was likely due to the result of institutional referral bias. PMID- 20736125 TI - Relationship between feeding schedules and gastric distress during retinopathy of prematurity screening eye examinations. AB - PURPOSE: To determine whether a relationship exists between the timing of feeding before retinopathy of prematurity (ROP) eye examinations and gastric side effects or distress associated with this examination. METHODS: A prospective, randomized, single-masked study was conducted involving infants in the neonatal intensive care unit who required an ROP eye examination and who received normal or full enteral feeding over a 1 year period. Infants were randomly assigned to 1 of 2 study arms: feeding 1 hour before examination (arm 1) or feeding schedule adjusted to ensure no feeding within 2 hours before examination (arm 2). Physiological data, including blood pressure and pulse rate, before, during and after examination, crying time during the examination, presence of vomiting and gastric aspirates, and gastric aspirates volume 24 hours after the examination, were recorded. RESULTS: A total of 34 infants were enrolled, with 57 separate eye examinations conducted. There was 19% less crying (p = 0.016) in arm 1 versus arm 2. Vomiting was 3-fold less in arm 1 versus arm 2 (4.2% vs 12.5%, p = 0.38). Gastric aspirates was less in arm 1 versus arm 2 (p = 0.18). Diastolic blood pressure was lower and respiratory rate greater during the examination in arm 1 (p < 0.05), whereas pulse rate was greater at the start of the examination in arm 1 (p < 0.05). CONCLUSIONS: Feeding neonatal intensive care unit infants 1 hour before compared with withholding feeding 2 or more hours before ROP examinations may reduce stress during the examination, as measured by percentage crying during the examination, with no increased incidence of vomiting or gastric aspirates. PMID- 20736126 TI - Bilateral persistent fetal vasculature: a study of 11 cases. AB - PURPOSE: To describe the clinical and radiologic features of patients with bilateral persistent fetal vasculature (PFV). METHODS: All patients diagnosed with symmetric, bilateral PFV over a 3.5-year period were included in this representative, observational case series. Only patients with more or less symmetrical disease in both eyes were included. Examination under anesthesia was performed in all but 1 case. B-scan ultrasonography of the eye was performed in all cases. A computed tomographic or magnetic resonance imaging scan was done if the ocular ultrasonography was inconclusive. A systemic workup was performed to rule out associated systemic anomalies. RESULTS: The study group included 11 patients. Of the 22 eyes studied, 20 (91%) showed features of both the anterior and the posterior forms of PFV. Two children tested positive for IgM rubella antibodies. Ten eyes (45.5%) had a horizontal corneal diameter of less than 10 mm. Fifteen eyes (68.2%) had cataract at presentation. Intraocular pressure was >21 mm Hg in 17 eyes (77.3%). CONCLUSIONS: Microcornea and cataract were common findings. Bilateral PFV cases were more commonly associated with combined anterior and posterior PFV. Bilateral PFV, although infrequent, should be considered in the differential diagnosis of bilateral leukocoria. PMID- 20736127 TI - Novel RDH12 sequence variations in Leber congenital amaurosis. AB - Leber congenital amaurosis (LCA) designates a severe congenital retinal dystrophy generally inherited in an autosomal-recessive manner and accounting for 5% of inherited retinopathies. Its main clinical features are severe visual loss, sensory nystagmus, amaurotic pupils, and unrecordable electroretinographic response. LCA has been associated with sequence variations of 14 different genes; in approximately 30% of all cases pathogenic mutations remain to be determined. We report 2 patients with a clinical phenotype of LCA associated with novel mutations of the RDH12 gene. PMID- 20736128 TI - Spontaneous disconnection of glaucoma tube shunt extenders. AB - Glaucoma drainage implants are frequently used in children with severe forms of glaucoma, and tube extenders are sometimes required to compensate for ocular growth or when the intraocular portion of the tube is thought to be too short. We report 2 cases of spontaneous disconnection of a tube extender, occurring 8 months after insertion in one case and 3 years later in the other. In both cases the tube was removed and the patient treated with endoscopic diode laser photocoagulation. PMID- 20736130 TI - Persistent fetal vasculature and spontaneous hyphema in a patient with Klippel Trenaunay-Weber syndrome. PMID- 20736131 TI - Anti-Mullerian hormone serum levels predict response to controlled ovarian hyperstimulation but not embryo quality or pregnancy outcome in oocyte donation. AB - The objective of this retrospective cross-sectional study was to evaluate the value of basal serum anti-Mullerian hormone (AMH) levels as a predictor of ovarian response and pregnancy outcome in a donor egg program. The study showed that AMH was superior to other biomarkers of ovarian reserve in predicting low and high response in young women selected as oocyte donors, but that it was not predictive of embryo morphology or pregnancy outcome in the recipient population. PMID- 20736133 TI - Has the English strategy to reduce health inequalities failed? PMID- 20736132 TI - Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O methyltransferase. AB - OBJECTIVE: To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro. DESIGN: Laboratory study. SETTING: University hospitals. PATIENTS(S): Not applicable. INTERVENTIONS(S): Not applicable. MAIN OUTCOME MEASURE(S): HuLM cells were treated with 1,25 dihydroxyvitamin D3 (vitamin D), and cell proliferation was assayed by the methylthiazolyl tetrazolium technique. proliferating cell nuclear antigen (PCNA), BCL-2, BCL-w, cyclin-dependent kinase (CDK) 1, and catechol-O-methyltransferase (COMT) protein levels were analyzed by Western blotting. COMT mRNA and enzyme activity were assayed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and high-performance liquid chromatography analysis, respectively. The role of COMT was evaluated in stable HuLM cells by silencing COMT expression. RESULT(S): Vitamin D inhibited the growth of HuLM cells by 47+/ 0.03% at 1 MUM and by 38+/-0.02% at 0.1 MUM compared with control cells at 120 hours of treatment. Vitamin D inhibited extracellular signal-regulated kinase activation and down-regulated the expression of BCL-2, BCL-w, CDK1, and PCNA. Western blot, RT-PCR, and enzyme assay of COMT demonstrated inhibitory effects of vitamin D on COMT expression and enzyme activity. Silencing endogenous COMT expression abolished vitamin D-mediated inhibition of HuLM cell proliferation. CONCLUSION(S): Vitamin D inhibits growth of HuLM cells through the down regulation of PCNA, CDK1, and BCL-2 and suppresses COMT expression and activity in HuLM cells. Thus, hypovitaminosis D appears to be a risk factor for uterine fibroids. PMID- 20736134 TI - Paricalcitol, a synthetic vitamin D analog: a candidate for combination therapy with biological agents in rheumatoid arthritis. AB - Biologic agents, especially TNFalpha inhibitors, appear to be very effective in treatment of rheumatoid arthritis (RA). Although the use of biologic agents has greatly improved the therapeutic efficacy in management of RA, biologic therapies for RA treatment have several limitations. These agents fail to achieve complete remission in substantial portion of RA patients. Also certain adverse events have been observed, including serious bacterial infections and reactivation of latent tuberculosis. Previous reports demonstrated that TNFalpha inhibitors are more efficacious in combination with other drugs such as methotrexate. In this report, we suggest that paricalcitol, a synthetic vitamin D analog is another candidate molecule for combination therapy with TNFalpha inhibitors in RA. PMID- 20736135 TI - Adsorption of monocomponent enzymes in enzyme mixture analyzed quantitatively during hydrolysis of lignocellulose substrates. AB - The adsorption of purified Trichoderma reesei cellulases (TrCel7A, TrCel6A and TrCel5A) and xylanase TrXyn11 and Aspergillus niger beta-glucosidase AnCel3A was studied in enzyme mixture during hydrolysis of two pretreated lignocellulosic materials, steam pretreated and catalytically delignified spruce, along with microcrystalline cellulose (Avicel). The enzyme mixture was compiled to resemble the composition of commercial cellulase preparations. The hydrolysis was carried out at 35 degrees C to mimic the temperature of the simultaneous saccharification and fermentation (SSF). Enzyme adsorption was followed by analyzing the activity and the protein amount of the individual free enzymes in the hydrolysis supernatant. Most enzymes adsorbed quickly at early stages of the hydrolysis and remained bound throughout the hydrolysis, although the conversion reached was fairly high. Only with the catalytically oxidized spruce samples, the bound enzymes started to be released as the hydrolysis degree reached 80%. The results based on enzyme activities and protein assay were in good accordance. PMID- 20736137 TI - Incorporating the loss function into discriminative clustering of structured outputs. AB - Clustering using the Hilbert Schmidt independence criterion (CLUHSIC) is a recent clustering algorithm that maximizes the dependence between cluster labels and data observations according to the Hilbert Schmidt independence criterion (HSIC). It is unique in that structure information on the cluster outputs can be easily utilized in the clustering process. However, while the choice of the loss function is known to be very important in supervised learning with structured outputs, we will show in this paper that CLUHSIC is implicitly using the often inappropriate zero-one loss. We propose an extension called CLUHSICAL (which stands for "Clustering using HSIC and loss") which explicitly considers both the output dependency and loss function. Its optimization problem has the same form as CLUHSIC, except that its partition matrix is constructed in a different manner. Experimental results on a number of datasets with structured outputs show that CLUHSICAL often outperforms CLUHSIC in terms of both structured loss and clustering accuracy. PMID- 20736136 TI - Does chronic pain alter the normal interaction between cardiovascular and pain regulatory systems? Pain modulation in the hypertensive-monoarthritic rat. AB - Hypertension-associated hypoalgesia is widely recognized in acute pain conditions. In chronic pain states, however, the relationship between blood pressure and pain sensitivity is still ill-defined, with different authors reporting negative, positive, or even no relationship at all. This work addresses this issue, using complete Freund's adjuvant (CFA)-induced monoarthritis in different models of hypertension: Spontaneous (spontaneously hypertensive rats, SHR), induced by infusion of angiotensin II (ANG) or 1,3-dipropyl-8 sulfophenylxanthine (DPSPX, an adenosine receptors' antagonist), and renal artery ligation (RAL). Nociceptive responses associated with monoarthritis were evaluated by different behavioral tests (von Frey, ankle-bend and CatWalk) and by quantification of Fos expression at the dorsal horn upon noxious stimulation. In all hypertension models, higher von Frey thresholds and lower Fos expression were detected in hypertensive rats with chronic inflammatory pain, as compared to normotensive monoarthritic rats. In SHR and DPSPX, but not ANG or RAL models, hypertensive animals displayed lower inflammation than normotensives. Ankle-bend and CatWalk results indicated lower pain sensitivity in hypertensive rats only in SHR and DPSPX models. The present study shows the importance of using multiple models of hypertension, and evaluating pain responses by various methods, to better understand the complexity of the interactions between pain and cardiovascular regulatory systems. PERSPECTIVE: This study used different models of hypertension to investigate whether chronic pain alters the normal integration of cardiovascular and pain regulatory systems. A complete understanding of the mechanisms underlying the complex interactions between these systems may disclose future therapeutic approaches to treat hypertension/chronic pain comorbidity states. PMID- 20736138 TI - Equivalences between neural-autoregressive time series models and fuzzy systems. AB - Soft computing (SC) emerged as an integrating framework for a number of techniques that could complement one another quite well (artificial neural networks, fuzzy systems, evolutionary algorithms, probabilistic reasoning). Since its inception, a distinctive goal has been to dig out the deep relationships among their components. This paper considers two wide families of SC models. On the one hand, the regime-switching autoregressive paradigm is a recent development in statistical time series modeling, and it includes a set of models closely related to artificial neural networks. On the other hand, we consider fuzzy rule-based systems in the framework of time series analysis. This paper discloses original results establishing functional equivalences between models of these two classes, and hence opens the door to a productive line of research where results and techniques from one area can be applied in the other. As a consequence of the equivalences presented in this paper, we prove the asymptotic stationarity of a class of fuzzy rule-based systems. Simulations based on information criteria show the importance of the selection of the proper membership function. PMID- 20736139 TI - Contextual object localization with multiple kernel nearest neighbor. AB - Recently, many object localization models have shown that incorporating contextual cues can greatly improve accuracy over using appearance features alone. Therefore, many of these models have explored different types of contextual sources, but only considering one level of contextual interaction at the time. Thus, what context could truly contribute to object localization, through integrating cues from all levels, simultaneously, remains an open question. Moreover, the relative importance of the different contextual levels and appearance features across different object classes remains to be explored. Here we introduce a novel framework for multiple class object localization that incorporates different levels of contextual interactions. We study contextual interactions at the pixel, region and object level based upon three different sources of context: semantic, boundary support, and contextual neighborhoods. Our framework learns a single similarity metric from multiple kernels, combining pixel and region interactions with appearance features, and then applies a conditional random field to incorporate object level interactions. To effectively integrate different types of feature descriptions, we extend the large margin nearest neighbor to a novel algorithm that supports multiple kernels. We perform experiments on three challenging image databases: Graz-02, MSRC and PASCAL VOC 2007. Experimental results show that our model outperforms current state-of-the art contextual frameworks and reveals individual contributions for each contextual interaction level as well as appearance features, indicating their relative importance for object localization. PMID- 20736140 TI - Bathing epilepsy: a video case of an autonomic seizure. AB - A six-year-old Moroccan boy experienced nausea, paleness and oral automatisms after almost every shower. A clinical diagnosis of bathing epilepsy was assumed. A video-EEG recording was taken during and after a shower and confirmed ictal high voltage repetitive slow waves over the left temporal lobe. Bathing epilepsy or water immersion epilepsy is a rare form of reflex epilepsy often presenting with autonomic seizures. The onset is usually in the first year of life and the evolution is benign. [Published with video sequences]. PMID- 20736141 TI - Assessment of magnesium status for diagnosis and therapy. AB - Magnesium is an essential element needed for health. Even though only 1% of the total body magnesium is present in blood, the serum magnesium concentration (SMC) is the predominant test used by medicine to assess magnesium status in patients. The traditional method to establish a reference interval for the SMC is flawed by the large number of "normal" individuals who have a subtle chronic negative magnesium balance due to a significant decrease in magnesium intake over the past century. Evidence-based medicine should be used to establish the appropriate lower limit of the reference interval for health and I recommend 0.85 mmol/L based on current literature. The decrease in magnesium in the diet has led to chronic latent magnesium deficiency in a large number of people since their SMC is still within the reference interval due to primarily the bone magnesium supplementing the SMC. These individuals need adjustment of their diet or magnesium supplementation to achieve a normal magnesium status for health. PMID- 20736142 TI - Oral magnesium supplementation improves vascular function in elderly diabetic patients. AB - Magnesium (Mg) ions directly influence vascular tone and responsiveness and are cofactors for acetylcholine-induced endothelium-dependent relaxation. Alterations in extracellular Mg are able to modify the formation and release of nitric oxide (NO), altering arterial smooth muscle tone. Previous in vivo studies in humans have shown that parenteral or oral Mg supplementation increase endothelial dependent vasodilation. The aim of the present study was to evaluate the effects of Mg oral supplementation on endothelial function in elderly diabetic and hypertensive subjects. Sixty elderly (>= 65 years) diabetic patients were recruited (mean age: 71.1 +/- 6.1 years; M/F: 35/25). Endothelial function, evaluated by non-invasive flow-mediated dilatation of the brachial artery, as well as anthropometric and laboratory data, including ionized Mg (Mg-ion), were measured in all patients before and after one-month. Thirty patients underwent oral Mg supplementation with 4.5 g/day of Mg pidolate (368 mg/day of Mg ion), while the rest were used as a control group. The usual management of diabetes and hypertension was not changed during the month of study participation for all the patients. In the group of patients that underwent Mg supplementation, Mg-ion concentration significantly increased from 0.42 +/- 0.05 mmol/L to 0.49 +/- 0.06 mmol/L; p < 0.05. Mg intervention resulted in a significant improvement of the post-ischemic endothelial-dependent flow-mediated dilation (from 3.3 +/- 3.6% to 8.4 +/- 3.9%; p < 0.05). No significant differences were found, either in ion-Mg or endothelial function, in the control group. In conclusion, the present study suggests that oral Mg improves endothelial function in diabetic elderly subjects. PMID- 20736143 TI - Characterization of serum interleukin-15 in healthy volunteers and patients with early arthritis to assess its potential use as a biomarker. AB - As interleukin-15 (IL-15) has been implicated in the pathophysiology of rheumatoid arthritis, we analysed the serum IL-15 (sIL-15) levels in healthy subjects and patients with early arthritis to establish a cut-off point that might serve to define elevated sIL-15. This is an initial step to determine whether sIL-15 has the potential for use as a biomarker for patients with early arthritis. The IL-15 concentration was measured in serum obtained from 161 healthy controls and from 174 patients with early arthritis, and the relationship between the expression of the two IL-15 mRNA variants and the sIL-15 levels was also assessed. In healthy controls, the median sIL-15 value was 0.83 [interquartile range (IQR) 0-8.68] pg/mL; there was no significant difference in the sIL-15 values according to gender [median level in males was 1.99 (IQR: 0 8.68) pg/mL and in females 0.50 (0-8.25) pg/mL: p = 0.821]. Moreover, sIL-15 levels did not correlate with age (r = 0.033, p = 0.685), and they did not display a clear circadian rhythm in healthy donors, with the median values for IL 15 close to zero at each time tested. In the light of these findings, we considered that sIL-15 was elevated if its concentration was above 20 pg/mL, since this cut-off point corresponded to the 90th percentile for this healthy population. We found that 30% of the patients with early arthritis had sIL-15 values > 20 pg/mL. The levels of sIL-15 did not correlate with disease duration in early arthritis patients, nor did they fluctuate with changes in disease activity over the follow-up period. In addition, the high level of sIL15 in patients was not associated with alterations in the alternative splicing of the IL-15 mRNA, favouring the variant that produces the protein with a long signal peptide for secretion. Serum IL-15 levels were increased in a subpopulation of patients with early arthritis, indicating that this measure may serve as a biomarker for this condition. Further studies will be necessary to determine whether the clinical evolution or response to treatment of patients with high sIL 15 levels differs. PMID- 20736144 TI - Superimposed segmental dermatomyositis: an emerging new paradigm. PMID- 20736149 TI - Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study. AB - BACKGROUND: The MERIT study evaluated maraviroc versus efavirenz, both with zidovudine/lamivudine, in treatment-naive patients with CCR5-tropic (R5) HIV-1. Post hoc analyses previously assessed week 48 outcomes in patients rescreened with R5 virus by a more sensitive tropism assay. METHODS: Week 96 efficacy (post hoc, n = 614) and safety (n = 721) were assessed. RESULTS: Proportions of subjects <50 copies/mL (58.8% maraviroc, 62.7% efavirenz) and time to loss of virologic response (TLOVR) responders (<50 copies/mL: 60.5% vs 60.7%) were similar. Maraviroc recipients had greater CD4 increases (+ 212 vs + 171 cells/mm(3)) and fewer adverse event discontinuations (6.1% vs 15.5%), malignancies, and category C events. CONCLUSION: Week 96 data confirm week 48 observations in MERIT. PMID- 20736150 TI - Comparative cost-efficacy analysis of darunavir/ritonavir and other ritonavir boosted protease inhibitors for first-line treatment of HIV-1 infection in the United States. AB - PURPOSE: A comprehensive study comparing the costs and efficacies of darunavir/ritonavir 800/100 mg qd and the other ritonavir-boosted (/r) protease inhibitors (PIs) recommended for treatment-naive individuals with HIV-1 infection would help health care decision makers identify the value of each boosted PI. METHODS: A cost-efficacy model was developed to compare the five recommended boosted PIs, each used with a tenofovir-based nucleotide/nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by virologic response (ie, HIV-1 ribonucleic acid < 50 copies/mL) at 48 weeks, based on a systematic review and meta-analysis of recent clinical trials. One-year antiretroviral therapy costs and 48-week efficacy values were used to generate the efficiency frontier and cost-efficacy ratios. RESULTS: Darunavir/r was the most efficacious boosted PI, with an incremental cost-efficacy ratio of $27,390 per additional individual with virologic response, compared with fosamprenavir/r. All other regimens were dominated. Darunavir/r combination therapy also had one of the lowest average costs ($26,287) per individual with virologic response, resulting in a maximal number of individuals successfully treated within a fixed budget. The model results were robust in variability and sensitivity analyses. CONCLUSION: Darunavir/r 800/100 mg qd combination therapy represents a cost efficacious option for treatment-naive individuals with HIV-1 infection in the United States. PMID- 20736151 TI - Impact of baseline antiretroviral resistance status on efficacy outcomes among patients receiving maraviroc plus optimized background therapy in the MOTIVATE 1 and 2 trials. AB - PURPOSE: The MOTIVATE studies assessed maraviroc with optimized background therapy (OBT) in treatment-experienced patients with R5 HIV-1. This post hoc analysis compared outcomes between patients with and without HIV-1 resistance to epsilon3 classes of antiretrovirals at screening (triple-class-resistant [TCR] versus not-TCR [nTCR]). METHODS: Week 48 changes (N = 635) in HIV-1 RNA and CD4+ cells were compared between TCR and nTCR groups receiving twice-daily maraviroc+OBT or placebo+OBT. RESULTS: HIV-1 RNA change from baseline on maraviroc was significantly greater in the nTCR group (-2.05 vs -1.74 log(10) copies/mL; 95% CI difference 0.05-0.58 log(10)) though proportions <400 or <50 copies/mL were not. Week 48 CD4 increases were significantly greater in the nTCR group overall (mean +150 vs +110 cells/mm(3); 95% CI difference 18-62 cells/mm(3)) and in those with <50 RNA copies/mL (nTCR +192 vs +126 cells/mm(3); 95% CI difference, 19-93 cells/mm(3)) or receiving > or = 2 active OBT agents (weighted score; nTCR +184 vs +125 cells/mm3; 95% CI difference 8-110 cells/mm(3)). CONCLUSIONS: Virologic suppression on maraviroc was greater in the nTCR than the TCR group, though proportions <50 or 400 copies/mL were not significantly different. Optimal CD4 increases on maraviroc appeared to accrue from initiation before development of TCR virus. PMID- 20736152 TI - Neuropsychiatric adverse events with ritonavir-boosted darunavir monotherapy in HIV-infected individuals: a randomised prospective study. AB - BACKGROUND: Protease inhibitor monotherapy is an attractive treatment option for HIV-infected subjects. Data assessing neuropsychiatric events with the use of protease inhibitor monotherapy are sparse. METHODS: Clinician- and patient reported neuropsychiatric events were assessed over 48 weeks in HIV-infected subjects on stable antiretroviral therapy, with a plasma HIV RNA <50 copies/mL, randomised to commence on a one to one basis darunavir/ritonavir (800/100 mg once daily) alone (DRVrMono) or with nucleoside analogues (DRVrNRTI). Patient-reported events were assessed by the Functional Assessment of HIV Infection (FAHI) questionnaire and included an assessment of cognitive function. RESULTS: Of 256 subjects enrolled, clinician-reported grade 1-4 adverse events of the nervous system (all cause) were seen in 16% of patients in each treatment arm. FAHI questionnaires were completed by 206 subjects at 48 weeks. No differences in cognitive functioning or other FAHI scores were observed between study treatment groups: Cognitive Functioning score [mean (SD)] 8.9 (2.4) and 9.0 (2.6) in DRVrMono arm and 8.8 (2.6) and 8.9 (2.8) in DRVrNRTI arm at baseline and week 48, respectively (P value for difference = .76). CONCLUSION: In this exploratory analysis, no differences in the evolution of neuropsychiatric adverse events over 48 weeks are observed in HIV-infected subjects randomised to switch antiretroviral therapy to darunavir/ritonavir with or without nucleoside reverse transcriptase inhibitors. PMID- 20736154 TI - Bylines. Reforming the way we provide care. PMID- 20736153 TI - Simplified maintenance therapy with abacavir/lamivudine and atazanavir after discontinuation of ritonavir. PMID- 20736156 TI - Medical home 101: the pharmacist's role in this growing patient-centered care model. AB - The medical-home model is an innovative way to provide patient-centered care using a team approach. For senior care pharmacists who thrive on teamwork and embrace culture change, this can be a rewarding practice model. The challenge is finding organizations and physicians employing the medical-home model who understand the value of having a pharmacist on this team. However, once pharmacists get their foot in the door of the medical home, they can have a significant impact. PMID- 20736157 TI - Coping successfully with aging. AB - Aging is associated with physical decline, often accompanied by pathology and disability that can cause unhappiness and dissatisfaction. Despite this, many elders report a high level of satisfaction. This article discusses the anxiety associated with aging that some people experience, highlights research findings and models of aging, and pays particular attention to how elders compensate and cope with loss. Long-term care practitioners can help residents deflect negative stereotypes and improve their own attitudes about aging. PMID- 20736158 TI - Drug utilization and cost for erythropoiesis-stimulating agents in a long-term care resident population with chronic kidney disease. AB - OBJECTIVE: To compare drug-utilization patterns and costs in patients with chronic kidney disease (CKD), not on dialysis, yet receiving epoetin alfa (EPO) or darbepoetin alfa (DARB) in a long-term care setting. DESIGN: A retrospective analysis of pharmacy dispensing from January 2007 through March 2009, was conducted using the AnalytiCareSM LTC database. SETTING: Long-term care. PATIENTS, PARTICIPANTS: Patients>or=18 years of age, with >or=1 EPO or DARB dose dispensed, were included. Patients dispensed both agents, diagnosed with cancer, receiving chemotherapy, radiation therapy, or renal dialysis, were excluded. MAIN OUTCOME MEASURES: Mean cumulative erythropoiesis-stimulating agent (ESA) dose was used to calculate drug cost (using April 2009 wholesale acquisition cost) and dose ratio (Units EPO:mcg DARB). Results were also stratified by payer types. RESULTS: A total of 2,259 patients were identified (EPO 1,640; DARB 619). EPO patients were slightly older (76.1 vs. 74.8 years of age, P=0.021), with similar proportion of women, compared with DARB patients. Mean (SD) cumulative dose was 98,420 (122,381) Units for EPO and 360 (428) mcg for DARB, resulting in a dose ratio of 273:1 (Units EPO:mcg DARB). The corresponding drug cost was 42% higher with DARB than with EPO ($1,734 vs. $1,217, P<0.001). Stratified analysis by payer types yielded similar results (dose ratios: 299:1 and 270:1 [Units EPO:mcg DARB]); cost premiums: 30% and 44% for Medicare Part A/Facility and Medicare Part D/Medicaid groups, respectively. CONCLUSIONS: This study of long-term care CKD patients receiving ESAs reported 42% higher drug cost with DARB compared with EPO and a dose ratio of 273:1. PMID- 20736159 TI - Medication education and consultation at a senior dining program for independently living seniors. AB - OBJECTIVE: To determine if pharmacist involvement within a senior dining program benefits diners by addressing their medication-related questions, using educational sessions, and providing individual consultations. SETTING: Catholic Charities Senior Dining sites in central Minnesota. PRACTICE DESCRIPTION: Pharmacists went to three senior dining sites, providing educational sessions and individual consultations to independently living senior diners. PRACTICE INNOVATION: Pharmacists developed a program, in a nontraditional setting, that used educational sessions and individual consultations to assist seniors with their medication-related questions. MAIN OUTCOME MEASUREMENTS: The number of diner questions, significant issues raised, issues addressed, and level of diner satisfaction. RESULTS: Pharmacists made 36 visits from January to December 2009. During those visits they presented educational talks to 3,089 diners, and 12.4% of all diners spoke individually with pharmacists. Pharmacists addressed 581 questions or concerns from 384 diners. Significant issues were noted in 25.8% of individual consultations (144 questions). The most common significant issues included: adverse drug reactions (59), indications without treatment (27), and drug interactions (23). Nonopioid analgesics, antilipemics, and antihypertensive medications were most commonly involved in significant issues. Satisfaction surveys were strongly positive, with 97% indicating pharmacists had addressed their medication-related concern; only 3% did not reply. Almost half (42.7%) of satisfaction surveys indicated the diner would change something as a result of meeting with the pharmacist. CONCLUSION: Pharmacist availability in a nontraditional setting can assist seniors with addressing potentially significant medication-related issues. Independently living seniors will seek out information from a pharmacist in a convenient setting. PMID- 20736160 TI - New hierarchical phosphorylation pathway of the translational repressor eIF4E binding protein 1 (4E-BP1) in ischemia-reperfusion stress. AB - Eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) is a translational repressor that is characterized by its capacity to bind specifically to eIF4E and inhibit its interaction with eIF4G. Phosphorylation of 4E-BP1 regulates eIF4E availability, and therefore, cap-dependent translation, in cell stress. This study reports a physiological study of 4E-BP1 regulation by phosphorylation using control conditions and a stress-induced translational repression condition, ischemia-reperfusion (IR) stress, in brain tissue. In control conditions, 4E-BP1 was found in four phosphorylation states that were detected by two-dimensional gel electrophoresis and Western blotting, which corresponded to Thr(69)-phosphorylated alone, Thr(69)- and Thr(36)/Thr(45) phosphorylated, all these plus Ser(64) phosphorylation, and dephosphorylation of the sites analyzed. In control or IR conditions, no Thr(36)/Thr(45) phosphorylation alone was detected without Thr(69) phosphorylation, and neither was Ser(64) phosphorylation without Thr(36)/Thr(45)/Thr(69) phosphorylation detected. Ischemic stress induced 4E-BP1 dephosphorylation at Thr(69), Thr(36)/Thr(45), and Ser(64) residues, with 4E-BP1 remaining phosphorylated at Thr(69) alone or dephosphorylated. In the subsequent reperfusion, 4E-BP1 phosphorylation was induced at Thr(36)/Thr(45) and Ser(64), in addition to Thr(69). Changes in 4E-BP1 phosphorylation after IR were according to those found for Akt and mammalian target of rapamycin (mTOR) kinases. These results demonstrate a new hierarchical phosphorylation for 4E-BP1 regulation in which Thr(69) is phosphorylated first followed by Thr(36)/Thr(45) phosphorylation, and Ser(64) is phosphorylated last. Thr(69) phosphorylation alone allows binding to eIF4E, and subsequent Thr(36)/Thr(45) phosphorylation was sufficient to dissociate 4E-BP1 from eIF4E, which led to eIF4E-4G interaction. These data help to elucidate the physiological role of 4E-BP1 phosphorylation in controlling protein synthesis. PMID- 20736161 TI - Functional differences of invariant and highly conserved residues in the extracellular domain of the glycoprotein hormone receptors. AB - Multiple interactions exist between human follicle-stimulating hormone (FSH) and the N-terminal hormone-binding fragment of the human FSH receptor (FSHR) extracellular domain (ECD). Binding of the other human glycoprotein hormones to their cognate human receptors (luteinizing hormone receptor (LHR) and thyroid stimulating hormone receptor (TSHR)) was expected to be similar. This study focuses on amino acid residues in beta-strands 2 (Lys(74)), 4 (Tyr(124), Asn(129), and Thr(130)), and 5 (Asp(150) and Asp(153)) of the FSHR ECD identified in the human FSH.FSHR ECD crystal structure as contact sites with the common glycoprotein hormone alpha-subunit, and on noncontact residues in beta-strands 2 (Ser(78)) and 8 (Asp(224) and Ser(226)) as controls. These nine residues are either invariant or highly conserved in LHR and TSHR. Mutagenesis and functional characterization of these residues in all three human receptors allowed an assessment of their contribution to binding and receptor activation. Surprisingly, the six reported alpha-subunit contact residues of the FSHR ECD could be replaced without significant loss of FSH binding, while cAMP signaling potency was diminished significantly with several replacements. Comparative studies of the homologous residues in LHR and TSHR revealed both similarities and differences. The results for FSH/FSHR were analyzed on the basis of the crystal structure of the FSH.FSHR ECD complex, and comparative modeling was used to generate structures for domains, proteins, and complexes for which no structures were available. Although structural information of hormone-receptor interaction allowed the identification of hormone-receptor contact sites, functional analysis of each contact site was necessary to assess its contribution to hormone binding and receptor activation. PMID- 20736162 TI - Transamination is required for {alpha}-ketoisocaproate but not leucine to stimulate insulin secretion. AB - It remains unclear how alpha-ketoisocaproate (KIC) and leucine are metabolized to stimulate insulin secretion. Mitochondrial BCATm (branched-chain aminotransferase) catalyzes reversible transamination of leucine and alpha ketoglutarate to KIC and glutamate, the first step of leucine catabolism. We investigated the biochemical mechanisms of KIC and leucine-stimulated insulin secretion (KICSIS and LSIS, respectively) using BCATm(-/-) mice. In static incubation, BCATm disruption abolished insulin secretion by KIC, D,L-alpha-keto beta-methylvalerate, and alpha-ketocaproate without altering stimulation by glucose, leucine, or alpha-ketoglutarate. Similarly, during pancreas perfusions in BCATm(-/-) mice, glucose and arginine stimulated insulin release, whereas KICSIS was largely abolished. During islet perifusions, KIC and 2 mM glutamine caused robust dose-dependent insulin secretion in BCATm(+/+) not BCATm(-/-) islets, whereas LSIS was unaffected. Consistently, in contrast to BCATm(+/+) islets, the increases of the ATP concentration and NADPH/NADP(+) ratio in response to KIC were largely blunted in BCATm(-/-) islets. Compared with nontreated islets, the combination of KIC/glutamine (10/2 mM) did not influence alpha-ketoglutarate concentrations but caused 120 and 33% increases in malate in BCATm(+/+) and BCATm(-/-) islets, respectively. Although leucine oxidation and KIC transamination were blocked in BCATm(-/-) islets, KIC oxidation was unaltered. These data indicate that KICSIS requires transamination of KIC and glutamate to leucine and alpha-ketoglutarate, respectively. LSIS does not require leucine catabolism and may be through leucine activation of glutamate dehydrogenase. Thus, KICSIS and LSIS occur by enhancing the metabolism of glutamine/glutamate to alpha-ketoglutarate, which, in turn, is metabolized to produce the intracellular signals such as ATP and NADPH for insulin secretion. PMID- 20736163 TI - A novel cytoplasmic adaptor for retinoic acid receptor (RAR) and thyroid receptor functions as a Derepressor of RAR in the absence of retinoic acid. AB - In most mammalian cells, the retinoic acid receptor (RAR) is nuclear rather than cytoplasmic, regardless of its cognate ligand, retinoic acid (RA). In testis Sertoli cells, however, RAR is retained in the cytoplasm and moves to the nucleus only when RA is supplied. This led us to identify a protein that regulates the translocation of RAR. From yeast two-hybrid screening, we identified a novel RAR interacting protein called CART1 (cytoplasmic adaptor for RAR and TR). Systematic interaction assays using deletion mutants showed that the C-terminal CoRNR box of CART1 was responsible for the interaction with the NCoR binding region of RAR and TR. Such interaction was impaired in the presence of ligand RA, as further determined by GST pulldown assays in vitro and immunoprecipitation assays in vivo. Fluorescence microscopy showed that unliganded RAR was captured by CART1 in the cytoplasm, whereas liganded RAR was liberated and moved to the nucleus. Overexpression of CART1 blocked the transcriptional repressing activity of unliganded apoRAR, mediated by corepressor NCoR in the nucleus. CART1 siRNA treatment in a mouse Sertoli cell line, TM4, allowed RAR to move to the nucleus and blocked the derepressing function of CART1, suggesting that CART1 might be a cytoplasmic, testis-specific derepressor of RAR. PMID- 20736164 TI - Regulation of epidermal growth factor receptor ubiquitination and trafficking by the USP8.STAM complex. AB - Reversible ubiquitination of activated receptor complexes signals their sorting between recycling and degradation and thereby dictates receptor fate. The deubiquitinating enzyme ubiquitin-specific protease 8 (USP8/UBPy) has been previously implicated in the regulation of the epidermal growth factor receptor (EGFR); however, the molecular mechanisms governing its recruitment and activity in this context remain unclear. Herein, we investigate the role of USP8 in countering ligand-induced ubiquitination and down-regulation of EGFR and characterize a subset of protein-protein interaction determinants critical for this function. USP8 depletion accelerates receptor turnover, whereas loss of hepatocyte growth factor-regulated substrate (Hrs) rescues this phenotype, indicating that USP8 protects EGFR from degradation via an Hrs-dependent pathway. Catalytic inactivation of USP8 incurs EGFR hyperubiquitination and promotes receptor localization to endosomes marked by high ubiquitin content. These phenotypes require the central region of USP8, containing three extended Arg-X-X Lys (RXXK) motifs that specify direct low affinity interactions with the SH3 domain(s) of ESCRT-0 proteins, STAM1/2. The USP8.STAM complex critically impinges on receptor ubiquitination status and modulates ubiquitin dynamics on EGFR positive endosomes. Consequently, USP8-mediated deubiquitination slows progression of EGFR past the early-to-recycling endosome circuit in a manner dependent upon the RXXK motifs. Collectively, these findings demonstrate a role for the USP8.STAM complex as a protective mechanism regulating early endosomal sorting of EGFR between pathways destined for lysosomal degradation and recycling. PMID- 20736165 TI - NHE3 activity is dependent on direct phosphoinositide binding at the N terminus of its intracellular cytosolic region. AB - The small intestinal BB Na(+)/H(+) antiporter NHE3 accounts for the majority of intestinal sodium and water absorption. It is highly regulated with both postprandial inhibition and stimulation sequentially occurring. Phosphatidylinositide 4,5-bisphosphate (PI(4,5)P(2)) and phosphatidylinositide 3,4,5-trisphosphate (PI(3,4,5)P(3)) binding is involved with regulation of multiple transporters. We tested the hypothesis that phosphoinositides bind NHE3 under basal conditions and are necessary for its acute regulation. His(6) proteins were made from the NHE3 C-terminal region divided into four parts as follows: F1 (amino acids 475-589), F2 (amino acids 590-667), F3 (amino acids 668 747), and F4 (amino acids 748-832) and purified by a nickel column. Mutations were made in the F1 region of NHE3 and cloned in pet30a and pcDNA3.1 vectors. PI(4,5)P(2) and PI(3,4,5)P(3) bound only to the NHE3 F1 fusion protein (amino acids 475-589) on liposomal pulldown assays. Mutations were made in the putative lipid binding region of the F1 domain and studied for alterations in lipid binding and Na(+)/H(+) exchange as follows: Y501A/R503A/K505A; F509A/R511A/R512A; R511L/R512L; R520/FR527F; and R551L/R552L. Our results indicate the following. 1) The F1 domain of the NHE3 C terminus has phosphoinositide binding regions. 2) Mutations of these regions alter PI(4,5)P(2) and PI(3,4,5)P(3) binding and basal NHE3 activity. 3) The magnitude of serum stimulation of NHE3 correlates with PI(4,5)P(2) and PI(3,4,5)P(3) binding of NHE3. 4) Wortmannin inhibition of PI3K did not correlate with PI(4,5)P(2) or PI(3,4,5)P(3) binding of NHE3. Two functionally distinct phosphoinositide binding regions (Tyr(501)-Arg(512) and Arg(520)-Arg(552)) are present in the NHE3 F1 domain; both regions are important for serum stimulation, but they display differences in phosphoinositide binding, and the latter but not the former alters NHE3 surface expression. PMID- 20736166 TI - Blocking interferon {beta} stimulates vascular smooth muscle cell proliferation and arteriogenesis. AB - Increased interferon (IFN)-beta signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFNbeta on collateral artery growth in mice have been reported. The mechanisms of IFNbeta-induced inhibition of arteriogenesis are unknown. In stimulated monocytes from patients with chronic total coronary artery occlusion and decreased arteriogenic response, whole genome expression analysis showed increased expression of IFNbeta-regulated genes. Immunohistochemically, the IFNbeta receptor was localized in the vascular media of murine collateral arteries. Treatment of vascular smooth muscle cells (VSMC) with IFNbeta resulted in an attenuated proliferation, cell-cycle arrest, and increased expression of cyclin-dependent kinase inhibitor-1A (p21). The growth inhibitory effect of IFNbeta was attenuated by inhibition of p21 by RNA interference. IFNbeta-treated THP1 monocytes showed enhanced apoptosis. Subsequently, we tested if collateral artery growth can be stimulated by inhibition of IFNbeta-signaling. RNA interference of the IFNbeta receptor-1 (IFNAR1) increased VSMC proliferation, cell cycle progression, and reduced p21 gene expression. IFNbeta signaling and FAS and TRAIL expression were attenuated in monocytes from IFNAR1(-/-) mice, indicating reduced monocyte apoptosis. Hindlimb perfusion restoration 1 week after femoral artery ligation was improved in IFNAR1(-/-) mice compared with wild-type mice as assessed by infusion of fluorescent microspheres. These results demonstrate that IFNbeta inhibits collateral artery growth and VSMC proliferation through p21-dependent cell cycle arrest and induction of monocyte apoptosis. Inhibition of IFNbeta stimulates VSMC proliferation and collateral artery growth. PMID- 20736167 TI - Direct association of Sprouty-related protein with an EVH1 domain (SPRED) 1 or SPRED2 with DYRK1A modifies substrate/kinase interactions. AB - The mammalian SPRED (Sprouty-related protein with an EVH1 domain) proteins include a family of three members, SPRED1-3. Currently, little is known about their biochemistry. The best described, SPRED1, has been shown to inhibit the Ras/ERK pathway downstream of Ras. All three SPREDs have a cysteine-rich domain (CRD) that has high homology to the CRD of the Sprouty family of proteins, several of which are also Ras/ERK inhibitors. In the belief that binding partners would clarify SPRED function, we assayed for their associated proteins. Here, we describe the direct and endogenous interaction of SPRED1 and SPRED2 with the novel kinase, DYRK1A. DYRK1A has become the subject of recent research focus as it plays a central role in Caenorhabditis elegans oocyte maturation and egg activation, and there is strong evidence that it could be involved in Down syndrome in humans. Both SPRED1 and SPRED2 inhibit the ability of DYRK1A to phosphorylate its substrates, Tau and STAT3. This inhibition occurs via an interaction of the CRD of the SPREDs with the kinase domain of DYRK1A. DYRK1A substrates must bind to the kinase to enable phosphorylation, and SPRED proteins compete for the same binding site to modify this process. Our accumulated evidence indicates that the SPRED proteins are likely physiological modifiers of DYRK1A. PMID- 20736168 TI - Overoxidation of 2-Cys peroxiredoxin in prokaryotes: cyanobacterial 2-Cys peroxiredoxins sensitive to oxidative stress. AB - In eukaryotic organisms, hydrogen peroxide has a dual effect; it is potentially toxic for the cell but also has an important signaling activity. According to the previously proposed floodgate hypothesis, the signaling activity of hydrogen peroxide in eukaryotes requires a transient increase in its concentration, which is due to the inactivation by overoxidation of 2-Cys peroxiredoxin (2-Cys Prx). Sensitivity to overoxidation depends on the structural GGLG and YF motifs present in eukaryotic 2-Cys Prxs and is believed to be absent from prokaryotic enzymes, thus representing a paradoxical gain of function exclusive to eukaryotic organisms. Here we show that 2-Cys Prxs from several prokaryotic organisms, including cyanobacteria, contain the GG(L/V/I)G and YF motifs characteristic of sensitive enzymes. In search of the existence of overoxidation-sensitive 2-Cys Prxs in prokaryotes, we have analyzed the sensitivity to overoxidation of 2-Cys Prxs from two cyanobacterial strains, Anabaena sp. PCC7120 and Synechocystis sp. PCC6803. In vitro analysis of wild type and mutant variants of the Anabaena 2-Cys Prx showed that this enzyme is overoxidized at the peroxidatic cysteine residue, thus constituting an exception among prokaryotes. Moreover, the 2-Cys Prx from Anabaena is readily and reversibly overoxidized in vivo in response to high light and hydrogen peroxide, showing higher sensitivity to overoxidation than the Synechocystis enzyme. These cyanobacterial strains have different strategies to cope with hydrogen peroxide. While Synechocystis has low content of less sensitive 2-Cys Prx and high catalase activity, Anabaena contains abundant and sensitive 2-Cys Prx, but low catalase activity, which is remarkably similar to the chloroplast system. PMID- 20736169 TI - Characterization of 5-chloro-5-deoxy-D-ribose 1-dehydrogenase in chloroethylmalonyl coenzyme A biosynthesis: substrate and reaction profiling. AB - SalM is a short-chain dehydrogenase/reductase enzyme from the marine actinomycete Salinispora tropica that is involved in the biosynthesis of chloroethylmalonyl CoA, a novel halogenated polyketide synthase extender unit of the proteasome inhibitor salinosporamide A. SalM was heterologously overexpressed in Escherichia coli and characterized in vitro for its substrate specificity, kinetics, and reaction profile. A sensitive real-time (13)C NMR assay was developed to visualize the oxidation of 5-chloro-5-deoxy-D-ribose to 5-chloro-5-deoxy-D-ribono gamma-lactone in an NAD(+)-dependent reaction, followed by spontaneous lactone hydrolysis to 5-chloro-5-deoxy-D-ribonate. Although short-chain dehydrogenase/reductase enzymes are widely regarded as metal-independent, a strong divalent metal cation dependence for Mg(2+), Ca(2+), or Mn(2+) was observed with SalM. Oxidative activity was also measured with the alternative substrates D-erythrose and D-ribose, making SalM the first reported stereospecific non-phosphorylative ribose 1-dehydrogenase. PMID- 20736170 TI - Metabolism of pentose sugars in the hyperthermophilic archaea Sulfolobus solfataricus and Sulfolobus acidocaldarius. AB - We have previously shown that the hyperthermophilic archaeon, Sulfolobus solfataricus, catabolizes d-glucose and d-galactose to pyruvate and glyceraldehyde via a non-phosphorylative version of the Entner-Doudoroff pathway. At each step, one enzyme is active with both C6 epimers, leading to a metabolically promiscuous pathway. On further investigation, the catalytic promiscuity of the first enzyme in this pathway, glucose dehydrogenase, has been shown to extend to the C5 sugars, D-xylose and L-arabinose. In the current paper we establish that this promiscuity for C6 and C5 metabolites is also exhibited by the third enzyme in the pathway, 2-keto-3-deoxygluconate aldolase, but that the second step requires a specific C5-dehydratase, the gluconate dehydratase being active only with C6 metabolites. The products of this pathway for the catabolism of D-xylose and L-arabinose are pyruvate and glycolaldehyde, pyruvate entering the citric acid cycle after oxidative decarboxylation to acetyl-coenzyme A. We have identified and characterized the enzymes, both native and recombinant, that catalyze the conversion of glycolaldehyde to glycolate and then to glyoxylate, which can enter the citric acid cycle via the action of malate synthase. Evidence is also presented that similar enzymes for this pentose sugar pathway are present in Sulfolobus acidocaldarius, and metabolic tracer studies in this archaeon demonstrate its in vivo operation in parallel with a route involving no aldol cleavage of the 2-keto-3-deoxy-pentanoates but direct conversion to the citric acid cycle C5-metabolite, 2-oxoglutarate. PMID- 20736171 TI - The role of the exopolyphosphatase PPX in avoidance by Neisseria meningitidis of complement-mediated killing. AB - The complement system is critical for immunity against the important human pathogen Neisseria meningitidis. We describe the isolation of a meningococcal mutant lacking PPX, an exopolyphosphatase responsible for cleaving cellular polyphosphate, a polymer of tens to hundreds of orthophosphate residues found in virtually all living cells. Bacteria lacking PPX exhibit increased resistance to complement-mediated killing. By site directed mutagenesis, we define amino acids necessary for the biochemical activity of meningococcal PPX, including a conserved glutamate (Glu(117)) and residues in the Walker B box predicted to be involved in binding to phosphate. We show that the biochemical activity of PPX is necessary for interactions with the complement. The relative resistance of the ppx mutant does not result from changes in structures (such as capsule, lipopolysaccharide, and factor H-binding protein), which are known to be required for evasion of this key aspect of host immunity. Instead, expression of PPX modifies the interaction of N. meningitidis with the alternative pathway of complement activation. PMID- 20736172 TI - Identification of a lipid peroxidation product as the source of oxidation specific epitopes recognized by anti-DNA autoantibodies. AB - Lipid peroxidation in tissue and in tissue fractions represents a degradative process, which is the consequence of the production and the propagation of free radical reactions primarily involving membrane polyunsaturated fatty acids, and has been implicated in the pathogenesis of numerous diseases, including systemic lupus erythematosus (SLE). We have found that bovine serum albumin incubated with peroxidized polyunsaturated fatty acids significantly cross-reacted with the sera from MRL-lpr mice, a representative murine model of SLE. To identify the active substances responsible for the generation of autoantigenic epitopes recognized by the SLE sera, we performed the activity-guiding separation of a principal source from 13-hydroperoxy-9Z,11E-octadecadienoic acid and identified 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of omega6 polyunsaturated fatty acids, as the source of the autoantigenic epitopes. When the age-dependent change in the antibody titer against the ONE-modified protein was measured in the sera from MRL-lpr mice and control MRL-MpJ mice, all of the MRL-lpr mice developed an anti-ONE titer, which was comparable with the anti-DNA titer. Strikingly, a subset of the anti-DNA monoclonal antibodies generated from the SLE mice showing recognition specificity toward DNA cross-reacted with the ONE-specific epitopes. Furthermore, these dual-specific antibodies rapidly bound and internalized into living cells. These findings raised the possibility that the enhanced lipid peroxidation followed by the generation of ONE may be involved in the pathogenesis of autoimmune disorders. PMID- 20736173 TI - Divergent intracellular sorting of Fc{gamma}RIIA and Fc{gamma}RIIB2. AB - The human low affinity FcgammaRII family includes both the activating receptor FcgammaRIIA and the inhibitory receptor FcgammaRIIB2. These receptors have opposing signaling functions but are both capable of internalizing IgG-containing immune complexes through clathrin-mediated endocytosis. We demonstrate that upon engagement by multivalent aggregated human IgG, FcgammaRIIA expressed in ts20 Chinese hamster fibroblasts is delivered along with its ligand to lysosomal compartments for degradation, while FcgammaRIIB2 dissociates from the ligand and is routed separately into the recycling pathway. FcgammaRIIA sorting to lysosomes requires receptor multimerization, but does not require either Src family kinase activity or ubiquitylation of receptor lysine residues. The sorting of FcgammaRIIB2 away from a degradative fate is not due to its lower affinity for IgG and occurs even upon persistent receptor aggregation. Upon co-engagement of FcgammaRIIA and FcgammaRIIB2, the receptors are sorted independently to distinct final fates after dissociation of co-clustering ligand. These results reveal fundamental differences in the trafficking behavior of different Fcgamma receptors. PMID- 20736174 TI - Cathepsin X-deficient gastric epithelial cells in co-culture with macrophages: characterization of cytokine response and migration capability after Helicobacter pylori infection. AB - Our previous studies have shown an association between Helicobacter pylori infection, the strong up-regulation of cathepsin X (CTSX, also called cathepsin Z/P), and the development of gastric cancer. In the present study, we analyzed primary and conventional gastric epithelial cell lines to establish an optimal in vitro mouse model system for the examination of H. pylori-induced overexpression of Ctsx in a functional way. Gastric epithelial cells were isolated from stomachs of wild-type C57BL6/N and Ctsx(-/-) mice and compared with the gastric cancer cell line CLS103. Indirect co-cultures of epithelial cells and macrophages were infected with H. pylori strain SS1 and analyzed for the expression of cathepsins, cytokines, and adhesion factors. Cellular interactions, migration capability, and adherence of H. pylori were assessed using time-lapse video microscopy and colony forming assays. Isolated primary cells from wild-type and transgenic mice revealed qualities and expression profiles similar to those of corresponding tissue samples. Adherence of H. pylori was significantly higher in primary compared with commercially cells. Thus, induction of cathepsins, cytokines, and adhesion proteins was detected solely in primary cells and co-cultured macrophages. Microarray and migration experiments indicated that Ctsx is involved in B/T-cell proliferation/migration and adhesion of macrophages. Primary epithelial cells from stomach of Ctsx(-/-) mice represent an excellent model of H. pylori gastritis to elaborate the special functions of Ctsx in regulating the immune response to H. pylori. PMID- 20736175 TI - Recombinant membrane-targeted form of CD59 inhibits the growth of choroidal neovascular complex in mice. AB - This study was designed to explore the effect of recombinant, membrane-targeted CD59 (rCD59-APT542) on the growth and size of fully developed neovascular complex using the murine model of laser-induced choroidal neovascularization (CNV). CNV was induced by laser photocoagulation in C57BL/6 mice using an argon laser, and the animals received rCD59-APT542 via intravitreal (ivt) route. Western blot analysis, immunohistochemistry, and total complement hemolytic assay demonstrated that exogenously administered rCD59-APT542 was incorporated as well as retained in RPE and choroid and was functionally active in vivo. Single ivt injection during the growth of the CNV (i.e. at day 3 post-laser) resulted in ~79% inhibition of the further growth of neovascular complex. The size of the CNV complex was significantly (p < 0.05) reduced by the administration of rCD59 APT542 after the CNV complex has fully developed (i.e. at day 7 post-laser). Treatment with rCD59-APT542 blocked the formation of membrane attack complex (MAC), increased apoptosis and decreased cell proliferation in the neovascular complex. On the basis of results presented here we conclude that recombinant membrane targeted CD59 inhibited the growth of the CNV complex and reduced the size of fully developed CNV in the laser-induced mouse model. We propose that a combination of two mechanisms: increased apoptosis and decreased cell proliferation, both resulting from local inhibition of MAC, may be responsible for inhibition of CNV by rCD59-APT542. PMID- 20736176 TI - Cot/tpl2 (MAP3K8) mediates myeloperoxidase activity and hypernociception following peripheral inflammation. AB - Cot/tpl2 (also known as MAP3K8) has emerged as a new and potentially interesting therapeutic anti-inflammatory target. Here, we report the first study of Cot/tpl2 involvement in acute peripheral inflammation in vivo. Six hours after an intraplantar injection of zymosan, Cot/tpl2(-/-) mice showed a 47% reduction in myeloperoxidase activity, concomitant with a 46% lower neutrophil recruitment and a 40% decreased luminol-mediated bioluminescence imaging in vivo. Accordingly, Cot/tpl2 deficiency provoked a 25-30% reduction in luminol-mediated bioluminescence and neutrophil recruitment together with a 65% lower macrophage recruitment 4 h following zymosan-induced peritonitis. Significantly impaired levels of G-CSF and GM-CSF and of other cytokines such as TNFalpha, IL-1beta, and IL-6, as well as some chemokines such as MCP-1, MIP-1beta, and keratinocyte derived chemokine, were detected during the acute zymosan-induced intraplantar inflammatory response in Cot/tpl2(-/-) mice. Moreover, Cot/tpl2 deficiency dramatically decreased the production of the hypernociceptive ligand NGF at the inflammatory site during the course of inflammation. Most importantly, Cot/tpl2 deficiency significantly reduced zymosan-induced inflammatory hypernociception in mice, with a most pronounced effect of a 50% decrease compared with wild type (WT) at 24 h following intraplantar injection of zymosan. At this time, Cot/tpl2( /-) mice showed significantly reduced NGF, TNFalpha, and prostaglandin E(2) levels compared with WT littermates. In conclusion, our study demonstrates an important role of Cot/tpl2 in the NGF, G-CSF, and GM-CSF production and myeloperoxidase activity in the acute inflammatory response process and its implication in inflammatory hypernociception. PMID- 20736177 TI - Intersubunit hydrophobic interactions in Pf1 filamentous phage. AB - Magic angle spinning solid-state NMR has been used to study the structural changes in the Pf1 filamentous bacteriophage, which occur near 10 degrees C. Comparisons of NMR spectra recorded above and below 10 degrees C reveal reversible perturbations in many NMR chemical shifts, most of which are assigned to atoms of hydrophobic side chains of the 46-residue subunit. The changes mainly involve groups located in patches on the interfaces between neighboring capsid subunits. The observations show that the transition adjusts the hydrophobic interfaces between fairly rigid subunits. The low temperature form has been generally more amenable to structure determination; spin diffusion experiments on this form revealed unambiguous contacts between side chains of neighboring subunits. These contacts are important constraints for structure modeling. PMID- 20736178 TI - Double strand break unwinding and resection by the mycobacterial helicase nuclease AdnAB in the presence of single strand DNA-binding protein (SSB). AB - Mycobacterial AdnAB is a heterodimeric DNA helicase-nuclease and 3' to 5' DNA translocase implicated in the repair of double strand breaks (DSBs). The AdnA and AdnB subunits are each composed of an N-terminal motor domain and a C-terminal nuclease domain. Inclusion of mycobacterial single strand DNA-binding protein (SSB) in reactions containing linear plasmid dsDNA allowed us to study the AdnAB helicase under conditions in which the unwound single strands are coated by SSB and thereby prevented from reannealing or promoting ongoing ATP hydrolysis. We found that the AdnAB motor catalyzed processive unwinding of 2.7-11.2-kbp linear duplex DNAs at a rate of ~250 bp s(-1), while hydrolyzing ~5 ATPs per bp unwound. Crippling the AdnA phosphohydrolase active site did not affect the rate of unwinding but lowered energy consumption slightly, to ~4.2 ATPs bp(-1). Mutation of the AdnB phosphohydrolase abolished duplex unwinding, consistent with a model in which the "leading" AdnB motor propagates a Y-fork by translocation along the 3' DNA strand, ahead of the "lagging" AdnA motor domain. By tracking the resection of the 5' and 3' strands at the DSB ends, we illuminated a division of labor among the AdnA and AdnB nuclease modules during dsDNA unwinding, whereby the AdnA nuclease processes the unwound 5' strand to liberate a short oligonucleotide product, and the AdnB nuclease incises the 3' strand on which the motor translocates. These results extend our understanding of presynaptic DSB processing by AdnAB and engender instructive comparisons with the RecBCD and AddAB clades of bacterial helicase-nuclease machines. PMID- 20736179 TI - Television viewing and asthma: spurious relationship? PMID- 20736181 TI - The consequences of applying NICE chest pain guidelines to an acute medical population: a role for cardiac computed tomography. AB - BACKGROUND: Cardiac computed tomography (CCT) is a well-validated investigation for the non-invasive assessment of coronary artery disease (CAD). The National Institute for Clinical Excellence (NICE) have recently released guidelines incorporating CCT into the diagnostic algorithm for chest pain of recent onset. AIM: To assess the frequency of eligibility for CCT in medical admissions with suspected cardiac chest pain using criteria defined by NICE. DESIGN: A retrospective, observational study, set in a teaching hospital acute medical unit. METHODS: A total of 198 consecutive patients admitted over a 4-month period with suspected cardiac chest pain (57% male; mean age 63.5 years) were assessed for eligibility for CCT based on NICE guideline criteria. RESULTS: Of the 198 patients admitted, 65 (33%) patients were excluded by a raised troponin I or ischaemic ECG changes; 100 (51%) patients were excluded by pain categorized as non-anginal and 171 (86%) patients were excluded by a modified Diamond Forrester score outside the range 10-29%. Applying NICE criteria to this population ultimately resulted in 2 (1%) patients recommended for CCT, 12 (6%) for functional cardiac testing and 17 (9%) for invasive angiography. CONCLUSION: Applying current NICE guidelines for chest pain of recent onset to medical admissions results in a lesser uptake of CCT than functional testing and invasive angiography. If the NICE guidelines are revised to include patients with an intermediate pre-test probability of CAD, CCT may have a greater role. PMID- 20736180 TI - The phosphate clamp: a small and independent motif for nucleic acid backbone recognition. AB - The 1.7 A X-ray crystal structure of the B-DNA dodecamer, [d(CGCGAATTCGCG)]2 (DDD)-bound non-covalently to a platinum(II) complex, [{Pt(NH3)3}2-u-{trans Pt(NH3)2(NH2(CH2)6NH2)2}](NO3)6 (1, TriplatinNC-A,) shows the trinuclear cation extended along the phosphate backbone and bridging the minor groove. The square planar tetra-am(m)ine Pt(II) units form bidentate N-O-N complexes with OP atoms, in a Phosphate Clamp motif. The geometry is conserved and the interaction prefers O2P over O1P atoms (frequency of interaction is O2P > O1P, base and sugar oxygens > N). The binding mode is very similar to that reported for the DDD and [{trans Pt(NH3)2(NH2(CH2)6(NH3(+))}2-u-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}](NO3)8 (3, TriplatinNC), which exhibits in vivo anti-tumour activity. In the present case, only three sets of Phosphate Clamps were found because one of the three Pt(II) coordination spheres was not clearly observed and was characterized as a bare Pt2(+) ion. Based on the electron density, the relative occupancy of DDD and the sum of three Pt(II) atoms in the DDD-1 complex was 1:1.69, whereas the ratio for DDD-2 was 1:2.85, almost the mixing ratio in the crystallization drop. The high repetition and geometric regularity of the motif suggests that it can be developed as a modular nucleic acid binding device with general utility. PMID- 20736182 TI - A basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson's disease. AB - AIM: To evaluate relationship between odour identification, taste threshold, dopamine transporter scan (DaTSCAN) and motor function in early Parkinson's disease (PD) and their diagnostic accuracy. METHODS: Seventy-three patients with early parkinsonism were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), DaTSCAN, electrogustometry (EGM) threshold and University of Pennsylvania Smell Identification Test (UPSIT). Olfactory Event-Related potentials (OERP) were performed on 49 patients. At follow-up (mean 15.3 months), patients were diagnosed as 'PD' or 'non-PD'. DaTSCAN images were assessed visually and semi-quantitatively by QuantiSPECT. RESULTS: The sensitivity of UPSIT (86%) was not significantly different from that of the DaTSCAN (92%). UPSIT correlated moderately with DaTSCAN uptake (r = 0.44; P < 0.005) and UPDRS score (r = 0.43; P < 0.05) and weakly with symptom duration (r = 0.25; P < 0.05). In the PD group, OERP showed increased latency but no change in amplitude and no correlation with DaTSCAN. EGM thresholds were impaired in 22% of the PD group but they did not correlate with any other test parameters. DaTSCAN-UPSIT discordance was found in nine patients with PD, but neither was diagnostically superior. CONCLUSION: Our patients with early PD have a frequent and severe olfactory deficit that correlates with disease severity, symptom duration and DaTSCAN but not EGM. The sensitivities of UPSIT and DaTSCAN are high at 86% and 92%, respectively. Although DaTSCAN is superior for 'localization', UPSIT is considerably 'cheaper', and neither is disease specific. EGM threshold impairment in PD is independent of the smell deficit, and probably signifies advanced disease. PMID- 20736186 TI - Prehospital cooling by cold infusion: searching for the optimal infusion regimen. AB - BACKGROUND: The cooling efficacy of intravenous administration of cold crystalloids can be enhanced by optimisation of the procedure. This study assessed the temperature stability of different application regimens of cold normal saline (NS) in simulated prehospital conditions. METHODS: Twelve different application regimens of 4 degrees C cold NS (volumes of 250, 500 and 1000 ml applied at infusion rates of 1000, 2000, 4000 and 6000 ml/h) were investigated for infusion temperature changes during administration to an artificial detention reservoir in simulated prehospital conditions. RESULTS: An increase in infusion temperature was observed in all regimens, with an average of 8.1 +/- 3.3 degrees C (p<0.001). This was most intense during application of the residual 20% of the initial volume. The lowest rewarming was exhibited in regimens with 250 and 500 ml bags applied at an infusion rate of 6000 ml/h and 250 ml applied at 4000 ml/h. More intense, but clinically acceptable, rewarming presented in regimens with 500 and 1000 ml bags administered at 4000 ml/h, 1000 ml at 6000 ml/h and 250 ml applied at 2000 ml/h. Other regimens were burdened by excessive rewarming. CONCLUSION: Rewarming of cold NS during application in prehospital conditions is a typical occurrence. Considering that the use of 250 ml bags means the infusion must be exchanged too frequently during cooling, the use of 500 or 1000 ml NS bags applied at an infusion rate of >=4000 ml/h and termination of the infusion when 80% of the infusion volume has been administered is regarded as optimal. PMID- 20736187 TI - Corticomotoneuronal function and hyperexcitability in acquired neuromyotonia. AB - Acquired neuromyotonia encompasses a group of inflammatory disorders characterized by symptoms reflecting peripheral nerve hyperexcitability, which may be clinically confused in the early stages with amyotrophic lateral sclerosis. Despite a clear peripheral nerve focus, it remains unclear whether the ectopic activity in acquired neuromyotonia receives a central contribution. To clarify whether cortical hyperexcitability contributes to development of clinical features of acquired neuromyotonia, the present study investigated whether threshold tracking transcranial magnetic stimulation could detect cortical hyperexcitability in acquired neuromyotonia, and whether this technique could differentiate acquired neuromyotonia from amyotrophic lateral sclerosis. Cortical excitability studies were undertaken in 18 patients with acquired neuromyotonia and 104 patients with amyotrophic lateral sclerosis, with results compared to 62 normal controls. Short-interval intracortical inhibition in patients with acquired neuromyotonia was significantly different when compared to patients with amyotrophic lateral sclerosis (averaged short interval intracortical inhibition acquired neuromyotonia 11.3 +/- 1.9%; amyotrophic lateral sclerosis 2.6 +/- 0.9%, P < 0.001). In addition, the motor evoked potential amplitudes (acquired neuromyotonia 21.0 +/- 3.1%; amyotrophic lateral sclerosis 38.1 +/- 2.2%, P < 0.0001), intracortical facilitation (acquired neuromyotonia -0.9 +/- 1.3%; amyotrophic lateral sclerosis -2.3 +/- 0.6%, P < 0.0001), resting motor thresholds (acquired neuromyotonia 62.2 +/- 1.6%; amyotrophic lateral sclerosis 57.2 +/- 0.9%, P < 0.05) and cortical silent period durations (acquired neuromyotonia 212.8 +/- 6.9 ms; amyotrophic lateral sclerosis 181.1 +/- 4.3 ms, P < 0.0001) were significantly different between patients with acquired neuromyotonia and amyotrophic lateral sclerosis. Threshold tracking transcranial magnetic stimulation established corticomotoneuronal integrity in acquired neuromyotonia, arguing against a contribution of central processes to the development of nerve hyperexcitability in acquired neuromyotonia. PMID- 20736188 TI - Clinicopathological features of acute autonomic and sensory neuropathy. AB - Acute autonomic and sensory neuropathy is a rare disorder that has been only anecdotally reported. We characterized the clinical, electrophysiological, pathological and prognostic features of 21 patients with acute autonomic and sensory neuropathy. An antecedent event, mostly an upper respiratory tract or gastrointestinal tract infection, was reported in two-thirds of patients. Profound autonomic failure with various degrees of sensory impairment characterized the neuropathic features in all patients. The initial symptoms were those related to autonomic disturbance or superficial sensory impairment in all patients, while deep sensory impairment accompanied by sensory ataxia subsequently appeared in 12 patients. The severity of sensory ataxia tended to become worse as the duration from the onset to the peak phase of neuropathy became longer (P<0.001). The distribution of sensory manifestations included the proximal regions of the limbs, face, scalp and trunk in most patients. It tended to be asymmetrical and segmental, rather than presenting as a symmetric polyneuropathy. Pain of the involved region was a common and serious symptom. In addition to autonomic and sensory symptoms, coughing episodes, psychiatric symptoms, sleep apnoea and aspiration, pneumonia made it difficult to manage the clinical condition. Nerve conduction studies revealed the reduction of sensory nerve action potentials in patients with sensory ataxia, while it was relatively preserved in patients without sensory ataxia. Magnetic resonance imaging of the spinal cord revealed a high-intensity area in the posterior column on T(2)* weighted gradient echo image in patients with sensory ataxia but not in those without it. Sural nerve biopsy revealed small-fibre predominant axonal loss without evidence of nerve regeneration. In an autopsy case with impairment of both superficial and deep sensations, we observed severe neuronal cell loss in the thoracic sympathetic and dorsal root ganglia, and Auerbach's plexus with well preserved anterior hone cells. Myelinated fibres in the anterior spinal root were preserved, while those in the posterior spinal root and the posterior column of the spinal cord were depleted. Although recovery of sensory impairment was poor, autonomic dysfunction was ameliorated to some degree within several months in most patients. In conclusion, an immune-mediated mechanism may be associated with acute autonomic and sensory neuropathy. Small neuronal cells in the autonomic and sensory ganglia may be affected in the initial phase, and subsequently, large neuronal cells in the sensory ganglia are damaged. PMID- 20736189 TI - Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. AB - Concussive head injury opens a temporary window of brain vulnerability due to the impairment of cellular energetic metabolism. As experimentally demonstrated, a second mild injury occurring during this period can lead to severe brain damage, a condition clinically described as the second impact syndrome. To corroborate the validity of proton magnetic resonance spectroscopy in monitoring cerebral metabolic changes following mild traumatic brain injury, apart from the magnetic field strength (1.5 or 3.0 T) and mode of acquisition, we undertook a multicentre prospective study in which a cohort of 40 athletes suffering from concussion and a group of 30 control healthy subjects were admitted. Athletes (aged 16-35 years) were recruited and examined at three different institutions between September 2007 and June 2009. They underwent assessment of brain metabolism at 3, 15, 22 and 30 days post-injury through proton magnetic resonance spectroscopy for the determination of N-acetylaspartate, creatine and choline-containing compounds. Values of these representative brain metabolites were compared with those observed in the group of non-injured controls. Comparison of spectroscopic data, obtained in controls using different field strength and/or mode of acquisition, did not show any difference in the brain metabolite ratios. Athletes with concussion exhibited the most significant alteration of metabolite ratios at Day 3 post-injury (N-acetylaspartate/creatine: -17.6%, N-acetylaspartate/choline: 21.4%; P < 0.001 with respect to controls). On average, metabolic disturbance gradually recovered, initially in a slow fashion and, following Day 15, more rapidly. At 30 days post-injury, all athletes showed complete recovery, having metabolite ratios returned to values detected in controls. Athletes self-declared symptom clearance between 3 and 15 days after concussion. Results indicate that N acetylaspartate determination by proton magnetic resonance spectroscopy represents a non-invasive tool to accurately measure changes in cerebral energy metabolism occurring in mild traumatic brain injury. In particular, this metabolic evaluation may significantly improve, along with other clinical assessments, the management of athletes suffering from concussion. Further studies to verify the effects of a second concussive event occurring at different time points of the recovery curve of brain metabolism are needed. PMID- 20736190 TI - Magnetic resonance imaging markers of Parkinson's disease nigrostriatal signature. AB - One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson's disease and 22 control subjects underwent 3-T magnetic resonance imaging with T2*-weighted, whole-brain T1 weighted and diffusion tensor imaging scans. The mean R2* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson's disease and control subjects. Comparisons were also performed using voxel-based analysis of R2*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson's disease displayed significantly higher R2* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson's disease from controls. The markers comprising discriminating combinations were R2* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson's physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R2*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson's disease and, possibly, of other subcortical pathologies. PMID- 20736191 TI - Unplanned redundant publication. A consequence of too many cardiovascular journals? PMID- 20736192 TI - Timing of invasive treatment after fibrinolysis in ST elevation myocardial infarction--a meta-analysis of immediate or early routine versus deferred or ischemia-guided randomised controlled trials. AB - CONTEXT: Controversy remains over the optimal timing of percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) who have initially been treated with fibrinolytic agents. OBJECTIVE: A meta analysis of studies was performed comparing immediate or early angiography after fibrinolysis versus a more conservative strategy of deferred PCI or ischaemia guided management. Data sources MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov Study selection Nine contemporary randomised controlled trials eligible for inclusion enrolling a total of 3325 patients were identified. Follow-up ranged between 1 and 12 months. DATA EXTRACTION: Data were extracted by two independent reviewers using a standard form and cross-checked. Results There was suggestive evidence for a reduction in the risk of total mortality in patients undergoing immediate or early PCI. There were no significant differences in the risk of stroke or major bleeding. Conclusions These results support the current recommendation of a routine early invasive strategy in STEMI patients after successful fibrinolysis. PMID- 20736193 TI - Obstructive endocardial thrombosis in endomyocardial fibrosis. PMID- 20736194 TI - 'Stack of coins' indicative of arrhythmogenic right-ventricular dysplasia. PMID- 20736196 TI - Test occlusion of Fontan fenestration: unique contribution of interventional MRI. PMID- 20736197 TI - Atrial biopsy evidence of Fabry disease causing lone atrial fibrillation. PMID- 20736198 TI - Device failure weeks to months after transcatheter closure of secundum type atrial septal defects. PMID- 20736199 TI - Aspirin and coronary artery disease. PMID- 20736200 TI - 18F-FDG positron emission tomography CT and assessment of aortitis. PMID- 20736201 TI - Migration of a transcatheter aortic valve in the left ventricular outflow tract. PMID- 20736203 TI - Meta-analysis of the effect of comprehensive smoke-free legislation on acute coronary events. AB - OBJECTIVE: To assess the evidence for a reduced risk of acute coronary events following comprehensive smoke-free legislation. METHODS: Two independent systematic reviews were undertaken using PubMed, Embase and Science Direct with no date restrictions imposed. Meta-analysis was undertaken using a random effects model to obtain a pooled estimate of the relative risk. Linear regression was used to examine possible bias and meta-regression was used to investigate possible causes of heterogeneity. MAIN OUTCOME MEASURE: Acute coronary events. RESULTS: The 17 eligible studies (10 from North America, 6 from Europe and 1 from Australasia) provided 35 estimates of effect size. Apart from five subgroup analyses, all of the published results suggested a reduction in the incidence of acute coronary events following the introduction of smoke-free legislation. Meta analysis produced a pooled estimate of the relative risk of 0.90 (95% CI 0.86 to 0.94). There was significant heterogeneity (overall I(2)=95.1%, p<0.001) but there was no evidence of small study bias (p=0.714). On univariate random effects meta-regression analysis, studies with longer data collection following legislation produced greater estimates of risk reduction and remained significant after adjustment for other study characteristics (adjusted coefficient -0.005, 95% CI -0.007 to -0.002, multiplicity adjusted p=0.006). CONCLUSIONS: There is now a large body of evidence supporting a reduction in acute coronary events following the implementation of comprehensive smoke-free legislation, with the effect increasing over time from implementation. Countries that have not yet adopted smoke-free legislation should be encouraged to do so. PMID- 20736202 TI - The NCDR ACTION Registry-GWTG: transforming contemporary acute myocardial infarction clinical care. AB - AIMS: The NCDR ACTION Registry-GWTG collects detailed in-hospital clinical, process-of-care and outcomes data for patients admitted with acute myocardial infarction (AMI) in the USA. The registry is a national AMI surveillance system that contributes to the scientific enquiry process of AMI care through the facilitation of local and national quality improvement efforts. INTERVENTIONS: No treatments are mandated, participating centres receive routine quality-of-care and outcomes performance feedback reports and access to quality of care tools, such as dosing algorithms and standing orders. POPULATION: AMI patients are retrospectively identified. No informed consent is required, as data are anonymised. From January 2007 to date, 147 165 records have been submitted from 383 participating US hospitals. Patients with a primary diagnosis of ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction are eligible for enrolment in the registry. These patients must have ischemic symptoms and electrocardiogram changes, and/or positive cardiac markers within 24 hours of initial presentation. BASELINE DATA: Approximately 350 fields encompassing patient demographics, medical history and risk factors, hospital presentation, initial cardiac status, medications and associated doses, reperfusion strategy, procedures, laboratory values, and outcomes. Data are manually entered by study personnel; there are non-financial incentives at the hospital level. Completeness within the registry is noteworthy with most fields at less than 5% missing. ENDPOINTS: Main outcome measures include American College of Cardiology/American Heart Association myocardial infarction performance indicators, as well as in-hospital patient outcomes. Data are available for research by application to: http://www.ncdr.com. PMID- 20736204 TI - Inorganic nitrate and the cardiovascular system. AB - Fruit and vegetable-rich diets reduce blood pressure and risk of ischaemic stroke and ischaemic heart disease. While the cardioprotective effects of a fruit and vegetable-rich diet are unequivocal, the exact mechanisms of this effect remain uncertain. Recent evidence has highlighted the possibility that dietary nitrate, an inorganic anion found in large quantities in vegetables (particularly green leafy vegetables), may have a part to play. This beneficial activity lies in the processing in vivo of nitrate to nitrite and thence to the pleiotropic molecule nitric oxide. In this review, recent preclinical and clinical evidence identifying the mechanisms involved in nitrate bioactivity, and the evidence supporting the potential utility of exploitation of this pathway for the prevention and/or treatment of cardiovascular diseases are discussed. PMID- 20736205 TI - Iatrogenic Flecainide toxicity. PMID- 20736206 TI - Angiographic, IVUS and OCT evaluation of the long-term impact of coronary disease severity at the site of overlapping drug-eluting and bare metal stents: a substudy of the ODESSA trial. AB - BACKGROUND: A potentially adverse vascular response to overlapping drug eluting stents (DES) has been suggested in current research. OBJECTIVE: To evaluate the impact of baseline disease severity at the site of stent overlap. METHODS AND RESULTS: This is a substudy of ODESSA, a prospective, randomised controlled trial designed to evaluate healing of overlapping stents. 71/77 patients with a total of 86 overlapping stents were studied: 25 sirolimus, 24 paclitaxel, 26 zotarolimus-eluting stents; and 11 bare metal stents (BMS). Patients were categorised into high-grade stenosis (HGS, >= 70% diameter stenosis) and low grade stenosis (LGS, <70%) at the site of stent overlap. Angiography and intravascular ultrasound were performed after stent deployment and repeated at 6 months, together with additional optical coherence tomography. Images were analysed by an independent core laboratory. End points were binary restenosis, percentage neointimal hyperplasia (%NIH), mean lumen and stent areas and degree of strut coverage/apposition at overlapping stents at 6 months. Stent overlaps occurred in 49 HGS and 37 LGS. Restenosis was found in 5/6 HGS versus 0/5 LGS treated with overlapping BMS (p=0.01) and 4/43 HGS versus 0/32 LGS treated with overlapping DES. There was a trend towards higher %NIH at BMS overlap in HGS versus LGS (p=0.07). DES overlaps had lower lumen and stent areas and similar %NIH in HGS versus LGS. Any uncovered or malapposed struts occurred more often in overlapping DES at LGS than at HGS (59.4% vs 32.6%, p=0.03). CONCLUSIONS: Overlapping DES in normal-appearing coronary segments showed a higher incidence of uncovered or malapposed struts, while restenosis occurred exclusively in overlapping stents at HGS. These findings should be considered when deploying overlapping stents. PMID- 20736207 TI - Burr induced guide-tip damage during rotational atherectomy of an aberrant left main stem. PMID- 20736208 TI - Impact of implementation of evidence-based strategies to reduce door-to-balloon time in patients presenting with STEMI: continuous data analysis and feedback using a statistical process control plot. AB - BACKGROUND: Strategies to reduce DTB (door-to-balloon) time have been previously described. However, there is no well-established data-monitoring system that can be used for prompt feedback. The aims of this study were to use statistical process control (SPC) methodology to measure current processes, to provide real time feedback on the impact of a change in service delivery and to identify individual outliers for specific investigation. METHODS: A prospective study was conducted in a tertiary centre in North England. Data were collected for 841 consecutive STEMI patients from the local district undergoing PPCI. The impact on median DTB time after changes in protocols were prospectively determined. RESULTS: Median DTB times fell significantly as a result of changes in protocol. The upper control limit (UCL) decreased from 209 to 86 min and narrower control limits indicated improved performance. The main outliers included patients presenting to the Accident and Emergency department and patients who developed STEMI while being treated in non-cardiology wards for other reasons (18.3% of the study population). CONCLUSIONS: SPC provides a statistically robust mechanism for assessing the effect of process redesign interventions, and in this context provides a clear visual representation of DTB times for individual patients. Identification of significant outliers allows investigation of any variation with a special cause. It allows a unit to identify when a system of service delivery, albeit stable, is inadequate and needs redesign and can monitor the impact of changes in protocol. PMID- 20736210 TI - Impact of clopidogrel loading dose on clinical outcome in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. AB - CONTEXT: Enhanced platelet inhibition by clopidogrel decreases the risk of ischemic events but carries a risk for a concomitant increase in bleeding. OBJECTIVES: To compare the efficacy and safety of two clopidogrel loading regimens (300mg vs. 600mg) in patients undergoing percutaneous coronary intervention (PCI) at one month after start of therapy. DATA SOURCES: A systematic literature search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases using predefined search terms for relevant articles in any language. STUDY SELECTION AND DATA EXTRACTION: Randomised controlled trials and non randomised studies reporting adjusted effect estimates were included. Summary estimates of the risks ratios (RRs) with therapy were calculated using a random effect model. Outcomes evaluated were combined major adverse cardiovascular events (MACE) and major bleedings. Results Seven studies met the inclusion criteria and included 25,383 patients. A 600mg clopidogrel loading was associated with a 34% relative risk reduction of MACE (RR=0.66; 95% confidence intervals CI=0.52-0.84; p<0.001). Sub-analysis revealed a 47% risk reduction of MACE in randomised trials (RR=0.53; 95%CI=0.32-0.88; p=0.01) and a 31% relative risk reduction in non-randomised trials (RR=0.69; 95%CI=0.54-0.90; p=0.005) in patients receiving 600mg loading with clopidogrel. In patients suffering from acute coronary syndrome, 600mg clopidogrel loading was associated with a 24% relative risk reduction in MACE (RR=0.76; 95%CI=0.60-0.95; p=0.02). Importantly, the 600mg clopidogrel loading dose was not associated with an increased risk of major bleedings (RR=0.91; 95%CI=0.73-1.15; p=0.44). CONCLUSIONS: This meta analysis demonstrates that intensified clopidogrel loading with 600mg reduces the rate of major cardiovascular events without increase in major bleeding compared to 300mg in patients undergoing PCI during one month follow-up. PMID- 20736211 TI - Cardiac computed tomography in endocarditis. PMID- 20736213 TI - X-ray diagnosis of early gastric cancer. PMID- 20736214 TI - Effects of bleomycin for epidermoid carcinoma of head and neck. PMID- 20736215 TI - Flexible bronchofiberscope. PMID- 20736216 TI - Development of computer systems for radiotherapy of cancer. PMID- 20736219 TI - Recent knowledge of the relationship between Helicobacter pylori and gastric cancer and recent progress of gastroendoscopic diagnosis and treatment for gastric cancer. AB - Gastric cancer is a multi-step process and multi-factorial disease. However, Helicobacter pylori plays the most important role in gastric carcinogenesis because most gastric cancers including both intestinal type and diffuse type arise from mucosa infected by H. pylori. The relationship between H. pylori infection and gastric cancer has been proved in epidemiological studies, animal experiments with Mongolian gerbils, and clinical prospective studies. Significant preventive effect of H. pylori eradication was reported in Japanese randomized study for secondary gastric cancer after endoscopic resection of primary gastric cancer and meta-analysis of randomized studies. The Japanese Society for Helicobacter Research has published a guideline recommending that H. pylori infection should be treated by eradication therapy to suppress the incidence of gastric cancer. The development of endoscopic technology has advanced the diagnosis and treatment of gastric cancer. In the diagnosis of gastric cancer, image enhancement endoscopy including magnifying observation with narrow-band imaging system and microscopic magnifying observation opens the possibility of optical biopsy. Endoscopic resection for early stage of gastric cancer has been established as proper treatment of early gastric cancer. Recently endoscopic submucosal dissection had made en bloc resection possible for mucosal cancers >2 cm in diameter. Because of endoscopic submucosal dissection, endoscopic resection is indicated in a greater number of cases. Although the use of endoscopic treatment for gastric cancer has been increasing steadily, long-term outcome data is necessary. PMID- 20736220 TI - Changes and current state of diagnosis of lung cancer after development of the flexible bronchofiberscope. AB - The flexible bronchofiberscope developed by Ikeda et al. has brought about revolutionary changes in the diagnosis and treatment of lung cancer. Advances in this device are continuing to emerge and lesions even smaller than those visible to the naked eye can now be visualized. In addition, the use of ultrasound now enables diagnosis of extramural bronchial lesions. Bronchoscopy is also used for the treatment of early hilar lung cancer, and in patients with airway stenosis due to advanced cancer, laser therapy, brachytherapy, and stenting can be performed. The bronchofiberscope is also very useful for tissue sampling from the lung periphery. Further advances in computed tomography imaging have enabled bronchoscopy under computed tomography fluoroscopy, and virtual bronchoscopy images can be generated from computed tomography imaging. Navigation systems have been developed to show the target bronchus where instruments such as forceps should be guided. Computed tomography imaging has made remarkable advances, and computed tomography now plays a central role in chest imaging, including early detection of lesions by low-dose computed tomography, qualitative diagnosis by high-resolution computed tomography and diagnosis of disease progression by contrast computed tomography. Ikeda et al. introduced the concept of personal health data recording system to manage these various images but the technology was not mature enough at that time for implementation. With modern advances in information technology, this is likely to be realized using an electronic health record system. PMID- 20736221 TI - The developments and achievements of endoscopic surgery, robotic surgery and function-preserving surgery. AB - The breakthrough in laparoscopic surgery has been the development of a charge coupled device camera system and Mouret performing cholecystectomy in 1987. The short-term benefits of laparoscopic surgery are widely accepted and the long-term benefit of less incidence of bowel obstruction can be expected. The important developments have been the articulating instrumentation via new laparoscopic access ports. Since 2007, single-incision laparoscopic surgery has spread all over the world. Not only single-scar but also no-scar operation is a current topic. In 2004, Kalloo reported the flexible transgastric peritoneoscopy as a novel approach to therapeutic interventions. In 2007, Marescaux reported transvaginal cholecystectomy in a patient. The breakthrough in robotic surgery was the development of the da Vinci Surgical System. It was introduced to Keio University Hospital in March 2000. Precision in the surgery will reach a higher level with the use of robotics. In collaboration with the faculty of technology and science, Keio University, the combined master-slave manipulator has been developed. The haptic forceps, which measure the elasticity of organs, have also been developed. The first possible sites of lymphatic metastasis are known as sentinel nodes. Otani reported vagus-sparing segmental gastrectomy under sentinel node navigation. This kind of function-preserving surgery will be performed frequently if the results of the multicenter prospective trial of the dual tracer method are favorable. Indocyanine green fluorescence-guided method using the HyperEye charge-coupled device camera system can be a highly sensitive method without using the radioactive colloid. 'Minimally invasive, function-preserving and precise surgery under sentinel node navigation in community hospital' may be a goal for us. PMID- 20736222 TI - Development of palliative medicine for cancer patients in Japan: from isolated voluntary effort to integrated multidisciplinary network. AB - The paradigm of palliative care in cancer medicine has shifted from only care of terminally ill patients to earlier intervention for them in the recent 15 years. The concept of palliative medicine was founded in Japan in the 1970s. During the past 15 years, various new drugs and interventions have been introduced mainly for pain control, which is one of the major problems in the area of palliative medicine in cancer. According to the aim of the Cancer Control Act established in Japan (2006), patients and their families will be able to access easily integrated high-quality cancer care wherever they live at the time of 2016. Systematic and continuous education for medical staff is mandatory, and a major breakthrough for achieving this purpose would be to increase the number of courses and faculties in palliative medicine at most universities in Japan. PMID- 20736223 TI - Oncology Certified Nurse Specialist in Japan. AB - The purpose of this article is to review a historical perspective of the Certified Nurse Specialist role and current trends in nursing education and practice of the Oncology Certified Nurse Specialist. Since the initiation of Certified Nurse Specialist credentialing system in 1995, 193 Oncology Certified Nurse Specialists have practiced in clinical settings. The Oncology Certified Nurse Specialist credentials committee, the Association of Nursing Programs in University and the Association of Oncology Certified Nurse Specialists play the important part to maintain a high level of Oncology Certified Nurse Specialist competencies in Japan. The Oncology Certified Nurse Specialist should promote the outcomes research to assess the effectiveness of nursing intervention by the Oncology Certified Nurse Specialist, and participate in the interdisciplinary research by collaborating with other health professionals to realize the ongoing cancer reforms in Japan. PMID- 20736224 TI - The third hand--a simple but useful tool for holding the sheath during transapical transcatheter aortic valve implantation. AB - Transapical aortic valve implantation is an evolving technology for treating high risk patients with symptomatic aortic stenosis. The transition to a catheter based implantation technique inherits one fundamental change: the native valve stays in place and is no longer removed. The selection of the correct plane of the aortic annulus, therefore, is mandatory. In addition, exact alignment of the sheath and catheters according to axis of the ascending aorta is imperative for correct implantation. That is why any additional movements have to be avoided. To aid in better workflow, we developed an easy-to-use cheap holder for the introduction sheath. By using a rigid table mount instrument holder the sheath can easily be fixed in the desired orientation, abolishing any movement and reducing the X-ray load to the implanting surgeon. PMID- 20736225 TI - Is an involved circumferential resection margin following oesphagectomy for cancer an important prognostic indicator? AB - A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether an involved circumferential resection margin (CRM) following oesophagectomy for cancer is an independent predictor of poor long-term survival. Six hundred and fourteen papers were found using the reported search, of which seven represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. Of these studies, four were conducted on patients who predominantly did not receive preoperative chemotherapy and showed conflicting results as to the prognostic significance of CRM involvement. However, three later studies conducted on patients who predominantly did receive preoperative chemotherapy showed that CRM involvement to be an independent predictor of long-term survival. We conclude that for patients who undergo oesophagectomy alone as a treatment for oesophageal cancer, the prognostic importance of CRM involvement is unclear. However, for patients who undergo preoperative chemotherapy prior to surgery, there does appear to be emerging evidence supporting the concept that CRM involvement is an independent predictor of poor long-term outcome. PMID- 20736226 TI - Left atrial metastasis from hepatocellular carcinoma with liver cirrhosis. AB - Surgical treatment in hepatocellular carcinoma patients with cardiac involvement is challenging, and its prognosis remains unclear because of its rarity. A 48 year-old male hepatocellular carcinoma patient presented with right atrial involvement through the inferior vena cava and a left atrial mass, which nearly occluded the mitral valve, and extended from a pulmonary metastasis. Emergent surgery was performed due to sudden severe respiratory failure despite profound liver cirrhosis (Child-Pugh class B). Nevertheless, the patients postoperative course was uneventful, and over six months of follow-up, he has shown no remarkable symptoms and has maintained a tolerable liver function. PMID- 20736227 TI - Identification of low circulatory transforming growth factor beta-1 in patients with degenerative heart valve disease. AB - Transforming growth factor beta-1 (TGF-beta1) is an immunosuppressive cytokine. It exerts cardioprotection during acute myocardial ischaemia, promoting healing of the injured myocytes. Lower plasma concentrations of TGF-beta1 have been identified in patients with coronary artery disease (CAD) compared to those with normal coronary arteries. We measured plasma TGF-beta1 concentrations in patients with CAD compared to those with degenerative heart valves (DHVs) and normal coronary arteries. The mean concentration of TGF-beta1 in patients with valvular heart disease was significantly lower (18.67 MUg/l) than the mean in the coronary artery bypass graft (CABG) group (26.46 MUg/l). There was no correlation between the patient characteristics and preoperative concentration of TGF-beta1. It is possible that the lower plasma concentration of TGF-beta1 in patients with valvular heart disease and the lack of its regulatory effect results in the increased inflammation and calcification seen in DHVs. PMID- 20736228 TI - Progression of lupus-like disease drives the appearance of complement-activating IgG antibodies in MRL/lpr mice. AB - OBJECTIVES: Nucleic acids are known to induce complement activation, which results in the masking and removal of apoptotic cells exposing nuclear components. Dysregulation of these events is characteristic of SLE, a systemic autoimmune disease characterized by the appearance of ANAs. In this study, we aimed to investigate the relationship between development of ANAs and their effect on complement activation by nucleic acids. METHODS: We used protein array technology to characterize complement activation by murine mAbs and polyclonal antibodies against various forms of nucleic acid. Serum samples from MRL/lpr mice were collected, starting before the onset of the disease till 6 months of age. Binding of IgG and its subclasses to dsDNA, ssDNA, RNA, plasmid DNA and nucleosome complexes was determined, along with C3 fixation. RESULTS: We show that complement C3 binding to various forms of nucleic acid that serve as targets in lupus is absent in normal serum. The addition of dsDNA-specific mAbs to normal serum results in the deposition of complement C3 to nucleic acids. In MRL/lpr mice, IgG antibodies against various nuclear antigens appear with ageing and disease progression. C3 binding to the antigens is somewhat delayed and suggests that accumulation or maturation of pathogenic antibodies is required for inducing C3 binding to ICs containing nucleic acids. CONCLUSIONS: C3 deposition on nuclear antigens, therefore, reflects the state of disease progression in this murine model of SLE. PMID- 20736229 TI - Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. AB - The intestinal microbiota consists of over 1000 species, which play key roles in gut physiology and homeostasis. Imbalances in the composition of this bacterial community can lead to transient intestinal dysfunctions and chronic disease states. Understanding how to manipulate this ecosystem is thus essential for treating many disorders. In this study, we took advantage of recently developed tools for deep sequencing and phylogenetic clustering to examine the long-term effects of exogenous microbiota transplantation combined with and without an antibiotic pretreatment. In our rat model, deep sequencing revealed an intestinal bacterial diversity exceeding that of the human gut by a factor of two to three. The transplantation produced a marked increase in the microbial diversity of the recipients, which stemmed from both capture of new phylotypes and increase in abundance of others. However, when transplantation was performed after antibiotic intake, the resulting state simply combined the reshaping effects of the individual treatments (including the reduced diversity from antibiotic treatment alone). Therefore, lowering the recipient bacterial load by antibiotic intake prior to transplantation did not increase establishment of the donor phylotypes, although some dominant lineages still transferred successfully. Remarkably, all of these effects were observed after 1 mo of treatment and persisted after 3 mo. Overall, our results indicate that the indigenous gut microbial composition is more plastic that previously anticipated. However, since antibiotic pretreatment counterintuitively interferes with the establishment of an exogenous community, such plasticity is likely conditioned more by the altered microbiome gut homeostasis caused by antibiotics than by the primary bacterial loss. PMID- 20736231 TI - Sugammadex reversal of rocuronium-induced neuromuscular block in Caesarean section patients: a series of seven cases. AB - Sugammadex is a selective relaxant-binding agent, which reverses rocuronium induced neuromuscular blocks of any depth by chemical encapsulation of rocuronium in the plasma in various groups of patients. We reported seven Caesarean section cases, undergoing general anaesthesia with thiopental (6 mg kg-1) and rocuronium (0.6 mg kg-1) who were given desflurane and fentanyl for maintenance of anaesthesia after delivery. The action of rocuronium may be prolonged in pregnant women. At the end of the operation, all patients had a significant degree of neuromuscular block. In five patients, there was no single twitch response and no TOF ratio, one patient had one twitch detectable, and in one patient, a TOF ratio of 3% was detected. The recommended dose of sugammadex for reversal of profound block (4 mg kg-1) or moderate block (2 mg kg-1) was given. In all patients, sugammadex provided rapid and sufficient reversal to TOF >0.9 within 2 min. All patients were monitored after operation, and no signs of recurarization occurred in any patient and no signs of neuromuscular weakness were observed. PMID- 20736230 TI - A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. AB - Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, remain poorly understood. We determined VDR binding throughout the human genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After calcitriol stimulation, we identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near autoimmune and cancer associated genes identified from genome-wide association (GWA) studies. Notable genes with VDR binding included IRF8, associated with MS, and PTPN2 associated with Crohn's disease and T1D. Furthermore, a number of single nucleotide polymorphism associations from GWA were located directly within VDR binding intervals, for example, rs13385731 associated with SLE and rs947474 associated with T1D. We also observed significant enrichment of VDR intervals within regions of positive selection among individuals of Asian and European descent. ChIP-seq determination of transcription factor binding, in combination with GWA data, provides a powerful approach to further understanding the molecular bases of complex diseases. PMID- 20736232 TI - Predictive validity of a selection centre testing non-technical skills for recruitment to training in anaesthesia. AB - BACKGROUND: Assessment centres are an accepted method of recruitment in industry and are gaining popularity within medicine. We describe the development and validation of a selection centre for recruitment to speciality training in anaesthesia based on an assessment centre model incorporating the rating of candidate's non-technical skills. METHODS: Expert consensus identified non technical skills suitable for assessment at the point of selection. Four stations structured interview, portfolio review, presentation, and simulation-were developed, the latter two being realistic scenarios of work-related tasks. Evaluation of the selection centre focused on applicant and assessor feedback ratings, inter-rater agreement, and internal consistency reliability coefficients. Predictive validity was sought via correlations of selection centre scores with subsequent workplace-based ratings of appointed trainees. RESULTS: Two hundred and twenty-four candidates were assessed over two consecutive annual recruitment rounds; 68 were appointed and followed up during training. Candidates and assessors demonstrated strong approval of the selection centre with more than 70% of ratings 'good' or 'excellent'. Mean inter-rater agreement coefficients ranged from 0.62 to 0.77 and internal consistency reliability of the selection centre score was high (Cronbach's alpha=0.88-0.91). The overall selection centre score was a good predictor of workplace performance during the first year of appointment. CONCLUSIONS: An assessment centre model based on the rating of non technical skills can produce a reliable and valid selection tool for recruitment to speciality training in anaesthesia. Early results on predictive validity are encouraging and justify further development and evaluation. PMID- 20736233 TI - High-volume local infiltration analgesia combined with intravenous or local ketorolac+morphine compared with epidural analgesia after total knee arthroplasty. AB - BACKGROUND: Recently, high-volume local infiltration analgesia (LIA) in total knee arthroplasty (TKA) has been introduced, but dosage, timing, and effects of adjuvants are still debated. METHODS: We randomized 102 patients undergoing TKA to receive either epidural analgesia (EDA group) or LIA (ropivacaine 150 mg and epinephrine 0.5 mg) combined with ketorolac 30 mg and morphine 5 mg given either locally (LIA group) or i.v. (LIAiv group). Epidural analgesia was maintained for 48 h. Intra-articular re-injection via a catheter with ropivacaine 142.5 mg and either intra-articular or i.v. ketorolac 30 mg was given 24 h after surgery. Pain scores, morphine consumption, side-effects, and readiness for hospital discharge were studied. RESULTS: At discharge from the postoperative anaesthetic care unit, verbal pain scores were lower in the EDA group (P=0.004), but discharge was delayed [difference 101 min, 95% CI: (23, 178), P=0.007]. Group LIA reported lower pain scores at rest beyond 24 h after surgery [mean VAS (sd) at 24/48/72 h: LIA group 16/12/10 (14)/(13)/(11); LIAiv group 22/18/15 (17)/(15)/(12); EDA group 27/30/21 (21)/(29)/(19)]. Both the LIA and the LIAiv groups were mobilized faster and were earlier ready for hospital discharge [3.5 days (LIA group) vs 4 days (LIAiv group) vs 5.5 days (EDA group); P<0.001]. Cumulated morphine consumption (72 h) was lowest for the LIA group [80 vs 101 mg (EDA group) vs 118 mg (LIAiv group), P=0.007]. CONCLUSIONS: LIA with local adjuvants compared with epidural analgesia results in reduced opioid consumption, faster mobilization, and earlier readiness for hospital discharge. Ketorolac and morphine are more efficient when given locally than systemically. The study has been registered at clinicaltrials.gov (NCT00562627) before onset of participant enrolment: http://clinicaltrials.gov/ct2/show/NCT00562627?term=spreng&rank=2 (April 21, 2010). PMID- 20736234 TI - Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity. AB - OBJECTIVES: The genetic barrier to development of raltegravir resistance is considered to be low, requiring at least one primary integrase mutation: Y143C, Q148H/K/R or N155H to confer raltegravir therapy failure. However, during continued raltegravir treatment failure, additional mutations may be selected. In a patient failing raltegravir therapy, we investigated the impact of multiple integrase mutations on resistance and viral replication. Furthermore, in vivo fitness was investigated during failure of raltegravir-containing highly active antiretroviral therapy and after raltegravir was discontinued from the regimen. METHODS: Patient-derived viral integrase genes were cloned into a reference strain. These recombinant viruses were used to determine the contribution of individual integrase mutations to raltegravir resistance and replication capacity in vitro. To determine in vivo fitness, the relative proportion of specific integrase mutations was monitored over time by in-depth clonal analysis of the viral integrase at baseline, during and after raltegravir treatment. RESULTS: Raltegravir therapy failure was associated with the initial selection of primary resistance mutation N155H. This mutation conferred a 3.8-fold reduction in raltegravir susceptibility and a severe reduction in viral replication. Acquisition of integrase mutation Q95K increased resistance (6.2-fold) and partly restored viral replication. Selection of a third mutation, V151I, further increased raltegravir resistance (20-fold), but decreased viral replication. After prolonged raltegravir interruption, raltegravir resistance mutations were lost, demonstrating the reduced replication capacity of the resistant virus. CONCLUSIONS: We describe selection of Q95K as a secondary resistance mutation during raltegravir therapy failure. In the background of N155H, Q95K enhances raltegravir and elvitegravir resistance and improves the impaired replication of the virus. PMID- 20736235 TI - Determination of antibiotic dosage adjustments in patients with renal impairment: elements for success. AB - This report reviews a contemporary methodology for determining antibiotic dosage modifications among patients with renal impairment. Historically, the approach to identifying renal dosage adjustments has focused on achieving comparable concentration-time profiles between patients with renal impairment and those with normal kidney function. While this approach is intuitive, it fails to incorporate the relationship between antibiotic exposure and effect in the renal dose selection process. A candidate renal dosing scheme that is worthy of incorporation into clinical practice should balance the probability of achieving the exposure target associated with success against the risks of toxicity and the emergence of resistance. This review describes a methodology for optimally identifying dosage adjustments in patients with impaired renal function using extended-infusion piperacillin/tazobactam as an illustrative example. PMID- 20736237 TI - MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression. AB - AIMS: non-coding RNA has been recently demonstrated to be a novel mechanism for modulation of gene expression at the post-transcriptional level. The importance of microRNAs in the cardiovascular system is now apparent. Mutations of distinct microRNAs have provided evidence for fundamental roles of microRNAs during cardiovascular development. However, there is limited information about global microRNA profiles during mouse heart development. In this study, we have gained insight from the expression profiles of microRNAs during mouse ventricular development by microarray and qRT-PCR analysis. METHODS AND RESULTS: our microarray analysis reveals that relatively few microRNAs display either increasing or decreasing expression profiles during ventricular chamber formation. Interestingly, most of the differentially expressed microRNAs display a rather discrete peak of expression at particular developmental stages. Furthermore, we demonstrate that microRNA-27b (miR-27b) displays an overt myocardial expression during heart development and that the transcription factor encoding gene Mef2c is an miR-27b target. CONCLUSION: our data present a comprehensive profile of microRNA expression during ventricular maturation, providing an entry point for investigation of the functional roles of the most abundantly and differentially expressed microRNAs during cardiogenesis. PMID- 20736236 TI - Lack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesions. AB - AIM: prostaglandin E(2), by ligation of its receptor EP4, suppresses the production of inflammatory cytokines and chemokines in macrophages in vitro. Thus, activation of EP4 may constitute an endogenous anti-inflammatory pathway. This study investigated the role of EP4 in atherosclerosis in vivo, and particularly its impact on inflammation. METHODS AND RESULTS: Ldlr(-/-) mice transplanted with EP4(+/+) or EP4(-/-) bone marrow consumed a high-fat diet for 5 or 10 weeks. Allogenic bone marrow transplantation promoted exacerbation of atherosclerosis irrespective of EP4 genotype, compatible with prior observations of exacerbated atherogenesis by allogenicity. EP4 deficiency had little effect on plaque size or morphology in early atherosclerosis, but at the later time point, mice deficient in EP4 displayed enhanced inflammation in their atherosclerotic plaques. Expression of monocyte chemoattractant protein-1 and interferon-gamma inducible protein 10 increased, and there was a corresponding increase in macrophage and T-cell infiltration. These plaques also contained fewer smooth muscle cells. Despite these changes, mice deficient in EP4 in bone marrow-derived cells at an advanced stage had similar lesion size (in both aorta and aortic root) as mice with EP4. CONCLUSION: this study shows that in advanced atherosclerosis, EP4 deficiency did not alter atherosclerotic lesion size, but yielded plaques with exacerbated inflammation and altered lesion composition. PMID- 20736238 TI - GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons. AB - AIMS: glucagon-like peptide 1 (GLP-1) is an incretin hormone released from the gut in response to food intake. Whereas GLP-1 acts in the periphery to inhibit glucagon secretion and stimulate insulin release, it also acts in the central nervous system to mediate autonomic control of feeding, body temperature, and cardiovascular function. Because of its role as an incretin hormone, GLP-1 receptor analogs are used as a treatment for type 2 diabetes. Central or peripheral administration of GLP-1 increases blood pressure and heart rate, possibly by activating brainstem autonomic nuclei and increasing vagus nerve activity. However, the mechanism(s) by which GLP-1 receptor stimulation affects cardiovascular function are unknown. We used the long-lasting GLP-1 receptor agonist Exendin-4 (Ex-4) to test the hypothesis that GLP-1 signalling modulates central parasympathetic control of heart rate. METHODS AND RESULTS: using a telemetry system, we assessed heart rate in mice during central Ex-4 administration. Heart rate was increased by both acute and chronic central Ex-4 administration. Spectral analysis indicated that the high frequency and low frequency powers of heart rate variability were diminished by Ex-4 treatment. Finally, Ex-4 decreased both excitatory glutamatergic and inhibitory glycinergic neurotransmission to preganglionic parasympathetic cardiac vagal neurons. CONCLUSION: these data suggest that central GLP-1 receptor stimulation diminishes parasympathetic modulation of the heart thereby increasing heart rate. PMID- 20736240 TI - Simply say yes to NO? Nitric oxide (NO) sensor-based assessment of coronary endothelial function. PMID- 20736241 TI - Black race is associated with digital artery endothelial dysfunction: results from the Heart SCORE study. AB - AIMS: We evaluated whether black race is independently associated with arterial endothelial dysfunction. The pathophysiological basis for race-related differences in cardiovascular disease (CVD) risk has not been established. Endothelial dysfunction, which precedes obstructive atherosclerotic disease, may contribute to CVD disparities. Accordingly, we evaluated race-related differences in digital pulse amplitude tonometry (PAT) response to an endothelium-dependent vasodilatory stimulus. METHODS AND RESULTS: A total of 1377 subjects (41% black; mean age 58.5 +/- 7.5 years; 67% female) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study underwent assessment of digital pulse amplitude response to forearm occlusion-induced hyperaemia. The response was measured as a PAT ratio of hyperaemia:baseline pulse amplitude in a finger that was subject to hyperaemic stimulus divided by this same ratio in a control finger on the contralateral arm which did not undergo forearm occlusion, expressed as the natural logarithm. The average PAT ratio was significantly lower in blacks compared with whites (0.67 +/- 0.44 vs. 0.80 +/- 0.46, P < 0.001), signifying greater endothelial dysfunction in blacks. Black race was independently correlated with lower PAT ratio. This finding was consistent across all Framingham risk strata. Adjusted analyses showed significant gender-race interactions. With white women serving as the referent group, parameter estimates for lower PAT ratio in ascending order were as follows: black males (t = -6.93, P < 0.0001); white males (t = -3.31, P = 0.001); and black females (t = -1.12, P = 0.26). CONCLUSION: Our findings indicate that black race is independently associated with arterial endothelial dysfunction. Racial differences in CVD risk may be related, in part, to race-related differences in endothelial dysfunction. PMID- 20736239 TI - Cardiac mast cells: the centrepiece in adverse myocardial remodelling. AB - Increased numbers of mast cells have been reported in explanted human hearts with dilated cardiomyopathy and in animal models of experimentally induced hypertension, myocardial infarction, and chronic volume overload secondary to aortocaval fistula and mitral regurgitation. Accordingly, mast cells have been implicated to have a major role in the pathophysiology of these cardiovascular disorders. In vitro studies have verified that mast cell proteases are capable of activating collagenase, gelatinases and stromelysin. Recent results have shown that with chronic ventricular volume overload, there is an elevation in mast cell density, which is associated with a concomitant increase in matrix metalloproteinase (MMP) activity and extracellular matrix degradation. However, the role of the cardiac mast cell is not one dimensional, with evidence from hypertension and cardiac transplantation studies suggesting that they can also assume a pro-fibrotic phenotype in the heart. These adverse events do not occur in mast cell deficient rodents or when cardiac mast cells are pharmacologically prevented from degranulating. This review is focused on the regulation and dual roles of cardiac mast cells in: (i) activating MMPs and causing myocardial fibrillar collagen degradation and (ii) causing fibrosis in the stressed, injured or diseased heart. Moreover, there is strong evidence that premenopausal female cardioprotection may at least partly be due to gender differences in cardiac mast cells. This too will be addressed. PMID- 20736242 TI - Platelet activation: yet another strike against routine TRANSFUSION. PMID- 20736243 TI - Update on the diagnosis and treatment of Pneumocystis pneumonia. AB - Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ transplantation, and in patients with hematological and solid malignancies. Patients with hematologic disorders and solid organ and hematopoietic stem cell transplantation are currently the most vulnerable groups at risk for developing this infection. However, any patient with an impaired immunity, such as those receiving moderate doses of oral steroids for greater than 4 weeks or those receiving other immunosuppressive medications are at also at significant risk. PMID- 20736244 TI - Should blood flow during cardiopulmonary bypass be individualized more than to body surface area? AB - Blood flow during cardiopulmonary bypass (CPB) is calculated on body surface area (BSA). Increasing comorbidity, age and weight of today's cardiac patients question this calculation as it may not reflect individual metabolic requirement. The hypothesis was that a measured cardiac index (CI) prior to normothermic CPB is a better estimate. A cross-over study, with random allocation to CPB blood flow for 20 minutes based on either a calculation (2.4 L/min/m(2)) or on CI, with a switch to the opposite flow for another 20 minutes, was performed. Twenty-two elective cardiac surgery patients with normal ventricular function were included. Effect parameters were cerebral oxygenation, mixed venous saturation and arterial lactate. CI varied from 1.9 to 3.1 L/min/m(2) (median 2.4 L/min/m(2)). No differences in effect parameters were seen. In conclusion, a CPB blood flow based on an individual estimate did not improve cerebral and systemic oxygenation compared to a blood flow based on BSA. PMID- 20736245 TI - A method for evaluating treatment switching criteria in multiple sclerosis. AB - BACKGROUND AND OBJECTIVE: We investigated a method to evaluate a treatment switching approach, namely treatment change after one multiple sclerosis (MS) relapse. METHODS: Patients who experienced a relapse while on a first-line disease-modifying therapy, glatiramer acetate, were identified. Based on their subsequent course, patients were divided into two groups: those who changed treatment and those who did not. Patients were allowed to change to any other treatment. Subsequent annualized relapse rate and time to next relapse were compared in the two groups. Since patients were not randomized to treatment group, negative binomial and Cox regression models were used to control for several potential clinical confounders, including relapse severity, relapse duration, age, disease duration and presence of previous/combination therapy. In addition, an inverse probability of treatment weighting model was used to control for confounding. Several secondary analyses investigated patient subgroups. RESULTS: Statistical modeling showed that there was no significant difference between groups in terms of relapse rate (rate ratio; 95% CI = 0.68; 0.35, 1.31) and time to next relapse (hazard ratio; 95% CI = 0.61; 0.30, 1.25). All secondary analyses confirmed these results. In addition, no significant difference in time to sustained progression on the Expanded Disability Status Scale was observed (p > 0.05). Our approach allowed investigation of the choice to change treatment after a relapse. CONCLUSIONS: Our results showed that a single relapse may not be sufficient to indicate treatment failure. Although clinical confounders were addressed in our modeling, unmeasured confounders, particularly the presence of magnetic resonance imaging activity, may have biased our conclusion. PMID- 20736246 TI - Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis. AB - BACKGROUND: Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. OBJECTIVES: Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. METHODS: Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. RESULTS: HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 * 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. CONCLUSIONS: HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis. PMID- 20736248 TI - Measurement of lipoprotein particle sizes using dynamic light scattering. AB - BACKGROUND: A simple method for the measurement of LDL particle sizes is needed in clinical laboratories because a predominance of small, dense LDL (sd LDL) has been associated with coronary heart disease. We applied dynamic light scattering (DLS) to measure lipoprotein particle sizes, with special reference to sd LDL. METHODS: Human serum lipoproteins isolated by a combination of ultracentrifugation and gel chromatography, or by sequential ultracentrifugation, were measured for particle size using DLS. RESULTS: The sizes of polystyrene beads, with diameters of 21 and 28 nm according to the manufacturer, were determined by DLS as 19.3 +/- 1.0 nm (mean +/- SD, n = 11) and 25.5 +/- 1.0 nm, respectively. The coefficients of variation for the 21 and 28 nm beads were 5.1% and 3.8% (within-run, n = 11), and 2.9% and 6.2% (between-run, n = 3), respectively. The lipoprotein sizes determined by DLS for lipoprotein fractions isolated by chromatography were consistent with the elution profile. Whole serum, four isolated lipoprotein fractions (CM + VLDL + IDL, large LDL, sd LDL and HDL) and a non-lipoprotein fraction isolated by sequential ultracentrifugation were determined by DLS to be 13.1 +/- 7.5, 37.0 +/- 5.2, 21.5 +/- 0.8, 20.3 +/- 1.1, 8.6 +/- 1.5 and 8.8 +/- 2.0 nm, respectively. CONCLUSIONS: The proposed DLS method can differentiate the sizes of isolated lipoprotein particles, including large LDL and sd LDL, and might be used in clinical laboratories in combination with convenient lipoprotein separation. PMID- 20736247 TI - A web-based communication system for integrated care in cerebral palsy: design features, technical feasibility and usability. AB - We developed a secure, web-based system for parent-professional and inter professional communication. The aim was to improve communication in the care of children with cerebral palsy. We conducted a six-month trial of the system in three Dutch health-care regions. The participants were the parents of 30 cerebral palsy patients and 120 professional staff involved in their care. Information about system usage was extracted from the system's database. The experience of the parents and professionals was evaluated by a questionnaire after six months. The system proved to be technically robust and reliable. A total of 21 parents (70%) and 66 professionals (55%) used the system. The parents submitted 111 questions and 59 responses, with a mean of 5 questions (range 1-17) and 3 responses (range 1-9) per parent. The professionals submitted 79 questions and 237 responses, with a mean of 2 questions (range 1-8) and 4 responses (range 1 23) per professional. Most parents (95%) and some professionals (30%) reported value in using the system, which ranged from efficiency and accessibility to flexibility and transparency. The web-based communication system was technically feasible and produced improved parent-professional and inter-professional communication. It may be especially valuable if frequent interventions or consultations about a child's care are required, involving complex care networks of different professionals and organisations. PMID- 20736249 TI - 1,5-Anhydroglucitol levels are low irrespective of plasma glucose levels in patients with chronic liver disease. AB - BACKGROUND: Serum 1,5-anhydroglucitol (1,5-AG) is a known marker reflecting recent glycaemic control. In this study, we examined serum 1,5-AG levels in chronic liver disease (CLD) patients with and without diabetes mellitus. METHODS: Eighty patients with CLD were compared with 667 subjects without CLD. Glycaemic control of the CLD patients was evaluated by estimated glycated haemoglobin (HbA(1C)) calculated using the equation by Rohlfing et al. from mean plasma glucose because CLD patients have apparently low HbA(1C). RESULTS: When the study participants were divided into subgroups stratified by HbA(1C) levels, the CLD patients whose estimated HbA(1C) levels were less than 7.0% showed significantly lower 1,5-AG than their counterparts of the control subjects. Stepwise multivariable analysis revealed that estimated HbA(1C) was the significant explanatory variable for 1,5-AG in the CLD patients. However, in the CLD patients with estimated HbA(1C) less than 5.8%, only hepaplastin test was the significant explanatory variable for 1,5-AG. CONCLUSIONS: Serum 1,5-AG levels are low irrespective of plasma glucose levels in the CLD patients with and without diabetes. The CLD patients who had low serum 1,5-AG levels were associated with deteriorated liver function. PMID- 20736250 TI - A double heterozygote for familial hypercholesterolaemia and familial defective apolipoprotein B-100. AB - Autosomal dominant hypercholesterolaemia is genetically heterogeneous, but most commonly (approximately 93%) caused by mutations in low-density lipoprotein receptor (LDLR), where the disease is known as familial hypercholesterolaemia (FH), or apolipoprotein B-100 (APOB) (approximately 5.5%), where the disease is known as familial defective APOB (FDB), while in approximately 2% of patients the mutation is in the proprotein convertase subtilisin/kexin type 9 gene. Homozygous FH having inheritance of two LDLR mutations is a rare but recognized syndrome associated with an extreme hypercholesterolaemia and early-onset coronary artery disease. We present a 15-year-old girl with untreated total cholesterol levels of 8.8 mmol/L who was heterozygous for both the LDLR p.Leu479Pro and APOB p.Arg3527Gln mutation. Cascade testing confirmed the paternal origin of the LDLR mutation and revealed a maternal diagnosis of FDB. This case provides further evidence that the combined effect of an LDLR and an APOB mutation give rise to a phenotype more severe than either mutation alone and is more severe than homozygous FDB, but less severe than homozygous FH. It also highlights the need to consider the presence of additional mutations in families where relatives have varying phenotypes. PMID- 20736251 TI - Five novel mutations of SRD5A2 found in eight Chinese patients with 46,XY disorders of sex development. AB - Individuals with male karyotype (46,XY) affected by 5alpha-reductase type 2 deficiency, a rare autosomal recessive inherited disorder, can have an almost female phenotype or partially virilized external genitalia. Mutations in the steroid-5-alpha-reductase (SRD5A2) gene, leading to functional impairment of 5alpha-reductase type 2, are responsible for this disorder. Our present study analyzed SRD5A2 gene mutations in eight unrelated 46,XY Chinese patients with disorders of sex development. Direct sequencing of genomic DNA for SRD5A2 gene revealed the presence of one homozygous (p.Q6X) and seven compound heterozygous mutations (p.G203S/R227Q, p.L20P/R227Q, p.Q6X/p.A228V, p.C222Ffs232X/p.R246Q, p.W140X/F219Sfs278X, p.Q71X/L185Tfs192X and p.Q6X/p.N193S) in our patients. Among them, p.C222Ffs232X, p.A228V, p.Q71X, L185Tfs192X and p.W140X mutations have not been previously reported. These novel mutations may provide us new insights into the molecular mechanism of 5alpha-reductase type 2 deficiency. Seven out of eight patients had at least one variant in exon 4, and 8 of 12 (66.7%) mutations were located in exon 4. The expanded mutation database of the SRD5A2 gene should benefit patients in the diagnosis and treatment of this disease. PMID- 20736252 TI - Identification of epistatic effects using a protein-protein interaction database. AB - Epistasis (i.e. gene-gene interaction) has long been recognized as an important mechanism underlying the complexity of the genetic architecture of human traits. Definitions of epistasis range from the purely molecular to the traditional statistical measures of interaction. The statistical detection of epistasis usually does not map onto or easily relate to the biological interactions between genetic variations through their combined influence on gene expression or through their interactions at the gene product (i.e. protein) or DNA level. Recently, greater high-dimensional data on protein-protein interaction (PPI) and gene expression profiles have been collected that enumerates sets of biological interactions. To better align statistical and molecular models of epistasis, we present an example of how to incorporate the PPI information into the statistical analysis of interactions between copy number variations (CNVs). Among the 23 640 pairs of known human PPIs and the 1141 common CNVs detected among HapMap samples, we identified 37 pairs of CNVs overlapping with both genes of a PPI pair. Two CNV pairs provided sufficient genotype variation to search for epistatic effects on gene expression. Using 47 294 probe-specific gene expression levels as the outcomes, five epistatic effects were identified with P-value less than 10(-6). We found a CNV-CNV interaction significantly associated with gene expression of TP53TG3 (P-value of 2 * 10(-20)). The proteins associated with the CNV pair also bind TP53 which regulates the transcription of TP53TG3. This study demonstrates that using PPI data can assist in targeting statistical hypothesis testing to biological plausible epistatic interaction that reflects molecular mechanisms. PMID- 20736253 TI - Does the choice of phosphate binder affect trace element levels in chronic kidney disease patients treated by regular haemodialysis? AB - BACKGROUND: Ion exchange resins have been reported to bind copper and zinc. As the phosphate binder sevelamer hydrochloride is an ion exchange resin, we audited trace element levels in our haemodialysis cohort to determine whether sevelamer prescription affected trace element levels compared with other phosphate binders. METHODS: Samples for zinc, copper and selenium were taken in special tubes and measured by atomic absorption spectroscopy or inductively coupled plasma-mass spectrometry from 211 patients attending an inner city university hospital main dialysis centre. RESULTS: Of the patients, 12.9% were prescribed oral or intravenous trace element supplementation. Of the remainder, 5.5% of patients had low plasma copper, 37.4% low zinc and 45.6% low selenium. There was no difference in copper (16.7 +/- 0.2 vs 16.8 +/- 0.4 MUmol/L, respectively) and zinc (12.0 +/- 0.3 vs 11.6 +/- 0.2 MUmol/L) comparing patients prescribed sevelamer compared with other phosphate binders. Despite a high prevalence of statin prescription, total cholesterol (3.42 +/- 0.12 vs 3.89 +/- 0.08, P < 0.01), LDL-cholesterol (1.46 +/- 0.1 vs 2.00 +/- 0.07, P < 0.01) and total cholesterol/HDL-cholesterol ratio (2.82 +/- 0.15 vs 3.5216.7 +/- 0.2 vs 16.8 +/- 0.4 MUmol/L, P < 0.01) were lower in the sevelamer group compared with those prescribed other phosphate binders. On logistic regression analysis, serum zinc levels were associated with serum albumin (F 20.36, beta 0.174, CL 0.086-0.265, P < 0.001) and dialysis vintage (F 8.1, beta 0.008, CL 0.002-0.013, P = 0.005), copper levels with log CRP (F 31.4, beta 3.04, CL 0-1.97, P < 0.001) and urine volume (F 5.1, beta - 0.01, CL - 0.002-0, P = 0.024), and selenium levels with serum albumin (F 23.2, beta 0.016, CL 0.02-0.1, P < 0.001) and race (F 31.4, beta 3.62, P = 0.032), with selenium levels being greater in non-Caucasoids (0.9 +/- 0.02 vs 0.76 +/- 0.02 MUmol/L, P < 0.01). CONCLUSIONS: Trace element and micronutrient deficiencies were relatively common in this inner city population of outpatient haemodialysis patients. However, the prescription of different phosphate binders did not have an observable effect on serum copper and zinc levels, but those prescribed sevelamer did have lower lipid profiles compared with those prescribed other phosphate binders. Trace element concentrations were more associated with albumin, a marker of general nutritional status, with some differences according to ethnicity, most likely due to differences in dietary intake. PMID- 20736254 TI - Investigating fatigue in primary care. PMID- 20736255 TI - Who benefits from treating prehypertension? PMID- 20736256 TI - Whooping cough outbreak hits several US states. PMID- 20736262 TI - Special feature on the occasion of the 25th anniversary of NDT. PMID- 20736263 TI - The five most cited NDT articles from 1985 to 1993. PMID- 20736264 TI - The five most cited NDT articles from 1993 to 1999. PMID- 20736265 TI - The five most cited NDT papers from 2005 to 2009. PMID- 20736266 TI - Donor-recipient age matching improves years of graft function in deceased-donor kidney transplantation. AB - BACKGROUND: Donor and recipient age in kidney transplantation are known to affect graft and patient survival. In deceased-donor (DD) transplantation, donor and recipient age matching are being increasingly accepted as part of the kidney allocation programme. The aims of this study are to evaluate the effect of donor and recipient age on transplant outcomes and to determine the effect of changing existing allocation criteria to allocation based on age matching of donors and recipients on total graft years of function. METHODS: Using the Australia and New Zealand Dialysis and Transplant Registry, all DD kidney transplant recipients in Australia and New Zealand between 1991 and 2006 were analysed (n = 4616). Outcomes analysed were overall graft failure, death with functioning graft and serum creatinine. We calculated the mean time to graft loss ('years of graft function') for donor and recipient age cut-offs as 60 and 55 years, respectively, over up to 16 years follow-up. We then examined the gain in graft years if all older kidneys were allocated to older recipients. RESULTS: Older donors were associated with higher risk of overall graft failure [adjusted hazard ratio (HR) = 1.79, 95% confidence interval (95% CI) = 1.45, 2.21 and HR = 1.29, 95% CI = 1.09, 1.53, respectively] at 1-8 years post-transplant and higher serum creatinine at 1 and 5 years post-transplant (mean differences 32.74 micromol/L, 95% CI 27.60, 37.89 and 38.17 micromol/L, 95% CI 27.58, 48.77, respectively). Overall, young and old recipients with young donor kidneys have an additional two to three mean graft years compared to those receiving older donor kidneys. CONCLUSION: Donor and recipient age matching is an effective method of organ allocation to improve total graft years. PMID- 20736267 TI - Education of ESRD patients on dialysis modality selection: 'intensive haemodialysis first'. PMID- 20736268 TI - Migraine and risk of haemorrhagic stroke in women: prospective cohort study. AB - OBJECTIVES: To examine the association between migraine and migraine aura status with risk of haemorrhagic stroke. DESIGN: Prospective cohort study. SETTING: Women's Health Study, United States. PARTICIPANTS: 27,860 women aged >or=45 who were free from stroke or other major disease at baseline and had provided information on self reported migraine, aura status, and lipid values. MAIN OUTCOME MEASURES: Time to first haemorrhagic stroke and subtypes of haemorrhagic stroke. RESULTS: At baseline, 5130 (18%) women reported any history of migraine; of the 3612 with active migraine (migraine in the previous year), 1435 (40%) described having aura. During a mean of 13.6 years of follow-up, 85 haemorrhagic strokes were confirmed after review of medical records. Compared with women without a history of migraine, there was no increased risk of haemorrhagic stroke in those who reported any history of migraine (adjusted hazard ratio 0.98, 95% confidence interval 0.56 to 1.71, P=0.93). In contrast, risk was increased in women with active migraine with aura (2.25, 1.11 to 4.54, P=0.024). The age adjusted increased risk was stronger for intracerebral haemorrhage (2.78, 1.09 to 7.07, P=0.032) and for fatal events (3.56, 1.23 to 10.31, P=0.02). Four additional haemorrhagic stroke events were attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura had no increased risk for haemorrhagic stroke. CONCLUSION: Migraine with aura might, in addition to ischaemic events, also be a risk factor for haemorrhagic stroke. The relatively low number of events and attributable risk should caution against definitive conclusions and call for further confirmation of these observations. PMID- 20736269 TI - Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study. AB - OBJECTIVE: To estimate whether migraine in mid-life is associated with mortality from cardiovascular disease, other causes, and all causes. DESIGN: Population based cohort study. SETTING: Reykjavik, Iceland. PARTICIPANTS: 18,725 men and women, born 1907-35 and living in Reykjavik and adjacent communities. MAIN OUTCOME MEASURES: Mortality from cardiovascular disease, non-cardiovascular disease, and all causes. Questionnaires and clinical measures were obtained in mid-life (mean age 53, range 33-81) in the Reykjavik Study (1967-91). Headache was classified as migraine without aura, migraine with aura, or non-migraine headache. Median follow-up was 25.9 years (0.1-40.2 years), with 470,990 person years and 10,358 deaths: 4323 from cardiovascular disease and 6035 from other causes. We used Cox regression to estimate risk of death in those with migraine compared with others, after adjusting for baseline risk factors. RESULTS: People with migraine with aura were at increased risk of all cause mortality (adjusted (for sex and multivariables) hazard ratio 1.21, 95% confidence interval 1.12 to 1.30) and mortality from cardiovascular disease (1.27, 1.13 to 1.43) compared with people with no headache, while those with migraine without aura and non migraine headache were not. Further examination of mortality from cardiovascular disease shows that people with migraine with aura were at increased risk of mortality from coronary heart disease (1.28, 1.11 to 1.49) and stroke (1.40, 1.10 to 1.78). Women with migraine with aura were also at increased risk of mortality from non-cardiovascular disease (1.19, 1.06 to 1.35). CONCLUSIONS: Migraine with aura is an independent risk factor for cardiovascular and all cause mortality in men and women. The risk of mortality from coronary heart disease and stroke mortality is modestly increased in people with migraine, particularly those with aura. PMID- 20736270 TI - Commentary: practicalities of seeking consent and gaining understanding. PMID- 20736271 TI - Consent for blood transfusion. PMID- 20736272 TI - Migraine with aura and the risk of increased mortality. PMID- 20736273 TI - New kids on the block. PMID- 20736274 TI - Surgery and spondylosis. Inappropriate partners. PMID- 20736275 TI - Small studies in meta-analyses. Making the best of a little. PMID- 20736276 TI - NICE on bacterial meningitis. Possible additions to summary. PMID- 20736277 TI - Mildly abnormal liver tests. Don't forget coeliac disease and drug history. PMID- 20736278 TI - Mildly abnormal liver tests. Myth of gamma glutamyltransferase. PMID- 20736279 TI - War on drugs. Is drugs policy the great game? PMID- 20736280 TI - Hyperintensities on MRI. White matter and depression. PMID- 20736281 TI - Funding care for older people. Government guidance caused rise in long term care spending. PMID- 20736282 TI - Inequalities in mortality. Study rates, not standardised mortality ratios. PMID- 20736283 TI - Orphan drugs. Relating price determination to disease prevalence. PMID- 20736284 TI - Colorectal cancer screening. Randomised trials of flexible sigmoidoscopy. PMID- 20736286 TI - Axolotl Nanog activity in mouse embryonic stem cells demonstrates that ground state pluripotency is conserved from urodele amphibians to mammals. AB - Cells in the pluripotent ground state can give rise to somatic cells and germ cells, and the acquisition of pluripotency is dependent on the expression of Nanog. Pluripotency is conserved in the primitive ectoderm of embryos from mammals and urodele amphibians, and here we report the isolation of a Nanog ortholog from axolotls (axNanog). axNanog does not contain a tryptophan repeat domain and is expressed as a monomer in the axolotl animal cap. The monomeric form is sufficient to regulate pluripotency in mouse embryonic stem cells, but axNanog dimers are required to rescue LIF-independent self-renewal. Our results show that protein interactions mediated by Nanog dimerization promote proliferation. More importantly, they demonstrate that the mechanisms governing pluripotency are conserved from urodele amphibians to mammals. PMID- 20736288 TI - Moesin1 and Ve-cadherin are required in endothelial cells during in vivo tubulogenesis. AB - Endothelial tubulogenesis is a crucial step in the formation of functional blood vessels during angiogenesis and vasculogenesis. Here, we use in vivo imaging of living zebrafish embryos expressing fluorescent fusion proteins of beta-Actin, alpha-Catenin, and the ERM family member Moesin1 (Moesin a), to define a novel cord hollowing process that occurs during the initial stages of tubulogenesis in intersegmental vessels (ISVs) in the embryo. We show that the primary lumen elongates along cell junctions between at least two endothelial cells during embryonic angiogenesis. Moesin1-EGFP is enriched around structures that resemble intracellular vacuoles, which fuse with the luminal membrane during expansion of the primary lumen. Analysis of silent heart mutant embryos shows that initial lumen formation in the ISVs is not dependent on blood flow; however, stabilization of a newly formed lumen is dependent upon blood flow. Zebrafish moesin1 knockdown and cell transplantation experiments demonstrate that Moesin1 is required in the endothelial cells of the ISVs for in vivo lumen formation. Our analyses suggest that Moesin1 contributes to the maintenance of apical/basal cell polarity of the ISVs as defined by adherens junctions. Knockdown of the adherens junction protein Ve-cadherin disrupts formation of the apical membrane and lumen in a cell-autonomous manner. We suggest that Ve-cadherin and Moesin1 function to establish and maintain apical/basal polarity during multicellular lumen formation in the ISVs. PMID- 20736287 TI - HLH54F is required for the specification and migration of longitudinal gut muscle founders from the caudal mesoderm of Drosophila. AB - HLH54F, the Drosophila ortholog of the vertebrate basic helix-loop-helix domain encoding genes capsulin and musculin, is expressed in the founder cells and developing muscle fibers of the longitudinal midgut muscles. These cells descend from the posterior-most portion of the mesoderm, termed the caudal visceral mesoderm (CVM), and migrate onto the trunk visceral mesoderm prior to undergoing myoblast fusion and muscle fiber formation. We show that HLH54F expression in the CVM is regulated by a combination of terminal patterning genes and snail. We generated HLH54F mutations and show that this gene is crucial for the specification, migration and survival of the CVM cells and the longitudinal midgut muscle founders. HLH54F mutant embryos, larvae, and adults lack all longitudinal midgut muscles, which causes defects in gut morphology and integrity. The function of HLH54F as a direct activator of gene expression is exemplified by our analysis of a CVM-specific enhancer from the Dorsocross locus, which requires combined inputs from HLH54F and Biniou in a feed-forward fashion. We conclude that HLH54F is the earliest specific regulator of CVM development and that it plays a pivotal role in all major aspects of development and differentiation of this largely twist-independent population of mesodermal cells. PMID- 20736289 TI - The EGR family gene egrh-1 functions non-autonomously in the control of oocyte meiotic maturation and ovulation in C. elegans. AB - Oocyte production, maturation and ovulation must be coordinated with sperm availability for successful fertilization. In C. elegans this coordination involves signals from the sperm to the oocyte and somatic gonad, which stimulate maturation and ovulation. We have found that the C. elegans early growth response factor family member EGRH-1 inhibits oocyte maturation and ovulation until sperm are available. In the absence of sperm, egrh-1 mutants exhibit derepressed oocyte maturation marked by MAPK activation and ovulation. egrh-1 mutants exhibit ectopic oocyte differentiation in the distal gonadal arm and accumulate abnormal and degraded oocytes proximally. These defects result in reduced brood size and partially penetrant embryonic lethality. We have found that endogenous EGRH-1 protein and an egrh-1::gfp reporter gene are expressed in the sheath and distal tip cells of the somatic gonad, the gut and other non-gonadal tissues, as well as in sperm, but expression is not observed in oocytes. Results of tissue-specific egrh-1(RNAi) experiments and genetic mosaic analyses revealed that EGRH-1 function is necessary in the soma and, surprisingly, this function is required in both the gut and the somatic gonad. Based on transformation rescue experiments we hypothesize that EGRH-1 in the somatic gonad inhibits oocyte maturation and ovulation. PMID- 20736291 TI - Emergency preparedness--an early childhood educator's perspective. AB - As early childhood educators who participated in the discussion of optimal scene management involving children and families in the event of a radiological/nuclear event, the authors would suggest consideration be given to the formal preparation for evacuation of educators and families and how to ensure that families are provided factual and updated information. PMID- 20736290 TI - The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear. AB - Inner ear neurogenesis is positively regulated by the pro-neural bHLH transcription factors Ngn1 and NeuroD, but the factors that act upstream of this regulation are not well understood. Recent evidence in mouse and Drosophila suggests that neural development depends on proper chromatin remodeling, both for maintenance of neural stem cells and for proper neuronal differentiation. Here, we show that CHD7, an ATP-dependent chromatin remodeling enzyme mutated in human CHARGE syndrome, is necessary for proliferation of inner ear neuroblasts and inner ear morphogenesis. Conditional deletion of Chd7 in the developing otocyst using Foxg1-Cre resulted in cochlear hypoplasia and complete absence of the semicircular canals and cristae. Conditional knockout and null otocysts also had reductions in vestibulo-cochlear ganglion size and neuron number in combination with reduced expression of Ngn1, Otx2 and Fgf10, concurrent with expansion of the neural fate suppressor Tbx1 and reduced cellular proliferation. Heterozygosity for Chd7 mutations had no major effects on expression of otic patterning genes or on cell survival, but resulted in decreased proliferation within the neurogenic domain. These data indicate that epigenetic regulation of gene expression by CHD7 must be tightly coordinated for proper development of inner ear neuroblasts. PMID- 20736292 TI - Real-time three-dimensional speckle tracking echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony. AB - AIMS: left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in chronic heart failure patients. Current methods used to evaluate LVMD are technically challenging and do not assess all the components of LVMD simultaneously. We analysed real-time 3D speckle tracking (3DST) echocardiography as a novel method to assess LVMD. METHODS AND RESULTS: three-dimensional ST was performed in 60 unselected patients (71 +/- 9 years old; 39% with ischaemic cardiomyopathy) who were referred to optimize and to control of a CRT device; implanted according to current guidelines (9 added to be excluded from the protocol). Two standardized conditions [right ventricular (RV) versus an optimized biventricular (BiV) pacing modality] were tested. These two pacing modalities lead to two distinct electrical activation patterns. We sought to test the capability of 3DST to distinguish these two patterns. The LV ejection fraction was 24 +/- 9 in the RV mode and 29 +/- 10% in BiV. By 3DST, we measured global end-systolic LV deformation and dyssynchrony (standard deviation of the time to peak/16 LV segment). The 3D radial strain increased from 13.8 +/- 5.7 in the RV to 15.9 +/- 6.5% in theBiV mode, and the dyssynchrony index decreased from 15.1 +/- 5.0 to 11.8 +/- 4.1%. 3D longitudinal strain increased from -6.9 +/- 2.8 in the RV to 7.8 +/- 3.2% in the BiV mode, and the dyssynchrony index decreased from 14.2 +/- 4.8 to 11.5 +/- 5.0% (P < 0.01 for all). The 3D area strain (AS) increased from 15.4 +/- 6 in the RV to -18.3 +/- 7.0% in the BiV mode, and the dyssynchrony index decreased from 12.2 +/- 5.1 to 9.5 +/- 4.5% (P < 0.001 for all). CONCLUSION: When image quality is optimal, 3DST might offer a new rapid method to quantify global LVMD in CRT candidates. In a comparison of the utility of various 3D strain measurements, the 3D AS appears to be closed to the ideal parameter that we are looking for. PMID- 20736293 TI - Genome-wide analysis of thiourea-modulated salinity stress-responsive transcripts in seeds of Brassica juncea: identification of signalling and effector components of stress tolerance. AB - BACKGROUND AND AIMS: Abiotic stresses including salinity are the major constraints to crop production. In this regard, the use of thiourea (TU) in imparting salinity-stress tolerance to Indian mustard (Brassica juncea) has been demonstrated earlier. To gain an insight into the mechanism of TU action, various molecular and biochemical studies were conducted. METHODS: Microarray analysis was performed in seeds subjected to distilled water (control), 1 m NaCl, 1 m NaCl + 6.5 mm TU and 6.5 mm TU alone for 1 h. Real-time PCR validation of selected genes and biochemical studies were conducted under similar treatments at 1 h and 6 h. KEY RESULTS: The microarray analysis revealed a differential expression profile of 33 genes in NaCl- and NaCl + TU-treated seeds, most of which are established markers of stress tolerance. The temporal regulation of eight selected genes by real-time PCR indicated their early and co-ordinated induction at 1 h in NaCl + TU only. Besides, NaCl + TU-treated seeds also maintained a higher level of abscisic acid, reduced to oxidized glutathione (GSH : GSSG) ratio and activities of catalase, phenylalanine ammonia lyase and glutathione-S transferases, as compared with that of NaCl treatment. The addition of LaCl(3) (a specific calcium-channel blocker) restricted the responses of TU both at molecular and biochemical level suggesting the possible involvement of a cytosolic calcium burst in the TU-mediated response. The TU-alone treatment was comparable to that of the control; however, it reduced the expression of some transcription factors and heat-shock proteins presumably due to the stabilization of the corresponding proteins. CONCLUSIONS: The TU treatment co-ordinately regulates different signalling and effector mechanisms at an early stage to alleviate stress even under a high degree of salinity. This also indicates the potential of TU to be used as an effective bioregulator to impart salinity tolerance under field conditions. PMID- 20736294 TI - Imatinib upregulates compensatory integrin signaling in a mouse model of gastrointestinal stromal tumor and is more effective when combined with dasatinib. AB - Activating mutations in the Kit receptor tyrosine kinase are associated with gastrointestinal stromal tumor (GIST). Imatinib inhibits Kit and is front-line therapy for GIST. However, imatinib most often elicits a partial response or stable disease, and most GIST patients who initially respond to imatinib eventually acquire resistance. Thus, improved treatment strategies for GIST are needed. We investigated the role of Src family kinases (SFK) in tumorigenesis in a mouse model of human GIST. The SFKs Src and Lyn were active in GIST, and surprisingly, imatinib treatment stimulated their phosphorylation/activation. We show that integrin signaling activates focal adhesion kinase and, consequently, SFKs in GIST and that imatinib enhances integrin signaling, implying a role for the extracellular matrix and integrin signaling in tumor maintenance and imatinib resistance. Dasatinib, an inhibitor of SFKs and Kit, inhibited SFK and focal adhesion kinase activation in GIST but also inhibited Kit and Kit-dependent downstream signaling pathways including phosphoinositide 3-kinase and mitogen activated protein kinase, but not signal transducer and activator of transcription (STAT) signaling. Whereas dasatinib and imatinib alone both produced a minimal histopathologic response, combination therapy improved their efficacy, leading to increased necrosis in GIST. These results highlight the importance of SFK and STAT signaling in GIST and suggest that the clinical efficacy of imatinib may be limited by the stimulation of integrin signaling. PMID- 20736295 TI - Regional control of tumor growth. AB - Tumors implanted near the scapulae have been shown to grow four times faster than the same tumors implanted at the iliac crest. Although there were marked differences in the vascularization of tumors from these two different sites, the mechanism controlling regional angiogenesis was not identified. Here, we show site-specific growth of intraperitoneal tumor implants in the mouse abdomen. Our data indicate that the angiogenic response of the host differs significantly between the upper and lower sites in the mouse abdomen and reveal that the expansion of tumor mass is restricted to sites with low angiogenic responses, such as the bowel mesentery in the lower abdomen. We show that, in this model, this suppression of angiogenesis is due to an expression gradient of thrombospondin-1 (TSP-1), a potent endogenous angiogenesis inhibitor. Mice with a targeted deletion of TSP-1 no longer show regional restriction of tumor growth. The physiologic relevance of these findings may be seen in patients with peritoneal carcinomatosis, whereby tumors spread within the peritoneal cavity and show differential growth in the upper and lower abdomen. We hypothesize that the difference in tumor growth in these patients may be due to a gradient of TSP-1 expression in stroma. Finally, our studies suggest that upregulation of TSP-1 in tumor cells is one method to suppress the growth of tumors in the upper abdomen. PMID- 20736296 TI - Autophagy induction with RAD001 enhances chemosensitivity and radiosensitivity through Met inhibition in papillary thyroid cancer. AB - Although autophagy is generally considered a prosurvival mechanism that preserves viability, there is evidence that it could drive an alternative programmed cell death pathway in cells with defects in apoptosis. Because the inhibition of autophagic activity promotes resistance to both chemotherapy and external beam radiation in papillary thyroid cancer (PTC), we determined if RAD001, a potent activator of autophagy, improves the efficacy of either therapy. We found that RAD001 increased the expression level of light chain 3-II, a marker for autophagy, as well as autophagosome formation in cell lines and in human PTC ex vivo. RAD001 sensitized PTC to doxorubicin and external beam radiation in a synergistic fashion, suggesting that combination therapy could improve therapeutic response at less toxic concentrations. The effects of RAD001 were abrogated by RNAi knockdown of the autophagy-related gene 5, suggesting that RAD001 acts, in part, by enhancing autophagy. Because the synergistic activity of RAD001 with doxorubicin and external radiation suggests distinct and complementary mechanisms of action, we characterized how autophagy modulates signaling pathways in PTC. To do so, we performed kinome profiling and discovered that autophagic activation resulted in Src phosphorylation and Met dephosphorylation. Src inhibition did not reverse the effects of RAD001, whereas Met inhibition reversed the effects of autophagy blockade on chemosensitivity. These results suggest that the anticancer effects of autophagic activation are mediated largely through Met. We conclude that RAD001 induces autophagy, which enhances the therapeutic response to cytotoxic chemotherapy and external beam radiation in PTC. PMID- 20736297 TI - Cyclin-dependent kinase 4-mediated phosphorylation inhibits Smad3 activity in cyclin D-overexpressing breast cancer cells. AB - Smad3, a component of the transforming growth factor beta signaling cascade, contributes to G(1) arrest in breast cancer cells. Cyclin D1/cyclin-dependent kinase 4 (CDK4) promotes G(1)-S-phase transition, and CDK phosphorylation of Smad3 has been associated with inhibition of Smad3 activity. We hypothesized that overexpression of cyclin D1 exerts tumorigenic effects in breast cancer cells through CDK4-mediated phosphorylation and inhibition of Smad3 and release of G(1) arrest. Real-time quantitative reverse transcription-PCR and immunoblotting were used to evaluate expression of study proteins in cyclin D1-overexpressing breast cancer cells. Smad3 transcriptional activity and cell cycle control were examined in cells transfected with wild-type (WT) Smad3 or Smad3 with single or multiple CDK phosphorylation site mutations (M) in the presence or absence of the CDK4 inhibitor or cotransfection with cdk4 small interfering RNA (siRNA). Transfection of the Smad3 5M construct resulted in decreased c-myc and higher p15(INK4B) expression. Compared with WT Smad3, overexpression of the Smad3 T8, T178, 4M, or 5M mutant constructs resulted in higher Smad3 transcriptional activity. Compared with cells transfected with WT Smad3, Smad3 transcriptional activity was higher in cells overexpressing Smad3 mutant constructs and treated with the CDK4 inhibitor or transfected with cdk4 siRNA. Cells transfected with Smad3 T8 or T178 and treated with the CDK4 inhibitor showed an increase in the G(1) cell population. Inhibition of CDK-mediated Smad3 phosphorylation released cyclin D1 regulated blockade of Smad3 transcriptional activity and recovered cell cycle arrest in breast cancer cells. Targeted inhibition of CDK4 activity may have a role in the treatment of cyclin D-overexpressing breast cancers. PMID- 20736298 TI - Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. AB - OBJECTIVES: A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2(+) previously treated advanced breast cancer or metastatic breast cancer (MBC). Here, we report final analyses of overall survival. PATIENTS AND METHODS: Women with HER-2(+) MBC who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab, were randomized to lapatinib (1,250 mg/day) plus capecitabine (2,000 mg/m(2)) or capecitabine monotherapy (2,500 mg/m(2)) on days 1-14 of a 21-day cycle. RESULTS: At enrollment termination, 399 patients were randomized, and nine were being screened and were offered combination treatment. In total, 207 and 201 patients were enrolled to combination therapy and monotherapy, respectively. Thirty-six patients receiving monotherapy crossed over to combination therapy following enrollment termination. The median overall survival times were 75.0 weeks for the combination arm and 64.7 weeks for the monotherapy arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.71-1.08; p = .210). A Cox regression analysis considering crossover as a time-dependent covariate suggested a 20% lower risk for death for patients treated with combination therapy (HR, 0.80; 95% CI, 0.64-0.99; p = .043). The low incidence of serious adverse events was consistent with previously reported rates. CONCLUSIONS: Although premature enrollment termination and subsequent crossover resulted in insufficient power to detect differences in overall survival, exploratory analyses demonstrate a trend toward a survival advantage with lapatinib plus capecitabine. These data continue to support the efficacy of lapatinib in patients with HER-2(+) MBC. PMID- 20736299 TI - Smoking and ethics: what are the duties of oncologists? AB - The World Health Organization's 2009 report on the world's tobacco epidemic predicts that, unchecked, tobacco use will kill a billion people in this century. Oncologists have a special professional role to play in combating this epidemic. Based on two views of professionalism, this editorial argues that oncologists have three duties. First, oncologists should be role models. They should not smoke themselves and urge their colleagues to do the same. Second, oncologists must strongly advise their own patients to stop smoking and advocate for tobacco free environments in their patients' communities. Third, oncologists have duties to their international colleagues. They should share their experience in combating tobacco use with them, encourage and assist them to quit smoking, and help them advocate for smoke-free environments. Further, oncologists should work to ratify the Framework Convention on Tobacco Control in their own country. PMID- 20736300 TI - The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin. AB - Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. In this study, we tested the hypothesis that dermal fibroblasts regulate the constitutive skin color of individuals ranging from very light to very dark. We used microarray analysis to compare gene expression patterns in fibroblasts derived from lighter skin types compared to darker skin types, with a focus on secreted proteins. We identified a number of genes that differ dramatically in expression and, among the expressed proteins, neuregulin 1, which is secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting that it is one of the major factors determining human skin color. PMID- 20736301 TI - Chemokine expression and control of muscle cell migration during myogenesis. AB - Adult regenerative myogenesis is vital for restoring normal tissue structure after muscle injury. Muscle regeneration is dependent on progenitor satellite cells, which proliferate in response to injury, and their progeny differentiate and undergo cell-cell fusion to form regenerating myofibers. Myogenic progenitor cells must be precisely regulated and positioned for proper cell fusion to occur. Chemokines are secreted proteins that share both leukocyte chemoattractant and cytokine-like behavior and affect the physiology of a number of cell types. We investigated the steady-state mRNA levels of 84 chemokines, chemokine receptors and signaling molecules, to obtain a comprehensive view of chemokine expression by muscle cells during myogenesis in vitro. A large number of chemokines and chemokine receptors were expressed by primary mouse muscle cells, especially during times of extensive cell-cell fusion. Furthermore, muscle cells exhibited different migratory behavior throughout myogenesis in vitro. One receptor-ligand pair, CXCR4-SDF-1alpha (CXCL12), regulated migration of both proliferating and terminally differentiated muscle cells, and was necessary for proper fusion of muscle cells. Given the large number of chemokines and chemokine receptors directly expressed by muscle cells, these proteins might have a greater role in myogenesis than previously appreciated. PMID- 20736304 TI - Phosphorylation of STIM1 at ERK1/2 target sites modulates store-operated calcium entry. AB - Store-operated calcium entry (SOCE) is an important Ca2+ entry pathway that regulates many cell functions. Upon store depletion, STIM1, a transmembrane protein located in the endoplasmic reticulum (ER), aggregates and relocates close to the plasma membrane (PM) where it activates store-operated calcium channels (SOCs). Although STIM1 was early defined as a phosphoprotein, the contribution of the phosphorylation has been elusive. In the present work, STIM1 was found to be a target of extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in vitro, and we have defined the ERK1/2-phosphorylated sites on the STIM1 sequence. Using HEK293 cells stably transfected for the expression of tagged STIM1, we found that alanine substitution mutants of ERK1/2 target sites reduced SOCE significantly, suggesting that phosphorylation of these residues are required to fully accomplish SOCE. Indeed, the ERK1/2 inhibitors PD184352 and PD0325901 decreased SOCE in transfected cells. Conversely, 12-O-tetradecanoylphorbol-13-acetate, which activates ERK1/2, enhanced SOCE in cells expressing wild-type tagged STIM1, but did not potentiate Ca2+ influx in cells expressing serine to alanine mutations in ERK1/2 target sites of STIM1. Alanine substitution mutations decreased Ca2+ influx without disturbing the aggregation of STIM1 upon store depletion and without affecting the relocalization in ER-PM punctae. However, our results suggest that STIM1 phosphorylation at ERK1/2 target sites can modulate SOCE by altering STIM1 binding to SOCs, because a significant decrease in FRET efficiency was observed between alanine substitution mutants of STIM1-GFP and ORAI1-CFP. PMID- 20736302 TI - Regulation of mixed-lineage kinase activation in JNK-dependent morphogenesis. AB - Normal cells respond appropriately to various signals, while sustaining proper developmental programs and tissue homeostasis. Inappropriate signal reception, response or attenuation, can upset the normal balance of signaling within cells, leading to dysfunction or tissue malformation. To understand the molecular mechanisms that regulate protein-kinase-based signaling in the context of tissue morphogenesis, we analyzed the domain requirements of Drosophila Slpr, a mixed lineage kinase (MLK), for Jun N-terminal kinase (JNK) signaling. The N-terminal half of Slpr is involved in regulated signaling whereas the C-terminal half promotes cortical protein localization. The SH3 domain negatively regulates Slpr activity consistent with autoinhibition via a conserved proline motif. Also, like many kinases, conserved residues in the activation segment of the catalytic domain regulate Slpr. Threonine 295, in particular, is essential for function. Slpr activation requires dual input from the MAP4K Misshapen (Msn), through its C terminal regulatory domain, and the GTPase Rac, which both bind to the LZ-CRIB region of Slpr in vitro. Although Rac is sufficient to activate JNK signaling, our results indicate that there are Slpr-independent functions for Rac in dorsal closure. Finally, expression of various Slpr constructs alone or with upstream activators reveals a wide-ranging response at the cell and tissue level. PMID- 20736303 TI - Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle. AB - Regulation of actin filament assembly is essential for efficient contractile activity in striated muscle. Leiomodin is an actin-binding protein and homolog of the pointed-end capping protein, tropomodulin. These proteins are structurally similar, sharing a common domain organization that includes two actin-binding sites. Leiomodin also contains a unique C-terminal extension that has a third actin-binding WH2 domain. Recently, the striated-muscle-specific isoform of leiomodin (Lmod2) was reported to be an actin nucleator in cardiomyocytes. Here, we have identified a function of Lmod2 in the regulation of thin filament lengths. We show that Lmod2 localizes to the pointed ends of thin filaments, where it competes for binding with tropomodulin-1 (Tmod1). Overexpression of Lmod2 results in loss of Tmod1 assembly and elongation of the thin filaments from their pointed ends. The Lmod2 WH2 domain is required for lengthening because its removal results in a molecule that caps the pointed ends similarly to Tmod1. Furthermore, Lmod2 transcripts are first detected in the heart after it has begun to beat, suggesting that the primary function of Lmod2 is to maintain thin filament lengths in the mature heart. Thus, Lmod2 antagonizes the function of Tmod1, and together, these molecules might fine-tune thin filament lengths. PMID- 20736305 TI - SPICE--a previously uncharacterized protein required for centriole duplication and mitotic chromosome congression. AB - Proper assembly and function of a bipolar mitotic spindle is crucial for faithful bidirectional chromosome segregation during cell division. In animal cells, the two poles of the mitotic spindle are organized by centrosomes, microtubule organizing structures composed of a pair of centrioles surrounded by the so called pericentriolar material. Proteomic studies have revealed a large number of centrosome proteins, but many remain uncharacterized. Here, we characterize SPICE, a protein that localizes to spindle microtubules in mitosis and to centrioles throughout the cell cycle. RNAi-mediated depletion of SPICE in human cells impairs centriole duplication and causes severe mitotic defects. SPICE depletion compromises spindle architecture, spindle pole integrity and chromosome congression, even in cells in which centriole duplication has occurred. Our data suggest that SPICE is an important dual-function regulator required for centriole duplication and for proper bipolar spindle formation and chromosome congression in mitosis. PMID- 20736307 TI - ERK5 is required for VEGF-mediated survival and tubular morphogenesis of primary human microvascular endothelial cells. AB - Extracellular signal-regulated kinase 5 (ERK5) is activated in response to environmental stress and growth factors. Gene ablation of Erk5 in mice is embryonically lethal as a result of disruption of cardiovascular development and vascular integrity. We investigated vascular endothelial growth factor (VEGF) mediated ERK5 activation in primary human dermal microvascular endothelial cells (HDMECs) undergoing proliferation on a gelatin matrix, and tubular morphogenesis within a collagen gel matrix. VEGF induced sustained ERK5 activation on both matrices. However, manipulation of ERK5 activity by siRNA-mediated gene silencing disrupted tubular morphogenesis without impacting proliferation. Overexpression of constitutively active MEK5 and ERK5 stimulated tubular morphogenesis in the absence of VEGF. Analysis of intracellular signalling revealed that ERK5 regulated AKT phosphorylation. On a collagen gel, ERK5 regulated VEGF-mediated phosphorylation of the pro-apoptotic protein BAD and increased expression of the anti-apoptotic protein BCL2, resulting in decreased caspase-3 activity and apoptosis suppression. Our findings suggest that ERK5 is required for AKT phosphorylation and cell survival and is crucial for endothelial cell differentiation in response to VEGF. PMID- 20736306 TI - Formation of extra centrosomal structures is dependent on beta-catenin. AB - beta-Catenin has important roles in cell-cell adhesion and in the regulation of gene transcription. Mutations that stabilize beta-catenin are common in cancer, but it remains unclear how these mutations contribute to cancer progression. beta Catenin is also a centrosomal component involved in centrosome separation. Centrosomes nucleate interphase microtubules and the bipolar mitotic spindle in normal cells, but their organization and function in human cancers are abnormal. Here, we show that expression of stabilized mutant beta-catenin, which mimics mutations found in cancer, results in extra non-microtubule nucleating structures that contain a subset of centrosome proteins including gamma-tubulin and centrin, but not polo-like kinase 4 (Plk4), SAS-6 or pericentrin. A transcriptionally inactive form of beta-catenin also gives rise to abnormal structures of centrosome proteins. HCT116 human colon cancer cell lines, from which the mutant beta-catenin allele has been deleted, have reduced numbers of cells with abnormal centrosome structures and S-phase-arrested, amplified centrosomes. RNAi-mediated depletion of beta-catenin from centrosomes inhibits S-phase-arrested amplification of centrosomes. These results indicate that beta-catenin is required for centrosome amplification, and mutations in beta-catenin might contribute to the formation of abnormal centrosomes observed in cancers. PMID- 20736308 TI - beta-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release. AB - The dystrophin-glycoprotein complex (DGC) links the extracellular matrix and actin cytoskeleton. Caveolae form membrane arrays on smooth muscle cells; we investigated the mechanism for this organization. Caveolin-1 and beta dystroglycan, the core transmembrane DGC subunit, colocalize in airway smooth muscle. Immunoprecipitation revealed the association of caveolin-1 with beta dystroglycan. Disruption of actin filaments disordered caveolae arrays, reduced association of beta-dystroglycan and caveolin-1 to lipid rafts, and suppressed the sensitivity and responsiveness of methacholine-induced intracellular Ca2+ release. We generated novel human airway smooth muscle cell lines expressing shRNA to stably silence beta-dystroglycan expression. In these myocytes, caveolae arrays were disorganized, caveolae structural proteins caveolin-1 and PTRF/cavin were displaced, the signaling proteins PLCbeta1 and G(alphaq), which are required for receptor-mediated Ca2+ release, were absent from caveolae, and the sensitivity and responsiveness of methacholine-induced intracellular Ca2+ release, was diminished. These data reveal an interaction between caveolin-1 and beta-dystroglycan and demonstrate that this association, in concert with anchorage to the actin cytoskeleton, underpins the spatial organization and functional role of caveolae in receptor-mediated Ca2+ release, which is an essential initiator step in smooth muscle contraction. PMID- 20736309 TI - The myotubularin phosphatase MTMR4 regulates sorting from early endosomes. AB - Phosphatidylinositol 3-phosphate [PtdIns(3)P] regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11- and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4(C407A), the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of MTMR4(C407A), which acts as a dominant-negative construct, significantly accelerated Tfn recycling. However, in MTMR4 knockdown cells Tfn recycling was unchanged, suggesting that other MTMs might also contribute to recycling. MTMR4 regulated the subcellular distribution of Rab11 and, in cells with RNAi-mediated knockdown of MTMR4, Rab11 was directed away from the pericentriolar recycling compartment. The subcellular distribution of VAMP3, a v-SNARE protein that resides in recycling endosomes and endosome-derived transport vesicles, was also regulated by MTMR4. Therefore, MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway. PMID- 20736311 TI - Multisite phosphorylation of Erk5 in mitosis. AB - The MAP kinase Erk5 plays important roles in cellular proliferation, and has recently been implicated in the regulation of mitosis. The classic pathway of Erk5 activation involves dual phosphorylation at its TEY microdomain by the upstream regulating kinase MEK5. Here we describe a second pathway that controls Erk5 phosphorylation. This pathway is activated in mitotic cells and involves kinase activities distinct from MEK5. Studies aimed at identifying these kinases suggested that CDK1 activity is required to sustain Erk5 phosphorylation in mitosis, as treatment with RO3306, a CDK1 inhibitor, reversed mitotic phosphorylation of Erk5. Moreover, CDK1 co-precipitated with Erk5 in mitotic cells. The mitotic phosphorylation of Erk5 occurs at multiple sites located at its unique C-terminal region, within an Erk5 subdomain that has formerly been implicated in the control of the subcellular location of Erk5. Furthermore, molecular studies indicated that phosphorylation at these sites may participate in the control of the transit of Erk5 between the cytosol and the nucleus, in addition to regulating its transcriptional activity. Together, our results demonstrate the existence of a second Erk5 phosphorylation pathway, that is activated in mitosis, and that may participate in the regulation of Erk5 functions. PMID- 20736310 TI - Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy. AB - The mucolipin (TRPML) subfamily of transient receptor potential (TRP) cation channels consists of three members that play various roles in the regulation of membrane and protein sorting along endo-lysosomal pathways. Loss-of-function mutations in TRPML1 cause the neurodegenerative lysosomal storage disorder, mucolipidosis type IV (MLIV), whereas a gain-of-function mutation in TRPML3 is principally implicated in the hearing-impaired and abnormally pigmented varitint waddler mouse. Currently, TRPML2 is not implicated in any pathological disorder, but we have recently shown that it is a functional cation channel that physically interacts with TRPML1 and TRPML3 to potentially regulate lysosomal integrity. Here, we show that mutant TRPMLs heteromultimerize with other mutant and wild type TRPMLs to regulate cell viability and starvation-induced autophagy, a process that mediates macromolecular and organellar turnover under cell starvation conditions. Heteromultimerization of dominant-negative TRPMLs with constitutively active TRPMLs rescues cells from the cytotoxic effects of TRPML constitutive activity. Moreover, dominant-negative TRPML1 channels, including a mutant channel directly implicated in MLIV pathology, also inhibit starvation induced autophagy by interacting with and affecting native TRPML channel function. Collectively, our results indicate that heteromultimerization of TRPML channels plays a role in various TRPML-regulated mechanisms. PMID- 20736312 TI - Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion. AB - Upon stimulation with angiogenic factors, vascular endothelial cells (ECs) secrete a negative-feedback regulator of angiogenesis, vasohibin-1 (VASH1). Because VASH1 lacks a classical signal sequence, it is not clear how ECs secrete VASH1. We isolated a small vasohibin-binding protein (SVBP) composed of 66 amino acids. The level of Svbp mRNA was relatively high in the bone marrow, spleen and testes of mice. In cultured ECs, Vash1 mRNA was induced by VEGF, and Svbp mRNA was expressed constitutively. The interaction between VASH1 and SVBP was confirmed using the BIAcore system and immunoprecipitation analysis. Immunocytochemical analysis revealed that SVBP colocalized with VASH1 in ECs. In polarized epithelial cells, SVBP accumulated on the apical side, whereas VASH1 was present throughout the cells and partially colocalized with SVBP. Transfection of SVBP enhanced VASH1 secretion, whereas knockdown of endogenous SVBP markedly reduced VASH1 secretion. SVBP increased the solubility of VASH1 protein in detergent solution and inhibited the ubiquitylation of VASH1 protein. Moreover, co-transfection of SVBP significantly augmented the inhibitory effect of VASH1 on EC migration. These results indicate that SVBP acts as a secretory chaperone for VASH1 and contributes to the anti-angiogenic activity of VASH1. PMID- 20736313 TI - Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells. AB - Ovarian folliculogenesis is driven by the combined action of endocrine cues and paracrine factors. The oocyte secretes powerful mitogens, such as growth differentiation factor 9 (GDF9), that regulate granulosa cell proliferation, metabolism, steroidogenesis and differentiation. This study investigated the role of the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase 1 and 2 (ERK1/2; also known as MAPK3/1) signaling pathway on GDF9 action on granulosa cells. Results show that mitogenic action of the oocyte is prevented by pharmacological inhibition of the EGFR-ERK1/2 pathway. Importantly, EGFR ERK1/2 activity as well as rous sarcoma oncogene family kinases (SFK) are required for signaling through SMADs, mediating GDF9, activin A and TGFbeta1 mitogenic action in granulosa cells. GDF9 could not activate ERK1/2 or affect EGF stimulated ERK1/2 in granulosa cells. However, induction of the SMAD3-specific CAGA reporter by GDF9 in granulosa cells required active EGFR, SFKs and ERK1/2 as did GDF9-responsive gene expression. Finally, the EGFR-SFKs-ERK1/2 pathway was shown to be required for the maintenance of phosphorylation of the SMAD3 linker region. Together our results suggest that receptivity of granulosa cells to oocyte-secreted factors, including GDF9, is regulated by the level of activation of the EGFR and resulting ERK1/2 activity, through the requisite permissive phosphorylation of SMAD3 in the linker region. Our results indicate that oocyte secreted TGFbeta-like ligands and EGFR-ERK1/2 signaling are cooperatively required for the unique granulosa cell response to the signal from oocytes mediating granulosa cell survival and proliferation and hence the promotion of follicle growth and ovulation. PMID- 20736314 TI - Exocytosis, dependent on Ca2+ release from Ca2+ stores, is regulated by Ca2+ microdomains. AB - The relationship between the cellular Ca2+ signal and secretory vesicle fusion (exocytosis) is a key determinant of the regulation of the kinetics and magnitude of the secretory response. Here, we have investigated secretion in cells where the exocytic response is controlled by Ca2+ release from intracellular Ca2+ stores. Using live-cell two-photon microscopy that simultaneously records Ca2+signals and exocytic responses, we provide evidence that secretion is controlled by changes in Ca2+ concentration [Ca2+] in relatively large-volume microdomains. Our evidence includes: (1) long latencies (>2 seconds) between the rise in [Ca2+] and exocytosis, (2) observation of exocytosis all along the lumen and not clustered around Ca2+ release hot-spots, (3) high affinity (Kd=1.75 microM) Ca2+dependence of exocytosis, (4) significant reduction in exocytosis in the presence of cytosolic EGTA, (5) spatial exclusion of secretory granules from the cell membrane by the endoplasmic reticulum, and (6) inability of local Ca2+ responses to trigger exocytosis. These results strongly indicate that the control of exocytosis, triggered by Ca2+ release from stores, is through the regulation of cytosolic[Ca2+] within a microdomain. PMID- 20736316 TI - Spatially defined Dsh-Lgl interaction contributes to directional tissue morphogenesis. AB - The process of epithelial morphogenesis defines the structure of epidermal tissue sheets. One such sheet, the ventral epidermis of the Drosophila embryo, shows both intricate segmental patterning and complex cell organization. Within a segment, cells produce hair-like denticles in a stereotypical and highly organized pattern over the surface of the tissue. To understand the cell biological basis of this process, we examined cell shapes and alignments, and looked for molecules that showed an asymmetric distribution in this tissue. We found that apical polarity determinants and adherens junctions were enriched at the dorsal and ventral borders of cells, whereas basolateral determinants were enriched at the anterior and posterior borders. We report that the basolateral determinant Lgl has a novel function in the planar organization of the embryonic epidermis, and this function depends on Dsh and myosin. We conclude that apical basal proteins, used to establish polarity within a cell, can be independently co opted to function in epithelial morphogenesis. PMID- 20736315 TI - Specific replication origins promote DNA amplification in fission yeast. AB - To ensure equal replication of the genome in every eukaryotic cell cycle, replication origins fire only once each S phase and do not fire after passive replication. Failure in these controls can lead to local amplification, contributing to genome instability and the development of cancer. To identify features of replication origins important for such amplification, we have investigated origin firing and local genome amplification in the presence of excess helicase loaders Cdc18 and Cdt1 in fission yeast. We find that S phase controls are attenuated and coordination of origin firing is lost, resulting in local amplification. Specific origins are necessary for amplification but act only within a permissive chromosomal context. Origins associated with amplification are highly AT-rich, fire efficiently and early during mitotic S phase, and are located in large intergenic regions. We propose that these features predispose replication origins to re-fire within a single S phase, or to remain active after passive replication. PMID- 20736318 TI - Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: improvement of fasting glycemia in diabetic db/db mice. AB - Excessive hepatic glucose production through the gluconeogenesis pathway is partially responsible for the elevated glucose levels observed in patients with type 2 diabetes mellitus (T2DM). The forkhead transcription factor forkhead box O1 (Foxo1) plays a crucial role in mediating the effect of insulin on hepatic gluconeogenesis. Here, using a db/db mouse model, we demonstrate the effectiveness of Foxo1 inhibitor, an orally active small-molecule compound, as a therapeutic drug for treating T2DM. Using mass spectrometric affinity screening, we discovered a series of compounds that bind to Foxo1, identifying among them the compound, 5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4 dihydroquinoline-3-carboxylic acid (AS1842856), which potently inhibits human Foxo1 transactivation and reduces glucose production through the inhibition of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase mRNA levels in a rat hepatic cell line. Oral administration of AS1842856 to diabetic db/db mice led to a drastic decrease in fasting plasma glucose level via the inhibition of hepatic gluconeogenic genes, whereas administration to normal mice had no effect on the fasting plasma glucose level. Treatment with AS1842856 also suppressed an increase in plasma glucose level caused by pyruvate injection in both normal and db/db mice. Taken together, these findings indicate that the Foxo1 inhibitor represents a new class of drugs for use in treating T2DM. PMID- 20736317 TI - A common prostate cancer risk variant 5' of microseminoprotein-beta (MSMB) is a strong predictor of circulating beta-microseminoprotein (MSP) levels in multiple populations. AB - BACKGROUND: beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer. METHODS: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. RESULTS: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10(-8)), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 * 10(-6)), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. CONCLUSIONS: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. IMPACT: This supports the hypothesis that rs10993994 may be the biologically functional allele. PMID- 20736319 TI - An updated and simplified method for bile duct cannulation of rats. AB - The single bile duct cannulated rat model was used for short-term intestinal absorption studies. Rats were randomly assigned to three groups: (A) bile duct cannulated, (B) control laparotomy and (C) no treatment. The body weight and health of the rats were monitored before and until day 5 after surgery, while bile flow was measured in group A on day 2. On the fifth day, tail vein blood was harvested, and alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin were quantified. Analysis of variance showed no significant difference between the groups for these parameters. This study demonstrated the suitability of a surgical rat model feasible for evaluation of the impact of bile in pharmacokinetic studies. PMID- 20736320 TI - Differences between human and rat intestinal and hepatic bisphenol A glucuronidation and the influence of alamethicin on in vitro kinetic measurements. AB - The extent to which membrane-disrupting agents, such as alamethicin, may alter cofactor transport and influence in vitro kinetic measurements of glucuronidation is a major concern regarding the characterization and extrapolation of inter- and intraspecies pharmacokinetics of bisphenol A (BPA). An additional concern is the omission of a BPA intestinal metabolism component in current pharmacokinetic models used to assess oral exposure. In this study, BPA glucuronidation in native hepatic microsomes from female rat and female human liver displayed higher V(max) values than that in males. In the presence of alamethicin, all hepatic V(max) values increased; however, this increase was disproportionately greater in males and gender differences were no longer observed. Female rats exhibited a much higher K(m) than all other species and genders; the addition of alamethicin had little influence on K(m) values for any of the test systems. The dissimilar K(m) measured for female rat suggests that different UDP-glucuronosyltransferase (UGT) enzyme(s) are involved in BPA glucuronidation. The presence of different UGTs in female rat was confirmed using Hill coefficients measured from diclofenac mediated chemical inhibition assays within hepatic microsomes and purified human UGT2B7 and UGT2B15. Mixed-gender human intestinal microsomes showed little BPA glucuronidation reactivity compared with those from male rat intestine. Male rat intestinal microsomes in the presence of alamethicin exhibited a V(max) that was nearly 30-fold higher than that for mixed human microsomes. The species and gender metabolic differences we observed between rat and human liver and intestine provide key information for delineating BPA pharmacokinetics needed for human health risk assessment. PMID- 20736321 TI - Expression and functional analysis of hepatic cytochromes P450, nuclear receptors, and membrane transporters in 10- and 25-week-old db/db mice. AB - Proper characterization of animal models used for efficacy and safety assessment is crucial. The present study focuses on characterizing proteins that are important components of the absorption, distribution, metabolism, and elimination of xenobiotics. Hepatic gene expression of Cyp2b10, Cyp2c29, Cyp3a11, Cyp2e1, Cyp4a10, Nr1i2, Nr1i3, slco1a1, slco1a4, slco1b2, abcb1b, abcc2, and abcg2 was examined using the real-time polymerase chain reaction method in male db/db mice, a commonly used type II diabetes model. We evaluated age and disease effects on gene expression and enzymatic activity in 10- and 25-week-old db/db and 25-week old C57BLKS/J (strain-matched lean control) mice. Functional analysis was conducted in hepatic microsomes for Cyp2b, Cyp2c, and Cyp3a using cytochrome P450 specific substrates. There were no significant age- or disease-dependent changes in the expression of Cyp3a11 and Cyp3a activity in the db/db mice. The mRNA levels and the activities of Cyp2b10 and Cyp2c29 in the 25-week-old db/db mice decreased significantly compared with those of the 10-week-old db/db mice. There was a significant age-dependent increase in Cyp4a10 expression noted. The most marked expression change in db/db mice versus a control was the ~400-fold reduction of mRNA expression of slco1a1. Slco1a4 and sloc1b2 showed increased expression compared with that in an age-matched control, whereas abcb1b showed decreased expression. No expression changes were observed for Cyp2e1, Nr1i2, Nr1i3, abcc2, and abcg2. Our data demonstrate that significant expression and activity differences exist between the db/db and the lean control mice, which are probably age- and disease-dependent. PMID- 20736322 TI - The Chinese herbal medicine Sophora flavescens activates pregnane X receptor. AB - Sophora flavescens (SF) is an herbal medicine widely used for the treatment of viral hepatitis, cancer, viral myocarditis, gastrointestinal hemorrhage, and skin diseases. It was recently reported that SF up-regulates CYP3A expression. The mechanism of SF-induced CYP3A expression is unknown. In the current study, we tested the hypothesis that SF-induced CYP3A expression is mediated by the activation of pregnane X receptor (PXR). We used two cell lines, DPX2 and HepaRG, to investigate the role of PXR in SF-induced CYP3A expression. The DPX2 cell line is derived from HepG2 cells with the stable transfection of human PXR and a luciferase reporter gene linked with a human PXR response element identified in the CYP3A4 gene promoter. In DPX2 cells, SF activated PXR in a concentration dependent manner. We used a metabolomic approach to identify the chemical constituents in SF, which were further analyzed for their effect on PXR activation and CYP3A regulation. One chemical in SF, N-methylcytisine, was identified as an individual chemical that activated PXR. HepaRG is a highly differentiated hepatoma cell line that mimics human hepatocytes. In HepaRG cells, N-methylcytisine significantly induced CYP3A4 expression, and this induction was suppressed by the PXR antagonist sulforaphane. These results suggest that SF induces CYP3A expression via the activation of PXR. PMID- 20736323 TI - Evaluation of the effects of cytochrome P450 nonsynonymous single-nucleotide polymorphisms on tanshinol borneol ester metabolism and inhibition potential. AB - Nonsynonymous single-nucleotide polymorphisms (nsSNPs) in cytochrome P450 (P450) genes may affect drug metabolism and drug-drug interactions (DDIs), potentially leading to adverse drug reactions. Functional characterization of the nsSNPs in P450 genes is important to help us understand the impact of genetic factors on P450-mediated drug metabolism and DDIs. To evaluate the effects of P450 nsSNPs on the metabolism and inhibition potential of a candidate drug, tanshinol borneol ester (DBZ), we obtained and experimentally validated eight yeast-expressed human P450 isoforms and their nsSNP variants and tested DBZ using these recombinant P450 enzymes. The results suggested that CYP2C8 is the major enzyme responsible for DBZ metabolism. In addition, compared with prototypic CYP2C8, the allelic variant, CYP2C8.3, produced a 54% decrease in the intrinsic clearance of DBZ. The inhibitory potency of DBZ toward CYP3A4 was greater than that toward other P450 isoforms, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. Moreover, the inhibitory potency toward three CYP3A4 allelic variants, CYP3A4.2, CYP3A4.12, and CYP3A4.16, was reduced 2- to 10-fold relative to prototype CYP3A4. These results provide useful information for understanding the influence of P450 genetic polymorphisms on DBZ metabolism and may help to design future clinical trials of DBZ. Our results suggest applications for in vitro P450 assays both for basic research in pharmacogenomics and for drug development. PMID- 20736324 TI - Forkhead box protein A1 regulates UDP-glucuronosyltransferase 2B15 gene transcription in LNCaP prostate cancer cells. AB - The UDP-glucuronosyltransferases (UGTs) 2B15 and 2B17 are the major UGTs involved in the inactivation and elimination of the active androgens, dihydrotestosterone and testosterone. Although regulation of these UGT genes by various endogenous and exogenous ligands, including steroid hormones and bile acids, is well documented, the mechanisms controlling their basal gene expression are poorly understood. We recently reported that Forkhead box protein A1 (FOXA1) regulates the basal expression of the UGT2B17 gene in prostate cancer cells. In this study, we show that FOXA1 also regulates basal expression of the UGT2B15 gene in the prostate cell line LNCaP (lymph node carcinoma of the prostate). FOXA1 binds to a site -208 to -217 base pairs relative to the UGT2B15 translation start site, as shown by electromobility shift and chromatin immunoprecipitation assays. Mutation of this site prevents binding and substantially decreases basal UGT2B15 promoter activity. Silencing of FOXA1 expression by small interfering RNA significantly reduced UGT2B15 transcript levels, further confirming a crucial role of FOXA1 in controlling UGT2B15 gene expression. Because local inactivation of active androgens by UGT2B15 and UGT2B17 has been shown to be a major determinant of androgen response and signaling activity, regulation of the UGT2B15 and UGT2B17 genes by FOXA1 may have an important role in the maintenance of androgen homeostasis within prostate cancer cells. PMID- 20736325 TI - Pregnane X receptor and constitutive androstane receptor at the crossroads of drug metabolism and energy metabolism. AB - The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are two closely related and liver-enriched nuclear hormone receptors originally defined as xenobiotic receptors. PXR and CAR regulate the transcription of drug metabolizing enzymes and transporters, which are essential in protecting our bodies from the accumulation of harmful chemicals. An increasing body of evidence suggests that PXR and CAR also have an endobiotic function that impacts energy homeostasis through the regulation of glucose and lipids metabolism. Of note and in contrast, disruptions of energy homeostasis, such as those observed in obesity and diabetes, also have a major impact on drug metabolism. This review will focus on recent progress in our understanding of the integral role of PXR and CAR in drug metabolism and energy homeostasis. PMID- 20736326 TI - Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. AB - PURPOSE: The success of cancer immunotherapy depends on the balance between effector T cells and suppressive immune regulatory mechanisms within the tumor microenvironment. In this study we investigated whether transient monoclonal antibody-mediated depletion of CD25(high) regulatory T cells (Treg) is capable of enhancing the immunostimulatory efficacy of dendritic cell vaccines. EXPERIMENTAL DESIGN: Thirty HLA-A2.1(+) metastatic melanoma patients were vaccinated with mature dendritic cells pulsed with tumor peptide and keyhole limpet hemocyanin (KLH). Half of the patients were pretreated with daclizumab, a humanized antibody against the interleukin-2 (IL-2) receptor alpha-chain (CD25), either four or eight days before dendritic cell vaccinations. Clinical and immunologic parameters were determined. RESULTS: Daclizumab efficiently depleted all CD25(high) immune cells, including CD4(+)FoxP3(+)CD25(high) cells, from the peripheral blood within four days of administration. Thirty days after administration, daclizumab was cleared from the circulation and all CD25(+) cells reappeared. The presence of daclizumab during dendritic cell vaccinations prevented the induction of specific antibodies in vivo but not the presence of antigen-specific T cells. Daclizumab, however, did prevent these CD25(+) T cells from acquiring effector functions. Consequently, significantly less patients pretreated with daclizumab developed functional, vaccine-specific effector T cells and antibodies compared with controls. Daclizumab pretreatment had no significant effect on progression-free survival compared with the control group. CONCLUSIONS: Although daclizumab depleted the CD4(+)FoxP3(+)CD25(high) Tregs from the peripheral circulation, it did not enhance the efficacy of the dendritic cell vaccine. Residual daclizumab functionally suppressed de novo induced CD25(+) effector cells during dendritic cell vaccinations. Our results indicate that for immunotherapeutic benefit of transient Treg depletion, timing and dosing as well as Treg specificity are extremely important. PMID- 20736327 TI - Inconsistent labeling of food effect for oral agents across therapeutic areas: differences between oncology and non-oncology products. AB - PURPOSE: Several recent oral oncology drugs were labeled for administration in fasted states despite the fact that food increases their bioavailability. Because this was inconsistent with the principles of oral drug delivery, we hypothesized that there were inconsistencies across therapeutic areas. EXPERIMENTAL DESIGN: Oral agents approved by the U.S. Food and Drug Administration from January 2000 to May 2009 were included in our study. Comparison of the food labeling patterns between oncology and non-oncology drugs was made using Fisher's exact test. RESULTS: Of the 99 drugs evaluated, 34 showed significant food effects on bioavailability. When food markedly enhanced bioavailability, eight out of nine non-oncology drugs were labeled "fed" to take advantage of the food-drug interaction, whereas all oncology drugs (n = 3) were labeled to be administered in "fasted" states (Fisher's exact test, P = 0.01). CONCLUSIONS: Drug labeling patterns with respect to food-drug interactions observed with oncology drugs are in contradiction with fundamental pharmacologic principles, as exemplified in the labeling of non-oncology drugs. . PMID- 20736328 TI - Prediction of stage, grade, and survival in bladder cancer using genome-wide expression data: a validation study. AB - PURPOSE: To evaluate performances of published gene signatures for the assessment of urothelial carcinoma. EXPERIMENTAL DESIGN: We evaluated 28 published gene signatures designed for diagnostic and prognostic purposes of urothelial cancer. The investigated signatures include eight signatures for stage, five for grade, four for progression, and six for survival. We used two algorithms for classification, nearest centroid classification and support vector machine, and Cox regression to evaluate signature performance in four independent data sets. RESULTS: The overlap of genes among the signatures was low, ranging from 11% among stage signatures to 0.6% among survival signatures. The published signatures predicted muscle-invasive and high-grade tumors with accuracies in the range of 70% to 90%. The performance for a given signature varied considerably with the validation data set used, and interestingly, some of the best performing signatures were not designed for the tested classification problem. In addition, several nonbladder-derived gene signatures performed equally well. Large randomly selected gene signatures performed better than the published signatures, and by systematically increasing signature size, we show that signatures with >150 genes are needed to obtain robust performance in independent validation data sets. None of the published survival signatures performed better than random assignments when applied to independent validation data. CONCLUSION: We conclude that gene expression signatures with >150 genes predict muscle-invasive growth and high grade tumors with robust accuracies. Special considerations have to be taken when designing gene signatures for outcome in bladder cancer. PMID- 20736329 TI - Notch1 expression predicts an unfavorable prognosis and serves as a therapeutic target of patients with neuroblastoma. AB - PURPOSE: Notch signaling has been implicated to play a critical role in the tumorigenesis of neuroblastoma (NB) and can modulate calreticulin (CRT) expression that strongly correlates with tumor differentiation and favorable prognosis of NB. We thus sought to determine how Notch regulates CRT expression and affects NB tumor behavior. EXPERIMENTAL DESIGN: The Notch-dependent regulation of CRT expression in cultured NB cells was analyzed by confocal microscopy and Western blotting. Notch1 protein expression in 85 NB tumors was examined by immunohistochemistry and correlated with the clinicopathologic/biological characters of NB patients. The progression of NB tumors in response to attenuated Notch signaling was examined by using a xenograft mouse model. RESULTS: We showed that CRT is essential for the neuronal differentiation of NB cells elicited by inhibition of Notch signaling. This effect was mediated by a c-Jun-NH(2)-kinase-dependent pathway. Furthermore, NB tumors with elevated Notch1 protein expression were strongly correlated with advanced tumor stages, MYCN amplification, an undifferentiated histology, as well as a low CRT expression level. Most importantly, the opposing effect between Notch1 and CRT could reciprocally affect the survival of NB patients. The administration of a gamma-secretase inhibitor into a xenograft mouse model of NB significantly suppressed the tumor progression. CONCLUSIONS: Our findings provide the first evidence that a c-Jun-NH(2)-kinase-CRT-dependent pathway is essential for the neuronal differentiation elicited by Notch signaling blockade and that Notch1 and CRT can synergistically predict the clinical outcomes of NB patients. The present data suggest that Notch signaling could be a therapeutic target for NB. PMID- 20736330 TI - The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group. AB - PURPOSE: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. EXPERIMENTAL DESIGN: We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing. RESULTS: The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005). CONCLUSIONS: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA driven algorithms to determine whether biopsy is indicated. PMID- 20736331 TI - Food and oral antineoplastics: more than meets the eye. AB - Food can alter the bioavailability of orally administered drugs. Description of food effects in product labels and information about administration in relation to food are influenced by a variety of factors. Because food effects can change drug efficacy and toxicity, it is important that physicians and patients be aware of them. PMID- 20736332 TI - Radiation doses and cancer risks from breast imaging studies. AB - PURPOSE: To compare radiation doses and lifetime attributable risks (LARs) of radiation-induced cancer incidence and mortality from breast imaging studies involving the use of ionizing radiation. MATERIALS AND METHODS: Recent literature on radiation doses from radiologic procedures and organ doses from nuclear medicine procedures, along with Biologic Effects of Ionizing Radiation (BEIR) VII age-dependent risk data, is used to estimate LARs of radiation-induced cancer incidence and mortality from breast imaging studies involving ionizing radiation, including screen-film mammography, digital mammography, digital breast tomosynthesis, dedicated breast computed tomography, breast-specific gamma imaging (BSGI), and positron emission mammography (PEM). RESULTS: Two-view digital mammography and screen-film mammography involve average mean glandular radiation doses of 3.7 and 4.7 mGy, respectively. According to BEIR VII data, these studies are associated, respectively, with LARs of fatal breast cancer of 1.3 and 1.7 cases per 100,000 women aged 40 years at exposure and less than one case per one million women aged 80 years at exposure. Annual screening digital or screen-film mammography performed in women aged 40-80 years is associated with an LAR of fatal breast cancer of 20-25 cases in 100,000. A single BSGI study involving a label-recommended dose of 740-1100 MBq (20-30 mCi) of technetium 99m sestamibi is estimated to involve an LAR of fatal cancer that is 20-30 times that of digital mammography in women aged 40 years. A single PEM study involving a labeled dose of 370 MBq (10 mCi) of fluorine 18 fluorodeoxyglucose is estimated to involve an LAR of fatal cancer that is 23 times higher than that of digital mammography in women aged 40 years. CONCLUSION: A single BSGI or PEM study is associated with a fatal radiation-induced cancer risk higher than or comparable to that of annual screening mammography in women aged 40-80 years. PMID- 20736333 TI - Addressing overutilization in medical imaging. AB - The growth in medical imaging over the past 2 decades has yielded unarguable benefits to patients in terms of longer lives of higher quality. This growth reflects new technologies and applications, including high-tech services such as multisection computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET). Some part of the growth, however, can be attributed to the overutilization of imaging services. This report examines the causes of the overutilization of imaging and identifies ways of addressing the causes so that overutilization can be reduced. In August 2009, the American Board of Radiology Foundation hosted a 2-day summit to discuss the causes and effects of the overutilization of imaging. More than 60 organizations were represented at the meeting, including health care accreditation and certification entities, foundations, government agencies, hospital and health systems, insurers, medical societies, health care quality consortia, and standards and regulatory agencies. Key forces influencing overutilization were identified. These include the payment mechanisms and financial incentives in the U.S. health care system; the practice behavior of referring physicians; self-referral, including referral for additional radiologic examinations; defensive medicine; missed educational opportunities when inappropriate procedures are requested; patient expectations; and duplicate imaging studies. Summit participants suggested several areas for improvement to reduce overutilization, including a national collaborative effort to develop evidence-based appropriateness criteria for imaging; greater use of practice guidelines in requesting and conducting imaging studies; decision support at point of care; education of referring physicians, patients, and the public; accreditation of imaging facilities; management of self-referral and defensive medicine; and payment reform. PMID- 20736334 TI - Prevention of colitis-associated carcinogenesis with infliximab. AB - The emergence of infliximab was an epochal event in the treatment of inflammatory bowel disease (IBD). Because colitis-associated cancers arose in the setting of chronic inflammation, during which "inflammation-dysplasia-carcinoma sequence" prevails and anti-inflammatory agents can prevent carcinogenesis, we hypothesized whether infliximab can prevent colitic cancer in animal models for which C57BL/6 mice were exposed to 15 cycles of dextran sulfate sodium (DSS), with each cycle consisting of 0.7% DSS for 1 week followed by sterilized water for 10 days. Infliximab (4 mg/kg i.v.) was given on the 1st, 3rd, and 7th weeks or 25th, 27th, and 31st weeks of cycle according to "step-up" versus "top-down" strategy. Molecular change about inflammation and carcinogenesis was compared between groups. Multiple colorectal tumors developed in 75% to 80% of control mice, whereas only 16.7% of mice treated with infliximab on the 1st, 3rd, and 7th weeks developed colon tumors. Significant decreases in tumor necrosis factor-alpha level, mast cell number, and the expression of inflammatory cytokines were observed in top-down strategy using infliximab. The expression and activity of matrix metalloproteinase-9 (MMP-9) and MMP-11 were significantly decreased in mice treated with infliximab accompanied with attenuated numbers of "beta-catenin accumulated crypts." In animal group where infliximab was administered at later stage of 25th, 27th, and 31st weeks, no reduction in tumorigenesis was noted. These biological effects of infliximab were further explored in in vitro experiment using Raw264.7 and Jurkat T cells. Conclusively, earlier and intensive therapy with infliximab should be considered for either mitigating clinical course or preventing ultimate development of colitic cancer in high-risk IBD patients. PMID- 20736335 TI - Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention. AB - Emerging data are suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion, agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of nontoxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through molecular modeling, we found that carnosol, a dietary diterpene, fits within the ligand-binding domain of both AR and ER-alpha. Using a time-resolved fluorescence resonance energy transfer assay, we found that carnosol interacts with both AR and ER-alpha and additional experiments confirmed that it functions as a receptor antagonist with no agonist effects. LNCaP, 22Rv1, and MCF7 cells treated with carnosol (20-40 mumol/L) showed decreased protein expression of AR and ER-alpha. Oral administration of carnosol at 30 mg/kg 5 days weekly for 28 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 36% (P = 0.028) and was associated with a decrease in serum prostate-specific antigen by 26% (P = 0.0042). These properties make carnosol unique to any known antiandrogen or antiestrogen investigated thus far for the simultaneous disruption of AR and ER-alpha. We suggest that carnosol may be developed or chemically modified through more rigorous structure-activity relationship studies for a new class of investigational agents-a dual AR/ER modulator. PMID- 20736336 TI - Differential assembly of 16S rRNA domains during 30S subunit formation. AB - Rapid and accurate assembly of the ribosomal subunits, which are responsible for protein synthesis, is required to sustain cell growth. Our best understanding of the interaction of 30S ribosomal subunit components (16S ribosomal RNA [rRNA] and 20 ribosomal proteins [r-proteins]) comes from in vitro work using Escherichia coli ribosomal components. However, detailed information regarding the essential elements involved in the assembly of 30S subunits still remains elusive. Here, we defined a set of rRNA nucleotides that are critical for the assembly of the small ribosomal subunit in E. coli. Using an RNA modification interference approach, we identified 54 nucleotides in 16S rRNA whose modification prevents the formation of a functional small ribosomal subunit. The majority of these nucleotides are located in the head and interdomain junction of the 30S subunit, suggesting that these regions are critical for small subunit assembly. In vivo analysis of specific identified sites, using engineered mutations in 16S rRNA, revealed defective protein synthesis capability, aberrant polysome profiles, and abnormal 16S rRNA processing, indicating the importance of these residues in vivo. These studies reveal that specific segments of 16S rRNA are more critical for small subunit assembly than others, and suggest a hierarchy of importance. PMID- 20736338 TI - DRIMM-Synteny: decomposing genomes into evolutionary conserved segments. AB - MOTIVATION: The rapidly increasing set of sequenced genomes highlights the importance of identifying the synteny blocks in multiple and/or highly duplicated genomes. Most synteny block reconstruction algorithms use genes shared over all genomes to construct the synteny blocks for multiple genomes. However, the number of genes shared among all genomes quickly decreases with the increase in the number of genomes. RESULTS: We propose the Duplications and Rearrangements In Multiple Mammals (DRIMM)-Synteny algorithm to address this bottleneck and apply it to analyzing genomic architectures of yeast, plant and mammalian genomes. We further combine synteny block generation with rearrangement analysis to reconstruct the ancestral preduplicated yeast genome. CONTACT: kspham@cs.ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20736337 TI - The sensitivity of memory consolidation and reconsolidation to inhibitors of protein synthesis and kinases: computational analysis. AB - Memory consolidation and reconsolidation require kinase activation and protein synthesis. Blocking either process during or shortly after training or recall disrupts memory stabilization, which suggests the existence of a critical time window during which these processes are necessary. Using a computational model of kinase synthesis and activation, we investigated the ways in which the dynamics of molecular positive-feedback loops may contribute to the time window for memory stabilization and memory maintenance. In the models, training triggered a transition in the amount of kinase between two stable states, which represented consolidation. Simulating protein synthesis inhibition (PSI) from before to 40 min after training blocked or delayed consolidation. Beyond 40 min, substantial (>95%) PSI had little effect despite the fact that the elevated amount of kinase was maintained by increased protein synthesis. However, PSI made established memories labile to perturbations. Simulations of kinase inhibition produced similar results. In addition, similar properties were found in several other models that also included positive-feedback loops. Even though our models are based on simplifications of the actual mechanisms of molecular consolidation, they illustrate the practical difficulty of empirically measuring "time windows" for consolidation. This is particularly true when consolidation and reconsolidation of memory depends, in part, on the dynamics of molecular positive feedback loops. PMID- 20736339 TI - Circoletto: visualizing sequence similarity with Circos. AB - SUMMARY: We present Circoletto, an online visualization tool based on Circos, which provides a fast, aesthetically pleasing and informative overview of sequence similarity search results. AVAILABILITY AND IMPLEMENTATION: Online version and downloadable software package for offline use (source code in PERL) freely available at http://bat.ina.certh.gr/tools/circoletto/ CONTACT: ndarz@certh.gr PMID- 20736340 TI - Deep and wide digging for binding motifs in ChIP-Seq data. AB - SUMMARY: ChIP-Seq data are a new challenge for motif discovery. Such a data typically consists of thousands of DNA segments with base-specific coverage values. We present a new version of our DNA motif discovery software ChIPMunk adapted for ChIP-Seq data. ChIPMunk is an iterative algorithm that combines greedy optimization with bootstrapping and uses coverage profiles as motif positional preferences. ChIPMunk does not require truncation of long DNA segments and it is practical for processing up to tens of thousands of data sequences. Comparison with traditional (MEME) or ChIP-Seq-oriented (HMS) motif discovery tools shows that ChIPMunk identifies the correct motifs with the same or better quality but works dramatically faster. AVAILABILITY AND IMPLEMENTATION: ChIPMunk is freely available within the ru_genetika Java package: http://line.imb.ac.ru/ChIPMunk. Web-based version is also available. CONTACT: ivan.kulakovskiy@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20736341 TI - Obtaining better quality final clustering by merging a collection of clusterings. AB - MOTIVATION: Clustering methods including k-means, SOM, UPGMA, DAA, CLICK, GENECLUSTER, CAST, DHC, PMETIS and KMETIS have been widely used in biological studies for gene expression, protein localization, sequence recognition and more. All these clustering methods have some benefits and drawbacks. We propose a novel graph-based clustering software called COMUSA for combining the benefits of a collection of clusterings into a final clustering having better overall quality. RESULTS: COMUSA implementation is compared with PMETIS, KMETIS and k-means. Experimental results on artificial, real and biological datasets demonstrate the effectiveness of our method. COMUSA produces very good quality clusters in a short amount of time. AVAILABILITY: http://www.cs.umb.edu/~smimarog/comusa CONTACT: selim.mimaroglu@bahcesehir.edu.tr PMID- 20736342 TI - ICPS: an integrative cancer profiler system. AB - Founded upon the database of 570 public signatures, ICPS is a web-based application to obtain biomarker profiles among 11 common cancers by integrating genomic alterations with transcription signatures on the basis of a previously developed integrative pipeline. ICPS supports both public data and user's in house data, and performs meta-analysis at a cancer subtype level by combining heterogeneous datasets. Finally, ICPS returns the robust gene signature containing potential cancer biomarkers that may be useful to carcinogenesis study and clinical cancer diagnosis. AVAILABILITY: http://server.bioicps.org CONTACT: zhxy@mail.tsinghua.edu.cn; zxy-dcs@mail.tsinghua.edu.cn PMID- 20736343 TI - Detecting two-locus associations allowing for interactions in genome-wide association studies. AB - MOTIVATION: Genome-wide association studies (GWASs) aim to identify genetic susceptibility to complex diseases by assaying and analyzing hundreds of thousands of single nucleotide polymorphisms (SNPs). Although traditional single locus statistical tests have identified many genetic determinants of susceptibility, those findings cannot completely explain genetic contributions to complex diseases. Marchini and coauthors demonstrated the importance of testing two-locus associations allowing for interactions through a wide range of simulation studies. However, such a test is computationally demanding as we need to test hundreds of billions of SNP pairs in GWAS. Here, we provide a method to address this computational burden for dichotomous phenotypes. RESULTS: We have applied our method on nine datasets from GWAS, including the aged-related macular degeneration (AMD) dataset, the Parkinson's disease dataset and seven datasets from the Wellcome Trust Case Control Consortium (WTCCC). Our method has discovered many associations that were not identified before. The running time for the AMD dataset, the Parkinson's disease dataset and each of seven WTCCC datasets are 2.5, 82 and 90 h on a standard 3.0 GHz desktop with 4 G memory running Windows XP system. Our experiment results demonstrate that our method is feasible for the full-scale analyses of both single- and two-locus associations allowing for interactions in GWAS. AVAILABILITY: http://bioinformatics.ust.hk/SNPAssociation.zip CONTACT: nelsontang@cuhk.edu.hk; eeyu@ust.hk; SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20736344 TI - The novel tryptamine derivative JNJ-26854165 induces wild-type p53- and E2F1 mediated apoptosis in acute myeloid and lymphoid leukemias. AB - The development of small-molecule activators of p53 is currently focused on malignancies containing a wild-type p53 genotype, which is present in most leukemias. JNJ-26854165 is one such p53-activating agent, but its mechanism of action remains to be elucidated. Here, we report the effects of JNJ-26854165 in acute leukemias. JNJ-26854165 treatment induced p53-mediated apoptosis in acute leukemia cells with wild-type p53, in which p53 rapidly drives transcription independent apoptosis followed by activation of a transcription-dependent pathway. JNJ-26854165 accelerated the proteasome-mediated degradation of p21 and antagonized the transcriptional induction of p21 by p53. Interestingly, JNJ 26854165 induced S-phase delay and upregulated E2F1 expression in p53 mutant cells, resulting in apoptosis preferentially of S-phase cells. E2F1 knockdown blocked apoptosis induced by JNJ-26854165 in p53 mutant cells. Apoptotic activity of JNJ-26854165 against primary acute leukemia cells was maintained in leukemia/stroma cocultures, unlike doxorubicin, which has reduced cytrotoxicity in coculture systems. JNJ-26854165 synergizes with 1-beta arabinofuranosylcytosine or doxorubicin to induce p53-mediated apoptosis. Our data suggest that JNJ-26854165 may provide a novel therapeutic approach for the treatment of acute leukemias. The presence of p53-independent apoptotic activity in addition to p53-mediated apoptosis induction, if operational in vivo, may prevent the selection of p53 mutant subclones during therapy. PMID- 20736345 TI - Substitution of adenovirus serotype 3 hexon onto a serotype 5 oncolytic adenovirus reduces factor X binding, decreases liver tropism, and improves antitumor efficacy. AB - Following intravascular delivery, an important route of administration for many clinical applications, the liver is the predominant site of adenovirus serotype 5 (Ad5) sequestration, thereby posing a risk of toxicity. In this regard, it has recently been shown that the Ad5 capsid binds to the blood coagulation factor X (FX) via the Ad5 hexon protein. This interaction mediates the majority of Ad5 liver transduction. Patient FX levels can be diminished by the administration of warfarin, a vitamin K inhibitor in the liver that decreases FX production; however, warfarin is a potent anticoagulant and can have a number of undesired side effects. Therefore, genetic modification of the virus to ablate FX binding is the preferred approach. Modifications of the hexon protein, specifically within the hypervariable 5 (HVR5) and 7 (HVR7) regions, have produced Ad5 vectors that show minimal liver sequestration. Our laboratory has pioneered adenovirus hexon modifications, including insertion of peptide ligands into the hypervariable regions and substitution of the adenovirus hexon with hexon proteins from alternate serotypes. Substitution of the adenovirus serotype 3 (Ad3) hexon protein onto the Ad5 capsid has been further characterized with regard to its interaction with FX and incorporated into an infectivity-enhanced conditionally replicative adenovirus (CRAd). In vitro evaluation of these hexon modified vectors showed decreased binding to FX and decreased cell transduction via FX-mediated pathways. Furthermore, in vivo biodistribution studies in mice exhibited a decrease in liver sequestration. With the use of xenograft tumor models, the antitumor efficacy of the hexon-modified CRAds was enhanced over nonmodified controls. PMID- 20736347 TI - Thyroid hormone receptors are down-regulated in skeletal muscle of patients with non-thyroidal illness syndrome secondary to non-septic shock. AB - AIM: Non-thyroidal illness syndrome (NTIS) is related to changes in thyroid hormone (TH) physiology. Skeletal muscle (SM) plays a major role in metabolism, and TH regulates SM phenotype and metabolism. We aimed to characterize the SM of non-septic shock NTIS patients in terms of: i) expression of genes and proteins involved in TH metabolism and actions; and ii) NFKB's pathway activation, a responsible factor for some of the phenotypic changes in NTIS. We also investigated whether the patient's serum can induce in vitro the effects observed in vivo. METHODS: Serum samples and SM biopsies from 14 patients with non-septic shock NTIS and 11 controls. Gene and protein expression and NFKB1 activation were analyzed by quantitative PCR and immunoblotting. Human SM cell (HSkMC) cultures to investigate the effects of patient's serum on TH action mediators. RESULTS: Patients with non-septic shock NTIS showed higher levels of pro-inflammatory cytokines than controls. Expression of TRbeta (THRB), TRalpha1 (THRA), and retinoid X receptor gamma (RXRG) was decreased in NTIS patients. RXRA gene expression was higher, but its protein was lower in NTIS than controls, suggesting the existence of a post-transcriptional mechanism that down-regulates protein levels. NFKB1 pathway activation was not different between NTIS and control patients. HSkMC incubated with patient's serum increased TH receptor and RXRG gene expression after 48 h. CONCLUSIONS: Patients with non-septic shock NTIS showed decreased expression of TH receptors and RXRs, which were not related to increased activation of the NFKB1 pathway. These findings could not be replicated in cultures of HSkMCs incubated in the patient's serum. PMID- 20736346 TI - Activating stress-activated protein kinase-mediated cell death and inhibiting epidermal growth factor receptor signaling: a promising therapeutic strategy for prostate cancer. AB - Epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling, such as the Raf, mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase 1/2 cascades. EGFR activation has been implicated in the transition of prostate cancer from androgen dependence to independence. Therefore, inhibition of EGFR may effectively suppress prostate cancer growth and progression. The goal of this study was to determine whether the natural compound psoralidin alters EGFR-mediated signaling resulting in the inhibition of prostate cancer growth. Results suggest that inhibition of EGFR alone (by serum deprivation) fails to induce stress-mediated protein kinases (SAPK), namely, Jun NH(2)-terminal kinase/c-Jun signaling, in androgen independent prostate cancer (AIPC) cells. Treatment with psoralidin, however, inhibited both constitutive and EGF-induced EGFR activation and simultaneously triggered SAPK signaling, resulting in the induction of apoptosis in AIPC cells. In addition, psoralidin downregulated EGFR-regulated MAPK signaling and inhibited cell proliferation in AIPC cells. Oral administration of psoralidin effectively suppressed PC-3 xenograft tumors in nude mice. Compared with control tumors, inhibition of pEGFR expression and an increase in the phosphorylation, activation, and nuclear translocation of c-Jun were observed in psoralidin treated tumor sections. Our studies suggest that psoralidin may be a potent therapeutic agent that modulates EGFR-mediated key epigenetic events in AIPC. PMID- 20736348 TI - Nephromyces, a beneficial apicomplexan symbiont in marine animals. AB - With malaria parasites (Plasmodium spp.), Toxoplasma, and many other species of medical and veterinary importance its iconic representatives, the protistan phylum Apicomplexa has long been defined as a group composed entirely of parasites and pathogens. We present here a report of a beneficial apicomplexan: the mutualistic marine endosymbiont Nephromyces. For more than a century, the peculiar structural and developmental features of Nephromyces, and its unusual habitat, have thwarted characterization of the phylogenetic affinities of this eukaryotic microbe. Using short-subunit ribosomal DNA (SSU rDNA) sequences as key evidence, with sequence identity confirmed by fluorescence in situ hybridization (FISH), we show that Nephromyces, originally classified as a chytrid fungus, is actually an apicomplexan. Inferences from rDNA data are further supported by the several apicomplexan-like structural features in Nephromyces, including especially the strong resemblance of Nephromyces infective stages to apicomplexan sporozoites. The striking emergence of the mutualistic Nephromyces from a quintessentially parasitic clade accentuates the promise of this organism, and the three-partner symbiosis of which it is a part, as a model for probing the factors underlying the evolution of mutualism, pathogenicity, and infectious disease. PMID- 20736349 TI - En masse in vitro functional profiling of the axonal mechanosensitivity of sensory neurons. AB - Perception of the environment relies on somatosensory neurons. Mechanosensory, proprioceptor and many nociceptor subtypes of these neurons have specific mechanosensitivity profiles to adequately differentiate stimulus patterns. Nevertheless, the cellular basis of differential mechanosensation remains largely elusive. Successful transduction of sensory information relies on the recruitment of sensory neurons and mechanosensation occurring at their peripheral axonal endings in vivo. Conspicuously, existing in vitro models aimed to decipher molecular mechanisms of mechanosensation test single sensory neuron somata at any one time. Here, we introduce a compartmental in vitro chamber design to deliver precisely controlled mechanical stimulation of sensory axons with synchronous real-time imaging of Ca(2+) transients in neuronal somata that reliably reflect action potential firing patterns. We report of three previously not characterized types of mechanosensitive neuron subpopulations with distinct intrinsic axonal properties tuned specifically to static indentation or vibration stimuli, showing that different classes of sensory neurons are tuned to specific types of mechanical stimuli. Primary receptor currents of vibration neurons display rapidly adapting conductance reliably detected for every single stimulus during vibration and are consistently converted into action potentials. This result allows for the characterization of two critical steps of mechanosensation in vivo: primary signal detection and signal conversion into specific action potential firing patterns in axons. PMID- 20736350 TI - Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. AB - TAR DNA-binding protein-43 (TDP-43), a DNA/RNA-binding protein involved in RNA transcription and splicing, has been associated with the pathophysiology of neurodegenerative diseases, including ALS. However, the function of TDP-43 in motor neurons remains undefined. Here we use both gain- and loss-of-function approaches to determine roles of TDP-43 in motor neurons. Mice expressing human TDP-43 in neurons exhibited growth retardation and premature death that are characterized by abnormal intranuclear inclusions composed of TDP-43 and fused in sarcoma/translocated in liposarcoma (FUS/TLS), and massive accumulation of mitochondria in TDP-43-negative cytoplasmic inclusions in motor neurons, lack of mitochondria in motor axon terminals, and immature neuromuscular junctions. Whereas an elevated level of TDP-43 disrupts the normal nuclear distribution of survival motor neuron (SMN)-associated Gemini of coiled bodies (GEMs) in motor neurons, its absence prevents the formation of GEMs in the nuclei of these cells. Moreover, transcriptome-wide deep sequencing analysis revealed that a decrease in abundance of neurofilament transcripts contributed to the reduction of caliber of motor axons in TDP-43 mice. In concert, our findings indicate that TDP-43 participates in pathways critical for motor neuron physiology, including those that regulate the normal distributions of SMN-associated GEMs in the nucleus and mitochondria in the cytoplasm. PMID- 20736351 TI - Translationally controlled tumor protein is a conserved mitotic growth integrator in animals and plants. AB - The growth of an organism and its size determination require the tight regulation of cell proliferation and cell growth. However, the mechanisms and regulatory networks that control and integrate these processes remain poorly understood. Here, we address the biological role of Arabidopsis translationally controlled tumor protein (AtTCTP) and test its shared functions in animals and plants. The data support a role of plant AtTCTP as a positive regulator of mitotic growth by specifically controlling the duration of the cell cycle. We show that, in contrast to animal TCTP, plant AtTCTP is not implicated in regulating postmitotic growth. Consistent with this finding, plant AtTCTP can fully rescue cell proliferation defects in Drosophila loss of function for dTCTP. Furthermore, Drosophila dTCTP is able to fully rescue cell proliferation defects in Arabidopsis tctp knockouts. Our data provide evidence that TCTP function in regulating cell division is part of a conserved growth regulatory pathway shared between plants and animals. The study also suggests that, although the cell division machinery is shared in all multicellular organisms to control growth, cell expansion can be uncoupled from cell division in plants but not in animals. PMID- 20736352 TI - The brain's fight against aging. PMID- 20736353 TI - Dynamics of heat shock protein 90 C-terminal dimerization is an important part of its conformational cycle. AB - The molecular chaperone heat shock protein 90 (Hsp90) is an important and abundant protein in eukaryotic cells, essential for the activation of a large set of signal transduction and regulatory proteins. During the functional cycle, the Hsp90 dimer performs large conformational rearrangements. The transient N terminal dimerization of Hsp90 has been extensively investigated, under the assumption that the C-terminal interface is stably dimerized. Using a fluorescence-based single molecule assay and Hsp90 dimers caged in lipid vesicles, we were able to separately observe and kinetically analyze N- and C terminal dimerizations. Surprisingly, the C-terminal dimer opens and closes with fast kinetics. The occupancy of the unexpected C-terminal open conformation can be modulated by nucleotides bound to the N-terminal domain and by N-terminal deletion mutations, clearly showing a communication between the two terminal domains. Moreover our findings suggest that the C- and N-terminal dimerizations are anticorrelated. This changes our view on the conformational cycle of Hsp90 and shows the interaction of two dimerization domains. PMID- 20736363 TI - Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss. AB - Inactivation of the Apc gene is recognized as the key early event in the development of sporadic colorectal cancer (CRC), where its loss leads to constitutive activation of beta-catenin/T-cell factor 4 signaling and hence transcription of Wnt target genes such as c-Myc. Our and other previous studies have shown that although cyclin D1 is required for adenoma formation, it is not immediately upregulated following Apc loss within the intestine, suggesting that proliferation following acute Apc loss may be dependent on another D-type cyclin. In this study, we investigated the expression and functional relevance of cyclin D2 following Apc loss in the intestinal epithelium. Cyclin D2 is upregulated immediately following Apc loss, which corresponded with a significant increase in cyclin-dependent kinase 4 (CDK4) and hyperphosphorylated Rb levels. Deficiency of cyclin D2 resulted in a reduction in enterocyte proliferation and crypt size within Apc-deficient intestinal epithelium. Moreover, cyclin D2 dramatically reduced tumor growth and development in Apc(Min/+) mice. Importantly, cyclin D2 knockout did not affect proliferation of normal enterocytes, and furthermore, CDK4/6 inhibition also suppressed the proliferation of adenomatous cells and not normal cells from Apc(Min/+) mice. Taken together, these results indicate that cyclin D-CDK4/6 complexes are required for the efficient proliferation of cells with deregulated Wnt signaling, and inhibiting this complex may be an effective chemopreventative strategy in CRC. PMID- 20736364 TI - HER-2 signaling, acquisition of growth factor independence, and regulation of biological networks associated with cell transformation. AB - Activated oncogenes are the dominant drivers of malignant progression in human cancer, yet little is known about how the transformation from proto-oncogene to activated oncogene drives the expression of transformed phenotypes. An isogenic model of HER-2-mediated transformation of human mammary epithelial cells was used along with HER-2-amplified human breast cancers to investigate how HER-2 activation alters its properties as a signaling molecule and changes the networks of HER-2-regulated genes. Our results show that full oncogenic activation of HER 2 is the result of a transition in which activated HER-2 acquires dominant signaling properties that qualitatively alter the network of genes regulated by the activated oncogene compared with the proto-oncogene. Consequently, gene expression programs related to invasion, cell stress, and stemness become regulated by HER-2 in a manner not observed in nontransformed cells, even when HER-2 is overexpressed. Our results offer novel insights into biological processes that come under the control of HER-2 after it acquires full oncogenic potential. PMID- 20736365 TI - Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. AB - Expression profiling has identified metastasis-associated microRNAs (miRNA) but technical limitations hinder the discovery of metastasis-suppressing miRNAs. In this study, we sought metastasis-suppressing miRNAs by functional screening. Individual miRNAs were lentivirally introduced into metastatic MDA-MB-231 breast cancer cells and analyzed for effects on cell migration, a critical step in cancer metastasis. Among 486 miRNAs screened, 14 were identified that included all of the members of the miRNA-196 family (miR-196a1, miR-196a2, and miR-196b). Enforced expression of miR-196a1/2 or miR-196b abrogated in vitro invasion and in vivo spontaneous metastasis of breast cancer cells, indicating that members of the miR-196 family are potent metastasis suppressors. We found that miR-196 inhibited the expression of transcription factor HOXC8. Functional linkage was implied by small interfering RNA-mediated knockdown of HOXC8, which suppressed cell migration and metastasis, and by ectopic expression of HOXC8, which prevented the effects of miR-196 on cell migration and metastasis. Unlike other metastasis-associated miRNAs that have been described, the expressions of miR-196 were not correlated with breast cancer cell migration or the metastatic status of clinical breast tumor specimens. Instead, we detected an excellent correlation between the ratio of miR-196 to HOXC8 messages and the migratory behavior of breast cancer cell lines as well as the metastatic status of clinical samples. Our findings identify miRNA-196s as potent metastasis suppressors and reveal that the ratio of miR-196s to HOXC8 mRNA might be an indicator of the metastatic capability of breast tumors. PMID- 20736366 TI - Chemotrap-1: an engineered soluble receptor that blocks chemokine-induced migration of metastatic cancer cells in vivo. AB - Cancer and dendritic cells recognize and migrate toward chemokines secreted from lymphatics and use this mechanism to invade the lymphatic system, and cancer cells metastasize through it. The lymphatic-secreted chemokine ligand CCL21 has been identified as a key regulatory molecule in the switch to a metastatic phenotype in melanoma and breast cancer cells. However, it is not known whether CCL21 inhibition is a potential therapeutic strategy for inhibition of metastasis. Here, we describe an engineered CCL21-soluble inhibitor, Chemotrap-1, which inhibits migration of metastatic melanoma cells in vivo. Two-hybrid, pull down, and coimmunoprecipitation assays allowed us to identify a naturally occurring human zinc finger protein with CCL21 chemokine-binding properties. Further analyses revealed a short peptide (~70 amino acids), with a predicted coiled-coil structure, which is sufficient for association with CCL21. This CCL21 chemokine-binding peptide was then fused to the Fc region of human IgG1 to generate Chemotrap-1, a human chemokine-binding Fc fusion protein. Surface plasmon resonance and chemotaxis assays showed that Chemotrap-1 binds CCL21 and inhibits CCL21-induced migration of melanoma cells in vitro with subnanomolar affinity. In addition, Chemotrap-1 blocked migration of melanoma cells toward lymphatic endothelial cells in vitro and in vivo. Finally, Chemotrap-1 strongly reduced lymphatic invasion, tracking, and metastasis of CCR7-expressing melanoma cells in vivo. Together, these results show that CCL21 chemokine inhibition by Chemotrap-1 is a potential therapeutic strategy for metastasis and provide further support for the hypothesis that lymphatic-mediated metastasis is a chemokine-dependent process. PMID- 20736367 TI - Secreted and membrane-bound isoforms of protease ADAM9 have opposing effects on breast cancer cell migration. AB - Tumor cell migration is mediated by cell-autonomous signaling mechanisms as well as paracrine and autocrine factors secreted by activated stromal cells in the tumor microenvironment. Like other members of the ADAM (a disintegrin and metalloproteinase) family, the integrin-binding metalloproteinase ADAM9 modulates cell-cell and cell-matrix interactions as well as ectodomain shedding of cell surface receptors and ligands, thereby modifying intracellular and extracellular signaling. ADAM9 transcripts are alternatively spliced to express a transmembrane protein (ADAM9-L) and a secreted variant (ADAM9-S). In this study, we show that ADAM9-S promotes breast cancer cell migration in a manner requiring its metalloproteinase activity, whereas ADAM9-L suppresses cell migration independent of its metalloproteinase activity. Suppression of migration by ADAM9-L requires a functional disintegrin domain and integrin binding. Expression analysis revealed that both ADAM9 isoforms are expressed in breast cancer cell lines and tissues. Therefore, relative levels of membrane-tethered and secreted variants of ADAM9 are a key determinant in manifestation of aggressive migratory phenotypes associated with breast cancer progression. PMID- 20736368 TI - Aberrant silencing of cancer-related genes by CpG hypermethylation occurs independently of their spatial organization in the nucleus. AB - Aberrant promoter DNA-hypermethylation and repressive chromatin constitutes a frequent mechanism of gene inactivation in cancer. There is great interest in dissecting the mechanisms underlying this abnormal silencing. Studies have shown changes in the nuclear organization of chromatin in tumor cells as well as the association of aberrant methylation with long-range silencing of neighboring genes. Furthermore, certain tumors show a high incidence of promoter methylation termed as the CpG island methylator phenotype. Here, we have analyzed the role of nuclear chromatin architecture for genes in hypermethylated inactive versus nonmethylated active states and its relation with long-range silencing and CpG island methylator phenotype. Using combined immunostaining for active/repressive chromatin marks and fluorescence in situ hybridization in colorectal cancer cell lines, we show that aberrant silencing of these genes occurs without requirement for their being positioned at heterochromatic domains. Importantly, hypermethylation, even when associated with long-range epigenetic silencing of neighboring genes, occurs independent of their euchromatic or heterochromatic location. Together, these results indicate that, in cancer, extensive changes around promoter chromatin of individual genes or gene clusters could potentially occur locally without preference for nuclear position and/or causing repositioning. These findings have important implications for understanding relationships between nuclear organization and gene expression patterns in cancer. PMID- 20736369 TI - Interaction with vascular endothelium enhances survival in primary chronic lymphocytic leukemia cells via NF-kappaB activation and de novo gene transcription. AB - Chronic lymphocytic leukemia (CLL) cells rapidly undergo apoptosis in vitro, suggesting that the in vivo microenvironment provides crucial antiapoptotic signals. Overexpression of the antiapoptotic proteins Bcl-2 and Mcl-1 is a hallmark of CLL, and their expression is further enhanced in the lymphoid tissues. However, the high levels of Mcl-1 found in peripheral blood samples, coupled with its short half-life, led us to hypothesize that it must be actively maintained in the peripheral circulation. Coculture of CLL cells with human vascular endothelial cells significantly enhanced tumor cell survival, an effect that was not observed with normal B cells. This was associated with elevated levels of the antiapoptotic proteins Bcl-2, Mcl-1, and Bcl-X(L) and marked increased expression of CD38 and CD49d, both of which are associated with clinically aggressive disease. Because CD38, CD49d, and some Bcl-2 family genes are transcriptional targets for NF-kappaB, we assessed NF-kappaB activation following coculture with endothelial cells. DNA binding of the NF-kappaB subunit Rel A was significantly increased and strongly correlated with changes in transcription of CD38, CD49d, BCL2, MCL1, and BCLXL, effects that were reversed by a peptide inhibitor of Rel A. These effects were not observed following coculture with nonendothelial cell lines. Therefore, CLL cells receive specific survival signals following interaction with endothelial cells mediated through the activation of NF-kappaB and the induction of downstream target genes. This type of interaction in the peripheral vasculature may explain the constitutive NF kappaB activation and the overexpression of Bcl-2 family proteins commonly seen in this disease. PMID- 20736370 TI - Spontaneous tumorigenesis in mice overexpressing the p53-negative regulator Mdm4. AB - High levels of the critical p53 inhibitor Mdm4 is common in tumors that retain a wild-type p53 allele, suggesting that Mdm4 overexpression is an important mechanism for p53 inactivation during tumorigenesis. To test this hypothesis in vivo, we generated transgenic mice with widespread expression of Mdm4. Two independent lines of transgenic mice, Mdm4(Tg1) and Mdm4(Tg15), developed spontaneous tumors, the most prevalent of which were sarcomas. To determine whether overexpression of Mdm4 also cooperated with p53 heterozygosity to induce tumorigenesis, we generated Mdm4(Tg1) p53(+/-) mice. These mice had significantly accelerated tumorigenesis and a distinct tumor spectrum with more carcinomas and significantly fewer lymphomas than p53(+/-) or Mdm4(Tg1) mice. Importantly, the remaining wild-type p53 allele was retained in most Mdm4(Tg1) p53(+/-) tumors. Mdm4 is thus a bona fide oncogene in vivo and cooperates with p53 heterozygosity to drive tumorigenesis. These Mdm4 mice will be invaluable for in vivo drug studies of Mdm4 inhibitors. PMID- 20736371 TI - Deficiency of splicing factor 1 suppresses the occurrence of testicular germ cell tumors. AB - Testicular germ cell tumors (TGCT) originate from germ cells. The 129-Ter and M19 (129.MOLF-Chr19 consomic) mouse strains have extremely high incidences of TGCTs. We found that the expression levels of Sf1-encoded splicing factor 1 (SF1) can modulate the incidence of TGCTs. We generated mice with inactivated Sf1. Sf1 null mice (Sf1-/-) died before birth. Mice with one intact allele of Sf1 (Sf1+/-) were viable but expressed reduced levels of Sf1. When Sf1-deficient mice (Sf1+/-) were crossed to the 129-Ter and M19 strains, we observed decreased incidence of TGCTs in Sf1+/-;Ter and Sf1+/-;M19/+ mice compared with that in control cohorts. Therefore, Sf1 deficiency protects against TGCT development in both strains. Sf1 is expressed in the testes. We found that Sf1 levels vary significantly in the testes of inbred strains such as 129 and MOLF, and as such Sf1 is an oncogenic tumor-susceptibility factor from 129. Our results also highlight the complications involved in evaluating Sf1 levels and TGCT incidences. When a large number of tumor-promoting factors are present in a strain, the protective effect of lower Sf1 levels is masked. However, when the dosage of tumor-promoting factors is reduced, the protective effect of lower Sf1 levels becomes apparent. SF1 is involved in splicing of specific pre-mRNAs in cells. Alternate splicing generates the complex proteosome in eukaryotic cells. Our data indicate that Sf1 levels in mouse strains correlate with their incidences of TGCTs and implicate the importance of splicing mechanisms in germ cell tumorigenesis. PMID- 20736372 TI - Human papillomavirus seropositivity synergizes with MDM2 variants to increase the risk of oral squamous cell carcinoma. AB - The increasing incidence of oral squamous cell carcinoma (OSCC) in young adults has been associated with sexually transmitted infections of human papillomavirus (HPV), particularly HPV16. Given the roles of p53 in tumor suppression and of HPV E6 and MDM2 oncoproteins in p53 degradation, we evaluated HPV16 L1 seropositivity and MDM2 promoter variants to examine their possible associations with OSCC risk in a case-control study of 325 patients and 335 cancer-free matched controls. Compared with individuals having MDM2-rs2279744 GT or GG genotypes and HPV16 L1 seronegativity, the TT genotype and HPV16 L1 seronegativity were found to be associated with an odds ratio (OR) of 1.25 [95% confidence interval (CI), 1.06 2.19] for OSCC risk, and GT/GG and HPV16 L1 seropositivity were associated with an OR of 2.81 (95% CI, 1.67-4.74). For those with both the TT genotype and HPV16 L1 seropositivity, the associated OR was 5.57 (95% CI, 2.93-10.6). Similar results were observed for the MDM2-rs937283 polymorphism. Moreover, there was a borderline significant or significant interaction between the individual or combined MDM2 genotypes of the two polymorphisms and HPV16 L1 seropositivity (P(int) = 0.060 for MDM2-rs2279744, P(int) = 0.009 for MDM2-rs937283, and P(int) = 0.005 for the combined MDM2 genotypes) on risk of OSCC. Notably, that effect modification was particularly pronounced in never smokers and never drinkers, and for oropharyngeal as opposed to oral cavity cancer. Taken together, our results indicate that the risk of OSCC associated with HPV16 L1 seropositivity is modified by MDM2 promoter polymorphisms. PMID- 20736373 TI - Aminoflavone, a ligand of the aryl hydrocarbon receptor, inhibits HIF-1alpha expression in an AhR-independent fashion. AB - Aminoflavone (AF), the active component of a novel anticancer agent (AFP464) in phase I clinical trials, is a ligand of the aryl hydrocarbon receptor (AhR). AhR dimerizes with HIF-1beta/AhR, which is shared with HIF-1alpha, a transcription factor critical for the response of cells to oxygen deprivation. To address whether pharmacologic activation of the AhR pathway might be a potential mechanism for inhibition of HIF-1, we tested the effects of AF on HIF-1 expression. AF inhibited HIF-1alpha transcriptional activity and protein accumulation in MCF-7 cells. However, inhibition of HIF-1alpha by AF was independent from a functional AhR pathway. Indeed, AF inhibited HIF-1alpha expression in Ah(R100) cells, in which the AhR pathway is functionally impaired, yet did not induce cytotoxicity, providing evidence that these effects are mediated by distinct signaling pathways. Moreover, AF was inactive in MDA-MB-231 cells, yet inhibited HIF-1alpha in MDA-MB-231 cells transfected with the SULT1A1 gene. AF inhibited HIF-1alpha mRNA expression by approximately 50%. Notably, actinomycin-D completely abrogated the ability of AF to downregulate HIF-1alpha mRNA, indicating that active transcription was required for the inhibition of HIF 1alpha expression. Finally, AF inhibited HIF-1alpha protein accumulation and the expression of HIF-1 target genes in MCF-7 xenografts. These results show that AF inhibits HIF-1alpha in an AhR-independent fashion, and they unveil additional activities of AF that may be relevant for its further clinical development. PMID- 20736374 TI - Matrix metalloproteinase-9 regulates tumor cell invasion through cleavage of protease nexin-1. AB - Matrix metalloproteinase-9 (MMP-9) expression is known to enhance the invasion and metastasis of tumor cells. In previous work based on a proteomic screen, we identified the serpin protease nexin-1 (PN-1) as a potential target of MMP-9. Here, we show that PN-1 is a substrate for MMP-9 and establish a link between PN 1 degradation by MMP-9 and regulation of invasion. PN-1 levels increased in prostate carcinoma cells after downregulation of MMP-9 and in tissues of MMP-9 deficient mice, consistent with PN-1 degradation by MMP-9. We identified three MMP-9 cleavage sites in PN-1 and showed that mutations in those sites made PN-1 more resistant to MMP-9. Urokinase plasminogen activator (uPA) is inhibited by PN 1. MMP-9 augmented uPA activity in the medium of PC3-ML cells by degrading PN-1. Prostate cancer cells, overexpressing PN-1 or treated with MMP-9 shRNA, had reduced cell invasion in Matrigel. PN-1 siRNA restored uPA activity and the invasive capacity. PN-1 mutated in the serpin inhibitory domain, the reactive center loop, failed to inhibit uPA and to reduce Matrigel invasion. This study shows a novel molecular pathway in which MMP-9 regulates uPA activity and tumor cell invasion through cleavage of PN-1. PMID- 20736375 TI - Functional roles of multiple feedback loops in extracellular signal-regulated kinase and Wnt signaling pathways that regulate epithelial-mesenchymal transition. AB - Epithelial-mesenchymal transition (EMT) is a key event in the generation of invasive tumor cells. A hallmark of EMT is the repression of E-cadherin expression, which is regulated by various signal transduction pathways including extracellular signal-regulated kinase (ERK) and Wnt. These pathways are highly interconnected via multiple coupled feedback loops (CFL). As the function of such coupled feedback regulations is difficult to analyze experimentally, we used a systems biology approach where computational models were designed to predict biological effects that result from the complex interplay of CFLs. Using epidermal growth factor (EGF) and Wnt as input and E-cadherin transcriptional regulation as output, we established an ordinary differential equation model of the ERK and Wnt signaling network containing six feedback links and used extensive computer simulations to analyze the effects of these feedback links in isolation and different combinations. The results show that the feedbacks can generate a rich dynamic behavior leading to various dose-response patterns and have a decisive role in determining network responses to EGF and Wnt. In particular, we made two important findings: first, that coupled positive feedback loops composed of phosphorylation of Raf kinase inhibitor RKIP by ERK and transcriptional repression of RKIP by Snail have an essential role in causing a switch-like behavior of E-cadherin expression; and second, that RKIP expression inhibits EMT progression by preventing E-cadherin suppression. Taken together, our findings provide us with a system-level understanding of how RKIP can regulate EMT progression and may explain why RKIP is downregulated in so many metastatic cancer cells. PMID- 20736376 TI - DNA methylation analysis determines the high frequency of genic hypomethylation and low frequency of hypermethylation events in plasma cell tumors. AB - Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow, which evolves from a premalignant stage called monoclonal gammopathy of undetermined significance (MGUS). In some patients, an intermediate stage referred to as smoldering multiple myeloma (SMM) is clinically recognized, with the full-bore malignancy termed MM. We conducted a study to assess differential CpG methylation at 1,500 genic loci during MM progression and profiled CD138(+) plasma cells from MGUS, SMM, and MM specimens; human myeloma cell lines; and normal plasma cell (NPC) samples. We showed that the number of differentially methylated loci (DML) increased with tumor grade, and the vast majority were due to hypomethylation. Hierarchical clustering analysis revealed samples that coclustered tightly with NPC. These cases, referred to as "normal-like," contained significantly fewer DML when compared with their non-normal-like counterparts and displayed overall methylation levels resembling NPC. This study represents one of the first methylome interrogation studies in MM and points toward global hypomethylation at genic CpG loci as an important and early mechanism driving myelomagenesis. Determining the set of critical genes and pathways based on the myeloma methylome is expected to lead to an improved understanding of biological mechanisms involved in myelomagenesis. PMID- 20736377 TI - Gamma-secretase inhibitors enhance temozolomide treatment of human gliomas by inhibiting neurosphere repopulation and xenograft recurrence. AB - Malignant gliomas are treated with a combination of surgery, radiation, and temozolomide (TMZ), but these therapies ultimately fail due to tumor recurrence. In glioma cultures, TMZ treatment significantly decreases neurosphere formation; however, a small percentage of cells survive and repopulate the culture. A promising target for glioma therapy is the Notch signaling pathway. Notch activity is upregulated in many gliomas and can be suppressed using gamma secretase inhibitors (GSI). Using a neurosphere recovery assay and xenograft experiments, we analyzed if the addition of GSIs with TMZ treatment could inhibit repopulation and tumor recurrence. We show that TMZ + GSI treatment decreased neurosphere formation and inhibited neurosphere recovery. This enhancement of TMZ treatment occurred through inhibition of the Notch pathway and depended on the sequence of drug administration. In addition, ex vivo TMZ + GSI treatment of glioma xenografts in immunocompromised mice extended tumor latency and survival, and in vivo TMZ + GSI treatment blocked tumor progression in 50% of mice with preexisting tumors. These data show the importance of the Notch pathway in chemoprotection and repopulation of TMZ-treated gliomas. The addition of GSIs to current treatments is a promising approach to decrease brain tumor recurrence. PMID- 20736379 TI - Delayed cure from CIED infections: losing only time without risk for patient outcome? PMID- 20736378 TI - Loss of PTEN binding adapter protein NHERF1 from plasma membrane in glioblastoma contributes to PTEN inactivation. AB - Glioblastoma multiforme (GBM) is a severe brain malignancy with limited treatment and dismal prognosis. The tumor suppressor PTEN, a major inhibitor of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway, is frequently deleted in GBM tumors. PTEN antagonizes PI3K by dephosphorylating PI3K phosphoinositide substrates at the plasma membrane. The PTEN binding adapter protein NHERF1/EBP50 is overexpressed in GBM but its effects on tumorigenesis have yet to be determined. Here, we show that NHERF1 is localized to the plasma membrane in normal astrocytes and to the cytoplasm of GBM tumor cells. This cytoplasmic shift paralleled an altered membrane distribution of wild-type PTEN with consecutive Akt activation. Membrane re-targeting of NHERF1 in GBM cells recruited PTEN to the membrane and suppressed Akt activation and cell proliferation. Conversely, NHERF1 depletion in GBM cells with membrane-localized NHERF1 increased cell proliferation and Akt activation. Our findings define a tumor suppressor role for NHERF1 at the plasma membrane, and reveal a novel mechanism for PI3K/Akt activation through PTEN inactivation caused by a loss of membrane-localized NHERF1. PMID- 20736380 TI - Association between short sleep duration and obesity among South korean adolescents. AB - Short sleep duration and obesity are common health concerns in youth. This study of South Korean adolescents explores the association between the two conditions analyzing secondary data from the 2007 Korea Youth Risk Behavior Web-Based Survey. The sample is representative of the South Korean adolescent population (N = 73,836). For data analysis, analysis of variance, chi-square test, and logistic regression were used. Findings indicated that (a) sleep duration is inversely associated with levels of body mass index, F(4, 72654) = 240.07, p < .0001, and risks for overweight and obesity, chi(2)(4, 72659) = 27.41, p < .0001; and (b) after controlling for obesity-related factors, reduced sleep is strongly associated with a greater risk for overweight and obesity, OR = 0.94, p < .0001. Given the important link between sleep and obesity, health professionals should consider sleep habits as a significant factor in obesity-related problems of youth. PMID- 20736381 TI - Mobility adaptations of older adults: a secondary analysis. AB - The purpose of this secondary study was to describe the mobility adaptations of community-living older adults. The primary study, designed to understand weakness and aging from the perspective of older adults, revealed that older adults viewed weakness as a progression from inability to an end point of 'giving up,' which prompted the use of adaptation strategies to preserve mobility and to counter a self-identity of being weak. A qualitative descriptive design guided the primary study of 15 community-living older adults, who participated in in-depth interviews. A systematic secondary analysis using Baltes and Baltes' theory of Selective Optimization with Compensation (SOC) showed that older adults used selection, optimization, and compensation adaptations across a range of mobility behaviors. The SOC model offered a framework for profiling older adults' agency and motivations in meeting mobility challenges as they age and provided the basis for targeted interventions to maximize mobility with aging. PMID- 20736382 TI - Nutritional symptom and body composition outcomes of aerobic exercise in women with breast cancer. AB - The purpose of this secondary analysis was to examine the nutritional symptoms and body composition outcomes of aerobic exercise in women with breast cancer. A single-blind clinical trial, randomized to tailored Pro-Self((c)) exercise during and after chemotherapy, after chemotherapy only, or no Pro-Self (usual care). One hundred women, average age 49.9 years (SD = 9.6), participated. Mild taste changes, nausea, constipation, and anorexia were experienced by 47% to 55% at baseline and end of treatment but diminished post treatment. No group differences were found in total nutritional symptoms or symptom severity. Intervention group participants maintained lean body mass; control group participants had nonsignificant lean body mass loss. Issues related to self-report, protocol adherence, and generalizability limit findings. Aerobic exercise is useful in achieving healthy weight and body composition, but the intensity and duration achieved during cancer treatment and recovery did not produce significant changes. PMID- 20736383 TI - Suppression of the vacuolar invertase gene prevents cold-induced sweetening in potato. AB - Potato (Solanum tuberosum) is the third most important food crop in the world. Potato tubers must be stored at cold temperatures to prevent sprouting, minimize disease losses, and supply consumers and the processing industry with high quality tubers throughout the year. Unfortunately, cold storage triggers an accumulation of reducing sugars in tubers. High-temperature processing of these tubers results in dark-colored, bitter-tasting products. Such products also have elevated amounts of acrylamide, a neurotoxin and potential carcinogen. We demonstrate that silencing the potato vacuolar acid invertase gene VInv prevents reducing sugar accumulation in cold-stored tubers. Potato chips processed from VInv silencing lines showed a 15-fold acrylamide reduction and were light in color even when tubers were stored at 4 degrees C. Comparable, low levels of VInv gene expression were observed in cold-stored tubers from wild potato germplasm stocks that are resistant to cold-induced sweetening. Thus, both processing quality and acrylamide problems in potato can be controlled effectively by suppression of the VInv gene through biotechnology or targeted breeding. PMID- 20736384 TI - Improving the sensitivity of blood culture for Streptococcus pneumoniae. AB - Isolation of Streptococcus pneumoniae is jeopardized by low sensitivity of blood culture, autolysis and contamination with fast-growing organism(s). We performed an immunochromatographic (ICT) test for S. pneumoniae on chocolatized blood culture bottles and also sub-cultured contaminated bottles on a selective medium, thus identifying an additional eight and three cases, respectively, and improving the detection of pneumococcus by 23% (48% vs. 59%). Prescreening of culture bottles in a blinded fashion could rationalize the use of ICT with ~99% accuracy. These two approaches can aid microbiology laboratories in resource-poor countries to substantially improve rates of detection of S. pneumoniae. PMID- 20736385 TI - Sample size calculation and power analysis: a quick review. AB - Diabetes educators conducting research need a basic understanding of statistical concepts so study findings are useful and can be read with confidence. Selecting an adequate sample size is a key step that needs to be considered early in the process of designing a research study. A sample size too small will not provide reliable answers to the study questions asked or research hypotheses needing to be tested. A sample size that is too big can make the study unwieldy, wasting both time and effort. An adequate sample size uses resources and time in the most cost-effective manner and is essential to producing useful research findings. The purpose of this article is to understand the importance of selecting an adequate sample size in gaining information from a small group (sample) that can be generalized to a larger group (population) along with discussing power analyses. PMID- 20736386 TI - Physical activity preferences and type 2 diabetes: exploring demographic, cognitive, and behavioral differences. AB - PURPOSE: The purpose of this study was to examine physical activity counseling and program preferences in a sample of adults with type 2 diabetes. Specifically, the objectives were to determine physical activity preferences (objective 1), and whether there were any significant differences between age and/or sex groups for these preferences (objective 1a). A subsidiary objective was to explore potential associations of key social-cognitive constructs (ie, self-efficacy and social support) with physical activity preferences (objective 2). METHODS: This exploratory study consisted of a quantitative, secondary analysis of survey data from a national sample of adults with type 2 diabetes (N = 244). A qualitative follow-up employing telephone interviews was conducted with 14 individuals. RESULTS: Consistent with hypotheses, walking was the most preferred physical activity behavior and there was a preference for engaging in physical activity with others. There were significant (P values < .05) differences in counseling and program preferences between demographic (age and sex), and physical activity cognitive scores. For example, a significantly (P < .05) higher physical activity intensity preference was found in men and younger participants. CONCLUSIONS: Tailoring interventions and physical activity programs to the specific preferences of individuals is an important component for health professionals and researchers in facilitating this behavior. PMID- 20736387 TI - Understanding GLP-1 analogs and enhancing patients success. AB - Recent research into the mechanisms of type 2 diabetes reveals intricate interactions among many hormonal processes. Ultimately, these pathways lead to hyperglycemia, pancreatic beta-cell failure, and the emergence of type 2 diabetes. The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), are now known to play major roles in endogenous glucose control, including regulation of insulin, glucagon, and hepatic glucose metabolism. Investigation of the incretin system has led to development of drugs that mimic or enhance the endogenous hormones, including GLP 1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. This supplement describes the role of incretin hormones in the pathophysiology of type 2 diabetes and their potential as therapeutic targets for disease management. In addition, safety and efficacy profiles of the GLP-1 receptor agonists are reviewed, and the advantages and limitations of these medications are discussed from the perspective of promoting their successful implementation in individualized treatment regimens. As understanding of the underlying pathophysiology and pathogenesis of type 2 diabetes advances, the number of new therapeutic approaches expands. GLP-1 receptor agonists address several aspects of the pathophysiology of type 2 diabetes. A large body of data reveals the efficacy, safety, and tolerability of these drugs. A clear understanding of the evidence base for these drugs will translate into improved education of patients regarding their options to improve glycemic control and, ultimately, to better patient care. PMID- 20736388 TI - Self-reported and laboratory-based responses to stress in children with recurrent pain and anxiety. AB - OBJECTIVE: To examine heart rate (HR) responses to and coping with stress in children with recurrent abdominal pain (RAP), anxiety, and healthy controls. METHODS: A clinical sample (children with RAP and children with anxiety) was compared to control children on self-reported and HR responses to stress and a laboratory test of pain tolerance and intensity (cold pressor). RESULTS: Children in the clinical sample had elevated HRs compared to healthy controls before, during, and after laboratory tasks. Self-reported stress reactivity to social stress was positively correlated with HR at all study time intervals. Secondary control coping with social stress was negatively correlated with HR at most study time intervals. Internalizing symptoms were positively correlated with HR and self-reported stress reactivity. CONCLUSIONS: Stress reactivity, as reflected in both self-reported and HR responses to laboratory stressors, is related to the presence of both RAP and anxiety in children. PMID- 20736389 TI - From caregiver psychological distress to adolescent glycemic control: the mediating role of perceived burden around diabetes management. AB - OBJECTIVE: To examine whether perceived caregiver burden around diabetes management mediated the relationship between caregivers' psychological distress and adolescents' glycemic control. METHODS: Across three visits spanning 9 months, caregivers of 147 adolescents with type 1 diabetes completed measures of anxiety and depressive symptoms and a measure of perceived burden specific to diabetes management. Adolescents' glycemic control was also measured. RESULTS: Perceived burden mediated the relationship between caregiver depressive symptoms and adolescents' glycemic control. The overall model was significant, F(10,132) = 5.0, p < .001, R(2) = 0.27. Fifty percent of the relationship was explained by diabetes-specific burden. The relationship between caregiver anxiety symptoms and adolescent glycemic control was partially mediated by diabetes-specific burden, F(10,133) = 5.7, p < .001, R(2) = 0.30, explaining 26% of this relationship. DISCUSSION: A variable linking caregiver psychological distress to adolescent glycemic control is perceived caregiver burden around diabetes management. Implications for clinical practice include targeting caregiver psychological functioning and reducing global and diabetes-specific distress. PMID- 20736391 TI - Well controlled, double-blind, placebo-controlled trials of classical Ayurvedic treatment are possible in rheumatoid arthritis. PMID- 20736390 TI - Anti-cyclic citrullinated peptide antibodies are a collection of anti citrullinated protein antibodies and contain overlapping and non-overlapping reactivities. AB - OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are a hallmark of rheumatoid arthritis and are believed to play a role in disease pathogenesis. These antibodies are typically detected in ELISA with citrullinated peptides (eg, CCP2) or proteins as antigens. The absolute concentration of anti-CCP antibodies in serum is unknown. Although antibodies to several citrullinated proteins can mainly be detected within anti-CCP-positive sera, it is currently unknown whether anti-CCP antibodies are in fact ACPA. Likewise, it is unknown to what extent antibody responses to different citrullinated antigens are crossreactive. METHODS: An affinity purification method was established in which citrullinated antigen-specific antibodies were eluted from ELISA plates and then used for detection of other citrullinated antigens in ELISA or western blot. For additional crossreactivity studies, ELISA-based inhibition assays were performed with citrullinated or control peptides as inhibitors. RESULTS: The concentration of anti-CCP IgG antibodies was estimated to be at least 30 MUg/ml in patients with high anti-CCP levels (>1600 MUg/ml). Affinity-purified anti-CCP antibodies were able to recognise citrullinated fibrinogen (cit-fib) and citrullinated myelin basic protein (cit-MBP) on western blot. Furthermore, antibodies specific for cit-fib and cit-MBP were crossreactive. However, additional crossreactivity studies indicated that non-overlapping antibody responses to citrullinated peptides can also exist in patients. CONCLUSIONS: This report shows for the first time that anti-CCP antibodies recognise multiple citrullinated proteins and are thus a collection of ACPA. More importantly, the data indicate that different ACPA responses are crossreactive, but that crossreactivity is not complete, as distinct non-crossreactive responses can also be detected in patients with RA. PMID- 20736392 TI - Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index. AB - OBJECTIVES: To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis. METHODS: A total of 283 patients with vasculitis from 11 European centres were evaluated in a cross sectional study using the VDI and CDA. RESULTS: Wegener's granulomatosis (58.4%) and microscopic polyangiitis (11.0%) were the most common diagnoses. Agreement between VDI and CDA scores (Spearman's correlation) was 0.90 (95% CI 0.87 to 0.92). There was good correlation between individual comparably evaluated organ systems (Spearman's correlation 0.70-0.94). Interobserver reliability (assessed by intraclass correlation coefficient (ICC)) was 0.94 (95% CI 0.89 to 0.98) for VDI and 0.78 (95% CI 0.63 to 0.93) for CDA. Intraobserver reliability was 0.92 (95% CI 0.83 to 1.00) for VDI and 0.87 (95% CI 0.75 to 1.00) for CDA. A total of 13 items were not used in the VDI compared to 23 in the CDA. Observers agreed that the CDA covered the full spectrum of damage attributable to vasculitis but was more time consuming and thus possibly less feasible for clinical and research purposes. CONCLUSIONS: The VDI and CDA capture reliable data on damage among patients with vasculitis. The CDA captures more detail but is more complex and less practical than the VDI. Further evolution of damage assessment in vasculitis is likely to include key elements from both instruments. PMID- 20736393 TI - Clinical and radiographic disease course of hand osteoarthritis and determinants of outcome after 6 years. AB - OBJECTIVE: To investigate the long-term clinical and radiographic disease course of hand osteoarthritis (OA) and determinants of outcome. METHODS: Clinical and radiographic measures were obtained at baseline and after 6 years in 289 patients with hand OA (mean age 59.5 years, 83.0% women). Clinical outcomes were self reported pain and functional limitations assessed with the Australian/Canadian Osteoarthritis Hand Index (AUSCAN). Poor clinical outcome was defined as a follow up score not fulfilling the Patient Acceptable Symptom State. Radiographic outcome was assessed by osteophytes and joint space narrowing (JSN) on standardised hand radiographs using the Osteoarthritis Research Society International (OARSI) atlas. Radiographic progression was defined as a change in osteophytes or JSN, above the smallest detectable change. Change in outcome measures was calculated and baseline determinants for poor clinical outcome and radiographic progression were assessed using logistic regression analysis. RESULTS: Clinical change showed great variation, with half of the population reporting deterioration. Poor outcome in pain was related to high levels of functional limitations and a high number of painful joints at baseline. Poor outcome on functional limitations was related to high baseline pain levels. Radiographic progression was present in 52.5% of patients and associated with high baseline levels of pain, nodes, osteophytes and the presence of erosive OA and nodal OA. Clinical change and radiographic progression were not related. CONCLUSIONS: This study gives insight in the clinical and radiographic course of hand OA as well as determinants of outcome. These findings enable better patient information on prognosis. The relationship between clinical and radiographic outcome needs further investigation. PMID- 20736395 TI - Update on the causes, investigation and management of empyema in childhood. AB - Despite being recognised for over two millennia and having an increasing incidence in many countries, the management of childhood empyema remains controversial. This review examines the recent literature on its causes and investigation then focuses on its treatment. Following a trial of appropriate intravenous antibiotics, the evidence would currently support the use of chest drain insertion with urokinase instillation as first line treatment with video assisted thoracoscopic surgery to be used for failure of medical management. A treatment algorithm is proposed to guide clinical practice. PMID- 20736396 TI - Which antibiotic first in meningococcal disease? A national survey. PMID- 20736397 TI - Joint effect of maternal depression and intimate partner violence on increased risk of child death in rural Ethiopia. AB - OBJECTIVES: To assess independent and interaction effect of experience of intimate partner violence and depression on risk of child death. DESIGN: Community-based cohort design. SETTING: The study was conducted within the demographic surveillance site of Butajira Rural Health Program in south central Ethiopia. PARTICIPANTS: Women (n=561) who gave birth to a live child. MAIN OUTCOME MEASURES: Exposure status comprising physical, sexual and emotional violence by intimate partner was based on the WHO multi-country questionnaire on violence against women. Depression status was measured using the Composite International Diagnostic Interview. Risk of child death and its association with maternal exposure to violence and/or being depressed was analysed by incidence, rate ratios and interaction. RESULTS: The child death in the cohort was 42.1 (95% CI, 32.7 to 53.5) children per 1000 person years, and maternal depression is associated with child death. The risk of child death increases when maternal depression is combined with physical and emotional violence (RR=4.0; 95% CI, 1.6 to 10.1) and (RR=3.7; 95% CI, 1.3 to 10.4), showing a synergistic interaction. CONCLUSION: An awareness of the devastating consequences on child survival in low income setting of violence against women and depression is needed among public health workers as well as clinicians, for both community and clinical interventions. PMID- 20736398 TI - Survey of the use of therapeutic hypothermia post cardiac arrest. AB - OBJECTIVES: Therapeutic hypothermia improves neurological outcome in adults after ventricular fibrillation cardiac arrest and neonates with hypoxic ischaemic encephalopathy. There is currently no clinical research to support its use in the paediatric population. This survey aims to ascertain current practice in the UK, and attitudes and opinions to guide the feasibility of a UK multicentre, randomised, controlled trial of therapeutic hypothermia after cardiac arrest in children (The Cold-PACK Post Arrest Cooling in Kids study). METHODS: Anonymous survey of UK paediatric intensive care consultants (n=149). RESULTS: A total of 113 (76%) of 149 surveys were returned; 65% responded that they do not know if therapeutic hypothermia improves survival after cardiac arrest. Despite this, 48% 'always' or 'often' use therapeutic hypothermia after return of spontaneous circulation following cardiac arrest in children. Among those who never use therapeutic hypothermia (33%) the commonest explanation given was 'not enough research evidence' (91%). With respect to the dose of therapeutic hypothermia the median duration of cooling used is 24-48 h (range 4-72 h) and median target temperature 34 degrees C to 35 degrees C (range 32 degrees C to 37 degrees C); 68% target a temperature range higher than that applied in the published adult and neonatal studies (33+/-1 degrees C). There was strong support for a trial of therapeutic hypothermia being ethical (89%) and using deferred consent (85%). CONCLUSIONS: Wide variation in UK practice in the use of therapeutic hypothermia and a state of clinical equipoise is demonstrated by this survey, which shows important support for UK multicentre collaboration in a future trial of therapeutic hypothermia after cardiac arrest. PMID- 20736400 TI - Accuracy of tympanic and infrared skin thermometers in children. AB - BACKGROUND: Rectal measurement is considered a gold standard in many healthcare systems for body temperature measurement in children. Although this method has several disadvantages, an ideal alternative thermometer has not yet been introduced. However tympanic and infrared skin thermometers are potential alternatives. METHODS: A prospective cohort study was performed including 100 children between 0 and 18 years of age admitted to the general paediatric ward of Spaarne Hospital in The Netherlands between January and March 2009. The objectives of this study are to evaluate the accuracy of tympanic and two types of infrared skin thermometers (Beurer and Thermofocus) compared to rectal measurement and furthermore to evaluate the influence of different variables on temperature measurements. RESULTS: Compared to rectal measurement (37.56 degrees C), the mean temperatures of the tympanic (37.29 degrees C), Beurer (36.79 degrees C) and Thermofocus (37.30 degrees C) thermometers differed significantly (p<0.001). Mean and SD of differences between rectal temperature and temperature measured with these alternative devices varied significantly (p<0.001). Sensitivity, specificity, positive and negative predictive values for detecting rectal fever measured with the tympanic, Beurer and Thermofocus thermometers are unacceptable, especially for the Beurer thermometer. This difference in temperature between rectal and the alternative thermometers remained after stratification on gender, age, skin colour and otoscopic abnormalities. CONCLUSIONS: In this study the authors demonstrated that the tympanic, Beurer and Thermofocus thermometers cannot reliably predict rectal temperature. Therefore the authors do not advise replacement of rectal measurement as the gold standard for detecting fever in children by one of these devices. When rectal measurement is not used, the infrared skin thermometers appear to perform less well than tympanic measurements. PMID- 20736402 TI - Type 2 deiodinase and brown fat: the heat is on--or off. PMID- 20736401 TI - Deep-sea oil plume enriches indigenous oil-degrading bacteria. AB - The biological effects and expected fate of the vast amount of oil in the Gulf of Mexico from the Deepwater Horizon blowout are unknown owing to the depth and magnitude of this event. Here, we report that the dispersed hydrocarbon plume stimulated deep-sea indigenous gamma-Proteobacteria that are closely related to known petroleum degraders. Hydrocarbon-degrading genes coincided with the concentration of various oil contaminants. Changes in hydrocarbon composition with distance from the source and incubation experiments with environmental isolates demonstrated faster-than-expected hydrocarbon biodegradation rates at 5 degrees C. Based on these results, the potential exists for intrinsic bioremediation of the oil plume in the deep-water column without substantial oxygen drawdown. PMID- 20736403 TI - Neurokinin B and kisspeptin: sexual partners or single agents? PMID- 20736404 TI - "The curse": a 21st century perspective of models of its molecular basis. PMID- 20736405 TI - Invaders from the spleen: an unexpected origin of the leukocytes participating in ovulation. PMID- 20736406 TI - SH2B1--the adaptor protein that could. PMID- 20736407 TI - Characterization of macaque pulmonary fluid proteome during monkeypox infection: dynamics of host response. AB - Understanding viral pathogenesis is challenging because of confounding factors, including nonabrasive access to infected tissues and high abundance of inflammatory mediators that may mask mechanistic details. In diseases such as influenza and smallpox where the primary cause of mortality results from complications in the lung, the characterization of lung fluid offers a unique opportunity to study host-pathogen interactions with minimal effect on infected animals. This investigation characterizes the global proteome response in the pulmonary fluid, bronchoalveolar lavage fluid, of macaques during upper respiratory infection by monkeypox virus (MPXV), a close relative of the causative agent of smallpox, variola virus. These results are compared and contrasted against infections by vaccinia virus (VV), a low pathogenic relative of MPXV, and with extracellular fluid from MPXV-infected HeLa cells. To identify changes in the pulmonary protein compartment, macaque lung fluid was sampled twice prior to infection, serving as base line, and up to six times following intrabronchial infection with either MPXV or VV. Increased expression of inflammatory proteins was observed in response to both viruses. Although the increased expression resolved for a subset of proteins, such as C-reactive protein, S100A8, and S100A9, high expression levels persisted for other proteins, including vitamin D-binding protein and fibrinogen gamma. Structural and metabolic proteins were substantially decreased in lung fluid exclusively during MPXV and not VV infection. Decreases in structural and metabolic proteins were similarly observed in the extracellular fluid of MPXV-infected HeLa cells. Results from this study suggest that the host inflammatory response may not be the only facilitator of viral pathogenesis, but rather maintaining pulmonary structural integrity could be a key factor influencing disease progression and mortality. PMID- 20736409 TI - Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins. AB - The mammalian spermatozoon has many cellular compartments, such as head and tail, permitting it to interact with the female reproductive tract and fertilize the egg. It acquires this fertilizing potential during transit through the epididymis, which secretes proteins that coat different sperm domains. Optimal levels of these proteins provide the spermatozoon with its ability to move to, bind to, fuse with, and penetrate the egg; otherwise male infertility results. As few human epididymal proteins have been characterized, this work was performed to generate a database of human epididymal sperm-located proteins involved in maturation. Two-dimensional gel electrophoresis of epididymal tissue and luminal fluid proteins, followed by identification using MALDI-TOF/MS or MALDI-TOF/TOF, revealed over a thousand spots in gels comprising 745 abundant nonstructural proteins, 408 in luminal fluids, of which 207 were present on spermatozoa. Antibodies raised to 619 recombinant or synthetic peptides, used in Western blots, histological sections, and washed sperm preparations to confirm antibody quality and protein expression, indicated their regional location in the epididymal epithelium and highly specific locations on washed functional spermatozoa. Sperm function tests suggested the role of some proteins in motility and protection against oxidative attack. A large database of these proteins, characterized by size, pI, chromosomal location, and function, was given a unified terminology reflecting their sperm domain location. These novel, secreted human epididymal proteins are potential targets for a posttesticular contraceptive acting to provide rapid, reversible, functional sterility in men and they are also biomarkers that could be used in noninvasive assessments of male fertility. PMID- 20736408 TI - Mass spectrometry based glycoproteomics--from a proteomics perspective. AB - Glycosylation is one of the most important and common forms of protein post translational modification that is involved in many physiological functions and biological pathways. Altered glycosylation has been associated with a variety of diseases, including cancer, inflammatory and degenerative diseases. Glycoproteins are becoming important targets for the development of biomarkers for disease diagnosis, prognosis, and therapeutic response to drugs. The emerging technology of glycoproteomics, which focuses on glycoproteome analysis, is increasingly becoming an important tool for biomarker discovery. An in-depth, comprehensive identification of aberrant glycoproteins, and further, quantitative detection of specific glycosylation abnormalities in a complex environment require a concerted approach drawing from a variety of techniques. This report provides an overview of the recent advances in mass spectrometry based glycoproteomic methods and technology, in the context of biomarker discovery and clinical application. PMID- 20736410 TI - Development of a novel cross-linking strategy for fast and accurate identification of cross-linked peptides of protein complexes. AB - Knowledge of elaborate structures of protein complexes is fundamental for understanding their functions and regulations. Although cross-linking coupled with mass spectrometry (MS) has been presented as a feasible strategy for structural elucidation of large multisubunit protein complexes, this method has proven challenging because of technical difficulties in unambiguous identification of cross-linked peptides and determination of cross-linked sites by MS analysis. In this work, we developed a novel cross-linking strategy using a newly designed MS-cleavable cross-linker, disuccinimidyl sulfoxide (DSSO). DSSO contains two symmetric collision-induced dissociation (CID)-cleavable sites that allow effective identification of DSSO-cross-linked peptides based on their distinct fragmentation patterns unique to cross-linking types (i.e. interlink, intralink, and dead end). The CID-induced separation of interlinked peptides in MS/MS permits MS(3) analysis of single peptide chain fragment ions with defined modifications (due to DSSO remnants) for easy interpretation and unambiguous identification using existing database searching tools. Integration of data analyses from three generated data sets (MS, MS/MS, and MS(3)) allows high confidence identification of DSSO cross-linked peptides. The efficacy of the newly developed DSSO-based cross-linking strategy was demonstrated using model peptides and proteins. In addition, this method was successfully used for structural characterization of the yeast 20 S proteasome complex. In total, 13 non-redundant interlinked peptides of the 20 S proteasome were identified, representing the first application of an MS-cleavable cross-linker for the characterization of a multisubunit protein complex. Given its effectiveness and simplicity, this cross-linking strategy can find a broad range of applications in elucidating the structural topology of proteins and protein complexes. PMID- 20736411 TI - From whole-body sections down to cellular level, multiscale imaging of phospholipids by MALDI mass spectrometry. AB - Significant progress in instrumentation and sample preparation approaches have recently expanded the potential of MALDI imaging mass spectrometry to the analysis of phospholipids and other endogenous metabolites naturally occurring in tissue specimens. Here we explore some of the requirements necessary for the successful analysis and imaging of phospholipids from thin tissue sections of various dimensions by MALDI time-of-flight mass spectrometry. We address methodology issues relative to the imaging of whole-body sections such as those cut from model laboratory animals, sections of intermediate dimensions typically prepared from individual organs, as well as the requirements for imaging areas of interests from these sections at a cellular scale spatial resolution. We also review existing limitations of MALDI imaging MS technology relative to compound identification. Finally, we conclude with a perspective on important issues relative to data exploitation and management that need to be solved to maximize biological understanding of the tissue specimen investigated. PMID- 20736415 TI - How to use acylcarnitine profiles to help diagnose inborn errors of metabolism. PMID- 20736414 TI - Explanation of inequality in utilization of ambulatory care before and after universal health insurance in Thailand. AB - Thailand implemented a Universal Coverage Scheme (UCS) of national health insurance in April 2001 to finance equitable access to health care. This paper compares inequalities in health service use before and after the UCS, and analyses the trend and determinants of inequality. The national Health and Welfare Surveys of 2001 and 2005 are used for this study. The concentration index for use of ambulatory care among the population reporting a recent illness is used as a measure of health inequality, decomposed into contributing demographic, socio-economic, geographic and health insurance determinants. As a result of the UCS, the uninsured group fell from 24% in 2001 to 3% in 2005 and health service patterns changed. Use of public primary health care facilities such as health centres became more concentrated among the poor, while use of provincial/general hospitals became more concentrated among the better-off. Decomposition analysis shows that the increasingly common use of health centres among the poor in 2005 was substantially associated with those with lower income, residence in the rural northeast and the introduction of the UCS. The increasing use of provincial/general hospitals and private clinics among the better-off in 2005 was substantially associated with the government and private employee insurance schemes. Although the UCS scheme has achieved its objective in increasing insurance coverage and utilization of primary health services, our findings point to the need for future policies to focus on the quality of this primary care and equitable referrals to secondary and tertiary health facilities when required. PMID- 20736413 TI - Alterations in the proteome of the NHERF1 knockout mouse jejunal brush border membrane vesicles. AB - Na/H exchanger regulatory factor 1 (NHERF1) is a scaffold protein made up of two PDZ domains and an ERM binding domain. It is in the brush border of multiple epithelial cells where it modulates 1) Na absorption by regulating NHE3 complexes and cytoskeletal association, 2) Cl secretion through trafficking of CFTR, and 3) Na-coupled phosphate absorption through membrane retention of NaPi2a. To further understand the role of NHERF1 in regulation of small intestinal Na absorptive cell function, with emphasis on apical membrane transport regulation, quantitative proteomic analysis was performed on brush border membrane vesicles (BBMV) prepared from wild-type (WT) and homozygous NHERF1 knockout mouse jejunal villus Na absorptive cells. Jejunal architecture appeared normal in NHERF1 null; however, there was increased proliferative activity, as indicated by increased crypt BrdU staining. LC-MS/MS analysis using iTRAQ to compare WT and NHERF1 null BBMV identified 463 proteins present in both WT and NHERF1 null BBMV of simultaneously prepared and studied samples. Seventeen proteins had an altered amount of expression between WT and NHERF1 null in two or more separate preparations, and 149 total proteins were altered in at least one BBMV preparation. The classes of the majority of proteins altered included transport proteins, signaling and trafficking proteins, and proteins involved in proliferation and cell division. Affected proteins also included tight junction and adherens junction proteins, cytoskeletal proteins, as well as metabolic and BB digestive enzymes. Changes in abundance of several proteins were confirmed by immunoblotting [increased CEACAM1, decreased ezrin (p-ezrin), NHERF3, PLCbeta3, E cadherin, p120, beta-catenin]. The changes in the jejunal BBMV proteome of NHERF1 null mice are consistent with a more complex role of NHERF1 than just forming signaling complexes and anchoring proteins to the apical membrane and include at least alterations in proteins involved in transport, signaling, and proliferation. PMID- 20736417 TI - Placental histology related to fetal brain sonography. AB - BACKGROUND: Chronic hypoxia and inflammatory processes can induce placental disturbances that may indirectly lead to perinatal brain injury. OBJECTIVE: To study histological features of the placenta in relation to echogenicity changes in the periventricular white matter, ventricular system and basal ganglia/thalami of the fetal brain. DESIGN: Prospective study of 77 fetuses between 26 and 34 weeks gestational age with their placentas. The pregnancies were complicated by hypertensive disorders (n=42) or preterm labour (n=35). RESULTS: Of the placentas 79% showed uteroplacental hypoperfusion, inflammation or a combination. Transvaginal ultrasound examination of the brain revealed echogenicity changes in 73% of the fetuses (44 mild, 29 moderate). Moderate brain echogenicity changes (periventricular echodensity (PVE) grade IB: increased echogenicity brighter than choroid plexus, intraventricular echodensity (IVE) grade II and III: echodensity filling ventricle respectively <50% and >=50%; basal ganglia/thalamic echodensity (BGTE): locally increased echogenicity within basal ganglia/thalami) were equally distributed over cases with uteroplacental hypoperfusion and inflammatory features in the placenta. PVE grade IB was always associated with placental pathology. The sensitivity and negative predictive value of placental pathology for moderate echogenicity changes were high (0.91 and 0.88, respectively), while the specificity and positive predictive value were low (0.27 and 0.34, respectively). CONCLUSIONS: Normal placental histology predicted no or mild echogenicity changes, supporting the view that the latter are physiological. Placental pathology was always present in cases with grade IB PVE, presumed to represent mild or early forms of white matter injury. Both uteroplacental hypoperfusion and inflammatory features were seen in placentas from pregnancies with hypertensive disorders. PMID- 20736416 TI - Does bronchopulmonary dysplasia contribute to the occurrence of cerebral palsy among infants born before 28 weeks of gestation? AB - OBJECTIVE: To evaluate the relationships among cerebral palsy (CP) phenotypes and bronchopulmonary dysplasia (BPD) severity and, in the process, to generate hypotheses regarding causal pathways linking BPD to CP. STUDY DESIGN: We studied 1047 infants born before the 28th week of gestation. Receipt of supplemental oxygen at 36 weeks postmenstrual age (PMA), with or without the need for mechanical ventilation (MV) at 36 weeks PMA, defined two levels of BPD. At 24 months, the children underwent neurologic examinations and CP diagnoses were made using an algorithm based on topographic localisation. RESULTS: The 536 infants with BPD were at increased risk of all three CP phenotypes. In time-oriented multivariable analyses that adjusted for potential confounders, receipt of supplemental oxygen without MV at 36 weeks PMA (BPD) was not associated with increased risk of any CP phenotype. In contrast, BPD accompanied by MV at 36 weeks PMA (BPD/MV) was associated with a nearly sixfold increased risk of quadriparesis and a fourfold increased risk of diparesis. CONCLUSIONS: Combined treatment with both MV and supplemental oxygen at 36 weeks PMA strongly predicts the more common bilateral CP phenotypes. BPD without MV at 36 weeks PMA was not significantly associated with any form of CP. PMID- 20736412 TI - Vascular smooth muscle phenotypic diversity and function. AB - The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts. PMID- 20736418 TI - Intravascular pressure augments cerebral arterial constriction by inducing voltage-insensitive Ca2+ waves. AB - This study examined whether elevated intravascular pressure stimulates asynchronous Ca(2+) waves in cerebral arterial smooth muscle cells and if their generation contributes to myogenic tone development. The endothelium was removed from rat cerebral arteries, which were then mounted in an arteriograph, pressurized (20-100 mmHg) and examined under a variety of experimental conditions. Diameter and membrane potential (V(M)) were monitored using conventional techniques; Ca(2+) wave generation and myosin light chain (MLC(20))/MYPT1 (myosin phosphatase targeting subunit) phosphorylation were assessed by confocal microscopy and Western blot analysis, respectively. Elevating intravascular pressure increased the proportion of smooth muscle cells firing asynchronous Ca(2+) waves as well as event frequency. Ca(2+) wave augmentation occurred primarily at lower intravascular pressures (<60 mmHg) and ryanodine, a plant alkaloid that depletes the sarcoplasmic reticulum (SR) of Ca(2+), eliminated these events. Ca(2+) wave generation was voltage insensitive as Ca(2+) channel blockade and perturbations in extracellular [K(+)] had little effect on measured parameters. Ryanodine-induced inhibition of Ca(2+) waves attenuated myogenic tone and MLC(20) phosphorylation without altering arterial V(M). Thapsigargin, an SR Ca(2+)-ATPase inhibitor also attenuated Ca(2+) waves, pressure-induced constriction and MLC(20) phosphorylation. The SR-driven component of the myogenic response was proportionally greater at lower intravascular pressures and subsequent MYPT1 phosphorylation measures revealed that SR Ca(2+) waves facilitated pressure-induced MLC(20) phosphorylation through mechanisms that include myosin light chain phosphatase inhibition. Cumulatively, our findings show that mechanical stimuli augment Ca(2+) wave generation in arterial smooth muscle and that these transient events facilitate tone development particularly at lower intravascular pressures by providing a proportion of the Ca(2+) required to directly control MLC(20) phosphorylation. PMID- 20736419 TI - CO2-dependent opening of connexin 26 and related beta connexins. AB - We have previously shown connexin mediated CO(2)-dependent ATP release from the surface of the medulla oblongata. Given the localization of connexin 26 (Cx26) to the chemosensing areas of the medulla, we have tested in a heterologous expression system (HeLa cells) whether Cx26 may be sensitive to changes in PCO2. Cx26 responded to an increase in PCO2 at constant extracellular pH by opening and to a decrease in PCO2 by closing. Furthermore, Cx26 was partially activated at a physiological PCO2 of around 40 mmHg. Cx26 in isolated patches responded to changes in PCO2, suggesting direct CO(2) sensitivity of the hemichannel to CO(2). Heterologous expression of Cx26 in HeLa cells was sufficient to endow them with the capacity to release ATP in a CO(2)-sensitive manner. We have examined other heterologously expressed connexins for their ability to respond to changes in PCO2. The closely related beta connexins Cx30 and Cx32 also displayed sensitivity to changes in PCO2, but with slightly different characteristics from Cx26. The more distant Cx43 exhibited CO(2)-dependent closing (possibly mediated through intracellular acidification), while Cx36 displayed no CO(2) sensitivity. These surprising findings suggest that connexins may play a hitherto unappreciated variety of signalling roles, and that Cx26 and related beta connexins may impart direct sensitivity to CO(2) throughout the brain. PMID- 20736420 TI - Transgene expression and effective gene silencing in vagal afferent neurons in vivo using recombinant adeno-associated virus vectors. AB - Vagal afferent fibres innervating thoracic structures such as the respiratory tract and oesophagus are diverse, comprising several subtypes of functionally distinct C-fibres and A-fibres. Both morphological and functional studies of these nerve subtypes would be advanced by selective, effective and long-term transduction of vagal afferent neurons with viral vectors. Here we addressed the hypothesis that vagal sensory neurons can be transduced with adeno-associated virus (AAV) vectors in vivo, in a manner that would be useful for morphological assessment of nerve terminals, using enhanced green fluorescent protein (eGFP), as well as for the selective knock-down of specific genes of interest in a tissue selective manner. We found that a direct microinjection of AAV vectors into the vagal nodose ganglia in vivo leads to selective, effective and long-lasting transduction of the vast majority of primary sensory vagal neurons without transduction of parasympathetic efferent neurons. The transduction of vagal neurons by pseudoserotype AAV2/8 vectors in vivo is sufficiently efficient such that it can be used to functionally silence TRPV1 gene expression using short hairpin RNA (shRNA). The eGFP encoded by AAV vectors is robustly transported to both the central and peripheral terminals of transduced vagal afferent neurons allowing for bright imaging of the nerve endings in living tissues and suitable for structure-function studies of vagal afferent nerve endings. Finally, the AAV2/8 vectors are efficiently taken up by the vagal nerve terminals in the visceral tissue and retrogradely transported to the cell body, allowing for tissue-specific transduction. PMID- 20736422 TI - Use of psychostimulants in patients with dementia. AB - OBJECTIVE: To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia. DATA SOURCES: Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed. STUDY SELECTION AND DATA EXTRACTION: All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate. DATA SYNTHESIS: Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities. CONCLUSIONS: Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection. PMID- 20736421 TI - Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. AB - Arterial PCO2, a major determinant of breathing, is detected by chemosensors located in the brainstem. These are important for maintaining physiological levels of PCO2 in the blood and brain, yet the mechanisms by which the brain senses CO(2) remain controversial. As ATP release at the ventral surface of the brainstem has been causally linked to the adaptive changes in ventilation in response to hypercapnia, we have studied the mechanisms of CO(2)-dependent ATP release in slices containing the ventral surface of the medulla oblongata. We found that CO(2)-dependent ATP release occurs in the absence of extracellular acidification and correlates directly with the level of PCO2. ATP release is independent of extracellular Ca(2+) and may occur via the opening of a gap junction hemichannel. As agents that act on connexin channels block this release, but compounds selective for pannexin-1 have no effect, we conclude that a connexin hemichannel is involved in CO(2)-dependent ATP release. We have used molecular, genetic and immunocytochemical techniques to demonstrate that in the medulla oblongata connexin 26 (Cx26) is preferentially expressed near the ventral surface. The leptomeninges, subpial astrocytes and astrocytes ensheathing penetrating blood vessels at the ventral surface of the medulla can be loaded with dye in a CO(2)-dependent manner, suggesting that gating of a hemichannel is involved in ATP release. This distribution of CO(2)-dependent dye loading closely mirrors that of Cx26 expression and colocalizes to glial fibrillary acidic protein (GFAP)-positive cells. In vivo, blockers with selectivity for Cx26 reduce hypercapnia-evoked ATP release and the consequent adaptive enhancement of breathing. We therefore propose that Cx26-mediated release of ATP in response to changes in PCO2 is an important mechanism contributing to central respiratory chemosensitivity. PMID- 20736423 TI - Intrapericardial triamcinolone administration for autoreactive pericarditis. AB - OBJECTIVE: To review published literature regarding the safety and effectiveness of intrapericardial triamcinolone for the treatment of autoreactive pericarditis. DATA SOURCES: Searches of MEDLINE (1966-June 2010) and Cochrane Database (1993 June 2010) were conducted. Limits included articles published in English reporting on human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Trials, studies, and case reports were eligible for inclusion if they evaluated the safety and/or efficacy of intrapericardial triamcinolone for the management of autoreactive pericarditis. DATA SYNTHESIS: Systemic corticosteroids offer an effective treatment option for autoreactive pericarditis; however, their use is limited by adverse effects and they are an independent risk factor for pericarditis recurrence. One case series and 3 open-label trials evaluating intrapericardial triamcinolone for the management of autoreactive pericarditis are reviewed. Included studies were limited by small sample sizes (N = 2-84), lack of control groups, short durations of follow-up (24 h to 12 mo), use of adjuvant agents, omission of patient demographic data, subjective report of symptom relief, and lack of consistent dose of intrapericardial triamcinolone. Despite these limitations, the data suggest symptom resolution and reduced pericarditis recurrence with administration of intrapericardial triamcinolone to patients with autoreactive pericarditis. CONCLUSIONS: There is growing evidence that intrapericardial triamcinolone is safe and effective for the management of autoreactive pericarditis. The appropriate regimen (dose and duration of treatment), adverse effect profile, and specific therapeutic role require further investigation. PMID- 20736424 TI - High-dose ciprofloxacin for serious gram-negative infection in an obese, critically ill patient receiving continuous venovenous hemodiafiltration. AB - OBJECTIVE: To describe the pharmacokinetic profile and clinical outcome associated with high-dose ciprofloxacin therapy in a patient with the triad of extreme obesity, multiple organ failure, and deep-seated infection. CASE SUMMARY: A 45-year-old, class 3 obese (185 kg; body mass index 53.7), critically ill trauma patient receiving continuous venovenous hemodiafiltration (CVVHDF) was treated with ciprofloxacin 800 mg intravenously every 12 hours for presumed Enterobacter aerogenes (ciprofloxacin minimum inhibitory concentration [MIC] <=1 MUg/mL) lumbar spine osteomyelitis. Four sequential plasma ciprofloxacin samples were obtained and analyzed to determine the steady-state pharmacokinetic profile. The observed steady-state maximum (C(max)) and calculated minimum (C(min)) ciprofloxacin plasma concentrations measured on treatment day 8 were 13 MUg/mL and 4.8 MUg/mL, respectively, corresponding to an estimated half-life, area under the curve (AUC(0-24)), total systemic clearance, and clearance by CVVHDF of 7.6 hours, 192 MUg.h/mL, 139 mL/min, and 26 mL/min, respectively. These concentrations produced AUC(0-24)/MIC ratios >125 and plasma C(max)/MIC ratios >10 for MICs <=1 MUg/mL. Intravenous colistin and polymyxin B lumbar wound irrigation were initiated on ciprofloxacin days 12 and 15, respectively, for concomitant multidrug-resistant Acinetobacter baumannii infection. Lumbar tissue cultures on day 24 of ciprofloxacin therapy demonstrated no growth, coinciding with overall improvement of the invasive wound. A week later, the patient developed worsening septic shock and died secondary to an occult subdiaphragmatic abscess. DISCUSSION: Pharmacodynamic outcome studies suggest that AUC(0-24)/MIC ratios >125 and plasma C(max)/MIC ratios >10 are good predictors of clinical and microbiologic success of ciprofloxacin against gram-negative pathogens. These pharmacodynamic goals were achieved in the plasma with high-dose ciprofloxacin for MICs <=1 MUg/mL. CONCLUSIONS: Critically ill obese patients with deep-seated infection involving organisms with MICs >0.5 MUg/mL likely require ciprofloxacin dosages greater than traditional daily doses of 400-800 mg during CVVHDF to achieve optimal pharmacodynamic targets. PMID- 20736425 TI - Pregnant women's beliefs about medications--a study among 866 Norwegian women. AB - BACKGROUND: Beliefs about medication may impact a woman's decision to take a needed medication during pregnancy. While many women will be faced with decisions regarding medication use during pregnancy, there is a paucity of research on this topic in the literature. OBJECTIVE: To study pregnant women's beliefs about medication and factors that determine those beliefs. METHODS: A questionnaire was posted at the University of Oslo's Web site for Internet surveys for 5 weeks from mid-September 2008 through October 2008. Seven general statements from the "Beliefs about Medicines" questionnaire and 9 pregnancy-specific statements were used to assess pregnant women's attitudes toward medication use during pregnancy. Other information, such as sociodemographic background and personal medication use during pregnancy, was also collected. RESULTS: A total of 866 pregnant women completed the questionnaire. Most women had a positive attitude toward medication in general, but believed pregnant women should be more restrictive regarding use than nonpregnant women. There was a significant association between women's education, occupation, and attitudes, with less educated women believing that medications in general were harmful and herbal remedies were safe, while women with a higher education were more reluctant to use any medication in pregnancy. Women with health-related occupations were more knowledgeable about the possible risks of untreated illness during pregnancy. There was also an association between pregnant women's attitudes and their use of prescribed penicillins and herbal remedies. CONCLUSIONS: Most pregnant women believe that medicines in general are helpful and safe to use. However, they are much more restrictive and unsure about use during pregnancy. Health-care professionals should be aware of such attitudes when advising a woman to take a needed medication during pregnancy. PMID- 20736426 TI - Treatment of recurrent Stenotrophomonas maltophilia ventilator-associated pneumonia with doxycycline and aerosolized colistin. AB - OBJECTIVE: To report a case of recurrent Stenotrophomonas maltophilia ventilator associated pneumonia (VAP) that was successfully treated with doxycycline and aerosolized colistin. CASE SUMMARY: A 28-year-old male was admitted with a severe head injury and required mechanical ventilation. The patient developed S. maltophilia VAP on hospital day 17, which was cured after 7 days of treatment with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). However, on day 34, the patient developed recurrent S. maltophilia VAP that did not respond clinically or demonstrate eradication on follow-up culture after 10 days of TMP/SMX. At that time, TMP/SMX was discontinued and treatment was initiated with intravenous doxycycline and aerosolized colistin. The VAP episode was cured after 14 days of treatment with doxycycline/aerosolized colistin. DISCUSSION: S. maltophilia is an emerging cause of VAP in some centers. This organism is associated with high mortality rates and has few treatment options because it is intrinsically resistant to most drug classes. Recent data suggest that doxycycline and aerosolized colistin each are effective in treatment of other multidrug-resistant organisms, such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, this is the first report describing the use of this antibiotic regimen for S. maltophilia. High-dose TMP/SMX is considered to be the drug of choice primarily based on excellent in vitro activity. Few data exist on how to treat patients who fail therapy with TMP/SMX or cannot receive that drug because of resistance, allergy, or adverse events. Thus, it is important to report alternative methods for treating this infection. CONCLUSIONS: The positive clinical response to doxycycline and aerosolized colistin seen in the patient described here suggests that this combination may be an alternative treatment in patients who fail initial treatment or cannot receive standard therapies. PMID- 20736427 TI - Medication history reconciliation by clinical pharmacists in elderly inpatients admitted from home or a nursing home. AB - BACKGROUND: Accurate medication histories at hospital admission are an important element of medication safety. Discrepancies may have clinically significant consequences, especially in the elderly population. OBJECTIVE: To assess the clinical pharmacist's performance in obtaining patients' medication histories and in reconciling these data with the medical records and medication orders and whether the patients' residential situation prior to hospitalization influences the number of drug discrepancies. METHODS: A prospective observational study was conducted at a 29-bed acute geriatric ward of a Belgian university hospital. Medication histories acquired by clinical pharmacists were compared with those documented in the medical records by the attending physicians. All discrepancies were identified and categorized by an independent pharmacist and were scored for their clinical relevance in consensus by a senior internist and a senior geriatrician. RESULTS: Of the 215 screened geriatric (aged >=65 years) patients admitted between October 27, 2007, and September 23, 2008, 197 were enrolled in the study. For patients living in the community, as well as those residing in a nursing home prior to hospitalization, clinical pharmacists identified significantly more preadmission drugs compared with physicians, with a median number of 8 correctly identified medications versus 6, respectively (p < 0.001). Extra identified drugs consisted of over-the-counter as well as prescription medications. Furthermore, 117 other medication discrepancies were noted, mainly related to erroneous drug identification and incorrect drug dose. In all, the clinical pharmacists identified 379 (24.2%) medication discrepancies, of which 188 (49.6%) were judged clinically relevant. CONCLUSIONS: Pharmacist-acquired medication histories enhance the medication reconciliation process, both in patients residing at home and in a nursing home prior to hospitalization. A focus should be placed on seamless care procedures that facilitate the transfer of medication histories between primary and secondary care in both of these populations. PMID- 20736428 TI - Oral contrast for abdominal computed tomography in children: the effects on gastric fluid volume. AB - BACKGROUND: Oral enteric contrast medium (ECM) is frequently administered to achieve visualization of the gastrointestinal tract during abdominal evaluation with computed tomography (CT). Administering oral ECM less than 2 hours before sedation/anesthesia violates the nothing-by-mouth guidelines and in theory may increase the risk of aspiration pneumonia. In this study we measured the residual gastric fluid when using a protocol in which ECM is administered up to 1 hour before anesthesia/sedation. We hypothesized that patients receiving ECM 1 hour before anesthesia/sedation would have residual gastric fluid volume (GFV) >0.4 mL/kg. METHODS: Anesthesia and radiology reports, CT images, and department incident reports were reviewed between January 2005 and June 2009 for all patients who required sedation/anesthesia for abdominal CT. For each patient, the volume of contrast or stomach fluid was calculated using a region of interest outlining the stomach portion containing high-attenuation fluid and low attenuation of other gastric contents. Information obtained from anesthesia/sedation reports included demographic characteristics, presenting pathology, drugs used for anesthesia/sedation induction and maintenance, airway interventions, method for securing endotracheal tube, and complications related to ECM administration, including oxygen desaturation, vomiting, coughing, bronchospasm, laryngospasm, and aspiration. RESULTS: We identified 365 patients (mean age = 32 months; range = 0.66 to 211.10 months) who received oral/IV contrast material before anesthesia/sedation for abdominal CT and 47 patients (mean age = 52 months; range = 0.63 to 215.84 months) who received only IV contrast material and followed the traditional fast. For those who received oral contrast, the mean contrast volume administered was 18.10 mL/kg (range = 1.5 to 82.76 mL/kg). The median GVF 1 hour after completing the oral contrast was significantly higher than that in patients who received only IV contrast (0.38 mL/kg vs. 0.15 mL/kg, P = 0.0049). GFV exceeded 0.4 mL/kg in 189 patients (178 of 365 [49%] in the oral contrast group vs. 11 of 47 [23%] in the IV contrast group) (chi(2) = 10.7874, P = 0.0010). Among those who received oral contrast, 207 patients had general anesthesia and 158 patients had deep sedation. Two cases of vomiting were reported in the general anesthesia group with no evidence of pulmonary aspiration identified. CONCLUSION: For children receiving an abdominal CT, the residual GFV exceeded 0.4 mL/kg in 49% (178/365) of those who received oral ECM up to 1 hour before anesthesia/sedation in comparison with 23% (11/47) of those who received IV-only contrast. PMID- 20736429 TI - High-fidelity simulation demonstrates the influence of anesthesiologists' age and years from residency on emergency cricothyroidotomy skills. AB - BACKGROUND: Age-related deterioration in both cognitive function and the capacity to control fine motor movements has been demonstrated in numerous studies. However, this decline has not been described with respect to complex clinical anesthesia skills. Cricothyroidotomy is an example of a complex, lifesaving procedure that requires competency in the domains of both cognitive processing and fine motor control. Proficiency in this skill is vital to minimize time to reestablish oxygenation during a "cannot intubate, cannot ventilate" scenario. In this prospective, controlled, single-blinded study, we tested the hypothesis that age affects the learning and performance of emergency percutaneous cricothyroidotomy in a high-fidelity simulated cannot intubate/cannot ventilate scenario. METHODS: Thirty-six staff anesthesiologists (19 aged younger than 45 years and 17 older than 45 years) managed a high-fidelity cannot intubate/cannot ventilate scenario in a high-fidelity simulator before and after a 1-hour standardized training session. The group division cutoff age of 45 years was based on the median age of our sample subject population before enrollment. The scenarios required the insertion of an emergency percutaneous cricothyroidotomy. We compared cricothyroidotomy skills in the older group with those in the younger group using procedural time, 5-point task-specific checklist score, and global rating scale score. Correlation based on age, years from residency, weekly clinical hours worked, previous continuing medical education in airway management, and previous simulation experience was also performed. RESULTS: In both prestandardization and poststandardization, age and years from residency correlated with procedural time, checklist scores, and global rating scores. Baseline, prestandardization variables were all better for the younger group, with a mean age of 37 years, compared with the older group, with a mean age of 58 years. Procedural time was 100 (72-128) seconds versus 152 (120-261) seconds. Checklist scores were 7.0 (6.1-8.0) versus 6.0 (4.8-8.0). Global rating scale scores were 22.0 (17.8-29.8) versus 17.5 (10.4-20.6). After the 1-hour standardized training session, the younger group continued to perform better than the older group with procedural time of 75 (66-91) seconds versus 87 (78-123) seconds, checklist scores of 10.0 (9.1-10.0) versus 9.0 (8.0-10.0), and global rating scale scores of 35.0 (32.1-35.0) versus 32.0 (29.0-33.8). Regression analysis was performed on the poststandardization data. Both age and years from residency independently affected procedural time, checklist scores, and global rating scale scores (all P < 0.05). CONCLUSIONS: Baseline proficiency with simulated emergency cricothyroidotomy is associated with age and years from residency. Despite standardized training, operator age and years from residency were associated with decreased proficiency. Further research should explore the potential of using age and years from residency as factors for implementing periodic continuing medical education. PMID- 20736430 TI - Transesophageal imaging of an internal mammary artery graft during repeat cardiac surgery. PMID- 20736431 TI - A critical review of the ability of continuous cardiac output monitors to measure trends in cardiac output. AB - Numerous cardiac output (CO) monitors have been produced that provide continuous rather than intermittent readings. Bland and Altman has become the standard method for validating their performance against older standards. However, the Bland and Altman method only assesses precision and does not assess how well a device detects serial changes in CO (trending ability). Currently, there is no consensus on how trending ability, or trend analysis, should be performed. Therefore, we performed a literature review to identify articles published between 1997 and 2009 that compared methods of continuous CO measurement. Identified articles were grouped according to measurement technique and statistical methodology. Articles that analyzed trending ability were reviewed with the aim of finding an acceptable statistical method. Two hundred two articles were identified. The most popular methods were pulse contour (69 articles), Doppler (54), bioimpedance (38), and transpulmonary or continuous thermodilution (27). Forty-one articles addressed trending, and of these only 23 provided an in-depth analysis. Several common statistical themes were identified: time plots, regression analysis, Bland and Altman using change in CO (DeltaCO), and the 4-quadrant plot, which used direction of change of DeltaCO to determine the concordance. This plot was further refined by exclusion of data when values were small. Receiver operating characteristic curves were used to define the exclusion zone. In animal studies, a reliable reference standard such as an aortic flowprobe was frequently used, and regression or time plots could be used to show trending. Clinical studies were more problematic because data collection points were fewer (8-10 per subject). The consensus was to use the 4-quadrant plot with exclusion zones and apply concordance analysis. A concordance rate of >92% when using a 15% zone indicated good trending. A new method of presenting trend data (DeltaCO) on a polar plot is proposed. Agreement was shown by the angle with the horizontal axis and DeltaCO by the distance from the center. Trending can be assessed by the vertical limits of the data, similar to the Bland and Altman method. PMID- 20736432 TI - Correlations between controlled endotracheal tube cuff pressure and postprocedural complications: a multicenter study. AB - BACKGROUND: Postoperative respiratory complications related to endotracheal intubation usually present as cough, sore throat, hoarseness, and blood-streaked expectorant. In this study, we investigated the short-term (hours) impact of measuring and controlling endotracheal tube cuff (ETTc) pressure on postprocedural complications. METHODS: Five hundred nine patients from 4 tertiary care university hospitals in Shanghai, China scheduled for elective surgery under general anesthesia were assigned to a control group without measuring ETTc pressure, and a study group with ETTc pressure measured and adjusted. The duration of the procedure and duration of endotracheal intubation were recorded. Twenty patients whose duration of endotracheal intubation was between 120 and 180 minutes were selected from each group and examined by fiberoptic bronchoscopy immediately after removing the endotracheal tube. Endotracheal intubation-related complications including cough, sore throat, hoarseness, and blood-streaked expectorant were recorded at 24 hours postextubation. RESULTS: There was no significant difference in sex, age, height, weight, procedure duration, and duration of endotracheal intubation between the 2 groups. The mean ETTc pressure measured after estimation by palpation of the pilot balloon of the study group was 43 +/- 23.3 mm Hg before adjustment (the highest was 210 mm Hg), and 20 +/- 3.1 mm Hg after adjustment (P < 0.001). The incidence of postprocedural sore throat, hoarseness, and blood-streaked expectoration in the control group was significantly higher than in the study group. As the duration of endotracheal intubation increased, the incidence of sore throat and blood-streaked expectoration in the control group increased. The incidence of sore throat in the study group also increased with increasing duration of endotracheal intubation. Fiberoptic bronchoscopy in the 20 patients showed that the tracheal mucosa was injured in varying degrees in both groups, but the injury was more severe in the control group than in the study group. CONCLUSIONS: ETTc pressure estimated by palpation with personal experience is often much higher than measured or what may be optimal. Proper control of ETTc pressure by a manometer helped reduce ETT related postprocedural respiratory complications such as cough, sore throat, hoarseness, and blood-streaked expectoration even in procedures of short duration (1-3 hours). PMID- 20736433 TI - Bradycardia during induction of anesthesia with sevoflurane in children with Down syndrome. AB - BACKGROUND: Bradycardia is a complication associated with inhaled induction of anesthesia with halothane in children with Down syndrome. Although bradycardia has been reported after anesthetic induction with sevoflurane in these children, the incidence is unknown. OBJECTIVES: In this study we compared the incidence and characteristics of bradycardia after induction of anesthesia with sevoflurane in children with Down syndrome to healthy controls. METHODS: We reviewed electronic anesthetic records of 209 children with Down syndrome and 268 healthy control patients who had inhaled induction of anesthesia with sevoflurane over an 8-year period. Data extracted from the medical record included demographics, history of congenital heart disease, heart rate, oxyhemoglobin saturation, expired sevoflurane concentrations, arterial blood pressure, and any treatment of bradycardia during the first 360 seconds after the start of induction of anesthesia. Bradycardia and hypotension were defined as heart rate and arterial blood pressure below the critical limits recommended for activating a pediatric rapid response team to the bedside of a hospitalized child for quick intervention. Factors associated with bradycardia were identified in a univariate analysis. A step-wise backward multiple logistic regression model was used to identify independent factors. Differences between the 2 groups were computed using Fisher's exact test or chi(2) tests for categorical data and t tests for continuous data. RESULTS: Univariate analysis demonstrated that Down syndrome, low ASA physical status, congenital heart disease, and mean sevoflurane concentrations were factors associated with bradycardia. However, multivariate analysis showed that only Down syndrome and low ASA physical status remained as independent factors associated with bradycardia. CONCLUSION: Bradycardia during anesthetic induction with sevoflurane was common in children with Down syndrome, with and without a history of congenital heart disease. PMID- 20736434 TI - 8-OH-DPAT prevents morphine-induced apoptosis in rat dorsal raphe nucleus: a possible mechanism for attenuating morphine tolerance. AB - BACKGROUND: Previously, we found that activation of serotonin 1A (5-HT1A) receptors in the dorsal raphe nucleus (DRN) decreased the development of tolerance to the analgesic effect of morphine. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. In this investigation we attempted to evaluate the effect of 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin), a specific 5-HT1A receptor agonist, on morphine-induced tolerance and apoptosis in rat DRN. METHODS: Nociception was assessed using a hotplate apparatus. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. RESULTS: Tolerance to the analgesic effect of morphine was complete by 10 days after morphine administration (5 mg/kg/d, i.p.), whereas a significant analgesic effect was observed through the 10th day in 8-OH-DPAT treated animals. Furthermore, the results showed that the number of TUNEL positive cells had been increased in morphine-tolerant rats (control group: morphine, i.p. + saline, intra-DRN) in comparison with the saline-treated animals. The results also indicated that 8-OH-DPAT (2, 4, and 8 MUg/rat/d) attenuated the number of apoptotic cells in the DRN in comparison with the control group. However, 8-OH-DPAT (8 MUg/rat/d, intra-DRN) failed to reduce morphine-induced apoptosis in the presence of the 5-HT1A receptor antagonist, NAN 190 (6 MUg/rat/d, intra-DRN). CONCLUSION: We found that intra-DRN injection of a specific 5-HT1A receptor agonist attenuated morphine-induced apoptosis in rat DRN, which may have a key role in morphine tolerance. PMID- 20736435 TI - A pilot study of respiratory inductance plethysmography as a safe, noninvasive detector of jet ventilation under general anesthesia. AB - BACKGROUND: High-frequency jet ventilation is an optimal mode of ventilation for many surgical procedures of the trachea and larynx but has limited monitoring modalities to assess adequacy of oxygenation and/or ventilation. Respiratory inductance plethysmography is a noninvasive monitor of chest and abdominal wall movement with well-established applications in the sleep laboratory. We performed an observational pilot study of respiratory inductance plethysmography as a detector of jet ventilation. METHODS: Twenty-five patients underwent microdirect suspension laryngoscopy with high-frequency jet ventilation under general anesthesia with total IV anesthesia. Inductotrace(r) bands (Ambulatory Monitoring Inc., Ardsley, NY) were applied to the chest and abdomen in all patients and data collected from oxygen administration through emergence at 50-Hz sampling frequency in the DC mode using a 12-bit A-D converter and custom programmed LabVIEW interface. The raw data were filtered and a detector was developed based on a type I, IIR peak comb filter to differentiate apnea, cardiogenic oscillations, and jet ventilation- associated respiratory excursion. The primary end point was the ability of the detector to identify the presence of jet ventilation. Receiver operating characteristic curves were generated for the aggregate data of all patients. RESULTS: Respiratory inductance plethysmography reliably detected jet ventilation. The data analysis program effectively extracted a relatively small amplitude jet ventilation signal from a baseline signal contaminated by cardiogenic noise. Sensitivity was in the range of 85%, with a filter bandwidth of 0.055 Hz. Increased sensitivity with increasing filter bandwidth was offset by a detection delay of 12.5 seconds. CONCLUSIONS: Respiratory inductance plethysmography was successfully used to detect high frequency jet ventilation in patients undergoing laryngotracheal surgery. This pilot study demonstrates the feasibility of respiratory inductance plethysmography as a monitor for use during jet ventilation. PMID- 20736438 TI - Review article: improving outcome after major surgery: pathophysiological considerations. AB - Surgical and anesthesia-related techniques may reduce physical stress for patients undergoing high-risk surgery, but major surgery is increasingly performed in patients with substantial comorbidities. Strategies for improving the outcome for such patients include approaches that both increase tissue oxygen delivery and reduce metabolic demand. However, these strategies have produced conflicting results. To understand the success and failure of attempts to improve postoperative outcome, the pathophysiology of perioperative hemodynamic, metabolic, and immunological alterations should be analyzed. Our aim in this review is to provide a survey of fields of opportunities for improving outcome after major surgery. The issues are approached from 3 different angles: the view of the patient, the view of the surgical intervention, and the view of the anesthesia. Special attention is also given to what could be considered the result of the interaction among the 3: perioperative inflammation and immune response. PMID- 20736436 TI - Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities. AB - BACKGROUND: In prior work, children born to mothers who received neuraxial anesthesia for cesarean delivery had a lower incidence of subsequent learning disabilities compared with vaginal delivery. The authors speculated that neuraxial anesthesia may reduce stress responses to delivery, which could affect subsequent neurodevelopmental outcomes. To further explore this possibility, we examined the association between the use of neuraxial labor analgesia and development of childhood learning disabilities in a population-based birth cohort of children delivered vaginally. METHODS: The educational and medical records of all children born to mothers residing in the area of 5 townships of Olmsted County, Minnesota from 1976 to 1982 and remaining in the community at age 5 years were reviewed to identify those with learning disabilities. Cox proportional hazards regression was used to compare the incidence of learning disabilities between children delivered vaginally with and without neuraxial labor analgesia, including analyses adjusted for factors of either potential clinical relevance or that differed between the 2 groups in univariate analysis. RESULTS: Of the study cohort, 4684 mothers delivered children vaginally, with 1495 receiving neuraxial labor analgesia. The presence of childhood learning disabilities in the cohort was not associated with use of labor neuraxial analgesia (adjusted hazard ratio, 1.05; 95%confidence interval, 0.85-1.31; P = 0.63). CONCLUSION: The use of neuraxial analgesia during labor and vaginal delivery was not independently associated with learning disabilities diagnosed before age 19 years. Future studies are needed to evaluate potential mechanisms of the previous finding indicating that the incidence of learning disabilities is lower in children born to mothers via cesarean delivery under neuraxial anesthesia compared with vaginal delivery. PMID- 20736439 TI - An adult patient with congenitally corrected transposition of the great arteries. PMID- 20736437 TI - Opioid-induced preconditioning is dependent on caveolin-3 expression. AB - We tested the hypothesis that caveolin-3 (Cav-3) is essential for opioid-induced preconditioning in vivo. Cav-3 overexpressing mice, Cav-3 knockout mice, and controls were exposed to myocardial ischemia/reperfusion (I/R) in the presence of SNC-121 (SNC), a delta-selective opioid agonist, or naloxone, a nonselective opioid antagonist. Controls were protected from I/R injury by SNC. No protection was produced by SNC in Cav-3 knockout mice. Cav-3 overexpressing mice showed innate protection from I/R compared with controls that was abolished by naloxone. Our results show that opioid-induced preconditioning is dependent on Cav-3 expression and that endogenous protection in Cav-3 overexpressing mice is opioid dependent. PMID- 20736440 TI - Survival after cardiac transplantation in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Heart transplant is a treatment option for selected patients with hypertrophic cardiomyopathy (HCM). However, the prevalence, clinical profile, and outcome of this subgroup of HCM patients are uncertain. Therefore, we sought to determine the occurrence, clinical characteristics, and prognosis of HCM patients who underwent cardiac transplantation in the United States during a 15-year period. METHODS AND RESULTS: Demographic, clinical, and survival outcomes of 26 706 adult (age >=18 years), heart-only transplant recipients between January 1990 and December 2004 were acquired from the United Network of Organ Sharing Registry. Pretransplant diagnoses were classified as follows: HCM (n=303, 1%) and non-HCM (26 403, 99%), comprising 3 patient subgroups: (1) ischemic cardiomyopathy (n=14 308, 54%), (2) dilated cardiomyopathy (n=11 760, 44%), and (3) restrictive cardiomyopathy (n=335, 1%). Study follow-up began at the time of heart transplant and was 76+/-44 months (mean+/-SD) among survivors. The 1-, 5-, and 10-year overall transplant survival for HCM patients was 85%, 75%, and 61%, respectively, with a trend toward greater survival compared with that of non-HCM transplant patients (82%, 70%, and 49%, respectively; log-rank test, P=0.05). However, propensity-matched, covariate-adjusted, Cox regression model analysis showed better survival over time (P<0.01) among the HCM patients. When HCM posttransplant survival was compared with that in each of the non-HCM patient subgroups, HCM patients had more favorable survival than did those transplanted for ischemic cardiomyopathy (P=0.02). In contrast, HCM posttransplant survival did not differ from that of patients transplanted for restrictive (P=0.08) or dilated (P=0.25) cardiomyopathy. CONCLUSIONS: HCM patients compose a small subset (1%) of the overall population of patients who undergo heart transplantation in the United States. Nonetheless, survival after transplant among HCM patients is comparable to that of patients transplanted for non-HCM cardiovascular diseases, with possible enhanced survival over time. PMID- 20736441 TI - Risk of cardiovascular events and all-cause mortality in patients treated with thiazolidinediones in a managed-care population. AB - BACKGROUND: This study directly compares risk of acute myocardial infarction (AMI), acute heart failure (AHF), or all-cause death among pioglitazone- and rosiglitazone-treated patients in a managed-care population. METHODS AND RESULTS: Patients >=18 years of age, newly initiated on rosiglitazone or pioglitazone between January 1, 2001, and December 12, 2005, were included. The date of the first pharmacy claim for rosiglitazone or pioglitazone was defined as index date. Patients were excluded if they had <1 year continuous eligibility preindex or a preindex insulin claim. Primary outcome measure was time to composite event of AMI, AHF or death among pioglitazone- and rosiglitazone-treated patients. The National Death Index database was accessed to obtain date of death for patients who died during the study period. Propensity score matching was used to control for potential confounders. The Cox proportional hazards model was used to evaluate effects of exposure to rosiglitazone and pioglitazone on time to event. A total of 36 628 patients (58% male; mean age, 54 years) were identified. Of the rosiglitazone-treated patients, 602 (4.16%) had an AMI, AHF, or death compared with 599 (4.14%) propensity score-matched pioglitazone-treated patients. No significant difference was observed between matched groups for risk of composite event (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15; P=0.666) when patients were followed from index date until end of study period, termination of enrollment status, or diagnosis of AMI/AHF/death. CONCLUSIONS: In this retrospective cohort study directly comparing rosiglitazone and pioglitazone with a propensity score-matched population that includes mortality data, no significant differences were found in the risk of AMI, AHF or death. PMID- 20736442 TI - National patterns of risk-standardized mortality and readmission for acute myocardial infarction and heart failure. Update on publicly reported outcomes measures based on the 2010 release. AB - BACKGROUND: Patient outcomes provide a critical perspective on quality of care. The Centers for Medicare and Medicaid Services (CMS) is publicly reporting hospital 30-day risk-standardized mortality rates (RSMRs) and risk-standardized readmission rates (RSRRs) for patients hospitalized with acute myocardial infarction (AMI) and heart failure (HF). We provide a national perspective on hospital performance for the 2010 release of these measures. METHODS AND RESULTS: The hospital RSMRs and RSRRs are calculated from Medicare claims data for fee-for service Medicare beneficiaries, 65 years or older, hospitalized with AMI or HF between July 1, 2006, and June 30, 2009. The rates are calculated using hierarchical logistic modeling to account for patient clustering, and are risk adjusted for age, sex, and patient comorbidities. The median RSMR for AMI was 16.0% and for HF was 10.8%. Both measures had a wide range of hospital performance with an absolute 5.2% difference between hospitals in the 5th versus 95th percentile for AMI and 5.0% for HF. The median RSRR for AMI was 19.9% and for HF was 24.5% (3.9% range for 5th to 95th percentile for AMI, 6.7% for HF). Distinct regional patterns were evident for both measures and both conditions. CONCLUSIONS: High RSRRs persist for AMI and HF and clinically meaningful variation exists for RSMRs and RSRRs for both conditions. Our results suggest continued opportunities for improvement in patient outcomes for HF and AMI. PMID- 20736443 TI - Rosuvastatin for primary prevention among individuals with elevated high sensitivity c-reactive protein and 5% to 10% and 10% to 20% 10-year risk. Implications of the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial for "intermediate risk". AB - BACKGROUND: Recent primary prevention guidelines issued in Canada endorse the use of statin therapy among individuals at "intermediate risk" who have elevated levels of high-sensitivity C-reactive protein (hsCRP). However, trial data directly addressing whether this recommendation defines a patient population in which statin therapy is effective have not previously been published. METHODS AND RESULTS: In the Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, which demonstrated a 44% reduction in first vascular events when rosuvastatin 20 mg was compared with placebo among 17 802 primary prevention patients with LDL cholesterol <130 mg/dL and hsCRP >=2 mg/L, 6091 participants (2525 women, 3566 men) had baseline estimated 10-year Framingham risks of 5% to 10% and 7340 participants (1404 women, 5936 men) had baseline estimated Framingham risk of 11% to 20%. In these 2 "intermediate risk" subgroups, relative risk reductions consistent with the overall trial treatment effect were observed (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; 5-year number needed to treat=40, P=0.005 for those with 5% to 10% risk; hazard ratio, 0.51; 95% confidence interval, 0.39 to 0.68, 5-year number needed to treat=18, P<0.0001 for those with 11% to 20% risk). Use of the Reynolds Risk Score to stratify the study population gave similar results but reclassified large numbers of individuals into lower- or higher-risk groups. The majority of women with elevated hsCRP who benefited from rosuvastatin were at 5% to 10% 10 year risk at study entry using either global risk scoring system. CONCLUSIONS: Consistent with recent evidence-based Canadian Cardiovascular Society guidelines for primary prevention, the JUPITER trial demonstrates that rosuvastatin 20 mg significantly reduces major cardiovascular events among men and women with elevated hsCRP and "intermediate risk" defined either as 5% to 10% or 10% to 20% 10-year risk. PMID- 20736444 TI - Polymer injection therapy to reverse remodel the papillary muscles: efficacy in reducing mitral regurgitation in a chronic ischemic model. AB - BACKGROUND: Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. METHODS AND RESULTS: Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8+/-1.2 to1.8+/-1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3+/-5.7 to 25.9+/-4.6 mm, P=0.02), tenting volume (1.8+/-0.7 to 1.4+/-0.5 mL, P=0.01), and leaflet closure area (8.8+/-1.3 cm(2)to 7.6+/-1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41+/-3% versus 40+/-3%, P=NS), end-systolic elastance, tau (82+/-36 ms to 72+/-26, P=NS), or LV stiffness coefficient (0.05+/ 0.04 to 0.03+/-0.01). CONCLUSIONS: PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position. PMID- 20736445 TI - Relationship between arterial and fibrous cap remodeling: a serial three-vessel intravascular ultrasound and optical coherence tomography study. AB - BACKGROUND: Positive arterial remodeling and thin fibrous cap are characteristics of rupture-prone or vulnerable plaque. The natural course of the fibrous cap thickness and the relationship between serial arterial remodeling and changes in fibrous cap thickness are unknown. Therefore, the purpose of this study was to evaluate the relationship between changes in fibrous cap thickness and arterial remodeling by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS) during 6-month follow-up. METHODS AND RESULTS: Both IVUS and OCT examinations were performed on 108 vessels from 36 patients with ischemic heart disease who underwent percutaneous coronary intervention. Fifty-eight fibroatheromas were selected from 82 nonsignificant, nonculprit lesions (angiographic diameter stenosis, 25% to 75%; plaque burden, >40% by IVUS). Fibroatheroma was defined by OCT as lipid-rich plaque in >1 quadrant that has lipid. Thickness of the fibrous cap was measured by OCT. IVUS and OCT examinations were repeated at 6-month follow-up. Serial changes and relationships between IVUS indices and fibrous cap thickness were investigated. Overall, fibrous cap thickness (98.1+/-38.9 to 96.9+/-44.5 MUm) as well as IVUS indices did not change significantly within 6 months. The percent changes in fibrous cap thickness correlated negatively and significantly (r=-0.54; P<0.0001; generalized estimating equation adjusted, r=-0.42; P=0.001) with the percent changes in external elastic membrane cross-sectional area. CONCLUSIONS: Arterial remodeling is related to changes in fibrous cap thickness. Positive arterial remodeling is not only an adaptive process, but also related to thinning of the fibrous cap. PMID- 20736446 TI - A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction. AB - BACKGROUND: Experimental studies have shown that induction of hypothermia before reperfusion of acute coronary occlusion reduces infarct size. Previous clinical studies, however, have not been able to show this effect, which is believed to be mainly because therapeutic temperature was not reached before reperfusion in the majority of the patients. We aimed to evaluate the safety and feasibility of rapidly induced hypothermia by infusion of cold saline and endovascular cooling catheter before reperfusion in patients with acute myocardial infarction. METHODS AND RESULTS: Twenty patients with acute myocardial infarction scheduled to undergo primary percutaneous coronary intervention were enrolled in this prospective, randomized study. After 4 +/- 2 days, myocardium at risk and infarct size were assessed by cardiac magnetic resonance using T2-weighted imaging and late gadolinium enhancement imaging, respectively. A core body temperature of <35 degrees C (34.7 +/- 0.3 degrees C) was achieved before reperfusion without significant delay in door-to-balloon time (43 +/- 7 minutes versus 40 +/- 6 minutes, hypothermia versus control, P=0.12). Despite similar duration of ischemia (174 +/- 51 minutes versus 174 +/- 62 minutes, hypothermia versus control, P=1.00), infarct size normalized to myocardium at risk was reduced by 38% in the hypothermia group compared with the control group (29.8 +/- 12.6% versus 48.0 +/- 21.6%, P=0.041). This was supported by a significant decrease in both peak and cumulative release of Troponin T in the hypothermia group (P=0.01 and P=0.03, respectively). CONCLUSIONS: The protocol demonstrates the ability to reach a core body temperature of <35 degrees C before reperfusion in all patients without delaying primary percutaneous coronary intervention and that combination hypothermia as an adjunct therapy in acute myocardial infarction may reduce infarct size at 3 days as measured by MRI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00417638. PMID- 20736447 TI - Coronary artery bypass grafting after recent or remote percutaneous coronary intervention in the Commonwealth of Massachusetts. AB - BACKGROUND: In this study, we sought to characterize the outcomes after isolated coronary artery bypass grafting (CABG) in patients with a history of remote (>=14 days), and recent (<14 days), percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients with PCI within 5 years of CABG were identified among 12 591 primary isolated CABG reported in the mandatory Massachusetts Adult Cardiac Surgery Database. Patients were excluded if they were out-of-state (n=1043, 8%), had undergone primary PCI for acute myocardial infarction (n=401, 3%), had a PCI CABG interval >5 years or unknown (n=136 and n=673, 1% and 5%). Patients with a history of remote and recent PCI were analyzed separately. Each CABG patient with PCI was matched to 3 patients without PCI using a propensity score. Outcomes were analyzed using generalized estimating equations and stratified proportional hazards models, with a mean follow-up of 4.1+/-1.2 years. There were 1117 CABG patients (9%) with prior PCI (n(remote)=823; n(recent)=294). In matched CABG patients with remote prior PCI, no differences were found in 30-day mortality (1.1% versus 1.5%; P=0.432), hospital morbidity (41% versus 40%; P=0.385) and overall survival (hazard ratio, [95% confidence interval] for death for prior PCI, 0.93 [0.74 to 1.18]; P=0.555). In matched CABG patients with recent prior PCI, hospital morbidity was higher (59% versus 45%; P<0.001), but no differences were found in 30-day mortality (3.5% versus 3.1%; P=0.754) and overall survival (HR, 1.18 [0.83 to 1.69]; P=0.353). CONCLUSIONS: In patients undergoing CABG, remote prior PCI (>=14 days) was not associated with adverse outcomes at 30 days or during long-term follow-up. PMID- 20736449 TI - The Platelet Activity After Clopidogrel Termination (PACT) study. AB - BACKGROUND: "Rebound" platelet hyperreactivity after discontinuation of clopidogrel has been proposed to lead to increased thrombotic risk, including late stent thrombosis. However the hypothesis that discontinuation of clopidogrel results in platelet hyperreactivity has never been rigorously tested. We therefore performed a randomized, double-blind, placebo-controlled, crossover study: the Platelet Activity after Clopidogrel Termination (PACT) study. METHODS AND RESULTS: Platelet reactivity in 15 healthy subjects was measured at baseline, during clopidogrel 75 mg or placebo daily for 14 days, and on days 1, 4, 8, 11, 15, and 45 after discontinuation of clopidogrel or placebo. Platelet reactivity was assessed by (1) platelet surface activated GPIIb-IIIa and surface P-selectin (by whole blood flow cytometry) in response to ADP 0.5, 1, and 20 MUmol/L; thrombin receptor activating peptide (TRAP) 1 and 20 MUmol/L; and collagen/epinephrine 5 MUg/mL/5 MUmol/L, (2) light transmission aggregation with ADP 2.5, 5, and 20 MUmol/L; TRAP 2 and 20 MUmol/L; and collagen 6 MUg/mL, (3) whole blood impedance aggregation with ADP 1.6 and 6.5 MUmol/L; TRAP 4 and 32 MUmol/L; and collagen 3.2 MUg/mL, and (4) plasma soluble CD40 ligand (by ELISA). Immature platelet fraction was measured in the Sysmex XE-2100. At no time point after discontinuation of clopidogrel was platelet reactivity, as determined by any assay end point, or the immature platelet fraction significantly greater than after discontinuation of placebo. CONCLUSIONS: This randomized, double-blind, placebo-controlled, crossover study demonstrates that discontinuation of clopidogrel does not result in "rebound" platelet hyperreactivity, as determined by multiple time points, assays, agonists, and agonist concentrations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00619073. PMID- 20736448 TI - Erythropoietin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized, double-blind trial. AB - BACKGROUND: Erythropoietin improves myocardial function in experimental models of myocardial infarction. The aim of the present study was to determine the value of erythropoietin in patients with acute ST-elevation myocardial infarction. METHODS AND RESULTS: This randomized, double-blind study included 138 patients admitted with acute ST-elevation myocardial infarction and treated with primary percutaneous coronary intervention. Patients were randomly assigned to receive epoetin-beta (3.33*104 U, n=68) or placebo (n=70) immediately and at 24 and 48 hours after percutaneous coronary intervention. The primary end point was left ventricular ejection fraction after 6 months measured by MRI. Other end points included infarct size at 5 days and 6 months. Clinical adverse events (death, recurrent myocardial infarction, stroke, and infarct-related artery revascularization) were investigated at 30 days and 6 months. Left ventricular ejection fraction at 6-month follow-up was 52.0+/-9.1% in the erythropoietin group compared with 51.8+/-9.3% in the placebo group (P=0.92). Five days after percutaneous coronary intervention, left ventricular ejection fraction was 49.4+/ 8.0% in the erythropoietin group and 50.8+/-7.3% in the placebo group (P=0.32); infarct size was 26.8+/-20.9% and 28.3+/-24.4% (P=0.76) and decreased to 17.3+/ 14.3% and 20.9+/-16.4% at 6-month follow-up (P=0.27). The cumulative 6-month incidence of death, recurrent myocardial infarction, stroke or target vessel revascularization was 13.2% in the erythropoietin group and 5.7% in the placebo group (hazard ratio, 2.36; 95% confidence interval, 0.73 to 7.66; P=0.15). CONCLUSIONS: In patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention, erythropoietin treatment did not improve left ventricular ejection fraction or reduce infarct size but may increase clinical adverse events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00390832. PMID- 20736450 TI - Functional compensation of primary and secondary metabolites by duplicate genes in Arabidopsis thaliana. AB - It is well known that knocking out a gene in an organism often causes no phenotypic effect. One possible explanation is the existence of duplicate genes; that is, the effect of knocking out a gene is compensated by a duplicate copy. Another explanation is the existence of alternative pathways. In terms of metabolic products, the relative roles of the two mechanisms have been extensively studied in yeast but not in any multi-cellular organisms. Here, to address the functional compensation of metabolic products by duplicate genes, we quantified 35 metabolic products from 1,976 genes in knockout mutants of Arabidopsis thaliana by a high-throughput Liquid chromatography-Mass spectrometer (LC-MS) analysis. We found that knocking out either a singleton gene or a duplicate gene with distant paralogs in the genome tends to induce stronger metabolic effects than knocking out a duplicate gene with a close paralog in the genome, indicating that only duplicate genes with close paralogs play a significant role in functional compensation for metabolic products in A. thaliana. To extend the analysis, we examined metabolic products with either high or low connectivity in a metabolic network. We found that the compensatory role of duplicate genes is less important when the metabolite has a high connectivity, indicating that functional compensation by alternative pathways is common in the case of high connectivity. In conclusion, recently duplicated genes play an important role in the compensation of metabolic products only when the number of alternative pathways is small. PMID- 20736451 TI - EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. AB - EZH2 is the catalytic subunit of the PRC2 Polycomb complex and mediates transcriptional repression through its histone methyltransferase activity. EZH2 is up-regulated in normal germinal center (GC) B cells and is implicated in lymphomagenesis. To explore the transcriptional programs controlled by EZH2, we performed chromatin immunoprecipitation (ChIP-on-chip) in GC cells and found that it binds approximately 1800 promoters, often associated with DNA sequences similar to Droso-phila Polycomb response elements. While EZH2 targets overlapped extensively between GC B cells and embryonic stem cells, we also observed a large GC-specific EZH2 regulatory program. These genes are preferentially histone 3 lysine 27-trimethylated and repressed in GC B cells and include several key cell cycle-related tumor suppressor genes. Accordingly, siRNA-mediated down-regulation of EZH2 in diffuse large B-cell lymphoma (DLBCL) cells resulted in acute cell cycle arrest at the G(1)/S transition and up-regulation of its tumor suppressor target genes. At the DNA level, EZH2-bound promoters are hypomethylated in GC B cells, but many of them are aberrantly hypermethylated in DLBCL, suggesting disruption of normal epigenetic processes in these cells. EZH2 is thus involved in regulating a specific epigenetic program in normal GCs, including silencing of antiproliferative genes, which may contribute to the malignant transformation of GC B cells into DLBCLs. PMID- 20736452 TI - The requirement for NKG2D in NK cell-mediated rejection of parental bone marrow grafts is determined by MHC class I expressed by the graft recipient. AB - Natural killer (NK) cells provide a unique barrier to semiallogeneic bone marrow (BM) transplantation. In the setting where the parents donate to the F1 offspring, rejection of parental bone marrow occurs. This "hybrid resistance" is completely NK cell dependent, as T cells in the F1 recipient tolerate parental grafts. Previously, we demonstrated that rejection of BALB/c parental BM by (BALB/c * C57BL/6) F1-recipient NK cells is dependent on the NKG2D-activating receptor, whereas rejection of parental C57BL/6 BM does not require NKG2D. BALB/c and B6 mice possess different NKG2D ligand genes and express these ligands differently on reconstituting BM cells. Herein, we show that the requirement for NKG2D in rejection depends on the major histocompatibility complex haplotype of donor cells and not the differences in the expression of NKG2D ligands. NKG2D stimulation of NK cell-mediated rejection was required to overcome inhibition induced by H-2D(d) when it engaged an inhibitory Ly49 receptor, whereas rejection of parental BM expressing the ligand, H-2K(b), did not require NKG2D. Thus, interactions between the inhibitory receptors on F1 NK cells and parental major histocompatibility complex class I ligands determine whether activation via NKG2D is required to achieve the threshold for rejection of parental BM grafts. PMID- 20736453 TI - Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance. AB - We analyzed prevalence, characteristics, clinical correlates, and prognostic significance of autoimmune cytopenia in patients with chronic lymphocytic leukemia. Seventy of 960 unselected patients (7%) had autoimmune cytopenia, of whom 19 were detected at diagnosis, 3 before diagnosis, and 48 during the course of the disease. Forty-nine patients had autoimmune hemolytic anemia, 20 had immune thrombocytopenic purpura, and 1 had both conditions. A clear association was observed between autoimmune cytopenia and poor prognostic variables (ie, high blood lymphocyte count, rapid blood lymphocyte doubling time, increased serum beta-2 microglobulin level, and high expression of zeta-associated protein 70 and CD38). Nevertheless, the outcome of patients with autoimmune cytopenia as a whole was not significantly different from that of patients without this complication. Furthermore, no differences were observed according to time at which cytopenia was detected (ie, at diagnosis, during course of disease). Importantly, patients with advanced (Binet stage C) disease because of an autoimmune mechanism had a significantly better survival than patients in advanced stage related to a massive bone marrow infiltration (median survivals: 7.4 years vs 3.7 years; P = .02). These results emphasize the importance of determining the origin of cytopenia in patients with chronic lymphocytic leukemia for both treatment and prognostic purposes. PMID- 20736454 TI - Defect of plasmacytoid dendritic cells in warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome patients. AB - Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome is a genetic disease that is caused by heterozygous mutations of the CXCR4 gene. These mutations confer an increased leukocyte response to the CXCR4-ligand CXCL12, resulting in abnormal homeostasis of many leukocyte types, including neutrophils and lymphocytes. Analysis of the myeloid and plasmacytoid dendritic cell blood counts in WHIM patients revealed a striking defect in the number of plasmacytoid dendritic cells as well as a partial reduction of the number of myeloid dendritic cells, compared with healthy subjects. Moreover, the production of interferon alpha by mononuclear cells in response to herpes simplex infection, or after stimulation with the Toll-like receptor 9 ligand CpG, was undetectable in WHIM patients. Because plasmacytoid dendritic cells play a key role in the defense against viruses and their generation and motility are in part dependent on CXCR4, we hypothesized that the susceptibility of WHIM patients to warts is related to the abnormal homeostasis of plasmacytoid dendritic cells. PMID- 20736456 TI - Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL. AB - The survival of diffuse large B-cell lymphoma patients varies considerably, reflecting the molecular diversity of tumors. In view of the controversy whether cytologic features, immunohistochemical markers or gene expression signatures may capture this molecular diversity, we investigated which features provide prognostic information in a prospective trial in the R-CHOP treatment era. Within the cohort of DLBCLs patients treated in the RICOVER-60 trial of the German High Grade Lymphoma Study Group (DSHNHL), we tested the prognostic impact of IB morphology in 949 patients. The expression of immunohistochemical markers CD5, CD10, BCL2, BCL6, human leukocyte antigen (HLA)-DR, interferon regulatory factor 4/multiple myeloma-1 (IRF4/MUM1), and Ki-67 was assessed in 506 patients. Expression of the immunohistochemical markers tested was of modest, if any, prognostic relevance. Moreover, the Hans algorithm using the expression patterns of CD10, BCL6, and interferon regulatory factor-4/multiple myeloma-1 failed to show prognostic significance in the entire cohort as well as in patient subgroups. IB morphology, however, emerged as a robust, significantly adverse prognostic factor in multivariate analysis, and its diagnosis showed a good reproducibility among expert hematopathologists. We conclude, therefore, that IB morphology in DLBCL is likely to capture some of the adverse molecular alterations that are currently not detectable in a routine diagnostic setting, and that its recognition has significant prognostic power. PMID- 20736455 TI - Protease-activated receptors mediate crosstalk between coagulation and fibrinolysis. AB - The coagulation and fibrinolytic systems contribute to malignancy by increasing angiogenesis, tumor growth, tumor invasion, and tumor metastasis. Oncogenic transformation increases the expression of tissue factor (TF) that results in local generation of coagulation proteases and activation of protease-activated receptor (PAR)-1 and PAR-2. We compared the PAR-dependent expression of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI)-1 in 2 murine mammary adencocarcinoma cell lines: metastatic 4T1 cells and nonmetastatic 67NR cells. 4T1 cells expressed TF, PAR-1 and PAR-2 whereas 67NR cells expressed TF and PAR-1. We also silenced PAR-1 or PAR-2 expression in the 4T1 cells. We discovered 2 distinct mechanisms for PAR-dependent expression of uPA and PAI-1. First, we found that factor Xa or thrombin activation of PAR-1 led to a rapid release of stored intracellular uPA into the culture supernatant. Second, thrombin transactivation of a PAR-1/PAR-2 complex resulted in increases in PAI-1 mRNA and protein expression. Cells lacking PAR-2 failed to express PAI-1 in response to thrombin and factor Xa did not activate the PAR-1/PAR-2 complex. Our results reveal how PAR-1 and PAR-2 on tumor cells mediate crosstalk between coagulation and fibrinolysis. PMID- 20736457 TI - The cover. Study of hands. PMID- 20736458 TI - A piece of my mind. Hope. PMID- 20736459 TI - Memories of Katrina continue to hinder mental health recovery in New Orleans. PMID- 20736460 TI - As use of foreign drug trials grows, FDA oversight may not be keeping up. PMID- 20736461 TI - FDA approves generic enoxaparin. PMID- 20736462 TI - FDA opioid safety plan promotes patient, physician education to prevent abuse. PMID- 20736463 TI - High-dose oral vitamin D supplementation and risk of falls in older women. PMID- 20736464 TI - High-dose oral vitamin D supplementation and risk of falls in older women. PMID- 20736465 TI - High-dose oral vitamin D supplementation and risk of falls in older women. PMID- 20736466 TI - High-dose oral vitamin D supplementation and risk of falls in older women. PMID- 20736467 TI - Traumatic brain injury and major depressive disorder. PMID- 20736468 TI - Genome-wide association study of genetic loci and Alzheimer disease. PMID- 20736469 TI - Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects. AB - CONTEXT: Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented. OBJECTIVE: To investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and risk of major birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based historical cohort study of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses (categorized according to a standardized classification scheme), and potential confounders. MAIN OUTCOME MEASURE: Prevalence odds ratios (PORs) of any major birth defect diagnosed within the first year of life by exposure to antiviral drugs. RESULTS: Among 1804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir in the first trimester, 40 infants (2.2%) were diagnosed with a major birth defect compared with 19,920 (2.4%) among the unexposed (adjusted POR, 0.89; 95% confidence interval [CI], 0.65-1.22). For individual antivirals, a major birth defect was diagnosed in 32 of 1561 infants (2.0%) with first-trimester exposure to acyclovir (adjusted POR, 0.82; 95% CI, 0.57-1.17) and in 7 of 229 infants (3.1%) with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56-2.62). Famciclovir exposure was uncommon (n = 26), with 1 infant (3.8%) diagnosed with a birth defect. Exploratory analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small. CONCLUSION: In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects. PMID- 20736470 TI - Elective intra-aortic balloon counterpulsation during high-risk percutaneous coronary intervention: a randomized controlled trial. AB - CONTEXT: Observational studies have previously reported that elective intra aortic balloon pump (IABP) insertion may improve outcomes following high-risk percutaneous coronary intervention (PCI). To date, this assertion has not been tested in a randomized trial. OBJECTIVE: To determine whether routine intra aortic balloon counterpulsation before PCI reduces major adverse cardiac and cardiovascular events (MACCE) in patients with severe left ventricular dysfunction and extensive coronary disease. DESIGN, SETTING, AND PATIENTS: The Balloon Pump-Assisted Coronary Intervention Study, a prospective, open, multicenter, randomized controlled trial conducted in 17 tertiary referral cardiac centers in the United Kingdom between December 2005 and January 2009. Patients (n = 301) had severe left ventricular dysfunction (ejection fraction < or = 30%) and extensive coronary disease (Jeopardy Score > or = 8/12); those with contraindications to or class I indications for IABP therapy were excluded. INTERVENTION: Elective insertion of IABP before PCI. MAIN OUTCOME MEASURES: Primary end point was MACCE, defined as death, acute myocardial infarction, cerebrovascular event, or further revascularization at hospital discharge (capped at 28 days). Secondary end points included all-cause mortality at 6 months, major procedural complications, bleeding, and access-site complications. RESULTS: MACCE at hospital discharge occurred in 15.2% (23/151) of the elective IABP and 16.0% (24/150) of the no planned IABP groups (P = .85; odds ratio [OR], 0.94 [95% confidence interval {CI}, 0.51-1.76]). All-cause mortality at 6 months was 4.6% and 7.4% in the respective groups (P = .32; OR, 0.61 [95% CI, 0.24-1.62]). Fewer major procedural complications occurred with elective IABP insertion compared with no planned IABP use (1.3% vs 10.7%, P < .001; OR, 0.11 [95% CI, 0.01-0.49]). Major or minor bleeding occurred in 19.2% and 11.3% (P = .06; OR, 1.86 [95% CI, 0.93-3.79]) and access-site complications in 3.3% and 0% (P = .06) of the elective and no planned IABP groups, respectively. CONCLUSIONS: Elective IABP insertion did not reduce the incidence of MACCE following PCI. These results do not support a strategy of routine IABP placement before PCI in all patients with severe left ventricular dysfunction and extensive coronary disease. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN40553718; clinicaltrials.gov Identifier: NCT00910481. PMID- 20736471 TI - Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. AB - CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) in adulthood is a prevalent, distressing, and impairing condition that is not fully treated by pharmacotherapy alone and lacks evidence-based psychosocial treatments. OBJECTIVE: To test cognitive behavioral therapy for ADHD in adults treated with medication but who still have clinically significant symptoms. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial assessing the efficacy of cognitive behavioral therapy for 86 symptomatic adults with ADHD who were already being treated with medication. The study was conducted at a US hospital between November 2004 and June 2008 (follow-up was conducted through July 2009). Of the 86 patients randomized, 79 completed treatment and 70 completed the follow-up assessments. INTERVENTIONS: Patients were randomized to 12 individual sessions of either cognitive behavioral therapy or relaxation with educational support (which is an attention-matched comparison). MAIN OUTCOME MEASURES: The primary measures were ADHD symptoms rated by an assessor (ADHD rating scale and Clinical Global Impression scale) at baseline, posttreatment, and at 6- and 12-month follow-up. The assessor was blinded to treatment condition assignment. The secondary outcome measure was self-report of ADHD symptoms. RESULTS: Cognitive behavioral therapy achieved lower posttreatment scores on both the Clinical Global Impression scale (magnitude -0.0531; 95% confidence interval [CI], -1.01 to -0.05; P = .03) and the ADHD rating scale (magnitude -4.631; 95% CI, -8.30 to -0.963; P = .02) compared with relaxation with educational support. Throughout treatment, self reported symptoms were also significantly more improved for cognitive behavioral therapy (beta = -0.41; 95% CI, -0.64 to -0.17; P <001), and there were more treatment responders in cognitive behavioral therapy for both the Clinical Global Impression scale (53% vs 23%; odds ratio [OR], 3.80; 95% CI, 1.50 to 9.59; P = .01) and the ADHD rating scale (67% vs 33%; OR, 4.29; 95% CI, 1.74 to 10.58; P = .002). Responders and partial responders in the cognitive behavioral therapy condition maintained their gains over 6 and 12 months. CONCLUSION: Among adults with persistent ADHD symptoms treated with medication, the use of cognitive behavioral therapy compared with relaxation with educational support resulted in improved ADHD symptoms, which were maintained at 12 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00118911. PMID- 20736472 TI - Genetic variants of the protein kinase C-beta 1 gene and development of end-stage renal disease in patients with type 2 diabetes. AB - CONTEXT: Protein kinase C-beta (PKC-beta) is a cell-signaling intermediate implicated in development of diabetic complications. OBJECTIVE: To examine the risk association of PKC-beta 1 gene (PRKCB1) polymorphisms and end-stage renal disease (ESRD) in an 8-year prospective cohort of Chinese patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: We genotyped 18 common tag single nucleotide polymorphisms (SNPs) that span the PRKCB1 gene (r(2) = 0.80) in 1172 Chinese patients (recruited 1995-1998) without renal disease at baseline. A validation cohort included an additional 1049 patients with early-onset diabetes who were free of renal disease at baseline and were recruited after 1998. MAIN OUTCOME MEASURES: Associations of PRKCB1 polymorphisms under additive, dominant, and recessive genetic models with new onset of ESRD (defined as estimated glomerular filtration rate <15 mL/min/1.73 m(2) or dialysis or renal-related death) were assessed by Cox proportional hazard regression, adjusted for all conventional risk factors including use of medications. RESULTS: After a mean (SD) of 7.9 (1.9) years, 90 patients (7.7%) progressed to ESRD. Four common SNPs were associated with ESRD (P < .05). The closely linked T allele at rs3760106 and G allele rs2575390 (r(2) = 0.98) showed the strongest association with ESRD (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.31-3.87; P = .003, and HR, 2.26; 95% CI, 1.31-3.88; P = .003, respectively). Four common variants predicted ESRD in separate models. The HR for ESRD increased with increasing number of risk alleles (P < .001) in the joint effect analysis. The adjusted risk for ESRD was 6.04 (95% CI, 2.00-18.31) for patients with 4 risk alleles compared with patients with 0 or 1 risk allele. Incidence was 4.4 per 1000 person-years (95% CI, 0.5-8.2) among individuals with 0 or 1 risk allele compared with 20.0 per 1000 person-years (95% CI, 8.8-31.1) in those carrying 4 risk alleles (6.9% of the cohort). These results were validated in a separate prospective cohort of young-onset diabetic patients. Of 1049 patients in the validation cohort, 151 (14.3%) developed chronic kidney disease (CKD) during follow-up, and there were significant associations between both the T allele of rs3760106 and the G allele of rs2575390 and development of CKD (HR, 1.68; 95% CI, 1.10-2.57; P = .02, and HR, 1.62; 95% CI, 1.07-2.47; P = .02, respectively). CONCLUSION: Genetic variants in the PRKCB1 gene were independently associated with development of ESRD in Chinese patients with type 2 diabetes. PMID- 20736473 TI - Does this coughing adolescent or adult patient have pertussis? AB - CONTEXT: Pertussis is often overlooked as a cause of chronic cough, especially in adolescents and adults. Several symptoms are classically thought to be suggestive of pertussis, but the diagnostic value of each of them is uncertain. OBJECTIVE: To systematically review the evidence regarding the diagnostic value of 3 classically described symptoms of pertussis: paroxysmal cough, posttussive emesis, and inspiratory whoop. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: We searched MEDLINE (January 1966-April 2010), EMBASE (January 1969 to April 2010), and the bibliographies of pertinent articles to identify relevant English-language studies. Articles were selected that included children older than 5 years, adolescents, or adults and confirmed the diagnosis of pertussis among patients with cough illness (of any duration) with an a priori-defined accepted reference standard. Two authors independently extracted data from articles that met selection criteria and resolved any discrepancies by consensus. DATA SYNTHESIS: Five prospective studies met inclusion criteria; 3 were used in the analysis. Presence of posttussive emesis (summary likelihood ratio [LR], 1.8; 95% confidence interval [CI], 1.4-2.2) or inspiratory whoop (summary LR, 1.9; 95% CI, 1.4-2.6) increases the likelihood of pertussis. Absence of paroxysmal cough (summary LR, 0.52; 95% CI, 0.27-1.0) or posttussive emesis (summary LR, 0.58; 95% CI, 0.44-0.77) reduced the likelihood. Absence of inspiratory whoop was less useful (summary LR, 0.78; 95% CI, 0.66-0.93). No studies evaluated combinations of findings. CONCLUSIONS: In a nonoutbreak setting, data to determine the diagnostic usefulness of symptoms classically associated with pertussis are limited and of relatively weak quality. The presence or absence of posttussive emesis or inspiratory whoop modestly change the likelihood of pertussis; therefore, clinicians must use their overall clinical impression to decide about additional testing or empirical treatment. PMID- 20736474 TI - Minimizing bias due to confounding by indication in comparative effectiveness research: the importance of restriction. PMID- 20736475 TI - Health care reform and chronic diseases: anticipating the health consequences. PMID- 20736476 TI - Comparative effectiveness--of what?: evaluating strategies to improve population health. PMID- 20736477 TI - The shared decision-making continuum. PMID- 20736478 TI - Acyclovir exposure and birth defects: an important advance, but more are needed. PMID- 20736479 TI - JAMA patient page. Pertussis. PMID- 20736482 TI - Bridging the synaptic cleft: lessons from orphan glutamate receptors. AB - For neurons to communicate, signals must cross the cell-to-cell distance at their points of contact. At the predominant cell-cell contact in the central nervous system, the chemical synapse, the synaptic cleft spans roughly 20 nanometers. To signal across this distance, the presynaptic neuron secretes a diffusible neurotransmitter, which is detected by receptors on the postsynaptic neuron. Although this signaling mechanism has become common knowledge, it remains unclear how synapses are maintained when they are not in immediate use. New evidence reveals how Nature solved this problem at a particular type of synapse in the cerebellum: Three old acquaintances bridge the cleft. The ionotropic glutamate receptor GluD2 constitutes the postsynaptic anchor that indirectly interacts with the presynaptic anchor neurexin through a presynaptically secreted soluble factor, a member of the C1q protein family named Cbln1. This trio collaborates to align pre- and postsynaptic sides. PMID- 20736483 TI - Self-induced patched receptor down-regulation modulates cell sensitivity to the hedgehog morphogen gradient. AB - Morphogens form signaling gradients that control patterning processes during development. Responding cells must perceive and interpret the concentration dependent information provided by the morphogen to generate precise patterns of gene expression and cell differentiation in developing tissues. Generally, the absolute number of activated, ligand-bound receptors determines cell perception of the morphogen. In contrast, cells interpret the morphogen Hedgehog (Hh) by measuring the ratio of bound to unbound molecules of its receptor Patched (Ptc). This ratio depends on both the Hh concentration and the absolute number of Ptc molecules. Here, I describe a posttranscriptional process that controls the absolute amount of Ptc present in a cell, which regulates gradient interpretation, wherein self-induced receptor down-regulation that is independent of ligand binding dictates the cell response to a morphogen gradient. PMID- 20736484 TI - Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. AB - Receptor tyrosine kinases (RTKs) activate pathways mediated by serine-threonine kinases, such as the PI3K (phosphatidylinositol 3-kinase)-Akt pathway, the Ras MAPK (mitogen-activated protein kinase)-RSK (ribosomal S6 kinase) pathway, and the mTOR (mammalian target of rapamycin)-p70 S6 pathway, that control important aspects of cell growth, proliferation, and survival. The Akt, RSK, and p70 S6 family of protein kinases transmits signals by phosphorylating substrates on an RxRxxS/T motif (R, arginine; S, serine; T, threonine; and x, any amino acid). We developed a large-scale proteomic approach to identify more than 300 substrates of this kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor (EGFR), or platelet-derived growth factor receptor alpha (PDGFRalpha) RTKs. We identified a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased by RTK inhibitors (RTKIs), as well as by inhibitors of the PI3K, mTOR, and MAPK pathways, and we determined the effects of small interfering RNA directed against these substrates on cell viability. Phosphorylation of the protein chaperone SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) at serine-305 was essential for PDGFRalpha stabilization and cell survival in PDGFRalpha-dependent cancer cells. Our approach provides a new view of RTK and Akt-RSK-S6 kinase signaling, revealing previously unidentified Akt-RSK-S6 kinase substrates that merit further consideration as targets for combination therapy with RTKIs. PMID- 20736485 TI - A direct and functional interaction between Go and Rab5 during G protein-coupled receptor signaling. AB - Rab5 is a small guanosine triphosphatase (GTPase) that regulates the early stages of endocytosis and is conserved in eukaryotes. Rab5 regulates the internalization of receptors and other membrane-associated signaling proteins. The function of Rab5 in these processes is considered relatively passive, so that the endocytic capacity of Rab5 is used during, for example, beta-arrestin-dependent internalization of G protein (heterotrimeric guanine nucleotide-binding protein) coupled receptors (GPCRs). Direct recruitment or activation of Rab5 by the components of these signaling pathways has not been reported. Here, we demonstrate an interaction of Drosophila Rab5 and an immediate transducer of GPCR signaling, the G protein G(o), in vitro and in vivo. Rab5 and G(o) bound to each other as purified proteins, as well as in fly extracts. In cellular assays, G(o) led to Rab5 activation and endosome fusion. We further showed that the G(o)-Rab5 interaction functioned in Drosophila planar cell polarity and Wingless signal transduction, pathways initiated by GPCRs of the Frizzled (Fz) family. Additionally, the recycling Rab GTPases Rab4 and Rab11 functioned in Fz- and G(o) mediated signaling to favor planar cell polarity over canonical Wingless signaling. The interplay between heterotrimeric G proteins and Rab GTPases controlled receptor internalization, revealing a previously uncharacterized regulatory mechanism in GPCR signaling. PMID- 20736486 TI - Cytokine storm in the pediatric oncology patient. AB - Cytokine storm is an immune reaction to an acute or chronic injury and may be caused by a disease itself or by treatment directed at an underlying disease. The result is an overwhelming release of cytokines which can cause a sepsis-like response and may lead to multi-system organ failure and even death. Because it occurs in various settings, oncology nurses need to be aware of this process when assessing the pediatric oncology patient. Early recognition and treatment initiation is imperative and may lead to better outcomes for the patient. PMID- 20736488 TI - Infant sex, family support and postpartum depression in a Chinese cohort. AB - OBJECTIVES: To assess the impact of prenatal and postnatal family support on the association between infant sex and postpartum depression (PPD). DESIGN: Prospective cohort study. SETTING: Pregnant women seen at Hunan Maternal and Infant Hospital, the First Affiliated and the Third Affiliated Hospitals of the Central South University in Changsha, Hunan, People's Republic of China from February to September 2007. PARTICIPANTS: 534 Pregnant women who were consecutively recruited from the participating hospital during their prenatal visits at 30-32 weeks of gestation and who completed the 2 weeks postpartum survey, with no recorded major psychiatric disorders and obstetric and/or pregnancy complications. MAIN OUTCOME MEASURE: PPD, which was defined as a score of 13 or higher of the Edinburgh Postnatal Depression Scale. RESULTS: Postnatal family support scores were much lower in women who gave birth to a female infant, and the OR of PPD was 3.67 (95% CI 2.31 to 5.84) for them as compared to women who gave birth to a male infant. After adjusting by postnatal support from all family members, husband and parents, the ORs of PPD for women who gave birth to a female infant decreased to 2.06 (95% CI 1.20 to 3.53), 2.89 (95% CI 1.76 to 4.77) and 2.20 (95% CI 1.28 to 3.77), respectively. DISCUSSION: Increased risk of PPD in Chinese women who gave birth to a female infant can be explained to large extent by inadequate or poor postpartum support from family members, particularly husband and parents. PMID- 20736487 TI - Do neighbourhoods matter? Neighbourhood disorder and long-term trends in serum cortisol levels. AB - BACKGROUND: Characteristics associated with low socioeconomic status neighbourhoods may put children at risk for unique chronic stressors that affect cortisol levels. This research sought to explore whether neighbourhood stressor exposure affected serum cortisol levels among children. METHODS: A total of 148 African and European-American children with an average age of 8.28 years participated in a longitudinal study evaluating ethnic differences in body composition and disease risk. Five waves of data were included in analyses. Mixed modelling was used to explore neighbourhood stressors, which was a composite index of five items for zip code level poverty and physical disorder, and serum cortisol outcomes for the full sample, by race/ethnicity and gender. Adjustments were made for individual level correlates age, pubertal status, gender and total fat mass. RESULTS: Neighborhood disorder was predictive of lower serum cortisol levels among African-American children (p<0.05), such that higher neighbourhood stressor exposure resulted in lower serum cortisol over time compared with individuals in socially ordered neighbourhoods. Neighbourhood disorder was marginally significant and predictive of higher serum cortisol among European American children (p<0.10). Transition to a higher pubertal status, nested in age was also predictive of lower serum cortisol levels (p<0.01) among European American children. CONCLUSION: Children who are exposed to negative socioenvironmental climates over time are more likely to have altered serum cortisol levels. This may be an adaptive mechanism to cope with stress; however, disrupted cortisol levels may have negative effects on general physical and mental health. PMID- 20736489 TI - The association of childhood height, leg length and other measures of skeletal growth with adult cardiovascular disease: the Boyd-Orr cohort. AB - BACKGROUND: Taller adults have a reduced risk of cardiovascular disease, and there is some evidence that pre-adolescent exposures, indexed by leg length, underlie this association. Associations with other aspects of skeletal size in childhood have not previously been investigated. METHODS: We have examined associations of cardiovascular mortality and morbidity with childhood height, shoulder breadth, leg, trunk and foot length using a cohort of children whose families participated in a 1937-9 survey of diet and health followed up for 59 years. RESULTS: Altogether 2642 traced participants had at least one anthropometric measurement; a subsample (n=1043), completed the Rose angina questionnaire and provided information about doctor-diagnosed ischaemic heart disease (IHD) in 1997-8. Childhood stature was weakly inversely associated with cardiovascular mortality, and leg length was the component with the strongest associations. There was evidence from secondary analyses that childhood anthropometric measurements were inversely related to early (age <65 years) rather than late cardiovascular mortality. Childhood stature was inversely associated with self-reported IHD and associations with leg length were strongest. Associations were somewhat attenuated in models including terms for having been breastfed and socioeconomic position. CONCLUSION: Pre-adult exposures are more strongly associated with cardiovascular morbidity than mortality, and they affect premature cardiovascular mortality more than later mortality. PMID- 20736490 TI - A finite element model of needle electrode spatial sensitivity. AB - We used the finite element (FE) method to estimate the spatial sensitivity of a needle electrode for bioimpedance measurements. This current conducting needle with an insulated shaft was inserted in a saline solution and the current was measured at the neutral electrode. Model resistance and reactance were calculated and successfully compared with measurements on a laboratory model. The sensitivity field was described graphically based on these FE simulations. PMID- 20736492 TI - Contour tracing for segmentation of mammographic masses. AB - CADx systems have the potential to support radiologists in the difficult task of discriminating benign and malignant mammographic lesions. The segmentation of mammographic masses from the background tissue is an important module of CADx systems designed for the characterization of mass lesions. In this work, a novel approach to this task is presented. The segmentation is performed by automatically tracing the mass' contour in-between manually provided landmark points defined on the mass' margin. The performance of the proposed approach is compared to the performance of implementations of three state-of-the-art approaches based on region growing and dynamic programming. For an unbiased comparison of the different segmentation approaches, optimal parameters are selected for each approach by means of tenfold cross-validation and a genetic algorithm. Furthermore, segmentation performance is evaluated on a dataset of ROI and ground-truth pairs. The proposed method outperforms the three state-of-the art methods. The benchmark dataset will be made available with publication of this paper and will be the first publicly available benchmark dataset for mass segmentation. PMID- 20736493 TI - The upper limits of the SNR in radiography and CT with polyenergetic x-rays. AB - The aim of the study is to determine the upper limits of the signal-to-noise ratio (SNR) in radiography and computed tomography (CT) with polyenergetic x-ray sources. In x-ray imaging, monoenergetic x-rays provide a higher SNR compared to polyenergetic x-rays. However, the SNR in polyenergetic x-ray imaging can be increased when a photon-counting detector is used and x-rays are optimally weighted according to their energies. For a particular contrast/background combination and at a fixed x-ray entrance skin exposure, the SNR in energy weighting x-ray imaging depends on tube voltage and can be maximized by selecting the optimal tube voltage. The SNR in energy-weighted x-ray images acquired at this optimal tube voltage is the highest SNR that can be achieved with polyenergetic x-ray sources. The optimal tube voltages and the highest SNR were calculated and compared to the SNR of monoenergetic x-ray imaging. Monoenergetic, energy-weighting polyenergetic and energy-integrating polyenergetic x-ray imagings were simulated at a fixed entrance skin exposure of 20 mR. The tube voltages varied in the range of 30-140 kVp with 10 kV steps. Contrast elements of CaCO(3), iodine, adipose and tumor with thicknesses of 280 mg cm(-2), 15 mg cm( 2), 1 g cm(-2) and 1 g cm(-2), respectively, inserted in a soft tissue background with 10 cm and 20 cm thicknesses, were used. The energy weighting also improves the contrast-to-noise ratio (CNR) in CT when monoenergetic CT projections are optimally weighted prior to CT reconstruction (projection-based weighting). Alternatively, monoenergetic CT images are reconstructed, optimally weighted and composed to yield a final CT image (image-based weighting). Both projection-based and image-based weighting methods improve the CNR in CT. An analytical approach was used to determine which of these two weighting methods provides the upper limit of the CNR in CT. The energy-weighting method was generalized and expanded as a weighting method applicable in areas other than x-ray and CT. An optimal x ray tube voltage providing the highest SNR in energy-weighting x-ray imaging was determined for each contrast/background combination. Depending on the imaging task, the highest SNR with energy-weighted polyenergetic x-rays was close to the SNR provided by monoenergetic x-rays. In CT, projection-based weighting provided higher CNR than image-based weighting, thus determining an upper limit of the CNR in CT. The weighting approach can be applied to imaging methods with contrast mechanisms other than x-ray interaction. A unique, task-dependent tube voltage exists in photon-counting x-ray and CT that provides the highest SNR with polyenergetic x-rays. The highest SNR achieved in photon-counting energy-weighted x-ray and CT can approach the SNR of monoenergetic x-ray and CT imaging, depending on the imaging task. PMID- 20736494 TI - Low-dose x-ray phase-contrast and absorption CT using equally sloped tomography. AB - Tomographic reconstruction from undersampled and noisy projections is often desirable in transmission CT modalities for purposes of low-dose tomography and fast acquisition imaging. However under such conditions, due to the violation of the Nyquist sampling criteria and the presence of noise, reconstructions with acceptable accuracy may not be possible. Recent experiments in transmission electron tomography and coherent diffraction microscopy have shown that the technique of equally sloped tomography (EST), an exact tomographic method utilizing an oversampling iterative Fourier-based reconstruction, provides more accurate image reconstructions when the number of projections is significantly undersampled relative to filtered back projection and algebraic iterative methods. Here we extend this technique by developing new reconstruction algorithms which allow for the incorporation of advanced mathematical regularization constraints, such as the nonlocal means total variational model, in a manner that is consistent with experimental projections. We then evaluate the resulting image quality of the developed algorithm through simulations and experiments at the European Synchrotron Radiation Facility on image quality phantoms using the x-ray absorption and phase contrast CT modalities. Both our simulation and experimental results have indicated that the method can reduce the number of projections by 60-75% in parallel beam modalities, while achieving comparable or better image quality than the conventional reconstructions. As large-scale and compact synchrotron radiation facilities are currently under rapid development worldwide, the implementation of low-dose x-ray absorption and phase-contrast CT can find broad applications in biology and medicine using these advanced x-ray sources. PMID- 20736496 TI - Evaluation of a 3D point cloud tetrahedral tomographic reconstruction method. AB - Tomographic reconstruction on an irregular grid may be superior to reconstruction on a regular grid. This is achieved through an appropriate choice of the image space model, the selection of an optimal set of points and the use of any available prior information during the reconstruction process. Accordingly, a number of reconstruction-related parameters must be optimized for best performance. In this work, a 3D point cloud tetrahedral mesh reconstruction method is evaluated for quantitative tasks. A linear image model is employed to obtain the reconstruction system matrix and five point generation strategies are studied. The evaluation is performed using the recovery coefficient, as well as voxel- and template-based estimates of bias and variance measures, computed over specific regions in the reconstructed image. A similar analysis is performed for regular grid reconstructions that use voxel basis functions. The maximum likelihood expectation maximization reconstruction algorithm is used. For the tetrahedral reconstructions, of the five point generation methods that are evaluated, three use image priors. For evaluation purposes, an object consisting of overlapping spheres with varying activity is simulated. The exact parallel projection data of this object are obtained analytically using a parallel projector, and multiple Poisson noise realizations of these exact data are generated and reconstructed using the different point generation strategies. The unconstrained nature of point placement in some of the irregular mesh-based reconstruction strategies has superior activity recovery for small, low-contrast image regions. The results show that, with an appropriately generated set of mesh points, the irregular grid reconstruction methods can out-perform reconstructions on a regular grid for mathematical phantoms, in terms of the performance measures evaluated. PMID- 20736495 TI - Comments on 'Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers'. AB - In a recent paper (Spinelli et al 2010 Phys. Med. Biol. 55 483-95) the authors report on their measurements and observations regarding the use of optical imaging of Cerenkov radiation to observe the distribution of radiotracer in a mouse. The paper, while broadly correct, develops a detailed model of the Cerenkov radiation spectrum that does not appropriately consider the particle energy and the distance travelled while velocity exceeds the Cerenkov threshold. Also, we note the authors' two different methods for determining the depth of the source appear in fact to be the same method if the first method properly accounts for the spectrum of the emitted radiation. PMID- 20736497 TI - A fillable micro-hollow sphere lesion detection phantom using superposition. AB - The lesion detection performance of SPECT and PET scanners is most commonly evaluated with a phantom containing hollow spheres in a background chamber at a specified radionuclide contrast ratio. However, there are limitations associated with a miniature version of a hollow sphere phantom for small-animal SPECT and PET scanners. One issue is that the 'wall effect' associated with zero activity in the sphere wall and fill port causes significant errors for small diameter spheres. Another issue is that there are practical difficulties in fabricating and in filling very small spheres (<3 mm diameter). The need for lesion detection performance assessment of small-animal scanners has motivated our development of a micro-hollow sphere phantom that utilizes the principle of superposition. The phantom is fabricated by stereolithography and has interchangeable sectors containing hollow spheres with volumes ranging from 1 to 14 microL (diameters ranging from 1.25 to 3.0 mm). A simple 60 degrees internal rotation switches the positions of three such sectors with their corresponding background regions. Raw data from scans of each rotated configuration are combined and reconstructed to yield superposition images. Since the sphere counts and background counts are acquired separately, the wall effect is eliminated. The raw data are subsampled randomly prior to summation and reconstruction to specify the desired sphere-to background contrast ratio of the superposition image. A set of images with multiple contrast ratios is generated for visual assessment of lesion detection thresholds. To demonstrate the utility of the phantom, data were acquired with a multi-pinhole SPECT/CT scanner. Micro-liter syringes were successful in filling the small hollow spheres, and the accuracy of the dispensed volume was validated through repeated filling and weighing of the spheres. The phantom's internal rotation and the data analysis process were successful in producing the expected superposition images. Visual inspection of the multi-contrast images provided simple determination of lesion detection thresholds for this scanner (4:1 ratio for 1.5 mm spheres and 3:1 ratio for 2.0 mm spheres) at a specified cumulated background concentration (30 kBq-min microL(-1)). In summary, the micro-hollow sphere phantom demonstrated its practical utility for lesion detection evaluation and is well suited for comparing the task-based performance of small-animal SPECT and PET scanners. PMID- 20736498 TI - The response of the new MD-V2-55 radiochromic film exposed to 60Co gamma rays. AB - The response of the new radiochromic MD-V2-55 film exposed to (60)Co gamma rays has been investigated. A HP Scanjet 7650 document flatbed scanner has been used to evaluate the response. Before studying the film response, the linearity and stability of the scanner were analysed using three calibrated neutral optical filters, finding that the scanner is linear up to an optical density equal to 1 and stable over a period of more than 6 months with a variation of about approximately 0.3% on the optical density for all filters. The warm-up effect of the scanner was also evaluated and a gradual increase of about 1% in the optical density was observed during the first 15 min of successive readings. Six 1 cm(2) pieces of film per absorbed dose were irradiated to doses ranging from 0.5 to 6500 Gy. The response of the film was evaluated at various spatial resolutions using the two scanning modes (transmission versus reflection) of the scanner. The data analysis was made by extracting all three colour channels from the film image. The results show that the spatial resolution does not have an effect on the absolute optical density, but strongly affects the relative uncertainty in the absorbed dose. A linear dependence of the optical density with absorbed dose is observed if the film is read in transmission mode, while in the reflection mode the optical density is described by a second-order polynomial function. The dose dynamic range of the dosimetry system depends significantly on the method used to evaluate the response of the film (about a factor of 3 on the maximum absorbed dose limit for the green and blue colour channels). Finally, a comparison between this new and an old dosimetry system was also made by scanning MD-55-2 in a Microtek ScanMaker E3 scanner under the same conditions as with the HP scanner. It is observed that the new film produces lower uncertainty in the measurement, which means that it is more uniform. Good agreement is obtained between the optical densities measured for both films read in different scanners. The optical density is statistically the same in the useful dose region using both digitizers, which can be attributed to the use of neutral optical filters with known optical density to calibrate the scanners. Based on these results, it is suggested to use calibrated neutral filters to standardize the systems when flat bed document scanners are used to evaluate the film response. PMID- 20736499 TI - Modeling the detectability of vesicoureteral reflux using microwave radiometry. AB - We present the modeling efforts on antenna design, frequency selection and receiver sensitivity estimation to detect vesicoureteral reflux (VUR) using microwave (MW) radiometry as warm urine from the bladder maintained at fever range temperature using a MW hyperthermia device reflows into the kidneys. The radiometer center frequency (f(c)), frequency band (Deltaf) and aperture radius (r(a)) of the physical antenna for kidney temperature monitoring are determined using a simplified universal antenna model with a circular aperture. Anatomical information extracted from the computed tomography (CT) images of children aged 4 6 years is used to construct a layered 3D tissue model. Radiometric antenna efficiency is evaluated in terms of the ratio of the power collected from the target at depth to the total power received by the antenna (eta). The power ratio of the theoretical antenna is used to design a microstrip log spiral antenna with directional radiation pattern over f(c) +/- Deltaf/2. Power received by the log spiral from the deep target is enhanced using a thin low-loss dielectric matching layer. A cylindrical metal cup is proposed to shield the antenna from electromagnetic interference (EMI). Transient thermal simulations are carried out to determine the minimum detectable change in the antenna brightness temperature (deltaT(B)) for 15-25 mL urine refluxes at 40-42 degrees C located 35 mm from the skin surface. Theoretical antenna simulations indicate maximum eta over 1.1-1.6 GHz for r(a) = 30-40 mm. Simulations of the 35 mm radius tapered log spiral yielded a higher power ratio over f(c) +/- Deltaf/2 for the 35-40 mm deep targets in the presence of an optimal matching layer. Radiometric temperature calculations indicate deltaT(B) 0.1 K for the 15 mL urine at 40 degrees C and 35 mm depth. Higher eta and deltaT(B) were observed for the antenna and matching layer inside the metal cup. Reflection measurements of the log spiral in a saline phantom are in agreement with the simulation data. The numerical study suggests that a radiometer with f(c) = 1.35 GHz, Deltaf = 500 MHz and detector sensitivity better than 0.1 K would be the appropriate tool to noninvasively detect VUR using the log spiral antenna. PMID- 20736500 TI - Block matching 3D random noise filtering for absorption optical projection tomography. AB - Absorption and emission optical projection tomography (OPT), alternatively referred to as optical computed tomography (optical-CT) and optical-emission computed tomography (optical-ECT), are recently developed three-dimensional imaging techniques with value for developmental biology and ex vivo gene expression studies. The techniques' principles are similar to the ones used for x ray computed tomography and are based on the approximation of negligible light scattering in optically cleared samples. The optical clearing is achieved by a chemical procedure which aims at substituting the cellular fluids within the sample with a cell membranes' index matching solution. Once cleared the sample presents very low scattering and is then illuminated with a light collimated beam whose intensity is captured in transillumination mode by a CCD camera. Different projection images of the sample are subsequently obtained over a 360 degrees full rotation, and a standard backprojection algorithm can be used in a similar fashion as for x-ray tomography in order to obtain absorption maps. Because not all biological samples present significant absorption contrast, it is not always possible to obtain projections with a good signal-to-noise ratio, a condition necessary to achieve high-quality tomographic reconstructions. Such is the case for example, for early stage's embryos. In this work we demonstrate how, through the use of a random noise removal algorithm, the image quality of the reconstructions can be considerably improved even when the noise is strongly present in the acquired projections. Specifically, we implemented a block matching 3D (BM3D) filter applying it separately on each acquired transillumination projection before performing a complete three-dimensional tomographical reconstruction. To test the efficiency of the adopted filtering scheme, a phantom and a real biological sample were processed. In both cases, the BM3D filter led to a signal-to-noise ratio increment of over 30 dB on severe noise-affected reconstructions revealing original-noise-hidden-image details. These results show the utility of the BM3D approach for OPT under typical conditions of very low light absorption, suggesting its implementation as an efficient alternative to other filtering schemes such as for example the median filter. PMID- 20736501 TI - Permeability assessment of the focused ultrasound-induced blood-brain barrier opening using dynamic contrast-enhanced MRI. AB - Focused ultrasound (FUS) in conjunction with microbubbles has been shown to successfully open the blood-brain barrier (BBB) in the mouse brain. In this study, we compute the BBB permeability after opening in vivo. The spatial permeability of the BBB-opened region was assessed using dynamic contrast enhanced MRI (DCE-MRI). The DCE-MR images were post-processed using the general kinetic model (GKM) and the reference region model (RRM). Permeability maps were generated and the K(trans) values were calculated for a predefined volume of interest in the sonicated and the control area for each mouse. The results demonstrated that K(trans) in the BBB-opened region (0.02 +/- 0.0123 for GKM and 0.03 +/- 0.0167 min(-1) for RRM) was at least two orders of magnitude higher when compared to the contra-lateral (control) side (0 and 8.5 x 10(-4) +/- 12 x 10(-4) min(-1), respectively). The permeability values obtained with the two models showed statistically significant agreement and excellent correlation (R(2) = 0.97). At histological examination, it was concluded that no macroscopic damage was induced. This study thus constitutes the first permeability assessment of FUS induced BBB opening using DCE-MRI, supporting the fact that the aforementioned technique may constitute a safe, non-invasive and efficacious drug delivery method. PMID- 20736502 TI - Visualization of lipid components in human coronary plaques using color fluorescence angioscopy. AB - BACKGROUND: If oxidized low-density lipoprotein (oxLDL), LDL, lysophosphatidylcholine (LPC) and apolipoprotein B (apoB) can be visualized simultaneously, their roles in the initiation, progression and destabilization of atherosclerotic plaques can be objectively evaluated. METHODS AND RESULTS: (1) The fluorescence characteristic of each atherogenic substance was investigated by microscopy using a band-pass filter (470 nm) and a band-absorption filter (520 nm) with homidium bromide (Ho) and trypan blue (TB) as indicators. (2) 50 excised human coronary plaques were classified by their autofluorescence into green, greenish-yellow and yellow, and the localization of oxLDL, LDL, LPC and apoB were investigated by color fluorescence angioscopy (CFA). The plaque colors were white, yellow and glistening yellow by conventional angioscopy. (1) OxLDL and LDL exhibited golden fluorescence, whereas LPC and apoB exhibited red fluorescence. (2) By CFA, 16 of 19 greenish-yellow and 1 of 8 yellow plaques exhibited red and golden fluorescence in a mosaic pattern, indicating co-deposition of oxLDL/LDL and LPC/apoB; 3 greenish-yellow and 7 yellow plaques exhibited red fluorescence, indicating solitary deposition of apoB; 23 green plaques infrequently exhibited these fluorescence colors. CONCLUSIONS: OxLDL/LDL and LPC/apoB were successfully visualized as co-deposited in greenish-yellow autofluorescence plaques, but only LPC/apoB in yellow autofluorescence plaques. PMID- 20736503 TI - A systolic parameter defined as the ratio of brachial pre-ejection period to brachial ejection time predicts cardiovascular events in patients with chronic kidney disease. AB - BACKGROUND: Patients with chronic kidney disease (CKD) are associated with an increased risk of cardiovascular (CV) events. An increase in the ratio of the pre ejection period (PEP) to ejection time (ET) is correlated with a decrease of left ventricular systolic function. Brachial PEP (bPEP) and brachial ET (bET) can be automatically determined from an ankle-brachial index (ABI)-form device. The aim of this study is to investigate whether bPEP/bET is a useful predictor for CV events in patients with CKD. METHODS AND RESULTS: We consecutively enrolled 242 CKD patients from our outpatient department of internal medicine. The bPEP and bET were measured using an ABI-form device. CV events were defined as cardiac death, stroke, myocardial infarction, and hospitalization for congestive heart failure. The study subjects were followed until the first episode of CV events occurred. The relative CV event risk was analyzed by Cox-regression methods. In the multivariate analysis, the presence of diabetes (hazard ratio (HR), 3.531; P=0.014), increased bPEP/bET (HR, 1.054; P=0.026), and decreased serum albumin level (HR, 0.525; P=0.005) were independent predictors for CV events. CONCLUSIONS: The study findings show that bPEP/bET is a useful predictor of CV events in CKD patients. Screening CKD patients by means of bPEP/bET might help to identify patients at high risk of increased CV events. PMID- 20736504 TI - Impact of left ventricular hypertrophy on the time-course of renal function in hypertensive patients - a subanalysis of the CASE-J trial -. AB - BACKGROUND: In this subanalysis of the CASE-J, which was conducted to compare the effects of candesartan and amlodipine in Japanese high-risk hypertensive patients, THE ASSOCIATION OF LEFT VENTRICULAR HYPERTROPHY (LVH) WITH RENAL FUNCTION IS CLARIFIED. METHODS AND RESULTS: Patients were divided into 2 groups: 1,082 patients with LVH and 2,119 patients without LVH. The primary endpoint was the change in the estimated glomerular filtration rate (eGFR). The eGFRs were increased from 63.6 to 65.1 ml . min(-1) . 1.73 m(-2) in patients with LVH and from 63.6 to 68.5 ml . min(-1) . 1.73 m(-2) in those without LVH. The improvement in the eGFR was greater in patients without LVH than in those with LVH (P=0.004). In patients with chronic kidney disease (CKD) patients, the eGFR increased from 52.7 to 60.5 ml . min(-1) . 1.73 m(-2) in patients without LVH, but from 53.1 to 57.2 ml . min(-1) . 1.73 m(-2) in those with LVH (P<0.001, patients without LVH vs patients with LVH). Furthermore, because the eGFR changed from 76.5 to 75.4 ml . min(-1) . 1.73 m(-2) in patients without CKD but with LVH, and from 76.5 to 77.5 ml . min(-1) . 1.73 m(-2) in those without either CKD or LVH, the final eGFR was higher in patients without LVH than in those with LVH (P=0.048). CONCLUSIONS: LVH related to the time-course of renal function in Japanese hypertensive patients. PMID- 20736505 TI - Comparison between the effect of omeprazole and rabeprazole on the antiplatelet action of clopidogrel. AB - BACKGROUND: Emerging data suggests that several proton pump inhibitors (PPIs), including omeprazole, might interfere with the antiplatelet action of clopidogrel. However, there is a lack of data for rabeprazole. This study aimed to investigate and compare the impact of omeprazole and rabeprazole on the antiplatelet action of clopidogrel among patients with coronary artery disease (CAD). METHODS AND RESULTS: A prospective, randomized, open-labeled study was conducted among 87 CAD patients receiving clopidogrel and aspirin. Forty three and 44 patients were randomized to receive omeprazole 20 mg and rabeprazole 20 mg once daily, respectively, for at least 2 weeks. Adenosine 5-diphosphate 20 umol/L induced platelet aggregation was performed before and after PPIs treatment. Mean maximal platelet aggregation (MPA) before and after PPIs treatment of both groups were compared. At baseline, there were no significant differences in the mean MPA between the omeprazole and rabeprazole groups (40.68 +/- 18.82% vs 36.42 +/- 21.39%; P=0.326). After a 2-week treatment with PPIs, the mean MPA in both groups significantly increased from baseline and there were no differences between the omeprazole and rabeprazole groups (55.73 +/- 19.66% vs 48.46 +/- 18.80%; P=0.141). CONCLUSIONS: Both omeprazole and rabeprazole decreased the antiplatelet effect of clopidogrel. Use of these agents resulted in a similar degree of interference on clopidogrel's action, as measured by ADP-induced platelet aggregation. PMID- 20736506 TI - Changes in cerebral oxygen saturation and blood flow during hypoxic gas ventilation therapy in HLHS and CoA/IAA complex with markedly increased pulmonary blood flow. AB - BACKGROUND: Hypoxic gas ventilation therapy has recently been performed to prevent post-birth increased pulmonary blood flow in cases of congenital heart diseases with increased pulmonary blood flow. However, how the oxygen supply to the tissues changes during breathing a hypoxic gas mixture, remains unknown. The changes in cerebral oxygen saturation and blood supply during hypoxic gas ventilation therapy using a nitrogen gas mixture were studied. METHODS AND RESULTS: Cerebral regional oxygen saturation (cerebral rSO(2)) was measured by near-infrared spectroscopy, and changes in middle cerebral artery (MCA) blood flow and an index of vascular resistance (RI) were assessed in 8 consecutive patients having congenital heart diseases with increased pulmonary blood flow. In all patients, urinary volume increased significantly, and the respiratory rate showed a clear decrease. Percutaneous oxygen saturation showed no significant change. The average of cerebral rSO(2) was 67.3% before hypoxic gas ventilation, but increased to 69.4%, 69.1%, and 70.7% within 1, 12, and 24 h after initiation of treatment, respectively. MCA blood flow significantly increased in the diastolic phase, and RI significantly improved from 0.80 to 0.68 within 12 h after initiation of therapy. CONCLUSIONS: These results indicate that hypoxic gas ventilation therapy does not decrease cerebral oxygen saturation, but safely improves the cerebral blood supply in cases of congenital heart diseases with increased pulmonary blood flow. PMID- 20736507 TI - Long-Term Prospective Study of 6104 Survivors of Arsenic Poisoning During Infancy Due to Contaminated Milk Powder in 1955. AB - BACKGROUND: In 1955, an outbreak of arsenic poisoning caused by ingestion of arsenic-contaminated dry milk occurred in western Japan. We assessed the excess mortality among Japanese who were poisoned during this episode as infants. METHODS: We identified and enrolled 6104 survivors (mean age at enrollment, 27.4 years) who had ingested contaminated milk when they were age 2 years or younger; they were followed until 2006 (mean duration of followup,24.3 years). Death certificates of subjects who died between 1982 and 2006 were examined to calculate cause specific standardized mortality ratios (SMRs) using the mortality rate among Osaka residents as the standard. RESULTS: There was no significant excess overall mortality (SMR: 1.1, 95% confidence interval: 1.0-1.2). However,significant excess mortality in both sexes was observed from diseases of the nervous system (3.7, 1.9-6.2). Excess mortality from all causes of death decreased to unity beyond 10 years after study enrollment. The 408 men who were unemployed at the time of enrollment in the study had a significantly elevated risk of death from diseases of the nervous system (25.3, 10.8-58.8), respiratory diseases (8.6, 3.1-16.8), circulatory diseases (3.2, 1.6-5.2), and external causes (2.6, 1.4-4.1). CONCLUSIONS: As compared with the general population, survivors of arsenic poisoning during infancy had a significantly higher mortality risk from diseases of the nervous system. PMID- 20736508 TI - Serotonergic modulation of absence-like seizures in groggy rats: a novel rat model of absence epilepsy. AB - To explore the role of the serotonergic system in modulating absence seizures, we examined the effects of 5-HT(1A) and 5-HT(2) agonists on the incidence of spike and-wave discharges (SWD) in Groggy (GRY) rats, a novel rat model of absence-like epilepsy. GRY rats exhibited spontaneous absence-like seizures characterized by the incidence of sudden immobile posture and synchronously-associated SWD. The total duration of SWD in GRY rats was about 300 - 400 s/15-min observation period under the control conditions. However, the incidence of SWD was markedly reduced either by the 5-HT(1A) agonist (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin [(+/ )8-OH-DPAT] or the 5-HT(2) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane [(+/-)DOI]. The 5-HT reuptake inhibitors, fluoxetine and clomipramine, also inhibited the SWD generation. In addition, the inhibitory effects of (+/-)8-OH-DPAT and (+/-)DOI were reversed by WAY-100135 (5-HT(1A) antagonist) and ritanserin (5-HT(2) antagonist), respectively. The present results suggest that the serotonergic system negatively regulates the incidence of absence seizures by stimulation of 5-HT(1A) and 5-HT(2) receptors. PMID- 20736509 TI - Multidrug resistance protein transporter and Ins(1,4,5)P3-sensitive Ca2+ signaling involved in adenosine triphosphate export via Gq protein-coupled NK2 receptor stimulation with neurokinin A. AB - The purpose of this study is to identify the membrane transport machinery and cell signaling involved in the neurokinin A-inducible release of adenosine triphosphate (ATP) as an autocrine/paracrine signal from cultured guinea-pig taenia coli (T. coli) smooth muscle cells (SMCs). ATP release evoked by neurokinin A was inhibited by L-659877, a NK(2)-receptor antagonist; by modulators for Ins(1,4,5)P(3)-sensitive Ca(2+)-signaling, U-73122, thapsigargin, and 2-APB; and by W-7, a calmodulin inhibitor, and staurosporine, a protein kinase C (PKC) inhibitor, but not by wortmannin, a phosphoinositide 3-kinase inhibitor. The evoked release was suppressed by a multidrug resistance protein (MRP)-transporter inhibitors, MK-571, indomethacin, and benzbromarone, but not by CFTR-inh 172, a CFTR-Cl(-) channel blocker, and alpha-glycyrrhetinic acid, a gap junction hemichannel blocker. Neurokinin A caused a marked accumulation of Ins(1,4,5)P(3) and an increase in [Ca(2+)](i) in the cultured cells. These findings suggest that stimulation of Gq/(11) protein-coupled NK(2) receptor with neurokinin A caused a substantial release of ATP from cultured T. coli SMCs and that the evoked release may be mediated by Ins(1,4,5)P(3)-sensitive Ca(2+) signaling, further by PKC and Ca(2+)/calmodulin signals, and finally by an activation of MRP transporters as the membrane device. PMID- 20736510 TI - Roles of beta- and alpha2-adrenoceptors within the central nucleus of the amygdala in the visceral pain-induced aversion in rats. AB - We investigated the roles of beta- and alpha(2)-adrenoceptors within the central nucleus of the amygdala (CeA) in the negative affective and sensory components of visceral pain in rats. We observed a dose-dependent reduction of intraperitoneal acetic acid-induced conditioned place aversion by bilateral injections of timolol, a beta-adrenoceptor antagonist, or clonidine, an alpha(2)-adrenoceptor agonist, without reducing writhing behaviors. These data suggest a pivotal role of intra-CeA adrenoceptors in the negative affective, but not sensory, component of visceral pain. PMID- 20736511 TI - Concentration-dependent inhibitory effect of irbesartan on renal uric acid transporters. AB - Hyperuricemia is currently recognized as a risk factor for cardiovascular diseases. It has been reported that the angiotensin II-receptor blocker (ARB) losartan decreases serum uric acid level. In this study, the effects of another ARB, irbesartan, on [(14)C]uric acid-transport activity of renal uric acid reabsorptive transporters URAT1 and URATv1 were examined with Xenopus oocytes expressing each transporter. The results showed that irbesartan (100-500 uM) inhibited the uptake of uric acid via both transporters. The inhibitory effects of irbesartan exceeded those of losartan and other ARBs, and the results suggest that irbesartan can reduce serum uric acid level. PMID- 20736512 TI - Phenoxazine derivatives suppress the infections caused by herpes simplex virus type-1 and herpes simplex virus type-2 intravaginally inoculated into mice. AB - We examined the in vivo antiviral activities of 2-amino-4,4alpha-dihydro-4alpha-7 dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4alpha-dihydro-4alpha-8-dimethyl 2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) against herpes viruses. The virus yield three days after administration, changes in the 6 degree's lesion scores, and the morbidity were assessed after herpes simplex virus type-1 (HSV-1) [acyclovir (ACV)-sensitive KOS strain or ACV-resistant A4-3 strain] or HSV-2 (ACV-sensitive UW 268 strain) was inoculated intravaginally to mice with administration of Phx-1, Phx-2, Phx-3, or ACV (0.2 mg per administration, 3 times daily) for 8 days starting from 1 day before virus inoculation to 7 days after infection. Phx-1, Phx-2, and Phx-3 extensively suppressed the virus yield of HSV-1. Only Phx-2 exerted moderate inhibitory effects against HSV-2 in mice. The lesion scores, as clinical signs manifested by infection of the KOS strain of HSV-1, were extensively suppressed by intravaginal application of Phx-1, Phx-2, or Phx-3. The lesion scores in HSV-2-infected mice indicated moderate suppression, when Phx-1, Phx-2, or Phx-3 was applied. Without treatment by one of the compounds, none of the HSV-1-infected mice died, but all the HSV-2-infected ones did. However, by the administration of Phx-1, Phx-2, or Phx-3 fairly improved the survival rates of the HSV-2-infected mice. Phx-2 showed dose-dependent anti-HSV-2 efficacy when administered at doses of 0.2 and 1 mg per administration. The present in vivo data suggest that the Phx-1, Phx-2, and Phx-3 are attractive candidates for agents to prevent both replication of HSV and aggravation of lesions caused by these viruses. PMID- 20736513 TI - Analysis of the fusion protein gene of Newcastle disease viruses isolated in Japan. AB - The complete nucleotide sequences of the fusion (F) protein gene of Newcastle disease viruses (NDV) isolated in Japan from 1930 to 2007 (45 strains total) were determined and genetically analyzed. In the deduced amino acid sequences of fusion protein, the 5 potential asparagine-linked glycosylation sites and 10 cysteine residues were all conserved in the NDV examined in this study. The major epitopes involved in virus neutralization are conserved in most of the NDV strains isolated in Japan except a few strains. By virus neutralization test, no major antigenic differences were observed among representative strains of each genotype in Japan. All chickens vaccinated with the B1 strain survived without clinical signs after challenge with 2 NDV strains isolated in Japan (velogenic strains, JP/Ibaraki/2000 and JP/Kagoshima/91), which possess amino acids substitutions involved in virus neutralization in the F protein gene. PMID- 20736514 TI - Experimental infection of bovine mammary gland with prototheca zopfii genotype 1. AB - Prototheca zopfii is divided into three genotypes, one of which, P. zopfii genotype 2, appears to be the main causative agent of bovine protothecal mastitis. However, the difference in pathogenicity between genotypes 1 and 2 has not been well investigated. In the present study, we experimentally infected normal bovine mammary gland with P. zopfii genotype 1 to investigate its pathogenicity. The mammary gland infected with P. zopfii genotype 1 showed no clinical signs. However, the histopathologic features of the infected mammary gland consisted of interstitial infiltrates of macrophages, plasma cells, lymphocytes, and fibroblasts with neutrophils in acinar lumens. Algae were present in macrophages and free in the alveolar lumens and the interstitium. Histopathology of the resultant tissue samples revealed that genotype 1 also induced a granulomatous lesion in the cow teat, similar to the mastitis lesion due to genotype 2. PMID- 20736515 TI - Use of contrast-enhanced CT in the diagnosis of abscesses in cattle. AB - We report here the non-contrast and contrast-enhanced computed tomography performed in two calves with brain abscess and multiple pulmonary abscesses with pharyngeal abscess, respectively. Contrast-enhanced computed tomography was useful in the diagnosis of these diseases in both calves. The diseases were confirmed by histopathological examination. PMID- 20736516 TI - Prekallikrein deficiency in a dog. AB - Prekallikrein (PK) deficiency is an uncommon disorder in dogs. In this report, we describe a case of a dog that was referred for neurological defects and had a prolonged activated partial thromboplastin time (aPTT) and normal prothrombin time (PT) with no hemostatic defects. By using human PK-deficient plasma, the dog was diagnosed to have PK deficiency. The nucleotide sequence of normal canine PK cDNA was determined and compared with the genomic sequences of PK in the affected dog. The comparison revealed that the dog had a point mutation in exon 8 that leads to an amino acid substitution in the fourth apple domain of PK. This is the first report showing a point mutation of PK in a dog with PK deficiency. PMID- 20736517 TI - Analysis of Syk expression in bovine lymphoma and persistent lymphocytosis induced by bovine leukemia virus. AB - Spleen tyrosine kinase (Syk) is closely related to various cell reactions. In B cells, Syk is involved in early B-cell receptor signaling, which affects cellular survival, proliferation and differentiation. Although the kinetics of Syk mRNA and its activity are variable in different types of tumor cells, Syk may have a relation to tumor progression in many human tumors, including B-cell lymphoma/leukemia. In this study we examined whether Syk mRNA expression was changed in bovine leukemia virus (BLV)-induced persistent lymphocytosis (PL) and lymphoma. As a result, we demonstrated that the Syk mRNA expression was significantly increased in PL samples, whereas it was decreased in tumor samples. Moreover one cow, which Syk mRNA expression has been lowest among PL cattle, developed lymphoma three months later and the expression significantly decreased. These data suggest that Syk mRNA expression dynamics is closely related to BLV induced disease. PMID- 20736518 TI - Antimicrobial susceptibility of Bordetella bronchiseptica isolates from pigs with respiratory diseases on farms in China. AB - One hundred and 63 Bordetella bronchiseptica isolates from pigs, consisting of 65 isolated in 2003 and 98 isolated in 2007, were tested for antimicrobial susceptibility to 17 antimicrobial agents by the disk diffusion method. All 163 B. bronchiseptica isolates were sensitive to polymyxin B and cefoperazone/sulbactam; the majority of the strains were sensitive to amikacin (149/163; 91.4%), gentamicin (132/163; 81.0%), ampicillin/sulbactam (127/163; 77.9%) and ciprofloxacin (115/163; 70.6%). A high level of resistance was found for furazolidone (100%), ampicillin (90.2%), cefazolin (89.0%), streptomycin (87.7%), amoxicillin/clavulanic acid (74.2%) and tetracycline (64.4%). Comparison of the data revealed that isolates with multiresistance to at least six or eight of the 17 antimicrobials used became more frequent, with the proportions increasing from 32.3% or 16.9% in 2003 to 90.8% or 41.8% in 2007. PMID- 20736519 TI - Central diabetes insipidus after transsphenoidal surgery in dogs with Cushing's disease. AB - Transsphenoidal surgery (TSS) is an effective treatment for canine Cushing's disease, as well as human Cushing's disease. In humans, only the pituitary adenoma tissue is resected by TSS. However, in dogs, the whole pituitary including normal tissue is resected. Hence, central diabetes insipidus (CDI) may complicate the postoperative course in almost all dogs with Cushing's disease treated by TSS. However, it is difficult to assess the duration of the postoperative CDI, and whether it may be transient or permanent. In this study, postoperative CDI in 21 dogs with Cushing's disease and its predicted prognosis by preoperative parameters was investigated. In this study, CDI after TSS was classified as either transient or permanent based on the requirement for desmopressin. Preoperative circulating serum cortisol concentrations and pre- and post-operative plasma AVP concentrations were not significantly different between the transient CDI dogs and permanent CDI dogs. The duration of postoperative CDI was not correlated to the signal intensity ratio (posterior lobe of the pituitary/cerebral cortex), which is obtained from preoperative magnetic resonance imaging (MRI). However, the pituitary height/brain area (P/B) ratio of the permanent CDI dogs was significantly greater than that of the transient CDI dogs. In addition, there was a significant difference between the enlarged pituitary (P/B ratio > 0.31) transient CDI dogs and the permanent CDI dogs. These results suggest that the incidence of postoperative permanent CDI is strongly influenced by the pituitary size. PMID- 20736520 TI - Comparative pharmacokinetics and metabolisms of caffeine in sheep breeds. AB - The purpose of this study was to investigate the effect of breed on the pharmacokinetics and metabolism of caffeine (CF) and the hepatic metabolic capacity in sheep. CF was administered as a single intravenous dose of 5 mg/kg b.w. in Morkaraman (MK), Akkaraman (AK) and Anatolia Merino (AM) sheep breeds. The plasma levels of CF and its primary metabolites, theobromine (TB), paraxanthine (PX) and theophylline (TP), were measured using high-performance liquid chromatography. Pharmacokinetic parameters of CF and its metabolites were calculated. Plasma TB+PX+TP/CF metabolic ratio was determined as an alternative to CF clearance for the determination of hepatic metabolic capacity. In the three breeds, all kinetic parameters of CF differed significantly (P<0.05) except for volume of distribution. Elimination of CF was slow in the MK (Cl(T); 0.03 +/- 0.01 l hr/kg, t(1/2lambdaz); 15.74 +/- 7.35 hr) and AM (Cl(T); 0.05 +/- 0.02 l hr/kg, t(1/2lambdaz); 9.68 +/- 5.21 hr) breeds when compared with the AK breed (Cl(T); 0.08 +/- 0.01 l hr/kg, t(1/2lambdaz); 6.84 +/- 0.79 hr). There was significant correlation (r(2)=0.904, P<0.01) between CF clearance and the plasma TB+PX+TP/CF ratio calculated at 7 hr after CF administration. The plasma TB+PX+TP/CF ratios were statistically different (P<0.05) among the breeds (MK, 0.155 +/- 0.062; AK, 0.468 +/- 0.107; AM, 0.254 +/- 0.099). These results suggest that the pattern of drug biotransformation should be consistently tested for all breeds within species. Further studies are needed to determine the biochemical and molecular events underlying such an effect. PMID- 20736521 TI - Ultrasound imaging of mammary glands in dairy heifers at different stages of growth. AB - To obtain B-mode ultrasound images of mammary glands in dairy heifers at different stages of growth, 25 clinically normal Holstein heifers were used. The heifers were divided into 5 groups (n=5/group) by stage of their growth: 2-month old (group 1), 5-month-old (group 2), postpuberty (group 3), mid (group 4), and late (group 5) pregnancy. Furthermore, the sections of mammary glands were observed grossly at postmortem examination in one heifer in each group. Ultrasound images varied with the development of mammary glands. In group 1, the mammary glands had distinctive ultrasonographic findings: an oval to fusiform homogeneous hypoechoic structure. In all groups except group 1, mammary tissue consists of two major areas: a homogeneous, medium echogenic area and a poorly defined, heterogeneous, hypoechoic area mostly in the superficial part. The superficial hypoechoic area spread more extensively and more irregularly with the development of mammary glands. Most pregnant heifers had irregular and extremely hypoechoic or anechoic areas like lactiferous sinus in the glands. The gross findings of mammary glands suggested that the hypoechoic areas of various shapes represented the lactiferous sinus and ducts. Thus, these results indicate that B mode ultrasound imaging can visualize the internal structures of udders and could be a useful tool for evaluation of mammary glands in heifers. PMID- 20736522 TI - In their own words: Interviews with Cell Cycle. Dr. Jiri Bartek on his highly cited paper published in Cell Cycle. PMID- 20736523 TI - A snapshot of medical student education in the United States and Canada: reports from 128 schools. Foreword. PMID- 20736525 TI - Keck School of Medicine of the University of Southern California. PMID- 20736524 TI - Loma Linda University School of Medicine. PMID- 20736526 TI - Stanford University School of Medicine. PMID- 20736527 TI - University of Colorado Denver School of Medicine. PMID- 20736528 TI - University of Connecticut School of Medicine. PMID- 20736529 TI - Yale University School of Medicine. PMID- 20736530 TI - The George Washington University School of Medicine and Health Sciences. PMID- 20736531 TI - Georgetown University School of Medicine. PMID- 20736532 TI - Howard University College of Medicine. PMID- 20736533 TI - Florida International University Herbert Wertheim College of Medicine. PMID- 20736534 TI - Florida State University College of Medicine. PMID- 20736535 TI - University of Central Florida College of Medicine. PMID- 20736536 TI - University of Florida College of Medicine. PMID- 20736537 TI - University of Miami Leonard M. Miller School of Medicine. PMID- 20736538 TI - University of South Florida College of Medicine. PMID- 20736539 TI - Emory University School of Medicine. PMID- 20736540 TI - Medical College of Georgia. PMID- 20736541 TI - Mercer University School of Medicine. PMID- 20736542 TI - Morehouse School of Medicine. PMID- 20736543 TI - University of Hawaii at Manoa John A. Burns School of Medicine. PMID- 20736544 TI - Chicago Medical School at Rosalind Franklin University of Medicine and Science. PMID- 20736545 TI - University of Chicago Division of the Biological Sciences Pritzker School of Medicine. PMID- 20736546 TI - Abraham Flexner and the era of medical education reform. AB - Many forces, including the influential report of Abraham Flexner, acted to reform medical education in the early 20th century. Most physicians were not prepared to adopt recent advances in health care due to their poor medical training. This deficit was recognized in the 20 years before Flexner's report by several organizations, including the Illinois State Board of Health, the American Medical Association, and the Association of American Medical Colleges. Before 1910, each organization had engaged in at least one review of medical schools using defined standards and had identified many of the existing deficits. The number of medical schools already had begun to decrease, dropping from 160 in 1905 to 133 in 1910. Flexner drew heavily, but not exclusively, on the standards for medical education previously developed by other organizations. He visited 155 medical schools in the United States and Canada between December 1908 and April 1910. His 1910 report included a conceptual model of how modern medical education should be conducted and descriptions of each medical school that were explicit in both praise and censure.In the decade following the Flexner Report the number of medical schools decreased from 133 to 85. The actions of state medical licensing boards to deny recognition to poor schools sealed their fate. The remaining schools had higher entrance requirements, longer terms, and better resources. The author describes key factors that contributed to the success of the changes recommended by Flexner and others, and then posits why Flexner is still remembered. PMID- 20736547 TI - University of Illinois College of Medicine at Chicago. PMID- 20736549 TI - University of Illinois College of Medicine at Rockford. PMID- 20736548 TI - Medical education in the United States and Canada, 2010. AB - The authors present an overview of the educational programs, infrastructure to support them, and the assessment strategies of 128 medical schools in the United States and Canada, based on reports submitted by those schools and published in this supplement to Academic Medicine. The authors explore many important changes that have occurred since the publication of the Flexner Report in 1910 as well as the progress that is evident since a similar collection of medical school reports was published in September 2000, also as a supplement to Academic Medicine. Drawing on the reports, the authors summarize, among other topics, the advances that have taken place in the support for faculty, the funding of medical student education, changes in pedagogy and assessment, and the expansion of medical education to distributed models and regional campuses.The authors observe that the reports from the 128 schools illustrate that medical student education has undergone and continues to undergo substantive change, has advanced markedly since the reforms stimulated by the Flexner Report, and has continued to evolve during the past decade. The reports illustrate the strength of support for the educational programs, even in a time of financial constraints, and the increasing recognition of the scholarly contributions of faculty through teaching. The authors provide examples of the changes in pedagogy and new topics in the required curriculum in the past decade and describe selected highlights of the 128 educational programs. PMID- 20736550 TI - Loyola University Chicago Stritch School of Medicine. PMID- 20736551 TI - Northwestern University The Feinberg School of Medicine. PMID- 20736552 TI - Rush Medical College. PMID- 20736553 TI - Southern Illinois University School of Medicine. PMID- 20736554 TI - Indiana University School of Medicine (IUSM). PMID- 20736555 TI - University of Iowa Carver College of Medicine. PMID- 20736557 TI - University of Kentucky (UK) College of Medicine. PMID- 20736556 TI - University of Kansas School of Medicine. PMID- 20736558 TI - University of Louisville School of Medicine. PMID- 20736559 TI - Louisiana State University Health Sciences Center School of Medicine at New Orleans. PMID- 20736560 TI - Tulane University School of Medicine. PMID- 20736561 TI - Johns Hopkins University School of Medicine. PMID- 20736562 TI - University of Maryland School of Medicine. PMID- 20736563 TI - A decade of reports calling for change in medical education: what do they say? AB - PURPOSE: To review the recommendations of 15 U.S. and Canadian reports, published in the last decade, that call for significant change in medical education. METHOD: The author selected for review 15 reports published over the last ten years that emphasize general recommendations for change in medical education in the United States and Canada and that represent a broad spectrum of sources. RESULTS: The purpose, methods, and content of each report are briefly described. The reports were selected because they address comprehensive change in medical education and have been recently published. The reports are categorized based on their inclusion of eight major themes: integrating the educational continuum, need for evaluation and research, new methods of financing, importance of leadership, emphasis on social accountability, use of new technology in education and medical practice, alignment with changes in the health care delivery system, and future directions in the health care workforce. The author provides an overview and synthesis of these reports and reveals a number of common themes to help medical educators implement changes in medical education in the next decade and beyond. CONCLUSIONS: There is remarkable congruence in the recommendations of the 15 reports. The author proposes that the problems facing contemporary medical education have been thoroughly identified and that it is time to set forth on meaningful new paths; many hopeful possibilities exist. PMID- 20736564 TI - Uniformed Services University of the Health Sciences F. Edward Hebert School of Medicine. PMID- 20736565 TI - Boston University School of Medicine. PMID- 20736566 TI - Harvard Medical School. PMID- 20736567 TI - University of Massachusetts Medical School. PMID- 20736568 TI - Tufts University School of Medicine. PMID- 20736569 TI - Michigan State University College of Human Medicine. PMID- 20736570 TI - University of Michigan Medical School. PMID- 20736571 TI - Wayne State University School of Medicine. PMID- 20736572 TI - Mayo Medical School. PMID- 20736573 TI - University of Minnesota Medical School. PMID- 20736574 TI - University of Missouri School of Medicine in Columbia. PMID- 20736575 TI - University of Missouri-Kansas City School of Medicine. PMID- 20736576 TI - Saint Louis University School of Medicine. PMID- 20736577 TI - Washington University in St. Louis School of Medicine. PMID- 20736578 TI - Creighton University School of Medicine. PMID- 20736579 TI - University of Nebraska College of Medicine. PMID- 20736580 TI - University of Nevada School of Medicine. PMID- 20736581 TI - Dartmouth Medical School. PMID- 20736582 TI - A tea-steeping or i-Doc model for medical education? AB - One hundred years after Abraham Flexner released his report Medical Education in the United States and Canada, the spirit of reform is alive again. Reports in the United States and Canada have called for significant changes to medical education that will allow doctors to adapt to complex environments, work in teams, and meet a wide range of social needs. These reports call for clear educational outcomes but also for a flexible, individualized approach to learning. Whether or not change will result has much to do with the alignment between what is proposed and the nature of current societal discourses about how medical education should be conducted. Currently, two powerful and competing models of competence development are operating at odds with one another. The traditional one is time-based (a "tea steeping" model, in which the student "steeps" in an educational program for a historically determined fixed time period to become a successful practitioner). This model directs attention to processes such as admission and curriculum design. The newer one is outcomes-based (an "i-Doc" model, a name suggested by the Apple i-Pod that infers that medical schools and residencies, like factories, can produce highly desirable products adapted to user needs and desires). This model focuses more on the functional capabilities of the end product (the graduate student, resident, or practicing physician). The author explores the implications of both time-based and outcomes-based models for medical education reform and proposes an integration of their best features. PMID- 20736583 TI - University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School. PMID- 20736584 TI - University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School. PMID- 20736585 TI - University of New Mexico School of Medicine. PMID- 20736586 TI - Albany Medical College. PMID- 20736587 TI - Albert Einstein College of Medicine of Yeshiva University. PMID- 20736588 TI - Columbia University College of Physicians and Surgeons. PMID- 20736589 TI - Mount Sinai School of Medicine. PMID- 20736590 TI - New York Medical College. PMID- 20736591 TI - New York University School of Medicine. PMID- 20736592 TI - University at Buffalo, School of Medicine and Biomedical Sciences, State University of New York. PMID- 20736593 TI - The University of Rochester School of Medicine and Dentistry. PMID- 20736594 TI - State University of New York, Downstate Medical Center College of Medicine. PMID- 20736595 TI - State University of New York Upstate Medical University College of Medicine. PMID- 20736596 TI - State University of New York, Stony Brook University Medical Center. PMID- 20736597 TI - Weill Cornell Medical College of Cornell University. PMID- 20736598 TI - Duke University School of Medicine. PMID- 20736599 TI - Brody School of Medicine, East Carolina University. PMID- 20736600 TI - The University of North Carolina at Chapel Hill School of Medicine. PMID- 20736601 TI - Wake Forest University School of Medicine. PMID- 20736602 TI - University of North Dakota School of Medicine and Health Sciences. PMID- 20736603 TI - Case Western Reserve University School of Medicine and Cleveland Clinic. PMID- 20736604 TI - Northeastern Ohio Universities College of Medicine. PMID- 20736605 TI - The 21st century faculty member in the educational process--what should be on the horizon? AB - One of Abraham Flexner's legacies was the concept of a professional faculty community responsible for teaching, scholarly work, and the creation and nurturing of the academic environment in medical schools. Dramatic shifts in society, health care, and educational practice have occurred over the century since Flexner's report, and these shifts have resulted in changes and challenges for medical school faculty. Fundamental principles that were articulated in Flexner's work remain relevant today: medicine is a profession, and as such is responsible for the education of the next generation of physicians; and the essential work of the medical school is the education of current and future generations of physicians. Medical schools must reconsider and restate the required characteristics and work of faculty members. Furthermore, we must develop a core faculty with primary responsibility for the educational program, the teaching of students, and the creation and nurturing of the academic environment. Enhancing the diversity of the faculty community, providing necessary faculty development, and further clarifying the forms of scholarly work in medicine are three ways that individual schools and national organizations can advance the educational mission through support of the faculty. PMID- 20736606 TI - The Ohio State University College of Medicine. PMID- 20736607 TI - University of Toledo College of Medicine. PMID- 20736608 TI - University of Cincinnati College of Medicine. PMID- 20736609 TI - Wright State University Boonshoft School of Medicine. PMID- 20736610 TI - University of Oklahoma College of Medicine. PMID- 20736611 TI - Oregon Health & Science University School of Medicine. PMID- 20736612 TI - Drexel University College of Medicine. PMID- 20736613 TI - Jefferson Medical College of Thomas Jefferson University. PMID- 20736614 TI - The Pennsylvania State University College of Medicine. PMID- 20736615 TI - University of Pennsylvania School of Medicine. PMID- 20736616 TI - University of Pittsburgh School of Medicine. PMID- 20736617 TI - Temple University School of Medicine. PMID- 20736618 TI - The Commonwealth Medical College. PMID- 20736619 TI - Universidad Central del Caribe School of Medicine. PMID- 20736620 TI - Ponce School of Medicine. PMID- 20736621 TI - The Warren Alpert Medical School of Brown University. PMID- 20736622 TI - Medical University of South Carolina College of Medicine. PMID- 20736623 TI - University of South Carolina School of Medicine. PMID- 20736624 TI - East Tennessee State University James H. Quillen College of Medicine. PMID- 20736625 TI - University of Tennessee Health Science Center, College of Medicine. PMID- 20736626 TI - Vanderbilt University School of Medicine. PMID- 20736627 TI - Baylor College of Medicine. PMID- 20736628 TI - Texas Tech University Health Sciences Center School of Medicine. PMID- 20736629 TI - Texas Tech University Health Sciences Center Paul L. Foster School of Medicine. PMID- 20736630 TI - University of Texas Medical Branch School of Medicine. PMID- 20736631 TI - Preparing medical students for the continual improvement of health and health care: Abraham Flexner and the new "public interest". AB - In 1910, in his recommendations for reforming medical education, Abraham Flexner responded to what he deemed to be the "public interest." Now, 100 years later, to respond to the current needs of society, the education of physicians must once again change. In addition to understanding the biological basis of health and disease, and mastering technical skills for treating individual patients, physicians will need to learn to navigate in and continually improve complex systems in order to improve the health of the patients and communities they serve. Physicians should not be mere participants in, much less victims of, such systems. Instead, they ought to be prepared to help lead those systems toward ever-higher-quality care for all. A number of innovative programs already exist for students and residents to help integrate improvement skills into professional preparation, and that goal is enjoying increasing support from major professional organizations and accrediting bodies. These experiences have shown that medical schools and residency programs will need to both teach the scientific foundations of system performance and provide opportunities for trainees to participate in team-based improvement of the real-world health systems in which they work. This significant curricular change, to meet the social need of the 21st century, will require educators and learners to embrace new core values, in addition to those held by the profession for generations. These include patient-centeredness, transparency, and stewardship of limited societal resources for health care. PMID- 20736632 TI - The University of Texas Medical School at Houston. PMID- 20736633 TI - University of Texas Health Science Center at San Antonio School of Medicine. PMID- 20736634 TI - University of Utah School of Medicine. PMID- 20736635 TI - University of Vermont College of Medicine. PMID- 20736636 TI - Virginia Commonwealth University School of Medicine. PMID- 20736637 TI - Virginia Tech Carilion School of Medicine and Research Institute. PMID- 20736638 TI - University of Virginia School of Medicine. PMID- 20736639 TI - University of Washington School of Medicine. PMID- 20736640 TI - West Virginia University School of Medicine. PMID- 20736641 TI - Medical College of Wisconsin. PMID- 20736642 TI - University of Wisconsin School of Medicine and Public Health. PMID- 20736643 TI - University of Calgary Faculty of Medicine. PMID- 20736644 TI - University of British Columbia Faculty of Medicine. PMID- 20736645 TI - Dalhousie University, Faculty of Medicine. PMID- 20736646 TI - Michael G. DeGroote School of Medicine Faculty of Health Sciences, McMaster University. PMID- 20736647 TI - Northern Ontario School of Medicine. PMID- 20736648 TI - University of Ottawa Faculty of Medicine. PMID- 20736649 TI - University of Toronto, Faculty of Medicine. PMID- 20736650 TI - McGill University Faculty of Medicine. PMID- 20736651 TI - Definitions and explanations of selected terms used in this supplement. PMID- 20736652 TI - University of Alabama School of Medicine. PMID- 20736653 TI - University of South Alabama College of Medicine. PMID- 20736654 TI - University of Arizona College of Medicine: Tucson and Phoenix. PMID- 20736655 TI - University of Arkansas for Medical Sciences College of Medicine. PMID- 20736656 TI - David Geffen School of Medicine at UCLA. PMID- 20736657 TI - The University of California, San Diego, School of Medicine. PMID- 20736658 TI - University of California, San Francisco, School of Medicine. PMID- 20736659 TI - An open letter to new medical students. PMID- 20736660 TI - Patient safety education: overreported and still lacking. PMID- 20736662 TI - An ethical imperative to use reprocessed medical equipment. PMID- 20736663 TI - Medical students need educators from a variety of backgrounds. PMID- 20736665 TI - Commentary: watching closely at a distance: key tensions in supervising resident physicians. AB - Graded responsibility and autonomy are integral features of medical education. High-quality patient care is paramount and is the ultimate responsibility of the attending physician. In the training setting, the teaching attending holds quality of care constant while balancing the amount of supervision and autonomy he or she gives the learner. Sterkenburg and colleagues focus on how faculty members make their decisions to entrust patient care to learners. Both this critical decision and the process of deciding, performed many times a day by teaching faculty, are at the heart of the confluence of providing quality patient care and developing the next generation of physicians. Sterkenburg and colleagues innovatively use a system of rating (with six sequentially more complex entrustable professional activities [EPAs]) and structured interviews to better understand the current practice of entrusting care. They defined gaps between when attending faculty feel residents are ready to perform a particular EPA, when the residents feel ready, and when the residents actually perform it. The tension between the imperative to ensure quality care and the competing imperative to grant graded autonomy can be described as "watching closely at a distance." The details of who should watch whom, when and what to watch, and how and how much to watch are all key issues for faculty and residents. Sterkenburg and colleagues provide a framework for further investigation (e.g., discerning the ideal level of supervision, developing a gold standard for assessing EPAs) into these critical medical education challenges. PMID- 20736666 TI - Commentary: what if high-quality care drove medical education? A multiattribute approach. AB - The current medical education model is based on the assumption that students progress from a mastery of basic mechanisms of human structure and function to an understanding of a variety of pathologies and treatments using sound scientific principles. In this commentary, the authors suggest another approach to developing medical school curricula. Starting with the major desired outcome of medical education, which they suggest should be high-quality medical care, educators can work backward using the attributes of quality as the basis for developing new medical curricula. The authors present, as an example, the Institute of Medicine definition of quality care--care that is safe, timely, effective, efficient, equitable, and patient-centered. These objectives and their attributes then can be useful for mapping current and future curricula in medical education and identifying deficits or possible excesses. A result of this approach might be the inclusion of such topics as epidemiology, process engineering, or aspects of the humanities or social sciences that build skills and knowledge in patient-centered care or safety while maintaining a balance with the need to preserve biomedical topics. Use of quality objectives and attributes to drive medical education should lead to improved alignment of the clinical and educational missions of academic medical centers, which, in turn, should lead to safer and higher quality care for patients. PMID- 20736667 TI - Artist's statement: Woe. PMID- 20736668 TI - Commentary: the role of mentored internships for systems engineering in improving health care delivery. AB - The authors advise the adoption of mentored internships in systems engineering, conducted at academic hospitals, directed by physicians, epidemiologists, and health administrators and overseen by faculty at attendant schools of engineering. Such internships are anticipated to directly address the immediate objectives of administrators and clinicians. Additionally, this affords future generations of health care engineers the opportunity to learn the language and methodology of the medical sciences to provide a common ground for the analysis and understanding of medical systems. In turn, this should foster collaboration between the principal stakeholders in health care delivery--practitioners, administrators, engineers, and researchers--in the collective efforts to improve the quality of services provided. PMID- 20736669 TI - When do supervising physicians decide to entrust residents with unsupervised tasks? AB - PURPOSE: Patient-care responsibilities stimulate trainee learning but training may compromise patient safety. The authors investigated factors guiding clinical supervisors' decisions to trust residents with critical patient-care tasks. METHOD: In a mixed quantitative and qualitative descriptive study carried out at University Medical Center Utrecht, Utrecht, the Netherlands, from March to September 2008, the authors surveyed attending anesthetists and resident anesthetists regarding when attendings should entrust each of six selected critical tasks to residents. The authors conducted structured interviews with both groups, using trigger case vignettes to solicit opinions on factors that affect entrustment decisions. RESULTS: Thirty-two attending anesthetists and 31 residents answered the questionnaire (response rate 58%), and 10 participants from each group were interviewed. Attendings varied in their opinions regarding how much independence to give residents, particularly postgraduate year (PGY) 2, 3, and 4 residents. PGY1 residents reported working above their expected level of competence but estimate their own ability as sufficient, whereas PGY5 residents reported working below their expected level of competence. The authors classified factors that determine entrustment into four groups: characteristics of the resident, the attending, the clinical context, and the critical task. CONCLUSIONS: Residents' and attendings' opinions and impressions differ regarding what is expected from residents, what residents actually do, and what residents think they can do safely. The authors list factors affecting why and when supervisors trust residents to proceed without supervision. Future studies should address drivers behind entrustment decisions, correlations with patient outcomes, and tools that enable faculty to justify their entrustment decisions. PMID- 20736670 TI - Improving resident education and patient safety: a method to balance initial caseloads at academic year-end transfer. AB - PURPOSE: In outpatient continuity clinics, incoming trainees may receive caseloads that are unbalanced in terms of the mental workload required from each resident. When significant, these imbalances may compromise resident learning and patient safety. Using data from psychiatric outpatient continuity clinics, this study tested a method for balancing initial caseloads. METHOD: Adapting prior research on mental workload, the authors developed and implemented a workload balancing method to balance initial caseloads regarding factors contributing to mental workload: number of patients, number of acute patients, complexity/time demands outside clinic, visits per month, and collaboration demands. For academic years 2006-2007, 2007-2008, 2008-2009, and 2009-2010, they compared these balanced caseloads with those that would have been created by the clinic's traditional method of largely preserving prior caseloads (with some redistribution to balance only the number of patients). The outcome measure was the intercaseload coefficient of variation for each of the chosen mental workload factors and for all factors combined. RESULTS: Compared with the traditional method, the workload-balancing method generated lower intercaseload variation for each mental workload factor. Also, this method reduced overall intercaseload variation for all factors combined by 50% to 61% in each of the intervention years. CONCLUSIONS: The workload-balancing method evenly distributes among resident panels factors known to contribute to mental workload. This method may reduce errors and stress likely to occur when residents inherit unbalanced caseloads that are overly challenging and, thus, may improve patient safety and resident learning. This model could be applicable to other caseload situations. PMID- 20736671 TI - Taking note of the perceived value and impact of medical student chart documentation on education and patient care. AB - PURPOSE: To determine the extent of restrictions to medical student documentation in patients' records and the opinions of medical education leaders about such restrictions' impact on medical student education and patient care. METHOD: Education deans (n = 126) of medical schools in the United States and Canada were surveyed to determine policies regarding placement of medical student notes in the patient record, the value of medical students' documentation in the medical record, and the use of electronic medical records (EMRs) for patient notes. The instrument was a 23-item anonymous Web survey. RESULTS: Seventy-nine deans responded. Over 90% believed student notes belong in medical records, but only 42% had a policy regarding this. Ninety-three percent indicated that without student notes, student education would be negatively affected. Fewer (56%) indicated that patient care would be negatively affected. Most thought limiting students' notes would negatively affect several other issues: feeling a part of the team (96%), preparation for internship (95%), and students' sense of involvement (94%). Half (52%) reported that fourth-year students could place notes in paper charts at "all" affiliated hospitals, and 6% reported that fourth year students could do so at "no" hospitals. CONCLUSIONS: Although students' ability to enter notes in patients' records is believed to be important for student education, only about half of all hospitals allow all students' notes in the EMR. Policies regarding placement of student notes should be implemented to ensure students' competency in note writing and their value as members of the patient care team. PMID- 20736672 TI - Does perspective-taking increase patient satisfaction in medical encounters? AB - PURPOSE: To assess whether perspective-taking, which researchers in other fields have shown to induce empathy, improves patient satisfaction in encounters between student-clinicians and standardized patients (SPs). METHOD: In three studies, randomly assigned students (N = 608) received either a perspective-taking instruction or a neutral instruction prior to a clinical skills examination in 2006-2007. SP satisfaction was the main outcome in all three studies. Study 1 involved 245 third-year medical students from two universities. Studies 2 and 3 extended Study 1 to examine generalizability across student and SP subpopulations. Study 2 (105 physician assistant students, one university) explored the effect of perspective-taking on African American SPs' satisfaction. Study 3 (258 third-year medical students, two universities) examined the intervention's effect on students with high and low baseline perspective-taking tendencies. RESULTS: Intervention students outscored controls in patient satisfaction in all studies: Study 1: P = .01, standardized effect size = 0.16; Study 2: P = .001, standardized effect size = 0.31; Study 3: P = .009, standardized effect size = 0.13. In Study 2, perspective-taking improved African American SPs' satisfaction. In Study 3, intervention students with high baseline perspective-taking tendencies outscored controls (P = .0004, standardized effect size = 0.25), whereas those with low perspective-taking tendencies did not (P = .72, standardized effect size = 0.00). CONCLUSIONS: Perspective-taking increased patient satisfaction in all three studies, across medical schools, clinical disciplines, and racially diverse students and SPs. Perspective-taking as a means for improving patient satisfaction deserves further exploration in clinical training and practice. PMID- 20736673 TI - Constructing a validity argument for the mini-Clinical Evaluation Exercise: a review of the research. AB - PURPOSE: The mini-Clinical Evaluation Exercise (mCEX) is increasingly being used to assess the clinical skills of medical trainees. Existing mCEX research has typically focused on isolated aspects of the instrument's reliability and validity. A more thorough validity analysis is necessary to inform use of the mCEX, particularly in light of increased interest in high-stakes applications of the methodology. METHOD: Kane's (2006) validity framework, in which a structured argument is developed to support the intended interpretation(s) of assessment results, was used to evaluate mCEX research published from 1995 to 2009. In this framework, evidence to support the argument is divided into four components (scoring, generalization, extrapolation, and interpretation/decision), each of which relates to different features of the assessment or resulting scores. The strength and limitations of the reviewed research were identified in relation to these components, and the findings were synthesized to highlight overall strengths and weaknesses of existing mCEX research. RESULTS: The scoring component yielded the most concerns relating to the validity of mCEX score interpretations. More research is needed to determine whether scoring-related issues, such as leniency error and high interitem correlations, limit the utility of the mCEX for providing feedback to trainees. Evidence within the generalization and extrapolation components is generally supportive of the validity of mCEX score interpretations. CONCLUSIONS: Careful evaluation of the circumstances of mCEX assessment will help to improve the quality of the resulting information. Future research should address issues of rater selection, training, and monitoring which can impact rating accuracy. PMID- 20736674 TI - Simulation training in central venous catheter insertion: improved performance in clinical practice. AB - PURPOSE: To determine whether simulation training of ultrasound (US)-guided central venous catheter (CVC) insertion skills on a partial task trainer improves cannulation and insertion success rates in clinical practice. METHOD: This prospective, randomized, controlled, single-blind study of first- and second-year residents occurred at a tertiary care teaching hospital from January 2007 to September 2008. The intervention group (n = 90) received a didactic and hands-on, competency-based simulation training course in US-guided CVC insertion, whereas the control group (n = 95) received training through a traditional, bedside apprenticeship model. Success at first cannulation and successful CVC insertion served as the primary outcomes. Secondary outcomes included reduction in technical errors and decreased mechanical complications. RESULTS: Blinded independent raters observed 495 CVC insertions by 115 residents over a 21-month period. Successful first cannulation occurred in 51% of the intervention group versus 37% of the control group (P = .03). CVC insertion success occurred for 78% of the intervention group versus 67% of the control group (P = .02). Simulation training was independently and significantly associated with success at first cannulation (odds ratio: 1.7; 95% confidence interval: 1.1-2.8) and with successful CVC insertion (odds ratio: 1.7; 95% confidence interval: 1.1-2.8)- both independent of US use, patient comorbidities, or resident specialty. No significant differences related to technical errors or mechanical complications existed between the two groups. CONCLUSIONS: Simulation training was associated with improved in-hospital performance of CVC insertion. Procedural simulation was associated with improved residents' skills and was more effective than traditional training. PMID- 20736676 TI - Medicine and the arts. Poetry by Pablo Neruda. Commentary. PMID- 20736675 TI - Moral controversy, directive counsel, and the doctor's role: findings from a national survey of obstetrician-gynecologists. AB - PURPOSE: To explore physicians' attitudes toward providing directive counsel when dealing with morally controversial medical decisions, and to examine associations between physicians' opinions and their demographic and religious characteristics. METHOD: In 2008-2009, the authors mailed a survey to a stratified, random sample of 1,800 U.S. obstetrician-gynecologists. They asked participants whether, when dealing with either typical or morally controversial medical decisions, "a physician should encourage patients to make the decision that the physician believes is best." RESULTS: Among eligible physicians, the response rate was 66%. Fifty-four percent of respondents rejected the use of directive counsel for typical medical decisions; 78% did so for morally controversial medical decisions. Physicians were less likely to refrain from directive counsel for typical medical decisions if they were older and foreign-born but more likely to refrain from directive counsel if they were more theologically pluralistic. Theological pluralism was the only characteristic significantly associated with refraining from directive counsel for morally controversial medical decisions. CONCLUSIONS: Providing nondirective counsel to their patients appears to have become the norm among certain obstetrician-gynecologists in the United States, particularly when dealing with morally controversial medical decisions. These physicians tend to be female, younger, U.S.-born, and more theologically pluralistic. Shifts toward refraining from directive counsel seem to relate to shifts in physicians' demographic, cultural, and religious characteristics. PMID- 20736678 TI - The impact of repeat information on examinee performance for a large-scale standardized-patient examination. AB - PURPOSE: The United States Medical Licensing Examination series Step 2 Clinical Skills (CS) examination is a high-stakes performance assessment that uses standardized patients (SPs) to assess the clinical skills of physicians. Each Step 2 CS examination form involves 12 SPs, each of whom portrays a different clinical scenario or case. Examinees who fail and repeat the examination may encounter repeat information--the same SP, the same case, or the same SP portraying the same case. The goal of this study was twofold: to investigate score gains for all repeat examinees, regardless of whether they experienced repeat information, and to perform additional analyses for only those examinees who did encounter repeat information. METHOD: The dataset consisted of 3,045 Step 2 CS repeat examinees who initially tested between April 2005 and December 2007. The authors used paired t tests and analysis of variance models to assess mean score gains (first attempt versus second attempt) and to determine standardized mean differences between encounters with repeat information and those without. The authors ran each set of analyses by test score component and by examinee subgroup. RESULTS: The authors observed significant mean score increases on second attempt examinations for the entire group of repeat examinees. However, they observed no significant score increases for the subgroup of examinees who encountered repeat information. CONCLUSIONS: Examinees taking Step 2 CS for the second time improve on average, and those with prior exposure to exam information do not appear to benefit unfairly from this exposure. PMID- 20736679 TI - Is physician engagement with Web-based CME associated with patients' baseline hemoglobin A1c levels? The Rural Diabetes Online Care study. AB - PURPOSE: To investigate the association between physician participants' levels of engagement in a Web-based educational intervention and their patients' baseline diabetes measures. METHOD: The authors conducted a randomized trial of online CME activities designed to improve diabetes care provided by family, general, and internal medicine physicians in rural areas of 11 southeastern states between September 2006 and July 2008. Using incidence rate ratios derived from negative binomial models, the relationship between physicians' engagement with the study Web site and baseline proportion of their patients having controlled diabetes (hemoglobin A1c < or = 7%) was explored. RESULTS: One hundred thirty-three participants (intervention = 64; control = 69) provided information for 1,637 patients with diabetes. In the intervention group, physicians in practices in the worst quartiles of A1c control were least engaged with the study Web site in nearly all dimensions. Total number of pages viewed decreased as quartile of A1c control worsened (137, 73, 68, 57; P = .007); similarly, for a given 10% increase in proportion of patients with controlled A1c, participants viewed 1.13 times more pages (95% CI: 1.02-1.26, P = .02). In the control group, engagement was neither correlated with A1c control nor different across quartiles of A1c control. CONCLUSIONS: Engagement in Web-based interventions is measurable and has important implications for research and education. Because physicians of patients with the greatest need for improvement in A1c control may not use online educational resources as intensely as others, other strategies may be necessary to engage these physicians in professional development activities. PMID- 20736680 TI - The development of a theory-based instrument to evaluate the effectiveness of continuing medical education. AB - PURPOSE: To determine the psychometric properties of a theoretically based continuing medical education (CME) evaluation instrument examining attitudinal determinants of physicians' changes in medical practices after a CME intervention. The instrument's scales represented constructs from the theory of planned behavior. METHOD: The authors based the template instrument on educational objectives of the CME intervention and adapted it to the clinical domain of preoperative breast cancer therapy. Development of the initial survey involved cognitive testing, pilot tests, and expert reviews. The authors asked 269 clinicians to complete the 35-item instrument before the CME intervention. Factor analysis and item analysis guided the development of the final six subscales: positive behavioral beliefs, negative behavioral beliefs, attitude toward the behavior, perceived behavior control (self-efficacy), subjective norms, and behavioral intention. RESULTS: Cognitive testing and pilot tests ensured the accuracy and clarity of the language and a reasonable survey length. Of the 269 clinicians, 168 (134 physicians) responded. Scales clustered according to the theoretical constructs. Items not loading in any subscales were eliminated. The final 25 items loaded on six subscales with loadings >0.54. Reliability for the subscales ranged from 0.73 to 0.93 (good for the scale development stage). The authors revised the instrument template and protocol after this initial study to increase the possibility of use in future CME evaluations. CONCLUSIONS: The levels of content and construct validity and reliability of the CME evaluation instrument are acceptable for evaluation of CME activities targeting physicians. Instruments adapted from this template could potentially evaluate future CME activities. PMID- 20736681 TI - The flickering of a heartbeat. PMID- 20736682 TI - A gender-based analysis of work patterns, fatigue, and work/life balance among physicians in postgraduate training. AB - PURPOSE: To document fatigue in New Zealand junior doctors in hospital-based clinical training positions and identify work patterns associated with work/life balance difficulties. This workforce has had a duty limitation of 72 hours/week since 1985. The authors chose a gender-based analytical approach because of the increasing proportion of female medical graduates. METHOD: The authors mailed a confidential questionnaire to all 2,154 eligible junior doctors in 2003. The 1,412 respondents were working > or = 40 hours/week (complete questionnaires from 1,366: response rate: 63%; 49% women). For each participant, the authors calculated a multidimensional fatigue risk score based on sleep and work patterns. RESULTS: Women were more likely to report never/rarely getting enough sleep (P < .05), never/rarely waking refreshed (P < .001), and excessive sleepiness (P < .05) and were less likely to live with children up to 12 years old (P < .001). Fatigue risk scores differed by specialty but not by gender.Fatigue risk scores in the highest tertile were an independent risk factor for reporting problems in social life (odds ratio: 3.83; 95% CI: 2.79-5.28), home life (3.37; 2.43-4.67), personal relationships (2.12; 1.57-2.86), and other commitments (3.06; 2.23-4.19).Qualitative analyses indicated a common desire among men and women for better work/life balance and for part-time work, particularly in relation to parenthood. CONCLUSIONS: Limitation of duty hours alone is insufficient to manage fatigue risk and difficulties in maintaining work/life balance. These findings have implications for schedule design, professional training, and workforce planning. PMID- 20736683 TI - Nutrition education in U.S. medical schools: latest update of a national survey. AB - PURPOSE: To quantify the number of required hours of nutrition education at U.S. medical schools and the types of courses in which the instruction was offered, and to compare these results with results from previous surveys. METHOD: The authors distributed to all 127 accredited U.S. medical schools (that were matriculating students at the time of this study) a two-page online survey devised by the Nutrition in Medicine Project at the University of North Carolina at Chapel Hill. From August 2008 through July 2009, the authors asked their contacts, most of whom were nutrition educators, to report the nutrition contact hours that were required for their medical students and whether those actual hours of nutrition education occurred in a designated nutrition course, within another course, or during clinical rotations. RESULTS: Respondents from 109 (86%) of the targeted medical schools completed some part of the survey. Most schools (103/109) required some form of nutrition education. Of the 105 schools answering questions about courses and contact hours, only 26 (25%) required a dedicated nutrition course; in 2004, 32 (30%) of 106 schools did. Overall, medical students received 19.6 contact hours of nutrition instruction during their medical school careers (range: 0-70 hours); the average in 2004 was 22.3 hours. Only 28 (27%) of the 105 schools met the minimum 25 required hours set by the National Academy of Sciences; in 2004, 40 (38%) of 104 schools did so. CONCLUSIONS: The amount of nutrition education that medical students receive continues to be inadequate. PMID- 20736684 TI - AM last page. Reliability and validity in educational measurement. PMID- 20736685 TI - Dizygotic twins discordant for HIV-1 despite vertical transmission prophylaxis: was human leukocyte antigen homozygosity of disadvantage to the infected twin? PMID- 20736686 TI - Deleterious pharmacokinetic interaction between bexarotene and efavirenz. PMID- 20736687 TI - Ethics and the standards of prevention in HIV prevention trials. PMID- 20736689 TI - Another tragedy on the Gulf Coast. PMID- 20736690 TI - Nurses and the Affordable Care Act. PMID- 20736692 TI - Rapid response teams. PMID- 20736693 TI - Vital signs. PMID- 20736696 TI - Do cell phones cause cancer? PMID- 20736694 TI - Safety and physical activity. PMID- 20736698 TI - Some pressure ulcers are unavoidable. PMID- 20736699 TI - Follow-up appointments may not reduce readmission risk in all patients. PMID- 20736702 TI - Adding insult to injury: five years after Katrina. PMID- 20736703 TI - Nurse-managed health centers. PMID- 20736704 TI - Public health billboard, Guinea-Bissau. PMID- 20736708 TI - Conservative management of fecal incontinence. AB - OVERVIEW: Although fecal incontinence can be both emotionally and socially debilitating, the embarrassment associated with it is so great that it often prevents patients from seeking much needed help from their health care providers. Nursing care begins with case finding and continues through conservative management, which has greatly improved over the past 15 years. This article summarizes the strategies that have proven most effective in uncovering and combating this prevalent yet seldom acknowledged condition. KEYWORDS: : defecation, diarrhea, fecal incontinence, feces, incontinence, incontinence of stool. PMID- 20736710 TI - Evidence-based practice, step by step: critical appraisal of the evidence: part II: digging deeper--examining the "keeper" studies. AB - This is the sixth article in a series from the Arizona State University College of Nursing and Health Innovation's Center for the Advancement of Evidence-Based Practice. Evidence-based practice (EBP) is a problem-solving approach to the delivery of health care that integrates the best evidence from studies and patient care data with clinician expertise and patient preferences and values. When delivered in a context of caring and in a supportive organizational culture, the highest quality of care and best patient outcomes can be achieved. The purpose of this series is to give nurses the knowledge and skills they need to implement EBP consistently, one step at a time. Articles will appear every two months to allow you time to incorporate information as you work toward implementing EBP at your institution. Also, we've scheduled "Chat with the Authors" calls every few months to provide a direct line to the experts to help you resolve questions. Details about how to participate in the next call will be published with November's Evidence-Based Practice, Step by Step. PMID- 20736711 TI - Putting patients first: patient-centered care: more than the sum of its parts. AB - This is the seventh and last in a series of articles from Planetree, an international non profit organization founded in 1978 that's "committed to improving medical care from the patient's perspective." For more information, go to www.planetree.org. To register for a free Webinar based on this series that starts on September 21, go to http://bit.ly/aezmEu. PMID- 20736712 TI - Environments and health: will the BP oil spill affect our health? PMID- 20736715 TI - Preoperative fasting doesn't mean nothing after midnight. PMID- 20736714 TI - Cultivating quality: an evidence-based approach to taking charge. PMID- 20736716 TI - Cleaning up the discharge process: a number of components--and personnel--are crucial to success. AB - The Pennsylvania Patient Safety Authority Reporting System is a confidential, statewide Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery facilities, and birthing centers, as well as some abortion facilities, must file information on medical errors. Safety Monitor is a column from the authority that informs nurses on issues that can affect patient safety and presents strategies they can easily integrate into practice. For more information on the authority, visit www.patientsafetyauthority.org. For the original article discussed in this column or for other articles on patient safety, click on "Patient Safety Advisories" and then "Advisory Library" in the left-hand navigation menu. PMID- 20736717 TI - I simulate, therefore I am nursed. PMID- 20736720 TI - The digital frontier: broadcasting simulations for nursing education. PMID- 20736721 TI - Developing a second life campus for online accelerated BSN students. PMID- 20736722 TI - Second life environment: a venue for interview skill development. PMID- 20736723 TI - eLearning, knowledge brokering, and nursing: strengthening collaborative practice in long-term care. AB - Interprofessional collaboration is vital to the delivery of quality care in long term care settings; however, caregivers in long-term care face barriers to participating in training programs to improve collaborative practices. Consequently, eLearning can be used to create an environment that combines convenient, individual learning with collaborative experiential learning. Findings of this study revealed that learners enjoyed the flexibility of the Working Together learning resource. They acquired new knowledge and skills that they were able to use in their practice setting to achieve higher levels of collaborative practice. Nurses were identified as team leaders because of their pivotal role in the long-term care home and collaboration with all patient care providers. Nurses are ideal as knowledge brokers for the collaborative practice team. Quantitative findings showed no change in learner's attitudes regarding collaborative practice; however, interviews provided examples of positive changes experienced. Face-to-face collaboration was found to be a challenge, and changes to organizations, systems, and technology need to be made to facilitate this process. The Working Together learning resource is an important first step toward strengthening collaboration in long-term care, and the pilot implementation provides insights that further our understanding of both interprofessional collaboration and effective eLearning. PMID- 20736724 TI - Combining simulation, instructor-produced videos, and online discussions to stimulate critical thinking in nursing students. AB - Combining the use of several different types of technology enables an instructor to develop teaching methods to address a specific problem area that students encounter and can greatly affect student learning. This article discusses a program that was developed that utilized SimMan, instructor-produced videos, and online discussion to stimulate critical thinking in beginning-level nursing students. The goal was to make the student aware of the importance of an initial thorough assessment of a client. This is especially difficult since new students are focused on learning the skills and have not had enough clinical experience to appreciate the importance of assessment. The first two videos show a nurse who makes a very incomplete assessment of the client and misses important observations. This leads to the patient (SimMan) going into respiratory distress. The third video demonstrates a complete assessment. The students viewed and discussed the first two videos online. After the third video, students posted their own reflections of this activity including what they learned and how this would change their behavior. The outcome showed an increased awareness of the importance of assessment. Instructors observed a change in behavior, which included early assessment of the client. PMID- 20736726 TI - The creation and evaluation of an ambulatory orthopedic surgical patient education web site to support empowerment. AB - The use and evaluation of Web sites in ambulatory surgery patients' education are rare; hence, innovative approaches to educate these patients should be adopted and evaluated. The aim of this study was to describe the creation of and evaluate the utility and usability of an ambulatory orthopedic surgical patient education Web site. A descriptive study design was used. The evaluators were 72 ambulatory orthopedic surgery patients receiving education through a Web site. The data were collected after education preoperatively and 2 weeks postoperatively. Two instruments were used: "Patients' Evaluation of Education" and "Diary of the Use of the Website." Web site evaluators' scores for utility of the Web site ranged from 57.56 to 87.87 of 100. Utility of the Web site evaluations was significantly higher (P < .05) 2 weeks postoperatively than immediately after the operation. Web site evaluators' scores for usability of the Web site ranged from 85.69 to 88.32. The use of this program as educational material for orthopedic surgery patients was supported by the patients' opinions of the usability and utility of the Web site. PMID- 20736727 TI - Stratifying computer literacy: a competency measurement strategy. AB - Institutions using a clinical information system which feeds an electronic medical record system must consider evaluation programs that measure the nurse's ability to use and understand the clinical data in the clinical information system. By measuring and tracking the nurse's level of computer literacy, training programs and system enhancements can be better designed. A well-designed system will lead to improved system acceptance and higher adoption rates. There is a need for a defined system implementation strategy that includes nursing staff assessment and system training formulated to fit the specific literacy levels of the majority users of the clinical information system, the nursing staff. Computer literacy in relation to the use of clinical information systems and electronic medical record adoption is the focus of this article. If a strategy based on Benner's novice to expert theory is implemented, computer literacy among frontline users could be assessed, and appropriate education and training programs can be developed. Ultimately, these programs would promote positive perception of the clinical information system, which would result in a better adoption rate of the electronic medical record. PMID- 20736728 TI - Pretest online discussion groups to augment teaching and learning. AB - Tests and final examination scores of three semesters of control students in a nursing foundation course were compared with tests and final examination scores of three semesters of participating students. Participating students were offered access to an asynchronous pretest online discussion activity with a faculty e moderator. While the simplified Bloom's revised taxonomy assisted in creating appropriate preparatory test and final examination questions for pretest online discussion, Salmon's five-stage online method provided direction to the e moderator on how to encourage students to achieve Bloom's higher-order thinking skills during the pretest online discussions. Statistical analysis showed the pretest online discussion activity had a generally positive impact on tests and final examination scores, when controlling for a number of possible confounding variables, including instructor, cumulative grade point average, age, and credit hours. PMID- 20736729 TI - The effects of a web-based supplementary program for facilitating nursing students' basic nursing skills. AB - This study examined the effects of an asynchronous Web-based supplementary learning program on the performance of nursing students' basic nursing skills. A posttest quasi-experimental design was used. Students in the intervention group (n = 62) were given login information to access the online program, while the control group (n = 99) was not. Data from both groups were collected before and 4 weeks after the intervention. An objective assessment of basic nursing skills was used to evaluate the level of skill demonstrated by the participants. Results indicate that the Web-based supplementary learning program is effective at strengthening students' basic nursing skills (P = .002). The findings also reveal that students in the intervention group showed higher-than-average satisfaction with the supplementary program (mean, 3.80 [SD, 0.81]). Thus, this Web-based program offers a learning opportunity for nursing students to enhance their skills beyond their formal lectures. PMID- 20736730 TI - Current opinion in allergy and clinical immunology. PMID- 20736731 TI - Next generation genetics in allergy. PMID- 20736732 TI - Genome-wide association studies on IgE regulation: are genetics of IgE also genetics of atopic disease? AB - PURPOSE OF REVIEW: Total IgE levels are considered a useful endophenotype for studying the genetics of atopic diseases. However, the role and significance of genetic factors influencing IgE regulation for atopic diseases as endpoints is unclear. RECENT FINDINGS: Recently, genome-wide association studies (GWASs) have been applied to atopic traits with considerable success. A total of seven published GWASs on asthma, one GWAS on eczema, and one GWAS on total IgE have reported 11 new loci. Most of these loci appear to be trait-specific. A notable exception is the Th2 cytokine cluster, where genetic variation seems to be relevant across atopic phenotypes. SUMMARY: GWASs have identified several novel asthma and eczema loci as well as novel loci for IgE levels. In this review, we evaluate the interrelation between these loci and summarize to which degree recent findings on IgE reflect genetic vulnerability for atopic disease. PMID- 20736733 TI - The cellular orchestra in skin allergy; are differences to lung and nose relevant? AB - PURPOSE OF REVIEW: It has been a long lasting question that although a similar peripheral allergen-specific immune response has been observed, why some patients show only atopic dermatitis, rhinitis and asthma alone or their combinations. The answer resides in the propensity of resident tissue cells and local antigen presenting cells and T cells for developing an allergic inflammatory immune response. Antigen-presenting cells introduce processed allergens to T helper lymphocytes, where a decision of developing different types of T cell immunity is given under the influence of several cytokines, chemokines, costimulatory signals and regulatory T cells. RECENT FINDINGS: We focused in this review article on effector T cell subsets, which have been recently described such as Th9, Th17 cells and Th22 cells, which are characterized by their IL-9 and IL-10, IL-17 (or IL-17A) and IL-22 expression, respectively together with other proinflammatory cytokines, which coordinate local tissue inflammation. Both naturally occurring CD4+CD25+ regulatory T (Treg) cells and inducible populations of allergen specific, IL-10-secreting Treg type 1 cells inhibit allergen-specific effector cells and have been shown to play a central role in the maintenance of peripheral homeostasis and the establishment of controlled immune responses in allergic inflammatory tissues. SUMMARY: Better understanding and characterization of newly described effector cell subsets and their interaction between antigen presenting cells and resident tissue cells will enlighten our knowledge on the mechanisms of allergic diseases. PMID- 20736734 TI - Current world literature. PMID- 20736736 TI - Disrupting the food-fat connection. PMID- 20736737 TI - Current Opinion in Endocrinology, Diabetes & Obesity. Current world literature. PMID- 20736739 TI - Nontyphoidal salmonellosis in Africa. AB - PURPOSE OF REVIEW: This review aims to identify and highlight important data published in the past 12 months which provide new information on nontyphoidal salmonellosis in Africa. RECENT FINDINGS: Recent reviews and clinical studies continue to emphasize the challenges of diagnosis and management of invasive nontyphoidal Salmonellae (NTS) disease as a major cause of mortality in African children and HIV-infected African adults. New observational evidence of the association between malaria and NTS disease in African children has been published. An improved understanding of disease pathogenesis has been provided with evidence of persistent intracellular infection in HIV-infected adults. Multidrug resistance of NTS is now widespread in the region. A novel variant of NTS has emerged which is now a common cause of invasive disease in African populations, and it shows evidence of adaptation to human host and has acquired virulence plasmids along with multidrug resistance. Recent studies have provided original data of the importance of humoral immunity in African children, which informs the development of vaccine. SUMMARY: NTS are a major cause of invasive disease in Africa. Recent studies provide a range of helpful insights and novel data which could inform strategies for improving management and especially prevention of this neglected disease. PMID- 20736740 TI - Current world literature. PMID- 20736741 TI - Reproducibility and performance of virtual karyotyping with SNP microarrays for the detection of chromosomal imbalances in formalin-fixed paraffin-embedded tissues. AB - BACKGROUND: Chromosomal imbalances are commonly seen in cancer and inherited genetic diseases. These imbalances may assist in the diagnosis, prognosis, and/or therapeutic management of certain neoplasms. Several methods for detecting chromosomal imbalances, such as, fluorescent in situ hybridization, array comparative genomic hybridization, and single nucleotide polymorphism (SNP) arrays have proven useful in formalin-fixed paraffin-embedded (FFPE) tissues. Here, we report the performance and reproducibility of virtual karyotyping of FFPE tissues with Affymetrix SNP arrays. METHODS: Virtual karyotypes from 442 FFPE tumor samples were generated using the Affymetrix GeneChip Mapping 10K Xba 2.0 and/or 250K Nsp SNP mapping arrays. Samples ranged from a few weeks to 17 years in archival storage. Virtual karyotypes were assessed for copy number changes, loss of heterozygosity, and acquired uniparental disomy. RESULTS: Overall, 75.3% of samples produced interpretable virtual karyotypes with the 10K arrays and 76.7% in the 250K arrays. Parameters for the selection of samples for hybridization were determined, which increased the success rate in both platforms to 81.3 and 92.6%, respectively. FFPE virtual karyotypes generated with both 10K Xba 2.0 and 250K Nsp arrays showed 100% concordance in intralaboratory and interlaboratory reproducibility studies. Samples older than 7 years showed decreased performance. CONCLUSIONS: SNP arrays are a reliable, reproducible, and robust platform for the virtual karyotyping of FFPE tumor tissues with performance characteristics adequate for clinical application. Parameters that most significantly affected sample performance were sample age and storage conditions. PMID- 20736742 TI - Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection. AB - Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2 induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis. PMID- 20736743 TI - HPV is detectable in virtually all abnormal cervical cytology samples after reinvestigation of HPV negatives with multiple alternative PCR tests. AB - The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens from around the world required investigations by multiple alternative polymerase chain reaction (PCR) assays. A similar approach may therefore be necessary to best characterize HPV prevalence and genotype distribution among cervical cytology samples. In an earlier study, 752 of 799 (94.1%) abnormal and 82 of 300 (27.3%) normal cytology specimens tested HPV positive after PCR using GP5+/6+primers. This study has reinvestigated the "HPV negative" abnormal samples (20 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 14 atypical squamous cells, cannot exclude HSIL, 6 high-grade squamous intraepithelial lesion) and an age-matched cohort of "HPV negative" normal (negative for an intraepithelial lesion or malignancy) samples by PCR using PGMY09/11, FAP59/64, and LCR-E7 primers. PGMY09/11-GP5+/6+ nested PCR was performed on samples that were HPV negative by PGMY09/11 PCR. After the first 3 assays, HPV was detected in 41 of 45 (91.1%) abnormal and in 10 of 47 (21.3%) normal samples (P<0.0001). Eighteen HPV genotypes were detected and in some samples the genotype that was identified differed between the tests. The nondetection of common HPV genotypes (eg, HPVs 6, 11, 16, and 18) was notable. High-grade histopathology was found for 2 patients with HPV52-positive cytopathology. Combined with our earlier study, HPV (40 different genotypes) is shown in 99.5% of abnormal samples (99.8% inclusive of the nested PCR data). These findings show that HPV genotype and prevalence estimates are dependent on the method(s) of detection and indicate that suboptimal analytical sensitivity for one or more of the less common high-risk HPV genotypes could lead to impaired clinical sensitivity. HPV may be causal in almost every instance of abnormal cervical cytology; however, passenger HPV that is incidental to an abnormality may also have been detected. PMID- 20736744 TI - Detection of TMPRSS2 gene deletions and translocations in carcinoma, intraepithelial neoplasia, and normal epithelium of the prostate by direct fluorescence in situ hybridization. AB - TMPRSS2 gene fusions with ETS transcription factor family members ERG, ETV1, or ETV4 have been recently discovered as a common molecular event in prostate cancer. Much attention has been focused on exploring their clinical application as a genetic tumor marker for the diagnosis, prognosis, and prediction of response to therapy. Although several studies have been done, the clinical utility of TMPRSS2 genetic alterations as biomarkers for prostate carcinoma remains indeterminate. In this study, we examined adenocarcinomas, prostatic intraepithelial neoplasia (PIN), and normal epithelium of the prostate retrieved from radical prostatectomy specimens to determine the frequency, specificity, tissue heterogeneity, and prognostic value of TMPRSS2 genetic alterations using a direct-labeled TMPRSS2 dual-color break-apart fluorescence in situ hybridization (FISH) probe cocktail designed to detect all known TMPRSS2-associated deletions or translocations. Seventy-one patients (161 samples) with normal prostate tissue, 60 patients (153 samples) with PIN, and 61 patients (142 samples) with carcinoma in formalin-fixed paraffin-embedded tissue microarrays were tested. None of the 161 normal prostate samples showed TMPRSS2 translocation or deletion. Sixty-two percent patients of prostate carcinomas demonstrated TMPRSS2 gene alterations, including 39% with translocation, 16% with deletion, and 7% with a mixed pattern. Tissue heterogeneity for TMPRSS2 gene alterations was identified in 28% of prostate carcinomas. No difference in the frequency of TMPRSS2 gene alterations was found between Gleason 6 and 7 tumors. Seventeen percent of PIN had TMPRSS2 gene alterations and showed the same FISH patterns as in the carcinomas from respective prostatectomy specimens. The TMPRSS2 dual-color break apart FISH probe cocktail provides a simple and reliable method for the detection of TMPRSS2-related genetic alterations in formalin-fixed paraffin-embedded tissue. TMPRSS2 genetic alterations detectable by this method are strictly restricted in prostate neoplasia, and can be identified in the majority of prostate carcinomas. Tissue heterogeneity for TMPRSS2 alterations is common, and it should be considered when sampling and evaluating biopsy specimens. PMID- 20736746 TI - Detection of ERCC1 118 polymorphisms in non-small-cell lung cancer by an improved fluorescence polarization assay. AB - Excision repair cross-complementing 1-118 single nucleotide polymorphisms (SNPs) have been reported as predictive markers of response to platinum-based chemotherapy. Currently, the most used methods for genotyping of SNPs are costly and time consuming. It is necessary to develop a method that is more accurate, cost-effective, and simple. An improved fluorescence polarization assay based on asymmetric polymerase chain reaction hybridization for screening excision repair cross-complementing 1-118 SNPs has been developed. Excision repair cross complementing 1-118 SNPs of all 907 samples were analyzed in sequence and improved fluorescence polarization assay in parallel. The sensitivity, specificity, and stability of the improved fluorescence polarization assay were measured. This study showed the accuracy, simplicity, and cost-effectiveness of the fluorescence polarization assay in the detection of excision repair cross complementing 1-118 SNPs in a panel of 907 samples. The fluorescence polarization assay was more accurate for the heterozygous sample than was the sequence assay. The minimum detection level established with the fluorescence polarization assay was 2.5 genome copies per reaction and no cross-reaction was observed. PMID- 20736745 TI - NRAS mutations are rare in colorectal cancer. AB - Activating mutations in members of the RAS oncogene family (KRAS, HRAS, and NRAS) have been found in a variety of human malignancies, suggesting a dominant role in carcinogenesis. In colon cancers, KRAS mutations are common and clearly contribute to malignant progression. The frequency of NRAS mutations and their relationship with clinical, pathologic, and molecular features remains uncertain. We developed and validated a Pyroseqencing assay to detect NRAS mutations at codons 12, 13, and 61. Using a collection of 225 colorectal cancers from 2 prospective cohort studies, we examined the relationship between NRAS mutations, clinical outcome, and other molecular features, including mutation of KRAS, BRAF, and PIK3CA, microsatellite instability, and the CpG island methylator phenotype. Finally, we examined whether NRAS mutation was associated with patient survival or prognosis. NRAS mutations were detected in 5 (2.2%) of the 225 colorectal cancers and tended to occur in left-sided cancers arising in women, but did not seem to be associated with any of the molecular features that were examined. PMID- 20736747 TI - BCL2 chromosomal translocation is not a general feature of the interdigitating dendritic cell sarcoma. AB - Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasia of interdigitating dendritic cells. Two single case reports documenting IDCS harboring t(14;18) translocation involving immunoglobulin heavy chain (IGH) and BCL2 have been reported recently; however, one of the 2 IDCS has a synchronous follicular lymphoma, the absence or presence of a follicular lymphoma in the remaining case is not mentioned. In this study, by using polymerase chain reaction and fluorescence in situ hybridization techniques, we have showed that there is neither t(14;18)/IGH-BCL2 nor IGH gene rearrangement in 4 de novo IDCS without a concurrent or known history of a B-cell lymphoma, including follicular lymphoma, indicating that BCL2 chromosomal translocation is not a general feature of de novo IDCS. PMID- 20736748 TI - Development of a fluorescent microsphere-based multiplex assay for simultaneous rapid detection of Mycobacterium tuberculosis complex and differentiation of M. tuberculosis and M. bovis in clinical samples. AB - A microsphere-based multiplex assay was developed, by using the xMAP technology, for the simultaneous rapid detection of the Mycobacterium tuberculosis complex (MTC) and the differentiation of M. tuberculosis and M. bovis. The assay simultaneously detected 4 target sequences, including specific insertion elements IS6110 and IS1081 of MTC, a 12.7- Kb fragment specific for M. tuberculosis, and an uninterrupted 229 bp sequence specific for M. bovis. The specificity of the assay was validated by testing on 13 species of mycobacteria reference strains, 22 isolated strains of M. tuberculosis and M. bovis, and 25 species of non mycobacteria microorganisms. The limit of detection of mycobacteria by the assay was up to 6 to 10 bacteria per reaction, and the sensitivity of detecting cloned DNA templates was 0.37 to 0.74 fg DNA per reaction. The intra-assay and interassay variation of the assay on the 4 gene targets were low (1.5% to 8.5% and 4.1% to 9.2%, respectively). Clinical performance of the assay was validated on human sputum and bovine tissue samples and compared with the culture. The assay detected 69.8% (90/129) of MTC positive, as compared with 36.4% (47/129) positive by culture on sputum samples, and 75.5% (37/49) of MTC positive as compared with 42.8% (21/49) positive by culture on bovine tissue samples. The assay detected 100% of the culture positive in both human and bovine samples. The tests identified 98.9% (89/90) as M. tuberculosis from the MTC-positive sputum samples, and identified 91.9% (34/37) as M. bovis from the MTC-positive bovine tissue samples. The detection of mycobacterial DNA by the microsphere-based multiplex assay could be completed within 2 hours. PMID- 20736749 TI - High prevalence of activated protein C resistance and factor V Leiden mutation in an Arab population and patients with venous thrombosis in Kuwait. AB - INTRODUCTION: Activated protein C resistance (APC-R) because of clotting factor V Leiden mutation (FVL; Arg506Gln; G1691A) is a risk factor for the development of venous thromboembolic disorders (VTE). APC-R/FVL was reported to be very high in White patients with VTE (15% to 65%) and healthy populations (1% to 15%), and to be very low or absent in non-White patients. Studies on Arab patients and populations were very inconsistent. This study reports APC-R and FVL in Arabs living in Kuwait. MATERIALS AND METHODS: Whole venous blood samples were collected from 400 patients with VTE and 200 healthy controls, all of whom were of Arab ethnicity living in Kuwait. The samples were used to separate plasma for an APC-R test, and DNA extraction for polymerase chain reaction and restricted fragment length polymorphism were performed. APC-R was on an automated hemostasis analyzer, and values less than 2.0 were reported as APC-R. Polymerase chain reaction and restricted fragment length polymorphism tests were performed using standard methods, and the results were reported as normal wild-type homozygous GG, FVL homozygous AA, or FVL heterozygous GA. RESULTS: Sixty-three out of 400 patients (15.75%) and 4 out of 200 healthy controls (2%) had APC-R and at least one copy of FVL. Fifty-one patients and 4 controls were heterozygous whereas only 12 patients were homozygous. CONCLUSION: The prevalence of APC-R and FVL is quite high in Arabs living in Kuwait, being comparable with the prevalence reported in Whites, although being toward the lowest values reported there. PMID- 20736750 TI - Role of postmortem genetic testing demonstrated in a case of glutaric aciduria type II. AB - Glutaric aciduria type II, or multiple acyl-CoA dehydrogenase deficiency, is a rare metabolic disorder inherited in an autosomal recessive manner. The condition can be caused by mutations in at least 3 genes, including ETFA, ETFB, and ETFDH. When this potentially lethal disorder is known for its clinical and biochemical heterogeneity, mutation analysis will be an invaluable part of diagnosis. We here described a Chinese adolescent boy who enjoyed good health earlier and presented at the age of 14 years with severe vomiting. His condition deteriorated rapidly and he succumbed shortly after. With a travel history before presentation and the late age of onset, diagnosis was particularly difficult. Findings in perimortem biochemical investigations and postmortem autopsy were guiding but not diagnostic. The diagnosis of glutaric aciduria type II was finally confirmed by mutation analysis performed by direct sequencing on genomic DNA from peripheral blood, which identified 2 different unreported missense mutations, c.502G>T (p.V168F) and c.786A>G (p.Q262R), in ETFA. The father and the mother were found to be heterozygous for the 2 mutations in ETFA respectively. Subsequent molecular family screening also ruled out the disease in his elder sister, who had a history of convulsion and a suspicious plasma acylcarnitine profile, and freed her from life-long supplementation. The case showed that molecular autopsies should be part of routine postmortem examination of unexplained sudden death in all age groups and DNA-friendly samples should be routinely collected and archived. In the era of personalized medicine with the power of modern genetics, molecular diagnosis should be obtained for heterogeneous diseases with different genetic defects but sharing similar clinical and/or biochemical phenotypes. PMID- 20736751 TI - Family & Community Health. From the editor. PMID- 20736752 TI - Foreword. Health of immigrant and border communities. PMID- 20736754 TI - Korean immigrant parents' evaluation of the delivery of a parenting program for cultural and linguistic appropriateness and usefulness. AB - The goal of this study was to evaluate the delivery of a parenting program to 17 Korean immigrants for cultural and linguistic appropriateness and usefulness regarding recruitment, retention, program content, and delivery methods. Focus group interview data were audiotaped, transcribed, and analyzed. Themes identified included fit between the parents' desire and what the program offered, effective recruitment and retention strategies, program content and videotapes: based on Western cultural background but useful, helpful role-play and homework, and recommendations (Korean language videotapes, longer classes, extended learning). The findings can be used in adopting the program to increase cultural and linguistic appropriateness. PMID- 20736753 TI - Cardiovascular health perceptions in multigenerational Korean immigrants. AB - Cardiovascular disease is prevalent in the Korean immigrants. Success of any health interventions depends heavily on our understanding of how health issues are perceived by the recipients. This study describes cardiovascular health perceptions using Photovoice, a qualitative methodology utilizing photography to initiate discussion, in multigenerational Korean immigrants (older adults, teenagers, children). Twenty Korean Americans (7 adults aged >or=50 years, 6 teenagers aged 13 to 19 years, 7 children aged 9 to 12 years) were recruited from the Korean communities in Seattle, Washington. Each subject was given a camera and asked to take 24 pictures of objects, scenes, and environments that represented their perceptions of cardiovascular health and related risk factors. Subjects were asked to pick 2 photos and present their thoughts about them in a tape-recorded group meeting. Key concepts were identified from the discussions. Themes identified promoting cardiovascular health included good diet, exercise, a clean environment, and spirituality. The themes identified as the risk factors for cardiovascular diseases included bad diet, smoking, pollution, and stress. Expression of the risk factors differed by the age group. The shared cultural background also influenced the perception of the risk factors. These observations support the findings that the culture and age-specific interventions may augment intervention effectiveness. PMID- 20736755 TI - Lessons from the field: Using photovoice with an ethnically diverse population in a HOPE VI evaluation. AB - An interdisciplinary research team evaluated a public housing revitalization project in northwest Washington State to assess the effects of relocation on residents and provide recommendations on assets in the new community. Researchers used photovoice as one method to gather data, asking participants to take photographs of their neighborhood and discuss the images with interviewers. This article addresses the challenges of using photovoice in a community that included immigrants from Cambodia, Vietnam, and Russia. The practical, ethical, and social challenges of using photovoice in ethnically diverse populations and implications for practice are discussed. PMID- 20736756 TI - How much do they know about sexual health?: Knowledge and information-seeking behaviors of Spanish-speaking immigrant adolescents in Curacao, Netherlands Antilles. AB - Scant HIV/AIDS prevalence data from Curacao suggest that 65.9% of the HIV/AIDS cases in the Netherlands Antilles are currently being documented in this country. The present cross-sectional qualitative study evaluated levels of knowledge of sexual health and information-seeking behavior of Spanish-speaking immigrant adolescents in Curacao. Findings point to a greater need for channels of sexual health information targeting adolescents that focus on the interpersonal aspects of sexuality, to encourage greater parental involvement in their adolescents' lives, and to improve communications between adolescents and their parents. Study findings also suggest the need for a more thoughtful and systematic exploration of the indications by participants that force/coercion specifically by older men including stepfathers was a reason for sexual initiation of many young Latina girls in Curacao. PMID- 20736757 TI - Preparing for a healthy future today: Folic acid formative research with young Latina adults. AB - Young Latina adults require targeted health messages to meet the unique needs of this life stage. Folic acid messages for the prevention of neural tube defects that are effective for other women might not be relevant to this group. The aim of this study was to identify barriers and motivators to folic acid consumption for this population and develop educational materials and messages that address their needs. This article presents 3 phases of formative research that formed the basis for the development of Spanish-language print materials and radio advertisements aimed at promoting folic acid consumption among young Latina adults. PMID- 20736758 TI - Sociocultural influences on the determinants of breast-feeding by Latina mothers in the Cincinnati area. AB - While breast-feeding initiation and duration among US Latina women appear to decrease with acculturation, health care providers in the Greater Cincinnati area have noted lower rates of breast-feeding among even first-generation Latina immigrants. This study's purpose was to identify determinants of breast-feeding for Latina mothers in Cincinnati through qualitative interviews and Spanish Breastfeeding Self-Efficacy Scale ratings. Our findings suggest that, along with similar levels of breast-feeding self-confidence, foreign-born Latina women in the Greater Cincinnati area share similar breast-feeding determinants with the general population. However, characteristics of these determinants and their impact vary because of unique pressures experienced by this community. PMID- 20736759 TI - Strategies for targeting health care disparities among Hispanics. AB - Hispanics are the largest minority group in United States and at a great risk for poor health outcomes linked to poor access to health care. Their large geographic distribution makes it critical that the underlying factors resulting in health care disparities among documented and undocumented Hispanics be addressed at local, state, and national levels. Health care systems should establish community partnership for effective strategies to address these disparities. This article presents factors identified in the literature that contribute to health care disparities among Hispanics and provides strategies for improving access to health care for health promotion. PMID- 20736760 TI - Exploring the efficacy of an environmental health intervention in Ciudad Juarez, Mexico. AB - This study explores the efficacy of an environmental health intervention in several poor colonias in Ciudad Juarez (Mexico). Parents of children with respiratory problems were given environment-friendly products intended to replace hazardous products used in the home, as well as information about environmental health. Parents were surveyed before and after to measure the effectiveness of the intervention and to gauge perceptions. There was a significant reduction in hazardous chemical use (eg, cleaning products and pesticides) and breathing problems. While the intervention focused on changing in-home behaviors, open ended responses revealed that parents were most concerned about outdoor environmental conditions over which they had less control. PMID- 20736762 TI - Expression of podoplanin in epithelial ovarian carcinomas and its potential as a marker for clear cell adenocarcinoma. AB - Podoplanin is a 43-kd mucin-type transmembrane glycoprotein that is a candidate marker for the pathologic diagnosis of mesothelioma and lymphatic endothelial cells and lymphangiogenesis. The aim of this study was to investigate podoplanin expression in epithelial ovarian carcinomas. Immunohistochemistry was performed on the paraffin-embedded tissues from 78 patients with epithelial ovarian carcinomas consisting of serous adenocarcinoma (SA), endometrioid adenocarcinoma (EM), mucinous adenocarcinoma (MA), and clear cell adenocarcinoma (CCC) cases. Only 36.8% (7/19) of SA, 33.3% (6/18) of EM, and 15.8% (3/19) of MA cases were positive for podoplanin expression, whereas 54.5% (12/22) of CCC samples were positive. Immunohistochemical scores (mean+/-SD) were 1.2+/-1.5, 1.9+/-2.6, 0.8+/ 1.6 and, 3.6+/-4.0 in SA, EM, MA, and CCC, respectively. Podoplanin expression was significantly stronger in CCC than in other histologic types. However, no significant correlation was observed between its expression and FIGO stage, the presence of endometriosis, lymph node metastasis, or recurrence. There was also no correlation between podoplanin expression and overall survival. We confirmed the expression of podoplanin in epithelial ovarian carcinomas, particularly in CCC. Podoplanin might have utility as a marker for CCC in pathologic diagnosis. Further investigation is needed to clarify the relationship between podoplanin expression and the biologic characteristics of CCC. PMID- 20736763 TI - Ovarian serous cystadenofibroma with signet ring-stromal cells: report of 2 cases. AB - We report 2 ovarian serous cystadenofibromas with signet ring cells within the stromal component. The signet ring-stromal cells were widespread in 1 case and focal in the other. Immunohistochemically, they were negative with cytokeratin and other epithelial markers and positive with mesenchymal markers. The occurrence of signet ring-stromal cells in ovarian serous cystadenofibromas is an unusual pseudoneoplastic phenomenon, which has not been reported previously, although signet ring cells may occur within a variety of ovarian stromal neoplasms, including fibromas, sclerosing stromal tumors, and signet ring-stromal tumors. In reporting these cases, we review ovarian stromal neoplasms and other lesions with signet ring cells. PMID- 20736764 TI - Ovarian adenosarcoma arising from benign cystadenoma and associated intraoperative consultation pitfalls. AB - An unusual case of ovarian adenosarcoma arising from a smooth-walled serous cystadenoma is described. The ovary was replaced by a multiloculated, fluid filled cyst without any solid or papillary areas. The malignant component was underdiagnosed during frozen section examination as benign cystadenoma because of the deceptively benign gross appearance of the tumor. On the permanent sections, a phyllodes-like pattern of stromal proliferation and periglandular condensation of atypical stromal cells with a mitotic count of 3 per 10 high-power fields was more apparent and led to the diagnosis of adenosarcoma. The malignant component could not be distinguished from the benign component using immunohistochemical analysis. To our knowledge, this is the first reported case of an adenosarcoma arising from a grossly benign cystadenoma and the third case in the literature of an adenosarcoma associated with a cystadeno(fibro)ma. This case also shows the challenges in differentiating adenosarcoma from a benign counterpart on both frozen and permanent sections. PMID- 20736765 TI - Bilateral ovarian well-differentiated Sertoli-Leydig cell tumors with heterologous elements associated with unilateral serous cystadenoma--a case report. AB - Bilateral Sertoli-Leydig cell tumors (SLCTs) of the ovary, especially in association with a cystadenoma, are exceedingly rare. Some SLCTs, usually of poor differentiation, show heterologous elements. We present a case of a 61-year-old woman with bilateral well-differentiated SLCTs in which the Sertoli-Leydig cell component showed leiomyogenic (heterologous) differentiation. Furthermore, on the left side it also was associated with a serous cystadenoma. PMID- 20736766 TI - Sertoli cell tumor with benign peritoneal implants associated with gonadoblastoma. AB - We present a unique case of bilateral gonadoblastoma in a 23-year-old patient with Swyer syndrome. The gonadoblastoma on both sides underwent synchronous neoplastic transformation, into a stage I germinoma in the right streak gonad and a highly differentiated Sertoli cell tumor in the left one. The latter was associated with a myriad of microscopic, Sertoli cell implants on the peritoneal surface, which were considered benign as they had a high grade of differentiation, minimal proliferative activity, and an absence of invasion. Most probably, the pathogenesis of this abdominal dissemination was iatrogenic, with implantation occurring mechanically as a result of the multiple laparoscopic biopsies performed on both of the streak gonads 2 months before the abdominal surgery. The pathogenesis of other benign abdominal implants is discussed. PMID- 20736767 TI - Lymphoepithelioma-like carcinoma of the ovary: a case report and review of the literature. AB - Lymphoepithelioma-like carcinoma (LELC), which is commonly reported in the nasopharynx and occasionally in other organs, remains a rare condition in gynecology. It is morphologically defined as a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltrate. We present a case of an 82-year-old woman with a 10 cm LELC of the ovary shown by inguinal lymph nodes. There was no peritoneal carcinomatosis. Cytoreductive surgery was performed to remove a left ovarian neoplasm and multiple involved lymph nodes. Cytoreduction was complete. The tumor was a mixed poorly undifferentiated ovarian carcinoma consisting of 95% LELC and 5% moderately differentiated serous adenocarcinoma. Immunohistochemistry showed a large infiltration of T lymphocytes and plasma cells. Epstein-Barr virus was not detected by immunolabeling and polymerase chain reaction. The patient was still alive at 24 months of follow-up. To our knowledge, this is the second case of ovarian LELC and the first description of the native tumor before chemotherapy. In conclusion, this rare tumor of the ovary is difficult to diagnose both preoperatively and perioperatively. However, clinicians and pathologists should be aware that ovarian tumors with massive involvement of lymph nodes and no peritoneal carcinomatosis are suggestive of such a diagnosis and that prognosis is relatively good. PMID- 20736768 TI - Leiomyosarcoma of the broad ligament with osteoclast-like giant cells and rhabdoid cells. AB - In this report we document an unusual co-mingling of rhabdoid and osteoclast like giant cells in a leiomyosarcoma arising from the broad ligament. A 38-year old female was found to have a rapidly enlarging adnexal mass which was resected and histologically found to be a leiomyosarcoma with marked pleomorphism. Completion surgery, shortly thereafter showed spread to the ileum, which was also resected. The tumor now showed a prominent population of both osteoclast-like giant cells and rhabdoid cells. Interestingly, the immunophenotype of the tumor had also changed with complete loss of desmin, caldesmon and only focal expression of smooth muscle actin. This is the first documentation of the coexistence of rhabdoid and osteoclast-like giant cells within a gynecological tract leiomyosarcoma. This tumor was characterized by rapid clinical progression despite extensive surgery and chemotherapy. These two cells types have individually been implicated as harbingers of a poor prognosis in leiomyosarcomas. Their prominence in the recurrent tumor and the loss of muscle marker expression are in keeping with biologic progression. PMID- 20736769 TI - Immature teratoma of the ovary with distant metastases: favorable prognosis and insights into chemotherapeutic retroconversion. AB - We present a case of a young woman with an immature teratoma of the right ovary that showed systemic metastases. The patient initially experienced abdominal distention at the age of 15 years. Radiographic assessment revealed a right ovarian tumor; thus, right salpingo-oophorectomy was performed, and the resected ovarian tumor showed a multilocular cystic lesion with partially solid areas. Pathologic diagnosis was an immature teratoma, grade 2. As brain, lung, and liver metastases were discovered within 2 years after the operation, sequential resections of the metastatic foci were performed before chemotherapy as well as during the early and late stages of chemotherapy. The resected specimens of each metastatic focus contained histologically more mature elements of the primary immature teratoma and exhibited a decrease in the Ki-67 labeling index, the later the resection was performed. As far as we know, this is the first case of brain metastasis stemming from an immature teratoma of the ovary. In addition, it was highly suggestive that chemotherapy itself was the main etiological factor for the promotion of maturation. The favorable prognosis of this malignant tumor even after brain metastasis was verified by the 10-year-survival of the patient. PMID- 20736770 TI - The significance of tumor involved adenomyosis in otherwise low-stage endometrioid adenocarcinoma. AB - Depth of myometrial invasion by endometrioid adenocarcinoma (EMAC) is one of the most important predictive factors of disease recurrence. It is unclear whether myoinvasion arising in carcinomatous involvement of adenomyosis (AM) changes prognosis. The purpose of this study was to evaluate the significance and frequency of the tumor involved AM in otherwise low-stage cancers. Eighty-two hysterectomies with EMAC with less than 50% myoinvasion (T1a, FIGO IA), AM, and at least 2 years of follow-up information were reviewed. The tumors were divided into 4 histologic groups: group 1, no involvement of AM by EMAC (n=38); group 2, tumor involved AM surrounded by endometrial stroma (n=31); group 3, tumor involved AM with incomplete peripheral endometrial stroma (n=10); and group 4, tumor involved AM with invasion into adjacent smooth muscle (n=3). Tumor involved AM was in the inner half of the myometrium in 35 cases and in the outer half of the myometrium in 9 cases. The only adverse outcome was vaginal recurrence, which was noted in 2 of 82 patients; both the patients were from the control group. None of the patients with deep-seated tumor involved AM had tumor recurrence. In otherwise low-stage tumors, our data support the concept that tumor involvement of the deeply located AM does not affect prognosis. Myometrial-based foci of well differentiated EMAC, completely or partially surrounded by endometrial stroma, most likely represents tumor colonized AM. Determining invasion out of these foci is subjective, and although limited by rarity in this study, carries no adverse outcome. Therefore, staging should be based on the myoinvasion noted at the native endomyometrial junction. PMID- 20736771 TI - WT1 immunoprofiling and comparison of malignant Mullerian mixed tumors of the female genital tract. AB - A malignant Mullerian mixed tumor (MMMT) is a biphasic homologous or heterologous malignancy of the female genital tract. WT1 (Wilms tumor 1) is both a tumor suppressor gene and oncogene overexpressed in the nuclei of some gynecologic carcinomas. Expression in MMMT is incompletely described. Whole sections from 16 MMMTs were stained with WT1 (N terminus) using a standard immunoperoxidase technique. There were 7 heterologous and 9 homologous tumors and 10 were endometrial, 5 were ovarian, and 1 was of peritoneal origin. The tissue and cell staining pattern and score (intensity by amount) were evaluated and correlated with the tumor subtype and anatomic location. Among the 16 tumors, 81.3% showed mostly stromal and cytoplasmic staining and a score of 3 or 6. Staining was positive in 80% of the endometrial and ovarian tumors and the 1 peritoneal tumor and in all heterologous and 66.7% of the homologous tumors. The immunoprofile correlated with tumor subtype but not with anatomic location. Stromal and epithelial staining was more frequent (83.3%) in homologous tumors and differed significantly (P=0.009) from the heterologous types where stromal staining prevailed (85.7%). MMMT is another genital tract malignancy which can over express WT1 and the immunoprofile may assist in tumor subtyping. PMID- 20736772 TI - Clinicopathologic features of 2 new cases of uterine tumors resembling ovarian sex cord tumors. AB - Uterine neoplasms showing an exclusive sex cord-like differentiation or focal low grade sarcoma differentiation, designated as uterine tumors resembling ovarian sex cord tumors (UTROSCTs), are rare, with only 48 cases described earlier in international literature. Generally, this entity is characterized by benign behavior. In this study, we report the clinical and pathologic features of 2 peculiar new cases of UTROSCTs. In these examples, the pathologic diagnosis of UTROSCT was made incidentally after the clinical diagnosis of a leiomyoma and endometrial polyp. On examination of small biopsies, the diagnosis was facilitated by specific immunohistochemical analysis using markers for the sex cord component. In 1 of these cases, the patient, because of her young age and her desire to preserve her fertility, was only treated by minimally invasive hysteroscopic surgery. In the other case, the neoplasm seemed to be the consequence of tamoxifen treatment for breast carcinoma. After diagnosis, in this second case, the woman underwent hysterectomy that showed a residue of the tumor and cervical metastasis from the earlier breast carcinoma. The differential diagnosis of UTROSCT and the role of immunohistochemistry in confirming a diagnosis are discussed. PMID- 20736773 TI - Overexpression of the Parkinson disease protein DJ-1 and its regulator PTEN in gestational trophoblastic disease. AB - DJ-1 is found to be important in human neurodegenerative diseases and cancers by regulating oxidative damage and apoptosis. DJ-1 is also a regulator of PTEN, a frequently mutated tumor suppressor gene in cancers. In this study, we investigated the expression of DJ-1 and PTEN in normal placentas and gestational trophoblastic disease in relation to apoptotic indices and p53 status. A total of 95 trophoblastic samples were retrieved for immunohistochemical study whereas 79 trophoblastic samples, 3 normal trophoblastic and 2 choriocarcinoma cell lines were collected for quantitative real time reverse transcription polymerase chain reaction detection. There was a significant correlation between DJ-1 and PTEN immunostaining indices in the trophoblastic samples (P=0.013). Significantly higher DJ-1 and PTEN immunoreactivity indices were found in the complete mole (P<0.01) and choricarcinoma (P<0.01) compared with the first trimester placenta. Quantitative real time reverse transcription polymerase chain reaction also detected significantly higher messenger ribonucleic acid expressions of DJ-1 and PTEN in hydatidiform moles (P<0.05) and choriocarcinomas (P<0.05) compared with the first trimester placentas. A significant negative correlation was found between DJ-1 and the apoptosis resistant gene Bcl-2 (P=0.031), whereas a positive correlation was shown between PTEN and wild-type p53 (P=0.019). Significant correlations between PTEN and embryonic stem cell transcription factors, Stat3 and Nanog, were also displayed (P=0.001, 0.015). Our findings showed, for the first time, overexpression of DJ-1 at both transcriptional and protein levels in gestational trophoblastic disease. Overexpressed DJ-1 may play a role in regulating apoptotic activities of trophoblasts in relation to PTEN and p53. PMID- 20736775 TI - Can a more detailed evaluation of excision margins refine cytologic follow-up of women post-LLETZ for high-grade dysplasia? AB - The relationship between dysplastic changes in the cervical epithelium and progression to in situ carcinoma and invasive carcinoma has been extensively studied. The removal of dysplastic epithelium through the long loop excision of the transformation zone (LLETZ) in 95% of the cases is curative. About 18% to 37% of LLETZ specimens with dysplasia at the margins have recurrent/residual disease. Earlier small studies suggest that the degree of dysplasia at the margins could predict for recurrence and allow a risk-based stratification of follow-up. We tested this hypothesis in a large group of women post-LLETZ for high-grade dysplasia with follow-up histology and cytology over a 12-year period. The cases were divided according to the excision margin status for dysplasia and if positive, low-grade or high-grade dysplasia. The groups were compared to assess whether the LLETZ specimens' margin status had an impact on the subsequent cytology or histology results. Positive follow-up results were defined as any grade of dysplasia in cytology or histology. Two thousand three hundred twenty one women had LLETZs containing high-grade dysplasia over the 12-year period. One thousand five hundred thirty-four (66.1%) women had full histology and cytology follow-up available. Eight hundred twenty (53.4%) LLETZ specimens had positive margins and 714 (46.6%) had negative margins. The grade of dysplasia at the margins was available in 796 cases (97%) with 115 (15%) showing low-grade dysplasia and 680 (85%) high-grade dysplasia. One hundred seventy (20.7%) of the specimens with positive margins had positive follow-up results compared with 105 (14.7%) of the specimens with negative margins. The presence of dysplasia at an LLETZ margin is associated with dysplasia on follow-up cytology and histology (P=0.0021); however, the grade of dysplasia at the excision margin is not predictive of recurrent/residual dysplasia. PMID- 20736774 TI - Incidental finding of placental choriocarcinoma after an uncomplicated term pregnancy: a case report with review of the literature. AB - Choriocarcinoma is frequently preceded by a complete mole, ectopic pregnancy, nonmolar intrauterine abortion, and uncommonly by a partial mole. Choriocarcinoma coexisting with or after an otherwise "normal" pregnancy is extremely rare, with an estimated occurrence of 1 per 160,000 pregnancies. We here report a case of a placental choriocarcinoma with no metastases in a full-term intrauterine pregnancy. The patient is a 29-year-old gravida 2 para 1 female, who had an uncomplicated full-term vaginal delivery of a healthy 3030 g female infant. Her current pregnancy was uneventful, and past medical history was significant for an elective termination of pregnancy 2 years ago at 8 weeks of gestation. Routine examination of the placenta showed a gray-tan nodule, measuring 2 cm in the largest dimension, with a papillary cut surface. Microscopically, this nodule was composed of highly atypical cytotrophoblastic cells and multinucleated atypical syncytiotrophoblastic cells, which were positive for beta-human chorionic gonadotrophin by immunostaining. Extensive necrosis and multiple foci of hemorrhage were present. The overall morphologic and immunohistochemical features were diagnostic for choriocarcinoma. Further investigations, including a full body computed tomography scan, showed no lesions suspicious for metastases. The patient is currently asymptomatic and being followed-up with monthly beta-human chorionic gonadotrophin levels, the most recent one being negative. By reporting this case and reviewing the literature, we support the opinion of a recent similar case report that the incidence of placental choriocarcinoma may actually be higher than expected, as placental examination after a normal spontaneous delivery is not routinely performed at most of the institutions. PMID- 20736776 TI - The first 2 cases of granulocyte colony-stimulating factor producing adenocarcinoma of the uterine cervix. AB - Granulocyte colony-stimulating factor (G-CSF)-producing nonhematopoietic malignancies have been reported in various organs, and most of them have been associated with poor clinical outcome. However, because of the rarity of the reported cases, information regarding the G-CSF-producing gynecological malignancies is limited. We report the first 2 cases of G-CSF-producing cervical adenocarcinomas, which exhibited an aggressive clinical course. At initial diagnosis, both patients exhibited marked leukocytosis without an obvious sign of infections. Of these, one was initially treated with definitive radiotherapy and the other was treated with radical surgery. However, both of these patients experienced recurrences in a short period and died from disease progression in less than 6 months. According to the facts that the tumor cells were positive for G-CSF, the elevated serum level of G-CSF, and their clinical course correlated well with the white blood cell count, we concluded that these tumors were G-CSF producing cancers. These cases strongly indicate the aggressive nature of the G CSF-producing cervical adenocarcinomas. PMID- 20736777 TI - Sebaceous glands in the uterine cervix and vaginal wall: congenital misplacement, metaplastic process, or both? PMID- 20736778 TI - Enterobious vermicularis (pinworm) infestation of the vulva: report of 2 cases of a pseudoneoplastic lesion mimicking squamous carcinoma. AB - Enterobious Vermicularis (pinworm) infestation outside the gastrointestinal tract is rare. We report 2 patients with vulval involvement, one of whom presented with a clinically suspicious, rapidly growing mass. The histology of both lesions showed similar features of epidermal proliferation in the form of hyperkeratosis, acanthosis, and papillomatosis; this pseudoepitheliomatous hyperplasia raised the possibility of a well-differentiated squamous carcinoma. There was associated inflammation in both cases, including large numbers of eosinophils in 1 case. On the surface or within the keratin layer, structures with the morphology of enterobious vermicularis eggs were identified. In reporting this unusual pseudoneoplastic phenomenon, we stress the necessity for the pathologist to consider and look for parasites in proliferative squamous lesions of the vulva, especially when there is an associated inflammatory infiltrate rich in eosinophils. PMID- 20736779 TI - Tubulo-squamous polyp of the vagina with sebaceous glands: novel features in an uncommon recently described entity. AB - Tubulo-squamous polyp of the vagina is a recently described histopathologic entity. This case report describes an as yet unreported morphologic feature of sebaceous glands in an example of this lesion. Further knowledge of the morphologic spectrum of this lesion should be of aid to histopathologists in its recognition. A brief review of currently available literature on this topic is also given. PMID- 20736780 TI - Adenocarcinoma arising in a rectovaginal fistula in Crohn disease. AB - Adenocarcinomas occurring in the vagina are rare. Their correct classification may be very challenging to both the gynecologist and the pathologist, but it is essential for appropriate therapy. Although most adenocarcinomas in the vagina arise from other sites in the female genital tract, a significant minority reflects metastasis from a colorectal site. We report a very unusual occurrence of an adenocarcinoma that presented as a mass in the vagina protruding through the introitus. It arose in a rectovaginal fistula consequent to chronic Crohn disease, but it did not extend to involve the colonic mucosa. Neither the initial clinical examination nor the pathologic examination suggested the correct diagnosis. We report this case to remind the gynecologists of the potential complications of Crohn disease, and to highlight for the pathologists the difficulty that is often encountered in the correct identification of the source of carcinomas that are found in the vagina. PMID- 20736781 TI - Myoepithelial carcinoma of the vulva mimicking bartholin gland abscess in a pregnant woman: case report and review of literature. AB - Myoepithelial tumors of the vulva are extremely rare, with only 8 cases reported in the literature to date. We report the first case of a high-grade myoepithelial vulvar carcinoma diagnosed in a 35-year-old woman during the 27th week of her pregnancy. The patient initially underwent a wide local excision of the lesion but noted rapid regrowth of the vulvar mass during the next 2 months before her delivery. Shortly thereafter, she underwent a classic radical Taussig-Basset total radical vulvectomy, bilateral superficial and deep inguinal groin node dissection, partial vaginectomy, and reconstruction of the vulva. However, the patient rapidly developed both locoregional and distant mestatatic disease, despite aggressive chemoradiotherapy, and she eventually succumbed to disseminated disease almost 20 months after her initial diagnosis. PMID- 20736782 TI - Minutes of the annual business meeting, Sunday, March 21, 2010: Mariott Wardman Park Hotel, Washington. PMID- 20736783 TI - Medical therapy of pericardial diseases: part I: idiopathic and infectious pericarditis. AB - The treatment of pericardial diseases is largely empirical because of the relative lack of randomized trials compared with other cardiovascular diseases. The main forms of pericardial diseases that can be encountered in the clinical setting include acute and recurrent pericarditis, pericardial effusion with or without cardiac tamponade, and constrictive pericarditis. Medical treatment should be targeted at the cause of the disease as much as possible. However, the cause of pericardial diseases may be varied and depends on the prevalence of specific diseases (especially tuberculosis). The search for an etiology is often inconclusive, and most cases are classified as idiopathic in developed countries where tuberculosis is relatively rare, whereas a tuberculous etiology is often presumed in developing countries where tuberculosis is endemic. The aim of the present article is to review current medical therapy for pericardial diseases, highlighting recent significant advances in clinical research, ongoing challenges and unmet needs. Following a probabilistic approach, the most common causes are considered (idiopathic, viral, tuberculous, purulent, connective tissue diseases and neoplastic pericardial disease). In this article, the therapy of idiopathic and more common forms of infectious pericarditis (viral and bacterial) is reviewed. PMID- 20736784 TI - Usefulness of frailty profile for targeting older heart failure patients in disease management programs: a cost-effectiveness, pilot study. AB - BACKGROUND: Disease management programs (DMP) improve outcomes in patients with heart failure. Because older heart failure patients represent a heterogeneous population, the aim of this study was to determine which patients benefit mostly from a DMP, by means of their frailty profile. SETTING: Heart failure outpatient clinic. METHODS: Consecutive (n = 173) patients aged more than 70 years were randomized to a multidisciplinary DMP (n = 86) or usual care (n = 87). A modified frailty score (range 1-6) was used as an index of global functional impairment. RESULTS: Mild to moderate frailty (frailty score = 2-3) was associated with significant improvements in outcomes (death and/or heart failure admission, heart failure admissions and all-cause admissions) in DMP patients vs. usual care. Even in more frail patients (frailty score = 4-6) a significant reduction in heart failure admissions was observed. By contrast, nonfrail patients (frailty score = 1) did not derive significant benefit. In the cost-effectiveness analysis, the mean savings per patient, stratified according to their frailty score, were 1003.31 euro for frailty score 1 (95% confidence interval -3717.00-1709.00), 1104.72 euro for frailty score 2 (-280.6-2491.00), 2635.42 euro for frailty score 3 (352.60-4917.00, P = 0.025) and 419.53 euro for frailty score 4-6 (-1909.00 2749.00). Intervention was therefore significantly cost saving in moderately frail, but not in nonfrail or severely frail patients. Thus, DMP was dominant (i.e. both less costly and more effective than usual care) in moderately frail patients. At sensitivity analysis, DMP remained dominant even to changes in cost of intervention and hospitalizations. CONCLUSION: This suggests that an intensive, hospital-based DMP appears to be more effective in older patients with mild-to-moderate levels of frailty. Thus, a multidimensional assessment of frailty seems to be a useful tool for appropriate selection of model of care. PMID- 20736785 TI - Orthopaedic Trauma Association 2009 Basic Science Focus Forum. Introduction. PMID- 20736786 TI - Trauma-induced inflammation and fracture healing. AB - Fracture healing is an extremely complex interaction of cells, biologic pathways, and molecules. Certainly, the inflammatory response is one of the initiating factors for bone healing. The inflammatory phase is a critical period characterized by low oxygen tension, impaired perfusion, and the migration of a wide array of cells and release of active molecules. Systemwide inflammatory conditions also modulate the primary processes of fracture management. Osteoprogenitor cells, mesenchymal cells, osteoblasts, and chondrocytes contribute to the healing and inflammatory response at the bone level. The inflammatory process is dependent on and propagates through proinflammatory cytokines, the transforming growth factor-beta superfamily with other growth factors, and the metalloproteinases and angiogenic factors. Interference with any of these pathways or proteins either promotes or more likely decreases fracture healing. This article reviews the initial inflammatory response to trauma as it pertains to musculoskeletal healing. PMID- 20736787 TI - Indomethacin reduces cell damage: shedding new light on compartment syndrome. AB - INTRODUCTION: Indomethacin may preserve tissue viability in compartment syndrome. The mechanism of improved tissue viability is unclear, but the anti-inflammatory effects may alter the relative contribution of tissue necrosis versus apoptosis to cellular injury. Existing studies have only considered indomethacin administration before induction of elevated intracompartment pressure. The purpose of this study was to determine the effect of timing of indomethacin administration on muscle damage in elevated intracompartment pressure and to assess apoptosis as a cause of tissue demise. METHODS: Twenty-four Wistar rats were randomized to elevated intracompartmental pressure (EICP) for either 45 or 90 minutes (30 mmHg). In the 45-minute cohort, indomethacin was withheld in Group 1 (CS45), given before induction of EICP in Group 2 (CS45Indo0), or given after 30 minutes of EICP/15 minutes before fasciotomy in Group 3 (CS45Indo30). In the 90-minute cohort, indomethacin was withheld in Group 4 (CS90) or given after 30 or 60 minutes of EICP in Groups 5 (CS90Indo30) and 6 (CS90Indo60). Intravital microscopy and fluorescent staining assessed capillary perfusion, cell damage, and inflammatory activation within extensor digitorum longus muscle. Apoptosis was assessed using spectrophotometric assessment of caspase levels. Groups 1 to 3 and 4 to 6 were compared using analysis of variance with P < 0.05 deemed significant. RESULTS: Perfusion and tissue viability improved in indomethacin treated groups. Nonperfused capillaries decreased from Group 1 (CS45) (50.1 +/- 2.5) to Group 2 (CS45Indo0) (38.4 +/- 1.8) and Group 3 (CS45Indo30) (14.13 +/- 1.73) (P < 0.05). Similarly, Group 5 (CS90Indo30) and Group 6 (CS90Indo60) had 25% fewer nonperfused capillaries compared with Group 4 (CS90) (P < 0.0001). Group 2 (CS45Indo0) and Group 3 (CS45Indo30) showed fewer damaged cells (1% +/- 0.5% and 8.7% +/- 2%) compared with Group 1 (CS45) (20% +/- 14%) (P < 0.0001). Group 5 (CS90Indo30) showed decreased cell damage (13% +/- 1%) compared with Group 4 (CS90) (18% +/- 1%) (P < 0.01). Group 6 (CS90Indo60) also showed decreased cell damage (11% +/- 1%) compared with Group 4 (CS90) (18% +/- 1%); however, this difference was not significant (P > 0.05). Apoptotic activity was present with elevated intracompartment pressure. At 30 minutes, there were elevated caspase levels in Group 4 and Group 6 EICP groups (0.47 +/- 0.08) compared with control subjects (0.19 +/- 0.02) (P < 0.003). However, indomethacin treated groups did not differ from control subjects with regard to caspase levels (P > 0.05). CONCLUSION: Indomethacin decreased cell damage and improved perfusion in elevated intracompartment pressure. The benefits of indomethacin were partially time-dependent; some improvement in tissue viability occurred regardless of timing of administration. Although apoptosis was common in elevated intracompartment pressure, the protective effect of indomethacin does not appear to be related to apoptosis. CLINICAL RELEVANCE: Adjuvant treatment with indomethacin may improve outcome in compartment syndrome. PMID- 20736788 TI - The genetics of heterotopic ossification: insight into the bone remodeling pathway. AB - OBJECTIVES: Heterotopic Ossification (HO) is a significant complication after trauma occurring in 12% to 25% of fractures. Although clinical predictors have been studied to determine the likelihood of developing HO, the results have been inconsistent. This study examines genetic predictors of the HO phenotype to identify the "at-risk" patient and increase the understanding of the genetic contribution to the formation of HO. METHODS: We examined the frequency of 61 single nucleotide polymorphisms (SNPs) in 1095 consecutive trauma patients with fractures. Radiographic studies of these patients were examined for HO in follow up. Ten percent of the patients in the study demonstrated radiographic evidence of HO. Multivariate logistic regression was used to analyze each SNP independently while adjusting for severity of injury (as measured by the Trauma and Injury Severity Score). RESULTS: Three SNPs (beta2-adrenergic receptor, toll like receptor 4, complement factor H) were identified that were associated with an increased or decreased frequency of HO. The less common polymorphism of the beta2-adrenergic receptor gene was associated with increased risk of HO. For toll like receptor 4 and complement factor H, the less common polymorphism was associated with a decreased risk of HO. CONCLUSIONS: The SNPs identified as predictors of HO formation are representative of the adrenergic system, immune system, and the alternative complement system. This represents the interplay of multiple pathways that affect bone remodeling, aberrations of which may be found in the genome. PMID- 20736789 TI - Mitochondrial damage associated molecular patterns from femoral reamings activate neutrophils through formyl peptide receptors and P44/42 MAP kinase. AB - HYPOTHESIS: Fractures and femoral reaming are associated with lung injury. The mechanisms linking fractures and inflammation are unclear, but tissue disruption might release mitochondria. Mitochondria are evolutionarily derived from bacteria and contain "damage associated molecular patterns" like formylated peptides that can activate immunocytes. We therefore studied whether fracture reaming releases mitochondrial damage associated molecular patterns (MTD) and how MTD act on immune cells. METHODS: Femur fracture reamings (FFx) from 10 patients were spun to remove bone particulates. Supernatants were assayed for mitochondrial DNA. Mitochondria were isolated from the residual reaming slurry, sonicated, and spun at 12,000 g. The resultant MTD were assayed for their ability to cause neutrophil (PMN) Ca transient production, p44/42 MAPK phosphorylation, interleukin-8 release, and matrix metalloproteinase-9 release with and without formyl peptide receptor-1 blockade. Rats were injected with MTD and whole lung assayed for p44/42 activation. RESULTS: Mitochondrial DNA appears at many thousand-fold normal plasma levels in FFx and at intermediate levels in patients' plasma, suggesting release from fracture to plasma. FFx MTD caused brisk PMN Ca flux, activated PMN p44/42 MAPK, and caused PMN release of interleukin-8 and matrix metalloproteinase-9. Responses to MTD were inhibited by formyl peptide receptor-1 blockade using cyclosporine H or anti-formyl peptide receptor-1. MTD injection caused P44/42 phosphorylation in rat lung. CONCLUSIONS: FFx reaming releases mitochondria into the wound and circulation. MTD then activates PMN. Release of damage signals like MTD from FFx may underlie activation of the cytokine cascades known to be associated with fracture fixation and lung injury. PMID- 20736790 TI - Arachidonic acid, eicosanoids, and fracture repair. AB - Not all fractures heal well or rapidly in the adult skeleton, and basic scientists and clinicians continue to search for ways to make fractures heal more predictably. It is a fundamental tenet of orthopaedics that skeletal injury is followed by inflammation and that this inflammatory response is the first stage in a sequence of events that culminate in skeletal repair. Modulating this response can affect the inflammatory stage and in turn subsequent stages that are required for healing. Literally dozens of studies in animals dating back to the 1970s have investigated the effects of commonly used anti-inflammatory medications on prostaglandin synthesis and fracture repair with strikingly uniform results. More recently, investigators have begun examining other means of modulating the early inflammatory stages after fracture in an effort to enhance fracture healing. This article reviews recent investigations into the potential role of leukotrienes as negative regulators of fracture healing and potential pharmacologic use of medications that block this effect. PMID- 20736791 TI - Growth factors: beyond bone morphogenetic proteins. AB - The current landscape of growth factors in orthopaedic trauma is dominated by the BMPs, as they are the most extensively studied growth factors in clinical applications pertaining to orthopaedic trauma. Despite this, their application and indications for use in trauma remain controversial. This article highlights a number of selected growth factors, other than BMPs, that are currently being investigated in orthopaedic trauma applications. These growth factors have shown significant promise in preclinical and early clinical investigation. PMID- 20736792 TI - Effect of human vascular endothelial growth factor gene transfer on endogenous vascular endothelial growth factor mRNA expression in a rat fibroblast and osteoblast culture model. AB - PURPOSE: Vascular endothelial growth factor (VEGF) plays an important role in promoting angiogenesis and osteogenesis during fracture repair. Our previous studies have shown that cell-based VEGF gene therapy enhances bone healing of a rabbit tibia segmental bone defect in vivo. The aim of this project was to examine the effect of exogenous human VEGF on the endogenous rat VEGF messenger RNA (mRNA) expression in a cell-based gene transfer model. METHODS: Rat fibroblasts and osteoblasts were harvested from the dermal tissue and periosteum, respectively, of Fisher 344 rats. The cells were then cultured and transfected with pcDNA-human VEGF using Superfect reagent (Qiagen). Four experimental groups were created: 1) fibroblast-VEGF; 2) osteoblast-VEGF; 3) nontransfected fibroblast controls; and 4) nontransfected osteoblast controls. The cultured cells were harvested at 1, 3, and 7 days after the gene transfection. The total mRNA was extracted (Trizol; Invitrogen); both human VEGF and rat VEGF mRNA were measured by reverse transcriptase-polymerase chain reaction and quantified by VisionWorksLS. RESULTS: The human VEGF165 mRNA was detected by reverse transcriptase-polymerase chain reaction from transfected fibroblasts and osteoblasts at 1, 3, and 7 days after gene transfection. The human VEGF165 levels peaked at Day 1 and then gradually reduced expression in both transfected fibroblasts and osteoblasts. Two endogenous rat VEGF isoforms were detected in this cell culture model: rat VEGF120 and rat VEGF164. We compared the rat VEGF120 and rat VEGF164 expression level of the fibroblasts or osteoblasts that were transfected with human VEGF165, with nontransfected control cells. Both the transfected fibroblasts and osteoblasts showed greater expression of rat VEGF164 than nontransfected controls at Day 1 (peak level) and Day 3, but not at Day 7. The expression of rat VEGF120 was lower in transfected fibroblasts, but higher in transfected osteoblasts, than the relevant control groups at any time point after transfection. In addition, human VEGF gene transfection increased osteoblast cell proliferation after 3 days. CONCLUSION: These in vitro results suggest that cell based human VEGF gene therapy is not only effective at causing human VEGF expression, but also enhances endogenous rat VEGF mRNA expression in both fibroblasts and osteoblasts, particularly the rat VEGF164 isoform. PMID- 20736793 TI - The effect of bone morphogenetic protein-2, bone morphogenetic protein-7, parathyroid hormone, and platelet-derived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone. AB - INTRODUCTION: It has been previously shown that in patients with osteoporosis, mesenchymal stem cell (MSC) growth rate and osteogenic potential is decreased contributing to inferior fracture consolidation. The aim of this study was to investigate the effect of bone morphogenetic protein-2 (BMP-2), BMP-7, parathyroid hormone (PTH), and platelet-derived growth factor (PDGF) on proliferation and osteogenic differentiation of MSCs derived from patients with osteoporosis. MATERIALS AND METHODS: Trabecular bone was obtained from 10 patients (four males, mean age 76 years) with lower extremity osteoporotic fractures. MSCs were isolated by enzymatic digestion. Functional assays of proliferation and osteogenic differentiation were performed under the influence of a wide range of concentrations of BMP-2, BMP-7, PTH, and PDGF-BB. Proliferation was assessed using CFU-F and XTT assays. Osteogenic differentiation was assessed by alkaline phosphatase activity and total calcium production. RESULTS: MSC proliferation was found to be stimulated by supplementation with BMP 7 and PDGF-BB, whereas BMP-2 and PTH had little effect. The largest increase in proliferation rate was observed after administration 100 ng/mL of BMP-7. All four molecules induced alkaline phosphatase activity and calcium production in growing osteoblasts with a dose-dependent effect noted. BMP-2 and BMP-7 at their highest studied concentration (100 ng/mL) produced a threefold increase in the osteogenic potential of MSCs. CONCLUSION: BMP-7, BMP-2, PTH, and PDGF-BB were observed to have a positive effect on osteogenic differentiation of MSCs. BMP-7 and PDGF-BB (in high doses) could be considered most potentially advantageous because they enhance both proliferation and osteogenic differentiation of MSCs derived from elderly osteoporotic bone. PMID- 20736794 TI - Matrix metalloproteinases that associate with and cleave bone morphogenetic protein-2 in vitro are elevated in hypertrophic fracture nonunion tissue. AB - OBJECTIVES: A delayed union or a nonunion of a fracture is a potentially adverse complication. Understanding the mechanisms of nonunion development may lead to improved treatment modalities. Proteases such as the matrix metalloproteinases play important roles in bone remodeling and repair, in which an imbalance or a nonfunctioning enzyme may lead to defects in bone healing (nonunion). The purpose of this pilot study was twofold: first to define an mRNA expression profile of all the matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases with thrombospondin motif (ADAMTS) enzymes, and their inhibitors (TIMPs) within fracture nonunion tissue, and second to compare this profile with mineralized fracture callus. METHODS: Using a systematic real-time polymerase chain reaction, we screened the gene expression profiles of all members of the MMPs, ADAMTS, and their inhibitor TIMPs on human fracture nonunion tissue and matched mineralized callus tissue. Significant results were further analyzed using Western immunoblotting, immunohistochemistry, and in vitro protein interaction assays with bone morphogenetic protein-2. RESULTS: This analysis confirmed MMP-7 and MMP 12 as two unidentified enzymes expressed in fracture nonunion tissue. Both MMP-7 and MMP-12 mRNAs were significantly elevated in nonunion tissue when compared with local mineralized callus from the same site (P < 0.001); the elevated protein levels of interest were visualized through immunoblotting and immunohistochemistry. In addition, these two MMPs were found to directly bind to and degrade bone morphogenetic protein-2 in vitro. CONCLUSION: Collectively, our findings indicate that tissue present at the site of hypertrophic nonunions commonly expresses significantly higher levels of MMP-7 and MMP-12 in relation to mineralized fracture callus. Both were found to directly inactivate bone morphogenetic protein-2 in vitro, the best established growth factor in bone formation and repair. PMID- 20736795 TI - Quantitative assessment of the bone morphogenetic protein expression from alternate bone graft harvesting sites. AB - OBJECTIVE: Bone morphogenetic proteins (BMPs) play important roles in the stimulation of osteogenesis and osteoinduction during bone fracture healing and their expression levels may be important for bone graft efficacy. The objective of this study was to determine if there are variations in the expression of BMPs and their receptors in various bone graft harvesting sites. We analyzed autogenous marrow aspirates obtained from three different graft sites for the mRNA levels of BMPs and their receptors. METHODS: Using real-time polymerase chain reaction, we analyzed the mRNA levels of BMPs and their receptors in autogenous bone marrow aspirates obtained from three different bone graft sites of 10 different human subjects. Collection of autogenous bone marrow from the iliac crest, the proximal humerus, and the proximal tibia was performed using standard sterile techniques in the operating room as part of surgery to treat an established fracture nonunion. RESULTS: The mRNA levels of BMP-2 and BMP-5 were the highest in the bone marrow aspirates from the three different sites, whereas the mRNA levels of the other osteoinductive BMPs (BMP-4, -5, -6, -7, -8, and -9) were lower. The mRNA levels of BMP-3, an inhibitor of osteogenesis, were the lowest in the bone marrow aspirates of all three different sites. There were no statistical significant differences in the mRNA levels of any of the BMPs or their receptors investigated in this study in the bone marrow of the three different sites. CONCLUSION: Because no statistical significant differences in the mRNA levels of the BMPs and their receptors were detected in the bone marrow aspirates from the three different sites, our findings suggest that potential differences of various graft sites in the augmentation of bone healing does not result from different expression levels of BMPs. PMID- 20736797 TI - Protective effect of P188 in the model of acute trauma to human ankle cartilage: the mechanism of action. AB - OBJECTIVE: Because P188 poloxamer is effective in promoting cell survival in models of acute trauma, the objectives were to understand the mechanism of its action focusing on glycogen synthase kinase-3 (GSK3) activation, interleukin-6 (IL-6), and p38 signaling. DESIGN: Sixteen normal human tali were impacted using a 4-mm diameter indenter with an impulse of 1 Ns. Eight-millimeter cartilage plugs containing the 4-mm impacted core and 4-mm adjacent nonimpacted ring were removed and cultured with or without P188. Cell lysates were analyzed using Western blots with antibodies against total and phosphorylated extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38, ATF 2, GSK3, Stat1, and Stat3. Additional tests were performed with the p38 inhibitor (p38i) SB203580. RESULTS: Studied pathways were activated after impaction with the peak of activity at 1 hour. P188 completely attenuated phosphorylation of Stat1 and ATF-2 and inhibited p38, Stat3, JNK, ERK, and GSK3. The p38i partially offset phosphorylation of Stat3, GSK3, and ERK suggesting a role of p38 in these three pathways. Additionally, the p38i improved cell survival (P = 0.053) and reduced apoptosis (by approximately 20%, P = 0.046, versus almost 40% by P188), thus confirming that P188 acts (at least in part) through the p38 pathway. CONCLUSION: Our results report a novel mechanism through which P188 exerts its protective effects on cartilage in the model of acute injury. In addition to its effect on cellular membrane, P188 affects stress-related p38 signaling, apoptosis related GSK3, and inflammation-related IL-6 signaling. Taken together, these findings suggest that P188 alone or in combination with proanabolic agents may have a therapeutic potential in preventing progressive cartilage degeneration and the development of posttraumatic osteoarthritis. PMID- 20736796 TI - Basic science of intra-articular fractures and posttraumatic osteoarthritis. AB - Intra-articular fractures represent the primary etiologic factor leading to posttraumatic osteoarthritis. The pathomechanisms linking intra-articular fractures to end-stage cartilage destruction are poorly understood. However, fracture-related chondrocyte death has been linked to posttraumatic osteoarthritis. Researchers have made significant progress in understanding the pathomechanical link between injury and chondrocyte death. This article reviews recent basic scientific progress investigating intraarticular fractures and fracture-related chondrocyte death and dysfunction. PMID- 20736798 TI - Optical coherence tomography detection of subclinical traumatic cartilage injury. AB - OBJECTIVES: Posttraumatic arthritis is a major cause of disability. Current clinical imaging modalities are unable to reliably evaluate articular cartilage damage before surface breakdown, when potentially reversible changes are occurring. Optical coherence tomography (OCT) is a nondestructive imaging technology that can detect degenerative changes in articular cartilage with an intact surface. This study tests the hypothesis that OCT detects acute articular cartilage injury after impact at energy levels resulting in chondrocyte death and microstructural changes, but insufficient to produce macroscopic surface damage. METHODS: Bovine osteochondral cores underwent OCT imaging and were divided into a control with no impact or were subjected to low (0.175 J) or moderate (0.35 J) energy impact. Cores were reimaged with OCT after impact and the OCT signal intensity quantified. A ratio of the superficial to deep layer intensities was calculated and compared before and after impact. Chondrocyte viability was determined 1 day after impact followed by histology and polarized microscopy. RESULTS: Macroscopic changes to the articular surface were not observed after low and moderate impact. The OCT signal intensity ratio demonstrated a 27% increase (P = 0.006) after low impact and a 38% increase (P = 0.001) after moderate impact. Cell death increased by 150% (P < 0.001) and 200% (P < 0.001) after low and moderate energy impacts, respectively. When compared with unimpacted controls, both Mankin histology and David-Vaudey polarized microscopy scores increased (P = 0.036 and P = 0.002, respectively) after moderate energy impact. CONCLUSIONS: This study shows that OCT detects acute cartilage changes after impact injury at levels insufficient to cause visible damage to the articular surface but sufficient to cause chondrocyte death and microscopic matrix damage. This finding supports the use of OCT to detect microstructural subsurface cartilage damage that is poorly visualized with conventional imaging. PMID- 20736799 TI - Infection. AB - Musculoskeletal infection is a clinical problem with significant direct healthcare costs. The prevalence of infection after closed, elective surgery is frequently estimated to be less than 2%, but in severe injuries, posttraumatic infection rates have been reported as 10% or greater. Although clinical infections are found outside the realm of medical devices, it is clear that the enormous increase of infections associated with the use of implants presents a major challenge worldwide. This review summarizes recent advances in the understanding, diagnosis, and treatment of musculoskeletal infections. PMID- 20736800 TI - The use of a biodegradable, load-bearing scaffold as a carrier for antibiotics in an infected open fracture model. AB - OBJECTIVES: Open fractures with bone loss are common, disabling injuries. Biodegradable, load-bearing scaffolds able to carry high concentrations of local antibiotics are an emerging technology to address these injuries. This study investigates the use of such scaffolds with gentamicin (along with bone morphogenetic protein) in an infected rat open fracture model to decrease osteomyelitis and promote fracture healing. METHODS: A contaminated open fracture was created in 32 Brown Norway rats. A comminuted femoral fracture was created, followed by crushing, and the 5-mm bone defect was inoculated with Staphylococcus aureus (10 colony-forming units/mL) and Escherichia coli (10 colony-forming units/mL). The scaffold was stabilized in the defect with an intramedullary Kirschner wire. Gentamicin was loaded onto the scaffolds at two doses, either 10 mg (n = 12) or 20 mg (n = 10). Controls (n = 10) received no antibiotics. All three groups had 10 microg bone morphogenetic protein loaded on the scaffold. Serial radiographs were obtained. Microbiologic analysis, microcomputed tomography, and histology were performed. RESULTS: There was a statistically significant difference in the radiographic evidence of osteomyelitis (P = 0.004) and callus formation (P = 0.021) between the treated and control groups. Bone culture analysis results were not significant for S. aureus (P = 0.29) or E. coli (P = 0.25). There was no difference in the mean scaffold volume or density of the three treatment groups. CONCLUSIONS: Our results suggest that gentamicin applied to a biodegradable scaffold is effective at decreasing radiographically defined osteomyelitis in an infected open fracture. PMID- 20736801 TI - Local antibiotic delivery using tailorable chitosan sponges: the future of infection control? AB - OBJECTIVES: Local antibiotic delivery is a viable and attractive option for preventing infection. Unfortunately, the current options are limited and often necessitate surgical removal. This study evaluates the ability of a biodegradable and biocompatible chitosan sponge to minimize infection by delivering local antibiotics within the wound. METHODS: A complex musculoskeletal wound was created on the hindlimb of goats and contaminated with Pseudomonas aeruginosa (lux) or Staphylococcus aureus (lux) bacteria. These bacteria are genetically engineered to emit photons, allowing for quantification with a photon-counting camera system. The wounds were closed and similarly debrided and irrigated with 9 L normal saline using bulb-syringe irrigation 6 hours after inoculation. Goats were assigned to different treatment groups: a control group with no adjunctive treatment and an experimental group using a chitosan sponge loaded with either amikacin (for wounds contaminated with P. aeruginosa) or vancomycin (for wounds contaminated with S. aureus). The wounds were closed after the procedure and evaluated 48 hours after initial contamination. Serum levels of the antibiotics were also measured at 6, 12, 24, 36, and 42 hours after treatment was initiated. RESULTS: The wounds treated with the antibiotic-loaded chitosan sponge had significantly less bacteria than the untreated wounds (P < 0.05). The highest serum levels were 6 hours after treatment but remained less than 15% of target serum levels for systemic treatment. At study end point, all sponges were between 60% and 100% degraded. CONCLUSIONS: The chitosan sponges are effective delivering the antibiotic and reducing the bacteria within the wounds. PMID- 20736802 TI - Negative pressure wound therapy reduces pseudomonas wound contamination more than Staphylococcus aureus. AB - PURPOSE: The purpose of this study is to determine if negative pressure wound therapy (NPWT) treatment results in fewer bacteria than wet-to-dry (WTD) dressings in a contaminated open fracture wound model. METHODS: For Study 1, complex wounds were created on the proximal left leg of goats. The wounds were inoculated with Pseudomonas aeruginosa. The wounds were debrided and irrigated 6 hours after inoculation. The first group received WTD dressing changes twice daily; the second and third groups received NPWT using systems from two different companies. All three groups received repeat debridements every 48 hours for 6 days. Bacteria quantification was performed both immediately before and after each debridement. For Study 2, the only changes were that Staphylococcus aureus was used and only one NPWT group was included. RESULTS: In Study 1, there were significantly fewer Pseudomonas in both NPWT groups at all imaging sessions after the initial debridement and irrigation. At the 6-day time point, the wounds in the NPWT groups were 43 +/- 14% and 68 +/- 6% of the baseline amount, respectively. The WTD groups were 464 +/- 102% of the baseline amount. In Study 2, NPWT did not reduce the S. aureus contamination within the wound. At the 6-day time point, the wounds in the NPWT and WTD groups contained 115 +/- 19% and 192 +/- 52% of the baseline values, respectively. CONCLUSION: NPWT showed a significant and sustained decrease in the Pseudomonas levels compared with WTD dressings at all time points. This beneficial effect was seen not seen in S. aureus. PMID- 20736803 TI - Chemotherapy-induced pulmonary toxicity in lung cancer patients. PMID- 20736804 TI - Receiver operating characteristic curve in diagnostic test assessment. AB - The performance of a diagnostic test in the case of a binary predictor can be evaluated using the measures of sensitivity and specificity. However, in many instances, we encounter predictors that are measured on a continuous or ordinal scale. In such cases, it is desirable to assess performance of a diagnostic test over the range of possible cutpoints for the predictor variable. This is achieved by a receiver operating characteristic (ROC) curve that includes all the possible decision thresholds from a diagnostic test result. In this brief report, we discuss the salient features of the ROC curve, as well as discuss and interpret the area under the ROC curve, and its utility in comparing two different tests or predictor variables of interest. PMID- 20736805 TI - Molecular predictors of sensitivity to the MET inhibitor PHA665752 in lung carcinoma cells. AB - BACKGROUND: No comprehensive data are available on the molecular predictors of sensitivity to MET inhibitor in lung carcinomas. METHODS: We examined the efficacy of the MET inhibitor PHA665752 in 41 cell lines of non-small lung carcinoma to determine whether sensitivity to the MET inhibitor is correlated with the (1) genetic statuses of MET, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, and KRAS, (2) MET phosphorylation and its downstream signaling pathways, or (3) epithelial-mesenchymal transition. RESULTS: Of the 41 cells, 8 were highly or intermediately sensitive to PHA665752, and the remainder were PHA665752 resistant. The sensitive cells (n = 8) included not only 4 of 4 MET-amplified cell lines but also 2 of 11 KRAS-mutated cell lines and 1 of 6 EGFR-mutated cell lines. Unlike the MET-amplified cell lines, both the MET-mutated cell lines were PHA665752 resistant. High phospho-MET was not restricted to the four MET-amplified cell lines. To the contrary, it was also found in 9 of 37 MET-nonamplified cell lines, including 3 of 6 EGFR-mutated cell lines and 4 of 11 KRAS-mutated cell lines. High phospho-MET was correlated with PHA665752 sensitivity in the entire panel of cell lines, especially in the KRAS mutated cells. The AKT and ERK pathways in the high phospho-MET cell lines were dependent on MET activation in MET-amplified and KRAS-mutated cells but not in EGFR-mutated and human epidermal growth factor receptor 2-amplified cells. CONCLUSIONS: MET amplification is an excellent predictor of PHA665752 sensitivity but not the sole predictor. High phospho-MET and dependence of the AKT and ERK pathways on MET activation may predict sensitivity to PHA665752, especially in KRAS-mutated cell lines. PMID- 20736806 TI - Insulin-like growth factor-1 receptor expression in thymic malignancies. AB - INTRODUCTION: Thymic epithelial tumors are rare mediastinal malignancies that can be invasive and difficult to treat. Insulin-like growth factor-1 receptor (IGF 1R) is a transmembrane receptor implicated in the regulation of cell metabolism, growth, and survival. As higher levels of IGF-1R protein expression may be associated with relative sensitivity to anti-IGF-1R antibody treatment, we investigated IGF-1R expression in thymic malignancies. METHODS: Sixty-three thymic tumors (56 thymomas and seven thymic carcinomas) were analyzed for total IGF-1R expression using immunohistochemistry with a specific antibody (clone G11, Roche-Ventana, Tucson, AZ). Expression levels were correlated with relevant clinical and pathologic variables, including epidermal growth factor receptor and KIT expression, and patient outcome. RESULTS: IGF-1R staining was negative in 13 (21%) cases, low (1+) in 20 (32%) cases, moderate (2+) in 20 (32%) cases, and high (3+) in 10 (16%) cases. Moderate to high IGF-1R staining was observed in 6 of 7 (86%) thymic carcinomas and in 24 of 56 (43%) thymomas (p = 0.039). Moderate to high IGF-1R staining was associated with high epidermal growth factor receptor staining (p = 0.015). By multivariate analysis, only tumor stage and histologic type were significant prognostic factors on time to progression (hazard ratio [HR] = 4.12, 95% confidence interval [CI]: 1.98-14.23; p = 0.010 and HR = 2.79, 95% CI: 1.62-12.50; p = 0.018, respectively). There was no association between IGF-1R expression and time to progression (HR = 3.07, 95% CI: 0.38-24.59; p = 0.291). CONCLUSION: A majority of thymic malignancies display moderate to high expression of IGF-1R. The lack of preclinical models prevented us to further study the functional consequences of anti-IGF-1R therapy in this setting. However, given correlations in other cancers, these data support the evaluation of anti-IGF-1R inhibitors in thymic tumors. PMID- 20736807 TI - Side-effects of long-term administration of erlotinib in patients with non-small cell lung cancer. AB - INTRODUCTION: Currently, the inhibitor of the epidermal growth factor receptor tyrosine kinase erlotinib is widely used for the treatment of non-small cell lung cancer. Patients with a mutation or deletion in the epidermal growth factor receptor gene will benefit most and are likely to receive the drug for long periods and willing to accept side effects if responding. METHODS: Twenty-two cases with prolonged administration of erlotinib (at least 6 months) and side effects are reported. Three cases with specific side effects are described in detail. RESULTS: In addition to the well-known side effects such as folliculitis and diarrhea, patients reported paronychia, fatigue, and hair changes. DISCUSSION: After prolonged administration of erlotinib in most patients, the initial side effects persist while other inconvenient ones may develop. This may lead to dose reductions or even cessation of treatment. PMID- 20736808 TI - Lung cancer with unusual presentation as a thin-walled cyst in a young nonsmoker. PMID- 20736809 TI - Atypical thymoma (World Health Organization Type B3) with neuroendocrine differentiation combined with hyperparathyroidism. PMID- 20736811 TI - Pulmonary pleomorphic carcinoma: diagnosis using small biopsy specimens. PMID- 20736812 TI - Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. AB - OBJECTIVE: In vitro treatment of Nf2-deficient cells with epidermal growth factor receptor (EGFR) inhibitors can reduce cellular proliferation. We sought to determine the activity of erlotinib for progressive vestibular schwannoma (VS) associated with neurofibromatosis 2 (NF2). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Eleven NF2 patients with progressive VS who were poor candidates for standard therapy. INTERVENTION: Erlotinib 150 mg daily. MAIN OUTCOME MEASURES: A radiographic response was defined as >or= 20% decrease in tumor volume compared with baseline. A hearing response was defined as a statistically significant increase in word recognition score (WRS) compared with baseline; a minor hearing response was defined as a 10 dB improvement in pure-tone average with stable WRS. RESULTS: : Before treatment, the median and mean annual volumetric growth rate for 11 index VS were 26% and 46%, respectively. Among 10 evaluable patients, the median time-to-tumor progression was 9.2 months. Three patients with stable disease experienced maximum tumor shrinkage of 4%, 13%, and 14%. Nine patients underwent audiologic evaluations. One experienced a transient hearing response, 2 experienced minor hearing responses, 3 remained stable, and 2 developed progressive hearing loss. The median time-to-progressive hearing loss was 9.2 months and to either tumor growth or progressive hearing loss was 7.1 months. Adverse treatment effects included mild-to-moderate rash, diarrhea, and hair thinning, with 2 episodes of grade 3 toxicity. CONCLUSION: Erlotinib treatment was not associated with radiographic or hearing responses in NF2 patients with progressive VS. Because a subset of patients experienced prolonged stable disease, time-to-progression may be more appropriate than radiographic or hearing response for anti-EGFR agents in NF2-associated VS. PMID- 20736813 TI - Darunavir concentrations exceed the protein-corrected EC50 for wild-type HIV in the semen of HIV-1-infected men. AB - Variable antiretroviral drug penetration into the genital tract may contribute to the differential evolution of HIV-1 and the emergence of drug resistance. We compared concentrations of darunavir in 34 time-matched blood plasma and seminal plasma samples from 18 HIV-1 positive men. Darunavir in seminal plasma were approximately 10-20% of that achieved in blood at matched time points postdrug ingestion. All seminal plasma darunavir were above the protein-corrected EC50 values for wild-type HIV-1. PMID- 20736814 TI - Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies. AB - BACKGROUND: The MOTIVATE-1 and 2 studies compared maraviroc (MVC) along with optimized background therapy (OBT) vs. placebo along with OBT in treatment experienced patients screened as having R5-HIV (original Monogram Trofile). A subset screened with non-R5 HIV were treated with MVC or placebo along with OBT in a sister safety trial, A4001029. This analysis retrospectively examined the performance of population-based sequence analysis of HIV-1 env V3-loop to predict coreceptor tropism. METHODS: Triplicate V3-loop sequences were generated using stored screening plasma samples and data was processed using custom software ('ReCall'), blinded to clinical response. Tropism was inferred using geno2pheno ('g2p'; 5% false positive rate). Primary outcomes were viral load changes after starting maraviroc; and concordance with prior screening Trofile results. RESULTS: Genotype and Trofile results were available for 1164 individuals with virological outcome data (N = 169 non-R5 by Trofile). Compared with Trofile, V3 genotyping had a specificity of 92.6% and a sensitivity of 67.4% for detecting non-R5 virus. However, when compared with clinical outcome, virological responses were consistently similar between Trofile and V3 genotype at weeks 8 and 24 following the initiation of therapy for patients categorized as R5. CONCLUSION: Despite differences in sensitivity for predicting non-R5 HIV, week 8 and 24 week virological responses were similar in this treatment-experienced population. These findings suggest the potential utility of V3 genotyping as an accessible assay to select patients who may benefit from maraviroc treatment. Optimization of the predictive tropism algorithm may lead to further improvement in the clinical utility of HIV genotypic tropism assays. PMID- 20736815 TI - Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AB - OBJECTIVE: Few studies have assessed longitudinal genital tract HIV-1 shedding. We determined patterns of genital tract HIV-1 RNA shedding over time among women with suppressed plasma viral load (PVL) on antiretroviral treatment. METHODS: Paired plasma and genital tract HIV-1 RNA were measured every 4 weeks. Participants were classified as persistent, intermittent, or nonshedders. Longitudinal analysis examined rates of genital tract shedding and the association with PVL, CD4 cell count, and genital tract infections. Markov transition models were used to describe the dynamics of HIV-1 RNA in plasma and genital tract using visit-to-visit transitions from and to detectable and undetectable PVL or genital tract HIV-1 RNA. RESULTS: Fifty-nine women contributed 582 study visits of whom 95 and 98% had below-detectable PVL and genital tract viral load, respectively, at baseline. Thirty-two of 59 women (54%) had detectable HIV-1 RNA at least once in the genital tract. Twenty-two of 59 (37%) women had detectable genital tract HIV-1 RNA during a study visit when PVL was undetectable; 6.8% of the women were persistent shedders, 31% were intermittent shedders, and 45.8% were nonshedders. Sampling three subcompartments increased detection of HIV-1 genital tract viral load compared to sampling a single subcompartment. Overall, genital tract HIV-1 RNA shedding in any subcompartment occurred at about 13% of visits. Shedding in at least one of the three subcompartments occurred at 9% of visits when PVL was undetectable (95% confidence interval 6-14%). CONCLUSION: Women with below-detectable PVL may have less risk of HIV sexual transmission on a population level, but may continue to be infectious on an individual level. PMID- 20736816 TI - Botulinum toxin type A injections for treatment of spastic equinus in cerebral palsy: a secondary analysis of factors predictive of favorable response. AB - OBJECTIVE: To investigate markers predicting favorable botulinum toxin injection outcomes in treating spastic equinus gait in children with cerebral palsy. DESIGN: Thirty-six children (21 boys and 15 girls, aged 1.5-9.6 yrs; 20 with unilateral and 16 with bilateral cerebral palsy levels I to IV with the Gross Motor Function Classification System) with 49 treated lower limbs were included. Passive range of movement, selective dorsiflexion, dynamic muscle length (modified Tardieu Scale), calf tone (modified Ashworth Scale), attainment of anticipated gait pattern (Goal Attainment Scale), and video gait analysis (Observational Gait Scale) were assessed before and 1, 2, and 4 mos after intervention. Participants were classified as poor or good responders, according to the Goal Attainment Scale response at 2 mos. RESULTS: Good response was noted in 23 (64%) children and 29 (59%) legs, whereas 13 (36%) children and 20 (41%) legs were defined as poor responders. In a multivariate regression analysis, the best predictors of good response per child were higher initial Observational Gait Scale total scores, one-level treatment, and normal cognition; and the best predictors per leg were good initial selective motor control in the ankle and capability of occasional flatfoot contact at pretreatment. CONCLUSIONS: These results suggest that children with less severe functional deficit, fair to good selective motor control in the ankle, and mild equinus gait respond best to focal botulinum toxin type A treatment, with an eye to flatfoot or heel strike contact. Likewise, children with higher cognitive level seem to derive functional benefit from the treatment. PMID- 20736817 TI - Oxygen uptake kinetics in older patients receiving postacute cardiac rehabilitation: effects of low-intensity aerobic training. AB - OBJECTIVE: Older patients who receive postacute cardiac rehabilitation improve their physical performance in terms of distance walked at the 6-min walk test. However, the slower and more complicated recovery, along with age-related chronic comorbidities, remarkably limits the intensity of aerobic training, which actually represents the core of cardiac rehabilitation. The aim of this study was to verify whether postacute cardiac rehabilitation also improves the cardiovascular adjustment to exercise, despite low-intensity aerobic training. DESIGN: Using a portable gas analyzer, we assessed the O(2) uptake kinetics during the 6-min walk test at the beginning and at the end of the rehabilitation in 84 patients aged 65 yrs and above. RESULTS: All patients significantly improved the distance walked at the 6-min walk test. The comparison of the time constants of O(2) uptake kinetics showed that 40% of patients also significantly improved the hemodynamic response to exercise. This improvement was independently associated with the report of sedentary lifestyle or low-intensity physical activity in the year before surgery and with longer time constants before physical training. CONCLUSIONS: Low-intensity aerobic training improves the cardiovascular adjustment to exercise selectively in patients with physical deconditioning. This confirms the notion that elderly frail patients are those who benefit most from cardiac rehabilitation. PMID- 20736818 TI - Active-passive bilateral therapy as a priming mechanism for individuals in the subacute phase of post-stroke recovery: a feasibility study. AB - OBJECTIVE: To assess the feasibility of treating inpatient stroke survivors with active-passive bilateral therapy as a motor priming technique before occupational therapy. DESIGN: Single case series with two matched pairs in the subacute post stroke rehabilitation phase. The test patients received active-passive bilateral therapy plus upper limb motor training. Control patients received only the motor training. RESULTS: Both Fugl-Meyer Upper Extremity scores and Action Research Arm Test scores improved in this small group of test and control patients. The magnitude of improvement was greater in test patients who received active-passive bilateral therapy plus unilateral training. CONCLUSIONS: We conclude that it is feasible and safe to administer active-passive bilateral therapy in a hospital setting. PMID- 20736819 TI - Intrathecal injection of anti-CX3CR1 neutralizing antibody delayed and attenuated pain facilitation in rat tibial bone cancer pain model. AB - This study was designed to investigate the effect of intrathecal injection of anti-CX3CR1 neutralizing antibody on pain behaviors in the rat tibial bone cancer pain model. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity to establish the rat model of bone cancer pain. Ambulatory pain, mechanical hindpaw withdrawal threshold, and latency of paw withdrawal to a thermal stimulus were observed. Haematoxylin/eosin staining was used to observe the bone damage on day 21. Intrathecal injection of anti-CX3CR1 neutralizing antibody both delayed the development of ambulatory pain and hyperalgesia and attenuated established pain facilitation, but had no effects on destruction of bone. Our results suggest that intrathecal injection of anti CX3CR1 neutralizing antibody delayed and attenuated pain facilitation in the rat tibial bone cancer pain model. PMID- 20736820 TI - Report of two FOP cases with 617G>A mutation in the ACVR1 gene from Chinese population. PMID- 20736821 TI - Antioxidant effects of cocoa and cocoa products ex vivo and in vivo: is there evidence from controlled intervention studies? AB - PURPOSE OF REVIEW: There is strong epidemiological evidence that the consumption of flavanol-rich cocoa products contributes to the prevention of cardiovascular diseases mediated partly by their strong antioxidant effects. We reviewed the recent literature to answer the question whether this antioxidant action can be confirmed by intervention studies in healthy study participants and specific patient groups. RECENT FINDINGS: In 19 controlled intervention studies (two in patients with cardiovascular diseases), markers of plasma antioxidant capacity and oxidative stress were analyzed after bolus and/or regular cocoa consumption. In both, healthy study participants and patients, total plasma antioxidant capacity as well as most markers of oxidative stress were not influenced by the intervention. Low-density lipoprotein oxidation ex vivo and in vivo decreased probably due to a direct beneficial effect of cocoa flavanols on lipid and protein oxidation. SUMMARY: Recent clinical trials do not provide sufficient evidence for an essential contribution of cocoa products to the overall antioxidant defense. Any recommendations for cocoa intake within preventive and therapeutic measures are presently not reasonable. PMID- 20736823 TI - Family satisfaction with critical care: measurements and messages. AB - PURPOSE OF REVIEW: Family satisfaction in the ICU reflects the extent to which perceived needs and expectations of family members of critically ill patients are met by healthcare professionals. Here, we present recently developed tools to assess family satisfaction, with a special focus on their psychometric properties. Assessing family satisfaction, however, is not of much use if it is not followed by interpretation of the results and, if needed, consecutive measures to improve care of the patients and their families, or improvement in communication and decision-making. Accordingly, this review will outline recent findings in this field. Finally, possible areas of future research are addressed. RECENT FINDINGS: To assess family satisfaction in the ICU, several domains deserve attention. They include, among others, care of the patient, counseling and emotional support of family members, information and decision-making. Overall, communication between physicians or nurses and members of the family remains a key topic, and there are many opportunities to improve. They include not only communication style, timing and appropriate wording but also, for example, assessments to see if information was adequately received and also understood. Whether unfulfilled needs of individual members of the family or of the family as a social system result in negative long-term sequels remains an open question. SUMMARY: Assessing and analyzing family satisfaction in the ICU ultimately will support healthcare professionals in their continuing effort to improve care of critically ill patients and their families. PMID- 20736822 TI - Nutritional determinants of mobility. AB - PURPOSE OF REVIEW: In many countries, persons over 65 are one of the fastest growing segments of the population. Mobility disability is one of the major risk factors for morbidity and mortality in this age group. There is increasing evidence that improved nutrition can reduce the risk of developing disability in older age. This review summarizes the recent literature showing the associations between different nutrients and mobility-related outcomes in older adults. RECENT FINDINGS: Recent studies suggested an association between low intake and low serum concentrations of micronutrients, such as antioxidants and vitamins, with measures of physical performance, muscle strength, and disability in older adults. SUMMARY: The role of low micronutrients as cross-sectional and longitudinal correlates of mobility disability is consistent with a growing number of studies showing that a diet rich in fruits and vegetables, such as the Mediterranean diet, has a beneficial role in healthy aging. PMID- 20736824 TI - Urinary hepcidin: an inverse biomarker of acute kidney injury after cardiopulmonary bypass? AB - PURPOSE OF REVIEW: In this review, we discuss the potential role of urinary hepcidin, a 2.8-kDa hormonal regulator of iron metabolism, as a biomarker of acute kidney injury (AKI) after cardiopulmonary bypass. RECENT FINDINGS: Hepcidin is one of the novel biomarkers of AKI that have been identified using hypothesis free, proteomic analysis of urine or plasma in patients who develop AKI. Collectively, these markers promise a new era for the early diagnosis and treatment of AKI in the ICU and an understanding of their biological role may also provide mechanistic insights into the pathogenesis of AKI. Although data confirming the association between urinary hepcidin and AKI are as yet limited, we believe hepcidin is of particular interest because hepcidin may be a biomarker specific to cardiopulmonary bypass-associated AKI; as a central regulator of iron metabolism, hepcidin could play a biological role in the pathogenesis of AKI after cardiopulmonary bypass; and hepcidin displays an intriguing negative association with AKI, in that a smaller increase in hepcidin from baseline after cardiopulmonary bypass appears to predict greater chance of developing AKI. SUMMARY: Smaller increases in urinary hepcidin, a central regulator of iron metabolism, may be associated with greater risk of AKI after cardiopulmonary bypass. Further research is required to establish the significance and nature of this association. PMID- 20736825 TI - Creatinine. AB - PURPOSE OF REVIEW: To summarize the history and current findings for creatinine as a renal biomarker and try to predict its future, looking at new biomarkers for kidneys (neutrophil gelatinase-associated lipocalin and cystatin C) and comparing current development to other diseases (troponins and procalcitonin). RECENT FINDINGS: In general, biomarkers are used for diagnosis, severity classification, outcome prediction, and most importantly, outcome modification. Creatinine can be used for the first three (except for outcome modification). Multiple clinical studies have shown that new renal biomarkers, especially neutrophil gelatinase associated lipocalin and cystatin C, can diagnose acute kidney injury more rapidly and accurately, have a better relationship with disease severity, and predict outcome of patients with acute kidney injury more accurately, than creatinine. However, to prove the true superiority of the new renal biomarkers to creatinine, more clinical studies will be required. Such studies include interventional ones that can improve outcome (especially mortality) of patients with acute kidney injury and ones showing relationship of the markers with beneficial effects of specific interventions. SUMMARY: Unless enough evidence accumulates, considering the history, familiarity, and recent findings related to outcome, creatinine will continue to be used and dominate in clinical practice. PMID- 20736826 TI - Human factors in critical care: towards standardized integrated human-centred systems of work. AB - PURPOSE OF REVIEW: Improvements in safety and quality benefit from a systems approach. Human factors is the study and practice of the relationship between humans and systems. This review examines recent advances in human factors in healthcare. RECENT FINDINGS: Early studies focused on understanding incidents, and on the translation of principles from aviation to healthcare, which demonstrated a useful but limited application of the human factors approach. More recent studies have begun to address the complexity of the relationship between human behaviour and technology, tasks, environment and organization. Human factors frameworks have been usefully applied that aid in these complex considerations, providing a better understanding of the healthcare system, and a much broader range of solutions to problems than checklists, protocols or training. In particular, in improving equipment design and procurement; improving job design by understanding the demands and tasks of individual healthcare practitioners; in improving what and when training is delivered; and the integration of these complex system components into a coherent whole. SUMMARY: The human factors approach is not yet mature in healthcare, but the importance is being increasingly recognized, and the breadth of application continually expanded. PMID- 20736827 TI - Team working in intensive care: current evidence and future endeavors. AB - PURPOSE OF REVIEW: It has recently been argued that the future of intensive care medicine will rely on high quality management and teamwork. Therefore, this review takes an organizational psychology perspective to examine the most recent research on the relationship between teamwork, care processes, and patient outcomes in intensive care. RECENT FINDINGS: Interdisciplinary communication within a team is crucial for the development of negotiated shared treatment goals and short-team patient outcomes. Interventions for maximizing team communication have received substantial interest in recent literature. Intensive care coordination is not a linear process, and intensive care teams often fail to discuss how to implement goals, trigger and align activities, or reflect on their performance. Despite a move toward interdisciplinary team working, clinical decision-making is still problematic and continues to be perceived as a top-down and authoritative process. The topic of team leadership in intensive care is underexplored and requires further research. SUMMARY: Based on findings from the most recent research evidence in medicine and management, four principles are identified for improving the effectiveness of team working in intensive care: engender professional efficacy, create stable teams and leaders, develop trust and participative safety, and enable frequent team reflexivity. PMID- 20736828 TI - Cystatin C in acute kidney injury. AB - PURPOSE OF REVIEW: This review will summarize and discuss the role of cystatin C in the diagnosis of acute kidney injury. RECENT FINDINGS: Cystatin C is easily measured and has the characteristics of an ideal marker of kidney function. Data suggest that cystatin C is modified by age, sex, muscle mass, obesity, smoking status, thyroid function, inflammation, and malignancy. These factors suggest the need for age-specific and sex-specific reference standards. Cystatin C-based glomerular filtration rate estimates may perform better than creatinine in selected patient populations (elderly, children, transplantation, cirrhosis, malnourished). Cystatin C has been evaluated for the early diagnosis of acute kidney injury (AKI) in several populations. Serum cystatin C has value for the diagnosis of acute kidney injury; however, it has often performed similarly to creatinine. Urinary cystatin C has potential as an early marker. SUMMARY: Cystatin C is an accurate biomarker for the early detection of AKI, and may, in selected populations, be superior to creatinine; however, data have been inconsistent. It also has reasonable discrimination for important outcomes such as death and renal replacement therapy (RRT). Additional studies are needed that focus on the cost-effectiveness of earlier detection of AKI with cystatin C compared with creatinine, and whether these biomarkers have complementary value. PMID- 20736829 TI - Urinary L-type fatty acid-binding protein as a new renal biomarker in critical care. AB - PURPOSE OF REVIEW: Acute kidney injury (AKI) remarkably increases the mortality of critically ill patients treated in ICUs. Recently, several renal biomarkers have been developed for the early detection of AKI. We review the potential of urinary L-type fatty acid-binding protein (L-FABP) as a new renal biomarker for AKI diagnosis in critical care. RECENT FINDINGS: In the kidney, L-FABP is expressed in renal proximal tubular epithelial cells and shed into urine rapidly in response to renal insults. By using human L-FABP transgenic mice, we reported that urinary L-FABP can detect AKI sensitively and reflect its severity accurately in animal models of AKI and sepsis. In clinical evaluations, the good performance of urinary L-FABP was demonstrated not only in pediatric postcardiopulmonary bypass surgery AKI and contrast media-induced AKI but also in septic shock patients complicated with AKI. SUMMARY: Recent data suggest that urinary L-FABP can contribute to the development of new AKI diagnostic tools in critical care. Combining with other renal markers such as neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), optimal threshold determination for distinguishing AKI from chronic renal failure should be explored before translation to the clinical. PMID- 20736830 TI - Nutritional assessment and support of the patient with acute heart failure. AB - PURPOSE OF REVIEW: A significant number of patients hospitalized with heart failure are malnourished. Depletion of micronutrients, which is known to occur in heart failure for a variety of reasons, may contribute to myocardial abnormalities noted in heart failure. In this review, we focus on nutritional supplementation strategies that might improve myocardial performance and, as a consequence, decrease mortality and morbidity in these patients. RECENT FINDINGS: The available data suggest that micronutrient and macronutrient supplementation may play a role in improving the myocardial metabolic abnormalities noted in heart failure. A recent trial of omega-3 fatty acid macronutrient supplementation showed a modest decrease in mortality and hospitalizations when used in patients with New York Heart Association class II-IV heart failure. SUMMARY: Recommendations for nutritional support in patients with heart failure are difficult to make due to a lack of large randomized trials. Supplementation with omega-3 fatty acids, and micronutrients such as thiamine, coenzyme Q-10 and carnitine has shown promise in several studies. Since the data is not conclusive, large trials are needed to address whether these positive findings are reproducible in a wider subset of patients. In addition, these trials should study the combination of different micronutrients and macronutrients since heart failure patients are rarely deficient in just one micronutrient or macronutrient. PMID- 20736831 TI - Evolving use of biomarkers for kidney injury in acute care settings. AB - PURPOSE OF REVIEW: Acute kidney injury is increasingly recognized in acute care settings in more recent years. Proper diagnosis and risk stratification for acute kidney injury is necessary for carrying out appropriate and cost-effective treatments in patients with acute kidney injury. Kidney markers serve as diagnostic and prognostic tools to give physicians a more complete perspective of renal insult. The aim of this review is to highlight some of the evidence from recent studies, involving kidney markers and provide current opinion on the accuracy of these markers. RECENT FINDINGS: Recent studies demonstrate that novel kidney markers such as cystatin C, interleukin-18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin serve as more accurate markers for acute kidney injury as compared with the more traditional marker, creatinine. Additionally, there seems to be a correlation between the concentrations of each marker and the level of deterioration of kidneys, patient recovery time, length of hospital stay, and hospital costs. SUMMARY: Each individual kidney marker possesses its own strengths and weaknesses in determining the onset and severity of acute kidney injury. However, in combination, a panel of kidney markers may serve as powerful tools in diagnosing kidney injury with high accuracy. PMID- 20736832 TI - Management of patients with coronary stents in the ICU. AB - PURPOSE OF REVIEW: To review the contemporary management of patients with coronary stents in the ICU. RECENT FINDINGS: Coronary stent patients admitted in the ICU may be at increased risk for stent thrombosis, a catastrophic complication with high morbidity and mortality. Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist significantly reduces the risk of stent thrombosis; however, it may occasionally need to be discontinued in case of bleeding or when high bleeding risk invasive procedures need to be performed. In such cases, if aspirin can be continued, it can provide some protection from complications. If all antiplatelet therapy needs to be discontinued, temporary administration of a short-acting antiplatelet agent, such as a small molecule glycoprotein IIb/IIIa inhibitor may be helpful. Close monitoring of coronary stent patients may allow prompt diagnosis and treatment of any cardiac complications in the ICU. SUMMARY: Awareness of the potential risks of coronary stent patients coupled with close monitoring and meticulous attention to the optimum antiplatelet therapy can optimize the outcomes of coronary patients admitted in the ICU. PMID- 20736833 TI - New nonculture-based methods for the diagnosis of invasive candidiasis. AB - PURPOSE OF REVIEW: Invasive candidiasis is a severe infectious complication occurring mostly in onco-hematologic and surgical patients. Its conventional diagnosis is insensitive and often late, leading to a delayed treatment and a high mortality. The purpose of this article is to review recent contributions in the nonconventional diagnostic approaches of invasive candidiasis, both for the detection of the epidose and the characterization of the etiologic agent. RECENT FINDINGS: Antigen-based tests to detect invasive candidiasis comprise a specific test, mannan, as well as a nonspecific test, beta-D-glucan. Both have a moderate sensitivity and a high specificity, and cannot be recommended alone as a negative screening tool or a positive syndrome driven diagnostic tool. Molecular-based tests still have not reached the stage of rapid, easy to use, standardized tests ideally complementing blood culture at the time of blood sampling. New tests (fluorescence in-situ hybridization or mass spectrometry) significantly reduce the delay of identification of Candida at the species level in positive blood cultures, and should have a positive impact on earlier appropriate antifungal therapy and possibly on outcome. SUMMARY: Both antigen-based and molecular tests appear as promising new tools to complement and accelerate the conventional diagnosis of invasive candidiasis with an expected significant impact on earlier and more focused treatment and on prognosis. PMID- 20736834 TI - Neuro-ophthalmic sarcoidosis. AB - PURPOSE OF REVIEW: Almost 100 years after its original description, sarcoidosis remains an enigmatic disease with unclear etiology and capricious symptomology, as well as a diagnostic challenge. This review coalesces current literature on the neuro-ophthalmic manifestations of sarcoidosis and discusses the epidemiology, etiology, clinical presentation, diagnosis, and management of this disease. RECENT FINDINGS: Recent investigations strongly identify a genetic component as well as a host of candidate antigenic triggers. Certain human leukocyte antigen polymorphisms may influence not only the susceptibility of individuals to sarcoidosis but also the course of the disease. Diagnostic advances include the finding of two additional potential biomarkers of sarcoidosis as well as the use of positron emission tomography technology in localization of disease sites for biopsy. In addition to the concomitant and alternative use of immunosuppressive agents to steroid therapy, disease remission in refractory neuro-ophthalmic sarcoidosis with tumor necrosis factor alpha inhibitors has also been reported. SUMMARY: Sarcoidosis can affect any part of the visual system; the most common neuro-ophthalmic presentation is optic neuropathy. Diagnosing the disease is problematic as the clinical presentation is nonspecific which may be associated with many other pathologies and no diagnostic finding is pathognomonic. In recent years, progress has been made in identifying new biomarkers and developing imaging techniques. Although corticosteroids remain the mainstay of therapy, many new pharmacological agents have been added to the treatment arsenal. PMID- 20736835 TI - Ophthalmologic manifestations commonly misdiagnosed as demyelinating events in multiple sclerosis patients. AB - PURPOSE OF REVIEW: Multiple sclerosis may affect both afferent and efferent visual pathways, and sometimes physicians err on ordinary ophthalmologic diagnosis due to overlapping symptoms between demyelinating and nondemyelinating visual diseases. The present article highlights nondemyelinating ocular occurrences due to physiologic or other pathologic processes that may appear in some patients. RECENT FINDINGS: Optic neuritis is representative of the most common and best-studied demyelinating visual occurrence in multiple sclerosis. However, other nondemyelinating visual disturbances also seen in the general population may be erroneously interpreted as being part of the underlying disease. This comparison has not been documented and may be helpful to overcome such difficulties. SUMMARY: Based on clinical history and some strategies of ophthalmologic examination, physicians can achieve the correct diagnosis. Some clinical situations, however, may be challenging and a multidisciplinary approach in the care of multiple sclerosis is warranted. PMID- 20736836 TI - Cardiac stress testing after surgery for congenital heart disease. AB - PURPOSE OF REVIEW: Heart failure is an important problem after surgical correction of congenital heart disease. Timely recognition may be difficult. Recent developments in exercise testing and stress-imaging may change the management of patients with congenital heart disease. RECENT FINDINGS: Exercise tests are commonly used in the follow-up of patients with congenital heart disease. Maximal exercise studies are not always feasible in this patient population. Variables of submaximal exercise and ventilator efficiency have shown a good correlation with variables of maximal exercise and have been suggested to relate to long-term cardiac function.For evaluation of submaximal exercise, stress imaging may reveal abnormal responses unrecognized at rest. Both physical exercise as well as pharmacological stress may be used in combination with various imaging modalities. For practical reasons, dobutamine is most widely used to generate and mimic stress and is well tolerated in low doses. Particularly in lesions affecting the right ventricle and with single ventricular physiology after the Fontan operation, magnetic resonance stress imaging has provided additional insight into the cardiac function. SUMMARY: The abnormal stress responses can potentially be used for risk assessment in the follow-up of patients with congenital cardiac disease. Further studies are required to provide common protocols for stress imaging. PMID- 20736837 TI - Emotional and behavioral sequelae of childhood maltreatment. AB - PURPOSE OF REVIEW: To summarize research on the emotional and behavioral consequences of childhood maltreatment published between January 2009 and April 2010. RECENT FINDINGS: Many studies published during this time frame replicated prior research studies that have shown that childhood maltreatment is a nonspecific risk factor for a range of different emotional and behavioral problems. Two research groups highlighted the high revictimization rate among abused girls, with more than one in five abused girls found to have subsequent experiences of rape by young adulthood. The association between physical and sexual abuse and subsequent perpetration of violence toward self and other was also demonstrated, with one study noting the particular vulnerability of sexually abused boys to these negative outcomes. In this study, sexually abused boys had a 15-fold increased risk of making a suicide attempt, and a 45-fold increased risk of perpetrating domestic violence. A three-generation longitudinal study of the intergenerational transmission of abuse is also highlighted in the review, together with emerging findings on genetic and environmental risk and protective factors associated with variability in child outcomes. SUMMARY: Maltreated children are at-risk for a host of negative outcomes. Although marked gains have been made in treating trauma-related psychopathology, these recent studies highlight the need to examine long-term outcomes of youths who have received state-of-the-art evidence-based interventions, and determine if there is a need for more comprehensive and sustained intervention approaches. PMID- 20736838 TI - Left outflow tract anomalies in children. AB - PURPOSE OF REVIEW: To provide a discussion of the current knowledge of the genetics of left outflow tract of the heart, including the aortic stenosis, in children. It addresses the available means of diagnosis for syndromic and nonsyndromic left outflow tract abnormalities and implications for at-risk family members. Options for prenatal testing and recommendations for cardiac follow-up are presented. RECENT FINDINGS: Left outflow tract cardiac anomalies in children present as a varied spectrum among and within families. Even nonsyndromic forms can be inherited in an autosomal dominant pattern. These can lead to significant complications in asymptomatic individuals, making diagnosis a challenge and underscoring the importance of evaluation of at-risk family members. SUMMARY: Improved understanding of the genetics of both syndromic and nonsyndromic left outflow tract disorders is hoped to lead to improved identification of affected children and greater ongoing cardiac follow-up for those potentially at risk. PMID- 20736839 TI - Dietary patterns and food groups are linked to the risk of urinary tract tumors in Argentina. AB - Epidemiological and laboratory research has shown that dietary components are associated with the risk of developing urinary tract tumors (UTT). The purpose of this case-control study, carried out between 2004 and 2008 in Cordoba, a Mediterranean city in Argentina, was to describe the role of dietary patterns and to investigate any association with the risk of developing UTT. One hundred and sixty-eight patients with histologically confirmed transitional UTT and 334 controls with acute, nonneoplastic, and nonurinary tract diseases from the same hospitals were studied. All patients were interviewed about their food habits and their exposure to a number of known or suspected risk factors for UTT. Multiple correspondence analysis was used to explore dietary patterns and data analyses were carried out by calculating odds ratios and their 95% confidence intervals by using multiple logistic regression. Two main dietary patterns identified were a 'prudent' pattern that was linked to controls and a 'western' pattern that was associated with cases. A frequent intake of vegetable oils, lean meats, grains, and fruits, the moderate use of alcohol (mainly red wine) together with potato and sweet consumption, and the habit of taking at least four meals per day, were associated with a reduced risk for UTT. In contrast, frequent consumption of infusions (mainly mate), potatoes, alcohol, sweets, and processed meat resulted in a high risk for UTT. The dietary patterns of our population have a role in the development of UTT, thus implying that appropriate nutritional education may decrease this risk. PMID- 20736840 TI - Parents' attitudes related to melanocytic nevus count in children. AB - Sun exposure, fair phototype, and a high common melanocytic nevus (MN) count have been identified as the most important risk factors for melanoma. MN are mainly acquired during childhood, and their relationship to sun exposure, sunburn, and light skin complexion is well documented. The purpose of this study was to investigate how the sun protection attitudes of parents and their offspring affect MN development in children. We designed a cross-sectional study in 828 9 year-old school children. Trained nurses counted the MN on each child's back and arms, depending on their size. Questionnaires filled by children and parents provided information about sun exposure, attitude towards the sun, and sun protection behaviors. Multivariate analysis showed that the childhood MN count was linked to fair phenotype--fair skin: rate ratio (RR)=3.80, 95% confidence interval (CI)=2.25-6.41; blue/green eyes: RR=1.2, 95% CI=1.11-1.34; blond hair: RR=1.25, 95% CI=1.10-1.41; history of sunburn: RR=1.13, 95% CI=1.03-1.23, seaside sun exposure--RR=1.14, 95% CI=1.01-1.28, and to their parents' behaviors during exposure to the sun--increase in the number of MN when parents used sunscreen: RR=1.23, 95% CI=1.08-1.40; decrease in MN count when parents wore a tee-shirt: RR=0.86, 95% CI=0.79-0.93. In conclusion, fair phenotype and sun exposure are known major risk factors for MN. Parents' behaviors influence their children and appeared in our analysis as another determinant predictor of MN count, being protective against (wearing a tee-shirt when exposed to sun) or increasing the risk (sunscreen use, reflecting higher sun exposure) for childhood MN development. PMID- 20736841 TI - Pulmonary infections and risk of lung cancer among persons with AIDS. AB - Lung cancer risk is significantly increased among persons with AIDS (PWA), and increased smoking may not explain all of the elevated risk, suggesting a role for additional cofactors. We investigated whether AIDS-defining pulmonary infections (recurrent pneumonia, Pneumocystis jirovecii pneumonia, and pulmonary tuberculosis) affected the risk of subsequent lung cancer over 10 years after AIDS onset among 322,675 PWA, whose records were linked with cancer registries in 11 US regions. We assessed lung cancer hazard ratios (HRs) using Cox regression and indirectly adjusted HRs for confounding by smoking. Individuals with recurrent pneumonia (n = 5317) were at significantly higher lung cancer risk than those without [HR = 1.63, 95% confidence interval (CI) = 1.08 to 2.46, adjusted for age, race, sex, HIV acquisition mode, CD4 count, and AIDS diagnosis year]. This association was especially strong among young PWA (<50 years HR = 1.99 vs. >=50 years HR = 1.10) and was significantly elevated during 5-10 years after recurrent pneumonia diagnosis (HR = 2.41; 95% CI = 1.07 to 5.47). Although attenuated, HRs for recurrent pneumonia remained nonsignificantly elevated after indirect adjustment for smoking. Lung cancer risk was unrelated to tuberculosis [(n = 13,878) HR = 1.12, 95% CI = 0.82 to 1.53] or Pneumocystis jirovecii pneumonia [(n = 69,771) HR = 0.97, 95% CI = 0.80 to 1.18]. The increased lung cancer risk associated with recurrent pneumonia supports the hypothesis that chronic pulmonary inflammation arising from infections contributes to lung carcinogenesis. PMID- 20736842 TI - Ocular ischemic syndrome secondary to carotid artery occlusion as a late complication of radiotherapy of nasopharyngeal carcinoma. AB - A 39-year-old Chinese man developed ocular ischemic syndrome (OIS) in both eyes 14 years after radiation therapy for nasopharyngeal squamous cell carcinoma. Digital subtraction angiography disclosed occlusion of common carotid arteries and stenosis of both vertebral arteries. Following stenting of the vertebral arteries, visual function improved and ophthalmoscopic abnormalities of OIS regressed in the right eye. Radiation therapy of the head and neck has a relatively high likelihood of causing vascular stenosis. However, we believe this to be the first reported case of OIS following radiotherapy for nasopharyngeal carcinoma. PMID- 20736843 TI - Parathyroid adenoma and chondrosarcoma after treatment of pediatric Hodgkin disease. AB - Treatment of Hodgkin disease (HD) with chemoradiotherapy in children is associated with increased risk for developing secondary neoplasms. Parathyroid adenoma (PTA) and chondrosarcoma (CS) are quite rare types of secondary neoplasms after HD. We describe a 5-year-old boy with stage IV HD, successfully treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone)/ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 35 Gy mantle radiotherapy who developed primary hyperparathyroidism because of benign PTA at the age of 20 years, and died of CS in thoracic vertebrae at the age of 22 years. Consecutive occurrence of PTA and CS after treatment of pediatric HD, to the best of our knowledge, has not been reported earlier. PMID- 20736844 TI - Treatment of pediatric Burkitt lymphoma in Turkey. AB - This study aimed to assess the demographic data and treatment results of children who were diagnosed with Burkitt lymphoma and treated according to the Berlin Frankfurt-Munster-95 (BFM) protocol in a single institution. A total of 48 patients (37 boys, 77%) with a median age of 8 years (range 2 to 16 years) at diagnosis, were evaluated. Primary tumor sites were abdomen (70.8%), head and neck (22.9%), peripheral lymph node (2%), bone (2%), and testis (2%). The 5-year overall survival (OS) and event-free survival (EFS) were 78.1+/-4% and 76.6+/-6%, respectively. In univariate analysis, hemoglobin level less than 10 g/dL, cerebrospinal fluid (CSF) positivity and dialysis requirement at diagnosis were found to be important reverse predictor factors for EFS (P; 0.001, 0.001, 0.004, respectively). In multivariate analysis, hemoglobin level less than 10 g/dL and dialysis at diagnosis were found to be important reverse predictor factors for EFS (P; 0.0001). The EFS of our patients was lower than the values achieved with BFM-95 protocol in other centers. This study provides evidence that low hemoglobin level, CSF positivity and dialysis at diagnosis were important predictor factors for EFS in children with Burkitt lymphoma. PMID- 20736845 TI - Bone status of children with hemophilia A assessed with quantitative ultrasound sonography (QUS) and dual energy X-ray absorptiometry (DXA). AB - Recent studies report reduced bone mineral density (BMD) even among young adults and children with hemophilia. Our aim was to assess bone status in children and adolescents with hemophilia with 2 methods: Quantitative UltraSonography (QUS) and Dual energy x-ray Absorptiometry (DXA), and consequently to investigate the degree of correlation between them. Twenty-seven patients (17 with severe hemophilia; residual factor activity <1% and 10 with moderate hemophilia) participated in the study. Mean age was 12.28+/-4.48 y (range: 4.94 to 18.00 y). All patients were evaluated with QUS at radius and at tibia and had DXA scan at lumbar spine. Anthropometric parameters were measured using standard techniques and joint evaluation was carried out using the Hemophilia Joint Health Score (HJHS). Only 2 out of 27 patients (7.5%) had BMD Z-scores <-2, whereas another 4 patients (15%) had BMD Z-scores between -1 and -2. QUS values in both radius and tibia were generally within the normal limits as only 1 patient had radius and another 1 had tibia QUS Z-score <-2. HJH scores were significantly although negatively correlated to Z-scores of tibia QUS (r=-0.455, P=0.034). No correlations were observed between lumbar BMD and radius or tibia QUS and no agreement was recorded between QUS and DXA in identifying patients at risk for osteoporosis (k=0.262). In conclusion, our study showed that only a small number of children and young adults with hemophilia have impaired bone properties as assessed both by DXA and QUS; no correlation was observed between these 2 methods. PMID- 20736846 TI - Parents of children surviving a brain tumor: burnout and the perceived disease related influence on everyday life. AB - Parents of children diagnosed with a brain tumor often report distress, even after successfully completed cancer treatment. The aim of this study was to examine predictors of burnout (ie stress-induced exhaustion) in parents of children who have had a brain tumor. Twenty-four mothers and 20 fathers completed self-report questionnaires on 2 occasions at an interval of 7 months. Controlling for generic stress, parents' perception of the influence of the disease on everyday life-predicted burnout symptoms. Moreover, parents' appraisal of a disease-related influence on everyday life showed stability, implying that parental stress may be chronic. The findings encourage furthermore investigation of chronic stress among parents of children diagnosed with cancer. PMID- 20736847 TI - Late toxicity in Wilms tumor patients treated with radiotherapy at 15 years of median follow-up. AB - BACKGROUND: We report the radiation-induced late morbidity observed in our prospective series of Wilms tumor patients treated at the Second University of Naples. METHODS: From April 1981 to April 2000, 98 patients were referred at our institution for treatment of Wilms tumor. Among them, 51 underwent radiotherapy and 34 patients had a minimum follow-up of 5 years. Doses of irradiation and treatment portals were those recommended by the guidelines of the Italian Association of Haematology and Paediatric Oncology according to risk stratification. All eligible patients were reviewed for follow-up every 6 months. Median follow-up was 181 months (range 60 to 264 months). RESULTS: Eleven out of 34 patients (32%) did not suffer from any significant late side effect. Out of the remaining 23 (68%), 14 (41%) suffered from scoliosis presenting between 60 and 180 months from completion of treatment. Muscular hypoplasia, length inequality, kyphosis, and iliac wing hypoplasia were seen respectively, in 4 (12%), 4 (12%), 5 (15%), and 3 (9%) patients. The incidence of intestinal occlusion was 20%. One patient had chronic renal insufficiency. Four out of 13 female patients reported ovarian failure. Three out of the 7 patients who had radiotherapy to the lung developed radiation-pneumonitis. Radiation-induced heart disease was seen in 3 (9%) patients. Three patients (9%) suffered from second malignancies arising within the irradiated volume. CONCLUSIONS: Our data confirm the high incidence of late radiation morbidity in patients undergoing adjuvant radiotherapy for Wilms tumor. For most organ systems there is a correlation between total dose, morbidity rates, and degree of severity. PMID- 20736848 TI - Aprepitant use in children, adolescents, and young adults for the control of chemotherapy-induced nausea and vomiting (CINV). AB - BACKGROUND: One of the most common and distressing side effects for cancer patients is chemotherapy-induced nausea and vomiting (CINV). New antiemetics, such as the NK-1 receptor inhibitor aprepitant, have been reported to improve control of this side effect in adults. However, little is known about its effect in the pediatric oncology population, with only a few reported cases in the literature. METHODS: This was a retrospective chart review on the use of aprepitant in the pediatric oncology population in our institution. RESULTS: Thirty-two charts and a total of 146 cycles of chemotherapy were reviewed. Mean age was 10 years. Highly emetogenic chemotherapy was used in 23/32 patients and moderately emetogenic chemotherapy in 9/32. Antiemetic regimens consisted of aprepitant+5-HT3 RA+dexamethasone (Regimen 1, 20/32 patients) or aprepitant +5 HT3 RA (Regimen 2, in 12/32). Eight out of thirty-two patients were chemotherapy naive and received aprepitant on their first cycle. In 24/32 patients, aprepitant was added later in their treatment, with 12/24 reporting resolution of CINV after its addition. CONCLUSIONS: Aprepitant when combined with standard antiemetics, was well tolerated in the pediatric oncology population studied. However, there is still a need to conduct prospective studies to determine the optimal efficacy of aprepitant in the pediatric oncology population. PMID- 20736849 TI - Radiation-induced glioblastoma multiforme in children treated for medulloblastoma with characteristics of both medulloblastoma and glioblastoma multiforme. AB - Outcomes for average-risk medulloblastoma are excellent with 5-year event-free survival and overall survival>80%. Treatment failures include radiation-induced glioblastomas (RIG), which are often diagnosed solely on imaging. Recent studies suggest that RIGs differ from spontaneous glioblastoma multiforme (GBM), based on microarray gene-expression profiling. Retrospective review of children with average-risk medulloblastoma treated from 1996 to 2003 included 16 patients with 5 treatment failures. One died of disease progression, 1 died as a result of radiation necrosis, and 3 children died of pathology-confirmed GBM. Of these 3 GBMs, one was studied with electron microscopy, cytogenetics, and gene-expression microarray analysis. This tumor had focal medulloblastoma and similarity by gene expression microarray with other RIGs. With both components in the recurrent tumor, we suggest it was in the process of transitioning from medulloblastoma to RIG, that is, "catching the tumor in the act." Some radiation-induced nervous system tumors may develop as a direct result of severe oncologic changes within the original tumor cells, with the tumor evolving into a different phenotypic tumor type. We recommend biopsy for tissue confirmation and genetic expression profile to shed light on the etiology of radiation-induced neoplasms. PMID- 20736850 TI - Glanzmann thrombasthenia detected because of knee hemarthrosis: a case report. AB - Glanzmann thrombasthenia (GT) is a rare bleeding syndrome, which is characterized by a lack of platelet aggregation. We report a case of GT that was first detected because of the presence of hemarthrosis of the knee. The patient was an 8-year old boy who presented with a sudden, painful left knee after outdoor games. Till the first visit to our hospital, he had not been diagnosed with GT despite a history of bleeding tendency, notably purpura in areas of easy bruising and prolonged bleeding time after abrasions and insect stings. Gross blood was found at arthrocentesis of the left knee, and GT was diagnosed on the basis of prolonged bleeding time, lack of platelet aggregation with ADP and collagen, and absence of platelet surface glycoprotein IIb/IIIa. Although hemarthrosis of GT is rare, this disease should be considered in a patient with bleeding tendency and prolonged bleeding time. PMID- 20736851 TI - ACDF with the PCB cage-plate system versus laminoplasty for multilevel cervical spondylotic myelopathy. AB - STUDY DESIGN: A nonrandomized controlled trial. OBJECTIVE: To compare the clinical outcomes, radiographic changes, and complications of patients with multilevel cervical spondylotic myelopathy who underwent ACDF with the plate cage benezech (PCB) implant system and laminoplasty. SUMMARY OF BACKGROUND DATA: Using anterior or posterior surgery for multilevel cervical spondylotic myelopathy continues to be the subject of considerable debate. Studies on the comparison of the 2 approaches are limited and few studies focus on anterior cervical discectomy and fusion (ACDF) versus laminoplasty. METHODS: We evaluated 52 consecutive patients (25 patients for the ACDF group and 27 patients for the laminoplasty group) at our institution from 2002 to 2007. The clinical and radiographic backgrounds of both the groups were comparable. The mean independent follow-up duration was 25.4 months and 24.5 months, respectively (P>0.05). The clinical outcomes, radiographic changes, and complications were compared between the 2 groups. RESULTS: As compared with the ACDF group, the laminoplasty group required a longer operative time (187.78 min vs. 115.92 min) and caused more operative blood loss (361.11 mL vs. 118.48 mL). Both the groups significantly improved the JOA score (P<0.001), and the recovery rate was similar (59.79% for the ACDF group vs. 59.54% for the laminoplasty group, P>0.05). The cervical ROM significantly decreased after surgery for both the groups (P<0.05), while the laminoplasty group had a lower decrease rate of ROM than the ACDF group (11.39% vs. 29.45%, P<0.05). The complications for the ACDF group were significantly more than the laminoplasty group (P<0.05). CONCLUSIONS: Both ACDF with the PCB system and laminoplasty are effective therapies for multilevel cervical spondylotic myelopathy. As compared with laminoplasty, ACDF with the PCB system requires a shorter operative time and causes less operative blood loss, but has a higher decrease rate of the cervical ROM and more complications. PMID- 20736852 TI - Puumala virus infection: radiologic findings. AB - A 33-year-old male patient was admitted to our nephrology department with rapidly deteriorating general health, fever, respiratory difficulties, and acute renal failure. Computed tomography of the thorax revealed interstitial edema with thickening of the interlobular septa, peribronchial cuffing, ground-glass opacities, and small pleural and pericardial effusions. Polymerase chain reaction tests verified Puumala virus infection. The patient recovered with supportive treatment. Hantavirus infection should be considered in the differential diagnosis of young patients who present with acute renal failure of an unknown origin and the nonspecific radiologic finding of noncardiogenic interstitial edema, which in combination with typical clinical symptoms and laboratory parameters, can be indicative of this disease. PMID- 20736853 TI - Lung cancer genomic signatures. AB - BACKGROUND: Lung cancer (LC) is the dominant cause of death by cancer in the world, being responsible for more than a million deaths annually. It is a highly lethal common tumor that is frequently diagnosed in advanced stages for which effective alternative therapeutics do not exist. In view of this, there is an urgent need to improve the diagnostic, prognostic, and therapeutic classification systems, currently based on clinicopathological criteria that do not adequately translate the enormous biologic complexity of this disease. METHODS: The advent of the human genome sequencing project and the concurrent development of many genomic-based technologies have allowed scientists to explore the possibility of using expression profiles to identify homogenous tumor subtypes, new prognostic factors of human cancer, response to a particular treatment, etc. and thereby select the best possible therapies while decreasing the risk of toxicities for the patients. Therefore, it is becoming increasingly important to identify the complete catalog of genes that are altered in cancer and to discriminate tumors accurately on the basis of their genetic background. RESULTS AND DISCUSSION: In this article, we present some of the works that has applied high-throughput technologies to LC research. In addition, we will give an overview of recent results in the field of LC genomics, with their effect on patient care, and discuss challenges and the potential future developments of this area. PMID- 20736855 TI - Survival differences by gender for resected non-small cell lung cancer: a retrospective analysis of 12,509 cases in a Japanese Lung Cancer Registry study. AB - INTRODUCTION: Women with non-small cell lung cancer (NSCLC) are more likely to have better survival than men. This study intended to assess gender differences in the survival of these patients in a large registry population. METHODS: In 2005, the Japanese Joint Committee for Lung Cancer Registration performed a nationwide retrospective registry study regarding the prognosis and clinicopathologic profiles of patients who underwent resection for primary lung neoplasms in 1999. The registry data of 12,509 patients with NSCLC were analyzed in terms of gender differences in prognosis and clinicopathologic features. RESULTS: There were 8353 (66.8%) men and 4156 (33.2%) women with a mean age at operation of 66.4 and 65.0 years, respectively (p < 0.001). Women had a higher incidence of adenocarcinoma (p < 0.001) and stage IA disease (p < 0.001) than men. The overall survival was significantly better in women than men. The 5-year survival rates (5-YSRs) for women and men were 75.6 and 57.9%, respectively (p = 0.0000). According to histology, the overall survival of women was significantly better than that of men for both adenocarcinoma (5-YSR, 77.7 versus 61.9%, p = 0.0000) and nonadenocarcinoma (5-YSR, 59.3 versus 53.1%, p = 0.035). In adenocarcinoma, women had a significantly better prognosis than men for pathologic stage I/II disease. However, in nonadenocarcinoma, there was no significant prognostic difference between the two genders in pathologic stage I/II disease. CONCLUSIONS: Women with NSCLC, especially with an adenocarcinoma histology, had better survival than men. Women were more likely to have adenocarcinoma and stage IA disease, which might account for the better prognosis in women. PMID- 20736854 TI - Erlotinib in advanced non-small cell lung cancer: efficacy and safety findings of the global phase IV Tarceva Lung Cancer Survival Treatment study. AB - INTRODUCTION: Erlotinib is a small molecule inhibitor of epidermal growth factor receptor tyrosine-kinase activity that has been shown to significantly increase survival for patients with previously treated advanced non-small cell lung cancer. Here, we report safety and efficacy data from a large, global, open label, phase IV trial of erlotinib (Tarceva Lung Cancer Survival Treatment). METHODS: Patients who had previously failed on chemotherapy or radiotherapy and were unsuitable for these treatments were treated with oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity. RESULTS: The disease control rate was 69% in 5394 patients for whom best response data were available. Survival data were available for 6580 patients. Median progression-free and overall survival times were 3.25 months and 7.9 months, respectively. The 1-year survival rate was 37.7%. Among the 6580 patients included in the safety analysis, 799 (12%) experienced one or more erlotinib-related adverse events (AEs, other than prespecified AEs defined in the protocol), and only 4% experienced an erlotinib-related serious AE. Of the 6580 patients for whom data were available, dose reductions were reported in 1096 (17%), the majority (95%) due to an erlotinib-related AE (most commonly rash 65% or diarrhea 10%). Treatment was discontinued for 337 patients (5%) because of erlotinib-related AEs. Incidence of erlotinib-related rash was investigated as a separate end point. Seventy-one percent of patients for whom data were available experienced erlotinib-related rash; of these, the majority of cases were grade 1/2 (59%). CONCLUSIONS: These data confirm the favorable efficacy and safety profile of erlotinib in a large heterogeneous non-small cell lung cancer population. PMID- 20736856 TI - A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307. AB - HYPOTHESIS: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. METHODS: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. RESULTS: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). CONCLUSION: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted. PMID- 20736858 TI - Results of a clinician-led evidence-based task force initiative relating to pressure ulcer risk assessment and prevention. AB - Integration of research findings into clinical practice is essential for achieving cost-effective, quality patient outcomes. Data confirm that nursing care in most settings is "empiric" and is based largely on untested assumptions, as opposed to being evidence-based. Process improvement efforts must engage clinicians in initiatives that promote the integration of research into clinical practice and acceptance of shared professional accountability for sustaining needed change. A clinician-led task force was assembled to identify and apply current evidence to clinical practice in the areas of risk assessment and prevention of hospital-acquired pressure ulcers in the inpatient setting. Data collected prior to and following our process improvement project demonstrated significant improvement in patient outcomes. PMID- 20736857 TI - Assessment of nurses' knowledge and practice in prevention and management of deep tissue injury and stage I pressure ulcer. AB - PURPOSE: The aim of this descriptive study was to determine nurses' knowledge and usual practice in prevention and management of deep tissue injury (DTI) and stage I pressure ulcers (PUs). SETTING AND SUBJECTS: The study was conducted in neurology, orthopedics, physiotherapy, rehabilitation, and intensive care units of 3 hospitals located in Ankara, Turkey. These units were selected because they care for patients at risk for developing PUs. The sample comprised 243 nurses. METHODS: A questionnaire was developed in consultation with wound care experts to measure nurses' knowledge and practice for preventing DTI and stage I PUs. The questionnaire form was provided to nurses who consented to participate in the study; the nurses completed the forms in the presence of the investigator. RESULTS: The mean score of correct answers was 48.85+/-11.99 of 100. Significant correlations were found between the percentage of correct answers and level of nursing education, previous experience with PU management, and participation in in-service training programs. CONCLUSION: The nurses in this study tended to lack sufficient knowledge regarding prevention and management of DTI and stage I PUs. PMID- 20736860 TI - The incontinence-associated dermatitis and its severity instrument: development and validation. AB - PURPOSE: To develop and test the validity and interrater reliability of the Incontinence-Associated Dermatitis and its Severity Instrument, a novel tool describing incontinence-associated dermatitis and its severity. METHODS: Investigators consulted 2 certified WOC nurse experts to determine face validity of the instrument. Seven additional certified WOC nurses evaluated the tool for content validity. The instrument was tested for interrater reliability by attendees at the 2007 WOCN Society National Conference and employees at a health care system in Minnesota. Criterion validity was determined by comparing IAD severity scores of testers with those of the 2 WOC experts and PI. RESULTS: Consultants determined that the instrument had face and content validity. Two hundred forty-seven attendees at the WOCN Society's National Conference (mean nursing experience 25+/-9 years [mean+/-SD]), 100 nursing staff in Minnesota: 84 staff nurses (mean nursing experience 17+/-12 years), and 16 nursing assistants (mean nursing experience 7+/-7 years) determined that the instrument has content validity. There were no significant differences in scores of IAD severity for the 4 cases among the 3 types of testers (P>.05). Overall agreement between the 347 raters and the experts using intraclass correlation was 0.98 (P=.006). CONCLUSION: The Incontinence-Associated Dermatitis and its Severity Instrument demonstrated good validity and interrater reliability and its development fulfills an unmet need in both research and clinical practice settings. PMID- 20736859 TI - Early Peristomal Skin Complications Reported by WOC Nurses. AB - PURPOSE: The range of peristomal skin complications reported in the literature varies from 10% to 70%. Inconsistent terminology as well as a lack of a standardized tracking tool may account for this variability. The purpose of this study was to describe peristomal skin complications seen by WOC nurses over a 1 year period using a standardized data collection tool and using the peristomal terminology developed by the WOCN Society. METHODS: A prospective research design was used to describe peristomal skin complications of ostomy patients seen within the first 2 months of ostomy surgery by WOC Central Virginia Affiliate nurses. The WOC nurses completed a peristomal skin complication form on each ostomy patient that was seen within 2 months of the original ostomy surgery regardless of whether or not he or she had a peristomal complication. Descriptive statistics were used to summarize data. SUBJECTS AND SETTING: Twelve WOC nurses saw a total of 89 patients over a 12-month period. Subjects had a median age of 61 years (range, 1-91 years). The sample included 46 females and 43 males. All patients were seen in the central Virginia area. Thirty-two patients were seen in hospital, 31 were seen in a home health setting, and 26 were seen in outpatient clinic. RESULTS: Forty-two patients (47%) had peristomal complications. The types of ostomies seen were 37 colostomies, 33 ileostomies, and 15 urinary conduits. Thirty-one patients had chemical damage to the peristomal skin (irritant dermatitis), 5 had mechanical injury, and 4 had Candida infections, 1 had an allergic reaction, and another had pyoderma gangrenosum. CONCLUSIONS: Research studies that describe peristomal skin complications over time and over multiple settings are limited. A central data repository using a standardized tool may be one way to monitor them and then begin to look at standardized evidence-based peristomal skin care. PMID- 20736861 TI - Interest in information about urinary incontinence among diabetic and nondiabetic heart failure patients. AB - PURPOSE: Diabetes mellitus (DM) and urinary incontinence (UI) are often prevalent in heart failure (HF) patients, rendering nursing management even more complex. The purpose of this study was to determine if differences existed between diabetic and nondiabetic HF patients regarding their interest in information about UI. DESIGN: Secondary analyses were conducted on survey and medical record data from 182 (97 hospitalized and 85 clinic) HF patients. All had reported UI at least once monthly. SUBJECTS AND SETTING: One hundred eighty-two patients with HF participated in the study; 97 were recruited while in hospital and 85 were recruited from a clinic setting. There were an equal number of participants with DM when compared to subjects without DM (n=91). The majority of subjects were white (64%), female (56%), and most perceived their health as fair to poor (74%). RESULTS: Eighty-three percent (N=151) had not asked for more UI information, while 64% indicated interest in learning more about UI. Using the transtheoretical model, participants with DM were more likely to be in the contemplation stage for behavioral change than those who did not have DM (79% vs 59%, P=.004). CONCLUSION: Few HF patients with UI (17%) had previously asked for more information about incontinence, but more than two-thirds (69%) indicated interest in learning more about UI. HF patients with DM were more likely to be in the contemplation stage for behavioral change related to UI than those without DM. PMID- 20736862 TI - Are toe pressures measured by a portable photophlethysmograph equivalent to standard laboratory tests? AB - PURPOSE: The purpose of this study was to determine if toe pressures (TPs) obtained by a registered nurse using a portable photophlethysmograph (PPG) were equivalent to TPs obtained by a registered vascular technologist (RVT) using standard laboratory equipment. DESIGN: A within-subjects, comparative design was used for the study. SETTING AND SUBJECTS: Thirty subjects referred to a vascular laboratory for arterial studies were recruited. All tests were performed in the outpatient vascular laboratory of a large, urban medical center. METHODOLOGY: Toe pressures were measured on subjects by the same RN and RVT during the same visit. Data were analyzed using the Bland-Altman method that compares bias (mean difference) and precision (limits of agreement) of measurements to previously determined criterion for clinically important limits of difference (+/-15 mm Hg) in order to assess equivalence and repeatability of measurements. Kappa statistic was calculated to assess RVT/RN agreement to detect lower extremity arterial disease (LEAD) (ie, TP<50 mm Hg). Sensitivity and specificity of the portable PPG measures were determined. RESULTS: Precision for RVT-RN TPs exceeded the previously determined cutoff criteria (+/-15 mm Hg), but precision for repeated RN PPG measures fell within the clinically important limits. Kappa statistic calculation (kappa=0.76) revealed substantial agreement (90%) between the RVT and RN measures to detect LEAD (<50 mm Hg). The portable PPG technique had good sensitivity (79%) and high specificity (95%) for detection of LEAD. CONCLUSION: Although TPs obtained by the portable PPG were not equivalent to standard laboratory tests, the portable technique agreed sufficiently with the RVT to detect LEAD. The good sensitivity and high specificity of the portable PPG make it suitable for nurses and other primary care providers to use for high-risk patients or patients with wounds, when the ankle brachial index either is elevated above 1.3 or cannot be performed. Photophlethysmograph is also suitable to assess healing potential and the need for referrals to the vascular laboratory, surgeon, or the need for adjunctive therapies. PMID- 20736863 TI - Epileptic hypersynchrony revisited. AB - Synchronization of neuronal responses, which allows coordination of distributed activity patterns, is instrumental in brain functioning, as altered neuronal synchronization is involved in a variety of brain pathologies. Epileptic hypersynchrony chiefly relies on brain wiring, which, in a broader sense, means including astrocytic release of gliotransmitters and electrotonic coupling through gap junctions, beyond classical synaptic connections. Epileptic hypersynchrony also relies on electrical field effects and ion concentration changes in the extracellular space, and it relates to intracellular mechanisms underlying neuronal hyperexcitability. The current lack of a specific impact of hypersynchrony on antiepileptic drug development might be next surpassed, as hypersynchrony seems to be a worthy and approachable, though challenging target of antiepileptic pharmacology. PMID- 20736864 TI - Tactile maze solving in congenitally blind individuals. AB - Vision is undoubtedly important for navigation although not essential as blind individuals outperform their blindfolded seeing counterparts in a variety of navigational tasks. It is believed that the blind's superior performance is because of their efficient use of proprioceptive signals and environmental cues such as temperature and echolocation. We hypothesize that by limiting these cues, blind individuals will lose their advantage compared with controls in spatial navigation tasks. We therefore evaluated the performance of blind and sighted individuals in small-scale, tactile multiple T mazes. Our results show that blindfolded sighted controls outperformed blind participants in the route learning tasks. This suggests that, contrary to indoor large-scale spaces, navigational skills inside small-scale spaces benefit from visual experience. PMID- 20736865 TI - The Drosophila calcineurin regulator, Sarah, is involved in male courtship. AB - The Drosophila Sarah (sra) gene encodes a regulator of the Ca2+/calmodulin dependent protein phosphatase, calcineurin, and plays an essential role in various biological processes. Here, we describe a novel role of sra in Drosophila male courtship behavior. sra null mutant males have reduced courtship activity. This reduced activity can be rescued by expressing sra in the mushroom bodies (MBs), brain structures important for memory formation and storage in Drosophila. In addition, overexpressing sra in the MBs, and transiently overexpressing sra during adulthood, inhibits male courtship. Our results indicate that a specific amount of sra in the MBs is required for wildtype male courtship activity. PMID- 20736867 TI - Calpastatin reduces toxicity of SOD1G93A in a culture model of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is an adult-onset, rapidly progressing, fatal disease occurring in both familial and sporadic forms. Mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) cause ALS through a gain of toxic function. Calpain activity is increased in mutant SOD1 (SOD1(G93A)) transgenic mice and in models of ischemia because of increased cytosolic calcium, which has been documented in motor neurons in rodent models of familial ALS and in sporadic ALS patients. We report that inhibition of calpain activity using calpastatin prevented the toxicity of SOD1(G93A) in motor neurons of dissociated spinal cord cultures, prolonging viability of and reducing the proportion containing SOD1(G93A) inclusions. The data support the central role of calcium dysregulation in ALS and identify a potential therapeutic pathway. PMID- 20736866 TI - Motor imagery of voluntary coughing: a functional MRI study using a support vector machine. AB - Investigating respiratory acts using motor imagery has the advantage that motion artifacts are much less likely to occur. To test whether motor imagery of voluntary coughing shows similar spatiotemporal activity patterns as compared to overt coughing, 12 participants underwent functional MRI scanning performing both tasks. We analyzed the data using a pattern classifier, that is, a support vector machine. Results showed that during imagined coughing, a number of brain areas reported previously to be involved in respiration showed more similarity in their spatiotemporal activity patterns with overt coughing than with a resting baseline. We conclude that motor imagery can be a suitable paradigm to investigate respiration, and that support vector machine analysis is potentially more sensitive and specific than a standard univariate analysis. PMID- 20736868 TI - Congenital ectopic cilia of the upper eyelid. AB - The authors report a 19-year-old woman with a cluster of ectopic cilia located in the temporal aspect of her right upper eyelid associated with symptomatic secretion from the cutaneous ostea of the cilia. Histologic examination revealed subcutaneous connective tissue interspersed with pilosebaceous follicles and apocrine glands. No evidence of lacrimal gland ducts or acini was found. PMID- 20736869 TI - Use of dissimilar trifocals to equalize fields of view for asymmetric orbital positions secondary to progressive facial hemiatrophy. AB - A 58-year-old woman presented, complaining that the vertical field of view (henceforth referred to as "field") through the middle (intermediate distance) segment of her right trifocal lens was disturbingly narrower than the left. She had undergone facial surgery for Parry-Romberg syndrome, after which right enophthalmos and hypo-orbit persisted. The longer lens-to-eye distance in the enophthalmic right eye caused the 7-mm vertical dimension of the middle segment to subtend a smaller angle at the right eye than the left, producing unequal fields. Trifocals with a larger 10-mm right eye intermediate segment vertical dimension and unchanged 7-mm left eye dimension made the angular fields through the segments nearly equal. Trifocal segments of unequal vertical dimensions were an effective solution to unequal fields of view secondary to monocular enophthalmos. PMID- 20736870 TI - Fibroma of the medial canthal area: a case report. AB - A 47-year-old women presented with a mass on the right medial canthal area for 10 years. On examination, an 18 * 12-mm sized, hard, unmovable subcutaneous mass was palpated. The tear meniscus was high, but the lacrimal outflow system was patent when irrigated. The mass was surgically excised. It was well-demarcated with a whitish pearl-like appearance and located between the orbicularis muscle and the anterior lacrimal crest. A silicone tube was intubated simultaneously. The microscopic examination of the specimen revealed dense collagen with scattered fibroblasts without mitosis or atypism, and stained positively for vimentin and negatively for S-100 and CD 34. Based on these findings, the lesion was diagnosed as a fibroma. No sign of recurrence was observed over 6 months of follow up. Although rare, fibroma should be included in the differential diagnosis of medial canthal tumors. Complete surgical excision offers a curative method of management. PMID- 20736871 TI - Operative treatment for segmental eyelid vitiligo. AB - PURPOSE: The purpose of this article is to describe a safer method of removing the epithelium from the eyelid in preparation for melanocyte transplantation in treating segmental eyelid vitiligo. METHODS: The Erbium yttrium-aluminum-garnet (YAG) laser was used for ablation of the epithelium on the nonpigmented skin of the eyelid. Subsequently, an epithelial skin graft containing melanocytes was applied to the affected area. An occlusive dressing was applied for 2 days. RESULTS: The skin graft was found to be viable on removal of the dressing, and pigment was evident within the first week. No scarring developed, and an outstanding result was evident within a few weeks and has persisted. CONCLUSIONS: Use of the Erbium YAG laser enabled us to perform the procedure safely in less than half an hour. The procedure was performed in an outpatient setting, using topical and local anesthesia. Previously, we were unwilling to offer treatment for depigmentation of the eyelid. This case demonstrates a safe method for treatment of eyelid vitiligo that can be performed by a surgeon experienced in use of the laser and epithelial grafting. PMID- 20736872 TI - Anatomy of the superior border of the lateral orbital wall: surgical implications in deep lateral orbital wall decompression surgery. AB - PURPOSE: To present the anatomical characteristics of the superior border of the lateral orbital wall and thereby reduce the risk of inadvertent dural damage during deep lateral orbital wall decompression. METHODS: Twenty-five orbits (13 right and 12 left) of 13 Asian cadavers (6 men and 7 women) aged 61 to 93 years at death (average, 79.5 years) were used. After removing the orbital content, the lateral orbital wall, and the skull and brain, the superior border of the lateral orbital wall was exposed, which was analyzed from an orbital cavity view and an intracranial cavity view. RESULTS: The anterior part of the superior border of the lateral orbital wall is parallel with the orbital roof; however, more posteriorly, as the orbital roof curves inferiorly, they become perpendicular. The cortical bone conspicuously separates the thin superior border from the orbital roof. In the junction between the superior and the posterior borders, a thick bone marrow exists. Complete removal of this bone marrow resulted in penetration in the junction of the anterior and middle cranial fossae. CONCLUSION: The authors documented the anatomy of the superior border of the lateral orbital wall, including the different relative positions between the superior border and the orbital roof in the anterior and posterior parts of the orbit. To avoid dural exposure, the cortical bone should not be exposed at the junction between the superior and posterior borders of the lateral orbital wall, which corresponds to the junction of the anterior and middle cranial fossae. PMID- 20736873 TI - Comparison of lateral and medial orbital decompression for the treatment of compressive optic neuropathy in thyroid eye disease. AB - PURPOSE: To compare the efficacy of lateral orbital decompression with medial orbital decompression for the treatment of compressive optic neuropathy (CON) caused by thyroid eye disease (TED). METHODS: A retrospective review of all patients undergoing orbital decompression for TED-associated CON between 2003 and 2008 was conducted. Clinical outcome measures included visual acuity, mean deviation on Humphrey visual field, Ishihara color plate testing, afferent pupillary defect, and Hertel exophthalmometry. A composite CON score was also calculated for each patient based on the 3 visual outcome measures, with a higher CON score reflecting greater disease severity. RESULTS: Twenty-eight eyes of 17 patients were included in the study. Ten orbits underwent lateral wall decompression, and 18 orbits underwent medial decompression. Both groups showed a significant postoperative improvement in visual acuity, Humphrey visual field testing, and color testing at 3 months following the initial surgery. The composite CON score improved 9.04 +/- 9.97 points after lateral decompression (p = 0.02) and 9.03 +/- 10.84 points after medial decompression (p = 0.003). There was no significant difference in the degree of improvement in any of the visual outcome measures between the lateral and medial groups. There was a statistically significant difference in the amount of proptosis reduction resulting from lateral decompression compared with medial decompression (6.3 versus 3.1 mm, respectively, p < 0.0001). CONCLUSIONS: Lateral orbital decompression and medial orbital decompression are both efficacious for the treatment of TED-associated CON. Lateral decompression also results in a greater proptosis reduction than medial decompression. PMID- 20736874 TI - Eyelid basal cell carcinoma developing in an epidermoid cyst: a previously unreported event. AB - A 72-year-old woman presented with a 3 * 2 * 1-mm right lower eyelid micronodular, whitish solid lesion at the nasal eyelid margin that had caused madarosis. Local excision led to the microscopic discovery of 2 epidermoid cysts, one of which harbored a basal cell carcinoma arising from its orthokeratinizing squamous cell lining. Poral openings indicated that the cysts represented follicular infundibular ectasias. BER-EP4-positive immunostaining confirmed the basal cell nature of the neoplasm. This is the first example in the eyelid of an epidermoid cyst displaying malignant transformation. No matter how innocent they may appear, all small cystic or noncystic eyelid lesions should be submitted for pathologic evaluation. PMID- 20736875 TI - Common denominators in retained orbital wooden foreign body. AB - PURPOSE: To identify some of the common denominators in the diverse presentation of retained orbital wooden foreign bodies. METHODS: A review of 9 cases of previously unrecognized retained orbital wooden foreign bodies. Intervention included surgical removal of the foreign bodies in 8 cases and fistula repair in 1 case after spontaneous foreign body extrusion. Outcome measures included return of normal vision, absence of motility disturbance, and resolution of pain, inflammation, eyelid abnormalities, and other symptoms. RESULTS: Presenting symptoms were diverse and included motility disturbance (5 of 9 patients), conjunctival injection with or without discharge (5 of 9 patients), decreased vision (4 of 9 patients), draining fistula (4 of 9 patients), and localized pain or sensation of tightness in the eyelid (4 of 9 patients). Uncommon symptoms included proptosis (2 of 9 patients), ptosis (2 of 9 patients), lower eyelid retraction (2 of 9 patients), and pain on ocular movement (1 of 9 patients). The interval between the injury and the diagnosis of retained wooden foreign body ranged from 10 days to 42 weeks. CONCLUSION: Occasionally, not all of the wooden pieces are removed at the time of initial orbital exploration, despite best efforts. Signs and symptoms of retained orbital wooden foreign body vary greatly. There is no single specific diagnostic or pathognomonic finding. Heightened awareness and a high index of suspicion are keys to proper diagnosis. It is important to have a properly worded consent that includes the possibility of residual wooden foreign bodies and the need for subsequent surgical exploration. PMID- 20736876 TI - The use of a radiofrequency unit for excisional biopsy of eyelid papillomas. AB - PURPOSE: To describe a technique for excisional biopsy of eyelid papillomatous lesions using a radiofrequency (RF) unit. METHOD: In this prospective, interventional case series, 64 patients with eyelid papillomatous lesions underwent excisional biopsy using an RF unit. RESULTS: The upper eyelid was involved in 34.5% and the lower eyelid was involved in 62.5% of cases, with 3% having lesions on both eyelids. Surgery was performed with no intraoperative or postoperative bleeding, avoiding wound sutures and bandage and with very good cosmetic results. On histopathologic examination, 72% of these lesions were squamous papilloma. Reoperation was needed in 2 patients. Over-resection and notching of the eyelid margin happened in one patient but improved 3 months after surgery. CONCLUSION: Use of an RF unit for excisional biopsy of eyelid papillomatous lesions is a safe and effective method. PMID- 20736877 TI - Severe genital ulceration in an acute epstein-barr virus infection. AB - Genital ulceration is a rare manifestation of infectious mononucleosis caused by Epstein-Barr virus (EBV). We report a girl with severe genital ulceration and tissue necrosis during primary EBV infection that required surgical debridement. The excised genital tissue was EBV polymerase chain reaction-positive whereas in situ hybridization was negative. This suggests that the ulceration was likely because of the inflammatory response to the virus and not because of the intense viral infection of the genitalia. PMID- 20736878 TI - Powassan virus infection presenting as acute disseminated encephalomyelitis in Tennessee. AB - Powassan virus is a rarely diagnosed cause of encephalitis, and is associated with significant neurologic sequelae. Although symptomatic infections with Powassan virus occur primarily in adults, we report a case of confirmed Powassan neuroinvasive disease in a child presenting to a Tennessee hospital, with symptoms and imaging studies suggestive of acute disseminated encephalomyelitis. PMID- 20736879 TI - Persistence of human bocavirus DNA in immunocompromised children. AB - Human bocavirus is frequently detected in immunocompetent as well as in immunocompromised children. However, the course of infection in immunocompromised children is still poorly investigated. In the present study, we describe 4 cases of repeat human bocavirus detection in the presence of severe immunodeficiency. In the view of homologous viral sequences identified in serial samples, possible persistence and reactivation in these patients are discussed. PMID- 20736880 TI - Quality of growth in exclusively breast-fed infants in the first six months of life: an Italian study. AB - Nutrition in early life, growth, and subsequent health over a lifetime are significantly interrelated. The aim of this study was to assess body composition changes in exclusively breast-fed infants from birth up to 6 mo of age. An observational, prospective, cohort study was conducted. Fifty-nine full-term, healthy, exclusively breast-fed infants underwent assessment of growth and body composition, using air-displacement plethysmograph (i.e. PEA POD) by Life Measurement, Inc. (Concord, CA). Body composition was assessed at birth, 2 wk, and 1, 2, 3, 4, 5, and 6 mo of age. Mean birth weight (g) and gestational age (wk) of the infants were 3170 +/- 420 and 39.21 +/- 1.29, respectively. Percentage of fat mass increased significantly over the first 4 mo (p < 0.001), both in boys and girls, with no differences detected between boys and girls at any time point. This article provides preliminary in-depth data on whole-body composition, in exclusively breast-fed infants during the first months of life. Further studies assessing larger sample sizes are desirable to develop reference body composition data. PMID- 20736881 TI - A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. AB - Severe hypoxic-ischemic encephalopathy (HIE) is a devastating condition that can lead to mortality and long-term disabilities in term newborns. No rapid and reliable laboratory test exists to assess the degree of neuronal injury in these patients. We propose two possible biomarkers: 1) phosphorylated axonal neurofilament heavy chain (pNF-H) protein, one of the major subunits of neurofilaments, found only in axonal cytoskeleton of neurons and 2) Ubiquitin C terminal hydrolase 1 (UCHL1 protein) that is heavily and specifically concentrated in neuronal perikarya and dendrites. High-serum pNF-H and UCHL1 levels are reported in subarachnoid hemorrhage and traumatic brain injury, suggesting that they are released into blood following neuronal injury. We hypothesized that serum pNF-H and UCHL1 were higher in neonates with moderate-to severe HIE than in healthy neonates. A time-limited enrollment of 14 consecutive patients with HIE and 14 healthy controls was performed. UCHL1 and pNF-H were correlated with clinical data and brain MRI. UCHL1 and pNF-H serum levels were higher in HIE versus controls. UCHL1 showed correlation with the 10-min Apgar score, and pNF-H showed correlation with abnormal brain MRI. Our findings suggest that serum UCHL1 and pNF-H could be explored as diagnostic and prognostic tools in neonatal HIE. PMID- 20736882 TI - Placental inflammation and fetal hemodynamics in a rat model of chorioamnionitis. AB - The relative contributions of inflammation and ischemia to the pathogenesis of periventricular leukomalacia (PVL) have not been elucidated. We hypothesized that fetal cardiovascular function and cerebral blood flow velocity (BFV) would be decreased in a rat model of chorioamnionitis. We also tested whether placental inflammation was related to proximity to the cervix in our model of chorioamnionitis [intracervical lipopolysaccharide (LPS) or vehicle (PBS) injection]. On embryonic d 15, Sprague-Dawley rats underwent baseline maternal and fetal echocardiography, followed by LPS or PBS injection, then serial echocardiographic evaluations until embryonic day (ED) 21. One hour after birth, pups had middle cerebral artery (MCA) BFV measured. Placentas of LPS-exposed pups exhibited uniform, higher inflammation grades (p < 0.001). All fetal BFVs increased with advancing GA (p < 0.001) whereas resistance index (RI) decreased (p < 0.001). There was no difference in fetal BFV between the groups other than a reduced gestation-related increase in descending aorta BFV in LPS-exposed rats (p < 0.05). Newborn pups exposed to LPS had lower heart rate (p = 0.006) and MCA BFV (p = 0.024) and higher RI (p = 0.003) and pulsatility index (PI; p = 0.004). In conclusion, intracervical LPS injection produces an inflammation independent of placental position, a blunted increase in gestation-related aortic BFV, and a decrease in MCA BFV in newborn pups. PMID- 20736883 TI - Airway response to exercise by forced oscillations in asthmatic children. AB - Forced expiratory volume in 1 s (FEV1) detection of exercise-induced bronchoconstriction (EIB) to identify asthma has good specificity but rather low sensitivity. The aim was to test whether sensitivity may be improved by measuring respiratory resistance (Rrs) by the forced oscillation technique (FOT). Forty seven asthmatic and 50 control children (5-12 y) were studied before and after running 6 min on a treadmill. Rrs in inspiration (Rrsi) and expiration (Rrse), FEV1 and Rrsi response to a deep inhalation (DI) were measured before and after exercise. In asthmatics versus controls, exercise induced significantly larger increases in Rrsi (p < 0.001) and larger decreases in FEV1 (p = 0.004). Asthmatics but not controls showed more bronchodilation by DI after exercise (p = 0.02). At specificity >0.90, sensitivity was 0.53 with 25% increase Rrsi and 0.45 with 27% increase Rrse or 5% decrease FEV1. It is concluded that the FOT improves sensitivity of exercise challenge, and the Rrsi response to DI may prove useful in identifying the mechanism of airway obstruction. PMID- 20736884 TI - Pathogenesis of renal injury in the megabladder mouse: a genetic model of congenital obstructive nephropathy. AB - Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder (mgb) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous mgb mice (mgb-/-). Renal ultrasound was used to stratify the disease state of mgb-/- mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (alpha-SMA), TGF-beta1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that mgb-/- mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in mgb-/- kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the mgb mouse represents a unique small animal model for the study of CON. PMID- 20736886 TI - Three-dimensional morphology and kinematics of the craniovertebral junction in rheumatoid arthritis. AB - STUDY DESIGN: A case-series study. OBJECTIVES: To measure the 3-dimensional (3D) morphology and kinematics of the craniovertebral junction (CVJ) using a 3D computed tomography (CT) model; to reveal abnormal patterns and the relationships between pathology and kinematics. SUMMARY OF BACKGROUND DATA: Evaluations using radiography, 2-dimensional (2D) CT and magnetic resonance imaging have limitations because of the complex 3D structure of the CVJ. METHODS: Twenty-four rheumatoid arthritis patients (21 females, 3 males) with cervical involvement underwent CT scanning of the cervical spine from the basilar process of the occipital bone to the first thoracic vertebra in neutral and flexed positions. The 3D morphology of the occipital condyle, atlas, and axis were classified based on the type of deformity observed. Periodontoid lesions (continuous bony lesions between the atlas and the odontoid process) were also noted. The 3D kinematics in the atlanto-occipital and atlantoaxial joints were evaluated using the volume merge method. RESULTS: Deformities in the atlanto-occipital joints appeared more frequently than those in the atlantoaxial joints. The most common instability pattern was flexural rotation during flexion at the CVJ. The direction of translational motions during flexion was posterior in the atlanto-occipital joint and anterior and caudal in the atlantoaxial joint. CONCLUSION: The results suggest that bilateral occipital condyle deformation, unilateral and bilateral mass collapse, and periodontoid lesions may affect flexion/extension rotational instability in the atlantoaxial joint. In addition, unilateral occipital condyle deformation and atlantoaxial joint stability may affect sagittal translational instability to the posterior side in the atlanto-occipital joint. The noninvasive 3D CT imaging technique employed here would be useful for predicting the prognosis of patients with rheumatoid deformities at the CVJ. PMID- 20736885 TI - PharmGKB summary: dopamine receptor D2. PMID- 20736887 TI - Is decompressive surgery effective for spinal cord sarcoidosis accompanied with compressive cervical myelopathy? AB - STUDY DESIGN: A retrospective multicenter study of series of 12 patients with spinal cord sarcoidosis who underwent surgery. OBJECTIVE: To evaluate the postoperative outcomes of patients with cervical spinal cord sarcoidosis accompanied with compressive myelopathy and effect of decompressive surgery on the prognosis of sarcoidosis. SUMMARY OF BACKGROUND DATA: Sarcoidosis is a chronic, multisystem noncaseating granulomatous disease. It is difficult to differentiate spinal cord sarcoidosis from cervical compressive myelopathy. There are no studies regarding the coexistence of compressive cervical myelopathy with cervical spinal cord sarcoidosis and the effect of decompressive surgery. METHODS: Nagoya Spine Group database included 1560 cases with cervical myelopathy treated with cervical laminectomy or laminoplasty from 2001 to 2005. A total of 12 patients (0.08% of cervical myelopathy) were identified spinal cord sarcoidosis treated with decompressive surgery. As a control subject, 8 patients with spinal cord sarcoidosis without compressive lesion who underwent high-dose steroid therapy without surgery were recruited. RESULTS: In the surgery group, enhancing lesions on magnetic resonance imaging (MRI) were mostly seen at C5-C6, coincident with the maximum compression level in all cases. Postoperative recovery rates in the surgery group at 1 week and 4 weeks were -7.4% and -1.1%, respectively. Only 5 cases had showed clinical improvement, and the condition of these 5 patients had worsened again at averaged 7.4 weeks after surgery. Postoperative oral steroid therapy was initiated at an average of 6.4 weeks and the average initial dose was 54.0 mg in the surgery group, while 51.3 mg in the nonsurgery group. The recovery rate of the Japanese Orthopedic Association score, which increased after steroid therapy, was better in the nonsurgery group (62.5%) than in the surgery group (18.6%) with significant difference (P < 0.01). CONCLUSION: The effect of decompression for spinal cord sarcoidosis with compressive myelopathy was not evident. Early diagnosis for sarcoidosis from other organ and steroid therapy should be needed. PMID- 20736888 TI - An increased kyphosis of the thoracolumbar junction is correlated to more axial vertebral rotation in thoracolumbar/lumbar adolescent idiopathic scoliosis. AB - STUDY DESIGN: A retrospective correlation study. OBJECTIVE: To identify radiographically if there is a correlation of the sagittal thoracolumbar alignment to the axial vertebral rotation and coronal scoliotic curvature in thoracolumbar/lumbar (TL/L) adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The consistent positive correlation between coronal angulations and axial rotation has been defined as a typical feature of AIS. However, the correlation of sagittal alignment transformation to axial and/or coronal deformity has not been definitely described, especially for primary TL/L AIS. METHODS: On standard anteroposterior and lateral radiographs of 43 patients with TL/L AIS, coronal and sagittal parameters including primary TL/L and compensatory thoracic curve, thoracic kyphosis, thoracolumbar junctional sagittal curve (TLJS), and lumbar lordosis, were evaluated using the Cobb method. Apical vertebral rotation (AVR) was evaluated using the Perdriolle torsionmeter. The correlation was investigated between all parameters. After the patients were divided into 2 subgroups according to the TLJS curvature, the average AVR and coronal TL/L Cobb were compared between the 2 groups. RESULTS: The average TLJS Cobb was 4.5 degrees +/- 8.8 degrees (range, -12.5 degrees -24.3 degrees ) with 28 cases (65.1% of all cases) in TLJS+ (kyphosis) group and 15 cases in TLJS- (lordosis) group. Significant correlations were observed between AVR and coronal TL/L curvature (P < 0.001), and between AVR and sagittal TLJS Cobb angle (P < 0.001). These correlations still existed when the partial correlation analysis was conducted. The correlation between sagittal TLJS and coronal TL/L curvature became nonsignificant (P = 0.405) when the partial correlation analysis was conducted with AVR as control variable. Besides, a significant difference of 7.0 degrees was observed in average AVR between TLJS+ and TLJS- subgroups (P < 0.001). CONCLUSION: From the standard anteroposterior and lateral radiographs, an increased kyphosis of the thoracolumbar junction was observed in TL/L AIS, and it was demonstrated to be positively correlated to more axial vertebral rotation of the scoliotic spine. PMID- 20736889 TI - Clinical outcomes and predictive factors relating to prognosis of conservative and surgical treatments for cervical spondylotic amyotrophy. AB - STUDY DESIGN: Retrospective clinical analyses of patients with cervical spondylotic amyotrophy (CSA). OBJECTIVE: To report the clinical outcomes and predictive factors relating to the prognosis in conservative and surgical treatments for CSA. SUMMARY OF BACKGROUND DATA: CSA is a clinical entity characterized by muscle atrophy in the upper extremity without marked sensory disturbance or spastic tetraparesis. The indications for, and outcomes of conservative and surgical treatments for CSA have not been clearly enunciated. METHODS: Ninety patients with CSA were enrolled in this study. All of them initially received continuous cervical traction for 2 to 3 weeks as inpatients. If this conservative treatment was ineffective, surgical intervention was carried out after informed consent was obtained. We investigated the outcome of conservative treatment, the predictive factors relating to the prognosis of the conservative treatment, and the outcome of surgery after initial conservative treatment failed. RESULTS: After initial conservative treatment, 42 patients (46.7%) showed excellent or good outcome, 29 patients underwent surgery, and 19 patients declined surgery. Consequently, 61 patients were conservatively followed up. At final follow-up, 40% of the patients still showed excellent or good neurologic status by conservative treatment, and this group was characterized by age <50 years, duration of symptoms <6 months, single-level stenosis, foraminal stenosis, and a good response to traction therapy. Additional 5 patients underwent surgery during follow-up because of deterioration of symptom, and 34 patients consequently underwent surgery at the final follow-up. Of 34, 28 (82%) patients who underwent surgery obtained neurologic improvement. CONCLUSION: The present study has demonstrated the outcome of conservative and of surgical treatments for CSA, together with the predictive factors relating to the prognosis. Conservative treatment should be initially tried on CSA patients, especially those with predictive factors relating to a better prognosis. However, if conservative treatment failed, surgical intervention was successful. PMID- 20736891 TI - Radiation exposure to the surgeon during open lumbar microdiscectomy and minimally invasive microdiscectomy: a prospective, controlled trial. AB - STUDY DESIGN: This is a prospective in vivo study comparing radiation exposure to the surgeon during 10 minimally invasive lumbar microdiscectomy cases with 10 traditional open discectomy cases as a control. OBJECTIVE: Radiation exposure to the eye, chest, and hand of the operating surgeon during minimally invasive surgery (MIS) and open lumbar microdiscectomy were measured. The Occupational Exposure Guidelines were used to calculate the allowable number of cases per year from the mean values at each of the 3 sites. SUMMARY OF BACKGROUND DATA: Fluoroscopy is a source of ionizing radiation and as such, is a potential health hazard with continued exposure during surgery. Presently, radiation exposure to the surgeon during MIS lumbar microdiscectomy is unknown. METHODS: Radiation exposure to the surgeon (millirads [mR]) per case was measured by digital dosimeters placed at the level of the thyroid/eye, chest, and dominant forearm. Other data collected included operative side and level, side of the surgeon, side of the x-ray source, total fluoroscopy time, and energy output. RESULTS: The average radiation exposure to the surgeon during open cases was thyroid/eye 0.16 +/- 0.22 mR, chest 0.21 +/- 0.23 mR, and hand 0.20 +/- 0.14 mR. During minimally invasive cases exposure to the thyroid/eye was 1.72 +/- 1.52 mR, the chest was 3.08 +/- 2.93 mR, and the hand was 4.45 +/- 3.75 mR. The difference between thyroid/ eye, chest, and hand exposure during open and minimally invasive cases was statistically significant (P = 0.010, P = 0.013, and P = 0.006, respectively). Surgeons standing in an adjacent substerile room during open cases were exposed to 0.2 mR per case. CONCLUSION: MIS lumbar microdiscectomy cases expose the surgeon to significantly more radiation than open microdiscectomy. One would need to perform 1623 MIS microdiscectomies to exceed the exposure limit for whole-body radiation, 8720 cases for the lens of the eye, and 11,235 cases for the hand. Standing in a substerile room during x-ray localization in open cases is not fully protective. PMID- 20736890 TI - Effects of torsion on intervertebral disc gene expression and biomechanics, using a rat tail model. AB - STUDY DESIGN: In vitro and in vivo rat tail model to assess effects of torsion on intervertebral disc biomechanics and gene expression. OBJECTIVE: Investigate effects of torsion on promoting biosynthesis and producing injury in rat caudal intervertebral discs. SUMMARY OF BACKGROUND DATA: Torsion is an important loading mode in the disc and increased torsional range of motion is associated with clinical symptoms from disc disruption. Altered elastin content is implicated in disc degeneration, but its effects on torsional loading are unknown. Although effects of compression have been studied, the effect of torsion on intervertebral disc gene expression is unknown. METHODS: In vitro biomechanical tests were performed in torsion on rat tail motion segments subjected to 4 treatments: elastase, collagenase, genipin, control. In vivo tests were performed on rats with Ilizarov-type fixators implanted to caudal motion segments with five 90 minute loading groups: 1 Hz cyclic torsion to +/- 5 +/- 15 degrees and +/- 30 degrees , static torsion to + 30 degrees , and sham. Anulus and nucleus tissues were separately analyzed using qRT-PCR for gene expression of anabolic, catabolic, and proinflammatory cytokine markers. RESULTS: In vitro tests showed decreased torsional stiffness following elastase treatment and no changes in stiffness with frequency. In vivo tests showed no significant changes in dynamic stiffness with time. Cyclic torsion upregulated elastin expression in the anulus fibrosus. Up regulation of TNF-alpha and IL-1beta was measured at +/-30 degrees . CONCLUSION: We conclude that strong differences in the disc response to cyclic torsion and compression are apparent with torsion increasing elastin expression and compression resulting in a more substantial increase in disc metabolism in the nucleus pulposus. Results highlight the importance of elastin in torsional loading and suggest that elastin remodels in response to shearing. Torsional loading can cause injury to the disc at excessive amplitudes that are detectable biologically before they are biomechanically. PMID- 20736893 TI - Predictors of Recovery After Conservative Treatment of AO-Type A Thoracolumbar Spine Fractures Without Neurological Deficit. AB - STUDY DESIGN: Prospective, correlational, exploratory, clinical research. OBJECTIVE: To identify the factors determining a patient's recovery after conservative treatment of compression fractures of the thoracolumbar spine. SUMMARY OF BACKGROUND DATA: The reported results of compression fractures are poor. These results are not influenced by the severity of compression, the fracture site, or the residual deformity. Otherwise, the factors that determine a patient's recovery are unknown. METHODS: In 48 conservatively treated patients the preinjury versus the 12-month follow-up differences (Delta) in back pain (visual analogue scale for pain), Oswestry disability index (ODI), and the Greenough and Fraser low back outcome scale were prospectively recorded. For these differences and for time lost from work and satisfaction, multiple linear regressions with combinations of 16 factors were performed. RESULTS: At 1 year, patients with an income-insurance were 9% (P = 0.096) more disabled than those without. They reported a 15% less favorable global outcome and 27% less participation. Smokers were 13% (P = 0.010) more disabled and 11% (P = 0.044) less satisfied. With each increase of the AO-fracture type from A1 to A3 the disability was 8% worse. Patients with pre-existent chronic low back pain (CLBP) returned two points (on a visual analogue scale [VAS] pain total of 10) more closely (P = 0.041) to their preinjury pain level than those without but were 21% (P = 0.001) less satisfied. Our model offers an explanation for more than 25% of the variability of DeltaODI and of the satisfaction. For sick leave, no significant predictors were found. CONCLUSION: Smoking and insurance status are the strongest negative predictors for recovery. LBP patients returned more closely to their preinjury back pain level, but were less satisfied. The AO fracture type had a marked influence on disability, the sagittal deformity had not. The time lost from work did not depend on patient or injury-related factors. LEVEL OF EVIDENCE: N/A. PMID- 20736892 TI - Combined pre- and retrovascular extraoral approach for tumors at lateral mass of the atlas. AB - STUDY DESIGN: a series of 9 patients surgically treated with a novel combined pre and retrovascular extraoral approach to lateral mass of the atlas (LMA) is examined. OBJECTIVE: to describe the efficacy of combined pre- and retrovascular extraoral approach in achieving a wide exposure and aggressive resection of tumors at the LMA. SUMMARY OF BACKGROUND DATA: the anatomic complexity and closeness to vital neurovascular structures raise technical difficulties in the surgical access to the LMA. Although various approaches, such as transoral approach, high anterior cervical approach, anterior lateral approach, and far lateral approach, have been reported in literature, wide exposure for the tumors at the LMA remains a unique challenge. METHODS: for our experience in the surgical exposure of the upper cervical spine, we have developed a combined pre- and retrovascular extraoral approach to the atlas since 2001. Nine patients with neoplastic lesions at the LMA were surgically treated through this combined approach. Reconstruction of stability was achieved by a posterior occipitocervical fusion through a posterior approach under the same anesthesia. RESULTS: this combined approach provided an excellent surgical field exposure to ensure the successful tumor resection while preventing the vertebral artery or nerve from injury. There was no operative mortality or severe morbidity in this series. Complications included 1 instance of transient dysphagia and 2 instances of transient trouble swallowing liquids. The symptoms of local pain and pharyngeal discomfort relieved, and patients suffering from spinal cord compression recovered well with 1 level of the Frankel scale when reevaluated 3 months after operation. With a follow-up period of 16 to 100 months, 1 patient with chondrosarcoma developed local recurrence at the 14th month of postoperation and died of respiratory and circulatory failure 39 months after surgery. No evidence of local recurrence was found in other patients. CONCLUSION: the combined pre- and retrovascular extraoral approach provides an advantageous alternative to previous reported approaches. For selected cases with tumor lesions at the LMA, this combined approach offers more benefits, through which a wide exposure with well-protected vertebral artery favoring radical excision could be achieved without complications normally associated with transoral surgery. PMID- 20736894 TI - Long-term outcomes of lumbar fusion among workers' compensation subjects: a historical cohort study. AB - STUDY DESIGN: Historical cohort study. OBJECTIVE: To determine objective outcomes of return to work (RTW), permanent disability, postsurgical complications, opiate utilization, and reoperation status for chronic low back pain subjects with lumbar fusion. Similarly, RTW status, permanent disability, and opiate utilization were also measured for nonsurgical controls. SUMMARY OF BACKGROUND DATA: A historical cohort study of workers' compensation (WC) subjects with lumbar arthrodesis and randomly selected controls to evaluate multiple objective outcomes has not been previously published. METHODS: A total of 725 lumbar fusion cases were compared to 725 controls who were randomly selected from a pool of WC subjects with chronic low back pain diagnoses with dates of injury between January 1, 1999 and December 31, 2001. The study ended on January 31, 2006. Main outcomes were reported as RTW status 2 years after the date of injury (for controls) or 2 years after date of surgery (for cases). Disability, reoperations, complications, opioid usage, and deaths were also deter-mined. RESULTS: Two years after fusion surgery, 26% (n = 188) of fusion cases had RTW, while 67% (n = 483) of nonsurgical controls had RTW (P <= 0.001) within 2 years from the date of injury. The reoperation rate was 27% (n = 194) for surgical patients. Of the lumbar fusion subjects, 36% (n = 264) had complications. Permanent disability rates were 11% (n = 82) for cases and 2% (n = 11) for nonoperative controls (P <= 0.001). Seventeen surgical patients and 11 controls died by the end of the study (P = 0.26). For lumbar fusion subjects, daily opioid use increased 41% after surgery, with 76% (n = 550) of cases continuing opioid use after surgery. Total number of days off work was more prolonged for cases compared to controls, 1140 and 316 days, respectively (P < 0.001). Final multi-variate, logistic regression analysis indicated the number of days off before surgery odds ratio [OR], 0.94 (95% confidence interval [CI], 0.92-0.97); legal representation OR, 3.43 (95% CI, 1.58-7.41); daily morphine usage OR, 0.83 (95% CI, 0.71-0.98); reoperation OR, 0.42 (95% CI, 0.26-0.69); and complications OR, 0.25 (95% CI, 0.07-0.90), are significant predictors of RTW for lumbar fusion patients. CONCLUSION: This Lumbar fusion for the diagnoses of disc degeneration, disc herniation, and/or radiculopathy in a WC setting is associated with significant increase in disability, opiate use, prolonged work loss, and poor RTW status. PMID- 20736895 TI - A review of analytical techniques for determination of glimepiride: present and perspectives. AB - Glimepiride is an oral antidiabetic drug in the sulfonylurea class, which is widely used in treatment of Type 2 diabetes and it is currently available in more than 60 countries worldwide. As a result of the importance of this oral hypoglycemic agent in the treatment of noninsulin-dependent diabetes mellitus, this work aims to compile the published analytical methods reported so far in the literature for determination of glimepiride in biologic samples and pharmaceutical formulations. Techniques like high-performance liquid chromatography with ultraviolet, array-diode, mass spectroscopy, evaporative light scattering and charged aerosol detections, liquid chromatography atmospheric pressure chemical ionization-mass spectrometry, liquid chromatography electrospray ionization-tandem mass spectrometry, semimicrobore high-performance liquid chromatography with column-switching, micellar electrokinetic chromatography, high-performance thin layer chromatography, polarography, and spectrophotometry have been used for analysis, from which it can be seen that high-performance liquid chromatography methods have been used most extensively. PMID- 20736896 TI - Population pharmacokinetics of mycophenolic acid and metabolites in patients with glomerulonephritis. AB - Mycophenolic acid (MPA) is an inosine monophosphate dehydrogenase inhibitor used for glomerulonephritis treatment. The objective of the current study was to develop a population pharmacokinetic model for MPA and metabolites in glomerulonephritis to enable appropriate design of MPA regimens in these patients with alterations in kidney structure and function. Thirty-nine patients with glomerulonephritis and receiving mycophenolate mofetil were recruited to participate in a 24-hour pharmacokinetic study. Blood was collected at times 0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours and urine was collected over the intervals of 0 to 6, 6 to 12, and 12 to 24 hours. Plasma and urine samples were assayed for MPA and MPA glucuronide (MPAG) by high-performance liquid chromatography and for acyl-MPA glucuronide (AcMPAG) by liquid chromatography/mass spectrometry. Population pharmacokinetic analysis and covariate model building were evaluated using Non-linear Mixed Effect Modeling software (NONMEM, Version 6.2.0; ICON Development Solutions, Ellicott City, MD). The final model for MPA and its metabolites consisted of nine discrete compartments; 1) depot gastrointestinal; 2) central MPA; 3) peripheral MPA; 4) gallbladder; 5) MPA urine; 6) MPAG central; 7) MPAG urine; 8) AcMPAG central; and 9) AcMPAG urine compartment. The MPA population mean estimates for apparent nonrenal clearance (ClNR/F) and apparent central volume of distribution were 14.3 L/hr and 21.1 L, respectively. The mean population estimate for apparent renal clearance (ClR/F) was dependent on estimated creatinine clearances (eClcr); 0.0975 L/hr for eClcr 80 mL/min or less and 0.157 L/hr for eClcr greater than 80 mL/min. Covariate analyses identified: eClcr on CLNR,MPA/F (P < 0.001), eClcr (with a cutoff value at 80 mL/min) on CLR,MPA/F (P < 0.025), serum albumin on CLNR,MPA/F (P < 0.01), eClcr on CLR,MPAG/F (P < 0.001), and eClcr on CLR,AcMPAG/F (P < 0.001). Evaluation of the final model by visual predictive check showed that most of the observed values were within the 95th percent prediction interval generated from 100 simulations of the final model. The current population pharmacokinetic model demonstrated eClcr and serum albumin influenced the renal and nonrenal components of Cl/F, suggesting patients with glomerulonephritis would have highly altered MPA exposures. PMID- 20736898 TI - Computerized tomography. Understanding the risks and benefits. PMID- 20736897 TI - Significance of intragraft CD138+ lymphocytes and p-S6RP in pediatric kidney transplant biopsies. AB - BACKGROUND: We have previously shown that intragraft CD20+ B cells are associated with acute cellular rejection (ACR) and allograft loss. Phosphorylation of S6 ribosomal protein, a downstream target of the PI3K/Akt/mTOR pathway, promotes growth and proliferation of cells and could identify metabolically active cells such as alloantibody secreting plasma cells. Because CD20+ lymphocytes can differentiate into CD138+ plasma cells, we aimed to identify functionally active plasma cells by using intragraft CD138 quantification and p-S6RP staining and correlate these results with allograft rejection, function, and survival. METHODS: We examined 46 renal transplant biopsies from 32 pediatric patients who were biopsied for clinical suspicion of rejection. Immunohistochemical staining for C4d, CD20, CD138, and p-S6RP was performed. Patient creatinine clearance and graft status was followed up postbiopsy. RESULTS: Patients with greater than or equal to six CD138+ cells/high power field (hpf) had worse graft survival with a hazard ratio of 3.4 (95% CI 1.3-9.2) 2 years postbiopsy compared with those with 0 to 5 cells/hpf (P=0.016). CD138+ cells were stained for p-S6RP, indicating functionally active plasma cells. They were associated with ACR (P=0.004) and deteriorating graft function (R=0.22, P=0.001). Intragraft CD20+ and CD138+ cells found together in ACR were associated with poorer graft survival than either marker alone, hazard ratio 1.5 (95% CI 1.1-2.2, P=0.01). CONCLUSIONS: A threshold of greater than or equal to six CD138+ metabolically active plasma cells per hpf, coexisting with CD20+ B cells, was associated with poor allograft function and survival. This may represent an additional antibody-mediated process present in the setting of ACR and could play an important role in characterization and treatment of transplant rejection. PMID- 20736899 TI - Increase in colonoscopies associated with decrease in colorectal cancer deaths. PMID- 20736900 TI - Removing disease-free breast after cancer diagnosis may not boost survival. PMID- 20736901 TI - Hysterectomy. Understand the options. PMID- 20736902 TI - Mayo Clinic office visit. Essential tremor. An interview with J. Eric Ahlskog, M.D., Ph.D. PMID- 20736903 TI - Flexible feet. Choices in running and walking shoes. PMID- 20736904 TI - The lowdown on sundowning. What causes "sundowning" in people with dementia? PMID- 20736905 TI - Goiter be gone. How is a goiter treated? PMID- 20736906 TI - Asymmetric synthesis of alpha-aminophosphonates using the inexpensive chiral catalyst 1,1'-binaphthol phosphate. AB - Asymmetric addition under mild conditions of dialkyl phosphites on aldimines derived from cinnamaldehyde catalyzed by the inexpensive chiral organocatalyst (R)-3,3'-[4-fluorophenyl](2)-1,1'-binaphthol phosphate has been found effective to give new alpha-amino-phosphonates 9 in moderate yields (30-65%) and enantiomeric excess (8.4%-61.9%). PMID- 20736907 TI - Yields and constituents of essential oil from cones of Pinaceae spp. natively grown in Turkey. AB - In this study, the yields and composition of essential oils obtained from the cones of Pinaceae family species natively grown in Turkey were investigated. Essential oils were obtained by hydrodistillation. Oil yields were 0.13-0.48 mL/100 g in pine cones, 0.42-0.59 mL/100g in fir, 0.36 mL/100g in spruce and 0.37 mL/100g in cedar. While alpha-pinene (47.1-14.8%) was the main constituent of P. slyvestris, P. nigra and P. halepensis, limonene (62.8%) in P. pinea and beta pinene (39.6%) in P. brutia were found in higher amounts. Like in P. pinea, limonene was the main compound in Cedrus libani (22.7%). In fir species the major compounds were alpha-pinene (70.6-53.0%) and beta-pinene (10.9-8.2%). Contrary to other species beta-pinene (32.7%) was found as a major compound in Picea orientalis. PMID- 20736908 TI - Antimicrobial and antioxidant activities of the root bark essential oil of Periploca sepium and its main component 2-hydroxy-4-methoxybenzaldehyde. AB - The root bark essential oil of Periploca sepium Bunge (Asclepiadaceae/ Apocynaceae) obtained by hydrodistillation was investigated by GC and GC-MS. 2 Hydroxy-4-methoxybenzaldehyde was found to be the main component (78.8% of the total) among 17 identified compounds. 2-Hydroxy-4-methoxybenzaldehyde was separated and purified by preparative thin layer chromatography, and was further identified by means of physicochemical and spectrometric analysis. Both the essential oil and 2-hydroxy-4-methoxybenzaldehyde exhibited antimicrobial activities on all test bacteria and fungi, with MBC/MFC values ranging from 125 microg/mL to 300 microg/mL, MIC values from 80 microg/mL to 300 microg/mL, and IC(50) values from 63.29 microg/mL to 167.30 microg/mL. They also showed moderate antioxidant activity in the DPPH free radical scavenging, beta-carotene bleaching and ferrozine-ferrous ions assays. The results indicated that the major portion of these antimicrobial and antioxidant activities was due to the presence of 2 hydroxy-4-methoxy-benzaldehyde in the oil, which could potentially be developed as an antimicrobial and antioxidant agent in the future. PMID- 20736909 TI - High molecular weight glucan of the culinary medicinal mushroom Agaricus bisporus is an alpha-glucan that forms complexes with low molecular weight galactan. AB - An alpha-glucan was isolated from the culinary medicinal mushroom A. bisporus by hot water extraction, ethanol precipitation and DEAE-cellulose chromatography. The resulting material showed a single HMW peak excluded from a Sephadex G50 column that could completely be degraded by alpha-amylase treatment. After heating in 1% SDS a small additional peak of low MW eluted from the G50 column. The monosaccharide composition of the main peak was evaluated by HPLC, and was found to consist of a majority of glucose (97.6%), and a minor proportion of galactose (2.4%). Methylation analysis and degradation by alpha-amylase indicated the presence of an alpha-glucan with a main chain consisting of (1(R)4)-linked units, substituted at O-6 by alpha-D-glucopyranose single-units in the relation 1:8. Mono- (13C-, 1H-NMR) and bidimensional [1H (obs.),13C-HSQC] spectroscopy analysis confirmed the alpha-configuration of the Glcp residues by low frequency resonances of C-1 at delta 100.6, 100.2, and 98.8 ppm and H-1 high field ones at delta 5.06, 5.11, and 4.74 ppm. The DEPT-13C-NMR allowed assigning the non substituted and O-substituted -CH(2) signals at delta 60.3/60.8 and 66.2 ppm, respectively. Other assignments were attributed to C-2, C-3, C-4, C-5 and C-6 of the non-reducing ends at delta 71.8; 72.8; 70.0; 71.3 and 60.3/60.8 ppm, respectively. The minor proportion of galactose that was demonstrated was probably derived from a complex between the alpha-glucan and a low molecular weight galactan. PMID- 20736910 TI - Chemical composition and toxicity against Sitophilus zeamais and Tribolium castaneum of the essential oil of Murraya exotica aerial parts. AB - In our screening program for new agrochemicals from Chinese medicinal herbs, Murraya exotica was found to possess insecticidal activity against the maize weevil, Sitophilus zeamais and red flour beetle, Tribolium castaneum. The essential oil of aerial parts of M. exotica was obtained by hydrodistillation and investigated by GC and GC-MS. The main components of M. exotica essential oil were spathulenol (17.7%), alpha-pinene (13.3%), caryophyllene oxide (8.6%), and alpha-caryophyllene (7.3%). Essential oil of M. exotica possessed fumigant toxicity against S. zeamais and T. castaneum adults with LC(50) values of 8.29 and 6.84 mg/L, respectively. The essential oils also show contact toxicity against S. zeamais and T. castaneum adults with LD(50) values of 11.41 and 20.94 microg/adult, respectively. PMID- 20736911 TI - Evaluation of the spatial distribution of gammaH2AX following ionizing radiation. AB - An early molecular response to DNA double-strand breaks (DSBs) is phosphorylation of the Ser-139 residue within the terminal SQEY motif of the histone H2AX. This phosphorylation of H2AX is mediated by the phosphatidyl-inosito 3-kinase (PI3K) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR). The phosphorylated form of H2AX, referred to as gammaH2AX, spreads to adjacent regions of chromatin from the site of the DSB, forming discrete foci, which are easily visualized by immunofluorescence microscopy. Analysis and quantitation of gammaH2AX foci has been widely used to evaluate DSB formation and repair, particularly in response to ionizing radiation and for evaluating the efficacy of various radiation modifying compounds and cytotoxic compounds. Given the exquisite specificity and sensitivity of this de novo marker of DSBs, it has provided new insights into the processes of DNA damage and repair in the context of chromatin. For example, in radiation biology the central paradigm is that the nuclear DNA is the critical target with respect to radiation sensitivity. Indeed, the general consensus in the field has largely been to view chromatin as a homogeneous template for DNA damage and repair. However, with the use of gammaH2AX as molecular marker of DSBs, a disparity in gamma-irradiation-induced gammaH2AX foci formation in euchromatin and heterochromatin has been observed. Recently, we used a panel of antibodies to either mono-, di- or tri- methylated histone H3 at lysine 9 (H3K9me1, H3K9me2, H3K9me3) which are epigenetic imprints of constitutive heterochromatin and transcriptional silencing and lysine 4 (H3K4me1, H3K4me2, H3K4me3), which are tightly correlated actively transcribing euchromatic regions, to investigate the spatial distribution of gammaH2AX following ionizing radiation. In accordance with the prevailing ideas regarding chromatin biology, our findings indicated a close correlation between gammaH2AX formation and active transcription. Here we demonstrate our immunofluorescence method for detection and quantitation of gammaH2AX foci in non-adherent cells, with a particular focus on co-localization with other epigenetic markers, image analysis and 3D-modeling. PMID- 20736912 TI - Murine echocardiography and ultrasound imaging. AB - Rodent models of cardiac pathophysiology represent a valuable research tool to investigate mechanism of disease as well as test new therapeutics. Echocardiography provides a powerful, non-invasive tool to serially assess cardiac morphometry and function in a living animal. However, using this technique on mice poses unique challenges owing to the small size and rapid heart rate of these animals. Until recently, few ultrasound systems were capable of performing quality echocardiography on mice, and those generally lacked the image resolution and frame rate necessary to obtain truly quantitative measurements. Newly released systems such as the VisualSonics Vevo2100 provide new tools for researchers to carefully and non-invasively investigate cardiac function in mice. This system generates high resolution images and provides analysis capabilities similar to those used with human patients. Although color Doppler has been available for over 30 years in humans, this valuable technology has only recently been possible in rodent ultrasound. Color Doppler has broad applications for echocardiography, including the ability to quickly assess flow directionality in vessels and through valves, and to rapidly identify valve regurgitation. Strain analysis is a critical advance that is utilized to quantitatively measure regional myocardial function. This technique has the potential to detect changes in pathology, or resolution of pathology, earlier than conventional techniques. Coupled with the addition of three-dimensional image reconstruction, volumetric assessment of whole-organs is possible, including visualization and assessment of cardiac and vascular structures. Murine-compatible contrast imaging can also allow for volumetric measurements and tissue perfusion assessment. PMID- 20736913 TI - Human fear conditioning conducted in full immersion 3-dimensional virtual reality. AB - Fear conditioning is a widely used paradigm in non-human animal research to investigate the neural mechanisms underlying fear and anxiety. A major challenge in conducting conditioning studies in humans is the ability to strongly manipulate or simulate the environmental contexts that are associated with conditioned emotional behaviors. In this regard, virtual reality (VR) technology is a promising tool. Yet, adapting this technology to meet experimental constraints requires special accommodations. Here we address the methodological issues involved when conducting fear conditioning in a fully immersive 6-sided VR environment and present fear conditioning data. In the real world, traumatic events occur in complex environments that are made up of many cues, engaging all of our sensory modalities. For example, cues that form the environmental configuration include not only visual elements, but aural, olfactory, and even tactile. In rodent studies of fear conditioning animals are fully immersed in a context that is rich with novel visual, tactile and olfactory cues. However, standard laboratory tests of fear conditioning in humans are typically conducted in a nondescript room in front of a flat or 2D computer screen and do not replicate the complexity of real world experiences. On the other hand, a major limitation of clinical studies aimed at reducing (extinguishing) fear and preventing relapse in anxiety disorders is that treatment occurs after participants have acquired a fear in an uncontrolled and largely unknown context. Thus the experimenters are left without information about the duration of exposure, the true nature of the stimulus, and associated background cues in the environment. In the absence of this information it can be difficult to truly extinguish a fear that is both cue and context-dependent. Virtual reality environments address these issues by providing the complexity of the real world, and at the same time allowing experimenters to constrain fear conditioning and extinction parameters to yield empirical data that can suggest better treatment options and/or analyze mechanistic hypotheses. In order to test the hypothesis that fear conditioning may be richly encoded and context specific when conducted in a fully immersive environment, we developed distinct virtual reality 3-D contexts in which participants experienced fear conditioning to virtual snakes or spiders. Auditory cues co-occurred with the CS in order to further evoke orienting responses and a feeling of "presence" in subjects. Skin conductance response served as the dependent measure of fear acquisition, memory retention and extinction. PMID- 20736914 TI - Studying the effects of matrix stiffness on cellular function using acrylamide based hydrogels. AB - Tissue stiffness is an important determinant of cellular function, and changes in tissue stiffness are commonly associated with fibrosis, cancer and cardiovascular disease. Traditional cell biological approaches to studying cellular function involve culturing cells on a rigid substratum (plastic dishes or glass coverslips) which cannot account for the effect of an elastic ECM or the variations in ECM stiffness between tissues. To model in vivo tissue compliance conditions in vitro, we and others use ECM-coated hydrogels. In our laboratory, the hydrogels are based on polyacrylamide which can mimic the range of tissue compliances seen biologically. "Reactive" cover slips are generated by incubation with NaOH followed by addition of 3-APTMS. Glutaraldehyde is used to cross-link the 3-APTMS and the polyacrylamide gel. A solution of acrylamide (AC), bis acrylamide (Bis-AC) and ammonium persulfate is used for the polymerization of the hydrogel. N-hydroxysuccinimide (NHS) is incorporated into the AC solution to crosslink ECM protein to the hydrogel. Following polymerization of the hydrogel, the gel surface is coated with an ECM protein of choice such as fibronectin, vitronectin, collagen, etc. The stiffness of a hydrogel can be determined by rheology or atomic force microscopy (AFM) and adjusted by varying the percentage of AC and/or bis-AC in the solution. In this manner, substratum stiffness can be matched to the stiffness of biological tissues which can also be quantified using rheology or AFM. Cells can then be seeded on these hydrogels and cultured based upon the experimental conditions required. Imaging of the cells and their recovery for molecular analysis is straightforward. For this article, we define soft substrata as those having elastic moduli (E) < 3000 Pascal and stiff substrata/tissues as those with E > 20,000 Pascal. PMID- 20736915 TI - A reverse genetic approach to test functional redundancy during embryogenesis. AB - Gene function during embryogenesis is typically defined by loss-of-function experiments, for example by targeted mutagenesis (knockout) in the mouse. In the zebrafish model, effective reverse genetic techniques have been developed using microinjection of gene-specific antisense morpholinos. Morpholinos target an mRNA through specific base-pairing and block gene function transiently by inhibiting translation or splicing for several days during embryogenesis (knockdown). However, in vertebrates such as mouse or zebrafish, some gene functions can be obscured by these approaches due to the presence of another gene that compensates for the loss. This is especially true for gene families containing sister genes that are co-expressed in the same developing tissues. In zebrafish, functional compensation can be tested in a relatively high-throughput manner, by co injection of morpholinos that target knockdown of both genes simultaneously. Likewise, using morpholinos, a genetic interaction between any two genes can be demonstrated by knockdown of both genes together at sub-threshold levels. For example, morpholinos can be titrated such that neither individual knockdown generates a phenotype. If, under these conditions, co-injection of both morpholinos causes a phenotype, a genetic interaction is shown. Here we demonstrate how to show functional redundancy in the context of two related GATA transcription factors. GATA factors are essential for specification of cardiac progenitors, but this is revealed only by the loss of both Gata5 and Gata6. We show how to carry out microinjection experiments, validate the morpholinos, and evaluate the compensated phenotype for cardiogenesis. PMID- 20736916 TI - Toxoplasma gondii cyst wall formation in activated bone marrow-derived macrophages and bradyzoite conditions. AB - Toxoplasma gondii is an obligate intracellular parasite that can invade any nucleated cell of warm-blooded animals. During infection, T. gondii disseminates as a fast replicating form called the tachyzoite. Tachyzoites convert into a slow growing encysted form called the bradyzoite by a signaling process that is not well characterized. Within animals, bradyzoite cysts are found in the central nervous system and muscle tissue and represent the chronic stage of infection. Conversion to bradyzoites can be simulated in tissue culture by CO2 starvation, using medium with high a pH, or the addition of interferon gamma (IFNgamma). Bradyzoites are characterized by the presence of a cyst wall, to which the lectin Dolichos biflorus agglutinin (DBA) binds. Fluorescently labeled DBA is used to visualize the cyst wall in parasites grown in human foreskin fibroblasts (HFFs) that have been exposed to low CO2 and high pH medium. Similarly, parasites residing in murine bone marrow-derived macrophages (BMMs) display a cyst wall detectable by DBA after the BMMs are activated with IFNgamma and lipopolysaccharide (LPS). This protocol will demonstrate how to induce conversion of T. gondii to bradyzoites using a high pH growth medium with low CO2 and activation of BMMs. Host cells will be cultured on coverslips, infected with tachyzoites and either activated with addition of IFNgamma and LPS (BMMs) or exposed to a high pH growth medium (HFFs) for three days. Upon completion of infections, host cells will be fixed, permeabilized, and blocked. Cyst walls will be visualized using rhodamine DBA with fluorescence microscopy. PMID- 20736917 TI - Induction and assessment of class switch recombination in purified murine B cells. AB - Humoral immunity is the branch of the immune system maintained by B cells and mediated through the secretion of antibodies. Upon B cell activation, the immunoglobulin locus undergoes a series of genetic modifications to alter the binding capacity and effector function of secreted antibodies. This process is highlighted by a genomic recombination event known as class switch recombination (CSR) in which the default IgM antibody isotype is substituted for one of IgG, IgA, or IgE. Each isotype possesses distinct effector functions thereby making CSR crucial to the maintenance of immunity. Diversification of the immunoglobulin locus is mediated by the enzyme activation-induced cytidine deaminase (AID). A schematic video describing this process in detail is available online (http://video.med.utoronto.ca/videoprojects/immunology/aam.html). AID's activity and the CSR pathway are commonly studied in the assessment of B cell function and humoral immunity in mice. The protocol outlined in this report presents a method of B cell isolation from murine spleens and subsequent stimulation with bacterial lipopolysaccharide (LPS) to induce class switching to IgG3 (for other antibody isotypes see Table 1). In addition, the fluorescent cell staining dye Carboxyfluorescein succinimidyl ester (CFSE) is used to monitor cell division of stimulated cells, a process crucial to isotype switching. The regulation of AID and the mechanism by which CSR occurs are still unclear and thus in vitro class switch assays provide a reliable method for testing these processes in various mouse models. These assays have been previously used in the context of gene deficiency using knockout mice. Furthermore, in vitro switching of B cells can be preceded by viral transduction to modulate gene expression by RNA knockdown or transgene expression. The data from these types of experiments have impacted our understanding of AID activity, resolution of the CSR reaction, and antibody mediated immunity in the mouse. PMID- 20736918 TI - Double fluorescence in situ hybridization in fresh brain sections. AB - Here we describe a modified version of a double fluorescence in situ hybridization (dFISH) method optimized for detecting two mRNAs of interest in fresh frozen brain sections. Our group has successfully used this approach to study gene co-regulation. More specifically, we have used this dFISH method to explore the anatomical organization, neurochemical properties, and the impact of sensory experience in central sensory circuits, at single cell resolution. This protocol has been validated in brain tissue from mice, rats and songbirds but is expected to be easily adaptable to other vertebrate species, as well as to an array of non-neural tissues. In this film we provide a detailed demonstration of the main steps of this procedure. PMID- 20736919 TI - Eye movement monitoring of memory. AB - Explicit (often verbal) reports are typically used to investigate memory (e.g. "Tell me what you remember about the person you saw at the bank yesterday."), however such reports can often be unreliable or sensitive to response bias, and may be unobtainable in some participant populations. Furthermore, explicit reports only reveal when information has reached consciousness and cannot comment on when memories were accessed during processing, regardless of whether the information is subsequently accessed in a conscious manner. Eye movement monitoring (eye tracking) provides a tool by which memory can be probed without asking participants to comment on the contents of their memories, and access of such memories can be revealed on-line. Video-based eye trackers (either head mounted or remote) use a system of cameras and infrared markers to examine the pupil and corneal reflection in each eye as the participant views a display monitor. For head-mounted eye trackers, infrared markers are also used to determine head position to allow for head movement and more precise localization of eye position. Here, we demonstrate the use of a head-mounted eye tracking system to investigate memory performance in neurologically-intact and neurologically-impaired adults. Eye movement monitoring procedures begin with the placement of the eye tracker on the participant, and setup of the head and eye cameras. Calibration and validation procedures are conducted to ensure accuracy of eye position recording. Real-time recordings of X,Y-coordinate positions on the display monitor are then converted and used to describe periods of time in which the eye is static (i.e. fixations) versus in motion (i.e., saccades). Fixations and saccades are time-locked with respect to the onset/offset of a visual display or another external event (e.g. button press). Experimental manipulations are constructed to examine how and when patterns of fixations and saccades are altered through different types of prior experience. The influence of memory is revealed in the extent to which scanning patterns to new images differ from scanning patterns to images that have been previously studied. Memory can also be interrogated for its specificity; for instance, eye movement patterns that differ between an identical and an altered version of a previously studied image reveal the storage of the altered detail in memory. These indices of memory can be compared across participant populations, thereby providing a powerful tool by which to examine the organization of memory in healthy individuals, and the specific changes that occur to memory with neurological insult or decline. PMID- 20736920 TI - Systemic and local drug delivery for treating diseases of the central nervous system in rodent models. AB - Thorough preclinical testing of central nervous system (CNS) therapeutics includes a consideration of routes of administration and agent biodistribution in assessing therapeutic efficacy. Between the two major classifications of administration, local vs. systemic, systemic delivery approaches are often preferred due to ease of administration. However, systemic delivery may result in suboptimal drug concentration being achieved in the CNS, and lead to erroneous conclusions regarding agent efficacy. Local drug delivery methods are more invasive, but may be necessary to achieve therapeutic CNS drug levels. Here, we demonstrate proper technique for three routes of systemic drug delivery: intravenous injection, intraperitoneal injection, and oral gavage. In addition, we show a method for local delivery to the brain: convection-enhanced delivery (CED). The use of fluorescently-labeled compounds is included for in vivo imaging and verification of proper drug administration. The methods are presented using murine models, but can easily be adapted for use in rats. PMID- 20736921 TI - The safety of osmotically acting cathartics in colonic cleansing. AB - Efficient cleansing of the colon before a colonoscopy or a radiological examination is essential. The osmotically acting cathartics (those given the Anatomical Therapeutic Chemical code A06AD) currently used for this purpose comprise products based on three main substances: sodium phosphate, combinations of polyethylene glycol and electrolyte lavage solutions (PEG-ELS), and magnesium citrate. All these preparations give adequate cleansing results and have similar profiles in terms of the frequency and type of mild to moderate adverse effects. However, serious adverse events, such as severe hyperphosphatemia and irreversible kidney damage owing to acute phosphate nephropathy, have been reported after use of sodium-phosphate-based products. The aim of this Review is to provide an update on the potential safety issues related to the use of osmotically acting cathartics, especially disturbances of renal function and water and electrolyte balance. The available evidence indicates that PEG-ELS based products are the safest option. Magnesium-citrate-based, hypertonic products should be administered with caution to elderly individuals and patients who are prone to develop disturbances in water and electrolyte balance. Sodium phosphate-based products can occasionally cause irreversible kidney damage and should not be routinely used in bowel-cleansing procedures. PMID- 20736922 TI - Addressing childhood obesity through increased physical activity. AB - Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today's young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive 'shame and blame' mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter) lives than their parents. PMID- 20736923 TI - Molecular diagnostics in transplantation. AB - The past few decades are characterized by an explosive evolution of genetics and molecular cell biology. Advances in chemistry and engineering have enabled increased data throughput, permitting the study of complete sets of molecules with increasing speed and accuracy using techniques such as genomics, transcriptomics, proteomics, and metabolomics. Prediction of long-term outcomes in transplantation is hampered by the absence of sufficiently robust biomarkers and a lack of adequate insight into the mechanisms of acute and chronic alloimmune injury and the adaptive mechanisms of immunological quiescence that may support transplantation tolerance. Here, we discuss some of the great opportunities that molecular diagnostic tools have to offer both basic scientists and translational researchers for bench-to-bedside clinical application in transplantation medicine, with special focus on genomics and genome-wide association studies, epigenetics (DNA methylation and histone modifications), gene expression studies and transcriptomics (including microRNA and small interfering RNA studies), proteomics and peptidomics, antibodyomics, metabolomics, chemical genomics and functional imaging with nanoparticles. We address the challenges and opportunities associated with the newer high throughput sequencing technologies, especially in the field of bioinformatics and biostatistics, and demonstrate the importance of integrative approaches. Although this Review focuses on transplantation research and clinical transplantation, the concepts addressed are valid for all translational research. PMID- 20736924 TI - B cells and transplantation tolerance. AB - Transplantation tolerance is a state of immune unresponsiveness (or benign responsiveness) to the presence of specific, nonself antigens in the absence of chronic immunosuppressive therapy. Renal transplant tolerance remains a desired yet generally unattained goal that would enable transplantation to be performed without the risk of graft rejection or the need for broadly immunosuppressive drugs, which can have toxic effects. Studies published in the past few years have provided evidence that B cells have an important role in both graft rejection and transplantation tolerance. Indeed, antibody-dependent and antibody-independent functions of B cells account for both tolerogenic and rejection-promoting immune responses in transplant recipients. This Review comprises a discussion of the mechanisms involved in the induction of B-cell tolerance and a survey of current and emerging therapies that target the effects of B cells in transplant recipients. PMID- 20736925 TI - SLE and pregnancy: the potential role for regulatory T cells. AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that disproportionally affects women, especially in their reproductive years. SLE is associated with considerable pregnancy-related morbidity--including fetal loss, preterm birth, fetal growth restriction and pre-eclampsia. CD4+CD25+ regulatory T (T(REG)) cells have a potent immunosuppressive function and contribute to immunological self-tolerance. These cells might be essential for successful placental development by ensuring fetal tolerance. The numbers of T(REG) cells are augmented during normal pregnancy and, conversely, diminished numbers are associated with pregnancy loss and pre-eclampsia. Several studies have shown that patients with SLE have decreased numbers of T(REG) cells that might be functionally defective. This defective T(REG) cell functioning could predispose women with SLE to pregnancy complications. This article provides an overview of current knowledge of the role and function of T(REG) cells in SLE and pregnancy and how these cells might contribute to improving pregnancy-related outcomes in patients with SLE in the future. PMID- 20736926 TI - A changing perspective: improving access to fertility preservation. AB - Approximately 120,000 young women are diagnosed with cancer every year in the USA. Many will have treatment that can reduce their fertility, although few will learn this fact before their treatment commences. This presents a tremendous quality of life issue post-treatment, as evidenced in this Perspectives by a personal account from a 23-year-old woman diagnosed with breast cancer. Clinicians must increase awareness about patients' desires for motherhood and awareness about their individual reproductive potential. We demonstrate novel evidence about the wide variability in ovarian reserve in women of similar age, using assessment by antral follicle count. We show how a unified approach between oncology and fertility teams can help patients better understand their risk of treatment-related infertility, as well as how to take effective measures to mitigate it. Finally, we present options for fertility preservation, based on the time point at which consultation occurs. PMID- 20736927 TI - Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/beta-catenin signalling. AB - Although the transcriptional regulatory events triggered by Oct-3/4 are well documented, understanding the proteomic networks that mediate the diverse functions of this POU domain homeobox protein remains a major challenge. Here, we present genetic and biochemical studies that suggest an unexpected novel strategy for Oct-3/4-dependent regulation of embryogenesis and cell lineage determination. Our data suggest that Oct-3/4 specifically interacts with nuclear beta-catenin and facilitates its proteasomal degradation, resulting in the maintenance of an undifferentiated, early embryonic phenotype both in Xenopus embryos and embryonic stem (ES) cells. Our data also show that Oct-3/4-mediated control of beta-catenin stability has an important function in regulating ES cell motility. Down regulation of Oct-3/4 increases beta-catenin protein levels, enhancing Wnt signalling and initiating invasive cellular activity characteristic of epithelial mesenchymal transition. Our data suggest a novel mode of regulation by which a delicate balance between beta-catenin, Tcf3 and Oct-3/4 regulates maintenance of stem cell identity. Altering the balance between these proteins can direct cell fate decisions and differentiation. PMID- 20736928 TI - Gene delivery of a mutant TGFbeta3 reduces markers of scar tissue formation after cutaneous wounding. AB - The transforming growth factor-beta (TGFbeta) family plays a critical regulatory role in repair and coordination of remodeling after cutaneous wounding. TGFbeta1 mediated chemotaxis promotes the recruitment of fibroblasts to the wound site and their resultant myofibroblastic transdifferentiation that is responsible for elastic fiber deposition and wound closure. TGFbeta3 has been implicated in an antagonistic role regulating overt wound closure and promoting ordered dermal remodeling. We generated a mutant form of TGFbeta3 (mutTGFbeta3) by ablating its binding site for the latency-associated TGFbeta binding protein (LTBP-1) in order to improve bioavailability and activity. The mutated cytokine is secreted as the stable latency-associated peptide (LAP)-associated form and is activated by normal intracellular and extracellular mechanisms including integrin-mediated activation but is not sequestered. We show localized intradermal transduction using a lentiviral vector expressing the mutTGFbeta3 in a mouse skin wounding model reduced re-epithelialization density and fibroblast/myofibroblast transdifferentiation within the wound area, both indicative of reduced scar tissue formation. PMID- 20736929 TI - High-efficiency transduction and correction of murine hemophilia B using AAV2 vectors devoid of multiple surface-exposed tyrosines. AB - Elimination of specific surface-exposed single tyrosine (Y) residues substantially improves hepatic gene transfer with adeno-associated virus type 2 (AAV2) vectors. Here, combinations of mutations in the seven potentially relevant Y residues were evaluated for further augmentation of transduction efficiency. These mutant capsids packaged viral genomes to similar titers and retained infectivity. A triple-mutant (Y444+500+730F) vector consistently had the highest level of in vivo gene transfer to murine hepatocytes, approximately threefold more efficient than the best single-mutants, and ~30-80-fold higher compared with the wild-type (WT) AAV2 capsids. Improvement of gene transfer was similar for both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors, indicating that these effects are independent of viral second-strand DNA synthesis. Furthermore, Y730F and triple-mutant vectors provided a long-term therapeutic and tolerogenic expression of human factor IX (hF.IX) in hemophilia B (HB) mice after administration of a vector dose that only results in subtherapeutic and transient expression with WT AAV2 encapsidated vectors. In summary, introduction of multiple tyrosine-mutations into the AAV2 capsid results in vectors that yield at least 30-fold improvement of transgene expression, thereby lowering the required therapeutic dose and potentially vector-related immunogenicity. Such vectors should be attractive for treatment of hemophilia and other genetic diseases. PMID- 20736931 TI - Nodal/Activin signaling predicts human pluripotent stem cell lines prone to differentiate toward the hematopoietic lineage. AB - Lineage-specific differentiation potential varies among different human pluripotent stem cell (hPSC) lines, becoming therefore highly desirable to prospectively know which hPSC lines exhibit the highest differentiation potential for a certain lineage. We have compared the hematopoietic potential of 14 human embryonic stem cell (hESC)/induced pluripotent stem cell (iPSC) lines. The emergence of hemogenic progenitors, primitive and mature blood cells, and colony forming unit (CFU) potential was analyzed at different time points. Significant differences in the propensity to differentiate toward blood were observed among hPSCs: some hPSCs exhibited good blood differentiation potential, whereas others barely displayed blood-differentiation capacity. Correlation studies revealed that the CFU potential robustly correlates with hemogenic progenitors and primitive but not mature blood cells. Developmental progression of mesoendodermal and hematopoietic transcription factors expression revealed no correlation with either hematopoietic initiation or maturation efficiency. Microarray studies showed distinct gene expression profile between hPSCs with good versus poor hematopoietic potential. Although neuroectoderm-associated genes were downregulated in hPSCs prone to hematopoietic differentiation many members of the Nodal/Activin signaling were upregulated, suggesting that this signaling predicts those hPSC lines with good blood-differentiation potential. The association between Nodal/Activin signaling and the hematopoietic differentiation potential was confirmed using loss- and gain-of-function functional assays. Our data reinforce the value of prospective comparative studies aimed at determining the lineage-specific differentiation potential among different hPSCs and indicate that Nodal/Activin signaling seems to predict those hPSC lines prone to hematopoietic specification. PMID- 20736930 TI - Advances in the field of lentivector-based transduction of T and B lymphocytes for gene therapy. AB - Efficient gene transfer into quiescent T and B lymphocytes for gene therapy or immunotherapy purposes may allow the treatment of several genetic dysfunctions of the hematopoietic system, such as immunodeficiencies, and the development of novel therapeutic strategies for cancers and acquired diseases. Lentiviral vectors (LVs) can transduce many types of nonproliferating cells, with the exception of some particular quiescent cell types such as resting T and B cells. In T cells, completion of reverse transcription (RT), nuclear import, and subsequent integration of the vesicular stomatitis virus G protein pseudotyped LV (VSVG-LV) genome does not occur efficiently unless they are activated via the T cell receptor (TCR) or by survival-cytokines inducing them to enter into the G(1b) phase of the cell cycle. Lentiviral transduction of B cells is another matter because even B-cell receptor-stimulation inducing proliferation is not sufficient to allow efficient VSVG-LV transduction. Recently, a new LV carrying the glycoproteins of measles virus (MV) at its surface was able to overcome vector restrictions in both quiescent T and B cells. Importantly, naive as well as memory T and B cells were efficiently transduced while no apparent activation, cell-cycle entry, or phenotypic switch were detected, which opens the door to a multitude of gene therapy and immunotherapy applications as reported here. PMID- 20736932 TI - Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy. AB - Liver-directed gene therapy with adeno-associated virus (AAV) vectors effectively treats mouse models of lysosomal storage diseases (LSDs). We asked whether these results were likely to translate to patients. To understand to what extent preexisting anti-AAV8 antibodies could impede AAV8-mediated liver transduction in primates, commonly preexposed to AAV, we quantified the effects of preexisting antibodies on liver transduction and subsequent transgene expression in mouse and nonhuman primate (NHP) models. Using the highest viral dose previously reported in a clinical trial, passive transfer of NHP sera containing relatively low anti AAV8 titers into mice blocked liver transduction, which could be partially overcome by increasing vector dose tenfold. Based on this and a survey of anti AAV8 titers in 112 humans, we predict that high-dose systemic gene therapy would successfully transduce liver in >50% of human patients. However, although high dose AAV8 administration to mice and monkeys with equivalent anti-AAV8 titers led to comparable liver vector copy numbers, the resulting transgene expression in primates was ~1.5-logs lower than mice. This suggests vector fate differs in these species and that strategies focused solely on overcoming preexisting vector specific antibodies may be insufficient to achieve clinically meaningful expression levels of LSD genes using a liver-directed gene therapy approach in patients. PMID- 20736933 TI - Utilization and predictors of early repeat colonoscopy in Medicare beneficiaries. AB - OBJECTIVES: Early repeat colonoscopy after an index examination may be justifiable, but may also reflect quality issues during the first examination. The aims of this study were to examine the use of second colonoscopy within 1 year of an index colonoscopy, and to examine patient and provider factors associated with use of early repeat colonoscopy. METHODS: We performed a retrospective cohort study using a 20% nationally representative sample of 2003 Medicare claims. Patients aged >= 66 years undergoing colonoscopy were included in this study. We identified the use of second colonoscopy and barium enema within 1 year of the index procedure. We used logistic regression analyses to examine the independent predictors of these procedures. RESULTS: We included 328,167 outpatient colonoscopies. In all, 5% had second colonoscopy and 2.2% had barium enema within 1 year of the index examination. Early repeat colonoscopy was more common if the index examination was performed by a family physician (odds ratio 1.39, 95% confidence interval 1.23-1.56), general surgeon (odds ratio 1.18, 95% confidence interval 1.10-1.27) or internist (odds ratio 1.12, 95% confidence interval 1.02-1.23) compared with a gastroenterologist, or after colonoscopies by an endoscopist in the lower quartiles of colonoscopy volume compared with endoscopists in the highest quartile. Increasing patient age and comorbidity, polyp detection, biopsy, polyp removal, incomplete index examination, and site of service were also significantly associated with early repeat colonoscopy. CONCLUSIONS: Early repeat colonoscopy is not unusual. The association of specialty and colonoscopy volume with early repeat colonoscopy suggests that there are modifiable processes of care or training that may prevent some of these repeat procedures. PMID- 20736934 TI - Outcome of patients with type 1 or 2 autoimmune pancreatitis. AB - OBJECTIVES: Autoimmune pancreatitis (AIP) is better described than before, but there is still no international consensus for definition, diagnosis, and treatment. Our aims were to analyze the short- and long-term outcome of patients with focus on pancreatic endocrine and exocrine functions, to search for predictive factors of relapse and pancreatic insufficiency, and to compare patients with type 1 and type 2 AIP. METHODS: All consecutive patients followed up for AIP in our center between 1999 and 2008 were included. Two groups were defined: (a) patients with type 1 AIP meeting HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to steroids) criteria; (b) patients with definitive/probable type 2 AIP including those with histologically confirmed idiopathic duct-centric pancreatitis ("definitive") or suggestive imaging, normal serum IgG4, and response to steroids ("probable"). AIP-related events and pancreatic exocrine/endocrine insufficiency were looked for during follow-up. Predictive factors of relapse and pancreatic insufficiency were analyzed. RESULTS: A total of 44 patients (22 males), median age 37.5 (19-73) years, were included: 28 patients (64%) with type 1 AIP and 16 patients (36%) with type 2 AIP. First-line treatment consisted of steroids or pancreatic resection in 59 and 27% of the patients, respectively. Median follow-up was 41 (5 130) months. Steroids were effective in all treated patients. Relapse was observed in 12 patients (27%), after a median delay of 6 months (1-70). Four patients received azathioprine because of steroid resistance/dependence. High serum IgG4 level, pain at time of diagnosis, and other organ involvement were associated with relapse (P<0.05). At the end point, pancreatic atrophy was observed in 35% of patients. Exocrine and endocrine insufficiencies were present in 34 and 39% of the patients, respectively. At univariate analysis, no factor was associated with exocrine insufficiency, although female gender (P=0.04), increasing age (P=0.006), and type 1 AIP (P=0.001) were associated with the occurrence of diabetes. Steroid/azathioprine treatment did not prevent pancreatic insufficiency. Type 2 AIP was more frequently associated with inflammatory bowel disease than type 1 AIP (31 and 3%, respectively), but relapse rates were similar in both groups. CONCLUSIONS: Relapse occurs in 27% of AIP patients and is more frequent in patients with high serum IgG4 levels at the time of diagnosis. Pancreatic atrophy and functional insufficiency occur in more than one-third of the patients within 3 years of diagnosis. The outcome of patients with type 2 AIP, a condition often associated with inflammatory bowel disease, is not different from that of patients with type 1 AIP, except for diabetes. PMID- 20736935 TI - Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. AB - OBJECTIVES: Recent studies have raised concerns on the clinical effectiveness of clopidogrel when taken in combination with proton pump inhibitors (PPIs), demonstrating an increase in the occurrence of cardiovascular events. In this study, the association between the co-administration of a PPI and clopidogrel and the occurrence of cardiovascular and gastrointestinal (GI) events in a large cohort in the Netherlands was investigated. METHODS: A retrospective study was conducted using data from 4 million individuals. New clopidogrel users were identified between January 2006 and December 2007 and followed over time. The Kaplan-Meier method and Cox proportional hazard regression [corrected]analysis were used to calculate the risk of cardiovascular and GI outcomes in clopidogrel patients with or without PPI use. RESULTS: A total of 18,139 new clopidogrel users were identified; 5,734 subjects (32%) used PPIs concurrently. Patients on PPIs were significantly older, used more co-medications and suffered from more comorbidities. Use of clopidogrel and PPIs was associated with an increased risk of myocardial infarction (hazard ratio (HR) 1.93, 95% confidence interval (CI) 1.40-2.65), unstable angina pectoris (HR 1.79, 95% CI 1.60-2.03), and the composite endpoint (HR 1.75, 95% CI 1.58-1.94) compared with clopidogrel users without PPIs. PPI users also had an increased risk of GI events compared with non PPI users (HR 4.76, 95% CI 1.18-19.17). CONCLUSIONS: New clopidogrel users on PPIs are at an increased risk of cardiovascular and GI complications compared with those who are not using a PPI. The inferior cardiovascular profile of clopidogrel users on PPIs and the occurrence of channeling bias may be important factors underlying this observation. PMID- 20736936 TI - A multicenter experience with infliximab for ulcerative colitis: outcomes and predictors of response, optimization, colectomy, and hospitalization. AB - OBJECTIVES: The objective of this study was to evaluate short- and long-term outcomes of infliximab in ulcerative colitis (UC), including infliximab optimization, colectomy, and hospitalization. METHODS: This was a retrospective multicenter study. All adult patients who received at least one infliximab infusion for UC were included. Cumulative probabilities of event-free survival were estimated by the Kaplan-Meier method. Independent predictors were identified using binary logistic regression or Cox proportional-hazards regression, and results were expressed as odds ratios or hazard ratios (HRs), respectively. RESULTS: Between January 2000 and August 2009, 191 UC patients received infliximab therapy. Median follow-up per patient was 18 months (interquartile range=25-75th, 8-32 months). Primary non-response was noted in 42 patients (22.0%). "Hemoglobin at infliximab initiation <= 9.4 g/dl" (odds ratio=4.35; 95% confidence interval (CI)=1.81-10.42) was a positive predictor of non-response to infliximab. Infliximab optimization was required in 36 (45.0%) of 80 patients on scheduled infliximab therapy. The only predictor of infliximab optimization was "infliximab indication for acute severe colitis" (HR=2.75; 95% CI=1.23-6.12). Thirty-six patients (18.8%) underwent colectomy. Predictors of colectomy were: "no clinical response after infliximab induction" (HR=7.06; 95% CI=3.36-14.83), "C-reactive protein at infliximab initiation > 10 mg/l" (HR=5.11; 95% CI=1.77 14.76), "infliximab indication for acute severe colitis" (HR=3.40; 95% CI=1.48 7.81), and "previous treatment with cyclosporine" (HR=2.53; 95% CI=1.22-5.28). Sixty-nine patients (36.1%) were hospitalized at least one time and UC-related hospitalizations rate was 29 per 100 patient-years (95% CI=24-35 per 100 patient years). Predictors of first hospitalization were: "no clinical response after infliximab induction" (HR=3.87; 95% CI=2.29-6.53), "infliximab indication for acute severe colitis" (HR=3.13, 95% CI=1.65-5.94), "disease duration at infliximab initiation <=50 months" (HR=2.14, 95% CI=1.25-3.66), "hemoglobin at infliximab initiation <=11.8 g/dl" (HR=1.77; 95% CI=1.03-3.04), and "previous treatment with methotrexate" (HR=0.30; 95% CI=0.09-0.97). CONCLUSIONS: Primary non-response to infliximab was noted in one fifth of patients and increased by seven and four the risks of colectomy and hospitalization, respectively. Infliximab optimization, colectomy, and hospitalization were required in half, one fifth, and one third of patients, respectively. Infliximab indication for acute severe colitis increased by three the risks of infliximab optimization, colectomy, and UC-related hospitalization. PMID- 20736937 TI - High prevalence of low-trauma fracture in chronic pancreatitis. AB - OBJECTIVES: Chronic pancreatitis (CP) is associated with risk factors that may negatively impact bone and mineral metabolism. The important clinical end point of osteoporosis is "low-trauma" fracture. The purpose of this study was to examine the prevalence of "low-trauma" fracture in patients with CP, compared with fracture rates in "high-risk" gastrointestinal (GI) illnesses, for which metabolic bone disease screening guidelines are in place. METHODS: This is a retrospective cohort database study examining patients with CP and "high-risk" GI illnesses seen at a single tertiary care center. Time points ranged between 31 July 1998 and 31 July 2008. The main outcome measure was "low-trauma" fracture prevalence using specific International Classification of Diseases, Ninth Revision, Clinical Modification fracture codes. RESULTS: A total of 3,192 CP patients and 1,461,207 non-CP patients were included in the study. The fracture prevalence (patients with fracture per total patients) was as follows: controls, 1.1% (16,208/1,436,699); Crohn's disease, 3.0% (182/6057); CP, 4.8% (154/3192); cirrhosis, 4.8% (805/16,658); celiac disease, 5.0% (74/1480); and postgastrectomy, 5.4% (17/313). Prevalence for each group was statistically greater than controls (P<0.001). CP fracture prevalence was greater than controls (P<0.001) and Crohn's disease (P<0.001), and comparable with the remaining "high risk" GI illness groups (P>0.05). The odds of fracture (odds ratio (OR), 95% confidence interval (CI)) compared with controls, adjusted for age, gender, and race was: CP 2.4 (2.1, 2.9); Crohn's disease 1.7 (1.5, 2.0); gastrectomy 2.5 (1.5, 4.1); cirrhosis 2.6 (2.4, 2.7); and celiac disease 2.7 (2.1, 3.4). The odds of fracture for each disease group were statistically greater than controls (P<0.0001). CONCLUSIONS: The prevalence of low-trauma fracture in CP patients is comparable with or higher than that of "high-risk" GI illnesses, for which osteoporosis screening guidelines exist. PMID- 20736938 TI - Morphometric evaluation of duodenal biopsies in celiac disease. AB - OBJECTIVES: The Marsh classification is a semiquantitative method for the diagnosis and monitoring of changes in duodenal biopsies in celiac disease. We have explored the possibility that quantitative changes in villous area and crypt length (morphometry) may provide better information on changes in duodenal morphology, particularly after the introduction of a gluten-free diet. METHODS: We measured villous height, apical and basal villous widths, and crypt length in 57 adults with celiac disease and 83 control subjects. Villous area was calculated as a trapezoid approximation. Serial changes in villous area and crypt length were determined at regular intervals for up to 4 years after the introduction of a gluten-free diet. Morphometric changes were also correlated with Marsh grade, self-reported adherence to a gluten-free diet, and changes in celiac serology. RESULTS: The gluten-free diet resulted in a progressive increase in villous area and a progressive decrease in crypt length. Morphometric improvement reached a plateau after 6-12 months with mean villous area attaining a value approximately half that of control subjects. Morphometric data were more sensitive than Marsh grade. Improvement in morphometric indices was significantly associated with the disappearance of anti-endomysial IgA antibody but not with dietary compliance. CONCLUSIONS: Morphometry is a sensitive way to document changes in duodenal biopsies in celiac disease. In adults treated with a gluten free diet, it is uncommon for villous area to return to values observed in control subjects, but morphometric improvement is associated with the disappearance of anti-endomysial IgA antibody. PMID- 20736939 TI - Outcome in cystic fibrosis liver disease. AB - OBJECTIVES: Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD. METHODS: This is a 7-year follow-up of 42 children with CFLD and their age- and sex-matched controls. Participants were reviewed clinically, biochemically, and radiologically at follow-up. RESULTS: Overall, 85% (72 of 84) of the original cohort were included, 36 CFLD participants and 36 CF controls. There was no significant difference in the number of deaths/transplants between groups (7 of 36 (19.4%) CFLD participants, 3 of 36 (8.3%) CF controls). There was a tendency for participants with CFLD to die younger than their respective CF controls. There was no difference in height, weight, body mass index, or pulmonary function between the groups. Nutritional parameters (sum skinfold thickness 31.6 vs. 42.3, P=0.03; mean upper arm fat area 15.08 vs. 10.59, P=0.001; Shwachman score 43.7 vs. 32.1, P=0.001) were worse among CFLD participants than among CF controls. Cystic fibrosis-related diabetes was more common in CFLD participants (11 of 27 (40.7%) vs. 5 of 33 (15.2%), P=0.02). Eight children (22.2%) with evidence of CFLD at baseline had no clinical evidence of liver disease as adults. CONCLUSIONS: Patients with CFLD have a more severe CF phenotype than do CF patients without liver disease. However, a subgroup of children with CFLD will not manifest clinically significant liver disease as adults. PMID- 20736940 TI - Epidemiology of peptic ulcer disease: endoscopic results of the systematic investigation of gastrointestinal disease in China. AB - OBJECTIVES: Complications of peptic ulcer disease (PUD) are common in China. Population-based estimates of the prevalence of PUD are needed to quantify and characterize the population at risk of these complications. METHODS: As part of a large epidemiological study, 3,600 randomly selected residents of Shanghai (aged 18-80 years) were asked to undergo endoscopy and to provide blood samples for Helicobacter pylori serology. All participants also completed a general information questionnaire and Chinese versions of the reflux disease questionnaire (RDQ) and Rome II questionnaire. Associations between PUD and other factors were analyzed using a multiple logistic regression model. RESULTS: In total, 3,153 individuals (87.6%) completed the survey. All underwent blood tests, and 1,030 patients (32.7%) agreed to undergo endoscopy. Results from 1,022 patients were suitable for analysis. In all, 176 participants (17.2%) had PUD (62 with gastric ulcer; 136 with duodenal ulcer). The prevalence of H. pylori infection was 73.3% in the total population and 92.6% among those with PUD. H. pylori infection was associated with the presence of PUD (odds ratio (OR), 6.77; 95% confidence interval (CI), 2.85-16.10). The majority (72.2%) of individuals with PUD had none of the upper gastrointestinal symptoms assessed by the RDQ. PUD was not significantly associated with symptom-defined gastroesophageal reflux disease (GERD) (OR, 0.80; 95% CI, 0.32-2.03), reflux esophagitis (OR, 1.46; 95% CI, 0.76-2.79) or dyspepsia (OR, 1.69; 95% CI, 0.94-3.04). CONCLUSIONS: The prevalence of endoscopically confirmed PUD in this Shanghai population (17.2%) is substantially higher than in Western populations (4.1%). The majority of individuals with PUD were asymptomatic. PMID- 20736941 TI - Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion. AB - OBJECTIVES: The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25-35% in the United States. Although a variety of pharmaceutical agents have been used to reduce the production of acid, alarming new evidence questions the long-term efficacy and safety of the agents. These issues coupled with the delayed onset of action and the return of symptoms in over 60% of the patients is less than satisfactory. The purpose of this study was to determine whether administration of a zinc salt could lead to a rapid and sustained increase in gastric pH in both animals and in humans and provide a new rapid acid suppression therapy. METHODS: Intracellular pH was measured with 2',7'-bis-(2-carboxyethyl)-5-and-6-carboxy-fluorescein in both human and rat gastric glands following an acid load+/-a secretagogue. In a separate series of studies, whole stomach acid secretion was monitored in rats. A final study used healthy human volunteers while monitoring with a gastric pH measurement received placebo, zinc salt, or a zinc salt and proton pump inhibitor (PPI). RESULTS: We demonstrate that exposure to ZnCl(2) immediately abolished secretagogue-induced acid secretion in isolated human and rat gastric glands, and in intact rat stomachs. Chronic low-dose zinc exposure effectively inhibited acid secretion in whole stomachs and isolated glands. In a randomized cross-over study in 12 volunteers, exposure to a single dose of ZnCl(2) raised intragastric pH for over 3 h, including a fast onset of effect. CONCLUSIONS: Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models. PMID- 20736942 TI - Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation. AB - BACKGROUND: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC). METHODS: We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC. RESULTS: Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (kappa value of 0.87). CONCLUSION: Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients. PMID- 20736943 TI - Nasal septum perforation: a side effect of bevacizumab chemotherapy in breast cancer patients. AB - BACKGROUND: Bevacizumab is an anti-vascular endothelial growth factor approved in association with paclitaxel or docetaxel as first line in patients (pts) with metastatic breast cancer. Rare cases of nasal septum perforations have been reported. We report our experience of nasal perforation in breast cancer pts receiving bevacizumab and chemotherapy either in the adjuvant or in the metastatic settings. METHODS: Between 1 January and 31 December 2009, 70 pts received bevacizumab together with chemotherapy. All the pts who had received bevacizumab were referred to the ENT specialist. Symptoms potentially related were looked for. Side effects were graded according to CTCAE. RESULTS: Five nasal septum perforations were diagnosed (5 out of 70; 7.14%). Bevacizumab dose was 15 mg kg(-1) 3 weekly. Three pts were metastatic. Bevacizumab was associated with docetaxel (100 mg m(-2) every 3 weeks) in two pts and with weekly paclitaxel in one. The last two pts received bevacizumab in combination with anthracyclin and then taxanes in the adjuvant setting. In these two cases, nasal septum perforation occurred at the time of docetaxel treatment. CONCLUSION: A high incidence of nasal septum perforation has been shown in pts with breast cancer receiving bevacizumab together with chemotherapy. Several mechanisms could be involved (mucositis, delayed tissue repair, antiangiogenic action of taxanes). PMID- 20736944 TI - Prolactin serum levels and breast cancer: relationships with risk factors and tumour characteristics among pre- and postmenopausal women in a population-based case-control study from Poland. AB - BACKGROUND: Previous prospective studies have found an association between prolactin (PRL) levels and increased risk of breast cancer. Using data from a population-based breast cancer case-control study conducted in two cities in Poland (2000-2003), we examined the association of PRL levels with breast cancer risk factors among controls and with tumour characteristics among the cases. METHODS: We analysed PRL serum levels among 773 controls without breast cancer matched on age and residence to 776 invasive breast cancer cases with available pretreatment serum. Tumours were centrally reviewed and prepared as tissue microarrays for immunohistochemical analysis. Breast cancer risk factors, assessed by interview, were related to serum PRL levels among controls using analysis of variance. Mean serum PRL levels by tumour characteristics are reported. These associations also were evaluated using polytomous logistic regression. RESULTS: Prolactin levels were associated with nulliparity in premenopausal (P=0.05) but not in postmenopausal women. Associations in postmenopausal women included an inverse association with increasing body mass index (P=0.0008) and direct association with use of recent/current hormone therapy (P=0.0006). In case-only analyses, higher PRL levels were more strongly associated with lobular compared with ductal carcinoma among postmenopausal women (P=0.02). Levels were not different by tumour size, grade, node involvement or oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status. CONCLUSIONS: Our analysis demonstrates that PRL levels are higher among premenopausal nulliparous as compared with parous women. Among postmenopausal women, levels were higher among hormone users and lower among obese women. These results may have value in understanding the mechanisms underlying several breast cancer risk factor associations. PMID- 20736945 TI - Investigation of low 5-year relative survival for breast cancer in a London cancer network. AB - BACKGROUND: Breast cancer 5-year relative survival is low in the North East London Cancer Network (NELCN). METHODS: We compared breast cancer that was diagnosed during 2001-2005 with that in the rest of London. RESULTS: North East London Cancer Network women more often lived in socioeconomic quintile 5 (42 vs 21%) and presented with advanced disease (11 vs 7%). Cox regression analysis showed the survival difference (hazard ratio: 1.27, 95% confidence interval (CI): 1.15-1.41) reduced to 1.00 (95% CI: 0.89-1.11) after adjustment for age, stage, socioeconomic deprivation, ethnicity and treatment. Major drivers were stage and deprivation. Excess mortality was in the first year. CONCLUSION: Late diagnosis occurs in NELCN. PMID- 20736947 TI - Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. AB - BACKGROUND: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). METHODS: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3 10 and the sensitivity (IC(50)) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. RESULTS: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC(50)) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. CONCLUSIONS: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease. PMID- 20736946 TI - Expression of parvin-beta is a prognostic factor for patients with urothelial cell carcinoma of the upper urinary tract. AB - BACKGROUND: Parvin-beta (ParvB), a potential tumour suppressor gene, is a focal adhesion protein. We evaluated the role of ParvB in the upper urinary tract urothelial cell carcinoma (UUT-UC). METHODS: ParvB mRNA and proteins levels in UUT-UC tissue were investigated by quantitative real-time polymerase chain reaction and western blot analysis, respectively. In addition, the expression of ParvB in tissues from patients with UUT-UC at different stages was evaluated by immunohistochemistry. Furthermore, biological functions of ParvB in urothelial cancer cells were investigated using a doxycycline-inducible overexpression system and siRNA. RESULTS: Western blot and mRNA analysis showed downregulation of ParvB expression in frozen UUT-UC tissue. Immunohistochemistry revealed high staining intensity of ParvB in normal urothelium, which decreased markedly at advanced stages of UUT-UC (P=0.0000). Moreover, ParvB was an independent prognostic indicator for disease-specific survival of patients with UUT-UC. Functional assays indicated that overexpression of ParvB in an urothelial cancer cell line resulted in decreased cell growth rate and ability to migrate. In contrast, knockdown of ParvB expression increased cell migration ability. CONCLUSIONS: Downregulation of ParvB expression significantly increased urothelial cancer cell growth and migration. Downexpression of ParvB level in UUT UC correlated with tumour stage, and was an independent unfavourable prognostic factor for disease-specific survival of patients with UUT-UC. PMID- 20736948 TI - MGMT gene promoter methylation correlates with tolerance of temozolomide treatment in melanoma but not with clinical outcome. AB - BACKGROUND: Despite limited clinical efficacy, treatment with dacarbazine or temozolomide (TMZ) remains the standard therapy for metastatic melanoma. In glioblastoma, promoter methylation of the counteracting DNA repair enzyme O(6) methylguanine-DNA-methyltransferase (MGMT) correlates with survival of patients exposed to TMZ in combination with radiotherapy. For melanoma, data are limited and controversial. METHODS: Biopsy samples from 122 patients with metastatic melanoma being treated with TMZ in two multicenter studies of the Dermatologic Cooperative Oncology Group were investigated for MGMT promoter methylation. We used the COBRA (combined bisulphite restriction analysis) technique to determine aberrant methylation of CpG islands in small amounts of genomic DNA isolated from paraffin-embedded tissue sections. To detect aberrant methylation, bisulphite treated DNA was amplified by PCR, enzyme restricted, and visualised by gel electrophoresis. RESULTS: Correlation with clinical data from 117 evaluable patients in a best-response evaluation indicated no statistically significant association between MGMT promoter methylation status and response. A methylated MGMT promoter was observed in 34.8% of responders and 23.4% of non-responders (P=0.29). In addition, no survival advantage for patients with a methylated MGMT promoter was detectable (P=0.79). Interestingly, we found a significant correlation between MGMT methylation and tolerance of therapy. Patients with a methylated MGMT promoter had more severe adverse events, requiring more TMZ dose reductions or discontinuations (P=0.007; OR 2.7 (95% CI: 1.32-5.7)). Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P=0.49). CONCLUSIONS: In advanced melanoma MGMT promoter, methylation correlates with tolerance of therapy, but not with clinical outcome. PMID- 20736949 TI - Combination of temozolomide with immunocytokine F16-IL2 for the treatment of glioblastoma. AB - BACKGROUND: Glioblastoma patients are still not cured by the treatments available at the moment. We investigated the therapeutic properties of temozolomide in combination with F16-IL2, a clinical-stage immunocytokine consisting of human interleukin (IL)-2 fused to the human antibody F16, specific to the A1 domain of tenascin-C. METHODS: We conducted three preclinical therapy studies, using subcutaneous and intracranial U87MG glioblastoma tumours xenografted in BALB/c nude mice. The same therapeutic schedule was used, consisting of five total administrations every third day, of 0.525 mg temozolomide, 20 microg F16-IL2, the combination, or the control solution. RESULTS: Immunohistochemical analysis of U87MG xenografts and of human glioblastoma specimens showed selective tumour staining of F16. A quantitative biodistribution confirmed the preferential tumour accumulation of radiolabelled F16-IL2. In the study with subcutaneous xenografts, the combination of F16-IL2 with temozolomide induced complete remission of the animals, which remained tumour free for over 160 days. The same treatment led to a consistent size reduction of intracranial xenografts and to a longer survival of animals. The immunocytokine promoted the recruitment of leukocytes into tumours of both models. CONCLUSION: The combined use of temozolomide with F16-IL2 deserves clinical investigations, which will be facilitated by the excellent safety profile in cynomolgus monkeys, and by the fact that F16-IL2 is in clinical trials in patients with cancer. PMID- 20736950 TI - Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. AB - BACKGROUND: The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours. METHODS: Two cohorts were compared: one was a group with young-onset PrCa, tested for germline BRCA2 mutations (6 of 263 cases had a germline BRAC2 mutation), and the second was a validation set consisting of a clinical set from Manchester of known BRCA2 mutuation carriers (15 cases) with PrCa. Survival data were compared with a control series of patients in a single clinic as determined by Kaplan-Meier estimates. Loss of heterozygosity was tested for in the DNA of tumour tissue of the young-onset group by typing four microsatellite markers that flanked the BRCA2 gene, followed by sequencing. RESULTS: Median survival of all PrCa cases with a germline BRCA2 mutation was shorter at 4.8 years than was survival in controls at 8.5 years (P=0.002). Loss of heterozygosity was found in the majority of tumours of BRCA2 mutation carriers. Multivariate analysis confirmed that the poorer survival of PrCa in BRCA2 mutation carriers is associated with the germline BRCA2 mutation per se. CONCLUSION: BRCA2 germline mutation is an independent prognostic factor for survival in PrCa. Such patients should not be managed with active surveillance as they have more aggressive disease. PMID- 20736951 TI - Enzastaurin inhibits invasion and metastasis in lung cancer by diverse molecules. AB - BACKGROUND: Enzastaurin (Enz) is a serine/threonine kinase inhibitor blocking protein kinase C (PKC)beta/AKT pathway. However, an ability of this compound to inhibit cancer invasion and metastasis is not yet clearly elucidated. METHODS: The ability of Enz to inhibit invasion and metastasis, and to target molecules was investigated in non-small cell lung cancer (NSCLC) by RT-PCR validated microarray, Matrigel, and in vivo chorionallantoic membrane (CAM) assays. RESULTS: Enzastaurin significantly reduced migration, invasion, and in vivo metastasis to lungs and liver (CAM assay) of diverse NSCLC cell lines. Genes promoting cancer progression (u-PAR, VEGFC, and HIF1alpha) and tumour suppression (VHL, RASSF1, and FHIT) of NSCLC were significantly (P<0.05) down- or upregulated after Enz treatment in H460, A549, and H1299 cells, respectively. Luciferase/chromatin immunoprecipitation analysis showed that Enz transcriptionally controls urokinase-type plasminogen activator receptor (u-PAR) expression by promoter inhibition through Sp1, Sp3, and c-Jun(AP-1). Moreover, siRNA knockdown of u-PAR re-sensitised Enz-resistant cells and induced apoptosis, suggesting u-PAR as a marker of Enz resistance. CONCLUSION: This study shows that Enz inhibits migration, invasion, and in vivo metastasis by targeting u-PAR, besides further targeting progression-related and tumour-suppressor genes in NSCLC. Together with u-PAR being a novel putative marker of Enz response, these data encourage molecularly tailored clinical studies on Enz in NSCLC therapy. PMID- 20736952 TI - Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer. AB - BACKGROUND: To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer. METHODS: Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT-PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk). RESULTS: Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly high risk, showing shorter DFS, P<0.001, and OAS, P=0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P<0.001 and P=0.075 for cohort B and P=0.043 and P<0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P=0.0065, OAS, not significant; cohort C: DFS, P=0.026, OAS, P<0.001. CONCLUSION: Activated leukocyte cell adhesion molecule and OPN mRNA expression has a strong discriminative impact on survival within cancer patients with low or negative expression of ER and HER2, so called 'high-risk' breast cancers, and might help in identifying patients who could benefit from new treatment approaches like targeted therapies in the adjuvant setting. PMID- 20736953 TI - Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp. MK756-CF1. AB - In the course of screening for a new type of androgen receptor (AR) antagonist, we isolated a novel compound, arabilin, with two structural isomers, spectinabilin and SNF4435C, produced by Streptomyces sp. MK756-CF1. Structure elucidation on the basis of the spectroscopic properties showed that arabilin is a novel polypropionate-derived metabolite with a p-nitrophenyl group and a substituted gamma-pyrone ring. Arabilin competitively blocked the binding of androgen to the ligand-binding domain of AR in vitro. In addition, arabilin inhibited androgen-induced prostate-specific antigen mRNA expression in prostate cancer LNCaP cells. PMID- 20736954 TI - Iron and early brain injury after subarachnoid hemorrhage. AB - Aneurysmal subarachnoid hemorrhage (SAH) affects approximately 27,000 Americans per year. Although delayed cerebral vasospasm is of high clinical significance, mortality within the first 2 days may approach 30%. In this issue of the Journal of Cerebral Blood Flow and Metabolism, Lee et al have studied the role of iron in early brain injury after experimental SAH. They found that iron chelation with deferoxamine reduced mortality and oxidative DNA damage, and lessened the induction of iron-handling proteins. Taken together, these results highlight the deleterious potential of blood breakdown products and provide an insight into future intervention. PMID- 20736955 TI - Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation. AB - The glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo (13)C nuclear magnetic resonance labeling with (13)C(2)acetate or (1-(13)C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal born redox equivalents to mitochondria in astrocytes. PMID- 20736957 TI - Cerebral 5-HT2A receptor and serotonin transporter binding in humans are not affected by the val66met BDNF polymorphism status or blood BDNF levels. AB - Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT(2A)) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT(2A) receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT(2A) receptor binding. In conclusion, val66met BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT(2A) or SERT binding. PMID- 20736956 TI - Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. AB - The purpose of this study was to investigate hemoglobin and iron handling after subarachnoid hemorrhage (SAH), examine the relationship between iron and neuroglial cell changes, and determine whether deferoxamine (DFX) can reduce SAH induced injury. The SAH was induced in Sprague-Dawley rats (n=110) using an endovascular perforation technique. Animals were treated with DFX (100 mg/kg) or vehicle 2 and 6 hours after SAH induction followed by every 12 hours for 3 days. Rats were killed at 6 hours, Days 1 and 3 to determine nonheme iron and examine iron-handling proteins using Western blot and immunohistochemistry. 8-Hydroxyl-2' deoxyguanosine and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were performed to assess oxidative DNA damage and neuronal cell death. After SAH, marked heme-oxygenase-1 (HO-1) upregulation at Day 3 (P<0.01) was accompanied by elevated nonheme iron (P<0.01), transferrin (Tf) (P<0.01), Tf receptor (P<0.05), and ferritin levels (P<0.01). Deferoxamine treatment reduced SAH-induced mortality (12% versus 29%, P<0.05), brain nonheme iron concentration, iron-handling protein expression, oxidative stress, and neuronal cell death at Day 3 (P<0.01) after SAH. These results suggest that iron overload in the acute phase of SAH causes oxidative injury leading to neuronal cell death. Deferoxamine effectively reduced oxidative stress and neuronal cell death, and may be a potential therapeutic agent for SAH. PMID- 20736958 TI - Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone. AB - Intracellular Ca(2+) release events ('Ca(2+) sparks') and transient activation of large-conductance Ca(2+)-activated potassium (BK) channels represent an important vasodilator pathway in the cerebral vasculature. Considering the frequent occurrence of cerebral artery constriction after subarachnoid hemorrhage (SAH), our objective was to determine whether Ca(2+) spark and BK channel activity were reduced in cerebral artery myocytes from SAH model rabbits. Using laser scanning confocal microscopy, we observed ~50% reduction in Ca(2+) spark activity, reflecting a decrease in the number of functional Ca(2+) spark discharge sites. Patch-clamp electrophysiology showed a similar reduction in Ca(2+) spark-induced transient BK currents, without change in BK channel density or single-channel properties. Consistent with a reduction in active Ca(2+) spark sites, quantitative real-time PCR and western blotting revealed decreased expression of ryanodine receptor type 2 (RyR-2) and increased expression of the RyR-2 stabilizing protein, FKBP12.6, in the cerebral arteries from SAH animals. Furthermore, inhibitors of Ca(2+) sparks (ryanodine) or BK channels (paxilline) constricted arteries from control, but not from SAH animals. This study shows that SAH-induced decreased subcellular Ca(2+) signaling events disable BK channel activity, leading to cerebral artery constriction. This phenomenon may contribute to decreased cerebral blood flow and poor outcome after aneurysmal SAH. PMID- 20736959 TI - Brain blood flow in Andean and Himalayan high-altitude populations: evidence of different traits for the same environmental constraint. AB - Humans have populated the Tibetan plateau much longer than the Andean Altiplano. It is thought that the difference in length of occupation of these altitudes has led to different responses to the stress of hypoxia. As such, Andean populations have higher hematocrit levels than Himalayans. In contrast, Himalayans have increased circulation to certain organ systems to meet tissue oxygen demand. In this study, we hypothesize that cerebral blood flow (CBF) is higher in Himalayans than in Andeans. Using a MEDLINE and EMBASE search, we included 10 studies that investigated CBF in Andeans and Himalayans between 3,658 and 4,330 m altitude. The CBF values were corrected for differences in hematocrit and arterial oxygen saturation. The data of these studies show a mean hematocrit of 50% in Himalayans and 54.1% in Andeans. Arterial oxygen saturation was 86.9% in Andeans and 88.4% in Himalayans. The CBF in Himalayans was slightly elevated compared with sea level subjects, and was 24% higher compared with Andeans. After correction for hematorit and arterial oxygen saturation, CBF was ~20% higher in Himalayans compared with Andeans. Altered brain metabolism in Andeans, and/or increased nitric oxide availability in Himalayans may have a role to explain this difference in brain blood flow. PMID- 20736960 TI - Simultaneous monitoring of tissue PO2 and NADH fluorescence during synaptic stimulation and spreading depression reveals a transient dissociation between oxygen utilization and mitochondrial redox state in rat hippocampal slices. AB - Nicotinamide adenine dinucleotide (NADH) imaging can be used to monitor neuronal activation and ascertain mitochondrial dysfunction, for example during hypoxia. During neuronal stimulation in vitro, NADH normally becomes more oxidized, indicating enhanced oxygen utilization. A subsequent NADH overshoot during activation or on recovery remains controversial and reflects either increased metabolic activity or limited oxygen availability. Tissue P(2) measurements, obtained simultaneously with NADH imaging in area CA1 in hippocampal slices, reveal that during prolonged train stimulation (ST) in 95% O(2), a persistent NADH oxidation is coupled with increased metabolic demand and oxygen utilization, for the duration of the stimulation. However, under conditions of either decreased oxygen supply (ST-50% O(2)) or enhanced metabolic demand (K(+)-induced spreading depression (K(+)-SD) 95% O(2)) the NADH oxidation is brief and the redox balance shifts early toward reduction, leading to a prolonged NADH overshoot. Yet, oxygen utilization remains elevated and is correlated with metabolic demand. Under these conditions, it appears that the rate of NAD(+) reduction may transiently exceed oxidation, to maintain an adequate oxygen flux and ATP production. In contrast, during SD in 50% O(2), the oxygen levels dropped to a point at which oxidative metabolism in the electron transport chain is limited and the rate of utilization declined. PMID- 20736962 TI - Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions. AB - 7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome. PMID- 20736961 TI - The contribution of L-arginine to the neurotoxicity of recombinant tissue plasminogen activator following cerebral ischemia: a review of rtPA neurotoxicity. AB - Alteplase is the only drug licensed for acute ischemic stroke, and in this formulation, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) is stabilized in a solution of L-arginine. Improved functional outcomes after alteplase administration have been shown in clinical trials, along with improved histological and behavioral measures in experimental models of embolic stroke. However, in animal models of mechanically induced ischemia, alteplase can exacerbate ischemic damage. We have systematically reviewed the literature of both rtPA and L-arginine administration in mechanical focal ischemia. The rtPA worsens ischemic damage under certain conditions, whereas L-arginine can have both beneficial and deleterious effects dependent on the time of administration. The interaction between rtPA and L-arginine may be leading to the production of nitric oxide, which can cause direct neurotoxicity, altered cerebral blood flow, and disruption of the neurovascular unit. We suggest that alternative formulations of rtPA, in the absence of L-arginine, would provide new insight into rtPA neurotoxicity, and have the potential to offer more efficacious thrombolytic therapy for ischemic stroke patients. PMID- 20736963 TI - Parametric mapping of [18F]fluoromisonidazole positron emission tomography using basis functions. AB - In this study, we show a basis function method (BAFPIC) for voxelwise calculation of kinetic parameters (K(1), k(2), k(3), K(i)) and blood volume using an irreversible two-tissue compartment model. BAFPIC was applied to rat ischaemic stroke micro-positron emission tomography data acquired with the hypoxia tracer [(18)F]fluoromisonidazole because irreversible two-tissue compartmental modelling provided good fits to data from both hypoxic and normoxic tissues. Simulated data show that BAFPIC produces kinetic parameters with significantly lower variability and bias than nonlinear least squares (NLLS) modelling in hypoxic tissue. The advantage of BAFPIC over NLLS is less pronounced in normoxic tissue. K(i) determined from BAFPIC has lower variability than that from the Patlak-Gjedde graphical analysis (PGA) by up to 40% and lower bias, except for normoxic tissue at mid-high noise levels. Consistent with the simulation results, BAFPIC parametric maps of real data suffer less noise-induced variability than do NLLS and PGA. Delineation of hypoxia on BAFPIC k(3) maps is aided by low variability in normoxic tissue, which matches that in K(i) maps. BAFPIC produces K(i) values that correlate well with those from PGA (r(2)=0.93 to 0.97; slope 0.99 to 1.05, absolute intercept <0.00002 mL/g per min). BAFPIC is a computationally efficient method of determining parametric maps with low bias and variance. PMID- 20736964 TI - Basal cerebral blood volume during the poststimulation undershoot in BOLD MRI of the human brain. AB - One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) response to functional challenges of the brain is the poststimulation undershoot, which has been suggested to originate from a delayed recovery of either cerebral blood volume (CBV) or cerebral metabolic rate of oxygen to baseline. Using bolus-tracking MRI in humans, we recently showed that relative CBV rapidly normalizes after the end of stimulation. As this observation contradicts at least part of the blood-pool contrast agent studies performed in animals, we reinvestigated the CBV contribution by dynamic T1 weighted three-dimensional MRI (8 seconds temporal resolution) and Vasovist at 3 T (12 subjects). Initially, we determined the time constants of individual BOLD responses. After injection of Vasovist, CBV-related T1-weighted signal changes revealed a signal increase during visual stimulation (1.7% +/- 0.4%), but no change relative to baseline in the poststimulation phase (0.2% +/- 0.3%). This finding renders the specific nature of the contrast agent unlikely to be responsible for the discrepancy between human and animal studies. With the assumption of normalized cerebral blood flow after stimulus cessation, a normalized CBV lends support to the idea that the BOLD MRI undershoot reflects a prolonged elevation of oxidative metabolism. PMID- 20736965 TI - Ascl1 lineage cells contribute to ischemia-induced neurogenesis and oligodendrogenesis. AB - Neural and oligodendrocyte progenitor cells in the adult brain express Ascl1 (also known as Mash1), a basic helix-loop-helix transcription factor. We examined the progeny and fate of this progenitor population in adult male Ascl1 CreER(TM);R26R-stop-yellow fluorescent protein mice subjected to right middle cerebral occlusion over 60 days after stroke using inducible Cre recombination to label Ascl1-expressing cells at poststroke days 2 to 6 in vivo. Seven days after stroke, a substantial increase in Ascl1 lineage cells was detected in the ipsilateral subventricular zone (SVZ), striatum, and corpus callosum. These cells exhibited proliferating progenitor cell phenotypes (Sox2(+), BrdU(+), and Ki67(+)). Although Ascl1 lineage cells in the ipsilateral SVZ gradually decreased during 14 to 60 days after stroke, Ascl1 lineage cells in the ischemic striatum revealed a remarkable increase during this period. Thirty and sixty days after stroke, Ascl1 lineage cells in the ischemic striatum gave rise to GABAergic neurons and mature oligodendrocytes. In contrast, none of the Ascl1 lineage cells in the contralateral striatum exhibited neuronal and oligodendrocyte phenotypes. Moreover, Ascl1 lineage cells in the corpus callosum were only fated to become mature oligodendrocytes. Our data suggest that Ascl1 lineage cells contribute to stroke-induced neurogenesis and oligodendrogenesis in the adult ischemic brain. PMID- 20736967 TI - Calcium and vitamin D intake and biochemical tests in short-stature children and adolescents. AB - BACKGROUND: Growth is highly dependent on the absorption of nutrients. Inadequate calcium and vitamin D intake may compromise bone mineralization and growth. There is a great deal of concern regarding calcium and vitamin D intake, as well as biochemical changes in children and adolescents, which led us to investigate calcium and vitamin D levels during growth. METHODS: Fifty-eight children and adolescents with short stature (z-score <3 s.d.) were evaluated from September 2005 to February 2007. Blood biochemical analyses and 24-h urine tests were performed and were used to evaluate calcium, phosphorus, creatinine, sodium, alkaline phosphatase, parathyroid hormone (PTH) and 25(OH)D levels. Dietary inquiries, repeated three times, were used to estimate the actual intake of these substances. RESULTS: A reduced calcium (608.6 mg/day) and vitamin D (72.5 IU/day) intake was observed. Calcium excretion in 24-h urine (56 mg/24 h) and calcium excretion by weight (2.0 mg/24 h/kg) showed scores that were below normal. A negative correlation between PTH and both dietary vitamin D (r=-0.46; P<0.01) and calcium intake (r =-0.41; P<0.001) was observed. CONCLUSIONS: The low calcium and vitamin D intake observed in short-stature children and adolescents was associated with biochemical results, and suggested that PTH and calcium excretion may be useful screening tests for evaluating dietary calcium and vitamin D. PMID- 20736966 TI - Autoregulation of cerebral blood flow to changes in arterial pressure in mild Alzheimer's disease. AB - Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75+/-6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent (15)O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107+/-13 to 92+/-9 mm Hg with intravenous nicardipine; (11)C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (-0.9+/-5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=-3.4 to 1.5), cortical borderzones (-1.9+/-5.0 mL per 100 g per minute, P=0.10, 95% CI=-4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (-0.3+/-4.4 mL per 100 g per minute, P=0.85, 95% CI=-3.3 to 3.9), or regions of peak (11)C-PIB uptake (-2.5+/-7.7 mL per 100 g per minute, P=0.30, 95% CI=-7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD. PMID- 20736968 TI - Thyroid volume in Swedish school children: a national, stratified, population based survey. AB - BACKGROUND/OBJECTIVES: Sweden has had a salt iodination program since 1936. This first national surveillance study on iodine nutrition infers an adequate level of urinary iodine concentration (UIC 125 MUg/l) and the aim is now to evaluate thyroid volume (Tvol) in the same national sample. SUBJECTS/METHODS: A stratified probability proportionate to size cluster sampling was used to obtain a representative national sample of Swedish children aged 6-12 years. Median Tvol obtained ultrasonographically and the prevalence of enlarged thyroid glands were compared with an international reference standard. Regional differences were evaluated through comparisons of Tvol between coastal and inland areas, urban and rural regions, and former goitre and non-goitre regions. RESULTS: Tvol was correlated with age, body surface area (BSA), weight, height and body mass index for both sexes (P<0.0001) but not with UIC. The most important predictors for Tvol were age (girls: P<0.0001, boys: P=0.001) and BSA (girls: P<0.0001, boys: P<0.01). Median Tvol was higher in Sweden than in the reference study (P<0.0001). The prevalence of goitre was higher in Sweden (correlated to age 22.3%, BSA 15.7%, weight 17.6%, height 12.9%) than in the international reference (correlated to age 2.5%, BSA 2.5%, weight 2.5%, height 2.5%) (P<0.0001). Thyroids were larger in boys from urban and former non-goitre areas. CONCLUSIONS: Tvols were higher in Swedish school children than in the international reference study although iodine intake is considered optimal in Sweden. These findings underline the importance of regular monitoring of iodine intake, especially with regard to the decreased intake of table salt that is likely to follow initiation of health campaigns. PMID- 20736969 TI - The fuel of evolution. PMID- 20736970 TI - Multiple genetic divergences and population expansions of a Mediterranean sandfly, Phlebotomus ariasi, in Europe during the Pleistocene glacial cycles. AB - Phlebotomus ariasi is one of the two sandflies transmitting the causative agent of zoonotic leishmaniasis, Leishmania infantum, in France and Iberia, and provides a rare case study of the postglacial re-colonization of France by a Mediterranean species. Four DNA sequences were analysed-mitochondrial cytochrome b (cyt b), nuclear elongation factor-1alpha (EF-1alpha) and two anonymous nuclear loci-for 14-15 French populations and single populations from northeast Spain, northwest Spain, Portugal and Morocco. The presence of cryptic sibling species was not revealed by phylogenetic analyses and testing for reproductive isolation between sympatric populations defined by the two most divergent cyt b haplogroups. No locus was shown to be under positive directional or balancing selection and, therefore, molecular variation was explained demographically. Each nuclear locus showed shallow isolation by distance from Portugal to the French Pyrenees, but for both cyt b and EF-1alpha there was then a step change to the upland Massif Central, where leading-edge populations showed low diversity at all loci. Multiple genetic divergences and population expansions were detected by analyses of cyt b and dated to the Pleistocene. Endemicity of one cyt b sub lineage suggested the presence of a refuge north of the Pyrenees during the last glacial period. Monopolization of the Massif Central by genetically differentiated populations of P. ariasi might possibly hinder the northwards spread of leishmaniasis. PMID- 20736971 TI - The quantitative-genetic and QTL architecture of trait integration and modularity in Brassica rapa across simulated seasonal settings. AB - Within organisms, groups of traits with different functions are frequently modular, such that variation among modules is independent and variation within modules is tightly integrated, or correlated. Here, we investigated patterns of trait integration and modularity in Brassica rapa in response to three simulated seasonal temperature/photoperiod conditions. The goals of this research were to use trait correlations to understand patterns of trait integration and modularity within and among floral, vegetative and phenological traits of B. rapa in each of three treatments, to examine the QTL architecture underlying patterns of trait integration and modularity, and to quantify how variation in temperature and photoperiod affects the correlation structure and QTL architecture of traits. All floral organs of B. rapa were strongly correlated, and contrary to expectations, floral and vegetative traits were also correlated. Extensive QTL co-localization suggests that covariation of these traits is likely due to pleiotropy, although physically linked loci that independently affect individual traits cannot be ruled out. Across treatments, the structure of genotypic and QTL correlations was generally conserved. Any observed variation in genetic architecture arose from genotype * environment interactions (GEIs) and attendant QTL * E in response to temperature but not photoperiod. PMID- 20736972 TI - The use of telomere length in ecology and evolutionary biology. AB - The measurement of telomere length (TL) is a genetic tool that is beginning to be employed widely in ecological and evolutionary studies as marker of age and fitness. The adoption of this approach has been accelerated by the development of telomere quantitative PCR, which enables the screening of large numbers of samples with little effort. However, the measurement and interpretation of TL change need to be done with a necessary level of rigour that has thus far often been missing where this approach has been employed in an ecological and evolutionary context. In this article, we critically review the literature available on the relationship between TL, age and fitness. We seek to familiarize geneticists, ecologists and evolutionary biologists with the shortcomings of the methods and the most common mistakes made while analysing TL. Prevention of these mistakes will ensure accuracy, reproducibility and comparability of TL studies in different species and allow the identification of ecological and evolutionary principles behind TL dynamics. PMID- 20736973 TI - Distinguishing the 4qA and 4qB variants is essential for the diagnosis of facioscapulohumeral muscular dystrophy in the Chinese population. AB - Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited muscular dystrophy with markedly clinical variability and complex genetic cause. Several reports pertaining to the Caucasian population have confirmed that there are 4qA and 4qB variants of the 4qter subtelomere, and FSHD is uniquely associated with the 4qA variant. However, few data relevant to the Chinese population have been published. In present paper, detailed clinical and genetic re-evaluations were performed in members of four special families who had been initially diagnosed as atypical or asymptomatic FSHD based only on the D4Z4 repeat length analysis. The FSHD-sized D4Z4 repeats in the probands from families 1, 2 and 3 were identified as 4qB variants. These patients were further confirmed as limb-girdle muscular dystrophy (LGMD2) or myotonic dystrophy (DM1) by molecular analyses. Specifically, we identified a 4qB variant on chromosome 10 in the healthy members of the fourth FSHD family with complex D4Z4 rearrangements of two exchanged repeat arrays. For the first time, we demonstrated in the Chinese population that D4Z4 contractions on the 4qB variant do not cause FSHD and 4qB variant on chromosome 10 might also represent intermediate structures in the transition from 4q to 10q. Furthermore, our results emphasize that D4Z4 repeat length analysis alone is not sufficient for the diagnosis of FSHD, especially when used as an exclusion criterion. This analysis should be accompanied by 4qA/4qB variant determination and integrated chromosome assignments, especially in patients with obscure and unclassified myopathies similar to atypical forms of FSHD. PMID- 20736974 TI - Statement of the ESHG on direct-to-consumer genetic testing for health-related purposes. AB - Many private companies offer direct-to-consumer (DTC) genetic testing services. Some tests may detect severe and highly penetrant monogenic disorders, while other tests are for genetic variants found associated with increased susceptibility for common and complex diseases in large-scale population studies. Through its Public and Professional Policy committee followed by member and expert consultation, the European Society of Human Genetics has developed the following policy on advertising and provision of predictive genetic tests by such DTC companies: (1) clinical utility of a genetic test shall be an essential criterion for deciding to offer this test to a person or a group of persons; (2) laboratories providing genetic tests should comply with accepted quality standards, including those regarding laboratory personnel qualifications; (3) information about the purpose and appropriateness of testing should be given before the test is done; (4) genetic counselling appropriate to the type of test and disease should be offered; and for some tests psychosocial evaluation and follow-up should be available; (5) privacy and confidentiality of sensitive genetic information should be secured and the data safely guarded; (6) special measures should be taken to avoid inappropriate testing of minors and other legally incapacitated persons; (7) all claims regarding genetic tests should be transparent; advertisement should be unbiased and marketing of genetic tests should be fair; (8) in biomedical research, health care and marketing, respect should be given to relevant ethical principles, as well as international treaties and recommendations regarding genetic testing; and (9) nationally approved guidelines considering all the above-mentioned aspects should be made and followed. PMID- 20736975 TI - Preparation and validation of the first WHO international genetic reference panel for Fragile X syndrome. AB - Fragile X syndrome is the most common inherited form of mental retardation. It is caused by expansion of a trinucleotide (CGG)n repeat sequence in the 5' untranslated region of the FMR1 gene, resulting in promoter hypermethylation and suppression of FMR1 transcription. Additionally, pre-mutation alleles in carrier males and females may result in Fragile X tremor ataxia syndrome and primary ovarian insufficiency, respectively. Fragile X is one of the most commonly requested molecular genetic tests worldwide. Quality assessment schemes have identified a wide disparity in allele sizing between laboratories. It is therefore important that clinical laboratories have access to characterized reference materials (RMs) to aid accurate allele sizing and diagnosis. With this in mind, a panel of genotyping RMs for Fragile X syndrome has been developed, which should be stable over many years and available to all diagnostic laboratories. Immortalized cell lines were produced by Epstein-Barr virus transformation of lymphocytes from consenting patients. Genomic DNA was extracted in bulk and RM aliquots were freeze-dried in glass ampoules. Twenty-one laboratories from seventeen countries participated in a collaborative study to assess their suitability. Participants evaluated the samples (blinded, in triplicate) in their routine methods alongside in-house and commercial controls. The panel of five genomic DNA samples was endorsed by the European Society of Human Genetics and approved as an International Standard by the Expert Committee on Biological Standardization at the World Health Organization. PMID- 20736976 TI - A genomic analysis identifies a novel component in the genetic structure of sub Saharan African populations. AB - Studies of large sets of single nucleotide polymorphism (SNP) data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2841 SNPs in 12 sub-Saharan African populations, including a previously unsampled region of southeastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the southeastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region. PMID- 20736977 TI - Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy. AB - This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000-2005 from 19 population-based registries in 11 European countries covering 2.5 million births were analysed. Cases included were livebirths diagnosed to 1 year of age, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly (TOPFA). In all, 465 cases of SCT were diagnosed between 2000 and 2005, a prevalence of 1.88 per 10,000 births (95% CI 1.71-2.06). Prevalence of XXX, XXY and XYY were 0.54 (95% CI 0.46-0.64), 1.04 (95% CI 0.92 1.17) and 0.30 (95% CI 0.24-0.38), respectively. In all, 415 (89%) were prenatally diagnosed and 151 (36%) of these resulted in TOPFA. There was wide country variation in prevalence (0.19-5.36 per 1000), proportion prenatally diagnosed (50-100%) and proportion of prenatally diagnosed resulting in TOPFA (13 67%). Prevalence of prenatally diagnosed cases was higher in countries with high prenatal detection rates of Down syndrome. The EUROCAT prevalence rate for SCTs diagnosed prenatally or up to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to differences in screening policies as well as organizational and cultural factors. PMID- 20736978 TI - Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. AB - Genome-wide high-resolution array analysis is rapidly becoming a reliable method of diagnostic investigation in individuals with mental retardation and congenital anomalies, leading to the identification of several novel microdeletion and microduplication syndromes. We have identified seven individuals with duplication on chromosome 14q11.2q13.1, who exhibited idiopathic developmental delay and cognitive impairment, severe speech delay, and developmental epilepsy. Among these cases, the minimal common duplicated region on chromosome 14q11.2q13.1 includes only three genes, FOXG1, C14orf23, and PRKD1. We propose that increased dosage of Forkhead Box G1 (FOXG1) is the best candidate to explain the abnormal neurodevelopmental phenotypes observed in our patients. Deletions and inactivating mutations of FOXG1 have been associated with a Rett-like syndrome characterized by hypotonia, irritability, developmental delay, hand stereotypies, and deceleration of head growth. FOXG1, encoding a brain-specific transcription factor, has an important role in the developing brain. In fact, in vivo studies in chicken brain demonstrated that overexpression of FOXG1 results in thickening of the neuroepithelium and outgrowth of the telencephalon and mesencephalum, secondary to a reduction in neuroepithelial cell apoptosis. PMID- 20736979 TI - A major Y-chromosome haplogroup R1b Holocene era founder effect in Central and Western Europe. AB - The phylogenetic relationships of numerous branches within the core Y-chromosome haplogroup R-M207 support a West Asian origin of haplogroup R1b, its initial differentiation there followed by a rapid spread of one of its sub-clades carrying the M269 mutation to Europe. Here, we present phylogeographically resolved data for 2043 M269-derived Y-chromosomes from 118 West Asian and European populations assessed for the M412 SNP that largely separates the majority of Central and West European R1b lineages from those observed in Eastern Europe, the Circum-Uralic region, the Near East, the Caucasus and Pakistan. Within the M412 dichotomy, the major S116 sub-clade shows a frequency peak in the upper Danube basin and Paris area with declining frequency toward Italy, Iberia, Southern France and British Isles. Although this frequency pattern closely approximates the spread of the Linearbandkeramik (LBK), Neolithic culture, an advent leading to a number of pre-historic cultural developments during the past <=10 thousand years, more complex pre-Neolithic scenarios remain possible for the L23(xM412) components in Southeast Europe and elsewhere. PMID- 20736980 TI - Dialysis: the stent graft for stenosis: let's appraise before we praise. PMID- 20736981 TI - Thrombotic microangiopathy: atypical HUS: current diagnostic and therapeutic approaches. PMID- 20736982 TI - Dialysis: prognostic value of blood pressure in patients on hemodialysis. PMID- 20736983 TI - Diabetic nephropathy: diabetic nephropathy-challenges in pathologic classification. PMID- 20736984 TI - Malignancy after renal transplantation: the role of immunosuppression. AB - Outcomes of kidney transplantation, in terms of graft and patient survival, have improved over the past few decades, partly as a result of the introduction of new immunosuppressive drugs. Many immunosuppressive agents are associated with an increased risk of cardiovascular events and an increased risk of cancer, however, which can compromise patient survival. Cancer is more common among solid-organ transplant recipients than it is in the general population or in patients on dialysis. In fact, malignancy is the third most common cause of death in renal transplant recipients. Immunosuppressive treatments used in renal transplant recipients can cause malignancy by supporting oncogenesis caused by certain viruses or by impairing immune surveillance thereby enabling faster tumor growth. In this Review, we describe the epidemiological and clinical characteristics of common tumor types occurring after kidney transplantation, and the etiopathogenetic factors that lead to their appearance, with a particular focus on the relationship between immunosuppressive treatment and malignancy. Immunosuppressive drugs associated with an increased risk of malignancy after transplantation are also discussed, as are immunosuppressive drugs that seem to have antioncogenic properties. PMID- 20736985 TI - Dyslipidemia in children with chronic kidney disease. AB - Dyslipidemia, a known risk factor for atherosclerosis, is frequent among both adults and children with chronic kidney disease. Here, we describe the prevalence and pattern of dyslipidemia from a cross-sectional analysis of 391 children aged 1-16 years, enrolled in the multicenter Chronic Kidney Disease in Children (CKiD) study, with a median glomerular filtration rate (GFR), measured by the plasma disappearance of iohexol, of 43 ml/min per 1.73 m2. Multivariate analysis was applied to adjust for age, gender, body mass index (BMI), GFR, and the urinary protein/creatinine ratio. Proteinuria was in the nephrotic range in 44 and the BMI exceeded the 95th percentile in 57 patients of this cohort. Baseline lipid analysis found a high prevalence of hypertriglyceridemia in 126, increased non HDL-C in 62, and reduced HDL-C in 83. Overall, 177 children had dyslipidemia, of whom 79 had combined dyslipidemia. Lower GFR was associated with higher triglycerides, lower HDL-C, and higher non-HDL-C. Nephrotic-range proteinuria was significantly associated with dyslipidemia and combined dyslipidemia. Compared with children with a GFR>50, children with a GFR<30 had significantly increased odds ratios for any dyslipidemia or for combined dyslipidemia. Hence, among children with moderate chronic kidney disease, dyslipidemia is common and is associated with lower GFR, nephrotic proteinuria, and non-renal factors including age and obesity. PMID- 20736986 TI - Vasopressin regulation of renal sodium excretion. AB - Vasopressin promotes renal water reabsorption decreasing excretion of free water to dilute plasma and lower serum osmolality. We have good understanding of the causes, mechanisms and consequences of this vasopressin-dependent renal water movement. In comparison, vasopressin actions on renal electrolytes including sodium excretion and its consequences have been less well understood. This is so for investigation and discussions of the renal actions of vasopressin are framed primarily around water metabolism rather than any direct effect on salt handling. The fact that water moves in biological systems, to include the mammalian kidney, only by osmosis passively down its concentration gradient is implicit in such discussion but often not overtly addressed. This can cause confusion. Moreover, although vasopressin action on renal sodium excretion via the V2 receptor is critical to water transport, it is masked easily being situational--for instance, dependent on hydration state. It is now clear that an increase in sodium reabsorption along the distal nephron (CNT + CD) mediated by activation of the epithelial Na(+) channel (ENaC) by vasopressin makes an important contribution to maintenance of the axial corticomedullary osmotic gradient necessary for maximal water reabsorption. Thus, we need to modify slightly our understanding of vasopressin and its renal actions to include the idea that while vasopressin decreases free water excretion to dilute plasma, it does this, in part, by promoting sodium reabsorption and consequently decreasing sodium excretion via ENaC activated along the distal nephron. PMID- 20736987 TI - Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation. AB - We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention. PMID- 20736988 TI - Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model. AB - The remnant kidney model in C57BL/6 mice does not develop progressive chronic kidney disease (CKD). In this study we modified the model to mimic features of human CKD and to define accelerants of disease progression using three strains of mice. Following the procedure, there was a progressive increase in albuminuria, progressive loss in renal function, severe glomerulosclerosis and interstitial fibrosis, hypertension, cardiac fibrosis, and anemia by 4 weeks in CD-1 mice and by 12 weeks in 129S3 mice. In contrast, even after 16 weeks, the C57BL/6 mice with a remnant kidney had modestly increased albuminuria without increased blood pressure and without developing CKD or cardiac fibrosis. The baseline blood pressure, determined by radiotelemetry in conscious animals, correlated with CKD progression rates in each strain. Administering angiotensin II overcame the resistance of C57BL/6 mice to CKD following renal mass reduction, displaying high blood pressure and albuminuria, severe glomerulosclerosis, and loss of renal function by 4 weeks. Decreasing blood pressure with olmesartan, but not hydralazine, in CD-1 mice with a remnant kidney reduced CKD progression and cardiac fibrosis. C57BL/6 mice with a remnant kidney and DOCA-salt hypertension developed modest CKD. Each strain had similar degrees of interstitial fibrosis in three different normotensive models of renal fibrosis. Thus, reducing renal mass in CD-1 or 129S3 mice mimics many features of human CKD. Angiotensin II can convert the C57BL/6 strain from CKD resistant to susceptible in this disease model. PMID- 20736989 TI - Scopolamine produces larger antidepressant and antianxiety effects in women than in men. AB - Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 MUg/kg). Following a single blind placebo lead-in, participants entered either a placebo-block/scopolamine block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group * block interaction (F=21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F=8.4, p=0.006). The treatment group * block interaction was also significant in males (F=3.8, p=0.043) and females (F=35.6, p<0.001) separately. A block * gender interaction (F=7.4, p=0.009) indicated that the response magnitude was larger in women. The treatment * block interaction was significant for the HAM-A across gender (F=12.0, p<0.001), and was significant for females (F=24.9, p<0.001) but not for males (F=1.3, p=0.30). When comparing the baseline block to study end, the block * gender interaction (F=12.6, p=0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men. PMID- 20736990 TI - What have we learned about trial design from NIMH-funded pragmatic trials? AB - At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: 'what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long term, large-scale trials of psychiatric treatments?' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of 'post hoc' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing. PMID- 20736992 TI - Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors. AB - Tobacco smoke exposure during development can result in lasting alterations in sensory processing and attention. This suggests that some constituent of smoke, such as the primary addictive component, nicotine, alters neurodevelopment. Although many effects of developmental nicotine exposure have been identified in humans and animal models, very few mechanistic studies have identified the molecular and anatomical basis for a defined behavioral consequence of developmental exposure. We show in this study that a mouse model of developmental nicotine exposure results in hypersensitive passive avoidance in adulthood. We have used transgenic mice in which beta2 subunit containing nicotinic acetylcholine receptors (beta2* nAChRs) are expressed exclusively on corticothalamic neurons (beta2 tr(CT) mice) to identify the receptor subtypes involved and also to define the circuit level site of action responsible for this persistent, nicotine-induced behavioral phenotype. Further characterization of the native nAChRs expressed in this circuit indicates that both (alpha4)(2)(beta2)(3) and (alpha4)(2)(beta2)(2)alpha5 nAChR subtypes are present in corticothalamic projections. Consistent with a role for (alpha4)(2)(beta2)(2)alpha5 nAChRs in mediating the effect of developmental nicotine exposure on adult passive avoidance behavior, constitutive deletion of the alpha5 nAChR subunit also alters this behavior. A critical period for this developmental consequence of nicotine exposure was defined by limiting exposure to the early post-natal period. Taken together, these studies identify a novel consequence of developmental nicotine exposure in the mouse, define the nAChR subtypes and neural circuit involved in this behavioral change and delimit the neurodevelopmental period critical for vulnerability to a behavioral alteration that persists into adulthood. PMID- 20736993 TI - Late prenatal immune activation in mice leads to behavioral and neurochemical abnormalities relevant to the negative symptoms of schizophrenia. AB - Based on the human epidemiological association between prenatal infection and higher risk of schizophrenia, a number of animal models have been established to explore the long-term brain and behavioral consequences of prenatal immune challenge. Accumulating evidence suggests that the vulnerability to specific forms of schizophrenia-related abnormalities is critically influenced by the precise timing of the prenatal immunological insult. In the present study, we tested the hypothesis whether late prenatal immune challenge in mice may induce long-term behavioral and neurochemical dysfunctions primarily associated with the negative symptoms of schizophrenia. We found that prenatal exposure to the viral mimic polyriboinosinic-polyribocytidilic acid (Poly-I:C; 5 mg/kg, i.v.) on gestation day (GD) 17 led to significant deficits in social interaction, anhedonic behavior, and alterations in the locomotor and stereotyped behavioral responses to acute apomorphine (APO) treatment in both male and female offspring. In addition, male but not female offspring born to immune challenged mothers displayed behavioral/cognitive inflexibility as indexed by the presence of an abnormally enhanced latent inhibition (LI) effect. Prenatal immune activation in late gestation also led to numerous, partly sex-specific changes in basal neurotransmitter levels, including reduced dopamine (DA) and glutamate contents in the prefrontal cortex and hippocampus, as well as reduced gamma-aminobutyric acid (GABA) and glycine contents in the hippocampus and prefrontal cortex, respectively. The constellation of behavioral and neurochemical abnormalities emerging after late prenatal Poly-I:C exposure in mice leads us to conclude that this immune-based experimental model provides a powerful neurodevelopmental animal model especially for (but not limited to) the negative symptoms of schizophrenia. PMID- 20736994 TI - Tractographic analysis of historical lesion surgery for depression. AB - Various surgical brain ablation procedures for the treatment of refractory depression were developed in the twentieth century. Most notably, key target sites were (i) the anterior cingulum, (ii) the anterior limb of the internal capsule, and (iii) the subcaudate white matter, which were regarded as effective targets. Long-term symptom remissions were better following lesions of the anterior internal capsule and subcaudate white matter than of the cingulum. It is possible that the observed clinical improvements of these various surgical procedures may reflect shared influences on presently unspecified brain affect regulating networks. Such possibilities can now be analyzed using modern brain connectivity procedures such as diffusion tensor imaging (DTI) tractography. We determined whether the shared connectivities of the above lesion sites in healthy volunteers might explain the therapeutic effects of the various surgical approaches. Accordingly, modestly sized historical lesions, especially of the anatomical overlap areas, were 'implanted' in brain-MRI scans of 53 healthy subjects. These were entered as seed regions for probabilistic DTI connectivity reconstructions. We analyzed for the shared connectivities of bilateral anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and stereotactic limbic leucotomy (a combination of the last two lesion sites). Shared connectivities between the four surgical approaches mapped onto the most mediobasal aspects of bilateral frontal lobe fibers, including the forceps minor and the anterior thalamic radiations that contacted subgenual cingulate regions. Anatomically, convergence of these shared connectivities may derive from the superolateral branch of the medial forebrain bundle (MFB), a structure that connects these frontal areas to the origin of the mesolimbic dopaminergic 'reward' system in the midbrain ventral tegmental area. Thus, all four surgical anti-depressant approaches may be promoting positive affect by converging influences onto the MFB. PMID- 20736991 TI - Serotonin and dopamine: unifying affective, activational, and decision functions. AB - Serotonin, like dopamine (DA), has long been implicated in adaptive behavior, including decision making and reinforcement learning. However, although the two neuromodulators are tightly related and have a similar degree of functional importance, compared with DA, we have a much less specific understanding about the mechanisms by which serotonin affects behavior. Here, we draw on recent work on computational models of dopaminergic function to suggest a framework by which many of the seemingly diverse functions associated with both DA and serotonin comprising both affective and activational ones, as well as a number of other functions not overtly related to either-can be seen as consequences of a single root mechanism. PMID- 20736995 TI - Resequencing of nicotinic acetylcholine receptor genes and association of common and rare variants with the Fagerstrom test for nicotine dependence. AB - Common single-nucleotide polymorphisms (SNPs) at nicotinic acetylcholine receptor (nAChR) subunit genes have previously been associated with measures of nicotine dependence. We investigated the contribution of common SNPs and rare single nucleotide variants (SNVs) in nAChR genes to Fagerstrom test for nicotine dependence (FTND) scores in treatment-seeking smokers. Exons of 10 genes were resequenced with next-generation sequencing technology in 448 European-American participants of a smoking cessation trial, and CHRNB2 and CHRNA4 were resequenced by Sanger technology to improve sequence coverage. A total of 214 SNP/SNVs were identified, of which 19.2% were excluded from analyses because of reduced completion rate, 73.9% had minor allele frequencies <5%, and 48.1% were novel relative to dbSNP build 129. We tested associations of 173 SNP/SNVs with the FTND score using data obtained from 430 individuals (18 were excluded because of reduced completion rate) using linear regression for common, the cohort allelic sum test and the weighted sum statistic for rare, and the multivariate distance matrix regression method for both common and rare SNP/SNVs. Association testing with common SNPs with adjustment for correlated tests within each gene identified a significant association with two CHRNB2 SNPs, eg, the minor allele of rs2072660 increased the mean FTND score by 0.6 Units (P=0.01). We observed a significant evidence for association with the FTND score of common and rare SNP/SNVs at CHRNA5 and CHRNB2, and of rare SNVs at CHRNA4. Both common and/or rare SNP/SNVs from multiple nAChR subunit genes are associated with the FTND score in this sample of treatment-seeking smokers. PMID- 20736996 TI - Disulfiram attenuates drug-primed reinstatement of cocaine seeking via inhibition of dopamine beta-hydroxylase. AB - The antialcoholism medication disulfiram (Antabuse) inhibits aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde upon ethanol ingestion and produces the aversive 'Antabuse reaction' that deters alcohol consumption. Disulfiram has also been shown to deter cocaine use, even in the absence of an interaction with alcohol, indicating the existence of an ALDH independent therapeutic mechanism. We hypothesized that disulfiram's inhibition of dopamine beta-hydroxylase (DBH), the catecholamine biosynthetic enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons, underlies the drug's ability to treat cocaine dependence. We tested the effects of disulfiram on cocaine and food self-administration behavior and drug-primed reinstatement of cocaine seeking in rats. We then compared the effects of disulfiram with those of the selective DBH inhibitor, nepicastat. Disulfiram, at a dose (100 mg/kg, i.p.) that reduced brain NE by ~40%, did not alter the response for food or cocaine on a fixed ratio 1 schedule, whereas it completely blocked cocaine-primed (10 mg/kg, i.p.) reinstatement of drug seeking following extinction. A lower dose of disulfiram (10 mg/kg) that did not reduce NE had no effect on cocaine-primed reinstatement. Nepicastat recapitulated the behavioral effects of disulfiram (100 mg/kg) at a dose (50 mg/kg, i.p.) that produced a similar reduction in brain NE. Food-primed reinstatement of food seeking was not impaired by DBH inhibition. Our results suggest that disulfiram's efficacy in the treatment of cocaine addiction is associated with the inhibition of DBH and interference with the ability of environmental stimuli to trigger relapse. PMID- 20736998 TI - Multistrain influenza protection induced by a nanoparticulate mucosal immunotherapeutic. AB - All commercial influenza vaccines elicit antibody responses that protect against seasonal infection, but this approach is limited by the need for annual vaccine reformulation that precludes efficient responses against epidemic and pandemic disease. In this study we describe a novel vaccination approach in which a nanoparticulate, liposome-based agent containing short, highly conserved influenza-derived peptides is delivered to the respiratory tract to elicit potent innate and selective T cell-based adaptive immune responses. Prepared without virus-specific peptides, mucosal immunostimulatory therapeutic (MIT) provided robust, but short-lived, protection against multiple, highly lethal strains of influenza in mice of diverse genetic backgrounds. MIT prepared with three highly conserved epitopes that elicited virus-specific memory T-cell responses but not neutralizing antibodies, termed MITpep, provided equivalent, but more durable, protection relative to MIT. Alveolar macrophages were more important than dendritic cells in determining the protective efficacy of MIT, which induced both canonical and non-canonical antiviral immune pathways. Through activation of airway mucosal innate and highly specific T-cell responses, MIT and MITpep represent novel approaches to antiviral protection that offer the possibility of universal protection against epidemic and pandemic influenza. PMID- 20737000 TI - The role of the gut as a primary lymphoid organ: CD8alphaalpha intraepithelial T lymphocytes in euthymic mice derive from very immature CD44+ thymocyte precursors. AB - Intestinal CD8alphaalpha intraepithelial T lymphocytes (T-IELs) have a key role in mucosal immunity and, unlike other T cells, were proposed to differentiate locally. In apparent contradiction, these cells were also shown to originate from a wave of thymus migrants colonizing the gut in the first 3 weeks after birth. We here identify previously uncharacterized very immature CD4(-)CD8(-)CD3( )CD44(+)CD25(int) thymocytes, which have not yet rearranged their T-cell antigen receptor (TCR), as having the capacity to leave the thymus, migrate to the blood, colonize the gut, and reconstitute CD8alphaalpha T-IEL, and show that this cell set is fully responsible for the generation of the CD8alphaalpha T-IEL pool. Thus, although the thymus may be fundamental for efficient T-cell commitment, CD8alphaalpha T-IEL' complete TCR rearrangements and TCR-alphabeta/gammadelta lineage commitment must occur in the gut. These results demonstrate a major role of the gut environment as a primary lymphoid organ. PMID- 20736997 TI - DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls. AB - Choice impulsivity has been linked to dopamine function and is consistently observed in attention deficit/hyperactivity disorder (ADHD) as a preference for smaller-immediate over larger-delayed rewards using choice-delay paradigms. More sophisticated delay discounting paradigms have yielded inconsistent results. Context and sample characteristics may have contributed to these variations. In this study we examine the effect of type (real vs hypothetical) and magnitude of reward as well as of variation in dopamine genes on choice impulsivity. We selected 36 male adolescents with ADHD-combined subtype (ADHD-CT) and 32 controls (mean age=15.42, SD=2.05) to form four roughly equally sized subgroups on the basis of DAT1(10/6) haplotype dosage (2 copies and <2 copies). Participants, who were also genotyped for the COMT(val158met) and DRD4(48bp-VNTR) polymorphisms, performed a hypothetical and a real-time discounting task and provided self ratings of trait impulsivity. The ADHD-CT group discounted rewards more steeply than controls only in the hypothetical task, with delay, but not reward magnitude, influencing choices. They also rated themselves as more impulsive compared with controls. DAT1(10/6) dosage and the COMT(Val158Met) genotype predicted trait impulsivity and discounting rates in the hypothetical task, but not in the real-time task. Our results directly link variation in genes putatively influencing dopamine signaling in the prefrontal cortex (COMT(Val158Met)) and the striatum (DAT1(10/6)) with discounting rates in a hypothetical task (but not a real-time task) and self-ratings of trait impulsivity in ADHD-CT and healthy controls. The lack of magnitude effects in the hypothetical task suggests that discounting in this task may be influenced by different processes in ADHD-CT than in healthy controls. PMID- 20737002 TI - Final report on carcinogens background document for cobalt-tungsten carbide: powders and hard metals. PMID- 20736999 TI - Single-chain recombinant HLA-DQ2.5/peptide molecules block alpha2-gliadin specific pathogenic CD4+ T-cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease. AB - Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4(+) T cells have a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. In this study, we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered alpha2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T-cell proliferation and inhibited proinflammatory cytokine secretion in human DQ2.5-restricted alpha2-gliadin specific T-cell clones obtained from patients with CD. The results from our in vitro studies suggest that HLA-DQ2.5-derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T-cell-mediated inflammation and the associated production of proinflammatory cytokines. PMID- 20737001 TI - IL-4Ralpha-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. AB - Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T(H)2 polarization of the host's immune response. We present data demonstrating N. brasiliensis-driven airway mucus production to be dependent on smooth muscle cell interleukin 4 receptor-alpha (IL-4Ralpha) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4Ralpha(-/lox) control mice, whereas global knockout (IL-4Ralpha(-/-)) and smooth muscle-specific IL-4Ralpha-deficient mice (SM MHC(Cre) IL-4Ralpha(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC(Cre) IL-4Ralpha(-/lox) mice was impaired along with a transient reduction in T-cell numbers in the lung. In vitro treatment of smooth muscle cells with secreted N. brasiliensis excretory secretory antigen (NES) induced IL-6 production. Decreased protein kinase C (PKC) dependent smooth muscle cell proliferation associated with cell cycle arrest was found in cells stimulated with NES. Together, these data demonstrate that both IL 4Ralpha and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections. PMID- 20737004 TI - Final report on carcinogens background document for glass wool fibers. PMID- 20737003 TI - Final report on carcinogens background document for formaldehyde. PMID- 20737005 TI - Final report on carcinogens background document for aristolochic acids. PMID- 20737006 TI - Final report on carcinogens background document for captafol. PMID- 20737007 TI - Final Report on Carcinogens background document for o-nitrotoluene. PMID- 20737008 TI - Final report on carcinogens background document for riddelliine. PMID- 20737009 TI - Final report on carcinogens background document for styrene. PMID- 20737010 TI - As for the Past, as for 2010. PMID- 20737011 TI - Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction. AB - BACKGROUND: In vitro function of stored platelet (PLT) con-centrates was analyzed after applying two different techniques of pathogen reduction technology (PRT) treatment, which could increase cellular injury during processing and storage. METHODS: Nine triple-dose PLT apheresis donations were split into 27 single units designated to riboflavin-UVB (M) or psoralen-UVA (I) treatment or remained untreated (C). Throughout 8 days of storage, samples were analyzed for annexin V release, the mitochondrial transmembrane potential (Deltapsi) and some classical markers of PLT quality (pH, LDH release, hypotonic shock response (HSR)). RESULTS: PLT count and LDH release of all units maintained initial ranges. All units exhibited a decrease in pH and HSR and an increase in annexin V release and Deltapsi disruption. Notably, throughout the entire storage period, annexin V release re-mained lowest in M units. Throughout 7 days of storage, M units remained comparable to C units (p > 0.05), whereas inferior values were observed with I units. Here, differences to C units reached significance by day 1 (pH: p < 0.0001), day 5 (annexin V release: p < 0.014), and day 7 (HSR, Deltapsi: p HO(3) + M in two series of experiments. At temperatures between 55.9 and 79.2 K, the OH radicals, created by pulsed laser photolysis of H(2)O(2) and observed by laser-induced fluorescence, decayed by pseudo-first-order kinetics to effectively zero concentration at longer times. The third-order rate constants derived from these experiments fit the expression: k(3rd)(o) (T) = (4.2 +/- 1.9) * 10(-34) (T/298 K)(-(3.5 +/- 0.3)) cm(6) molecule( 2) s(-1). At temperatures between 87.4 and 99.8 K, rate constants for the association reaction were determined allowing for the significant occurrence of the reverse dissociation reaction. The values of the derived rate constants are consistent with those obtained in the lower temperature range, though the errors are larger. The experimental values of k(3rd)(o) (T) are compared with (a) those for other association reactions involving species of similar complexity, and (b) values of k(3rd)(o) (T) estimated according to both the energy transfer (ET) and the radical-complex (RC) mechanisms. We conclude that the RC mechanism probably makes the major contribution to the association of OH + O(2) at the low temperatures of our experiments. PMID- 20737065 TI - 1,5,9,13-Tetraselena[13]ferrocenophane: synthesis, complexation, crystallographic and electrochemical study. AB - A novel macrocyclic ferrocenophane, 1,5,9,13-tetraselena[13]ferrocenophane (L), was synthesized. Reaction of L with [M(NCMe)(4)](PF(6))(2) (M = Pd and Pt) or [Cu(NCMe)(4)](PF(6)) led to complexes [ML](PF(6))(2) (M = Pd and Pt) or [CuL](PF(6)). The Ag(i) cation induced the formation of a one-dimensional polymer {[AgL](PF(6))}(n) due to its large ionic radius. The structures of L and its four complexes have been determined by X-ray crystallography. Electrochemical studies showed that, in [ML](PF(6))(2) (M = Pd and Pt), the half-wave potential of the 1,1'-ferrocenediyl group shifts to much more positive potentials due to the strong through-space interaction between the two metals (M...Fe). PMID- 20737064 TI - Combination of chiroptical, absorption and fluorescence spectroscopic methods reveals multiple, hydrophobicity-driven human serum albumin binding of the antimalarial atovaquone and related hydroxynaphthoquinone compounds. AB - High-affinity human serum albumin (HSA) binding of the C3-substituted antimalarial 2-hydroxy-1,4-naphthoquinone derivative atovaquone (ATQ) has been demonstrated and studied by circular dichroism (CD), UV/VIS absorption, fluorescence spectroscopy and affinity chromatography methods. The analysis of induced CD data generated upon HSA binding of ATQ revealed two high-affinity binding sites (K(a) ~ 2 * 10(6) M(-1)). CD interaction studies and displacement of specific fluorescent and radioactive marker ligands indicated the contribution of both principal drug binding sites of HSA to complexation of ATQ, and also suggested the possibility of simultaneous binding of ATQ and some other drugs (e.g. warfarin, phenylbutazone, diazepam). Comparison of UV/VIS spectra of ATQ measured in aqueous solutions indicated the prevalence of the anionic species formed by dissociation of the 2-hydroxyl group. HSA binding of related natural hydroxynaphthoquinones, lapachol and lawsone also induces similar CD spectra. The much weaker binding affinity of lawsone (K(a) ~ 10(4) M(-1)) bearing no C3 substituent highlights the importance of hydrophobic interactions in the strong HSA binding of ATQ and lapachol. Since neither drug exhibited significant binding to serum alpha(1)-acid glycoprotein, HSA must be the principal plasma protein for the binding and transportation of 2-hydroxy-1,4-naphthoquinone-type compounds which are ionized at physiological pH values. PMID- 20737070 TI - Exploitation of surface acoustic waves to drive size-dependent microparticle concentration within a droplet. AB - Ultrafast particle and cell concentration is essential to the success of subsequent analytical procedures and the development of miniaturized biological and chemical sensors. Here, surface acoustic wave (SAW) devices were used to excite a MHz-order acoustic wave that propagates into a microlitre droplet to drive spatial concentration and separation of two different sized suspended microparticles. The rapid concentration process, occurring within just three seconds to facilitate spatial partitioning between the two particle species, exploited two acoustic phenomena acting on the suspended particles: the drag force arising from acoustic streaming and the acoustic radiation force, both driving particles in different directions. This study elucidates the very intricate and interesting interplay of physics between fluid drag and acoustic forcing on the particles within a droplet, and, for the first time, demonstrates the existence of a frequency-dependent crossover particle size that can be used to effect species partitioning: depending on the operating frequency of the SAW device and the particle size, it is possible to cause one phenomenon to dominate over the other. A theoretical analysis revealed the extent to which each force would affect the particle trajectory (particle size range: 2-31 MUm), subsequently verified through experimentation. Based on these findings, 6 and 31 MUm polystyrene particles were successfully partitioned in a water droplet using a 20 MHz SAW device. This study reveals the suitability of using acoustic actuation methods for the useful partitioning of particle species within a discrete fluid volume. PMID- 20737071 TI - Studies on the reaction of glutathione and formaldehyde using NMR. AB - Within cells it is proposed that a major mechanism for the metabolism of formaldehyde is via its reaction with glutathione (GSH) to form S hydroxymethylglutathione (HMG), which undergoes subsequent oxidation. In addition to HMG and the previously reported (5R,10S)-5-(carboxymethylcarbamoyl)-7-oxo-3 thia-1,6-diazabicyclo[4.4.1]undecane-10-carboxylic acid (BiGF(2)), NMR studies on the reaction of GSH with formaldehyde reveal two previously unassigned monocyclic structures. The results imply that the biologically relevant reactions between aldehydes and peptides/proteins may be more complex than presently perceived. PMID- 20737072 TI - Anion complexation and sensing using modified urea and thiourea-based receptors. AB - This critical review highlights recent advances in the structurally modified (thio)urea-based receptors for anion complexation and sensing. Modifications of the (thio)urea structure are aimed at a better anion binding in terms of higher binding constant, anion selectivity and feasibility. Major (thio)urea receptors are reviewed as N-alkyl, N-aryl and N-amido/N-amino (thio)ureas. Hints for designing (thio)urea-based receptors for anions are discussed (102 references). PMID- 20737074 TI - Interaction of PqqE and PqqD in the pyrroloquinoline quinone (PQQ) biosynthetic pathway links PqqD to the radical SAM superfamily. AB - pqqD is one of six genes required for PQQ production in Klebsiella pneumoniae. Herein, we demonstrate that PqqD interacts specifically with the radical SAM enzyme PqqE, causing a perturbation in the electronic environment around the [4Fe 4S](+) clusters. This interaction redirects the role for PqqD in PQQ biosynthesis. PMID- 20737075 TI - Complete surface control of peptide nanospheres with detachable and attachable polymer brush layers. AB - The surfaces of biodegradable peptide nanospheres with density-controllable poly(ethylene glycol) (PEG) brush layers were amenable to high levels of control, from hydrophilic 'stealth' properties to hydrophobic adsorptive properties depending on the PEG density in response to environmental conditions 'intelligent' properties that are expected to be useful for novel drug delivery systems. PMID- 20737076 TI - Highly efficient and switchable electron-transfer system realised by peptide assisted J-type assembly of porphyrin. AB - We propose a new strategy for fabrication of a phase-separated bicontinuous system composed of low-molecular donor and acceptor that is built up through coordination-based orientation of pyridylated fullerene on a pi-conjugated zinc porphyrin J-type assembly. This complex system exhibits extremely efficient and switchable fluorescence quenching. PMID- 20737073 TI - Ion pair receptors. AB - Compared with simple ion receptors, which are able to bind either a cation or an anion, ion pair receptors bearing both a cation and an anion recognition site offer the promise of binding ion pairs or pairs of ions strongly as the result of direct or indirect cooperative interactions between co-bound ions. This critical review focuses on the recent progress in the design of ion pair receptors and summarizes the various binding modes that have been used to accommodate ion pairs (110 references). PMID- 20737077 TI - Synthesis of gold nanoparticles in a biocompatible fluid from sputtering deposition onto castor oil. AB - The sputtering of Au targets onto castor oil generates stable spherical gold nanoparticles (AuNPs) of 2.4 to 3.8 nm. The AuNP size increases with the discharge voltage and the mechanism of nucleation and growth are related to the energy of the atoms/clusters ejected from the target. PMID- 20737078 TI - Catalytic intramolecular aromatic C-H alkenylation of arenes with non-activated ketones: synthesis of 4-alkylene quinolin-2-ones. AB - The catalytic intramolecular aromatic C-H alkenylation of arenes with non activated ketone carbonyls has been realized for the first time, leading to the synthesis of antiviral 4-alkylene quinolin-2-ones, where the quaternary carbon adjacent to the ketone carbonyl plays an essential role in this catalytic reaction. PMID- 20737079 TI - Hollow silica nanospheres containing a silafluorene-fluorene conjugated polymer for aqueous TNT and RDX detection. AB - Attachment of a copolymer of silafluorene and fluorene to 100 nm hollow silica nanoparticles provides a new method to detect aqueous TNT and RDX with a low detection limit using the suspended fluorescent nanoshells. PMID- 20737080 TI - Continuous process for fabrication of size controlled polyimide nanoparticles using microfluidic system. AB - A new strategy has been developed for continuous preparation of polyimide nanoparticles within 10 s of short residence time using a system combining a micromixer and a micro heat exchanger, where the particle size can be controlled proportionally simply by varying the concentration of poly(amic acid) (PAA). PMID- 20737081 TI - Self-regeneration of a silylium ion catalyst in carbonyl reduction. AB - The silylium ion-catalysed reduction of carbonyl compounds to the alcohol oxidation level is accomplished by exploiting the unique reactivity of a ferrocenyl-substituted silane. PMID- 20737082 TI - Developing a polymeric semiconductor photocatalyst with visible light response. AB - A facile strategy based on the amidation reaction of anhydride and NH(2) group in carbon nitride polymer is developed to synthesize a new polymeric photocatalyst which responds to visible-light. The high photocatalytic activity may be due to the coupling anhydride groups promoting the separation of the photoinduced electrons and holes. PMID- 20737083 TI - Exact and truncated Coriolis coupling calculations for the S(1D)+HD reaction employing the ground adiabatic electronic state. AB - We present exact quantum differential cross sections and exact and estimated integral cross sections and branching ratios for the title reaction. We employ a time-dependent wavepacket method as implemented in the DIFFREALWAVE code including all Coriolis couplings and also an adapted DIFFREALWAVE code where the helicity quantum number and with this the Coriolis couplings have been truncated. Our exact differential cross sections at 0.453 eV total energy, one of the experimental energies, show good agreement with the experimental results for one of the product channels. While the truncated calculation present a significant reduction in the computational effort needed they overestimate the exact integral cross sections. PMID- 20737084 TI - Synthesis of the core ring system of the stemona alkaloids by cascade condensation, cyclization, intramolecular cycloaddition. AB - Condensation of an aldehyde with an alpha-amino-ester, followed by a tandem process involving cyclization to a seven-membered ring, deprotonation to an intermediate azomethine ylide and intramolecular dipolar cycloaddition gave tricyclic products related to stenine and neostenine. PMID- 20737085 TI - Live celloidosome structures based on the assembly of individual cells by colloid interactions. AB - A new class of colloid structures, celloidosomes, has been developed which represent hollow microcapsules whose membranes consist of a single monolayer of living cells. Two routes for producing these structures were designed based on templating of: (i) air bubbles and (ii) anisotropic microcrystals of calcium carbonate with living cells, which allowed us to fabricate celloidosomes of spherical, rhombohedral and needle-like morphologies. Air microbubbles were templated by yeast cells coated with poly(allylamine hydrochloride) (PAH), then coated with carboxymethylcellulose and rehydrated resulting in the formation of spherical multicellular structures. Similarly, calcium carbonate microcrystals of anisotropic shapes were coated with several consecutive layers of oppositely charged polyelectrolytes to obtain a positive surface charge which was used to immobilise yeast cells coated with anionic polyelectrolyte of their surfaces. After dissolving of sacrificial cores, hollow multicellular structures were obtained. The viability of the cells in the produced structures was confirmed by using fluorescein diacetate. In order to optimize the separation of celloidosomes from free cells magnetic nanoparticles were immobilised onto the surface of templates prior to the cells deposition, which greatly facilitated the separation using a permanent magnet. Two alternative approaches were developed to form celloidosome structures using magnetically functionalised core-shell microparticles which resulted in the formation of celloidosomes with needle-like and cubic-like geometries which follows the original morphology of the calcium carbonate microcrystals. Our methods for fabrication of celloidosomes may found applications in the development of novel symbiotic bio-structures, artificial multicellular organisms and in tissue engineering. The unusual structure of celloidosomes resembles the primitive forms of multicellular species, like Volvox, and other algae and could be regarded as one possible mechanism of the evolutionary development of multicellularity. PMID- 20737086 TI - Matrix-controlled photofragmentation of formamide: dynamics simulation in argon by nonadiabatic QM/MM method. AB - The short-time photodynamics (2 ps) of formamide embedded into an Ar matrix starting from the low-lying singlet excited S(1) (n(0)pi*) and S(2) (pipi*) states were explored using a nonadiabatic photodynamics QM/MM approach. The interaction between formamide and the Ar matrix is taken into account at the MM level by means of Lennard-Jones potentials. This is the first example of exploring photodissociation of formamide with full nonadiabatic dynamics in a matrix and it nicely illustrates importance of considering environmental effects on photodissociation behavior of the peptide bond. It is shown that embedding of the formamide molecule in the argon matrix has strong impact on the outcome of the process. This is illustrated by formation of the 1:1 complex between ammonia and CO and prevention of full separation of the NH(2) and HCO subunits in the NH(2) + HCO radical pair. In addition, the argon matrix strongly influences the lifetime of the S(1) state, which increases by 211 fs relative to the gas phase. PMID- 20737087 TI - Solvent-free microwave-assisted multi-component reaction for preparation of 2 amino-1-aryl-2-(cyclohex-1-enyl)ethanones as precursors of pseudoephedrine analogues. AB - Microwave irradiation of chloroacetylarenes and enamines induced an aza-Darzens reaction followed by rearrangement of the aziridinium intermediate to give (2 amino-3-alkenoyl)arenes that were reduced selectively to syn-beta-aminoalcohols as pseudo-ephedrine analogues. PMID- 20737088 TI - Mesoporous MFI zeolites with self-stacked morphology templated by cationic polymer. AB - Mesoporous MFI zeolites (including M-S-1 and M-ZSM-5) with intracrystal mesopores and self-stacked morphology have been synthesized via a hydrothermal route using cationic polymers as a template. PMID- 20737089 TI - ATP-modulated ionic transport through synthetic nanochannels. AB - Here, we demonstrate an anion controlled molecular gate based on synthetic ion channels modified with polyethyleneimine. For single conical nanochannels, addition of ATP leads to significant decrease in the rectified ion flux, representing the closure of the ionic gate. Complementary experiments performed with nanoporous membranes show that the flux of charged dye (NDS(2-)) through a cylindrical nanochannel array diminishes by the co-addition of ATP in the analyte solution. PMID- 20737090 TI - Visualization of oxygen reduction sites at Pt electrodes on YSZ by means of 18O tracer incorporation: the width of the electrochemically active zone. AB - In this study the electrochemically active region of oxygen incorporation into yttria stabilized zirconia (YSZ) was visualized by means of (18)O tracer incorporation experiments on dense Pt thin film microelectrodes combined with ToF SIMS analysis. The localization and the shape of the incorporation zone were found to strongly depend on the polarization of the electrode. In case of lower overpotentials the active zone next to the three phase boundary (TPB) was frame shaped and located beneath the Pt electrode. Increases in polarization led to an extension of the incorporation zone along the free YSZ surface. Owing to the low temperature of 300-330 degrees C a profile-broadening caused by diffusion in YSZ could be minimized and quantitatively separated from the measured profiles. The TPB-width (i.e. the decay length of electrochemical activity) was determined to be approximately 1.0-1.3 MUm at these temperatures. PMID- 20737098 TI - Infrared spectroscopic study of the amidation reaction of aminophenyl modified Au surfaces and p-nitrobenzoic acid as model system. AB - We have investigated the fundamental amidation reaction by a model system consisting of an electrochemically functionalised Au surface by aminophenyl and 4 nitrobenzoic acid activated by EEDQ. The development of the NO(2) related stretching vibrations with time reveals that the amidation process is very slow at Au surfaces and is completed after about 2 days. PMID- 20737104 TI - Imaging the life and death of tumors in living subjects: Preclinical PET imaging of proliferation and apoptosis. AB - Cancer is characterized by deregulation of cell proliferation and altered cell death apoptosis, which constitutes, in almost all instances, the minimal common platform upon which all neoplastic evolution occurs. The most implicit and clinically attractive anticancer strategies, therefore, consist of eliminating tumor cells by preventing their expansion and ultimately inducing cell death apoptosis. In this context, the non-invasive molecular assessment of tumor cell proliferation and apoptosis status using PET imaging constitutes a major strategy in preclinical studies to assess the efficacy of new anticancer therapeutics using small animal PET imaging, and in clinical settings for the monitoring of treatment responses in patients. For this purpose, a variety of PET tracers targeting specific molecular entities allowing the non-invasive measurement of biological processes, including cell proliferation and apoptosis, are under development for use in preclinical studies and clinical trials to non-invasively image in vivo the lifeline of tumors. PMID- 20737105 TI - Aqueous-phase synthesis of monodisperse plasmonic gold nanocrystals using shortened single-walled carbon nanotubes. AB - Monodisperse gold nanocrystals with unique near-infrared optical properties were synthesized by simple mixing of highly shortened and well disperse single-walled carbon nanotubes and chloroauric acid in water at ambient conditions with a step wise increase of gold ion concentration. PMID- 20737106 TI - Palladium-catalyzed acetoxylation of sp3 C-H bonds using molecular oxygen. AB - Molecular oxygen as oxidant to promote palladium-catalyzed acetoxylation of sp(3) C-H bonds to afford alpha-oxygenated products is reported. PMID- 20737107 TI - A rod packing microporous metal-organic framework with open metal sites for selective guest sorption and sensing of nitrobenzene. AB - A microporous MOF [Zn(4)(OH)(2)(1,2,4-BTC)(2)] (1,2,4-BTC = Benzene-1,2,4 tricarboxylate) with two immobilized open metal Zn(2+) sites was obtained by solvothermal reaction, which exhibits highly selective guest sorption and sensing of nitrobenzene. PMID- 20737108 TI - Synthesis of K48-linked diubiquitin using dual native chemical ligation at lysine. AB - The dual native chemical ligation at lysine strategy was revised by replacing the acid-labile Cbz protecting group with photolabile NVOC at the 4-mercaptolysine side chain. The optimized strategy was subsequently applied to the synthesis of K48-linked diubiquitin. PMID- 20737109 TI - Accelerated hole transfer across a molecular double barrier. AB - We report on a dyad in which photoinduced hole transfer through a non-uniform molecular double barrier is more than one order of magnitude more rapid than hole transfer across a comparable uniform (rectangular) tunneling barrier. PMID- 20737110 TI - High-nuclearity, mixed-valence Mn17, Mn18 and {Mn62}n complexes from the use of triethanolamine. AB - The use of both azide and triethanolamine, with or without the presence of carboxylate groups, has provided new Mn(17), Mn(18) and {Mn(62)}(n) complexes with aesthetically-pleasing cage, layered, and linked-chain-type structures; two are also new single-molecule magnets. PMID- 20737111 TI - An electrochemical tandem reaction: one-pot synthesis of homoallylic alcohols from alcohols in aqueous media. AB - A tandem electrosynthesis of homoallylic alcohols from alcohols in one-pot was realized. In virtue of this one-pot electrosynthesis, the traditional reaction substrates of allylation were broadened from carbonyl compounds to alcohols. PMID- 20737112 TI - Parathyroid scintigraphy protocols in Finland in 2010. Results of the query and current status. AB - The GOAL of this study was to describe current clinical parathyroid scintigraphy (PS) protocols in Finland. METHODS: all departments of nuclear medicine in Finland were contacted, and instructions regarding PS were requested. RESULTS: instructions regarding PS were received from all of the departments that perform PS (n = 19). Seven hundred and sixty-nine PS studies were performed in 2009 (between 7 and 209 per hospital). Three methods of PS were used. The dual-phase method with (99m)Tc-sestamibi is used in seven hospitals, the dual-tracer method with (123)I/(99m)Tc-sestamibi in eleven, and (99m)TcO4/(99m)Tc-sestamibi in one hospital. The activities of 99mTc-sestamibi, 123I and (99m)TcO4 were 150-800 MBq, 10-30 MBq and 50 MBq, respectively. The anterior image with parallel-hole collimators, the anterior image with pinhole collimator, the oblique angles with pinhole collimator, SPECT and hybrid CT with SPECT were acquired in 84%, 26%, 16%, 63%, and 42% of the hospitals, respectively. Because the imaging techniques were combined, one to four acquisitions were performed per patient. Scatter and attenuation correction were used in five protocols. A correction for crosstalk of (123)I and (99m)Tc gamma energies was not used, but the amount of crosstalk was decreased by using narrow or asymmetric energy windows in all dual isotope protocols. CONCLUSION: 19 hospitals used 18 different study protocols. Thus, significant variability exists in the current practice of PS in Finland. The protocols should be tested with known phantoms to determine any differences in sensitivities for detecting small active structures. Further studies with phantoms are needed to determine the optimal imaging techniques. The results of these phantom studies will provide guidelines for proposing national recommendations for PS. PMID- 20737113 TI - Effects of swimming on spirometric parameters and bronchial hyperresponsiveness in children and adolescents with moderate persistent atopic asthma. AB - OBJECTIVE: To investigate the medium-term benefits of a swimming program in schoolchildren and adolescents with moderate persistent atopic asthma (MPAA). METHODS: A randomized, prospective study of children and adolescents (age 7-18 years) with MPAA was carried out at the Hospital de Clinicas of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil. After a 1-month run-in period, 61 patients (34 female) were randomized into two groups, a swimming group (n = 30) and a control group (n = 31), and followed for 3 months. Both patient groups received inhaled fluticasone (dry powder, 250 mcg twice a day) and salbutamol as needed. The swim training program consisted of two weekly classes over a 3-month period for a total of 24 sessions. Both groups underwent spirometric assessment and methacholine challenge test--provocative concentration of methacholine causing a 20% fall in FEV1 (PC20)--before and after the study period. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured only in the swimming group. RESULTS: Significant increases in PC20 (pre-training, 0.31+/-0.25; post-training, 0.63+/-0.78; p = 0.008), MIP (pre-training, 67.08+/ 17.13 cm H2O; post-training 79.46+/-18.66; p < 0.001), and MEP (pre-training, 71.69+/-20.01 cm H2O; post-training, 78.92+/-21.45 cm H2O; p < 0.001) were found in the swimming group. CONCLUSION: Children and adolescents with MPAA subjected to a swim training program experienced a significant decrease in bronchial hyperresponsiveness, as determined by increased PC20 values, when compared with asthmatic controls who did not undergo swim training. Participants in the swimming group also showed improvement in elastic recoil of the chest wall. PMID- 20737115 TI - Responses of freshwater molluscs to environmental factors in Southern Brazil wetlands. AB - Freshwater molluscs play an important role in aquatic ecosystems, providing food for many fish species and vertebrates. Investigations on factors that determine mollusc species richness and distribution in wetland systems are scarce in the Neotropical region. The main goal of this study was to determine how much variation in mollusc richness and composition is explained by area, hydroperiod, altitude, water conductivity, and dominant aquatic vegetation. This survey was performed in an extensive area of a Neotropical region (approximately 280,000 km(2) in southern Brazil), with a large number of wetland systems (111) and covering a wide gradient of altitude and wetland surface area. The mollusc richness was positively associated with wetland area and negatively associated with altitude. The richness and composition of the freshwater molluscs were similar between permanent and intermittent wetlands and it did not differ significantly between aquatic bed and emergent wetlands. The first three axes of CCA explained 16.2% of the total variation in the composition of the freshwater mollusc observed. The variation in the composition had a correlation with wetland area, altitude and water conductivity. Our results showed that the wetlands are important habitats for molluscs in southern Brazil, and that the richness and the composition of molluscs were associated with area, altitude, water conductivity and dominant vegetation. PMID- 20737114 TI - Factors predicting early discontinuation of exclusive breastfeeding in the first month of life. AB - OBJECTIVE: To investigate factors associated with discontinuation of exclusive breastfeeding in the first month of lactation, in the city of Feira de Santana, Brazil. METHODS: Cohort study with follow-up of 1,309 mother-child pairs selected from all maternities in the municipality. Data were collected in hospital and in home visits during the first month of life. Logistic regression analysis was used to examine the relationship between outcome and variables of interest. RESULTS: Lack of prior breastfeeding experience (PR 1.24; 95%CI 1.75-1.43), cracked nipples (PR 1.25; 95%CI 1.09-1.43), use of fixed breastfeeding schedules (PR 1.42; 95%CI 1.09-1.84) and pacifier use (PR 1.53; 95%CI 1.34-1.76) were identified as factors predicting discontinuation of exclusive breastfeeding. CONCLUSIONS: Measures to prevent early discontinuation of exclusive breastfeeding must focus on women without breastfeeding experience and include prevention of nipple trauma, encourage breastfeeding on demand, and discourage the use of pacifiers. PMID- 20737116 TI - Catch-per-unit-effort: which estimator is best? AB - In this paper we examine the accuracy and precision of three indices of catch-per unit-effort (CPUE). We carried out simulations, generating catch data according to six probability distributions (normal, Poisson, lognormal, gamma, delta and negative binomial), three variance structures (constant, proportional to effort and proportional to the squared effort) and their magnitudes (tail weight). The Jackknife approach of the index is recommended, whenever catch is proportional to effort or even under small deviations from proportionality assumption, when a ratio estimator is to be applied and little is known about the underlying behaviour of variables, as is the case for most fishery studies. PMID- 20737117 TI - Biological monitoring of lotic ecosystems: the role of diatoms. AB - Increasing anthropogenic influence on lotic environments as a result of civilisation has captured public interest because of the consequent problems associated with deterioration of water quality. Various biological monitoring methods that provide a direct measure of ecological integrity by using the response of biota to environmental changes have been developed to monitor the ecological status of lotic environments. Diatoms have been used extensively in this regard and this review attempts to summarise the basic concepts associated with biological monitoring using benthic diatoms. Where possible, examples from work carried out in Brazil are used. PMID- 20737118 TI - [Guidelines on HIV/AIDS]. PMID- 20737119 TI - [Diagnosis of bacterial vaginosis in women attending a family planning clinic in the Metropolitan Region of Chile]. AB - In order to determine the prevalence of bacterial vaginosis (BV) among women attending a family health Center and to evaluate the accuracy of Amsel's diagnostic procedure relative to Nugent scoring for diagnosing this condition, we obtained vaginal specimens from 100 women under 50 years attending a FPC from April to November of 2006. Women were enrolled consecutively on a schedule basis and were not selected by symptoms of genital infection. VB was diagnosed in 32% women, without significant differences by age (p=0,114). 87.5% women declared one sexual partner in the last 6 months. The Amsel's method had a sensitivity of 62.1%, and a specificity of 92.3%, with positive and negative predictive values of 81.8% and 83.3% respectively, being the presence of clue cells the most accurate parameter. Nevertheless, the lack of microscopes in the clinical practice limits the use of the Amsel's criteria. In conclusion, VB is a prevalent infection in the study population, being not associated with age or sexual activity. Diagnosis should be performed by the Nugent method. PMID- 20737122 TI - [Serratia marcescens]. PMID- 20737121 TI - [Clinical use of diagnostic tests (Part 1): Analysis of the properties of a diagnostic test]. AB - Diagnostic tests are widely used in clinical practice. Qualitative analysis of diagnostic test properties (validity, reproducibility and safety) has been systematized using clinical epidemiology tools that have introduced a series of concepts such as sensitivity, specificity and predictive values. Based on data reported by a clinical investigation, the present article illustrates the theoretical background underlying these concepts, explains the methodology for their calculation, and analyzes their main strengths and limitations. A second article (Part 2: Clinical application and usefulness of a diagnostic test), describes the manner in which information provided by a test should be applied in order to correctly resolve a clinical dilemma. PMID- 20737123 TI - [Cryptosporidium parvum in wild gastropods as bioindicators of fecal contamination in terrestrial ecosystems]. AB - Cryptosporidium sp oocysts were detected in snails (Helix aspersa Miller) and slug (Deroceras reticulatum Miller) from the Valparaiso Region, Chile. Snails and slug were collected from public squares and private domestic gardens. Cryptosporidium sp oocysts were recovered from faeces of both species. Ziehl Neelsen stain, nested PCR, and sequencing analysis demonstrated a profile similar to that described for genotype C or 2 of the parasite. These results demonstrate that snails and slug could act as a reservoir and mechanic vector of C. parvum infection for humans and animals. Moreover, gastropods could serve as bioindicators of fecal soil contamination. PMID- 20737125 TI - [Historical notes on the management of infection during the development of surgery]. AB - Surgery and medicine have not evolved in parallel. There have been discrepancies, bellicosity, contempt and even separate university studies during a long time. The Saint Cosme Brotherhood, founded to supervise the professional practice of barbers (short robe surgeon-barbers) in France in 1260, was opposed by the Faculty of Medicine in Paris. The conflicting interests of the university, Brotherhood and Barbers, that persisted until the 18 th century, impaired the progress of surgery. In the first half of the 19 th century, the advance of surgery continued facing pain, hemorrhage and infection. The control of the latter had to consider antisepsis, asepsis and finally the appearance of antimicrobial substances, sulfonamides and antibiotics that allowed surgeons to approach and solve major problems of the specialty. PMID- 20737124 TI - [Isospora belli infection in HIV positive patients: report of two cases and literature review]. AB - Isosporosis is an infection caused by parasitic protozoa of the genus Isospora, coccidia affecting various different vertebrate species, including humans. It is an uncommon infection in our country and it is not a zoonosis. We present two cases of Isospora belli infection in HIV positive patients from the Valparaiso region. We discuss the clinical events caused by this agent, its epidemiology, cases published in the local and foreign literature, as well as its treatment and prevention measures. PMID- 20737127 TI - [Acquired immunodeficiency syndrome]. PMID- 20737129 TI - [Updated acute community-acquired pneumonia in adults: Guidelines for initial antimicrobial therapy based on local evidence from the South American Working Group (ConsenSur II)]. AB - Community-acquired pneumonia (CAP) in adults is probably one of the infections affecting ambulatory patients for which the highest diversity of guidelines has been written worldwide. Most of them agree in that antimicrobial therapy should be initially tailored according to either the severity of the infection or the presence of comorbidities and the etiologic pathogen. Nevertheless, a great variability may be noted among the different countries in the selection of the primary choice in the antimicrobial agents, even for the cases considered as at a low-risk class. This fact may be due to the many microbial causes of CAP and specialties involved, as well as the different health-care systems effecting on the availability or cost of antibiotics. However, many countries or regions adopt some of the guidelines or design their own recommendations regardless of the local data, probably because of the scarcity of such data. This is the reason why we have developed a guideline for the initial treatment of CAP by 2002 upon the basis of several local evidences in South America (ConsenSur I). However, several issues deserve to be currently rediscussed as follows: certain clinical scores other than the Physiological Severity index (PSI) have become more popular in clinical practice (i.e. CURB-65, CRB-65); some pathogens have emerged in the region, such as community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and Legionella spp; new evidences on the performance of the rapid test for the etiologic diagnosis in CAP have been reported (eg. urinary Legionella andpneumococcus antigens); new therapeutic considerations needs to be approached (i.e. dosage reformulation, duration of treatment, emergence of novel antibiotics and clinical impact of combined therapy). Like in the first version of the ConsenSur (ConsenSur I), the various current guidelines have helped to organize and stratify the present proposal, ConsenSur II. PMID- 20737130 TI - [New approach to photoepilation. Diode laser with SHR (Super Hair Removal) compared to alexandrite laser]. AB - BACKGROUND: Photoepilation has been an essential field of application of dermatologic laser therapy for many years. The present article evaluates whether the use of a new operation mode of a long-pulsed diode laser can be effective, nearly painless, with few side effects and independent of the skin type. To this aim, its use has been compared to an established method of photoepilation. MATERIAL AND METHODS: In a controlled prospective study with 18 (?=12, ?=6) patients aged between 22 and 58 years, the effects of photoepilation with the long-pulsed alexandrite laser and the long-pulsed diode laser, operated in the Super Hair Removal mode (SHR), were compared. RESULTS: The alexandrite laser is slightly more effective with fair skin types; the SHR mode is clearly more effective with dark skin types. Regarding painfulness, the SHR mode is clearly superior. In terms of speed, the two systems are comparable. The alexandrite laser is more user-friendly because of its light and small handpiece. CONCLUSION: The major advantages of the SHR mode are its effectiveness in dark skin types and its lack of pain. The alexandrite laser is slightly more effective with fair skin types, slightly faster and its handling is considerably more comfortable. None of the two systems has yet brought about a breakthrough with fair hair. PMID- 20737131 TI - [International rhinosurgery]. PMID- 20737132 TI - [Long-term results after Kirschner wire pinning of distal radius fractures]. AB - BACKGROUND: The purpose of this study was to investigate the outcome after K-wire pinning of distal radius fractures with a minimum follow-up period of 5 years. PATIENTS AND METHODS: A total of 189 patients with an isolated fracture of the distal radius were treated between 1998 and 2002 and 100 were evaluated at an average of 5.6 years after the surgery. At the final follow-up examination all patients were assessed clinically and bilateral radiographs were taken. RESULTS: Of the patients 37 had an A type fracture, 8 a B type and 55 a C type according to the AO classification and 86% achieved good to excellent results based on the Gartland and Werley and Disability of Arm, Shoulder, Hand (DASH) scores. Patients were divided in to two groups. Group A included patients with fractures with a primary palmar inclination greater than -20 degrees (range -20 degrees to 10 degrees ) and group B with fractures with a primary palmar inclination less than 20 degrees (range -45 degrees to -20 degrees ). Secondary loss of reduction was significant higher in group B compared to group A (group B: 8.3 degrees , group A: 1.6 degrees , p <0.05). In 8 out of 11 patients of group B an osteoporosis was found. Functionally no difference was detected between the two groups. Radial shortening of over 4 mm resulted in a significant reduction (36%) of prosupination and supination. No other influence of the radiological results on the functional or subjective outcome was found. Superficial infection of the K wire occurred in 6 cases, whereas early K-wire removal was performed in 2 cases, 8 patients complained of dysesthesia in the area of the superficial radial nerve and 5 patients developed an early stage of the complex regional pain syndrome. CONCLUSION: K-wire pinning cannot be routinely recommended. However, in cases of A2, A3 and C1 fractures, a primary dorsal dislocation of less than -20 degrees and in patients without low bone mineral density, K-wire pinning leads to a high rate of radiological, functional good results. PMID- 20737133 TI - [DuromTM hip resurfacing. Short- to midterm clinical and radiological outcome]. AB - BACKGROUND: Modern hip resurfacing as an alternative for stemmed total hip replacement therapy is associated with a specific risk profile. The aim of this study was therefore to assess the short- to midterm clinical and radiological outcome after introduction of the DuromTM Hip Resurfacing prosthesis in a consecutive series. MATERIALS AND METHODS: A total of 132 hips (119 patients, 34 female, mean age 48+/-8,3 years) were evaluated functionally (Harris Hip Score, UCLA and Tegner activity scores) and radiologically with a mean follow-up period of 29 (6-60) months. Furthermore, preoperative ASA- and Charnley-scores, perioperative parameters as well as complications were registered. RESULTS: During the observation period the Harris Hip Score improved by a mean of 36.6 points to 92.5+/-11.6 points (p<0.01). ULCA and Tegner scores improved by a mean of 3.1 and 1.6 to 7.1 and 4.0 points, respectively. Three patients (2.3%) needed revision surgery due to periprosthetic fracture, prosthesis infection, and aseptic loosening of the femoral component. In four patients (3.1%) an initial migration of the acetabular component not requiring surgical revision was observed radiologically. CONCLUSION: The DuromTM Hip Resurfacing prosthesis demonstrated a low revision rate and a good mid-term functional and radiological outcome. Due to acetabular cup migrations in a small number of patients we now use an implant with modified surface design. PMID- 20737135 TI - A randomized controlled trial of antenatal pelvic floor exercises to prevent and treat urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: the aim of the study was to evaluate the effect of antenatal pelvic floor muscle exercise (PFME) in the prevention and treatment of urinary incontinence during pregnancy and postpartum period. METHODS: three hundred women were randomly assigned to the PFME group and control group. Urinary symptoms were measured by Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire-7 (IIQ-7), and question of self-reported urinary incontinence. Questionnaire scores of the PFME and the control groups were compared and analyzed. RESULTS: during late pregnancy and the postpartum period, the PFME group had significantly lower total UDI-6 and IIQ-7 scores; their self report rate of urinary incontinence was also less than the control group. Additionally, we found whether in PFME or control, women who delivered vaginally were more likely to develop postpartum urinary leakage than women who delivered by cesarean section. CONCLUSIONS: PFME applied in pregnancy is effective in the treatment and prevention of urinary incontinence during pregnancy, and this effect may persist to postpartum period. PMID- 20737134 TI - Single versus double-row repair of the rotator cuff: does double-row repair with improved anatomical and biomechanical characteristics lead to better clinical outcome? AB - PURPOSE: Several techniques for arthroscopic repair of rotator cuff defects have been introduced over the past years. Besides established techniques such as single-row repairs, new techniques such as double-row reconstructions have gained increasing interest. The present article therefore provides an overview of the currently available literature on both repair techniques with respect to several anatomical, biomechanical, clinical and structural endpoints. METHODS: Systematic literature review of biomechanical, clinical and radiographic studies investigating or comparing single- and double-row techniques. These results were evaluated and compared to provide an overview on benefits and drawbacks of the respective repair type. RESULTS: Reconstructions of the tendon-to-bone unit for full-thickness tears in either single- or double-row technique differ with respect to several endpoints. Double-row repair techniques provide more anatomical reconstructions of the footprint and superior initial biomechanical characteristics when compared to single-row repair. With regard to clinical results, no significant differences were found while radiological data suggest a better structural tendon integrity following double-row fixation. CONCLUSION: Presently published clinical studies cannot emphasize a clearly superior technique at this time. Available biomechanical studies are in favour of double row repair. Radiographic studies suggest a beneficial effect of double-row reconstruction on structural integrity of the reattached tendon or reduced recurrent defect rates, respectively. PMID- 20737136 TI - Congenital vesicovaginal fistula with transverse vaginal septum presenting as menouria-a rare case report and brief review. AB - Menouria due to congenital vesicovaginal fistula is rare entity. We report a case of a 22-year-old female who presented with menouria. On evaluation, she had congenital vesicovaginal fistula and obstructing complete vaginal septum. McIndoe vaginoplasty and fistula repair through vaginal route was performed. PMID- 20737137 TI - Role of Nitrosomonas europaea NitABC iron transporter in the uptake of Fe3+ siderophore complexes. AB - Nitrosomonas europaea has a single three-gene operon (nitABC) encoding an iron ABC transporter system (NitABC). Phylogenetic analysis clustered the subunit NitB with Fe(3+)-ABC transporter permease components from other organisms. The N. europaea strain deficient in nitB (nitB::kan) grew well in either Fe-replete or Fe-limited media and in Fe-limited medium containing the catecholate-type siderophore, enterobactin or the citrate-based dihydroxamate-type siderophore, aerobactin. However, the nitB::kan mutant strain was unable to grow in Fe-limited media containing either the hydroxamate-type siderophores, ferrioxamine and ferrichrome or the mixed-chelating type siderophore, pyoverdine. Exposure of N. europaea cells to a ferrichrome analog coupled to the fluorescent moiety naphthalic diimide (Fhu-NI) led to increase in fluorescence in the wild type but not in nitB::kan mutant cells. Spheroplasts prepared from N. europaea wild type exposed to Fhu-NI analog retained the fluorescence, while spheroplasts of the nitB::kan mutant were not fluorescent. NitABC transports intact Fe(3+) ferrichrome complex into the cytoplasm and is an atypical ABC type iron transporter for Fe(3+) bound to ferrioxamine, ferrichrome or pyoverdine siderophores into the cytoplasm. The mechanisms to transport iron in either the Fe(3+) or Fe(2+) forms or Fe(3+) associated with enterobactin or aerobactin siderophores into the cell across the cytoplasmic membrane are as yet undetermined. PMID- 20737139 TI - Multi-walled carbon nanotubes as solid-phase extraction adsorbent for the ultra fast determination of chloramphenicol in egg, honey, and milk by fused-core C18 based high-performance liquid chromatography-tandem mass spectrometry. AB - In the present work, a high-performance liquid chromatography-tandem mass spectrometry method has been developed for the residue analysis of chloramphenicol (CAP) in several food matrices. Following the addition of D(5) CAP as internal standard, egg, honey, and milk were extracted and cleaned by means of solid-phase extraction, utilizing multi-walled carbon nanotubes as sorbent. The extracts were separated on a Halo fused-core C18 column (50 mm * 2.1 mm, 2.7 MUm) and quantified by a 4000 Q-trap mass spectrometer equipped with a TurboIonSprayTM interface using electrospray ionization and multiple-reaction monitoring mode. The method validation was performed according to the criteria of Commission Decision 2002/657/EC. The decision limit (CCalpha) and detection capability (CCbeta) of CAP in milk were calculated for m/z 320.8 > 151.9. Due to the existence of slight signal suppression, quantification was performed by matrix-matched calibration curves, ranging from 0.1 to 100 ng mL(-1), with regression coefficients of 0.9993, 0.9998, and 0.9997 for egg, honey, and milk, respectively. Mean recoveries of the CAP ranged from 95.8% to 102.3%, with the corresponding intra- and inter-day variation (relative standard deviation) less than 7.13% and 8.89%, respectively. The limit of detection and limit of quantification of the method were also reported. This method successfully applied to several food matrixes (egg, honey, and milk) and can serve as a monitoring tool to avoid unacceptable levels of residues of CAP entering the food chain. PMID- 20737138 TI - Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos. AB - The aim of the study is to examine the cancer-predictive values of SMRP (soluble mesothelin-related peptides), CA125, and CYFRA21-1 as potential tumor markers for lung cancer and malignant mesothelioma in a cohort of workers formerly exposed to asbestos. A voluntary surveillance program has been established for German workers with former asbestos exposure. A subgroup of 626 subjects with a mean age of 63 years (range 53-70 years) at baseline was enrolled in an extended health examination program with high-resolution computer tomography (HRCT) of the chest and blood drawing between 1993 and 1997. Serum concentrations of SMRP, CA125, and CYFRA21-1 were measured in archived serum samples in 2005 and 2006. A mortality follow-up was conducted through 2007. So far, 12 cases with lung cancer and 20 cases with malignant mesothelioma have been observed in this cohort. The average time between sample collection and diagnosis was 4.7 years. Analyzed biomarkers showed low sensitivities (5-25%) and positive predictive values (4-30%) for both cancer sites. Marker combinations resulted in sensitivities between 5 and 50% and positive predictive values ranging from 3 to 14%. Even in those cases, where biomarker concentrations were available within 36 months before diagnosis, no trend for increasing biomarker levels was observed. The analyzed tumor markers were characterized by high specificities, but low sensitivities. SMRP, CA125, and CYFRA21-1 alone or in combination were less suitable to serve as predictors for the diagnosis of lung cancer or malignant mesothelioma. However, a prospective study with annual sampling might reveal a better predictive value of these markers. PMID- 20737140 TI - Increases in hip and spine bone mineral density are predictive for vertebral antifracture efficacy with ibandronate. AB - The relationship between bisphosphonate-induced bone mineral density (BMD) gains and antifracture efficacy remains to be fully elucidated. Data from two antifracture studies were analyzed. Postmenopausal osteoporotic women received oral (2.5 mg daily, 20 mg intermittent) or intravenous (0.5 mg, 1 mg quarterly) ibandronate. Outcome measures included moving averages plots and logistic regression analyses of the relationship between BMD change and vertebral fracture rate. In moving averages plots, ibandronate-induced BMD gains were consistently associated with decreased fracture rates. In the oral study, total-hip BMD increases at years 2 and 3 and lumbar spine BMD increases at year 3 were associated with 3-year vertebral fracture rate (relative risk reduction [RRR] at year 3 for 1% change from baseline: hip, 7.9% [95% CI 2.1-13.5%, P = 0.0084]; lumbar spine, 4.7% [-0.1% to 9.3%, P = 0.0565]). In the intravenous study, total hip BMD increases at years 1, 2, and 3 and lumbar spine BMD increases at years 2 and 3 were significantly associated with vertebral fracture rate (RRR at year 3 for 1% change from baseline: hip, 11.6% [7.0-16.0%, P < 0.0001]; lumbar spine, 6.9% [2.9-10.6%, P = 0.0008]). In a pooled analysis, changes in total-hip and lumbar spine BMD were associated with 3-year vertebral fracture risk reduction and explained a substantial proportion of the antifracture effect (23-37% at 2 and 3 years). This analysis suggests that ibandronate-induced BMD gain in postmenopausal osteoporotic women is associated with vertebral fracture risk reduction. PMID- 20737141 TI - The need for new regulations on randomized clinical trials in surgical treatments. PMID- 20737142 TI - Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy. AB - INTRODUCTION: We performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies. METHODS: Nineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging. RESULTS: There was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P < 0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P. CONCLUSION: These results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications. PMID- 20737143 TI - Long-term outcome in patients treated for benign dural arteriovenous fistulas of the posterior fossa. AB - INTRODUCTION: Dural arteriovenous fistula (dAVF) draining into a dural sinus without recruitment of cortical veins is regarded as relatively benign lesion and treatment is advocated only if the patient is severely affected by the symptoms. The aim of this study was to compare the clinical outcomes in patients who received endovascular treatment or no treatment, respectively. METHODS: Twenty one patients presented consecutively with pulsating tinnitus as leading symptom and with angiographically proven dAVF at the transverse or sigmoid sinus (Borden I). Nine patients underwent different types of endovascular embolisation, and 12 patients were not treated. After a median follow-up period of 2.3 years, outcome was evaluated by assessing the patients' symptoms and scores on the mRS, EQ-5D, SF-36 and HIT-6 scales. RESULTS: Complete long-term closure of the dAFV was achieved in two out of nine cases; subtotal occlusion was found in seven patients. Pulsating tinnitus persisted less frequently in treated than in untreated patients. Neurologic symptoms occurred in both groups. Neither these findings nor the clinical outcome and scores on the quality-of-life scales varied substantially between the two groups. CONCLUSION: Partial treatment did not resolve the clinical symptoms of patients with "benign" dural AVF in the follow up and was not clearly superior to conservative management. These results suggest that embolisation should be offered only if there is a possibility of a complete cure without major periinterventional risks. Further studies should be performed to assess the risk-benefit ratio of pursuing more aggressive treatment strategies in patients with unbearable symptoms. PMID- 20737144 TI - Can induced hypothermia be assured during brain MRI in neonates with hypoxic ischemic encephalopathy? AB - Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1 degrees C (range: -0.8 to 0.8 degrees C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. PMID- 20737145 TI - Fetal tracheolaryngeal airway obstruction: prenatal evaluation by sonography and MRI. AB - We reviewed the sonographic and MRI findings of tracheolaryngeal obstruction in the fetus. Conditions that can cause tracheolaryngeal obstruction include extrinsic causes such as lymphatic malformation, cervical teratoma and vascular rings and intrinsic causes such as congenital high airway obstruction syndrome (CHAOS). Accurate distinction of these conditions by sonography or MRI can help facilitate parental counseling and management, including the decision to utilize the ex utero intrapartum treatment (EXIT) procedure. PMID- 20737147 TI - Magnetic resonance imaging appearance of anterior cruciate ligament reconstruction using Calaxo screws. AB - Bioabsorbable interference screws are commonly used to secure the graft during anterior cruciate ligament (ACL) reconstruction, in part because they result in less image degradation on subsequent magnetic resonance imaging (MRI). However, some bioabsorbable screws are associated with abnormalities on MRI examination not reported with metallic interference screws. We describe a finding on knee MRI examination after ACL reconstruction using a polylactide carbonate (PLC) bioabsorbable screw that we believe to be previously unreported with any other bioabsorbable screws. The finding raised suspicion of hemorrhage or infection, neither of which were present clinically. Analysis of tissue from the tibial tunnel suggested an explanation for the MRI finding: calcite crystals. An additional five patients with knee MRI examinations after ACL reconstruction using a PLC screw were reviewed and correlated with clinical findings with four having similar imaging abnormalities present. The PLC (Calaxo screw, Smith and Nephew, Andover, MA) screw used in these patients has been recalled in the United States and Europe by the manufacturer after a greater than expected incidence of adverse reactions, and legal action may be pending. PMID- 20737149 TI - Preclinical pharmacokinetic, toxicological and biomarker evaluation of SR16157, a novel dual-acting steroid sulfatase inhibitor and selective estrogen receptor modulator. AB - PURPOSE: SR16157 is a novel dual-acting inhibitor of estrogen action that irreversibly inhibits the estrogen biosynthetic enzyme steroid sulfatase (STS) and releases the selective estrogen receptor modulator SR16137, which blocks the estrogen receptor. SR16157 is a promising agent for the endocrine therapy of breast cancer. We conducted preclinical in vivo toxicity evaluations to determine the maximum-tolerated dose (MTD), target organ(s) of toxicity, reversibility, dose-limiting toxicity, no observable adverse effect level (NOAEL), and toxicokinetics (TK) and to investigate a potential biomarker for use in SR16157 clinical trials. METHODS: SR16157 was administered to female Fischer 344 rats or beagle dogs by oral gavage (po) or capsule. Intravenous (iv) groups were included for the determination of bioavailability. Endpoints evaluated included clinical observations, body weights, hematology, serum chemistry, pharmacokinetics, TK, pathology of tissues, and STS activity in liver, or peripheral blood mononuclear cells (PBMCs). RESULTS: For rats, the MTD (i.e., the highest dose that did not cause lethality but produced toxicity) was 33 mg/kg/day (198 mg/m(2)/day), and the NOAEL was <10 mg/kg/day (60 mg/m(2)/day). For dogs, the MTD was estimated to exceed 10 mg/kg/day (200 mg/m(2)/day), and the NOAEL was estimated to be at or above 2.5 mg/kg/day (50 mg/m(2)/day). CONCLUSIONS: Our studies demonstrate that SR16157 has excellent pharmacokinetic properties and an acceptable toxicological profile. Modulation of STS activity in PBMCs appeared to be a possible biomarker for use in future clinical trials of SR16157. PMID- 20737150 TI - Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry. AB - PURPOSE: The blood-brain barrier discriminates the access of several molecules to the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine pretreatment, to allow doxorubicin accumulation in the brain in an animal model. METHODS: Rats were pretreated with different doses of intraperitoneal morphine before injection of doxorubicin (12 mg/kg). Quantitative analysis of doxorubicin was performed by mass spectrometry. Acute heart and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. RESULTS: The concentration of doxorubicin was significantly higher in all brain areas of rats pretreated with morphine than in control tissues (P < 0.001). This was evident only at therapeutic morphine dose (10 mg/kg, three times over 24 h), while lower doses (2.5 and 5 mg/kg) were not associated with doxorubicin accumulation. Pretreatment with morphine did not induce an elevation of LDH activity or of lipid peroxidation compared to controls. CONCLUSION: Our data suggest that morphine pretreatment is able to allow doxorubicin penetration inside the brain, by modulating the blood-brain barrier. This is not associated with acute cardiac or renal toxicity. These preliminary results will enable us to generate novel therapeutic approaches to refractory or recurrent brain tumors, and might be useful in other human diseases of the central nervous system in which molecules usually stopped by the blood-brain barrier may have a therapeutic impact. PMID- 20737151 TI - [TNM 2010. What's new?]. AB - In the seventh edition of the TNM Classification of Malignant Tumours there are several entirely new classifications: upper aerodigestive mucosal melanoma, gastrointestinal stromal tumour, gastrointestinal carcinoid (neuroendocrine tumour), intrahepatic cholangiocarcinoma, Merkel cell carcinoma, uterine sarcomas, and adrenal cortical carcinoma. Significant modifications concern carcinomas of the oesophagus, oesophagogastric junction, stomach, appendix, biliary tract, lung, skin, prostate and ophthalmic tumours, which will be not addressed in this article. For several tumour entities only minor changes were introduced which might be of importance in daily practice. The new classifications and changes will be commented on without going into details. PMID- 20737153 TI - Silencing of the MYCN gene by siRNA delivered by folate receptor-targeted liposomes in LA-N-5 cells. AB - INTRODUCTION: MYCN amplification is highly associated with malignancy and correlates with poor prognosis in patients with neuroblastoma. MATERIALS AND METHODS: We developed a novel liposome-MYCN siRNA-folic acid complex, and the transfection efficacy was measured in LA-N-5 cells by cy-3 fluorescence density in each microgram of protein from the transfected cell lysate. MYCN expression and cell growth were studied with quantitative RT-PCR and MTT assays, and the expression of MYCN protein was studied with Western blot, respectively. An SCID mouse model with subcutaneous LA-N-5 xenografted tumor was established. The animals were divided into four groups (n = 5) and they were peritoneally injected with liposome-encapsulated MYCN siRNA (siRNA 125 MUg/kg/day), lipid-encapsulated control siRNA, MYCN siRNA, or liposome only, respectively, for 5 consecutive days. The animals were killed 24 h after the last injection, and the expression of MYCN mRNA in tumor tissue was detected by RT-PCR. RESULTS: Our results are as follows: the transfect efficacy reached 1808.5 +/- 140.2 pg siRNA/MUg protein in LA-N-5 lysates after treatment with 100 nmol/L MYCN siRNA encapsulated with lipid, and fluorescence could be visualized in 92% of LA-N-5 cells after transfection. At 72 h post-transfection, MYCN mRNA expression in LA-N-5 cells was downregulated by 79.2%, MYCN protein was downregulated by 71.3% and cell growth was inhibited by 66.2%, as measured by MTT assay. In the in vivo study, MYCN mRNA expression was knocked down 53.1% in tumor tissues with injection of liposome encapsulated MYCN siRNA as compared to control siRNA. CONCLUSION: These results suggest that targeted delivery of MYCN siRNA by folate receptor-targeted lipid vesicles into LA-N-5 cells is efficacious and capable of suppressing MYCN mRNA expression both in vitro and in vivo. PMID- 20737152 TI - Foam sclerotherapy using polidocanol for balloon-occluded retrograde transvenous obliteration (BRTO). AB - PURPOSE: To evaluate the clinical safety and effectiveness of foam sclerotherapy using polidocanol for the treatment of gastric fundal varices by balloon-occluded retrograde transvenous obliteration (BRTO). MATERIALS AND METHODS: From November 2005 to June 2009, foam sclerotherapy using polidocanol for the treatment of gastric fundal varices by BRTO was performed in 16 patients (male/female 11:5; age range 46-84 years, median 67 years). Foam was made of 3% polidocanol (Aethoxysklerol; Kreussler Pharma, Wiesbaden, Germany), room air, and contrast media, with a ratio of 1:2:1, respectively. The amount of polidocanol (2-24 mL; median 7 mL) depended on the volume of varices. RESULTS: Technical success was achieved in 15 of 16 patients (93.8%). Technical failure occurred in one patient. All patients were without pain during sclerotherapy. One patient experienced pulmonary edema after the procedure but completely recovered with medical treatment. There was no procedure-related mortality. Patients were followed by endoscopy, computed tomography, or both. Four patients were lost to follow-up. Clinical success was achieved in 10 of 11 patients (91%). Rebleeding occurred in one case during follow-up. CONCLUSIONS: Foam sclerotherapy using polidocanol is clinically safe and effective for the treatment of gastric fundal varices during BRTO. PMID- 20737154 TI - Gastric emptying and antireflux surgery. AB - PURPOSE: Absence of consistent data on the outcome of gastric emptying after fundoplication raises concerns about preoperative workup and surgical management. This study assessed how gastric emptying evolves after isolated fundoplication in order to determine whether a preoperative investigation and/or a concurrent gastric drainage procedure are justified. METHODS: Eleven children with GERD underwent both pre- and post-operative gastric emptying scintigraphy. No gastric drainage procedures were added to fundoplication. Scintigraphy was performed according to a standardized protocol (labeled meal, 300 ml + 500 MUCi (99m)Tc/m(2) bsa). Half-emptying time (t (1/2)), emptying rate and fractions of retention are expressed as the median followed by the [range]; statistical significance level was set at 5%. RESULTS: Postoperative t (1/2) (min) showed a much smaller dispersion and was significantly lower than preoperative one (76 [56;101] vs. 107 [57;186], p = 0.04) with a variation of -48 [-105;19]; there was no individual correlation between pre- and post-operative measurements (r = 0.25). The proportion of patients with delayed gastric emptying (t (1/2) > 100) was significantly lower in the postoperative scintigraphy (9 vs. 55%, p = 0.03). The postoperative emptying rate (%/h) was significantly faster (35.1 [18.9;41.7] vs. 28.5 [16.3;38.7], p = 0.05). The retentions (%) at 30 and 60 min were similar; at 90 and 120 min were significantly lower after surgery (45 [35;54] and 32 [24;46] vs. 53 [33;78] and 41 [25;66], p = 0.03 and 0.05). CONCLUSION: Gastric emptying accelerates significantly after fundoplication with a shift to normal values in the vast majority of patients. Scintigraphy does not predict the postoperative outcome. Therefore, concomitant drainage procedures seem unnecessary and preoperative gastric emptying study not useful. PMID- 20737155 TI - gamma-Catenin is an independent prognostic marker in early stage colorectal cancer. AB - PURPOSE: Expression and role of gamma-catenin in colorectal carcinogenesis is not well understood. We aimed at characterizing gamma-catenin's expression pattern during colorectal carcinogenesis. METHODS: The expression pattern of gamma catenin was characterized in adenomas, primary colorectal carcinomas, and their corresponding metastases. Since this descriptive immunohistochemical analysis revealed upregulation of gamma-catenin in the invasive front of both primary tumors and metastases, a tissue microarray (TMA) was performed, allowing for correlation of subcellular expression patterns with disease recurrence and cancer specific survival. Comparison of gamma-catenin expression with that of beta catenin was performed. RESULTS: In normal colonic epithelium and adenomas, gamma catenin was weakly expressed at the membrane. In central areas of primary colorectal carcinomas, membranous and cytoplasmatic expression was present, with cytoplasmatic and nuclear upregulation of gamma-catenin in the invasive fronts. Expression patterns found in metastases resembled those of their respective primary tumors. Subsequent TMA analysis showed that upregulation of cytoplasmatic gamma-catenin in the invasive fronts of curatively resected early T2 and T3 colorectal carcinomas was associated with shortened disease-free survival and an increased risk of death (p=0.003; hazard ratio = 2.98; 95% confidence interval, 1.44-6.18). CONCLUSIONS: The correlation of upregulated cellular gamma-catenin levels with higher recurrences and impaired survival suggests a tumor promoting role of gamma-catenin in colorectal cancer. gamma-Catenin may therefore serve as a marker for identifying patients who are at increased risk of disease recurrence who may benefit from closer follow-up and adjuvant therapy. PMID- 20737156 TI - Treatment of benign colorectal strictures by temporary stenting with self expanding stents. AB - BACKGROUND: The application of stents in benign colorectal strictures is considered controversial. The aim of the present study was to assess effectiveness and complications associated with colorectal stent placement in benign colorectal disease. PATIENTS AND METHODS: Fourteen patients with benign colorectal strictures who had undergone previous surgery (colorectal anastomotic stenosis, 13; neosphincter scar stenosis, one) were treated with covered self expanding metal stent or plastic stent. Placement of the stent was performed with combined endoscopy and contrast enhanced fluoroscopy. RESULTS: Self-expanding stents were successful implanted in all 14 patients without acute procedure related complications. All patients experienced immediate decompression after stent placement with expansion and patency of the stent. Relief of bowel obstruction for at least 12 months was achieved in seven of 14 patients (50%). Anastomotic fistula healed in four of six patients (67%). Despite the initial success of stenting, re-operations had to be performed in two of seven patients because of late recurrence of the stricture after a mean follow-up of 37 months. CONCLUSIONS: Temporary insertion of self-expanding stents is a safe procedure that may be effective in selected cases of benign colorectal stricture. However, repeat surgery will be necessary in a considerable number of patients due to primary or secondary failure of stenting. PMID- 20737157 TI - Administration of nonsteroidal anti-inflammatory drugs accelerates spontaneous healing of osteoid osteoma. AB - INTRODUCTION: It has been reported that osteoid osteoma may heal spontaneously. METHOD: To elucidate the efficacy of conservative treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for osteoid osteoma, clinical courses of the 15 patients with osteoid osteoma conservatively treated with NSAIDs were observed. Twelve out of the 15 patients took a usual dose of NSAIDs regularly (regular group). RESULTS: Except for one patient, all the patients of the regular group maintained pain-free state. Eight out of the 12 patients of the regular group were free of pain even after discontinuing NSAIDs in the average of 18.3 months (range 2-36 months). Because one patient of the regular group required twice the usual dose to maintain pain-free state, we performed surgical excision. The remaining three patients of the regular group were asymptomatic and still taking NSAIDs. The healing rate of the osteoid osteoma with regular dose of NSAIDs was 8/12 (67%) at the time of this study, which may be improved up to 11/12 (92%). On the other hand, mean period of time until spontaneous diminution of pain in the 14 patients conservatively observed without NSAIDs so far reported in the literature was 75 months (range 24-180 months). CONCLUSION: Thus, osteoid osteoma is highly likely to heal spontaneously and administration of NSAIDs accelerates spontaneous healing. Therefore, conservative treatment with NSAIDs can be an important option other than surgical excision in treating osteoid osteoma. PMID- 20737159 TI - Comment to: the use of silicone oil-RMN3 (Oxane HD) as heavier-than-water internal tamponade in complicated inferior retinal detachment surgery. PMID- 20737158 TI - Neurometabolic correlates of depression and disability in episodic cluster headache. AB - A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2 [fluorine-18]-fluoro-2-deoxy-D-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering. PMID- 20737161 TI - Effects of yellow filters on visual acuity, contrast sensitivity and reading under conditions of forward light scatter. AB - BACKGROUND: Yellow filters are sometimes recommended to people with low vision. Our aim was investigate the effects of three commercial yellow filters on visual acuity and contrast sensitivity (with and without glare) and reading (without glare) under conditions of forward light scatter (FLS). METHOD: Fifty-five healthy subjects were assessed with Corning Photochromic Filters (CPFs) 450, 511 and 527 and a filter producing FLS. The effects on log MAR visual acuity, Pelli Robson contrast sensitivity with and without glare, and reading (measured with MNRead charts) without glare were determined. RESULTS: Statistically significant differences were found between the overall effect of glare and between CPFs for visual acuity and contrast sensitivity. A gradual decline in visual acuity, contrast sensitivity and reading with increasing CPF absorption was noted. CONCLUSION: Effects of CPF450, 511, 527 on visual acuity, contrast sensitivity and reading under conditions of FLS were negative but not clinically significant. PMID- 20737163 TI - The symmetry of phenotype between eyes of patients with early and late bilateral age-related macular degeneration (AMD). AB - BACKGROUND: Macular degeneration is known to be a bilateral disease. This study set out to determine the symmetry of phenotype between eyes of patients with bilateral early AMD (or drusen) or late-stage AMD. This may be important information when considering the likelihood of anti-VEGF treatment. METHODS: This prospective, observational, cross-sectional study graded the color fundus photographs of both eyes of 1,114 Caucasian patients with either early or late stage AMD. Patients were recruited from a tertiary referral UK population. The main outcomes were phenotype, comparison of number, type and overall area of drusen in early AMD and symmetry of late AMD. RESULTS: The overall agreement of phenotype in the entire cohort of patients was 53%, kappa statistic (kappa)=0.31, (95% CI = 0.27-0.36). Within this group, a total of 271 patients were identified with bilateral soft and hard drusen (early AMD). Symmetry of phenotype within this group was high in terms of total of area of drusen (agreement = 79%, weighted kappa = 0.75) and number of drusen. In those with bilateral geographic atrophy (GA), symmetry between area of GA was moderate (agreement 72%, weighted kappa = 0.54), and in those with bilateral neovascular disease (choroidal neovascularization or pigment epithelial detachment), symmetry was poor (agreement 45%, weighted kappa = 0.16). Out of the entire cohort, 62% (n = 688) had neovascular disease in at least one eye and 37.5% of these had bilateral disease. CONCLUSIONS: The observed symmetry of phenotype between eyes with drusen appears to reduce in GA and neovascular forms of AMD. Overall, 53% of the cohort had symmetrical disease in terms of phenotype, 23% had neovascular disease in both eyes, 9.3% had GA in both eyes, and 39% of patients had neovascular disease in one eye and non-neovascular disease in the other. This may have implications for the potential need for anti-VEGF treatment of AMD in second eye involvement. PMID- 20737164 TI - What are the stimulation parameters that affect the extent of twitch force potentiation in the adductor pollicis muscle? AB - Muscle force potentiation affects force output during electrical stimulation. Few studies have examined stimulation train parameters that influence potentiation such as pulse number, stimulation frequency, train duration, and force-time integral and peak force produced during the train. Pulse-matched trains (100 pulses) at 7.5, 15, 25, 30, 50, and 100 Hz, and trains of varying pulse number (50, 100, and 200 pulses) at 30 and 50 Hz were delivered to the ulnar nerve of 10 (5 male, 5 female; 23.4 +/- 0.9 years), healthy individuals in random order. Single twitches of the adductor pollicis muscle were elicited before and after each train with a rest interval of at least 5 min between each train. No differences in potentiation occurred across the pulse-matched trains at frequencies of 15-50 Hz (38.9 +/- 5.4-44.6 +/- 5.5%). Twitch force potentiation following the highest (100 Hz) and lowest (7.5 Hz) frequency trains were not significantly different and were lower than the other 100 pulse-matched trains. As pulse number increased, potentiation increased for both the 30 and 50-Hz trains. There was a significant positive correlation between force potentiation and force-time integral produced by the stimulation train, r = 0.70. The results indicate that potentiation magnitude is dependent on the force-time integral produced during the test train and the number of pulses delivered, independent of stimulation frequency. PMID- 20737162 TI - Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease. AB - BACKGROUND: Endogenous uveitis is a sight-threatening disease. In addition to corticosteroids, immunosuppressive agents are commonly used to treat patients with severe course. Immunosuppressive drugs act nonspecifically, rather than providing a specific interaction with the critical pathogenetic pathways of uveitis. Better knowledge of the basic mechanisms underlying uveitis and of the molecules that are important for regulating inflammation has helped to create new and more specific treatment approaches. Biological therapy for inflammatory diseases employs substances that interfere with specific molecules or pathways induced in the body during the inflammatory process. METHODS: This review gives an overview on molecules that play a critical role in the pathogenetic process of uveitis, as has been observed in patients or the respective animal models, and summarizes the current experience with biologicals for the treatment of uveitis refractive to conventional immunosuppressives. PMID- 20737165 TI - Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists. AB - This investigation reports the effects of caffeinated chewing gum on fatigue and hormone response during repeated sprint performance with competitive cyclists. Nine male cyclists (mean +/- SD, age 24 +/- 7 years, VO(2max) 62.5 +/- 5.4 mL kg( 1) min(-1)) completed four high-intensity experimental sessions, consisting of four sets of 30 s sprints (5 sprints each set). Caffeine (240 mg) or placebo was administered via chewing gum following the second set of each experimental session. Testosterone and cortisol concentrations were assayed in saliva samples collected at rest and after each set of sprints. Mean power output in the first 10 sprints relative to the last 10 sprints declined by 5.8 +/- 4.0% in the placebo and 0.4 +/- 7.7% in the caffeine trials, respectively. The reduced fatigue in the caffeine trials equated to a 5.4% (90% confidence limit +/-3.6%, effect size 0.25; +/-0.16) performance enhancement in favour of caffeine. Salivary testosterone increased rapidly from rest (~53%) and prior to treatments in all trials. Following caffeine treatment, testosterone increased by a further 12 +/- 14% (ES 0.50; +/- 0.56) relative to the placebo condition. In contrast, cortisol concentrations were not elevated until after the third exercise set; following the caffeine treatment cortisol was reduced by 21 +/- 31% (ES -0.30; +/ 0.34) relative to placebo. The acute ingestion of caffeine via chewing gum attenuated fatigue during repeated, high-intensity sprint exercise in competitive cyclists. Furthermore, the delayed fatigue was associated with substantially elevated testosterone concentrations and decreased cortisol in the caffeine trials. PMID- 20737166 TI - Alterations in neuromuscular function and perceptual responses following acute eccentric cycling exercise. AB - Previous investigators have reported velocity-dependent strength loss for single joint actions following acute eccentric exercise. The extent to which velocity influences recovery of multi-joint function is not well documented. Our main purpose was to compare alterations in maximal cycling power produced across a range of pedaling rates following eccentric exercise. An additional purpose was to determine the extent to which changes in rating of perceived exertion (RPE) associated with submaximal cycling reflect changes in maximal cycling power. Eighteen cyclists performed baseline trials of maximal and submaximal single-leg concentric cycling immediately before and 24 and 48 h after acute submaximal single-leg eccentric (151 +/- 32 W, 487 +/- 107 s) and concentric (148 +/- 21 W, 488 +/- 79 s) cycling trials. Maximum cycling power (apex of power-pedaling rate relationship; P (max)) was assessed using inertial-load cycling, and powers produced at 65, 110 and 155 rpm were also analyzed. Compared to baseline, P (max) was reduced (11-13%) at 24-48 h in the eccentric leg (P < 0.001). Power produced at 65, 110 and 155 rpm was reduced by similar relative magnitudes (11-15%) at 24 48 h in the eccentric leg. RPE increased (15-18%) at 24-48 h in the eccentric leg (P < 0.001). Magnitudes of relative changes in RPE did not differ from those for P (max). There were no alterations in the concentric leg. Our results indicated a global, rather than velocity-specific, reduction in neuromuscular function. Such a global reduction does not support the notion of fiber-type specific damage from eccentric exercise. The similar relative changes in RPE and P (max) suggest that increased exertion may reflect the need to recruit additional motor units to produce the same submaximal power. PMID- 20737167 TI - Sex differences in force steadiness in three positions of the forearm. AB - The purpose of this study was to examine force steadiness in three positions of the forearm in young men and women across a variety of force levels. Eight young men and eight young women performed three maximum voluntary contractions (MVCs) in the neutral, supinated, and pronated forearm positions. Viewing a target line on a computer screen, subjects performed submaximal isometric contractions relative to their own MVC at 2.5, 5, 10, 25, 50, and 75% in each of the three forearm positions. Force steadiness was determined as the coefficient of variation (standard deviation around the mean force). A repeated-measures three way ANOVA was used to assess the differences in force steadiness between sex, position, and force level. Men were stronger than women in all three forearm positions. Overall, men were steadier than women across all force levels and forearm positions. The neutral and supinated positions were equally strong and steady, and the pronated position was the weakest and least steady position. The forearm was most steady between 25 and 75% MVC, and least steady at the lower force levels. When correlations were run between MVC and coefficient of variation at all force levels and all forearm positions, a strong negative relationship was found (r = -0.49). In conclusion, men were stronger, as well as steadier, than women. The neutral and supinated forearm positions were both stronger and steadier than the pronated position. Results suggest that one of the primary factors influencing sex differences in force steadiness is absolute strength. PMID- 20737168 TI - Characterization of phytoene synthases from cassava and their involvement in abiotic stress-mediated responses. AB - Abiotic stress stimuli induce the increased synthesis of abscisic acid (ABA), which is generated through the cleavage of xanthophyll precursors. To cope with the increased xanthophyll demand, maize and rice contain a third stress-induced gene copy, coding for phytoene synthase (PSY), which catalyzes the first carotenoid-specific reaction in the pathway. To investigate whether this specific response extends beyond the Poaceae, cassava was analyzed, an important tropical crop known for its drought tolerance. We also found three PSY genes in cassava, one of which (MePSY3) forms a separate branch with the stress-specific Poaceae homologs. However, MePSY3 transcripts were virtually absent in all tissues investigated and did not change upon abiotic stress treatment. In contrast, the two remaining PSY genes contributed differentially to carotenoid biosynthesis in leaves, roots, and flower organs and responded towards drought and salt-stress conditions. Detailed analyses of PSY and 9-cis-epoxycarotenoid cleavage dioxygenase (MeNCED) expression and resulting ABA levels revealed MePSY1 as the main stress-responsive paralog. In the presence of high carotenoid levels in leaves, MePSY1 appeared to support, but not to be rate-limiting for ABA formation; MeNCED represented the main driver. The inverse situation was found in roots where carotenoid levels are low. Moreover, ABA formation and the relative induction kinetics showed discrimination between drought and salt stress. Compared to rice as a drought-intolerant species, the drought response in cassava followed a different kinetic regime. The difference is thought to represent a component contributing to the large differences in the adaptation towards water supply. PMID- 20737169 TI - CpG island hypermethylator phenotype in gastric carcinoma and its clinicopathological features. AB - Gastric carcinoma (GC) is one of the human cancers in which promoter CpG island hypermethylation is frequently found. CpG island methylator phenotype (CIMP) refers to a subset of GCs which harbor concordant methylation of multiple promoter CpG island loci. However, little is known regarding clinicopathological features of CIMP-positive (CIMP-high) GC. Our study aimed to characterize clinicopathological features of CIMP-high GC. We analyzed 196 cases of GCs for their methylation status in 16 cancer-specific CpG island loci using MethyLight assay and arbitrarily defined CIMP-high GC as those with methylation at 13 or more CpG island loci. With exclusion of microsatellite instability-positive GC and EBV-positive GC from the analysis, CIMP-high GC (n = 10, 6.7%) demonstrated tendency toward higher cancer stage, infiltrative growth type, poor differentiation, and diffuse or mixed type of Lauren classification. CIMP-high GC showed significantly shortened survival compared with that of CIMP-negative GC. When CIMP-negative GC (methylation at 12 or less) was divided into CIMP intermediate and CIMP-low (methylation at one or none), CIMP-low exhibited better clinical outcome than CIMP-intermediate. Hypermethylation at 14 CpG island loci or more was closely associated with poor clinical outcome and found to be an independent prognostic factor. Our findings that CIMP-high GCs were featured with characteristic clinicopathological parameters, including poor prognosis are distinct from previous studies. More extensive, large-scaled study is necessary to validate the findings of the present study. PMID- 20737170 TI - Loss of WW domain-containing oxidoreductase expression in the progression and development of gastric carcinoma: clinical and histopathologic correlations. AB - The purpose of this study is to investigate the role of the WW domain-containing oxidoreductase (WWOX) tumor suppressor that maps to the common fragile site FRA16D (16q23.3-24.1) during the development of gastric carcinoma (GC), we examined the altered expression of WWOX in GC cell lines and tissue samples as well as the effects of restoration of the WWOX gene into WWOX-deficient GC cells. All GC cell lines (HSC-45, HSC-57, HSC-59, MKN-7, and MKN-74) showed reduced WWOX expression at the mRNA and protein levels and hypermethylation at the WWOX regulatory site was detected in HSC-45 and HSC-59 cells. Interestingly, treatment with the deacetylating agent trichostatin A and the demethylating agent 5-aza-2' deoxycytidine restored endogenous WWOX expression levels in HSC-59 cells. Restoration of the WWOX gene with Ad-WWOX into HSC-59 cells effectively suppressed cell growth and increased the population of cells in subG(1) DNA content. In GC tissue samples, the loss of WWOX expression was detected in 24 (33%) of 73 GC cases in accordance with the hypermethylation at the WWOX regulatory site. Surprisingly, negative immunoreactivity against WWOX showed a significant relationship with several clinicopathologic findings, including histology (P = 0.0001), depth of invasion (P = 0.0004), lymph node metastasis (P = 0.0003), vessel infiltration (lymphatic vessels, P = 0.0167 and venous vessels, P = 0.0005), and clinicopathologic stage (P = 0.001). These findings suggest that repression of WWOX expression may play an important role in stomach carcinogenesis. WWOX thus appears to be a good biomarker for molecular diagnosis of the grade of malignancy of GCs. PMID- 20737171 TI - Incisional hernia, midline versus low transverse incision: what is the ideal incision for specimen extraction and hand-assisted laparoscopy? AB - BACKGROUND: Minimally invasive surgery is associated with smaller surgical incisions than those of traditional midline laparotomy. However, most colorectal resections and all hand-assisted procedures require an incision either for specimen retrieval or insertion of the hand-assist device. The ideal site of this incision has not been evaluated with respect to the incidence of incisional hernia. This study compares the rates of incisional hernia associated with a standard midline laparotomy, a midline incision of reduced length, and a Pfannenstiel incision. METHODS: From March 2004 to July 2007, 512 consecutive patients were identified from a prospectively maintained database according to predefined inclusion and exclusion criteria. Patients were divided into three groups depending on the type of incision (open, midline, and Pfannenstiel). Demographic variables, rate of incisional hernia, and risk factors for hernia were compared among the groups. RESULTS: There were 142, 231, and 139 patients in the open, midline, and Pfannenstiel groups, respectively. All three groups were comparable with respect to age, gender, steroid use, diabetes, number of patients with malignancy, and duration of follow-up. The Pfannenstiel group had a higher mean BMI (p = 0.015) and the open group had a higher rate of wound infection (28.2%) compared to the other groups. Incidence of incisional hernia was similar for the open and midline groups (19.7 and 16%, p = 0.36). At a mean follow-up of 17.5 months, not a single patient with a Pfannenstiel incision developed an incisional hernia (p < 0.001). BMI (p = 0.019), follow-up (p < 0.001), and Pfannenstiel incision (p < 0.001) were found to be predictors (protectors) of incisional hernia on multivariate analysis. CONCLUSION: A Pfannenstiel incision is associated with the lowest rate of incisional hernia and should be the incision of choice for hand assistance and specimen extraction in minimally invasive colorectal resections wherever applicable. PMID- 20737172 TI - Suprapubic single-incision laparoscopic appendectomy: a nonvisible-scar surgical option. AB - BACKGROUND: At the present time, and given the increasing concern about body image, laparoscopic surgeons are faced with an increasing number of patients who want to conserve the umbilicus free of scars for cosmetic reasons. Single incision laparoscopic surgery (SILS) using the suprapubic approach for appendectomy, while keeping the advantages of SILS through an umbilical incision, leaves the visible abdomen without scars. Moreover, insertion of an additional port in patients with retrocecal or purulent or gangrenous acute appendicitis requiring intra-abdominal drainage is avoided. This report describes the initial experience with suprapubic SILS appendectomy. METHODS: Between September 2009 and December 2010, patients with acute appendicitis admitted to the General Surgery and Emergency Unit of the authors' institution and who agreed to undergo SILS appendectomy through the suprapubic approach were included in a prospective study. Demographics, clinical characteristics, and surgical outcome were recorded. RESULTS: A total of 20 patients (12 men and 8 women) with a mean age of 30 +/- 3 years underwent suprapubic SILS appendectomy. The mean duration of the operation was 40 +/- 7 min. Placement of a suction drain was necessary in four patients. The mean length of hospital stay was 2 +/- 0.5 days. The operation was completed successfully in all patients, and conversion to either multiport or open surgery was not required. No intraoperative or postoperative complications occurred. In all patients, the appearance of the suprapubic wound was good at 7 days after surgery. CONCLUSION: Suprapubic SILS appendectomy offers better, cosmetically appealing results than the standard umbilical access. In case of retrocecal or purulent or gangrenous acute appendicitis, the view provided via the suprapubic approach makes access to and dissection of the appendix easy, and it also enables exteriorization of a drain without adding new lateral incisions. PMID- 20737173 TI - Author's reply to the letter to the editor: "new technologies-based innovation changes surgical practice and research direction in solid cancers" (Reply to SEND 08-0644.R1). PMID- 20737175 TI - A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial. AB - BACKGROUND: We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial. METHODS: We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n = 15), TAI using DSM (DSM group, n = 15), and TAI using lipiodol and DSM (lipiodol + DSM group, n = 15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol + DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM. RESULTS: The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol + DSM group, respectively. The response rate tended to improve in the lipiodol + DSM group (lipiodol group vs. lipiodol + DSM group, P = 0.07). The median progression-free survival time was 177 days in the lipiodol group, 287 days in the DSM group, and 377 days in the lipiodol + DSM group. The progression free survival in the lipiodol + DSM group was significantly better than those in the DSM group (P = 0.020) and the lipiodol group (P = 0.035). There were no serious adverse effects among the 3 groups. CONCLUSIONS: TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival. PMID- 20737174 TI - Identification of risk factors for postoperative dysphagia after primary anti reflux surgery. AB - BACKGROUND: Transient postoperative dysphagia is not uncommon after antireflux surgery and usually runs a self-limiting course. However, a subset of patients report long-term dysphagia. The purpose of this study was to determine the risk factors for persistent postoperative dysphagia at 1 year after surgery. METHODS: All patients who underwent antireflux surgery were entered into a prospectively maintained database. After obtaining institutional review board approval, the database was queried to identify patients who underwent primary antireflux surgery and were at least 1 year from surgery. Postoperative severity of dysphagia was evaluated using a standardized questionnaire (scale 0-3). Patients with scores of 2 or 3 were defined as having significant dysphagia. RESULTS: A total of 316 consecutive patients underwent primary antireflux surgery by a single surgeon. Of these, 219 patients had 1 year postoperative symptom data. Significant postoperative dysphagia at 1 year was reported by 19 (9.1%) patients. Thirty-eight patients (18.3%) required postoperative dilation for dysphagia. Multivariate logistic regression analysis identified preoperative dysphagia (odds ratio (OR), 4.4; 95% confidence interval (CI), 1.2-15.5; p = 0.023) and preoperative delayed esophageal transit by barium swallow (OR, 8.2; 95% CI, 1.6 42.2; p = 0.012) as risk factors for postoperative dysphagia. Female gender was a risk factor for requiring dilation during the early postoperative period (OR, 3.6; 95% CI, 1.3-10.2; p = 0.016). No correlations were found with preoperative manometry. There also was no correlation between a need for early dilation and persistent dysphagia at 1 year of follow-up (p = 0.109). CONCLUSIONS: Patients with preoperative dysphagia and delayed esophageal transit on preoperative contrast study were significantly more likely to report moderate to severe postoperative dysphagia 1 year after antireflux surgery. This study confirms that the manometric criteria used to define esophageal dysmotility are not reliable to identify patients at risk for postfundoplication dysphagia, and that there is need for standardization of contrast swallow assessment of esophageal function. PMID- 20737176 TI - Working towards patient oriented outcome assessment in normal pressure hydrocephalus, what is the most important? AB - OBJECTIVE: To date, there is no standard outcome assessment scale for shunt treatment in normal pressure hydrocephalus (NPH). In designing such scale, the relative weight of each of the common presentations of the condition from the patient's or his/her carer's point of view should be taken into consideration. METHODS: A questionnaire was sent to 24 patients treated for NPH and their family/carer, assessing the patient and carer categorization of the preoperative main complaint, the weight they give to each of the common presentations of NPH and their satisfaction with treatment. RESULTS: Twenty-two patients and 20 carers replied. Gait disturbance was the main complaint from both patient's (86%) and carer's (75%) point of view. Similarly, gait disturbance was considered as the most important problem that needs improvement by both patients (77%) and carers (65%). Incontinence was considered the second most important area by 11 (50%) patients and seven (35%) carers. When asked to quantify their satisfaction out of 10, patients had a mean of 7.2 while carers gave a mean of 7.5. Comparing subjective perspective of improvement with that of objective improvement on 10 m walking test and neuropsychological assessment, all patients who improved objectively were perceived as improved to a satisfactory degree by carers. CONCLUSION: Walking/balance should be given far greater weight than other components of the NPH triad in future outcome assessment scales in accordance with patient/family perception. PMID- 20737177 TI - Histology and intramandibular course of the inferior alveolar nerve. AB - The morphology of the inferior alveolar nerve is a very important factor for all surgical procedures in the mandibular region. The aim of this anatomical and histological study was to describe the intramandibular course and the microscopic histology of the inferior alveolar nerve in the dissected human cadaver. Twenty partially dentulous hemimandible specimens from human cadavers were dissected and embalmed, and the findings were interpreted by standard and histological imaging. The result of this study showed that the inferior alveolar nerve comprises two larger nerves that are separately wrapped in perineural sheaths and spirally twisted around each other. The mental nerve exits through the mental foramen in the premolar region and the dental nerve continues from the premolar region as the incisive nerve in the incisive canal. These findings provide relevant data for clinical dentistry, especially when planning oral and dental operative treatment procedures in the mandibular region. PMID- 20737179 TI - A comparison of an interferon-gamma release assay and tuberculin skin test in refractory inflammatory disease patients screened for latent tuberculosis prior to the initiation of a first tumor necrosis factor alpha inhibitor. AB - Treatment with TNFalpha inhibitors increases risk of reactivating a latent tuberculosis?infection (LTBI). Therefore screening, prior to therapy with TNFalpha inhibitors, has been recommended, even in low-endemic areas such as well developed Western Europe countries. We evaluated interferon-gamma release assay (IGRA), as opposed to tuberculin skin test (TST), for detection of LTBI in refractory inflammatory disease patients prior to the initiation of a first TNFalpha inhibitor. In addition, we evaluated the impact of impaired cellular immunity on IGRA. Patients starting on TNFalpha inhibition were screened for LTBI by TST and IGRA (Quantiferon-TB Gold). Data on tuberculosis exposure and Bacillus Calmette-Guerin (BCG) vaccination were obtained. Cellular immunity was assessed by CD4(+) T lymphocyte cell count. Nine out of 56 patients (16.1%) tested positive for LTBI. A concordant positive result was present in three patients with a medical history of tuberculosis exposure. Six patients with discordant test results had either: (1) a negative TST and positive IGRA in combination with a medical history of tuberculosis exposure (n = 1) or (2) a positive TST and negative IGRA in combination with BCG vaccination (n = 3) or a medical history of tuberculosis exposure (n = 2). CD4(+) T lymphocyte cell counts were within normal limits, and no indeterminate results of IGRA were present. IGRA appears reliable for confirming TST and excluding a false positive TST (due to prior BCG vaccination) in this Dutch serie of patients. In addition, IGRA may detect one additional case of LTBI out of 56 patients that would otherwise be missed using solely TST. Immune suppression appears not to result significantly in lower CD4(+) T lymphocyte cell counts and indeterminate results of IGRA, despite systemic corticosteroid treatment in half of the patients. Confirmation in larger studies, including assessment of cost-effectiveness, is required. PMID- 20737178 TI - Characterization of bacterial strains capable of desulphurisation in soil and sediment samples from Antarctica. AB - The presence of sulphur in fossil fuels and the natural environment justifies the study of sulphur-utilising bacterial species and genes involved in the biodesulphurisation process. Technology has been developed based on the natural ability of microorganisms to remove sulphur from polycyclic aromatic hydrocarbon chains. This biotechnology aims to minimise the emission of sulphur oxides into the atmosphere during combustion and prevent the formation of acid rain. In this study, the isolation and characterization of desulphurising microorganisms in rhizosphere and bulk soil samples from Antarctica that were either contaminated with oil or uncontaminated was described. The growth of selected isolates and their capacity to utilise sulphur based on the formation of the terminal product of desulphurisation via the 4S pathway, 2-hydroxybiphenyl, was analysed. DNA was extracted from the isolates and BOX-PCR and DNA sequencing were performed to obtain a genomic diversity profile of cultivable desulphurising bacterial species. Fifty isolates were obtained showing the ability of utilising dibenzothiophene as a substrate and sulphur source for maintenance and growth when plated on selective media. However, only seven genetically diverse isolates tested positive for sulphur removal using the Gibbs assay. DNA sequencing revealed that these isolates were related to the genera Acinetobacter and Pseudomonas. PMID- 20737180 TI - Co-existence of Parkinson's disease and progressive supranuclear palsy: case report and a review of the literature. AB - Idiopathic Parkinson's disease (PD) and progressive supranuclear palsy (PSP) are distinct clinicopathological entities characterized by alpha-synuclein and tau pathology, respectively. They have occasionally been reported to co-exist in the same patient. We describe a rare case of a 73-year-old Caucasian woman diagnosed as idiopathic PD 5 years before her death yet at autopsy had not only PD, but also PSP. Although this patient fulfilled clinical criteria for idiopathic PD and did not have supranuclear ophthalmoplegia, she had several atypical features, including early postural instability with falls, early dysphagia, and a relatively rapid course. In conclusion, this case and a literature review highlight the co-existence of synuclein and tau pathology in the same patient and demonstrate that multiple diagnoses may exist in patients presenting with parkinsonism. The clinical heterogeneity seen in parkinsonism may reflect the occurrence of combined pathology. PMID- 20737181 TI - Temperature rise during Er:YAG cavity preparation of primary enamel. AB - This study aimed to assess in vitro thermal alterations taking place during the Er:YAG laser cavity preparation of primary tooth enamel at different energies and pulse repetition rates. Forty healthy human primary molars were bisected in a mesio-distal direction, thus providing 80 fragments. Two small orifices were made on the dentin surface to which type K thermocouples were attached. The fragments were individually fixed with wax in a cylindrical Plexiglass(r) abutment and randomly assigned to eight groups, according to the laser parameters (n = 10): G1 - 250 mJ/ 3 Hz, G2 - 250 mJ/ 4 Hz, G3 - 250 mJ/ 6 Hz, G4 - 250 mJ/10 Hz, G5 - 250 mJ/ 15 Hz, G6 - 300 mJ/ 3 Hz, G7 - 300 mJ/ 4 Hz and G8 - 300 mJ/ 6 Hz. An area of 4 mm(2) was delimited. Cavities were done (2 mm long * 2 mm wide * 1 mm thick) using non-contact (12 mm) and focused mode. Temperature values were registered from the start of laser irradiation until the end of cavity preparation. Data were analyzed by one-way ANOVA and Tukey test (p <= 0.05). Groups G1, G2, G6, and G7 were statistically similar and furnished the lowest mean values of temperature rise. The set 250 mJ/10 and 15 Hz yielded the highest temperature values. The sets 250 and 300 mJ and 6 Hz provided temperatures with mean values below the acceptable critical value, suggesting that these parameters ablate the primary tooth enamel. Moreover, the temperature elevation was directly related to the increase in the employed pulse repetition rates. In addition, there was no direct correlation between temperature rise and energy density. Therefore, it is important to use a lower pulse frequency, such as 300 mJ and 6 Hz, during cavity preparation in pediatric patients. PMID- 20737182 TI - Microtensile bond strength of composite resin to glass-infiltrated alumina composite conditioned with Er,Cr:YSGG laser. AB - Tribochemical silica-coating is the recommended conditioning method for improving glass-infiltrated alumina composite adhesion to resin cement. High-intensity lasers have been considered as an alternative for this purpose. This study evaluated the morphological effects of Er,Cr:YSGG laser irradiation on aluminous ceramic, and verified the microtensile bond strength of composite resin to ceramic following silica coating or laser irradiation. In-Ceram Alumina ceramic blocks were polished, submitted to airborne particle abrasion (110 MUm Al(2)O(3)), and conditioned with: (CG) tribochemical silica coating (110 MUm SiO(2)) + silanization (control group); (L1-L10) Er,Cr:YSGG laser (2.78 MUm, 20 Hz, 0.5 to 5.0 W) + silanization. Composite resin blocks were cemented to the ceramic blocks with resin cement. These sets were stored in 37 degrees C distilled water (24 h), embedded in acrylic resin, and sectioned to produce bar specimens that were submitted to microtensile testing. Bond strength values (MPa) were statistically analyzed (alpha <=0.05), and failure modes were determined. Additional ceramic blocks were conditioned for qualitative analysis of the topography under SEM. There were no significant differences among silicatization and laser treatments (p > 0.05). Microtensile bond strength ranged from 19.2 to 27.9 MPa, and coefficients of variation ranged from 30 to 55%. Mixed failure of adhesive interface was predominant in all groups (75-96%). No chromatic alteration, cracks or melting were observed after laser irradiation with all parameters tested. Surface conditioning of glass-infiltrated alumina composite with Er,Cr:YSGG laser should be considered an innovative alternative for promoting adhesion of ceramics to resin cement, since it resulted in similar bond strength values compared to the tribochemical treatment. PMID- 20737184 TI - Syndrome of inappropriate secretion of antidiuretic hormone induced by tacrolimus in a patient with systemic lupus erythematosus. AB - We describe the first reported case of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by low-dose tacrolimus in a patient with autoimmune disease. A 41-year-old man with systemic lupus erythematosus (SLE) developed hyponatremia induced by SIADH after administration of tacrolimus (0.06 mg/kg per day). In this case, the hyponatremia promptly resolved upon withdrawal of tacrolimus. This case strongly suggests that SIADH is a potentially important complication of tacrolimus administration, irrespective of dosage, and should be borne in mind whenever the drug is used. PMID- 20737183 TI - Low-level laser therapy (LLLT; 780 nm) acts differently on mRNA expression of anti- and pro-inflammatory mediators in an experimental model of collagenase induced tendinitis in rat. AB - Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Tendinopathies are directly related to unbalance in expression of pro- and anti-inflammatory cytokines which are responsible by degeneration process of tendinocytes. In the current study, we decided to investigate if LLLT could reduce mRNA expression for TNF-alpha, IL 1beta, IL-6, TGF-beta cytokines, and COX-2 enzyme. Forty-two male Wistar rats were divided randomly in seven groups, and tendinitis was induced with a collagenase intratendinea injection. The mRNA expression was evaluated by real time PCR in 7th and 14th days after tendinitis. LLLT irradiation with wavelength of 780 nm required for 75 s with a dose of 7.7 J/cm(2) was administered in distinct moments: 12 h and 7 days post tendinitis. At the 12 h after tendinitis, the animals were irradiated once in intercalate days until the 7th or 14th day in and them the animals were killed, respectively. In other series, 7 days after tendinitis, the animals were irradiated once in intercalated days until the 14th day and then the animals were killed. LLLT in both acute and chronic phases decreased IL-6, COX-2, and TGF-beta expression after tendinitis, respectively, when compared to tendinitis groups: IL-6, COX-2, and TGF-beta. The LLLT not altered IL-1beta expression in any time, but reduced the TNF-alpha expression; however, only at chronic phase. We conclude that LLLT administered with this protocol reduces one of features of tendinopathies that is mRNA expression for pro-inflammatory mediators. PMID- 20737185 TI - Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with peripherally administered ulinastatin. AB - A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP. PMID- 20737187 TI - The short-term outcome of the modified Sauve-Kapandji procedure regarding range of motion, carpal bone translation and bony shelf size. AB - The Sauve-Kapandji (S-K) procedure is a common treatment for rheumatoid wrists, but in some cases severe bone destruction makes this operative modality difficult to perform, while also resulting in a poor outcome. A modified S-K procedure for these wrists has been reported, but the clinical outcomes of the modified procedure are unclear. This study evaluated 24 wrists in 20 patients who underwent the modified S-K procedure. The mean follow-up period was 34.5 months. The clinical assessments were range of motion, carpal bone translation and bony shelf size. The range of motion and carpal bone translation were similar to those produced by the S-K procedure. In regard to bony shelf size, wrists with an excessively large bony shelf tended to have a progression of carpal bone translation toward the palmar direction due to the residual malposition of the ECU tendon. The modified S-K procedure appears to be a safe and effective surgical alternative for the treatment of severely destroyed rheumatoid wrists. Although the modified procedure allows for the adjustment of the bony shelf size, it should not be used with wrists that have an excessively large bony shelf. PMID- 20737186 TI - Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompanied by macrophage-activation syndrome. AB - We report a 57-year-old female case of intractable adult-onset Still's disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease. PMID- 20737188 TI - Coexistence of systemic lupus erythematosus, Hashimoto's thyroiditis and IgA nephropathy in the same patient. AB - Autoimmune disorders encompass a wide spectrum of diseases that progress with several clinical findings. They can be organ-specific (such as Hashimoto's thyroiditis) or they can involve multiple organs (such as SLE). The common characteristic of all these disorders is the production of different autoantibodies against various autoantigens along with inflammation. IgA nephropathy is the most common non-lupus glomerulopathy. It rarely coexists with SLE and has never been reported to coexist with Hashimoto's thyroiditis. In this case report, a female patient diagnosed with SLE and Hashimoto's thyroiditis and whose renal biopsy revealed IgA nephropathy is presented. PMID- 20737189 TI - Dystrophic calcinosis in a patient with rheumatoid arthritis. AB - We report a rare case of dystrophic calcinosis in a patient with rheumatoid arthritis in bilateral buttock lesions and the right elbow joint. The calcinosis was surgically removed because it caused severe local pain, possible infection, and difficulty in sitting. Because no recommended standard pharmacotherapy exists for dystrophic calcinosis, surgical treatment should be taken into consideration when calcinosis causes severe local pain or restricts activities of daily life. PMID- 20737190 TI - Simulation of flow of mixtures through anisotropic porous media using a lattice Boltzmann model. AB - We propose a description for transient penetration simulations of miscible and immiscible fluid mixtures into anisotropic porous media, using the lattice Boltzmann (LB) method. Our model incorporates hydrodynamic flow, advection diffusion, surface tension, and the possibility for global and local viscosity variations to consider various types of hardening fluids. The miscible mixture consists of two fluids, one governed by the hydrodynamic equations and one by advection-diffusion equations. We validate our model on standard problems like Poiseuille flow, the collision of a drop with an impermeable, solid interface and the deformation of the fluid due to surface tension forces. To demonstrate the applicability to complex geometries, we simulate the invasion process of mixtures into wood spruce samples. PMID- 20737191 TI - Multifocal VEP (mfVEP) reveals abnormal neuronal delays in diabetes. AB - This pilot study examined the diagnostic role of multifocal visually evoked potentials (mfVEP) in a small number of patients with diabetes. mfVEP, mfERG, and fundus photographs of both eyes of five patients with diabetes, three with nonproliferative diabetic retinopathy (NPDR) and two without NPDR were examined. Thirteen control subjects were also examined. Eighteen zones were constructed from the 60-element mfVEP stimulus array. mfVEP implicit time (IT) and amplitude (SNR) differences were tested between subject groups. We also examined whether there was a difference in function for patches with and without retinopathy in the NPDR group. Lastly, we compared mfVEP and mfERG results in the same patients. We found significant mfVEP IT differences between controls and all patients with diabetes, controls and diabetics without retinopathy, and between controls and diabetics with retinopathy. The subject groups did not differ significantly in terms of SNR. In the retinopathy group, ITs from zones with retinopathy were significantly longer than ITs from zones without retinopathy (P = 0.016). mfERG IT was more frequently abnormal than mfVEP IT. In addition, mfERG hexagons were twice as likely to be abnormal if the corresponding mfVEP zone was abnormal (P < 0.05). mfVEP implicit times are significantly delayed in patients with diabetes even when there is no retinopathy. These cortical response results are similar, albeit considerably less abnormal, than those previously reported for retinal (mfERG) responses in patients with diabetes. A correlation exists between the location of abnormal mfERG hexagons and abnormal mfVEP zones. PMID- 20737193 TI - The property/privacy conundrum over human tissue. AB - This paper analyzes court rulings on tissue samples as property and critiques objections that have been raised to the recognition of DNA samples as personal property. The cases are: Moore v. Regents of the University of California (1988, 1990), Greenberg v. Miami Children's Research Institute (2003), and Washington University v. Catalona (2007). The paper argues that it is possible for the law to support both individual privacy and property rights in DNA, recognizing nevertheless that some unresolved questions remain, including what exercising those rights means on a practical level. Finally, it offers suggestions for changes in law based on those considerations. PMID- 20737192 TI - Prognosis of oligodendroglial tumor with ring enhancement showing central necrotic portion. AB - Oligodendroglial tumors sometimes show heterogeneous ring enhancement with a central necrotic portion. We aimed to reveal the prognosis of such tumors based on such radiologic findings and compare them to other prognostic factors. Participants were 32 patients with oligodendroglioma (17 oligodendrogliomas, 15 anaplastic oligodendrogliomas) who underwent surgery from 2004 to 2008. We investigated tumor radiologic findings, locations, calcification, whether localized or diffuse type, and enhancement patterns. Of other prognostic factors, we analyzed age, sex, pathology, extent of removal, adjuvant therapy, genetic change in 1p and 19q, and MGMT methylation status. We checked for genetic abnormality in 1p and 19q using the FISH method. To investigate MGMT methylation, we performed methylation-specific PCR (MSP). Mean follow-up duration was 3.2 years. Median age was 42.4 years, and the male:female ratio was 21:11. Out of 17 oligodendrogliomas, 14 (82.4%) showed combined 1p/19q deletion, and 14 (82.4%), methylated MGMT. Among 15 anaplastic oligodendrogliomas, there were 7 (46.6%) with combined 1p/19q deletion and 11 (73.3%) with methylated MGMT. The 4-year recurrence-free survival and overall survival were 77.6 and 100% in oligodendrogliomas and 59.1 and 71.6% in anaplastic oligodendrogliomas, respectively. On univariate analysis, radiologic variable of ring enhancement pattern was statistically significant related with recurrence-free survival (P = 0.003). Variables such as sex (P = 0.03), combined 1p/19q loss (P = 0.04), tumor location (P = 0.02), and anaplastic pathology (P = 0.04) were significantly correlated with overall survival. Cox's regression model revealed that ring enhancement pattern was associated with frequent recurrence (ring enhancement, hazard ratio = 8.281, P = 0.04), and these showed 1p deletion only. Anaplastic oligodendrogliomas with ring enhancement like glioblastomas and without combined 1p/19q loss should receive close follow-up after treatment because of frequent recurrences. PMID- 20737194 TI - Genetic diversity of the killifish Aphanius fasciatus paralleling the environmental changes of Tarquinia salterns habitat. AB - The habitat in the Natural Reserve of the Tarquinia salterns, located on the Tyrrhenian coast of central Italy, has undergone dramatic alterations over the last 10 years. After salt production was terminated in 1997 the site was abandoned until 2002, with consequent degradation of habitat quality and stiffening of the environmental conditions. From 2003 to 2006 ecological rehabilitation of the site was carried out, restoring water circulation to its previous equilibrium. The genetic variation in the killifish Aphanius fasciatus inhabiting the salterns was monitored using allozymes from 1998. The results showed that the genetic variability of the killifish strongly reduced through time: a high number of rare alleles were lost and both heterozygosity and allele richness were significantly decreased. The most recent samples, taken after the ecological restoration, showed that to date the genetic erosion of A. fasciatus gene pool has slowed down, since no significant differences have been detected for any genetic variability parameter. Concerning the mechanisms leading to the impoverishment of the genetic variability, the strong loss of rare alleles suggests a role of genetic drift, which accords with the fluctuation of the effective population size recorded over the period of study and with the low gene flow typical of this species. The low levels of gene flow reported for this species imply that once lost, the genetic variability can rarely be restored through immigration from highly variable populations. PMID- 20737195 TI - Development of transgenic strains for the biological control of the Mexican fruit fly, Anastrepha ludens. AB - The Mexican fruit fly, Anastrepha ludens, is a highly significant agricultural pest species that has been genetically transformed with a piggyBac-based transposon vector system using independent vector and transposase helper plasmids. Minimum estimated germ-line transformation frequencies were approximately 13-21% per fertile G(0) individual, similar to previously reported frequencies using single vector-helper plasmids. Two vector constructs were tested with potential importance to transgenic strain development for mexfly biological control. The first allows post-integration stabilization of a transposon-vector by deletion of a terminal sequence necessary for mobilization. The complete pB[L1-EGFP-L2-DsRed-R1] vector was integrated into the Chiapas wild type strain with subsequent deletion of the L2-DsRed-R1 sub-vector carrying the piggyBac 3' terminal sequence. Quality control tests for three of the stabilization vector lines (previous to stabilization) assessed viability at all life stages, fertility, adult flight ability, and adult male sexual competitiveness. All three transgenic lines were less fit compared to the wild strain by approximately 5-10% in most tests, however, there was no significant difference in sexual competitiveness which is the major prerequisite for optimal strain release. The second vector, pB[XL-EGFP, Asbeta2-tub-DsRed.T3], has the DsRed.T3 fluorescent protein reporter gene regulated by the A. suspensa Asbeta2 tubulin promoter, that resulted in testis and sperm-specific DsRed fluorescence in transgenic male mexflies. Fluorescent sperm bundles were unambiguously observed in the spermathecae of non-transgenic females mated to transgenic males. One transgenic line apparently had a male-specific Y-chromosome insertion, having potential use for sexing by fluorescent-embryo sorting. All transgenic lines expressed easily detectable and stable fluorescence in adults allowing their identification after trapping in the field. PMID- 20737196 TI - A non-parametric mixture model for genome-enabled prediction of genetic value for a quantitative trait. AB - A Bayesian nonparametric form of regression based on Dirichlet process priors is adapted to the analysis of quantitative traits possibly affected by cryptic forms of gene action, and to the context of SNP-assisted genomic selection, where the main objective is to predict a genomic signal on phenotype. The procedure clusters unknown genotypes into groups with distinct genetic values, but in a setting in which the number of clusters is unknown a priori, so that standard methods for finite mixture analysis do not work. The central assumption is that genetic effects follow an unknown distribution with some "baseline" family, which is a normal process in the cases considered here. A Bayesian analysis based on the Gibbs sampler produces estimates of the number of clusters, posterior means of genetic effects, a measure of credibility in the baseline distribution, as well as estimates of parameters of the latter. The procedure is illustrated with a simulation representing two populations. In the first one, there are 3 unknown QTL, with additive, dominance and epistatic effects; in the second, there are 10 QTL with additive, dominance and additive * additive epistatic effects. In the two populations, baseline parameters are inferred correctly. The Dirichlet process model infers the number of unique genetic values correctly in the first population, but it produces an understatement in the second one; here, the true number of clusters is over 900, and the model gives a posterior mean estimate of about 140, probably because more replication of genotypes is needed for correct inference. The impact on inferences of the prior distribution of a key parameter (M), and of the extent of replication, was examined via an analysis of mean body weight in 192 paternal half-sib families of broiler chickens, where each sire was genotyped for nearly 7,000 SNPs. In this small sample, it was found that inference about the number of clusters was affected by the prior distribution of M. For a set of combinations of parameters of a given prior distribution, the effects of the prior dissipated when the number of replicate samples per genotype was increased. Thus, the Dirichlet process model seems to be useful for gauging the number of QTLs affecting the trait: if the number of clusters inferred is small, probably just a few QTLs code for the trait. If the number of clusters inferred is large, this may imply that standard parametric models based on the baseline distribution may suffice. However, priors may be influential, especially if sample size is not large and if only a few genotypic configurations have replicate phenotypes in the sample. PMID- 20737197 TI - The impact of C-MYC gene expression on gastric cancer cell. AB - The upregulation or mutation of C-MYC has been observed in gastric, colon, breast, and lung tumors and in Burkitt's lymphoma. However, little is known about the role C-MYC plays in gastric adenocarcinoma. In the present study, we intended to investigate the influence of C-MYC on the growth, proliferation, apoptosis, invasion, and cell cycle of the gastric cancer cell line SGC7901 and the gastric cell line HFE145. C-MYC cDNA was subcloned into a constitutive vector PCDNA3.1 followed by transfection in normal gastric cell line HFE145 by using liposome. Then stable transfectants were selected and appraised. Specific inhibition of C MYC was achieved using a vector-based siRNA system which was transfected in gastric cancer cell line SGC7901. The apoptosis and cell cycles of these clones were analyzed by using flow cytometric assay. The growth and proliferation were analyzed by cell growth curves and colony-forming assay, respectively. The invasion of these clones was analyzed by using cell migration assay. The C-MYC stable expression clones (HFE-Myc) and C-MYC RNAi cells (SGC-MR) were detected and compared with their control groups, respectively. HFE-Myc grew faster than HFE145 and HFE-PC (HFE145 transfected with PCDNA3.1 vector). SGC-MR1, 2 grew slower than SGC7901 and SGC-MS1, 2 (SGC7901 transfected with scrambled control duplexes). The cell counts of HFE-Myc in the third, fourth, fifth, sixth, and seventh days were significantly more than those of control groups (P < 0.05). Those of SGC-MR1, 2 in the fourth, fifth, sixth, and seventh days were significantly fewer than those of control groups (P < 0.05). Cell cycle analysis showed that proportions of HFE-Myc and SGC-MR cells in G0-G1 and G2-M were different significantly with their control groups, respectively (P < 0.05). The apoptosis rate of HFE-Myc was significantly higher than those of control groups (P < 0.05). Results of colony-forming assay showed that the colony formation rate of HFE-Myc was higher than those of control groups; otherwise, the rate of SGC-MR was lower than those of their control groups (P < 0.05). The results of cell migration assay showed that there were no significant differences between experimental groups and control groups (P > 0.05). In conclusion, C-MYC can promote the growth and proliferation of normal gastric cells, and knockdown of C MYC can restrain the growth and proliferation of gastric cancer cells. It can induce cell apoptosis and help tumor cell maintain malignant phenotype. But it can have not a detectable influence on the ability of invasion of gastric cancer cells. PMID- 20737199 TI - Videoconferencing at psychology internships: interns' perceptions of interactive television experiences and prospects. AB - This article reviews the use and perceptions of videoconferencing in psychology internship training from the perspective of interns. Videoconferencing offers a means of expanding training beyond conventional on-site models. Psychology interns completed an online survey about their experiences with videoconferencing and perspectives of its impact on training. Most participants encountered it in their didactics. Some used it for supervision or other purposes. Interns' perspectives were complex, with videoconferencing seen as supporting learning similar to conventional training in some ways, yet as less desirable overall. Direct comparisons between videoconferencing and on-site training revealed interns perceived videoconferencing as somewhat less effective, and as deleteriously affecting learning dynamics. Challenges and potential benefits of incorporating videoconferencing into psychology internship training were identified. Potential benefits include augmenting available internship training and increasing rural sites' access to training. PMID- 20737198 TI - Identification of biologically relevant compounds in aboveground and belowground induced volatile blends. AB - Plants under attack by aboveground herbivores emit complex blends of volatile organic compounds (VOCs). Specific compounds in these blends are used by parasitic wasps to find their hosts. Belowground induction causes shifts in the composition of aboveground induced VOC blends, which affect the preference of parasitic wasps. To identify which of the many volatiles in the complex VOC blends may explain parasitoid preference poses a challenge to ecologists. Here, we present a case study in which we use a novel bioinformatics approach to identify biologically relevant differences between VOC blends of feral cabbage (Brassica oleracea L.). The plants were induced aboveground or belowground with jasmonic acid (JA) and shoot feeding caterpillars (Pieris brassicae or P. rapae). We used Partial Least Squares--Discriminant Analysis (PLSDA) to integrate and visualize the relation between plant-emitted VOCs and the preference of female Cotesia glomerata. Overall, female wasps preferred JA-induced plants over controls, but they strongly preferred aboveground JA-induced plants over belowground JA-induced plants. PLSDA revealed that the emission of several monoterpenes was enhanced similarly in all JA-treated plants, whereas homoterpenes and sesquiterpenes increased exclusively in aboveground JA-induced plants. Wasps may use the ratio between these two classes of terpenes to discriminate between aboveground and belowground induced plants. Additionally, it shows that aboveground applied JA induces different VOC biosynthetic pathways than JA applied to the root. Our bioinformatic approach, thus, successfully identified which VOCs matched the preferences of the wasps in the various choice tests. Additionally, the analysis generated novel hypotheses about the role of JA as a signaling compound in aboveground and belowground induced responses in plants. PMID- 20737201 TI - Prospective evaluation of epstein-barr virus reactivation after stem cell transplantation: association with monoclonal gammopathy. AB - Epstein-Barr Virus (EBV) reactivation and EBV-related post-transplant lymphoproliferative disease (PTLD) have emerged as a severe complication after stem cell transplantation (SCT). We prospectively evaluated 104 consecutive patients receiving SCT either autologous or allogeneic. Fifty-two patients (50%) presented EBV DNA-emia and five of them developed PTLD proven or probable. PTLD rate was 9.6% among patients with EBV DNA-emia. One patient developed PTLD without EBV DNA-emia (0.96%). Overall PTLD incidence was 5.7%. No PTLD developed after autologous SCT. EBV DNA-emia was significantly more frequent after allogeneic than autologous SCT (60.7% vs 17.4%, p = 0.0002). At EBV reactivation, serum protein electrophoresis and immunofixation were assessed. Global incidence of gamma-peak after allogeneic SCT with EBV reactivation was 65.3% (32/49 patients) and monoclonal gammopathy (MG) was identified in 23/28 evaluable patients (82%). All patients with PTLD developed gamma-peak and in five of them MG was identified. MG is consistently associated with EBV DNA-emia and may help identification of progression to PTLD after allogeneic SCT. PMID- 20737200 TI - Quality measures for the diagnosis and non-operative management of carpal tunnel syndrome in occupational settings. AB - INTRODUCTION: Providing higher quality medical care to workers with occupationally associated carpal tunnel syndrome (CTS) may reduce disability, facilitate return to work, and lower the associated costs. Although many workers' compensation systems have adopted treatment guidelines to reduce the overuse of unnecessary care, limited attention has been paid to ensuring that the care workers do receive is high quality. Further, guidelines are not designed to enable objective assessments of quality of care. This study sought to develop quality measures for the diagnostic evaluation and non-operative management of CTS, including managing occupational activities and functional limitations. METHODS: Using a variation of the well-established RAND/UCLA Appropriateness Method, we developed draft quality measures using guidelines and literature reviews. Next, in a two-round modified-Delphi process, a multidisciplinary panel of 11 U.S. experts in CTS rated the measures on validity and feasibility. RESULTS: Of 40 draft measures, experts rated 31 (78%) valid and feasible. Nine measures pertained to diagnostic evaluation, such as assessing symptoms, signs, and risk factors. Eleven pertain to non-operative treatments, such as the use of splints, steroid injections, and medications. Eleven others address assessing the association between symptoms and work, managing occupational activities, and accommodating functional limitations. CONCLUSIONS: These measures will complement existing treatment guidelines by enabling providers, payers, policymakers, and researchers to assess quality of care for CTS in an objective, structured manner. Given the characteristics of previous measures developed with these methods, greater adherence to these measures will probably lead to improved patient outcomes at a population level. PMID- 20737202 TI - Profile of autoantibodies against phosphorylcholine and cross-reactivity to oxidation-specific neoantigens in selective IgA deficiency with or without autoimmune diseases. AB - Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency. PMID- 20737204 TI - Our environment and our gametes: what human ARTs can add to the discourse. PMID- 20737203 TI - In vitro maturation of oocytes via the pre-fabricated self-assembled artificial human ovary. AB - PURPOSE: create a 3-Dimensional artificial human ovary to mature human oocytes. METHODS: theca and granulosa cells were isolated from antral follicles of reproductive-aged women, seeded into micro-molded gels and self-assembled into complex 3D microtissues. Immunohistochemistry and live-dead staining confirmed theca cell identity and cellular viability at one week respectively. Placement of granulosa cell spheroids or cumulus-oocyte complexes into theca cell honeycomb openings resulted in creation of an artificial human ovary. Oocytes from this construct were assessed for polar body extrusion. RESULTS: theca and granulosa cells self-assembled into complex microtissues, remaining viable for one week. At 72 h after artificial human ovary construction, theca cells completely surrounded the granulosa spheroids or COCs without stromal invasion or disruption. Polar body extrusion occurred in one of three COCs assessed. CONCLUSIONS: an artifical human ovary can be created with self-assembled human theca and granulosa cell microtissues, and used for IVM and future oocyte toxicology studies. PMID- 20737205 TI - The associations between two polymorphisms in the interleukin-10 gene promoter and breast cancer risk. AB - The association between single-nucleotide polymorphisms (SNPs) in the interleukin 10 (IL-10) gene promoter and breast cancer risk is still ambiguous. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of the relationship between two genetic variants in the IL-10 gene promoter, -1082A > G (rs1800896) and -592C > A (rs1800872), and breast cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the corresponding strengths of association under the codominant, dominant, and recessive models. A total of ten studies (4,181 cases and 4,384 controls) were eligible for meta-analysis. There were six studies with 3,032 cases and 3,190 controls for rs1800872, and eight studies with 1,636 cases and 1,670 controls for rs1800896. Meta-analysis showed that neither of the two polymorphisms had any association with increased breast cancer risk (for rs1800896: OR = 1.060, 95% CI = 0.785-1.432 in the dominant model, and OR = 1.152, 95% CI = 0.958-1.386 in the recessive model; and for rs1800872: OR = 0.952, 95% CI = 0.859-1.056 in the dominant model, and OR = 0.892, 95% CI = 0.741 1.072 in the recessive model). The results did not change when the analyses were restricted in Caucasians, or in the studies fulfilling Hardy-Weinberg equilibrium, or according to source of controls. In outlier analysis, no individual study affected the overall OR dominantly, since omission of any single study made no material huge difference. In conclusion, the present meta-analysis suggests a lack of association between the two SNPs (rs1800896 and rs1800872) in the IL-10 gene promoter and breast cancer risk. Further studies, either with larger sample size or regarding other SNPs/haplotypes within the IL-10 gene, are needed to clarify the role of IL-10 in breast carcinogenesis. PMID- 20737206 TI - A recombination-based method to characterize human BRCA1 missense variants. AB - Many missense variants in BRCA1 are of unclear clinical significance. Functional and genetic approaches have been proposed for elucidating the clinical significance of such variants. The purpose of this study was to evaluate BRCA1 missense variants for their effect on both homologous recombination (HR) and non homologous end joining (NHEJ). HR frequency evaluation: HeLaG1 cells, containing a stably integrated plasmid that allows us to measure HR events by gene conversion events, were transfected with the pcDNA3beta expression vector containing the BRCA1-wild-type (BRCA1 wild type) or the BRCA1-unclassified variants (BRCA1-UCVs). The NHEJ was measured by a random plasmid integration assay. The assays suggested a BRCA1 involvement mainly in the NHEJ. As a matter of fact, the Y179C and the A1789T variant significantly altered the NHEJ activity as compared to the wild type, suggesting that they may be related to BRCA1 associated pathogenicity by affecting this function. The variants N550H and I1766S, and the mutation M1775R did not alter the NHEJ frequency. These data, besides proposing a method for the study of BRCA1 variants' effect on HR and NHEJ, highlighted the need for a range of functional assays to be performed to identify variants with altered function. PMID- 20737207 TI - Magnetic properties of the road dusts from two parks in Wuhan city, China: implications for mapping urban environment. AB - Magnetic parameters and heavy metal concentrations of road dusts collected from two parks with distance about 16 km in Wuhan city, China, were measured. The Guishan Park is circled by main roads with heavy traffic, and the Moshan Park is located on the downwind hills of steelworks and a power plant. Mean values of magnetic susceptibility (chi) and saturation magnetization (M (s)) of the dusts from the Moshan Park are 1.31 and 1.57 times those from the Guishan Park, respectively. Their magnetic mineralogy is dominated by pseudo-single domain magnetite; however, minor hematite was also identified in those from the Guishan Park. The dominant sources of non-natural magnetic particles and heavy metals were inferred as windblown emissions from the steelworks and the power plant for the Moshan Park, and road/railway traffics for the Guishan Park, respectively. Spatial variation in magnetic properties of road dust in the two parks and their different magnetic behavior propose that the magnetic measurements are sensitive to the different pollutant origins, as well as the urban environment, and that magnetic techniques have a high efficiency in mapping urban environment. Correlation between magnetic parameters and heavy metal concentrations is strongly site-specific: strong correlations were observed in the Moshan Park with correlation coefficients generally higher than 0.800, whereas correlations are poor in the Guishan Park. Therefore, it is strongly recommended that these relationships should be examined thoroughly before magnetic mapping. PMID- 20737208 TI - Blood cells of a sisorid catfish Glyptosternum maculatum (Siluriformes: Sisoridae), in Tibetan Plateau. AB - The peripheral blood cells of a sisorid catfish Glyptosternum maculatum were studied using light microscope and transmission electron microscope. The size of cells and nucleus, and the percentage of different leucocytes were also described. Erythrocytes and four types of leucocytes: lymphocytes, heterophils, monocytes, and thrombocytes were characterized in G. maculatum blood. The dividing erythrocytes could be found sporadically. A plasma cell was observed under a transmission electron microscope. The morphology and structure of blood cells of G. maculatum were basically similar to those of other fish species, although there were also main differences, such as larger erythrocytes than other catfishes, absence of basophils and acidophils, and various types of thrombocytes (five types: lone nucleus, fusiform, tadpole-like, oval, and in a cluster). PMID- 20737209 TI - Thiazides diuretics in the treatment of nephrolithiasis: are we using them in an evidence-based fashion? AB - In the 1980s a change occurred in hydrochlorothiazide prescribing practices for hypertension from high-dose (50 mg/day) to low-dose (12.5-25 mg/day) therapy. However, randomized controlled trials (RCT) for prevention of calcium-containing kidney stones (CCKS) employed only high doses (>= 50 mg/day). We hypothesized that these practices have resulted in underdosing of hydrochlorothiazide for prevention of CCKS. Patients with a filled prescription for thiazide diuretics that underwent a 24-h urine stone risk factor analysis were eligible. Those with evidence that thiazide was prescribed for CCKS were further analyzed. Of 107 patients, 102 were treated with hydrochlorothiazide, 4 with indapamide, and one with chlorthalidone. Only 35% of hydrochlorothiazide-treated patients received 50 mg/day; a dose previously shown to reduce stone recurrence. Fifty-two percent were prescribed 25 mg and 13% 12.5 mg daily, doses that were not studied in RCT. Evidence-based hydrochlorothiazide use was suboptimal regardless of where the patient received care (Nephrology or Endocrinology clinic). In a small subset of patients (n = 6) with 24-h urinary calcium excretion measured at baseline and after 2 hydrochlorothiazide doses (25 and >= 50 mg), there was a trend toward decreased urinary calcium excretion as the dose was increased from 25 to >= 50 mg/day (p = 0.051). Low-dose hydrochlorothiazide was often used for prevention of CCKS despite the fact that there is no evidence that it is effective in this setting. This may have resulted from a practice pattern of using lower doses for hypertension therapy or a lack of knowledge of RCT results in treatment of CCKS. PMID- 20737211 TI - Reflux parameters as modified by laparoscopic fundoplication in 40 patients with heartburn/regurgitation persisting despite PPI therapy: a study using impedance pH monitoring. AB - BACKGROUND: Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied. AIMS: The aim of this study was to assess reflux parameters and their relationship with symptoms before and after laparoscopic fundoplication, on and off PPI therapy, respectively, in patients with PPI-unresponsive heartburn/regurgitation and with a positive symptom-reflux association and/or abnormal reflux parameters detected on PPI therapy. METHODS: Impedance-pH monitoring was performed on high-dose PPI therapy and 3 months after laparoscopic fundoplication, off PPI therapy, in 40 patients with PPI-unresponsive heartburn/regurgitation. Symptoms were scored by a validated questionnaire. RESULTS: Esophageal acid exposure time as well as the number of total and proximal reflux events and of acid and weakly acidic refluxes decreased significantly after surgery: normal values were found in 100, 77, 95, 92 and 65% of cases, respectively. Weakly alkaline refluxes increased significantly postoperatively but neither before nor after intervention were associated with symptoms. All patients reported total/subtotal remission of heartburn/regurgitation 3 months after surgery. CONCLUSIONS: Laparoscopic fundoplication improves acid and weakly acidic reflux parameters when compared with PPI therapy. This improvement justifies the very high post-surgical symptom remission rate that we observed. Prolonged follow-up is warranted but our findings strongly support the surgical option in PPI failures. PMID- 20737210 TI - Rectal administration of Lactobacillus casei DG modifies flora composition and Toll-like receptor expression in colonic mucosa of patients with mild ulcerative colitis. AB - BACKGROUND: An imbalance in gut microbiota seems to contribute to the development of chronic inflammatory disorders of the gastrointestinal tract, such as ulcerative colitis (UC). Although it has been suggested that probiotic supplementation is an effective approach to colitis, its effects on intestinal flora and on mucosal cytokine balance have never been explored. AIM: To evaluate the effect of Lactobacillus casei (L. casei) DG, a probiotic strain, on colonic associated microbiota, mucosal cytokine balance, and toll-like receptor (TLR) expression. METHODS: Twenty-six patients with mild left-sided UC were randomly allocated to one of three groups for an 8-week treatment period: the first group of 7 patients received oral 5-aminosalicylic acid (5-ASA) alone, the second group of 8 patients received oral 5-ASA plus oral L. casei DG, and the third group of 11 patients received oral 5-ASA and rectal L. casei DG. Biopsies were collected from the sigmoid region to culture mucosal-associated microbes and to assess cytokine and TLR messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: 5-ASA alone or together with oral L. casei DG failed to affect colonic flora and TLR expression in a significant manner, but when coupled with rectally administered L. casei DG, it modified colonic microbiota by increasing Lactobacillus spp. and reducing Enterobacteriaceae. It also significantly reduced TLR-4 and interleukin (IL)-1beta mRNA levels and significantly increased mucosal IL-10. CONCLUSIONS: Manipulation of mucosal microbiota by L. casei DG and its effects on the mucosal immune system seem to be required to mediate the beneficial activities of probiotics in UC patients. PMID- 20737212 TI - CoMFA and CoMSIA of diverse pyrrolidine analogues as dipeptidyl peptidase IV inhibitors: active site requirements. AB - The inhibition of dipeptidyl peptidase IV (DPP-IV) has emerged as an attractive target in the treatment of type 2 diabetes. In view of this development, a critical analysis of structural requirements of the DPP-IV inhibitors is envisioned to identify the significant features toward design of selective inhibitors. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) contour plots of pyrrolidine based analogues are used to analyze the structural requirements of a DPP-IV active site. The CoMFA model has shown a cross-validated q (2) of 0.651 with a non-cross validated r (2) of 0.882 and explained 70.6% variance in the activity of external test compounds. In this, the steric and electrostatic fields have respectively contributed 59.8 and 40.2%, respectively, to the explained activity of the compounds. The CoMSIA model has shown optimum predictivity (cross-validated q (2) = 0.661; non-cross-validated r (2) = 0.803; external test set's predictive r (2) = 0.706) with four molecular fields namely, steric, electrostatic, hydrogen bond (HB)-donor, and HB-acceptor. The contour plots of molecular fields resulting from these studies have suggested: (i) steric restriction with small electron rich substituent at 2- and 3-position of pyrrolidine ring, (ii) presence of electropositive ring linker between the pyrrolidine head and aryl tail, (iii) presence of electron-rich groups around the aryl tail moiety, and (iv) presence of sulfonamide between the ring linker and aryl tail which would increase DPP-IV binding affinity of the compounds. These findings will help in the design of structurally related/new compounds as potential DPP-IV inhibitors. PMID- 20737213 TI - A mild and efficient method for the synthesis of a new class of furo[3,2 c]chromenes in aqueous media. AB - An efficient synthesis of 2-hydroxy-3-[2-oxo-2-phenylethylidene]-2-phenyl-2, 3 dihydro-4 H-furo[3, 2-c]chromene-4(2H)-one is described. This involves the reaction between dibenzoylacetylene and 4-hydroxycoumarine in the presence of NaH (10 mol %) in nearly quantitative yield. Treatment of this heterocyclic system with trimethyl chlorosilane in CHCl(3) leads quantitatively to 4-oxo-3-[2-oxo-2 phenylethylidene]-2-phenyl-3H, 4H-furo[3,2-c]chromene-1-ium chloride. Direct addition of nucleophiles, such as alcohols, amines or trialkyl phosphites to this salt in water as the solvent produces functionalized 2-phenyl-4H-furo[3,2-c] chromen derivatives in excellent yields. PMID- 20737214 TI - Comprehensive evaluation of patients suspected with deep vein thrombosis using indirect CT venography with multi-detector row technology: from protocol to interpretation. AB - With the increased availability of multi-detector row CT, indirect CT venography has become an important non-invasive image modality for patients with suspected deep vein thrombosis. Use of indirect CT venography can not only diagnose/exclude deep vein thrombosis, but can also determine if there are other anomalies or diseases which might contribute to the patient's symptoms. In this pictorial essay, we introduce the scanning protocol, post-processing techniques, and interpretation algorithm used in widely available 64 multi-detector row technology. We discuss several cases, including deep vein thrombosis in acute and chronic stages, anatomic variation, vena cava filter, and collateral veins. Lastly, we consider alternative diagnoses including varicose veins, infection, prosthesis failure of arthroplasty, traumatic vessel injury, and other musculoskeletal conditions. Radiologists should be familiar with the comprehensive interpretation of indirect CT venography to facilitate differential diagnosis and further treatment decision. PMID- 20737216 TI - Prognostic factors of a large retrospective series of mucinous borderline tumors of the ovary (excluding peritoneal pseudomyxoma). AB - BACKGROUND: To determine the prognosis and prognostic factors in a large series of mucinous borderline tumors of the ovary (MBOT). MATERIALS AND METHODS: A retrospective review of patients with MBOT treated or referred to our institution. Three inclusion criteria were defined: (1) centralized histological review by our expert pathologist, (2) exclusion of peritoneal pseudomyxoma and any synchronous malignant tumor in the abdominal cavity, and (3) available data on the management and outcomes of patients. RESULTS: From 1997 to 2004, 97 patients fulfilled inclusion criteria (95 stage I and 2 stage II disease). Of these, 9 patients had endocervical-like subtypes, 8 patients had stromal microinvasion, and 24 had intraepithelial carcinoma. Radical and conservative surgeries were performed, respectively, in 28 and 69 patients. After a median follow-up of 48 months, 13 patients had developed 14 recurrences: 7 were borderline and 7 were invasive lesions. The probability of recurrence in the form of carcinoma 5 and 10 years after the diagnosis was, respectively, 9 and 13%. The only prognostic factor for recurrence attaining statistical significance was the use of a cystectomy (compared with other surgeries relative risk [RR] = 5.6; P = 0.003; compared with salpingo-oophorectomy RR = 5.5; P = 0.012). CONCLUSIONS: In the present series of 97 MBOT, mainly early-stage disease and excluding peritoneal pseudomyxoma, the cumulative risk of recurrence in the form of invasive carcinoma at 10 years was 13%. MBOT do not appear to be such a "safe" disease. The only prognostic factor for recurrence was the use of a cystectomy, suggesting that a salpingo-oophorectomy should be preferred in cases of conservative treatment. PMID- 20737215 TI - Factors influencing the quality of life in patients with HIV in Malaysia. AB - PURPOSE: The aim of this study was to determine the socio-demographic, clinical and psychological factors influencing the quality of life (QOL) in patients with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS). METHODS: This was a cross-sectional study on 271 patients with HIV infection attending an HIV clinic in Kota Bharu, Malaysia. Participants completed the Malay version of the Functional Assessment of HIV Infection (FAHI) and Malay Hospital Anxiety Depression Scale (HADS). RESULTS: The patients functioned satisfactorily in the physical domain. They were mostly impaired in the social domain. Those who acquired the HIV infection via a heterosexual route seemed to have a significantly lower social well-being, while those who acquired HIV via drug injection were not associated with losses in the overall QOL or any of its domains. Non-disclosure paradoxically had a greater effect on social well-being. About 38% had possible anxiety, depression or both, and these emotional disturbances were significantly associated with total FAHI and its five domains. CONCLUSIONS: Psychological and social well-beings were more affected than physical well-being in out-patients with HIV infection in Kota Bharu, Malaysia. The study suggests that the patients with HIV infection should receive better psycho-education and psychological intervention. PMID- 20737217 TI - Salvage surgery for neck residue or recurrence of nasopharyngeal carcinoma: a 10 year experience. AB - BACKGROUND: To assess the outcome of and determine prognostic factors for neck residue or recurrence of nasopharyngeal carcinoma (NPC) in patients treated with a salvage neck dissection. MATERIALS AND METHODS: Over a 10-year period (from January 1998 through December 2007) in a tertiary hospital, we systematically reviewed the clinical charts of 355 patients with NPC who were diagnosed with neck residue or recurrence of nasopharyngeal carcinoma, after radical definitive radiotherapy with or without chemotherapy. RESULTS: The group with recurrent nodal disease consisted of 285 patients (80.3%), while the group with residual nodal disease included 70 patients (19.7%). There were no patients died of the surgery complications. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were 54.11, 35.01, and 55.59%, respectively, at 3 year, and 26.03, 22.65, and 27.84%, respectively, at 5-year. The local control rate in the neck was 70.92% at 3 years and 60.98% at 5 years. For all the 3 survival outcomes (OS, DFS, and DSS) and the local control rate of disease in the neck, there were significant differences between the "residue group" and "recurrence group." CONCLUSIONS: Radical neck dissection is proven to be safe and effective in the treatment of the neck failure. Our study has demonstrated that it may be possible to choose the selective lymph node dissection for patients of the residue group. PMID- 20737218 TI - Borderline resectable pancreatic cancer: definitions and the importance of multimodality therapy. PMID- 20737219 TI - Twelve-month follow-up results of a trial utilizing Axxent electronic brachytherapy to deliver intraoperative radiation therapy for early-stage breast cancer. AB - BACKGROUND: Accelerated partial breast irradiation (APBI) is emerging as a valid alternative to whole-breast radiation therapy (WBRT) in breast-conserving therapy (BCT) for early-stage breast cancer. Axxent electronic brachytherapy (EBX) is a form of portable, balloon-based APBI that utilizes an electronic source of kilovoltage irradiation delivery with minimal shielding requirements. As such, EBX becomes a logical and convenient modality for delivery of intraoperative radiation therapy (IORT). We report 1-year results and clinical outcomes of a trial that utilizes EBX to deliver IORT for patients with early-stage breast cancer. METHODS: Eleven patients were enrolled on an institutional review board (IRB)-approved protocol. Inclusion criteria were patient age >45 years, unifocal tumors with infiltrating ductal or ductal carcinoma in situ (DCIS) histology, tumors <=3 cm, and uninvolved lymph nodes. Preloaded radiation plans were used to deliver radiation prescription dose of 20 Gy to the balloon surface. RESULTS: The mean time for radiation delivery was 22 min; the total mean procedure time was 1 h 39 min. All margins of excision were negative on final pathology. At mean follow-up of 12 months, overall cosmesis was excellent in 10 of 11 patients. No infection, fat necrosis, desquamation, rib fracture or cancer recurrence has been observed. There was no evidence of fibrosis at last follow-up. CONCLUSION: IORT utilizing EBX is emerging as a feasible, well-tolerated alternative to postsurgical APBI. Further research and longer follow-up data on EBX and other IORT methods are needed to establish the clinical efficacy and safety of this treatment. PMID- 20737220 TI - Brain perfusion in adult patients with acute myeloblastic leukemia before and after cytosine arabinoside. AB - PURPOSE: High-dose (HD) cytosine arabinoside (ara-C) is a major treatment in acute myeloblastic leukemia (AML) that can lead to cerebellar complications, although electroencephalogram, computed tomography, and magnetic resonance imaging remain normal. We conducted a prospective study to evaluate brain perfusion with single-photon emission computed tomography (SPECT) in adult patients before and after receiving ara-C. PROCEDURES: Forty-three patients were pre-included, and 20 reached a complete remission. These 20 patients were definitively included and underwent three technetium-99m hexamethyl-propylene amine oxime (HMPAO) SPECT acquisitions with a double-head camera: SPECT1 at AML diagnosis, SPECT2 after induction (conventional ara-C dose), and SPECT3 during HD ara-C treatment. All the included patients underwent six series of neurological and cognitive examinations: N1, N2, and N3 at the time of SPECT1, SPECT2, and SPECT3, respectively; N4 during HD ara-C treatment; N5 (at 10 days); and N6 during follow-up (at 6 months). Statistical parametric mapping (SPM2) was used to test perfusion changes. A specific method based on random walk (RW) was used to analyze diffuse brain perfusion heterogeneity. RESULTS: No neurological adverse effect was observed, and all neurological and cognitive examinations remained normal. Between SPECT1 and SPECT2, SPM2 analysis showed a decrease in cerebral blood flow, i.e., in the cerebellum, in the occipitoparietal cortex, and in the thalamus. No significant difference was observed between SPECT2 and SPECT3 or between SPECT1 and SPECT3. RW analysis showed no significant difference in perfusion heterogeneity between the three SPECTs. CONCLUSIONS: HMPAO SPECT demonstrated a decrease in thalamus, cerebellar, and parieto-occipital perfusion after conventional doses of ara-C in AML patients, although the neurological examinations were normal and the patients had no neurological adverse effects. PMID- 20737221 TI - In vitro evaluation of magnetic resonance imaging contrast agents for labeling human liver cells: implications for clinical translation. AB - PURPOSE: Magnetic resonance imaging (MRI) is a promising approach for non invasive monitoring after liver cell transplantation. We compared in vitro labeling of human liver cells with nano-sized (SPIO) and micron-sized iron oxide particles (MPIO). PROCEDURES: The cellular iron load was quantified and phantom studies were performed using 3.0-T MRI. Transferrin receptor and ferritin gene expression, reactive oxygen species (ROS) formation, transaminase leakage, and urea synthesis were investigated over 6 days. RESULTS: Incubation with MPIO produced stronger signal extinctions in MRI at similar iron loads within shorter labeling time. MPIO had no negative effects on the cellular iron homeostasis or cell performance, whereas SPIO caused temporary ROS formation and non-physiologic activation of the iron metabolic pathway. CONCLUSIONS: Our findings suggest that MPIO are suited for clinical translation of strategies for cellular imaging with MRI. Attention should be paid to iron release and oxidative stress caused by biodegradable contrast agents. PMID- 20737222 TI - Early treatment response evaluation in patients with diffuse large B-cell lymphoma--a pilot study comparing volumetric MRI and PET/CT. AB - PURPOSE: The purpose of this study is to evaluate the time course of early chemotherapy response in patients with aggressive non-Hodgkin's lymphoma (NHL) by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). PROCEDURES: Eight patients with histologically proven aggressive NHL were imaged by MRI and PET/CT before treatment (E1), 1 week (E2), and two cycles (E3) after chemotherapy. RESULTS: The mean tumor volume on MRI was 276 mL at baseline; it decreased 58% at E2 (p < 0.05) and 65% further at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean maximum standardized uptake value (SUV(max)) of 20. The SUV(max) decreased 60% at E2 (p < 0.05) and 59% further at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden (mean 229 mL) decreased 66% at E2 (p < 0.05). The tumor volume on MRI correlated with the active tumor volume on fused PET/CT images in the same region of interest at both E1 and E2 (r = 0.88, p < 0.01, respectively). CONCLUSIONS: Standard chemotherapy causes rapid decrease of both tumor metabolic activity and volume as early as 1 week, which continues to decline during therapy. Both volumetric MRI and PET/CT are valuable tools for early treatment response evaluation of aggressive NHL. PMID- 20737223 TI - Maternal autoimmune thyroiditis and congenital malformations of newborns in a cohort of Slovak women. AB - BACKGROUND: Aim of this study was to compare the thyroidal status of mothers to children with and without congenital malformations (CM). METHODS: We examined 129 mothers of newborns with CM and 228 mothers without CM. The assessment included particular history, physical examination, thyroid ultrasonography, fT4, TSH, and anti-TPO measurement of mothers and comparison to birth proportions of newborns. RESULTS: The total volume of the thyroid gland and anti-TPO levels were significantly higher in mothers of the group with CM (p < 0.001 and p < 0.01, respectively). The birth weight and length were significantly lower in the group with congenital malformation when compared to controls (p < 0.0001 and p < 0.001, respectively). CONCLUSIONS: Based on the results of our study, we suggest that thyroid diseases of a mother might participate in congenital malformations of their newborn, although no direct association between thyroid autoantibodies and congenital malformations has been described as of yet. PMID- 20737224 TI - Chondrosis of the disc - risk factor for osteoporotic vertebral fractures (biomechanical analysis). AB - Based on biomechanical analysis, we present an until now unrecognised new view on pathological interactive relations in basic functional motor segments of the spine (vertebra - disc - vertebra), elevating the risk of osteoporotic vertebral fractures. They are classified as follows: 1. Degenerative alterations of intervertebral disc (chondrosis); 1a) decrease of intervertebral disc viscoelasticity; 1b) increase of compressive and tensile stress in the intervertebral disc. Loading the spine increases the compressive and tensile stress in the disc, afflicted by chondrosis, beyond physiological values. This increase conditions the non-physiological elevation of reaction compression forces in adjacent vertebrae, representing a fracture risk for endplates of these vertebrae. 2. Osteoporosis of vertebrae; 2a) decrease of vertebra elasticity and strength; 2b) phenomenon of local elevated compressive stress in the vertebra fracture site. In the vertebral body endplate infraction or fracture site develop a locus minoris of resistance and it contributes to the progression of breaking the vertebra and its whole compression by loading the spine with compressive force. With regard to the fact that above-mentioned risk factors are influenceable, we suggest preventive measures. PMID- 20737225 TI - [Principles and method of action of targeted therapies.] AB - Conventional cytotoxic therapy is usually characterized by low specificity and considerable side effects. Targeted therapy, by contrast, allows for a specific inhibition with an acceptable side effect profile. A prerequisite for the development of such a therapy, however, is the identification and characterization of the molecular mechanisms that lead to tumor growth. Antibody based targeted therapies usually attack cell membrane-bound or extracellular proteins, while tyrosin kinase inhibitors usually act at intracellular domains of transmembranous proteins. Both strategies ultimately lead to an inhibition of the signal transduction cascade and thereby block increased cell proliferation, metastasis, or the production of new blood or lymph vessels. PMID- 20737226 TI - Parametric maximum parsimonious reconstruction on trees. AB - We give a formal study of the relationships between the transition cost parameters and the generalized maximum parsimonious reconstructions of unknown (ancestral) binary character states {0,1} over a phylogenetic tree. As a main result, we show there are two thresholds lambda1n and lambda0n , generally confounded, associated to each node n of the phylogenetic tree and such that there exists a maximum parsimonious reconstruction associating state 1 to n (resp. state 0 to n) if the ratio "10-cost"/"01-cost" is smaller than lambda1n (resp. greater than lambda0n). We propose a dynamic programming algorithm computing these thresholds in a quadratic time with the size of tree.We briefly illustrate some possible applications of this work over a biological dataset. In particular, the thresholds provide a natural way to quantify the degree of support for states reconstructed as well as to determine what kind of evolutionary assumptions in terms of costs are necessary to a given reconstruction. PMID- 20737227 TI - An evolutionary reduction principle for mutation rates at multiple Loci. AB - A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (Evolutionary Biology, vol. 14, pp. 61-204, 1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models.A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface-a generalization of the hyperplane found by Zhivotovsky et al. (Proc. Natl. Acad. Sci. USA 91, 1079-1083, 1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance.Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains. PMID- 20737229 TI - Chronic care and education. PMID- 20737230 TI - Time for leadership in teaching about care of chronic illness. PMID- 20737228 TI - Chemopreventive effect of different ratios of fish oil and corn oil in experimental colon carcinogenesis. AB - n-3 Polyunsaturated fatty acids (PUFA) have a chemopreventive effect while n-6 PUFA promote carcinogenesis. The effect of these essential fatty acids may be related to oxidative stress. Therefore, the study was designed to evaluate the effect of different ratios of fish oil (FO) and corn oil (CO) in the prevention of colon cancer. Male Wistar rats were divided into control, dimethylhydrazine dihydrochloride (DMH) treated, FO + CO (1:1) and FO + CO (2.5:1). All the groups, except the control received a weekly injection of DMH for 4 weeks. The animals were sacrificed either 48 h later (initiation phase) or kept for 16 weeks (post initiation phase). DMH treatment in the initiation phase animals showed mild to moderate inflammation, decreased ROS and TrxR activity, increased antioxidants, apoptosis and ACF multiplicity. The post initiation study showed severe inflammation with hyperplasia, increased ACF multiplicity and ROS levels, a decrease in antioxidants and apoptosis. The FO + CO (1:1) treated animals showed severe inflammation, a decrease in ROS, an increase in antioxidants and apoptosis in the initiation phase. FO + CO (1:1) in the post initiation phase and FO + CO (2.5:1) in the initiation showed mild inflammation, increased ROS, apoptosis and decreased antioxidants. There was a decrease in ACF multiplicity and ROS levels, increased antioxidants and apoptosis in the post initiation phase study. The present study suggests that FO has a dose- and time-dependent chemopreventive effect in colon cancer mediated through oxidative stress and apoptosis. PMID- 20737231 TI - Resident continuity clinic: an oxymoron? PMID- 20737232 TI - A multi-institutional quality improvement initiative to transform education for chronic illness care in resident continuity practices. AB - BACKGROUND: There is a gap between the need for patient-centered, evidence-based primary care for the large burden of chronic illness in the US, and the training of resident physicians to provide that care. OBJECTIVE: To improve training for residents who provide chronic illness care in teaching practice settings. DESIGN: US teaching hospitals were invited to participate in one of two 18-month Breakthrough Series Collaboratives-either a national Collaborative, or a subsequent California Collaborative-to implement the Chronic Care Model (CCM) and related curriculum changes in resident practices. Most practices focused on patients with diabetes mellitus. Educational redesign strategies with related performance measures were developed for curricular innovations anchored in the CCM. In addition, three clinical measures-HbA1c <7%, LDL <100 mg/dL, and blood pressure 20 kg) as well as the duration of work with highly elevated arms was added up over the entire working life. RESULTS: The results of our study support a dose-response relationship between cumulative duration of work with highly elevated arms and symptomatic supraspinatus tendon tears. For a cumulative duration of >3,195 h work above shoulder level, the risk of a supraspinatus tendon rupture is elevated to 2.0 (95% CI 1.1-3.5), adjusted for age, region, lifting/carrying of heavy loads, handheld vibration, apparatus gymnastics/shot put/javelin/hammer throwing/wrestling, and tennis. The cumulative duration of carrying/lifting of heavy loads also yields a positive dose-response relation with disease (independent from work above shoulder level and from handheld vibration), with an adjusted odds ratio of 1.8 (95% CI 1.0-3.2) in the highest exposure category (>77 h). We find an increased risk for subjects exposed to handheld vibration with an adjusted OR of 3.2 (95% CI 1.7-5.9) in the highest exposure category (16 years or more in the job with exposure), but a clear dose response relationship is lacking. CONCLUSIONS: This study points to a potential etiologic role of long-term cumulative effects of work with highly elevated arms and heavy lifting/carrying on shoulder tendon disorders. PMID- 20737277 TI - Chigger mites (Acari, Trombiculidae) parasitizing small mammals in the Eastern Hindu Kush and some other Afghan areas. AB - Chigger mites of Afghanistan were studied on the base of collections made in Eastern and Central Hindu Kush, Kabul, and some other localities. Fifteen chigger species parasitizing nine species of Rodentia, two species of Lagomorpha, and one species of Soricomorpha were found, including 13 species which were not previously recorded in Afghanistan. Eco-geographical variability is observed in Shunsennia oudemansi: Individuals of this species from high-mountain localities of Eastern Hindu Kush are characterized by larger values of most morphometric characters than the specimens collected in Kabul. Vertical and horizontal distribution of chiggers and chigger-host relationships in Eastern Hindu Kush is discussed. Comparison of our data with that on chigger fauna in the region of Tirich Mir clearly demonstrates the role of the Eastern Hindu Kush main ridge as a border between different chigger faunas. PMID- 20737278 TI - Local warming at injection site helps alleviate pain after rocuronium administration. AB - PURPOSE: Various strategies have been proposed to reduce discomfort of pain after rocuronium injection. These studies have shown pretreatment of drugs such as fentanyl and lidocaine to be effective. In a prospective randomized study, we evaluated whether pretreatment with local warming at injection site using an air warming device could effectively alleviate pain induced by rocuronium. METHODS: Ninety patients undergoing spinal surgeries were randomly divided into two groups: group C (control) and group T (treatment). Patients in group T were subjected to warming at 40 degrees C for 1 min prior to injecting 1 ml (10 mg) of rocuronium at the site of venous access. Patients were then assessed for any discomfort and to quantify their discomfort on a 5-point scale. RESULTS: Age, sex, and weight were comparable between the two groups. Pain on rocuronium administration was reported by 88.9% patient in group C versus 66.7% in group T (p < 0.05). Severe pain was significantly less in group T (35.6% vs. 8.9%). CONCLUSION: Application of warmth over the vascular access prior to rocuronium administration effectively reduces injection-related pain. PMID- 20737279 TI - A case of cardiac herniation after extrapleural pneumonectomy for malignant thymoma. AB - A 44-year-old man underwent radical thymectomy for malignant thymoma 5 years ago. He subsequently underwent right extrapleural pneumonectomy because a right pleural metastatic lesion had developed. The operation was completed uneventfully. Immediately after arrival at the intensive care unit, the patient appeared restless and in pain. His heart rate increased to 140 bpm and then abruptly decreased to 20-30 bpm concomitant with profound systolic hypotension of 30-40 mmHg. Chest X-ray showed that the heart was shifted into the right thorax. Emergent re-thoracotomy was performed and the heart was found to be malrotated and herniated from an upper defect of the pericardial patch in the right thoracic cavity. The heart was returned to the pericardium and the defect was covered with a pericardial patch. The blood pressure and heart rate became stable. He was transferred to the surgical ward from the intensive care unit on the first postoperative day. The rest of the course was uneventful and the patient was discharged on the seventh postoperative day. The incidence of cardiac herniation after extrapleural pneumonectomy following chemotherapy for malignant pleural mesothelioma has been reported to be around 3%. The risk of cardiac herniation should always be considered, especially after extrapleural pneumonectomy. PMID- 20737280 TI - A novel external counterpulsation system for coronary artery disease and heart failure: pilot studies and initial clinical experiences. AB - External counterpulsation (ECP) is a beneficial and noninvasive treatment for coronary artery disease or heart failure; however, it still has a lot of limitations. We used a novel ECP system, Compact CP, the main feature of which is the double-lumen cuff that reduces the impact of cuff inflation and the size of the air compressor. The first lumen was a contact cuff that was attached to the legs with a constant pressure (8 kPa). The second lumen was a main cuff that was inflated and deflated with a driving pressure and synchronized to the cardiac cycle. In this report, we describe the results of four pilot studies in a total number of 39 healthy volunteers and initial clinical experiences of this system in three patients. The pilot studies demonstrated that the ECP system provided significant diastolic augmentation and systolic unloading. It also achieved a satisfactory diastolic/systolic pressure ratio (1.00 +/- 0.06) with a high comfort level at a driving pressure of 40 kPa. Higher pressure (50-70 kPa) increased the assist performance but decreased the comfort level. ECP was also applied with a patient with chronic refractory angina and two patients with postoperative heart failure following cardiac surgery. The clinical conditions improved. No adverse effect was observed. Our novel ECP system is safe, effective, and promising in the treatment of coronary artery disease or heart failure. Further clinical investigations are needed to support the significance of this system. PMID- 20737281 TI - Systematic survey of discrepancy rates in an international teleradiology service. AB - International teleradiology services (ITS) to the United States are based on the principle of deploying American board-certified radiologists across global time zones to optimally distribute the workload. While errors may be reduced by circumventing the traditional night call, there is limited evidence on the actual error rates of teleradiology groups. We have a comprehensive quality assurance (QA) process in our practice, which includes a review of discrepancies between preliminary reports and the final reports by the on-site radiologists. We analyzed the discrepancy QA data to determine the error rates. Archived QA data for 126,449 cases over a period of 1 year (2008) were analyzed for the discrepancy rate, nature of errors, and possible contributory factors. The scores ranged from 0 (no error) to 5 (clinically significant in the acute setting) based on the level of clinical significance. A novel modified Lorenz plot was used to estimate the degree of underreporting and to estimate the true error rate. An internal review of 200 cases was performed to validate the findings. Of the total, there was a total of 227 confirmed errors (0.18%, 95% CI, 0.16 to 0.20). Of these, the majority were levels 2 and 3 (minor error and error of long-term significance but not in the acute setting). Even after correction for underreporting, error rates were less than 1% for clinically significant errors. ITS is associated with very low rates of clinically significant errors. Due to limited feedback, particularly for minor errors, an internal review is important. PMID- 20737282 TI - Finite element-based injury metrics for pulmonary contusion via concurrent model optimization. AB - This study explores the relationship between impact severity and resulting pulmonary contusion (PC) for four impact conditions using a rat model of the injury. The force-deflection response from a Finite Element (FE) model of the lung was simultaneously matched to experimental data from distinct impacts via a genetic algorithm optimization. Sprague-Dawley rats underwent right-side thoracotomy prior to impact. Insults were applied directly to the lung via an instrumented piston. Five cohorts were tested: a sham group and four groups experiencing lung insults of varying degrees of severity. The values for impact velocity (V) and penetration depth (D) of the cohorts were Group 1, (V = 6.0 m . s(-1), D = 5.0 mm), Group 2, (V = 1.5 m . s(-1),D = 5.0 mm), Group 3, (V = 6 m . s(-1), D = 2.0 mm), and Group 4, (V = 1.5 m . s(-1), D = 2.0 mm). CT scans were acquired at 24 h, 48 h, and 1 week post-insult. Contusion volume was determined through segmentation. FE-based injury metrics for PC were determined at 24 h and 1 week post-impact, based on the observed volume of contusion and first principal strain. At 24 h post-impact, the volume of high radiopacity lung (HRL) was greatest for the severe impact group (mean HRL = 9.21 +/- 4.89) and was significantly greater than all other cohorts but Group 3. The concurrent optimization matched simulated and observed impact energy within one standard deviation for Group 1 (energy = 3.88 +/- 0.883 mJ, observed vs. 4.47 mJ, simulated) and Group 2 (energy = 1.46 +/- 0.403 mJ, observed vs. 1.50 mJ, simulated) impacts. Statistically significant relationships between HRL and impact energy are presented. The FEA-based injury metrics at 24 h post-contusion are epsilon(max) . epsilon(max) exceeding 94.5 s(-1), epsilon (max) exceeding 0.284 and epsilon(max) exceeding 470 s(-1). Thresholds for injury to the lung still present at 1 week post-impact were also determined. They are epsilon(max) . epsilon(max) exceeding 149 s(-1), epsilon (max) exceeding 0.343 and epsilon(max) exceeding 573 s(-1). A mesh sensitivity study found that thresholds based on strain rate were more sensitive to changes to mesh density than the threshold based on strain only. PMID- 20737285 TI - N-(2-(N',N'-diethylamino)ethyl)perylene-3,4-dicarboximide and its quaternized derivatives as fluorescence probes of acid, temperature, and solvent polarity. AB - In this manuscript, we report the fluorescence properties of N-(2-(N',N' diethylamino)ethyl)perylene-3,4-dicarboximide (1) and its quaternized derivative N-(2-(N',N'- diethyl-N'-methylammonium)ethyl)perylene-3,4-dicarboximide tosylate (2) in organic solvents. The effects of carboxylic acids and amines on the fluorescence properties of these compounds were investigated. In addition, we studied the aggregation and fluorescence properties of (2) and its 9-bromo substituted derivative (3) in aqueous solution. The fluorescent properties of these compounds change dramatically with the extent of aggregation, thus allowing these compounds to be used as fluorescent probes for changes in temperature and solvent polarity. For instance, the fluorescence emission intensity of 3 increases by about 28 times as the temperature of the solution increases from 10 degrees C to 85 degrees C. The fluorescent intensities of 2 and 3 in methanol are higher than that in water by about 8 and 25 times, respectively. PMID- 20737284 TI - Inhibition of endogenous hedgehog signaling protects against acute liver injury after ischemia reperfusion. AB - PURPOSE: Although Hedgehog (Hh) signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver injury after ischemia reperfusion (I/R) has not been considered. Therefore, we determined the expression pattern of Hh signaling and its role in liver injury following I/R using Hh antagonist cyclopamine (CYA). METHODS: Sprague-Dawley rats were randomly divided into three groups. Sham group underwent a sham operation with no liver I/R. Vehicle or CYA preconditioned I/R groups underwent liver ischemia for 90 min followed by reperfusion for 1 h. Liver tissue and blood were analyzed for gene expression, histological and biochemical evaluation. RESULTS: Hedgehog ligands were upregulated after reperfusion injury. Serum levels of aspartate transaminase and alanine transaminase, inflammatory cytokines, neutrophil infiltration, and tissue damage were significantly less in CYA-pretreated rats compared with vehicle-pretreated rats. CYA also decreased the phosphorylated form of JNK and ERK. CONCLUSIONS: This study provides evidence that endogenous Hh signaling is an early mediator of liver injury and inflammation after I/R. CYA abrogates normothermic I/R injury in rats by inhibiting the MAPK pathway and decreasing the acute inflammatory response. This novel strategy of preconditioning livers with Hh antagonist may have effective therapeutic potential in preventing acute liver injury. PMID- 20737286 TI - The trajectory of change for children and youth in residential treatment. AB - This study examined the symptom response trajectories for 225 children and youth throughout a period of residential treatment. With the 10-item Conners' Global Index (CGI) as the primary outcome measure, assessments were completed on a bi weekly basis during the average 4 month stay within the youth's residential treatment. Clients demonstrated an ongoing reduction of symptoms, and the severity of baseline symptoms influenced the trajectory of the symptom reduction. In addition, symptom reduction was characterized as logarithmic, particularly when controlling for the baseline severity of symptoms. Implications of these findings for administrators, practitioners, and researchers of residential treatment are discussed. PMID- 20737289 TI - TAT is not capable of transcellular delivery across an intact endothelial monolayer in vitro. AB - Developing delivery vehicles capable of penetrating cell barriers is critical for drug delivery to the brain due to the presence of the blood-brain barrier (BBB). Cell-penetrating peptides (CPPs) are one potential solution since they can enter cells; however, it is unclear whether CPPs can pass through cell barriers. In this study, the ability of the TAT CPP to cross an endothelial barrier without disrupting the integrity of its tight junctions was investigated. Endothelial cell monolayers (bEnd.3) were exposed to the TAT peptide, and cell integrity was quantified by zona occludens-1 immunofluorescence, trans-endothelial electrical resistance, and hydraulic conductivity. None of these parameters were significantly altered following exposure to TAT. To evaluate the passage of TAT through the monolayer, the permeability of a green fluorescent protein (GFP)-TAT fusion protein was not significantly different from the permeability of GFP or fluorescent dextrans of similar sizes. Furthermore, GFP-TAT was unable to significantly transduce astrocytes on the opposite side of the bEnd.3 monolayer. We conclude, therefore, that although TAT may not be an efficient delivery vehicle for trans-BBB delivery, our TAT construct may have utility in delivering therapeutic cargos to endothelial cells or to the brain parenchyma after BBB disruption. PMID- 20737288 TI - Differential response of endothelial cells to simvastatin when conditioned with steady, non-reversing pulsatile or oscillating shear stress. AB - Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 MUM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 MUM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 MUM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 MUM. A higher simvastatin concentration of 10 MUM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics. PMID- 20737287 TI - Influence of low levels of dietary aflatoxins on Eimeria tenella infections in broilers. AB - The present study was conducted to evaluate the adverse effects of an interaction between low levels of dietary aflatoxins (AF) and Eimeria tenella infection on broiler chicks. A set of 1-day-old chicks were raised for 35 days in the following groups: a control group, a group fed AF, a group fed AF and inoculated with E. tenella (AF + E.ten), and a group inoculated with E. tenella alone. AF in the contaminated diet were given at 200 ppb starting from the seventh day after hatching while E. tenella was inoculated at a dose of 5 * 10(4) sporulated oocysts per chick at the 14th day after hatching. Worsened performance traits and high mortality were all observed in the treated birds, particularly the AF + E.ten group. Lesion scores and oocyst outputs were not different within groups. Chickens fed with AF had significantly increased serum ALT and ALP activities as well as decreased albumin content. They also showed hepatomegaly, hepatocytic vacuolation and necrosis, an atrophied bursa of Fabricius, and a thymus with tissue depletion. E. tenella-infected broilers displayed a significant reduction in packed cell volume, hemoglobin content and lymphocyte percentage, and showed hemorrhagic typhlitis. The deficits in hepatic function and hematologic parameters as well as the gross pathological, and histopathological changes, were more common and more severe in the group that was exposed to both aflatoxicosis and coccidiosis than in the groups exposed to either treatment alone. Thus, the combination of aflatoxicosis and E. tenella infection may influence the course of coccidial infection due to additive effects. PMID- 20737290 TI - Novel approach for endothelializing vascular devices: understanding and exploiting elastin-endothelial interactions. AB - Elastin is an essential component of arteries which provides structural integrity and instructs smooth muscle cells to adopt a quiescent state. Despite interaction of endothelial cells with elastin in the internal elastic lamina, the potential for exploiting this interaction therapeutically has not been explored in detail. In this study, we show that tropoelastin (a precursor of elastin) stimulates endothelial cell migration and adhesion more than smooth muscle cells. The biological activity of tropoelastin on endothelial cells is contained in the VGVAPG domain and in the carboxy-terminal 17-amino acids. We show that the effects of the carboxy-terminal 17 amino acids, but not those of VGVAPG, are mediated by integrin alpha(V)beta(3). We demonstrate that tropoelastin covalently linked to stainless steel disks promotes adhesion of endothelial progenitor cells and endothelial cells to the metal surfaces. The adherent cells on the tropoelastin-coated metal surfaces form monolayers that can withstand and respond to arterial shear stress. Because of the unique effects of tropoelastin on endothelial and smooth muscle cells, coating intravascular devices with tropoelastin may stimulate their endothelialization, inhibit smooth muscle hyperplasia, and improve device performance. PMID- 20737283 TI - Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. AB - Almost 25 centuries ago, Hippocrates, the father of medicine, proclaimed "Let food be thy medicine and medicine be thy food." Exploring the association between diet and health continues today. For example, we now know that as many as 35% of all cancers can be prevented by dietary changes. Carcinogenesis is a multistep process involving the transformation, survival, proliferation, invasion, angiogenesis, and metastasis of the tumor and may take up to 30 years. The pathways associated with this process have been linked to chronic inflammation, a major mediator of tumor progression. The human body consists of about 13 trillion cells, almost all of which are turned over within 100 days, indicating that 70,000 cells undergo apoptosis every minute. Thus, apoptosis/cell death is a normal physiological process, and it is rare that a lack of apoptosis kills the patient. Almost 90% of all deaths due to cancer are linked to metastasis of the tumor. How our diet can prevent cancer is the focus of this review. Specifically, we will discuss how nutraceuticals, such as allicin, apigenin, berberine, butein, caffeic acid, capsaicin, catechin gallate, celastrol, curcumin, epigallocatechin gallate, fisetin, flavopiridol, gambogic acid, genistein, plumbagin, quercetin, resveratrol, sanguinarine, silibinin, sulforaphane, taxol, gamma-tocotrienol, and zerumbone, derived from spices, legumes, fruits, nuts, and vegetables, can modulate inflammatory pathways and thus affect the survival, proliferation, invasion, angiogenesis, and metastasis of the tumor. Various cell signaling pathways that are modulated by these agents will also be discussed. PMID- 20737291 TI - Cerebrospinal fluid flow dynamics in the central nervous system. AB - Cine-phase-contrast-MRI was used to measure the three-dimensional cerebrospinal fluid (CSF) flow field inside the central nervous system (CNS) of a healthy subject. Image reconstruction and grid generation tools were then used to develop a three-dimensional fluid-structure interaction model of the CSF flow inside the CNS. The CSF spaces were discretized using the finite-element method and the constitutive equations for fluid and solid motion solved in ADINA-FSI 8.6. Model predictions of CSF velocity magnitude and stroke volume were found to be in excellent agreement with the experimental data. CSF pressure gradients and amplitudes were computed in all regions of the CNS. The computed pressure gradients and amplitudes closely match values obtained clinically. The highest pressure amplitude of 77 Pa was predicted to occur in the lateral ventricles. The pressure gradient between the lateral ventricles and the lumbar region of the spinal canal did not exceed 132 Pa (~1 mmHg) at any time during the cardiac cycle. The pressure wave speed in the spinal canal was predicted and found to agree closely with values previously reported in the literature. Finally, the forward and backward motion of the CSF in the ventricles was visualized, revealing the complex mixing patterns in the CSF spaces. The mathematical model presented in this article is a prerequisite for developing a mechanistic understanding of the relationships among vasculature pulsations, CSF flow, and CSF pressure waves in the CNS. PMID- 20737293 TI - Glioma stem cells as a target for treatment. AB - Glioma cells with stem cell-like properties represent a minor subfraction of the total tumor cell population. These cells are highly chemo- and radioresistent and are held responsible for the inevitable recurrence of malignant gliomas. This review summarizes current strategies for targeting putative glioma stem cells. Target definition approaches comprise extrapolation and adaptation of therapies from general oncology, target identification by correlative molecular genetic analyses, and dedicated target discovery research. Targeting strategies include inhibition of tumor-specific signaling pathways, enhancement of tumor cell differentiation, radiosensitization, indirect targeting of the tumor stem cell niche, oncolytic virotherapy, and adhesion molecule blockade. PMID- 20737294 TI - Immune therapeutic targeting of glioma cancer stem cells. AB - Glioblastoma multiforme (GBM) is a lethal cancer that responds poorly to radiotherapy and chemotherapy. Glioma cancer stem cells (gCSCs) have been shown to recapitulate the characteristic features of GBM and to mediate chemotherapy and radiation resistance. Immunotherapeutic targeting of this cell population holds therapeutic promise but must be considered in the context of the immunosuppressive properties mediated by the gCSC. Recent findings have indicated that this goal will be challenging because the gCSC can suppress both the innate and adaptive immune systems by a variety of gCSC-secreted products and cell membrane interactions. In this review article, we will attempt to reconcile the disparate research findings regarding the potential of immune targeting of the gCSC and propose several novel solutions. PMID- 20737295 TI - How to reduce the effect of framing on messages about health. AB - BACKGROUND: Patients must be informed about risks before any treatment can be implemented. Yet serious problems in communicating these risks occur because of framing effects. OBJECTIVE: To investigate the effects of different information frames when communicating health risks to people with high and low numeracy and determine whether these effects can be countered or eliminated by using different types of visual displays (i.e., icon arrays, horizontal bars, vertical bars, or pies). DESIGN: Experiment on probabilistic, nationally representative US (n = 492) and German (n = 495) samples, conducted in summer 2008. OUTCOME MEASURES: Participants' risk perceptions of the medical risk expressed in positive (i.e., chances of surviving after surgery) and negative (i.e., chances of dying after surgery) terms. KEY RESULTS: Although low-numeracy people are more susceptible to framing than those with high numeracy, use of visual aids is an effective method to eliminate its effects. However, not all visual aids were equally effective: pie charts and vertical and horizontal bars almost completely removed the effect of framing. Icon arrays, however, led to a smaller decrease in the framing effect. CONCLUSIONS: Difficulties with understanding numerical information often do not reside in the mind, but in the representation of the problem. PMID- 20737298 TI - The use of cell-delivered gene therapy for the treatment of HIV/AIDS. AB - HIV/AIDS is a disease that impairs immune function, primarily by decreasing T lymphocyte count. Its progression can be contained by highly active antiretroviral therapy (HAART), but there are side effects that can be severe, and the development of resistance often forces the physician to modify the HAART regimen. There are no vaccines available for HIV. An alternative approach that could provide a path to a curative therapy is the use of cell-delivered gene therapy in which an anti-HIV gene(s) is introduced into hematopoietic cells to produce a population that is protected from the effects of HIV. In this paper, we review the field and discuss an approach using a short hairpin RNA to CCR5, an important co-receptor for HIV. PMID- 20737300 TI - Should eligible patients with T-cell lymphoma receive high-dose therapy and autologous stem cell transplant in the upfront setting? AB - Peripheral T-cell lymphomas (PTCL) are rare and aggressive subtypes of non Hodgkin's lymphoma. Compared to B cell lymphomas, the immunologic phenotype of PTCL portends a poorer prognosis, with the exception of anaplastic large cell lymphoma bearing the anaplastic lymphoma kinase protein. Patients with PTCL tend to present clinically in advanced disease states, show lower response rates to chemotherapy, and suffer from more frequent relapses and shorter remissions. The rarity of these lymphomas has made it difficult to carry out prospective, randomized trials delineating optimal treatments. Conventional and intensified chemotherapy have led to reasonable responses, but in many studies, frequent relapses. Consequently, high-dose chemotherapy and autologous stem cell transplantation (ASCT) have been actively studied in both the relapsed and upfront setting. In addition, the impact of disease status at transplantation is being investigated, though the optimal disease state at transplant is still a matter of debate, as is the timing of transplant. This article seeks to review the literature on the role of ASCT in PTCL, as well as to clarify what may be the optimal disease state in which to offer patients with PTCL autologous transplantation, if at all. PMID- 20737302 TI - Biographical sketch: Otto Heinrich Warburg, PhD, MD. AB - This biographical sketch of Otto Heinrich Warburg corresponds to the historic text, The Classic: The Chemical Constitution of Respiration Ferment (1928), available at DOI 10.1007/s11999-010-1534-y. PMID- 20737299 TI - Integration of metabolic reactions and gene regulation. AB - Metabolic reactions and gene regulation are two primary processes of cells. In response to environmental changes cells often adjust the regulatory programs and shift the metabolic states. An integrative investigation and modeling of these two processes would improve our understanding about the cellular systems and may generate substantial impacts in medicine, agriculture, environmental protection, and energy production. We review the studies of the various aspects of the crosstalk between metabolic reactions and gene regulation, including models, empirical evidence, and available databases. PMID- 20737303 TI - Acetabular component positioning using the transverse acetabular ligament: can you find it and does it help? AB - BACKGROUND: Several studies have reported that the transverse acetabular ligament (TAL) can be used to orient the acetabular component during total hip arthroplasty and that it can be identified in nearly all patients. QUESTIONS/PURPOSES: We attempted to determine how often the TAL could be identified during primary THA and its accuracy as a guide for acetabular component positioning. METHODS: In a prospective series of 63 patients (64 hips) undergoing primary THA, two surgeons attempted to identify the TAL and, if it was found, to use it for acetabular component orientation. Patients in whom the TAL was identified served as the study group and the ligament was used for cup orientation in those patients; the remaining patients in whom the ligament could not be identified served as a control group and had free-hand cup positioning. Anteversion was determined by radiographic measurement from true lateral views. RESULTS: The TAL was identified in only 30 hips (47%) and was more likely to be found in patients who did not have inferior acetabular osteophytes. Acetabular position was not improved using this ligament for reference. CONCLUSIONS: The TAL could not be routinely identified at surgery and when used for cup orientation it was no more accurate for cup positioning than free-hand technique. PMID- 20737301 TI - The impact of vaccination on rhinosinusitis and otitis media. AB - Routine childhood vaccination has affected frequency and bacteriology of acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS). Routine influenza vaccination moderately reduces AOM, and the Haemophilus influenzae type b vaccine likely had a minor role in AOM and ABRS. The conjugated pneumococcal vaccine has drastically reduced invasive pneumococcal disease and caused a moderate decrease in AOM and, likely, ABRS. The vaccine serotypes of Streptococcus pneumoniae have been all but eliminated, but other serotypes have emerged as potential causes of invasive disease. Antibiotic resistance in pneumococcal disease seems to have decreased. A decrease in the overall prevalence of S. pneumoniae may have resulted in an increased incidence of Staphylococcus aureus as a pathogen in AOM and ABRS due to the concept of bacterial interference. PMID- 20737305 TI - Further caries decline in Swiss recruits from 1996 to 2006. AB - Previous investigations showed a steady decline of the caries experience. The purpose of this study was to determine the caries experience of Swiss recruits in 2006 and to compare it to that of 1985 and 1996. The results of a parallel investigation which dealt with the periodontal health of the same recruits have already been published (Rothlisberger et al. 2007). Investigations on recruits in 1970 (Curilovic et al. 1972) and 1974 (Curilovic et al. 1980) used another methodology. Therefore, they were not included here for comparison. PMID- 20737306 TI - [Treatment strategy and pattern evaluation of 314 patients with recurrence of rectal cancer]. AB - OBJECTIVE: To evaluate the treatment strategy, prognosis and pattern of recurrence in patients with rectal cancer. METHODS: From May 1979 to November 2006, 314 patients with recurrence after rectal cancer resection were included in this study. Patients were divided into two groups: local recurrence (LR) and distant metastasis (DM). The clinicopathologic features, treatment strategies and prognosis were analyzed. RESULTS: Of the 314 patients with recurrence, 168 (53.5%) were LR with a mean recurrence-free interval (RFI) of (24.7+/-1.9) months and 146 (46.5%) were DM with a mean RFI of (22.7+/-1.9) months. Compared to the DM group, the patients in the LR group showed no significant difference in clinicopathological data except the time to recurrence (P<0.01), primary tumor location (P=0.043), and the postoperative use of chemoradiotherapy (P=0.007). Mean recurrence-specific survival(RSS) was (24.7+/-1.9) months for LR and the 3- and 5-year survival rates were 0.48 and 0.25. The 3- and 5-year survival rates in patients with DM were 0.33 and 0.16 with a mean RSS of (22.7+/-1.9) months. The difference was statistically significant (P<0.01). Cox regression analysis for RSS showed that the time to recurrence, TNM stage, and treatment strategy (including procedure and the use of postoperative chemoradiation) were independently prognosis factors for the patients with recurrence rectal cancer (all P<0.01). Subgroup analyses revealed no significant differences in RFI or RSS among different subgroups within either LR or DM groups. CONCLUSIONS: Patients of rectal cancer with LR have a better survival than those with DM. Moreover, radical resection can improve the prognosis of patients with recurrence of rectal cancer, especially for patients with early TNM stage of the primary tumor and later period of recurrence. PMID- 20737307 TI - [Accuracy comparison of preoperative histological assessment in differentiation and grading of rectal adenocarcinoma]. AB - OBJECTIVE: To compare the accuracy of preoperative assessment in differentiation and grading of rectal adenocarcinoma. METHODS: One hundred consecutive patients diagnosed as invasive rectal cancer by colonoscopy biopsy and undergone operation in the Changhai Hospital from March 2006 to May 2008 were studied retrospectively. Patient characteristics, examination records, operative and pathologic reports were reviewed. The slides of preoperative biopsy and postoperative pathologic specimen were reviewed to identify the differentiation by a single pathologist. The results of preoperative biopsy were compared to those of postoperative specimen which was considered as final diagnosis. The accuracy of preoperative assessment of differentiation was calculated. Patients were then divided into two groups based on the preoperative differentiation:the low-grade tumor including well and moderately differentiated tumors, and the high grade tumor consisting of poorly differentiated and undifferentiated tumors. The accuracy of grading was also calculated. RESULTS: The accuracy of preoperative assessment of differentiation was 72%, with 20% overgrading and 8% undergrading, while the accuracy of preoperative grading was 91%, with 4% overgrading and 5% undergrading. The accuracy of grading was significantly higher than that of specific differentiation(P<0.01). CONCLUSION: The grading of preoperative biopsy has high accuracy rate and should be considered in clinical practice. PMID- 20737308 TI - [Biofeedback therapy for fecal incontinence in patients with mid or low rectal cancer after restorative resection]. AB - OBJECTIVE: To investigate the efficacy of biofeedback therapy for fecal incontinence in patients with mid or low rectal cancer. METHODS: Twenty-four patients with mid or low rectal cancer received biofeedback treatments after restorative resection and therapeutic efficacy was evaluated using anorectal manometry and Vaizey and Wexner scoring systems. Eighteen inpatients without defecating difficulties were selected as control group. RESULTS: The parameters of anorectal manometry in patients with rectal cancer were significantly lower than those in the control group (P<0.01). After biofeedback therapy, the maximum squeeze pressure, resting pressure and maximum tolerated volume were significantly increased, from (118.3+/-42.9) mm Hg to (193.2+/-38.2) mm Hg, (27.8+/-9.0) mm Hg to (47.9+/-9.3) mm Hg,(97.5+/-52.8) ml to (189.1+/-39.0) ml, respectively (all P<0.01), while no significant difference in sensory threshold was observed (P=0.101). Post-treatment Vaizey (10.5+/-2.3 vs 12.9+/-2.8) and Wexner (7.5+/-2.5 vs 10.1+/-2.6) scores were significantly decreased compared with those before biofeedback (P<0.01). CONCLUSION: Biofeedback therapy can improve the anal function in patients with rectal cancer after restorative resection. PMID- 20737309 TI - [Clinicopathological and prognostic analysis of 23 poorly differentiated neuroendocrine carcinomas of the stomach]. AB - OBJECTIVE: To evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach. METHODS: Twenty three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed. RESULTS: Poorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter. CONCLUSIONS: Poorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival. PMID- 20737310 TI - [Clinicopathologic features, diagnosis and treatment of 38 neuroendocrine carcinoma in the digestive system]. AB - OBJECTIVE: To investigate the clinicopathologic features, diagnosis and treatment of neuroendocrine carcinoma (NEC) in the digestive system. METHODS: Thirty-eight patients with NEC from Jan 1985 to Mar 2008 were analyzed retrospectively and the related literatures were reviewed. RESULTS: There were 29 males and 9 females. Common symptoms were melena or hematochezia (n=21, 55%), abdominal pain (n=19, 50%), abdominal mass (n=15, 39%), constipation (n=14, 37%), rectal mass (n=12, 32%), abdominal distention (n=11,29%) and diarrhea (n=7,18%). All the patients received surgical treatment including 1 esophagectomy, 5 radical total gastrectomies, 1 palliation proximal gastric resection, 2 local gastric resections, 6 pancreaticoduodenectomies, 1 distal pancreatectomies, 3 partial small intestine resections, 7 radical right hemicolectomies, 5 Dixon operations, 3 Miles operations, and 4 local resections of rectal tumor. Thirty-six patients received follow-up. The follow-up time ranged from 3 months to 144 months (median, 70 months). The 1-, 3- and 5-year survival rates were 94.7%, 86.8%, and 57.9% respectively. The median survival time was 62 months. The survival time of the patients with carcinoma infiltration exceeding bowel muscularis propria was (36+/-5) months, significantly shorter than that of patients without carcinoma infiltration exceeding the bowel muscularis propria [(73+/-5) months, P<0.05]. The survival time of the patients with positive lymph node metastasis was (34+/ 7) months, significantly shorter than that of patients with negative lymph node metastasis [(74+/-5) months, P<0.05]. CONCLUSIONS: Clinical symptoms, signs of neuroendocrine carcinoma in the digestive system are nonspecific. The correct diagnosis should depend on histopathologic examination. Systematic treatments including radical resection of NEC are the preferable treatment. PMID- 20737311 TI - [Clinical characteristics of 103 lymph node metastasis in advanced proximal gastric cancer]. AB - OBJECTIVE: To explore the pattern of lymph node metastasis(LNM) in advanced proximal gastric cancer in order to guide lymphadenectomy. METHODS: Between September 2001 and December 2005, a total of 103 patients with advanced proximal gastric cancer underwent radical gastrectomy with D2 or>D2 lymphadenectomy. The clinical characteristics, pathologic features, and LNM were analyzed by univariate and multivariate analysis. RESULTS: LNM was observed in 81 of 103 cases(78.6%). The LNM was identified in 70.8% at N1, 38.3% at N2, 22.3% at N3. LNM frequency was found in groups No.3,No.1,No.2 and No.4Sa,4Sb (from the highest to the lowest) at N1, groups No.7, No.10, No.9, No.11, No.8a and No.4d at N2, and groups No.5, No.6, No.16 and No.12 at N3. Ordinal Logistic regression analysis showed that histopathological type, tumor size, depth of invasion, and distant metastasis were independent factors for lymph node metastasis in advanced proximal gastric cancer. CONCLUSIONS: The number of lymph node metastasis in advanced proximal gastric cancer is mainly associated with differentiation, tumor size, depth of invasion, and distant metastasis. It is essential to dissect the lymph nodes according to the risk of lymph node metastasis. PMID- 20737312 TI - [Treatment of obesity and type 2 diabetes mellitus by laparoscopic Roux-en-Y gastric bypass]. AB - OBJECTIVE: To investigate the efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) in the treatment for obesity and type 2 diabetes mellitus (DM). METHODS: Twenty-one cases of obesity and 9 cases of type 2 DM received the LRYGB. Weigh changes, excess body weight lose rate (EWL%) and blood glucose level were measured after surgery and occurrence of complications was observed postoperatively. RESULTS: LRYGB procedures in all the 30 cases were successfully performed with no conversion to open surgery. Average operation time was 168 minutes (110-270 mins), volume of blood loss during the surgery was 24.0 ml (10 75 ml). Twenty-one cases of simple obesity received follow-up from 2 months to 5 years. Body weight and BMI decreased significantly in one month [(85.1+/-10.1) kg vs (97.2+/-15.0) kg, 31.2+/-2.2 vs 35.3+/-3.5, both P<0.01] and to a minimal level in 2 to 3 years [(66.8+/-9.2) kg, 24.3+/-1.1], and then maintained at this level. EWL% was correspondingly higher (all P<0.05). Nine type 2 DM patients were followed up for 3 to 8 months, fasting blood glucose and blood glucose OGTT2 hours decreased significantly [(5.9+/-1.4) mmol/L vs (12.6+/-2.6) mmol/L, (7.8+/ 1.4) mmol/L vs (17.8+/-4.1) mmol/L, both P<0.05], of whom 4 patients with obesity decreased in BMI significantly (P<0.05), and 5 patients without obesity had no significant changes in BMI (P>0.05). Five cases (16.7%) had postoperative complications, including 1 case of death due to acute fulminant pancreatitis, 1 case of mesenteric hiatal hernia with obstruction in line for reoperation, and the other 3 cases of healing by conservative therapy. CONCLUSIONS: Treatment of obesity and type 2 DM by LRYGB surgery is feasible with significant short term result. Long term outcome needs further observation. PMID- 20737313 TI - [A prospective comparative study of three treatment options in patients with malignant gastric outlet obstruction]. AB - OBJECTIVE: To evaluate outcomes after different treatment options including endoscopic stent placement, surgical bypass, and percutaneous gastrostomy for malignant gastric outlet obstruction (GOO). METHODS: Thirty-nine patients with GOO secondary to unresectable primary or metastatic cancer were treated with endoscopic stent placement (group 1, n=13), surgical bypass (group 2, n=21), or percutaneous gastrostomy (group 3, n=5). QLQ-STO22 form was used to assess quality of life (QOL) at baseline, 1 month, and 3 months following intervention. RESULTS: Overall median survival time was 68 days. Median survival time in group 1 and group 2 was 85 and 72 days respectively, longer than that in group 3 (48 days, P<0.05). Fourteen patients (7 cases in group 1 and 7 cases in group 2) completed all three QOL surveys. All the patients in group 1 had significant improvement in dysphagia, dietary restrictions, dry mouth, and reflux (P<0.05). In group 2, dysphagia and dietary restrictions were significantly improved (P<0.05), while there were no significant improvements in dry mouth, reflux and pain (all P>0.05). CONCLUSION: Although the prognosis of malignant GOO is poor, endoscopic stent placement and surgical bypass may improve QOL of patients and therefore are reasonable alternatives for palliation. PMID- 20737314 TI - [Transabdominal rectopexy with mesh repair for full-thickness rectal prolapse in adults]. AB - OBJECTIVE: To investigate the efficacy of transabdominal rectopexy with mesh repair for adults with full-thickness rectal prolapse (II-III degree). METHODS: Between January 2005 and March 2009, 11 adult patients with full-thickness rectal prolapse (II-III degree) were treated by transabdominal rectopexy with mesh repair. Clinical data were analyzed retrospectively. RESULTS: Of the 11 cases of rectal prolapse, 7 cases were in II degree, 4 in III degree. Operative time ranged from 1.8 to 2.6 hours. Estimated blood loss during operation ranged from 50 to 300 ml. There was only one patient developed urinary retention postoperatively and no other complications were observed. After follow-up from 1 to 3 years, no recurrence was found. Patients had good anal function during the follow up. CONCLUSION: Transabdominal recopexy with mesh repair is a simple procedure with low recurrence rate. PMID- 20737315 TI - [Expression of Na+-H+ exchanger 1 in human gastric carcinoma tissue and its clinical significance]. AB - OBJECTIVE: To determine the expression of Na+/H+ exchanger 1(NHE1) in human gastric carcinoma tissue and to investigate the association between NHE1 expression and clinicopathological characteristics. METHODS: The expressions of NHE1 mRNA and protein were detected in both gastric carcinoma tissue (n=60) and adjacent gastric mucosa tissue (n=30) by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The association between the expression and the clinicopathological characteristics was analyzed. RESULTS: The relative expression levels of NHE1 mRNA and protein in gastric carcinoma tissue were 0.786+/-0.291 and 1.442+/-0.175, which were significantly higher than those in adjacent gastric mucosa tissue (0.369+/-0.052 and 0.348+/-0.029) (P<0.01). The expression of NHE1 mRNA was positively correlated with NHE1 protein in the gastric carcinoma tissue (r=0.264, P<0.05). The expressions of NHE1 mRNA and protein were associated with the depth of invasion, lymph node metastasis, and TNM staging (P<0.05). However, no statistical difference was found in age, gender, and tumor differentiation (P>0.05). CONCLUSION: The expression levels of NHE1 mRNA and protein are significantly up-regulated in gastric carcinoma tissue, which may be involved in the development of gastric carcinoma. PMID- 20737316 TI - [Expression of carcinoembryonic antigen receptor in digestive organs]. AB - OBJECTIVE: To explore the significance of the expression of carcinoembryonic antigen receptors (CEAR) in digestive organs. METHODS: Specimens were procured from 20 male BALB/c mice including esophagus, small intestine, stomach, colon, pancreas, and liver. Kupffer cells were obtained by density gradient centrifugation following enzymatic digestion of the fresh liver specimen. Immunohistochemistry and immunocytochemistry methods were used to detect CEAR in those organs or Kupffer cells. RESULTS: CEAR was found both in cytoplasm and nuclei of the digestive tract mucosal epithelial cells and pancreas islet cells, but only in the cytoplasm of liver cells, Kupffer cells, and smooth muscle cells of the whole digestive tract. The mean ranks of CEAR expression were 174.33 in the mucosal epithelial cells of colon, 160.70 in epithelial cells of small intestine, 139.18 in Kupffer cells, 137.43 in pancreas islet cells, 131.70 in liver cells, 124.23 in gastric epithelial cells, 77.15 in esophageal epithelial cells and 57.80-71.00 in smooth muscle cells of the entire digestive tract examined. There were significantly differences in the CEAR expression intensity among those positive cells (chi2=99.58, P<0.01) while CEAR was not present in submucosal connective tissue cells, pancreatic exocrine cells, or hepatic sinusoid endothelial cells. CONCLUSION: There are significantly differences in the expression of CEAR in the main digestive organs according to the different tissue and cells, which may play an important role in the carcinogenesis and hepatic metastasis from tumors of the digestive system. PMID- 20737317 TI - [Effect of COX-2 inhibitor on the expression of BCL-3 and cyclin D1 in human colon cancer cell line SW480]. AB - OBJECTIVE: To study the effects of NS398, a selective cyclooxygenase-2 (COX-2) inhibitor, on the transcription and translation of BCL-3 and its regulatory gene cyclin D1 in colon cancer cell line SW480. METHODS: Human colon cancer cells SW480 were divided into two groups: SW480 cells in experimental group were treated with NS398 in different concentrations(25 micromol/L, 50 micromol/L, 100 micromol/L and 200 micromol/L) for 48 h or 72 h. SW480 cells in control group were treated with media which did not contain NS398. Then the expressions of BCL 3 and cyclin D1 were detected by RT-PCR, Western blot, and immunocytochemistry. RESULTS: At 48 hours RT-PCR showed that BCL-3 mRNA and cyclin D1 mRNA decreased in a dose-dependent manner in the experimental group. However, there were no significant differences in the levels of BCL-3 protein and cyclin D1 protein between two groups (P>0.05). At 72 hours, BCL-3 protein and cyclin D1 protein also decreased in a dose-dependent manner in the experimental group. When the concentration of NS398 reached 100 micromol/L, the differences between the two groups in the expression of BCL-3 mRNA and protein became statistically significant (P<0.01). When the concentration of NS398 reached 50 micromol/L, the differences in the expression of cyclin D1 mRNA and protein were statistically significant (P<0.05). CONCLUSIONS: BCL-3 is expressed in colon cancer cell line SW480. COX-2 inhibitor can inhibit the expression of BCL-3 and cyclin D1 in a dose-dependent manner. NS398 may down-regulate the expression of cyclin D1 through BCL-3. PMID- 20737318 TI - [Effect of von Willebrand factor on the biological characteristics of colorectal cancer cells]. AB - OBJECTIVE: To study effect of von Willebrand factor (vWF) on the proliferation, adhesion and migration of human colorectal cancer cells. METHODS: Human colorectal cancer cell line SW480 was cultured in vitro, and the expression of vWF in SW480 cells was detected by immunocytochemistry. SW480 cells were treated with vWF antibody (vWFAb), and the morphological change was examined by inverted microscope. Cell proliferation and ability to adhere extracellular matrix IIII( collagen were detected with MTT. Migration ability of SW480 cells was assayed by Transwell. RESULTS: The human colorectal cancer cell line SW480 expressed vWF which was mainly in nucleus and slightly in cytoplasm. vWFAb significantly inhibited the proliferation ability of SW480 cells in dose- and time-dependent manner (P<0.05). After vWFAb treatment, SW480 cells adhesion decreased significantly (P<0.05), and transmembrane migration of cells significantly decreased (54.60+/-11.01 vs 97.27+/-10.01, P<0.01). CONCLUSIONS: Human colorectal cancer cells can express vWF. vWF in human colorectal cancer cells plays an important role in promoting proliferation, adhesion, and migration. PMID- 20737319 TI - The quality of life and factors associated with it in the medically hospitalised elderly. AB - AIM: The present study describes the quality of life (QOL) and explores health related factors associated with domains of the QOL in the acutely ill and hospitalised elderly. METHOD: In all, 484 elderly (65-101 years, 241 men) patients hospitalised in an acute medical unit participated. Their QOL (in its overall and physical, psychological, social and environmental domains) was assessed with the World Health Organisation's WHOQOL-BREF. The QOL was explored with multiple linear regression analysis. Health-related variables controlled for socio-demographic background were the independent variables. RESULTS: The overall QOL was good in two-thirds of the elderly patients. In multiple linear regression models, lower physical QOL was significantly associated with a number of medications, impaired personal activities of daily living (PADL), impaired cognition, depression and anxiety. Lower psychological QOL was significantly associated with impaired PADL, impaired cognition, depression and anxiety. Lower social QOL was significantly associated with depression and anxiety. Lower environmental QOL was significantly associated with female gender, impaired PADL, depression and anxiety. CONCLUSION: Our results indicate that improvement in the medical state, functional status and/or emotional condition of elderly medically hospitalised patients may improve their QOL. PMID- 20737320 TI - The mediating effect of self-efficacy on the relationship between health literacy and health status in Korean older adults: a short report. AB - OBJECTIVES: Limited health literacy has been shown to be associated with poor health status. However, research to date has not elucidated the factors that mediate the relationship between low literacy and poor health outcomes. The purpose of this study was to examine the mediating effect of self-efficacy on the relationship between health literacy and health status in Korean older adults. METHOD: A cross-sectional study of 103 community-dwelling Korean older adults was conducted from June 2007 to September 2007. RESULTS: The study found that low health literacy was associated with poorer physical and mental health status, and the effect of health literacy on physical and mental health status was mediated through self-efficacy. CONCLUSION: The study suggests that interventions to improve the delivery of care for older adults with low health literacy need to include not only improving the readability of health-related materials, but also enhancing the self-efficacy of each individual. PMID- 20737321 TI - Major depressive disorder in late life: a multifocus perspective on care needs. AB - BACKGROUND: The effectiveness of late-life depression treatment can be improved by tailoring interventions to patients' needs. Unmet needs perceived by patients suffering from a severe mental illness, e.g. depression, may have a negative impact on their recovery. AIM: The aim of this study is to gain insight into the needs of outpatients with late-life depression. METHOD: Ninety-nine outpatients (aged 58-92) receiving treatment for major depressive disorder were recruited from six specialized mental health care facilities in the Netherlands. They were interviewed using the Dutch version of the Camberwell Assessment of Needs for the Elderly (CANE-NL) to identify met and unmet needs. The Montgomery-Asberg Depression Rating Scale was administered to measure depression severity. RESULTS: Depression severity levels varied from remission (23%), mild (31%), moderate (31%) to severe depression (15%). The average number of needs reported was 8.86, comprising 6.5 met needs and 2.3 unmet needs. Most of the unique variance in depression severity was explained by psychological unmet needs, more in particular by needs representing psychological distress. The environmental, social or physical unmet needs, respectively, showed less or no meaningful predictive value for variance in depression severity. CONCLUSION: The psychological needs category of the CANE appeared to be the strongest predictor of depression severity. Systematic needs assessment may be considered as a necessary complement to medical examination and a prerequisite for the development of tailored treatment plans for older people with depression. PMID- 20737322 TI - Effectiveness of integrative and instrumental reminiscence therapies on depression symptoms reduction in institutionalized older adults: an empirical study. AB - OBJECTIVE: Reminiscence therapy is a psychological intervention which is specifically designed to address issues of particular relevance to older adults, such as depression. The latest approach to the research on therapeutic utility of reminiscence is gaining popularity among researchers and practitioners, and has yielded promising results. Specifying different types of reminiscence is a crucial component of the approach. The aim of this study was to examine the therapeutic effectiveness of integrative and instrumental types of reminiscence for the treatment of depression in institutionalized older adults dwelling in a nursing home. METHOD: The study employed a three-group pre-post-test design with random allocation to instrumental or integrative reminiscence or an active social discussion control condition. Twenty-nine institutionalized older adults (12 men and 17 women) with depressive symptoms varying from mild to severe constituted the sample. The interventions were implemented in a short-form group format. FINDINGS: Analysis of changes from pre-test to post-test revealed that integrative reminiscence therapy led to statistically significant reduction in symptoms of depression in contrast with the control group. Although instrumental reminiscence therapy also reduced depressive symptoms, this improvement was not statistically significant compared to the control group. CONCLUSION: This study provides additional support for the effectiveness of integrative reminiscence therapy as an intervention for depressed older adults living in residential care settings. This study also provides support for the hypothesis that certain types of reminiscence produce their own specific effects. PMID- 20737324 TI - Contamination aversion and repeated exposure to disgusting stimuli. AB - Recent research has highlighted the central role of disgust in the etiology and maintenance of contamination aversion (CA). Data would also suggest that, although amendable to the treatment of choice for CA (exposure and response prevention [ERP]), disgust is resistant to habituation. However, with regard to CA, it is not yet known if disgust's resistance to habituation is an artifact of the emotion or the disorder. Specifically, research has not yet indicated if severity of CA moderates the effect of ERP on disgust. Utilizing an undergraduate convenience sample (n=33), the present study compared emotional responding (disgust and fear) with repeated exposure to a disgusting contamination-relevant stimulus between participants who are high in contamination aversion (HCA; n=17) and low in contamination aversion (LCA; n=16). Results indicated that, habituation of disgust was slower than fear within the HCA group but not the LCA group. Contrasts revealed that the decay of fear across trials was faster for HCA participants when compared with LCA participants, although decay of disgust was similar between groups. These results indicate that habituation of disgust is slower than fear when elevated CA is present. PMID- 20737326 TI - Absence of cross-linking via trans-glutaminase in barnacle cement and redefinition of the cement. AB - Balanomorphan barnacles attach their calcareous bases to a variety of substrata, including others of the same species, through secretion of an underwater adhesive, commonly referred to as cement. In this multi-functional process of underwater attachment, curing of the adhesive is crucial for the formation of a secure attachment. To date, there has been no direct evidence presented to suggest the involvement of cross-linking or polymerization in the cement curing process, despite the emergence of this hypothesis in the recent literature. A recently proposed mechanism for cement curing involves glutamyl-lysine cross linking via the action of trans-glutaminase. However, in the opinion of the author, inadequate attention may have been paid to sample collection during the study and the conditions used in the analysis may not be adequate to support the conclusions of the paper. Indeed, further investigation, the results of which are presented here, did not provide any evidence to support adhesive curing via glutamyl-lysine cross-linking. Therefore, the hypothesis that the process of cement curing is similar to the clotting system of barnacle hemolymph is not compatible with the data reported so far. In order to allay any potential confusion, a new definition of the barnacle cement is proposed. PMID- 20737327 TI - The risk of biomaterial-associated infection after revision surgery due to an experimental primary implant infection. AB - The fate of secondary biomaterial implants was determined by bio-optical imaging and plate counting, after antibiotic treatment of biomaterials-associated infection (BAI) and surgical removal of an experimentally infected, primary implant. All primary implants and tissue samples from control mice showed bioluminescence and were culture-positive. In an antibiotic treated group, no bioluminescence was detected and only 20% of all primary implants and no tissue samples were culture-positive. After revision surgery, bioluminescence was detected in all control mice. All the implants and 80% of all tissue samples were culture-positive. In contrast, in the antibiotic treated group, 17% of all secondary implants and 33% of all tissue samples were culture-positive, despite antibiotic treatment. The study illustrates that due to the BAI of a primary implant, the infection risk of biomaterial implants is higher in revision surgery than in primary surgery, emphasizing the need for full clearance of the infection, as well as from surrounding tissues prior to implantation of a secondary implant. PMID- 20737328 TI - The Empathy Quotient: a cross-cultural comparison of the Italian version. AB - INTRODUCTION: The Empathy Quotient (EQ) is a self-report questionnaire that was developed to measure the cognitive, affective, and behavioural aspects of empathy. We evaluated its cross-cultural validity in an Italian sample. METHODS: A sample of 18- to 30-year-old undergraduate students of both sexes (N=256, males=118) were invited to fill in the Italian version of the EQ, as well as other measures of emotional competence and psychological distress. Results. The EQ had an excellent reliability (Cronbach's alpha=.79; test-retest at 1 month: Pearson's r=.85), and was normally distributed. Females scored higher than males, and more males (n=14, 11.9%) than females (n=4, 2.9%) scored lower than 30, the cutoff score that best differentiates autism spectrum conditions from controls. EQ was negatively related to the Toronto Alexithymia Scale (TAS) and positively related to the Marlowe-Crowne Social Desirability Scale (SDS). Principal component analysis retrieved the three-factor structure of the EQ. Lower emotional reactivity correlated with higher scores in measures of risk in both the schizophrenia-like (Peters et al. Delusions Inventory) and the bipolar (Hypomanic Personality Scale) spectra. CONCLUSIONS: The Italian version of the EQ has good validity, with an acceptable replication of the original three-factor solution, yielding three subscales with high internal and test-retest reliability. PMID- 20737329 TI - Analysis and interpretation of serial position data. AB - The representation of serial position in sequences is an important topic in a variety of cognitive areas including the domains of language, memory, and motor control. In the neuropsychological literature, serial position data have often been normalized across different lengths, and an improved procedure for this has recently been reported by Machtynger and Shallice (2009). Effects of length and a U-shaped normalized serial position curve have been criteria for identifying working memory deficits. We present simulations and analyses to illustrate some of the issues that arise when relating serial position data to specific theories. We show that critical distinctions are often difficult to make based on normalized data. We suggest that curves for different lengths are best presented in their raw form and that binomial regression can be used to answer specific questions about the effects of length, position, and linear or nonlinear shape that are critical to making theoretical distinctions. PMID- 20737331 TI - Naive judgements of stimulus-response compatibility. AB - An experiment is reported that is an extension of Payne (1995) and of Vu and Proctor (2003). These authors used various light/key arrangements to determine the ability of naive subjects to rate the usability of interface designs and found that naive judgements were not accurate, apart from selecting a best design. In this experiment, there were one, two, four and eight arrangements of lights and response keys with varying levels of compatibility between them. Response time is shown to be determined by two main factors: the level of response uncertainty (the number of light/key combinations); the correlation between stimulus-light and response key location, accounting for up to 93% of the experimental variance. Subjective response time (SRT), or judged response time, was responsive to the level of response uncertainty and also the correlation between light/key combinations, showing good correspondence to actual reaction times. It was found that SRT showed a stronger relationship to actual response time when subjects were presented with the full set of situations that they were to respond to, prior to judgements being made, rather than just individual sets for comparison. In interface design it is essential that, in order to reduce reaction times and error rates, there is a high level of user expectancy between locations of the stimulus and corresponding response. This research indicates how designs might be evaluated, based on the geometrical layout of stimuli and response arrangements. PMID- 20737330 TI - Intravaginal insertion in KwaZulu-Natal: sexual practices and preferences in the context of microbicide gel use. AB - Intravaginal insertion is often associated with the concept of 'dry' sex. All HIV prevention microbicides tested to date have been vaginally applied lubricant based gels. In this paper, we examine whether the use of intravaginal insertions could be in conflict with the introduction of vaginal microbicide gels. The Africa Centre site was part of the Microbicides Development Programme evaluating PRO2000/5 microbicide gel. We conducted in-depth-interviews and focus-group discussions with women enrolled in the trial as well as women and men from the community. The analysis focused on people's knowledge of intravaginal insertion in the community and trial participants' experience of using trial gels. Intravaginal use of a variety of products was widely acknowledged. We found that the experience of using trial gels - which made sex 'hot', 'tight' and 'dry' - matched the desired outcomes of intravaginal insertion. We found that vaginal 'dryness' described the removal of excessive amounts of unusual discharge, rather than the removal of normal vaginal secretions and that intravaginal insertion is not exclusively associated with a desire for 'dry' sex. Study findings provide evidence that vaginal microbicide gels may be more acceptable in communities where intravaginal insertion is practiced than was previously thought. PMID- 20737332 TI - How well do pilots sleep during long-haul flights? AB - It is imperative that shiftworkers in safety-critical workplaces obtain sufficient sleep to operate effectively. This presents a challenge to long-haul airline pilots who are required to supplement normal bed sleep with sleep on board an aircraft during flight. In the current study, the sleep/wake behaviour of 301 airline pilots operating long-haul flight patterns was monitored for at least 2 weeks using self-report sleep diaries and wrist activity monitors. The data indicate that sleep opportunities in on-board rest facilities during long haul flights result in a similar amount of sleep, but only 70% as much recovery, as duration-matched bed sleeps. STATEMENT OF RELEVANCE: This study indicates that in-flight sleep provides airline pilots with 70% as much restoration as duration matched bed sleep. To increase the restoration provided by in-flight sleep, airlines could take measures to improve the quality, or increase the amount, of sleep obtained by pilots during flights. PMID- 20737333 TI - Motivational mechanisms at the origin of control task violations: An analytical case study in the pharmaceutical industry. AB - The introduction of rules and procedures to guide front-line operators' behaviour and to decrease the frequency of errors is a growing safety strategy in complex risk systems. It is thought to be a useful way of controlling and standardising human practices and of increasing safety and quality. However, merely developing procedures does not ensure that they are followed. In this study, observation was used to collect information on procedural violations in a pharmaceutical company. Interviews were conducted with the operators and the prescriptors to better understand how and why these violations were occurring. Results showed that a small number of procedures were breached by the majority of operators and that the rules that were violated were the ones associated with a perception of minimum risk. Results suggest the rationality of operators is a response to cognitive and social influences, which must be taken into account when designing procedures. STATEMENT OF RELEVANCE: This paper is about violation and risk perception. This focus is relevant for ergonomic research and practice, taking into account the accumulation of rules and procedures that are found in work in order to improve safety. The results help to better understand the cognitive and social mechanisms underlying violations and give some insights for designing procedures. PMID- 20737334 TI - Application of artificial neural networks to a study of nursing burnout. AB - Nursing is generally considered to be a profession with high levels of emotional and physical stress that tend to increase. These high stress levels lead to a high risk of burnout. The objective was to assess whether artificial neural network (ANN) paradigms offer greater predictive accuracy than statistical methodologies, which are commonly used in the field of burnout. A radial basis function (RBF) network and hierarchical stepwise regression was used to assess burnout. The comparison of the two methodologies was carried out by analysing a sample of 462 nurses and student nurses. The subjects were from three hospitals in Madrid (Spain), who completed the 'Nursing Burnout Scale' survey. A RBF network was better suited for the analysis of burnout than hierarchical stepwise regression. The outcomes indicate furthermore that the relationship with the burnout process of the predictive variables age, job status, workload, experience with pain and death, conflictive interaction, role ambiguity and hardy personality is not entirely linear. The usage of ANNs in the field of burnout has been justified due to their superior ability to capture non-linear relationships, which is relevant for theory development. STATEMENT OF RELEVANCE: Due to the superior ability to capture non-linear relationships, ANNs are better suited to explain and predict burnout and its subdimensions than common statistical methods. From this perspective, more specific programmes to prevent burnout and its consequences in the workplace can be designed. PMID- 20737335 TI - Continuous assessment of work activities and posture in long-term care nurses. AB - The high prevalence of low back injuries in nursing has prompted the use of mechanical lift assists while overall assessment of activities and postures remains limited. The purpose of this study was to chronicle trunk posture and work tasks of long-term healthcare professionals. An inclinometer monitored trunk posture for 27 workers, 20 of whom were also observed continuously throughout their shift. Patient lifts and transfers accounted for less than 4% of the shift while patient care, unloaded standing and walking and miscellaneous tasks accounted for 85%. Manual lifts and transfers occurred twice as often as mechanically assisted lifts but took only half the time. The workers had a median trunk flexion angle of 9.2 degrees , spent 25% of their time flexed beyond 30 degrees and had peak flexion angles greater than 75 degrees in many tasks. Analysis of posture throughout the entire working shift indicates that, in addition to lifts and transfers, emphasis needs to be placed on patient care and miscellaneous activities when assessing injury risk for nurses. STATEMENT OF RELEVANCE: Patient handling has been the focus in the effort to reduce back pain and injury in nursing. In addition to the use of mechanical lifts, there is a need to examine other aspects of nursing, including patient care and other ancillary tasks, which comprise the majority of the work shift and, while often unloaded, exhibit extreme postures that may also lead to injury. PMID- 20737336 TI - Continuous assessment of low back loads in long-term care nurses. AB - Considerable effort has been spent evaluating aspects of low back injury risk in nursing yet comprehensive evaluation of all work tasks has been limited. The purpose of this study was to evaluate peak and cumulative lumbar spine loads experienced by personal support workers. A total of 20 female long-term care workers were observed and had trunk posture monitored via an inclinometer throughout their shift. When adjusted for an 8-h workday, workers experienced cumulative loads of 21.3 +/- 4.6 MNs, 1.8 +/- 0.6 MNs and 2.9 +/- 1.4 MNs for compression, lateral and anterior shear, respectively. Patient care, unloaded standing, walking and miscellaneous tasks accounted for almost 80% of cumulative compression, while lifts and transfers accounted for less than 10%. Mechanical lift assists reduced peak loads and contributed minimally to cumulative loading. These findings suggest that both peak and cumulative spine loads should be considered when evaluating injury risk in the nursing profession. STATEMENT OF RELEVANCE: This study has shown that tasks other than patient transfers and lifts are important in the assessment of low back injury risk in nurses. The method developed is a relatively straightforward approach that can be used to estimate peak and cumulative spine load to provide insight to risk of injury in many occupational settings. PMID- 20737337 TI - Acute biomechanical responses to a prolonged standing exposure in a simulated occupational setting. AB - Prolonged occupational standing has previously been associated with low back pain (LBP) development. The immediate effects of a bout of prolonged standing on subsequent functional movement performance have not been investigated. It is possible that including a period of prolonged standing may have acute, detrimental effects. The purpose of the study is to investigate the impact of a prolonged standing exposure on biomechanical profiles (trunk muscle activation, joint stiffness and kinematics) during three functional movements. A total of 23 volunteers without history of LBP performed lumbar flexion, single-leg stance and unloaded squat movements pre- and post 2 h of standing exposure. It was found that 40% of the participants developed LBP during the standing exposure. There was a decrease in vertebral joint rotation stiffness in lateral bending and increased centre of pressure excursion during unilateral stance following standing exposure. There may be adverse effects to prolonged standing if followed by activities requiring precise balance or resistance of side loads. STATEMENT OF RELEVANCE: Prolonged standing may result in decreases in balance reactions during narrow base conditions as well as in the capacity to effectively resist side loads at the trunk. Consideration should be given when prolonged standing is included in the workplace. PMID- 20737338 TI - Inter-observer reliability of forceful exertion analysis based on video recordings. AB - The objectives were to examine inter-observer reliability of job-level forceful exertion analyses and temporal agreement of detailed time study results. Three observers performed the analyses on 12 different jobs. Continuous duration, frequency and % time of lifting, pushing/pulling, power and pinch gripping exertions and estimated level of the exertions were obtained. Intraclass correlation coefficient and variance components were computed. Temporal agreement analyses of raw time study data were performed. The inter-observer reliability was good for most job-level exposure parameters (continuous duration, frequency and % time of forceful exertions), but only fair to moderate for the estimated level of forceful exertions. The finding that the between-observer variability was less than the between-exertion variability confirmed that the forceful exertion analysis method used in the present study can detect job exertion differences.Using three observers to perform detailed time studies on task activities and getting consensus of the majority can increase the between observer agreement up to 97%. STATEMENT OF RELEVANCE: The results inform researchers that inter-observer reliability for job-level exposure measurement of forceful exertion analysis obtained from detailed time studies is generally good, but the observers' ability in the estimation of forceful exertion level can be poor. It also provides information on the temporal agreement of detailed forceful exertion analysis and guidelines on achieving better agreement for studies where accurate synchronisation of task activities and direct physiological/biomechanical measurements is crucial. PMID- 20737339 TI - Physiological response of beach lifeguards in a rescue simulation with surf. AB - The objective of this study was to examine the physiological response of 14 lifeguards in a swimming pool simulation with 1.7 m waves and to study the efficiency of the torpedo buoy. The rescue time was determined with and without material, as were lactate levels, heart rate and VO(2max). The results obtained showed a VO(2 max) rate of 3.4 +/- 0.8 l/min without equipment and 3.3 +/- 0.8 l/min with equipment. Moreover, the time taken to swim towards the victim without equipment decreased by 7.7 s, while towing time was reduced by 10.8 s if said equipment was used. These results show that aquatic rescue makes considerable physiological demands on the swimmer and they also provide important data on the type of training and aptitude levels required by individuals wishing to join these rescue groups. The equipment currently used has a negative affect on the swim. STATEMENT OF RELEVANCE: The study shows that beach rescues make very high physiological demands on rescuers, thus underlining the need to perform entry tests for these highly demanding rescue teams. The auxiliary equipment is a help in the return time of rescue. However, it causes delays in the approach to the victim. PMID- 20737341 TI - Phthalates and food-contact materials: enforcing the 2008 European Union plastics legislation. AB - The migration of phthalates into foodstuffs from food-contact materials (FCM) is a well-known source of food contamination. In 2005, the European Food Safety Authority finalized its risk assessment for several of the classical phthalate plasticizers. In their risk management procedure the European Commission transformed the tolerable daily intakes established by the Authority into legislative limits for phthalates in both plastic and food simulants, while taking exposure from other sources into consideration. These limits have been into force since 1 July 2008. A detailed interpretation of the regulation of these substances was agreed upon in the European network of FCM reference laboratories. This paper reports results from a Danish control campaign of samples collected by official food inspectors and analysed by a newly validated analytical method run under accreditation. Samples were from FCM producers, FCM importers and importers of packed foodstuffs from third-party countries. Products containing phthalates above the current limits were found in several categories of FCM: conveyor belts (six of six), lids from packed foodstuffs in glasses (eight of 28), tubes for liquid foodstuffs (four of five) and gloves (five of 14). More than 20% of the samples analysed contained dibutylphthalate (DBP) or di (2-ethylhexyl)phthalate (DEHP) above the compositional limits of 0.05% and 0.1%, respectively. Analysis of residual phthalates in metal lid gaskets instead of analysis of phthalates in the food when controlling foodstuffs packed outside the European Union proved to be an efficient and simple control method. All findings of phthalates were associated with the use of plasticized polyvinylchloride (PVC). PMID- 20737342 TI - Carcinogenic risk assessment for emissions from clinical waste incineration and road traffic. AB - The most significant potentially carcinogenic substances arising from a state-of the-art clinical waste incinerator (CWI) and vehicle emissions were identified as polychlorinated dibenzo-p-dioxins, polycyclic aromatic hydrocarbons (PAHs), benzene, 1-butadiene, arsenic, cadmium, chromium and nickel. Long-term exposures of the notional maximum exposed individual (MEI) in the local environment, together with aggregate emissions from transport of clinical waste, were estimated. Mass emission rates of PAHs from the CWI to air were compared with previously published estimates of mass emissions to land from CWI bottom ash. Aggregate emissions from road transport of clinical waste were of a similar order to stack emissions from incineration. Mass emissions of PAHs to landfill generally greatly exceeded those from stack emissions. Emissions associated with operation of the CWI present a negligible contribution to overall cancer risk from PAHs and other carcinogens. Uncertainty in the quantitative risk estimates presented here is discussed in the context of these findings. PMID- 20737343 TI - A review of the literature on Native Hawaiian youth and drug use: implications for research and practice. AB - This article provides a comprehensive review of the recent literature on Native Hawaiian youth and substance use. Eight-hundred and twelve potential articles pertaining to Native Hawaiian youth and substance use published between 1995 to May 2009 were identified through an exhaustive literature search. The total number of articles was reduced to 32 articles, which were systematically coded and content analyzed. The findings indicated that the majority of studies focused on epidemiology, with relatively few of them focused on causal factors/etiology and systematic program development or evaluation. Gender differences in drug use were highlighted in several studies. Implications for culturally tailored interventions and future research are discussed. PMID- 20737345 TI - The Irish Traveller community: social capital and drug use. AB - The Irish Traveller community experiences severe marginalization, poverty, discrimination, and compromised health. Research indicates a distinct lack of structural understanding of Traveller negotiation of conflict within dominant sedentarist societal norms and values. Gender-based focus groups (n = 12) of Travellers (n = 57) were conducted as part of a large scale regional needs analysis for Travellers and substance use in Ireland and analyzed thematically using the social capital framework in terms of Traveller experiences within settled communities, exposure to drugs, and drug using contexts. Discriminatory experiences, low levels of institutional trust, and an influx of drug activity in Traveller communities are contributing to the neutralization of drug taking risk and the development of normative and reciprocal relationships in drug activities. A holistic, inter-governmental approach is needed to address social exclusion factors by reducing marginalization, preserving the Traveller ethnic identity, minimizing racist and discriminatory instances, understanding the Traveller risk environment, and fostering inclusive relationships with settled communities. PMID- 20737344 TI - Substance use and dependence among Native Hawaiians, Other Pacific Islanders, and Asian ethnic groups in the United States: contrasting multiple-race and single race prevalence rates from a national survey. AB - The percentage of multiracial youth appears to be increasing in the United States. However, little has been disseminated about problem behaviors among multiracial Native Hawaiians, Other Pacific Islanders, and Asians on a national level. Using the National Survey on Drug Use and Health, the authors compared multiple-race Native Hawaiians, Other Pacific Islanders, and Asians, while disaggregating by ethnic subgroups, with single-race individuals within respective Asian ethnic subgroups and Caucasians for prevalence of alcohol/drug use and dependence. For multiple-race Native Hawaiians, Other Pacific Islanders, and Asians, high rates of alcohol dependence were observed compared with both single-race Native Hawaiian, Other Pacific Islander, and Asian subgroups and single-race Caucasians; for some multiracial Native Hawaiians, Other Pacific Islanders, and Asians, high rates of drug dependence were also observed. PMID- 20737346 TI - Alcohol use among U.S. Muslim college students: risk and protective factors. AB - Drinking behavior among Muslim college students in the United States is unknown. To obtain estimates and examine risk factors, the authors conducted secondary data analysis of the public access database from the 2001 Harvard School of Public Health College Alcohol Study. Two variables were associated with drinking religious activities, which were protective against drinking, and parental approval of drinking, which was a risk factor for drinking. Although American Muslim students had a low rate of drinking in the past year (46.6%) compared to their U.S. college counterparts, they had a higher rate of alcohol consumption compared to their counterparts in predominately Muslim countries. PMID- 20737347 TI - Depressive symptoms in crack and inhalant users in Southern Brazil. AB - In this study the authors investigated depressive symptoms and correlated psychopathology in crack cocaine and inhalant users in Southern Brazil. Participants completed the Beck Depression Inventory, the Montgomery-Asberg Depression Rating Scale, and the Hamilton Depression Rating Scale. General psychopathology, hopelessness and suicidal tendencies were also investigated. Crack and inhalants users presented significant levels of depressive symptoms and psychiatric morbidity. These disorders were significantly associated with hopelessness and suicidal tendencies. These findings underscore the need for more rigorous and extensive screening efforts to detect and treat depressive symptoms in crack and inhalent users. PMID- 20737348 TI - Evaluation of chemical hazards at a criminal investigation section of a police department. Case studies. PMID- 20737349 TI - Remediating office environments of spore-forming bacteria. AB - This study examines decontamination processes that were developed on an emergency basis to eliminate Bacillus anthracis spores from deliberately contaminated buildings. The recommended steps include a survey with sampling, the removal of sensitive items, and HEPA vacuuming of all readily available surfaces, followed by biocide treatment and subsequent analyses for viable cells. There are several analytical challenges posed by this approach. These include the ability to discriminate the added strain from naturally occurring resident microbes, determining detection limits for anthrax spores in settled dusts, and detecting viable but nonculturable spores. There are also logistical issues relating to the various skill sets required from investigation to reconstruction. In the present study, a model office was constructed, and a strain of Bacillus pumilus was isolated from the carpet and reintroduced to the office in excess. The abundance of the B. pumilus strain was monitored in settled dust using a strain-specific, quantitative polymerase chain reaction (QPCR)-based detection method following repeated HEPA vacuum cleanings. The QPCR method had a limit of detection corresponding to < or = 10(2) colony forming units per gram of settled dust. QPCR results were compared with measures of dust recoveries and fungal glucan and endotoxin levels in the dust samples. The largest fraction (ca. 81%) of added spores was recovered during the first HEPA cleaning. Subsequent cleanings resulted in incrementally lower recoveries, with removal of 93% of the initial inoculum by the third HEPA vacuuming. HEPA vacuuming prior to removal of items such as office contents and furnishings would result in much less resuspension of dust and limiting the extent of contamination. This approach also ensures that residual contaminants are as low as can be reasonably achieved. PMID- 20737351 TI - Dysfunctions in understanding other minds in borderline personality disorder: a study using cartoon picture stories. AB - Patients with borderline personality disorder (BPD) are thought to be impaired in their ability to reflect on others' mental states. Only a few empirical studies have explored the idea that impaired mentalizing in BPD is associated with poor quality of parental care or parental separation during early childhood. Fifty patients diagnosed with BPD were examined using a cartoon task. Quality of parental care was assessed using a self-report measure for recalled parental child-rearing style. Patients with BPD did not differ from controls in their mentalizing abilities. In BPD, however, mentalizing correlated inversely with maternal overprotection, lack of emotional availability, and rejection. Moreover, maternal punishment and rejection and parental separation at an early developmental age were significant predictors of poor mentalizing skills in BPD. These findings suggest that the quality of parental care during early childhood plays a role in the development of mentalizing skills in BPD. PMID- 20737352 TI - Therapist predictors of early patient-rated working alliance: a multilevel approach. AB - The present study investigated whether and how various therapists' (N = 68) self reported characteristics relating to their therapeutic work predicted patients' (N = 335) early ratings of the working alliance in a naturalistic psychotherapy study. Results from multilevel modeling demonstrated that certain self-reports accounted well for the therapist effect in the early alliance. The effect of therapists' experiences of difficulties in practice was particularly strong: a negative influence of difficulties termed negative personal reaction (NPR) and a surprising positive influence of another factor, professional self-doubt (PSD), were found. The latter was interpreted as reflecting an attitude of therapist humbleness and sensitivity, which seems to facilitate alliance development. A negative impact of self-reported skills in using one's own and the patients' emotional reactions in the therapeutic relationship (advanced relational skills) was found when controlling for a warm interpersonal style. The negative effect of advanced relational skills depended on the level of NPR difficulties. The findings suggest that therapists should be cautious in using this kind of relational skill unless they experience relating to patients in a warm manner and report low levels of NPR in their practice. PMID- 20737353 TI - Click trains and the rate of information processing: does "speeding up" subjective time make other psychological processes run faster? AB - A series of experiments demonstrated that a 5-s train of clicks that have been shown in previous studies to increase the subjective duration of tones they precede (in a manner consistent with "speeding up" timing processes) could also have an effect on information-processing rate. Experiments used studies of simple and choice reaction time (Experiment 1), or mental arithmetic (Experiment 2). In general, preceding trials by clicks made response times significantly shorter than those for trials without clicks, but white noise had no effects on response times. Experiments 3 and 4 investigated the effects of clicks on performance on memory tasks, using variants of two classic experiments of cognitive psychology: Sperling's (1960) iconic memory task and Loftus, Johnson, and Shimamura's (1985) iconic masking task. In both experiments participants were able to recall or recognize significantly more information from stimuli preceded by clicks than those preceded by silence. PMID- 20737354 TI - Competition dynamics of second-language listening. AB - Spoken-word recognition in a nonnative language is particularly difficult where it depends on discrimination between confusable phonemes. Four experiments here examine whether this difficulty is in part due to phantom competition from "near words" in speech. Dutch listeners confuse English /ae/ and /epsilon/, which could lead to the sequence daf being interpreted as deaf, or lemp being interpreted as lamp. In auditory lexical decision, Dutch listeners indeed accepted such near words as real English words more often than English listeners did. In cross-modal priming, near-words extracted from word or phrase contexts (daf from DAFfodil, lemp from eviL EMPire) induced activation of corresponding real words (deaf; lamp) for Dutch, but again not for English, listeners. Finally, by the end of untruncated carrier words containing embedded words or near-words (definite; daffodil) no activation of the real embedded forms (deaf in definite) remained for English or Dutch listeners, but activation of embedded near-words (deaf in daffodil) did still remain, for Dutch listeners only. Misinterpretation of the initial vowel here favoured the phantom competitor and disfavoured the carrier (lexically represented as containing a different vowel). Thus, near-words compete for recognition and continue competing for longer than actually embedded words; nonnative listening indeed involves phantom competition. PMID- 20737355 TI - Phonological facilitation from pictures in a word association task: evidence for routine cascaded processing in spoken word production. AB - While most authors now agree that the language production system is in principle cascaded, the strength with which cascaded lemma-to-phoneme activation typically occurs is debated. Picture naming has been shown to be facilitated by phonologically related distractor pictures, but no such facilitation from pictures has been shown for word reading. Picture-picture paradigms have recently been suggested to represent an attentionally facilitated and unusually strong case of cascaded phonological facilitation, not typical of a more general weakly cascaded production system. We used a novel procedure based on picture-word interference paradigms, where participants made speeded verbal free association responses to presented words, with irrelevant picture distractors that were phonologically related to their predicted high-associate responses. Phonological facilitation effects from related picture names were observed on free associate verbal production latencies. These findings represent a far more general demonstration of routine cascaded language production and suggest that the strength and extent of cascaded activation is more substantial than that suggested by traditional picture-word paradigms. PMID- 20737356 TI - [Transparency and outcome orientation as means to improve psychotherapeutic services: a study to evaluate outpatient psychotherapy (TRANS-OP)]. AB - BACKGROUND: There is clear evidence for the efficacy of psychotherapy. However, there is a lack of large-scale naturalistic studies on the course of psychological problems and its predictors in people in psychotherapeutic routine care. MATERIAL AND METHODS: Between September 1998 and February 2000, 627 insurees of the "Deutsche Krankenversicherung", a major German health insurance company, who received outpatient psychotherapy (psychodynamic psychotherapy, analytic psychotherapy, or cognitive behavioral treatment), gave informed consent to participate in this study. During a two-year period, participants' health status was comprehensively assessed using standardised instruments. Hierarchical linear models were used to estimate courses of improvement in and transitions between the phases before, during, and after treatment. RESULTS: Psychological, interpersonal and physical problems improved substantially in all 3 forms of treatment. However, courses of improvement also varied among domains and form of treatment. The helping alliance was an ubiquitous, but not very strong predictor of treatment outcome. CONCLUSIONS: These results could be used as the basis for comprehensive quality management in psychotherapeutic care. PMID- 20737357 TI - [Early emulsification of silicone oil (2000 cs) in minimally invasive transconjunctival vitreoretinal surgery]. AB - BACKGROUND: The highly purified polydimethylsiloxane (PDMS) with a viscosity of 5000 centistokes (cs) is the preferred silicone oil endotamponade in vitreoretinal surgery (20 gauge) and shows high stability. In contrast in transconjunctival minimally invasive surgery (23 gauge) the application of 5000 cs. silicone oil shows substantial disadvantages because of time-consuming and difficult application procedure due to the small lumen of the used surgical equipment. Consequently silicone oils with lower viscosity like the 2000 cs silicone oil are being increasingly used in transconjunctival surgery. PATIENTS: We present two cases of early emulsification of the 2000 cs silicone oil (Siluron 2000 (c), Fluoron, Neu-Ulm, Germany) consisting of highly purified PDMS in the course of minimally invasive transconjunctival vitreoretinal surgery. In both cases 23 gauge vitrectomy with application of 2000 cs silicone oil was performed without any complication. The first case is a 34-year-old female with proliferative diabetic retinopathy who had already experienced several vitreoretinal operations. The present indication for vitrectomy was a persistent macular hole and vitreous haemorrhage. The second case is a 55-year-old pseudophakic patient with a retinal detachment after vitrectomy with gas endotamponade following rhegmatogenous retinal detachment. RESULTS: In the first case emulsification of silicone oil was seen on the second postoperative day. In the second case emulsification was discovered two weeks postoperatively. In both cases high intraocular pressure did not occur. CONCLUSION: With emerging performance of minimally invasive vitrectomy techniques the use of silicone oil with low viscosity in patients with conceivable endurance of the endotamponade appears to be beneficial. Up to now 10 patients have undergone 23 gauge vitrectomy with application of 2000 cs silicone oil without any complications in our clinic. In contrast, two cases demonstrated early emulsification of the 2000 cs silicone oil. To the best of our knowledge this complication has not been described before. PMID- 20737358 TI - Meningiomas involving the sphenoid wing outcome after microsurgical treatment--a clinical review of 73 cases. AB - OBJECTIVE: Sphenoid wing meningiomas represent a difficult to access subtype of intracranial meningiomas involving important neurovascular structures such as the optic nerve, cavernous sinus or carotid artery. They cause neurological compromises by direct compression of adjacent cranial nerves. Insidious and aggressive dural, bony, and orbital involvement produces several difficulties for adequate resection leading to higher rates of recurrence. METHODS: This retrospective case analysis consists of 73 patients who were surgically treated for meningiomas involving the sphenoid wing, where a pterional approach was performed between April 2001 and February 2006. 51 women and 22 men with a mean age of 59.4 years were operated on. The follow-up period ranged from 3-75 months (mean 29.8 months). Patients were divided into the following groups based on the site of the tumor: group 1: outer part of the sphenoid ridge (lateral, n=16); group 2: middle part of the sphenoid ridge (intermediate, n=5); group 3: inner part of the sphenoid ridge (medial, n=22); and group 4: spheno-orbital meningioma (n=30). RESULTS: The majority of patients presented with visual impairment (55%), followed by generalized headaches (36%) and visual field defects (33%). Total microscopic tumor resection was achieved in 35 patients (47.9%). Visual acuity improved in 58% of the patients, with 23% returning to normal vision. Preexisting cranial nerve deficits remained unchanged in the majority of patients (79%) and improved in 18%. Temporary new cranial nerve deficits occurred in 6 cases, and 1 patient (1%) developed permanent third nerve palsy. The mortality rate was 3% (2 patients) and the rate of permanent nonvisual morbidity was 7% (5 patients). 12 patients (16%) received postoperative radiotherapy. In 6 of 7 patients who were observed for at least 1 year after radiotherapy, stable tumor volume was noted at the follow-up review (mean 30.2 months, range 16-50 months), which provides a tumor growth control rate of 86%. The overall recurrence rate was 15% (11 of 73 patients). CONCLUSION: The result of this study affirms the safety of microsurgical treatment strategies, so that sufficient tumor control can be achieved with minimal morbidity and satisfying functional results in most cases. PMID- 20737359 TI - Meningiomas involving the sphenoid wing outcome after microsurgical treatment--a clinical review of 73 cases. PMID- 20737360 TI - Therapeutic approaches to complicated cholesteatoma of the external auditory canal: a case of associated facial paresis. AB - Spontaneous cholesteatoma of the external auditory canal (EAC) is an uncommon condition that is difficult to diagnose. In a patient with such a possibility, serious clinical investigation along with radiologic and histologic exploration should be performed early on because a delay in treatment can lead to severe complications. Given the rarity of EAC cholesteatoma, no therapeutic consensus has emerged. The type of management depends on the extensiveness of invasion and bone erosion and the status of the neighboring structures. The primary therapeutic objectives are to eradicate the cholesteatoma and then to fill in the residual cavity, which in our opinion can be best accomplished with a muscle flap and EAC reconstruction. Postoperative follow-up should be carried out to look for infections, stenosis, and recurrence. We report a new case of spontaneous EAC cholesteatoma, and we review its diagnostic and therapeutic challenges. PMID- 20737361 TI - Adult nasal dermoid sinus cyst. AB - Midline congenital nasal lesions are rarely encountered in adults. We present the case of a 31-year-old man with a nasal dermoid sinus cyst who presented with a nasal dorsal abscess. We review the embryology of nasal dermoid sinus cysts, and we discuss their presentation, evaluation, and management in adults. PMID- 20737362 TI - Report of a complete second branchial fistula. AB - We report a case of complete congenital branchial fistula with an internal opening near the tonsillar fossa. Cysts, fistulas, and sinuses of the second branchial cleft are the most common developmental anomalies arising from the branchial apparatus. In our case, a 43-year-old man presented with a several-year history of a discharging sinus from the right side of his neck, consistent with a branchial fistula. He underwent various investigations and finally was treated with a one-stage complete surgical excision of the fistula tract. We describe the general clinical presentation, investigations, and surgical outcome of this case. PMID- 20737363 TI - Cysts of the fossa of Rosenmuller: report of two cases. AB - Cystic lesions of the nasopharynx are rare. Two cases of mucous retention cysts originating from the fossa of Rosenmuller are described, together with their characteristic radiologic appearance, which allows differentiation from other types of lesions in this region. The differential diagnosis and treatment options are discussed. PMID- 20737364 TI - Sebaceous lymphadenoma: a case report and review of the literature. AB - An 80-year-old woman presented with a mass in her left parotid region. An ultrasound-guided core biopsy showed sebaceous glands with lymphoplasmacytic infiltration. Magnetic resonance imaging displayed a well-circumscribed lesion within the left parotid gland. The mass was completely excised, and the patient made a full recovery. Sebaceous lymphadenomas of the salivary glands are rare, benign tumors that are effectively treated by complete excision. The challenge that these tumors present lies in their accurate diagnosis. Because of their histologic similarity to related malignant tumors, such as mucoepidermoid carcinomas and sebaceous lymphadenocarcinomas, misdiagnosis could lead to unnecessarily radical treatment. We highlight the need for careful clinical and histologic diagnosis in tumors of the salivary glands. PMID- 20737365 TI - A case of head and neck cancer metastasizing to the axillary lymph nodes. AB - Metastases of head and neck cancers to the axillary lymph nodes are rare. Our review of the literature found only five such reports involving 10 patients. We describe a new case that occurred in a 69-year-old man who presented with a 6 week history of right neck swelling. Positron-emission tomography/computed tomography demonstrated high F18-fluorodeoxyglucose uptake in the neck and also in the right axilla. Fine-needle aspiration cytology revealed squamous cell carcinoma (SCC) at both sites. The patient underwent right-sided radical neck dissection with pectoralis major myocutaneous flap reconstruction and axillary node block dissection. The patient was subsequently treated with chemoradiotherapy, but 6 months later he developed an SCC in the lung. The lung lesion was also treated with chemotherapy, but the patient died 5 months later. Our case is unique among similar cases in that our patient had not undergone any previous treatment of the neck primary. We discuss the mechanism of this unusual presentation. PMID- 20737366 TI - Congenital cholesteatoma in the tympanic membrane. PMID- 20737367 TI - The internist's literature on chronic rhinosinusitis: an evaluation of the amount and quality of published information. AB - Most patients with chronic rhinosinusitis (CRS) are treated by internists, yet the information available to internists about CRS is rarely assessed. The author undertook a study to evaluate the amount and quality of information about CRS that is available to internists. Four information sources were analyzed: (1) five journals routinely read by internists, published over a 10-year period and searched on PubMed for the "exploded" terms chronic and sinusitis; (2) seven representative general and outpatient medicine texts, searched on MD Consult and STAT!Ref; (3) the 14th edition of the Medical Knowledge Self-Assessment Program (MKSAP 14), a review of internal medicine; and (4) four commonly used Internet databases. The five journals contained a total of 37,250 cited articles of various types over the study period; CRS was mentioned in only 19 of them. The standard medical texts offered little information about CRS, and MKSAP 14 did not mention CRS at all in the text, although it included some information in the questions and answers. Finally, among the online sources, UpToDate, a proprietary Internet database, offered an excellent discourse on CRS; in contrast, the Physicians' Information and Education Resource, maintained by the American College of Physicians, contained no information about CRS in its 436 subject modules. The author concludes that, with few exceptions, the literature routinely available to internists offers little information about CRS. PMID- 20737368 TI - Retail health clinics as a primary source of healthcare? PMID- 20737369 TI - The use of a lighted guidewire and telescope without fluoroscopy for balloon sinus ostia dilation. PMID- 20737370 TI - Laryngeal leiomyoma. PMID- 20737371 TI - Three-dimensional CT-guided custom implant for the repair of facial defects. PMID- 20737372 TI - Seldinger technique for in-office tracheoesophageal puncture. PMID- 20737373 TI - Delayed facial paresis following tympanomastoid surgery in a pediatric patient. AB - Despite the presence of normal facial nerve function in the immediate postoperative period, patients may develop facial nerve dysfunction anywhere from several hours to several days after otologic surgery. This delayed facial paresis, following a broad range of otologic surgeries, has been well described in adults but not in pediatric patients. Viral reactivation is increasingly implicated as the underlying etiology of delayed facial paresis. We present a case of delayed facial paresis in a pediatric patient with a clinical course consistent with viral reactivation. PMID- 20737374 TI - Intraglossal impaction of ingested fish bones: a case series. AB - Although foreign body ingestion and impaction in the pharynx or hypopharynx are quite commonly encountered at our institution, foreign body impaction in tongue tissue is rare. Six cases of foreign bodies embedded in the tongue were identified in a retrospective review spanning the years 1998 to 2007. All the foreign bodies were fish bones. Four of these patients required only tongue exploration to remove the bone; one required a partial glossectomy because of difficulties locating the bone; and one required incision and drainage of an intraglossal abscess that had developed, as well as a tracheostomy. All foreign bodies were successfully removed, with none of the patients experiencing altered sensation or problems with tongue mobility afterwards. PMID- 20737375 TI - Extramedullary plasmacytoma of the tongue base: a case report and clinical review of head and neck plasmacytoma. AB - Plasmacytomas of the head and neck are rare tumors characterized by a monoclonal proliferation of plasma cells. Very few cases of plasmacytoma of the tongue base have been reported. We present a new case of extramedullary plasmacytoma of the tongue base, we discuss its diagnosis and management, and we review the literature on plasmacytomas of the head and neck. PMID- 20737376 TI - Tonsillar metastasis of signet-ring cell adenocarcinoma of the colon. AB - Cases of primary colorectal signet-ring cell carcinoma metastatic to the tonsil are extremely rare. To the best of our knowledge, only 4 such cases have been previously reported in the literature. We report a new case in a 76-year-old white woman. She was treated with chemotherapy, but her disease continued to spread and she was eventually placed on comfort care and palliative radiation therapy. The manner in which tonsillar metastases evolve is still unknown, but some hypotheses have been proposed, and we briefly review these theories. PMID- 20737377 TI - Recurrent vascular leiomyoma of the larynx: clinical and histopathologic characteristics and treatment. AB - Laryngeal vascular leiomyomas are uncommon benign tumors that seldom recur following complete excision. The choice of excision procedure-via direct laryngoscopy or an open approach-is dictated by tumor size, the expected amount of blood loss, and any comorbidities the patient may have. We report an unusual case of a recurrent laryngeal vascular leiomyoma in a 64-year-old woman who also had a concurrent parathyroid adenoma and a history of breast carcinoma. A surgical resection via an external approach along with laser resection of a small glottic component was needed. PMID- 20737378 TI - Safety of percutaneous dilational tracheostomy in coagulopathic patients. AB - Coagulopathy is one of the relative contraindications to percutaneous dilational tracheostomy (PDT). We conducted a retrospective analysis of the records of 483 patients who had undergone PDT at Johns Hopkins Hospital from January 2000 through December 2007 to investigate the safety of PDT in those who were coagulopathic. The number of patients classified as coagulopathic varied greatly according to the particular diagnostic criteria used; 164 patients (33.95%) met one of the three diagnostic criteria (an abnormality in either prothrombin time, partial thromboplastin time, or platelet count), and 32 patients (6.63%) met two or three of these criteria. Complications occurred in 16 patients (3.31%), none of whom met two or more diagnostic criteria; bleeding accounted for 5 of these complications (1.04%). No statistically significant difference was seen in complication rates between the coagulopathic patients and the controls (noncoagulopathic patients). We conclude that in the hands of an experienced surgeon, PDT can be safely performed in patients with abnormal coagulation factors provided that the surgical team strictly adheres to a standardized protocol. PMID- 20737379 TI - Treatment of acute aortic dissection type A (AADA): technical considerations. AB - Aortic dissection is one of the the most common and lethal catastrophes involving the aorta. Speedy diagnosis, as well as appropriate therapy are essential for survival of the patients. Because the clinical presentation in patients suffering AADA can differ substantially, discussion concerning specific surgical therapy remains controversial. This implies questions regarding the treatment of the aortic root as well as the aortic arch and the proximal descending aorta. The current manuscript raises important issues regarding surgical treatment of AADA patients which are discussed in the light of the institutional policy in the author's department. PMID- 20737380 TI - Quality of life after acute type B dissection in the era of thoracic endovascular aortic repair. AB - BACKGROUND: Conservative management of acute type B aortic dissection is currently being challenged by primary thoracic endovascular aortic repair. Aim was to assess outcome and quality of life after these different approaches using an adjusted standard population as benchmark. PATIENTS AND METHODS: Observational study of a prospectively collected (January 2000 to December 2005) consecutive series of 87 patients with acute type B aortic dissection. Patients were 63 +/- 13 years old and 68 were men (78.2 %). Seventy-two were managed conservatively (83 %) and 15 invasively (12 by endovascular aortic repair). Follow-up was 36 +/- 19 months. Endpoints were early and late morbidity and mortality, and long-term quality of life as assessed by the Short Form health survey questionnaire. RESULTS: Patient cohorts were similar regarding age, risk profile and local disease. In the conservative cohort, four patients died during early (5.6 %) and eight during long-term follow-up (cumulative four years survival rate 79 %). Thirty-two patients needed secondary surgical management (44 %), i.e. delayed aortic repair (n = 11), or interventions on adjacent aortic sections or major branches (n = 21). In the surgical cohort no patient died, and no repeated interventions were necessary after the peri-operative period. Long-term quality of life scores were 100 (69-115) in conservatively and 94 (75-124) in invasively managed patients. Normal scores range from 85 to 115. CONCLUSIONS: Primary endovascular management of uncomplicated acute type B dissection is safe and leads to excellent long-term results, whereas secondary interventions were required with high incidence after initial conservative management. Long-term quality of life, however, returned to normal with any successful treatment strategy. PMID- 20737381 TI - Acute and long-term outcome of Silverhawk assisted atherectomy for femoro popliteal lesions according the TASC II classification: a single-center experience. AB - BACKGROUND: Directional atherectomy (DA) has become popular in some centers to remove atherosclerotic plaques in femoro-popliteal lesions. Although immediate and also short - term outcome data are promising, solid long-term data are warranted to justify the widespread use in daily practice. PATIENTS AND METHODS: In this prospective study de novo and restenotic lesions of the femoro-popliteal segments were treated with the Silverhawk device. 161 consecutive patients (164 lesions) with peripheral artery disease (PAD) Rutherford classes 2 to 5 were included from June 2002 to October 2004 and October 2006 to June 2007 (59 % male, mean age 67 +/- 11 years, range 40 to 88) and the outcome analyzed according to the TASC II classification. RESULTS: DA alone was performed successfully in 28 % (n = 46), adjunctive balloon angioplasty in 65 % (n = 107) and stenting in 7 % (n = 11). The overall technical success rate was 76 % (124 / 164) and the procedural success rate 95 % (154 / 164). At 12 months primary patency rate was 61 % (85 / 140) and the secondary patency rate was 75 % (105 / 140) in the entire cohort, being less favourable in TASC D compared to TASC A to C lesions (p = 0.034 and p < 0.001, respectively). Furthermore the restenosis rate differed trendwise (p = 0.06) between de novo and restenotic lesions. Changes in the ABI and the Rutherford classes were significantly in favour of TASC A to C lesions compared to TASC D after 12 months (p = 0.004). The event free survival (MI, TIA, or restenosis) was 48 % at 12 months and 38.5 % at 24 months. Predictor for restenosis in the multivariable analysis was only male gender (p=0.04). CONCLUSIONS: The results in TASC D lesions are inferior to those in the lesser stages. DA of femoro-popliteal arteries leads shows a trend to better long-term technical and clinical outcome in de novo lesions compared to restenotic lesions. PMID- 20737382 TI - Treadmill test is limited in elderly patients with peripheral arterial disease. AB - BACKGROUND: To describe the applicability and the performance of the treadmill test in elderly patients with peripheral arterial disease (PAD) and without PAD (non-PAD). PATIENTS AND METHODS: Fifty consecutive PAD and non-PAD elderly patients performed a progressive treadmill test. The proportion of patients who were unable to perform the test and the maximal walking distance were obtained. RESULTS: The proportion of patients who were unable to perform the treadmill test was similar between PAD (16.6 %) and non-PAD patients (12.5 %), P = .57. Maximal walking time for patients who performed the treadmill test was not different between PAD (232 +/- 218 s) and non-PAD patients (308 +/- 289 s), P = .37. CONCLUSIONS: The treadmill test is limited in almost 20 % of elderly patients with PAD and non-PAD. These results highlight the need for other forms of exercise stress tests in order to assess the peripheral limitation of patients with PAD. PMID- 20737383 TI - Bridging with enoxaparin using a half-therapeutic dose regimen: safety and efficacy. AB - BACKGROUND: Low molecular weight heparin is widely used during the interruption of long-term oral anticoagulation in patients undergoing surgery. The optimal dose is still a matter of debate. The 8th ACCP Guidelines primarily recommend therapeutic-dose or low-dose low molecular weight heparin after stratification of the thromboembolic risk. We investigated the efficacy and safety of a standardized bridging therapy with enoxaparin in a half-therapeutic dose in patients with a target INR of 2,0 to 3,0. PATIENTS AND METHODS: In our prospective registry we studied 198 consecutive patients receiving oral anticoagulant therapy with phenprocoumon and a planned surgery. Phenprocoumon was stopped 7 days before surgery and after reaching an INR less than 2,0 all patients received enoxaparin in a half-therapeutic dose (1 x 1 mg / kg body weight (bw)/day) until the day before surgery. Enoxaparin was continued with the same dose split into 2 x 0,5 mg / kg bw / day after the procedure. Phenprocoumon was resumed within day 1 to 14 after surgery depending on the bleeding risk as determined by the surgeon. All patients were followed up for 28 days after surgery. RESULTS: Major surgery was performed in 148 patients (75 %). 175 patients (88 % of the total) had an intermediate thromboembolic risk. On average, enoxaparin was administered for 19,5 days. One patient (0,5 %) experienced arterial thrombosis after surgery, and one patient (0,5 %) required a second surgical intervention due to severe bleeding. CONCLUSIONS: In patients receiving oral anticoagulant therapy with a target INR of 2,0-3,0 and at an intermediate risk of thromboembolic events who require interruption of oral anticoagulant therapy a half therapeutic dose of enoxaparin seems to be safe and effective for bridging. PMID- 20737384 TI - 1470 nm diode laser for endovenous ablation (EVLA) of incompetent saphenous veins - a prospective randomized pilot study comparing warm and cold tumescence anaesthesia. AB - BACKGROUND: Major side effects after endovenous laser ablation (EVLA) are pain and bruising. Low temperature of the tumescence fluid might cause additional venous constriction and a cooling effect around the vein. The aim of this study was to show outcome and side effects after EVLA of incompetent great saphenous veins (GSV) with a 1470 nm Diode laser (Ceralas E, biolitec) using cold or warm tumescence fluid for anaesthesia. PATIENTS AND METHODS: Between August and November 2007, 85 consecutive patients (85 legs) with an incompetent GSV were treated by EVLA. The patients were randomized in two groups. In 42 patients (Group A) a warm (37 degrees C) and in 43 patients (Group B) a cold (5 degrees C) tumescence fluid (TF) was used for local anaesthesia in the track of GSV. All patients were re-examined after 1, 10 and 30 days clinically and by duplex for complications and occlusion in the treated vein segment. Patient's satisfaction was assessed on a 0 to 4 points scale. RESULTS: In each group one patient was lost to follow-up. There was no significant difference concerning gender, age, C of CEAP, BMI or diameter of the treated vein. In Group A a mean of 462 ml TF and in Group B a mean of 428 ml TF were used. In Group A the mean LEED (average linear endovenous energy density) was 114 J / cm and in Group B 115 J / cm. In both groups occlusion of the treated veins was achieved for all patients. The diameter of the GSV at 3 cm below the sapheno-femoral junction shrunk from 1.0 to 0.7 cm in both groups. The modified CEAP clinical score improved in Group A from 2.9 to 0.7 (mean value) and in Group B from 3.0 to 1.1. The mean pain score on a scale from 0 to 4 during day 2 to day 10 was 1.2 in Group A and 1.0 in Group B. At this time patients in Group A took a mean of 3.4 and in Group B 1.7 analgetic tablets. Ecchymoses were rare in both groups (4 in Group A, 7 in Group B). CONCLUSIONS: In this prospective randomized comparative study the temperature of the tumescence fluid did not influence the occlusion rate when a high LEED was used. In both groups pain and ecchymoses are less frequent in this study with a 1470 nm diode laser than reported in studies with 810-980 nm systems. Cold tumescence fluid reduced pain slightly and reduced the intake of analgetics significantly. PMID- 20737385 TI - Endovascular treatment of mycotic pseudoaneurysms. AB - The surgical correction of ruptured intracranial infectious pseudoaneurysms is associated with high morbidity and mortality. An endovascular therapeutic approach has been introduced recently. This treatment is, compared to surgical intervention, less invasive, faster, more effective and safer, thus making it a gentler option, particularly for pediatric patients. Lower morbidity and mortality have been achieved thanks to the combination of prolonged administration of antibiotics, coil embolization, and parent artery occlusion. Two pediatric cases of bleeding mycotic pseudoaneurysm treated successfully with fibered coil embolization and long-term antibiotics are dealt with in this manuscript. PMID- 20737386 TI - Long-term antiplatelet treatment for innominate vein aneurysm. AB - Aneurysms of thoracic veins are rare lesions and their therapeutic management is not clearly determined. We present a 60-year old man with an asymptomatic right innominate vein aneurysm. The patient had been operated on 10 years ago for coronary artery bypass and was under antiplatelet treatment. In a retrospective inspection of his chest X-rays, we found that the aneurysm had been existent for at least 10 years. We suggested conservative treatment and over a 5-year follow up, the patient has remained asymptomatic. Our patient is alive 15 years with thoracic vein aneurysm and antiplatelet treatment. PMID- 20737388 TI - Stab injury of the superior mesenteric artery with life threatening bleeding - endovascular treatment with an unusual technique. AB - Endovascular microcoil embolization of the superior mesenteric artery (SMA) main trunk is not currently employed as a treatment for penetrating injury to the SMA in hemodynamically instable patients. Immediate laparotomy is the initial gold standard therapy. We report a case of successful SMA microcoil embolization with preservation of mesenteric perfusion by an unusual endovascular technique. PMID- 20737387 TI - "Silent" thrombosis of an abdominal aortic aneurysm not producing acute limb ischemia. AB - Thrombosis of an abdominal aortic aneurysm is a rare devastating complication with an estimated mortality rate of 50%. Simultaneous acute pain, pallor and coldness of the lower limbs, mottling from the level of iliac crests or umbilicus, paraplegia and absence of femoral pulses are all manifestations of a sudden and acute interruption of blood flow through the aneurysmatic aorta. We report a case of an occlusion of an abdominal aortic aneurysm during hospitalization which was not manifested with symptoms of limb ischemia. In this case we feature the rare and unusually "silent" presentation of the event. PMID- 20737389 TI - Pseudoaneurysm of the popliteal artery due to osteochondroma of the distal femur. AB - Osteochondroma is the most common type of benign bone tumour, and is most often found in the knee region. The lesion is usually clinically silent although it may cause different complications such as fractures of the tumour, bone deformities, neurological disorders, malignant transformation and in rare cases vascular disorders. Vascular disorders include stenosis, occlusions, thrombosis, arteriovenous fistula and in rare cases pseudoaneurysm formation. A delay in diagnosis especially of pseudoaneurysm formation may result in life-threatening situations, extensive operations and lengthy hospital stays. We report the case of a 22-year-old woman with an osteochondroma of the distal femur which caused pseudoaneurysm of the popliteal artery. PMID- 20737390 TI - New possibilities of maximal revascularization of the foot as a limb salvage procedure in diabetics. AB - Diabetics and patients with chronic renal insufficiency often have severe peripheral arterial disease of the distal lower limbs with obstructions of crural and pedal arteries and the imminent risk of critical ischemia and major amputation. Neuroischemic foot ulcers have been shown to fail to heal even after successful arterial revascularization. We report on two diabetic patients with the neuroischemic diabetic foot syndrome and different clinical outcomes after percutaneous transluminal angioplasty of chronic occluded crural arteries and discuss, whether endovascular revascularisation of infrapopliteal and pedal arteries, if possible with complete plantar arch, could promote ulcer healing in neuroischemic diabetic foot ulcers. PMID- 20737391 TI - [Asthma--in general practice and as an emergency]. PMID- 20737392 TI - [What is your diagnosis? Orthostatic proteinuria]. PMID- 20737393 TI - [Treatment of chronic hepatitis B and C - update 2010]. AB - The treatment of chronic hepatitis C and B has become more and more complex over the last years. Individualisation of therapy, depending of the natural history as well as on treatment response, is increasingly finding its way into clinical practice. In addition, a significant number of new molecules active, against the hepatitis C virus, are currently in clinical evaluation. The goal of this review is to provide an up-to-date overview on the current treatment options for patients with a chronic viral hepatitis. PMID- 20737394 TI - [The humeroradial impingement]. AB - Lateral pain of the elbow is frequently reported. Impingement of the humeroradial fold or a synovial fringe is a seldom evoked cause, sometimes ignored. Nonetheless, this etiology should be remembered in young adults performing sport activities and in heavy workers. Pain can be acute and inflammatory. Elective pain is usually elicited by the pressure on the humeroradial joint space, beneath the lateral epicondyle. Snapping, locking and restricted mobility can be observed. MRI-arthrogram is the best radiological examination to perform. Symptoms can be improved by conservative treatment but may warrant an arthroscopical resection. PMID- 20737396 TI - [Therapy of lymph node tuberculosis]. PMID- 20737395 TI - [MR-imaging of joints]. AB - Magnetic resonance (MR) imaging is a well established, non-invasive method in the evaluation of joint pathologies. Basically four different MR imaging techniques are used in the clinical routine: (1) conventional MR imaging of joints, (2) intravenously contrast-enhanced MR imaging of joints, (3) direct MR arthrography with intraarticular injection of contrast medium and (4) indirect MR arthrography after intravenous application of contrast medium. Additionally, a variety of new MR imaging techniques are available and currently used for clinical research. These techniques have a great potential for clinical use in the future. PMID- 20737397 TI - [Automobile accident of Mr. S. Elementary, Dr. Watson]. PMID- 20737398 TI - [Cumulative incidence of false-positive test results in lung cancer]. PMID- 20737399 TI - [Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients]. PMID- 20737401 TI - [CME ECG 30. Status after heart surgery intervention]. PMID- 20737402 TI - [Physician picture and literature puzzle]. PMID- 20737403 TI - [Physician's art column]. PMID- 20737410 TI - Novel episomal vectors and a highly efficient transformation procedure for the fission yeast Schizosaccharomyces japonicus. AB - Schizosaccharomyces japonicus is a fission yeast for which new genetic tools have recently been developed. Here, we report novel plasmid vectors with high transformation efficiency and an electroporation method for Sz. japonicus. We isolated 44 replicating segments from 12 166 transformants of Sz. japonicus genomic fragments and found a chromosomal fragment, RS1, as a new replicating sequence that conferred high transformation activity to Sz. japonicus cells. This sequence was cloned into a pUC19 vector with ura4(+) of Sz. pombe (pSJU11) or the kan gene on the kanMX6 module (pSJK11) as selection markers. These plasmids transformed Sz. japonicus cells in the early-log phase by electroporation at a frequency of 123 cfu/ug for pSJK11 and 301 cfu/ug for pSJU11, which were higher than previously reported autonomously replicating sequences. Although a portion of plasmids remained in host cells by integration into the chromosome via RS1 segment, the plasmids could be recovered from transformants. The plasmid copy number was estimated to be 1.88 copies per cell by Southern blot analysis using a Sz. pombe ura4(+) probe. The plasmid containing ade6(+) suppressed the auxotrophic growth of the ade6-domE mutant, indicating that the plasmid would be useful for suppressor screening and complementation assays in Sz. japonicus. Furthermore, pSJU11 transformed Sz. pombe cells with the same frequency as the pREP2 plasmid. This study is a report to demonstrate practical use of episomal plasmid vectors for genetic research in Sz. japonicus. PMID- 20737411 TI - Effectiveness of communication skills training of nurses on the quality of life and satisfaction with healthcare professionals among newly diagnosed cancer patients: a preliminary study. AB - INTRODUCTION: The importance of effective communication skills to sustain the cancer patient quality of life (QOL) and their satisfaction with healthcare professionals is well documented. This study aims to assess the effectiveness of communication skills training (CST) of nurses for patient QOL and their satisfaction with healthcare professionals just after being diagnosed with cancer. METHODS: This is a secondary analysis of a randomized controlled trial. Eight nurses, who mainly provide psychological and informational support for patients soon after they were informed of their cancer diagnosis by physicians at a cancer screening center, were randomly assigned to an experimental group attending a CST program (four nurses) or to a control group (four nurses). Eighty nine patients with gastric, colorectal, or breast cancer were supported and assessed by either group of nurses during the study period. The effectiveness for patient QOL and their satisfaction with healthcare professionals was assessed by administering the Short Form-8 Health Survey (SF-8) and a single-item VAS three times (1 week after diagnosis: T1; 1 month after diagnosis: T2; and 3 months after diagnosis: T3). RESULTS: Repeated measures analysis of variance showed a group-by-time significant increase of the mental aspects of SF-8 (F=3.48; P=0.03) and satisfaction with the nurse (F=3.18; p=0.04). CONCLUSIONS: Our findings underscore the importance of CST for healthcare professionals to improve the QOL of patients as well as their satisfaction with these professionals. PMID- 20737412 TI - Interaction patterns between parents with advanced cancer and their adolescent children. AB - OBJECTIVE: Advanced cancer profoundly affects those with the illness and their families. The interaction patterns between parents with advanced cancer and their adolescent children are likely to influence how a family experiences a parent's dying process. There is little information on such interactions. This study aimed to develop an explanatory model that explains interaction patterns between parents with advanced cancer and their adolescent children and to identify strategies to prepare children for their lives after a parent dies. METHODS: Semi structured interviews were conducted with 9 parents with advanced cancer, 7 of their spouses/partners, and 10 of their adolescent children. The interviews were recorded, transcribed verbatim, and analyzed using a constructionist grounded theory approach. RESULTS: Twenty-six family participants were interviewed. Their main concern was not having enough time together. In response, they described a four-stage process for optimizing the time they had left together: coming to know our time together is limited, spending more time together, extending our time together, and giving up our time together to end the suffering. The adolescents and their ill parents did not change their interaction patterns until they realized their time together was limited by the advanced cancer. Then they spent more time together to make things easier for each other. CONCLUSIONS: Time was of great importance to the parents and adolescents; all the participants structured their stories in relation to the concept of time. The model reflects the dynamic process by which families continuously adapt their relationships in the face of advanced cancer. PMID- 20737413 TI - In vitro effect of nickel on bovine spermatozoa motility and annexin V-labeled membrane changes. AB - In this study the effect of in vitro culture of bovine spermatozoa with nickel (NiCl(2)) on spermatozoa motility and membrane changes was analyzed. The spermatozoa motility significantly decreased after 120 min of culture at the concentration of 1000 MUM Ni ml(-1) (P < 0.05) and after 240 min of culture at the concentration of 500 and 1000 MUM Ni ml(-1) (P < 0.001) as compared with control. The progressive motility was the highest in the control group and in the groups with the lowest nickel concentrations (7.8 and 125 MUM Ni ml(-1)). The progressive spermatozoa motility was significantly altered even after 30 min of culture in the group with the highest nickel concentration (1000 MUM Ni ml(-1)). A significant decrease in progressive motility from the concentration of 250 MUM Ni ml(-1) was detected after 240 min of culture. Concentrations from 125 MUM Ni ml(-1) in various time periods of culture stimulated spermatozoa motility after 30 min (P < 0.001), but later an inhibitory effect was noted. After 240 min of in vitro spermatozoa culture with 125 MUM Ni ml(-1) a typical Annexin V fluorescence reaction was detected. Fluorescence was detected in mitochondrial segment of bovine spermatozoa. In spermatozoa exposed to higher nickel concentrations the Annexin V-positive reaction was detected also on the spermatozoa head membrane. In the group with the highest concentration and the longest time of exposure (1000 MUM Ni ml(-1); 240 min) the apoptotic Annexin-positive regions were detected not only in the mitochondrial part, but also in the spermatozoa head (acrosomal and postacrosomal part), showing significant alteration of spermatozoa membrane integrity. PMID- 20737415 TI - Influence of genetic matrix and crop year on chemical and sensory profiles of Italian monovarietal extra-virgin olive oils. AB - BACKGROUND: Commercial virgin olive oils belonging to the cultivars (Bosana, Carolea, Coratina, Frantoio, Itrana, Leccino, Moraiolo, Peranzana, Piantone di Mogliano and Ravece) most represented at the Italian National Review of Monovarietal olive oils (Rassegna Nazionale Italiana degli oli Monovarietali) were considered. The evaluation of the influence of the cultivar and of the crop year as well as their interaction on oil composition were statistically analysed by a complete factorial design by principal components analysis and by linear discriminant analysis. RESULTS: In fatty acids composition, the effect of the cultivar and crop year and their interaction were highly significant. The statistical analysis showed that the sensory attributes (olive fruity, grassy, fresh almond, artichoke, tomato, aromatic herbs, bitter and pungent) were strongly influenced by the cultivar. The prevalent effect of the cultivar on the sensory profile was also demonstrated by the low or absent level of significance observed in the crop year. CONCLUSION: The construction of a databank based on a large number of samples, which is available at URL http://www.olimonovarietali.it, has contributed to the reduction of the variable effects involved in the oil production process. Knowledge of the chemical and sensory profiles of the Italian monovarietal olive oils could start a certification process of these oils, thus giving greater guarantees about their origin. PMID- 20737414 TI - Developmental toxicity of dextromethorphan in zebrafish embryos/larvae. AB - Dextromethorphan is widely used in over-the-counter cough and cold medications. Its efficacy and safety for infants and young children remains to be clarified. The present study was designed to use zebrafish as a model to investigate the potential toxicity of dextromethorphan during embryonic and larval development. Three sets of zebrafish embryos/larvae were exposed to dextromethorphan at 24, 48 and 72 h post fertilization (hpf), respectively, during the embryonic/larval development. Compared with the 48 and 72 hpf exposure sets, the embryos/larvae in the 24 hpf exposure set showed much higher mortality rates which increased in a dose-dependent manner. Bradycardia and reduced blood flow were observed for the embryos/larvae treated with increasing concentrations of dextromethorphan. Morphological effects of dextromethorphan exposure, including yolk sac and cardiac edema, craniofacial malformation, lordosis, non-inflated swim bladder and missing gill, were also more frequent and severe among zebrafish embryos/larvae exposed to dextromethorphan at 24 hpf. Whether the more frequent and severe developmental toxicity of dextromethorphan observed among the embryos/larvae in the 24 hpf exposure set, as compared with the 48 and 72 hpf exposure sets, is due to the developmental expression of the phase I and phase II enzymes involved in the metabolism of dextromethorphan remains to be clarified. A reverse transcription-polymerase chain reaction analysis, nevertheless, revealed developmental stage-dependent expression of mRNAs encoding SULT3 ST1 and SULT3 ST3, two enzymes previously shown to be capable of sulfating dextrorphan, an active metabolite of dextromethorphan. PMID- 20737416 TI - Physicochemical and sensory characteristics of no-bake wheat-soy snack bars. AB - BACKGROUND: Health and wellness is a trend observed throughout ready-to-eat cereals, cereal health bars. Therefore, the main objectives of this research were to produce a low cost, acceptable, nutritious and healthy wheat- and soy-based bar under no-bake conditions. Also, the physical, chemical, microbial, acceptability and the nutritional value of this product were studied. Six different bars were produced: a wheat bar (WB), a wheat bar with coating (WBC), a wheat and soy bar with coating (WSBC), a soy bar with coating (SBC), a wheat bar with 3% glycerin (WB3%), and a wheat bar with 6% glycerine (WB6%). RESULTS: WB and WBC had the highest water activities while WSBC had the lowest. The three bars with coating had higher L and lower b values, which indicates that they were lighter and not as highly yellow coloured as the wheat samples. WSBC had the lowest value for hardness while the SBC and WBC had the highest. SBC received the highest scores for overall acceptability, appearance, sweetness, flavour and texture while WSBC received the second highest score in all categories. CONCLUSION: It appears that consumers prefer the soy varieties to the wheat bars. These types of bars can aid in feeding the general population, which is becoming increasingly concerned with nutrition and convenience. PMID- 20737419 TI - Minimum information about a flow cytometry experiment (MIFlowCyt) checklist (Numbered in accordance with MIFlowCyt 1.0 document). PMID- 20737418 TI - Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the Austrian Brain Tumor Registry, 1996-2006. AB - BACKGROUND: Atypical teratoid/rhabdoid tumors are highly malignant embryonal central nervous system (CNS) tumors that were defined as an entity in 1996. As compared with other malignant CNS tumors, their biological behavior is particularly aggressive, but patients may benefit from an intensified treatment. Atypical teratoid/rhabdoid tumors display a complex histomorphology, which renders them prone to misdiagnosis. They occur predominantly in young children, with an estimated prevalence of 1% to 2% among all pediatric CNS tumors. However, population-based data on the incidence of these tumors are not yet available. METHODS: A nation-wide survey of malignant high-grade CNS tumors (World Health Organization grade III/IV), diagnosed in children (aged birth to 14 years) from 1996 to 2006 was conducted by the Austrian Brain Tumor Registry. A central histopathology review was performed including the assessment of SMARCB1 (INI1) protein status. RESULTS: A total of 311 newly diagnosed, malignant CNS tumors were included. Atypical teratoid/rhabdoid tumors constituted the sixth most common entity (6.1%), referring to an age-standardized incidence rate of 1.38 per 1,000,000 person-years in children. Peak incidence was found in the birth to 2 years age group, where they were as common as CNS primitive neuroectodermal tumors and medulloblastomas. A total of 47.4% of atypical teratoid/rhabdoid tumors were initially diagnosed, whereas 52.6% were retrospectively detected by the central review. The 5-year survival of atypical teratoid/rhabdoid tumor patients was 39.5%, with 66.7% in the correctly diagnosed group versus 15.0% in the not recognized group (P = .0469). CONCLUSIONS: Clinicians and pathologists should be aware of the high incidence of atypical teratoid/rhabdoid tumors in young children to optimize diagnostic and therapeutic management of patients with these tumors. PMID- 20737420 TI - Neoadjuvant FOLFOX chemotherapy in 34 consecutive patients with mucinous peritoneal carcinomatosis of appendiceal origin. AB - BACKGROUND: A treatment option for patients with peritoneal mucinous carcinomatosis (PMCA) from an appendiceal neoplasm is cytoreductive surgery and perioperative intraperitoneal chemotherapy. Also, these patients are recommended for systemic chemotherapy using an oxaliplatin and 5-fluorouracil (FOLFOX) regimen. A major question concerns the proper timing (neoadjuvant vs. adjuvant) of the systemic chemotherapy. METHODS: In January of 2005 a prospective study was initiated to routinely treat patients with peritoneal dissemination of a mucinous adenocarcinoma of the appendix with neoadjuvant chemotherapy using FOLFOX. All patients had a clinical, CT, intraoperative, and histopathological assessment of chemotherapy effects. The study was closed in July of 2009. RESULTS: Thirty-four consecutive patients were available for evaluation. In the clinical evaluation and CT evaluation, 24 (71%) and 22 (65%), respectively, had stable disease on chemotherapy. By intraoperative examination 17 (50%) patients were observed to have progressed. By histopathology seven had a partial response and three patients a complete response (29%). CONCLUSIONS: In these carcinomatosis patients clinical and CT assessment of response to neoadjuvant chemotherapy seldom provided useful data over this short time period. Intraoperative findings indicated progression in 50% of patients. By histopathology, 29% of patients had a response. PMID- 20737417 TI - Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer: final patient-level results from Japan Clinical Oncology Group 9511 and Southwest Oncology Group 0124. AB - BACKGROUND: Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results. METHODS: Patients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m(2) Day 1 + irinotecan 60 mg/m(2) Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m(2) Day 1 + etoposide 100 mg/m(2) Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS). RESULTS: Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared. CONCLUSIONS: Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected. PMID- 20737421 TI - Establishment of an orthotopic transplantable gastric cancer animal model for studying the immunological effects of new cancer therapeutic modules. AB - Tumor cell growth is influenced by the cellular microenvironment including the presence of immune cells and blood vessels. Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene-treated ICR mice. MGCC3I cells showed epithelial-like morphology, multinuclear giant cell formation, and retained an intestinal phenotype, which are similar to human gastric cancer carcinoma cells. The expression of gastric cancer markers MUC1, MUC2, and MUC5AC, and oncogenes c-myc, c-met, cyclin E1, and cancer stem cell marker CD44 was determined in MGCC3I cells. MGCC3I cells formed poorly differentiated stomach tumors following orthotopic implantation into the stomachs of syngeneic ICR mice. Histone deacetylase inhibitors are recognized as a new class of anticancer drugs. The immunological therapeutic effects of the histone deacetylase inhibitors sodium butyrate and valproic acid were evaluated in this new animal tumor model. Sodium butyrate inhibited MGCC3I stomach tumor formation in animal models. Increased tumor infiltration by CD8 T cells and neutrophils was observed in mice treated with sodium butyrate or valproic acid. Depletion of CD8 T cells significantly attenuated tumor regression mediated by histone deacetylase inhibitors, which is correlated with enhancement of the MHC class I pathway in MGCC3I cells. Taken together, we have successfully established an orthotopic transplantable gastric tumor animal model and demonstrated its usefulness in revealing the role of CD8 T cells in the therapeutic effects of sodium butyrate. PMID- 20737422 TI - Sedentary work, low physical job demand, and obesity in US workers. AB - BACKGROUND: Little is known about the role of low physical activity at work (sedentary work or low physical job demand) in the increasing prevalence of obesity of US workers. METHODS: This cross-sectional and secondary data analysis included 1,001 male and 1,018 female workers (age range: 32-69) from the National Survey of Midlife Development in the United States (MIDUS) II study (2004-2006). Sedentary work and physical job demand were measured by questionnaire items. Total obesity (based on body mass index) and central obesity (based on waist circumference) were defined using WHO criteria. RESULTS: After controlling for covariates (socio-demographic, psychosocial working conditions, health status, and health behaviors), sedentary work, low physical job demand, or their combination increased the risk for total and central obesity in male workers, particularly when they worked longer than 40 hr per week. Sedentary work marginally increased the risk for total and central obesity in female workers. CONCLUSIONS: Low physical activity at work is a significant risk factor for total and central obesity in middle-aged US male workers. PMID- 20737423 TI - Barriers and enablers to returning to work from long-term sickness absence: Part I-A quantitative perspective. AB - BACKGROUND: Long-term sickness absence (LTSA) in the United Kingdom labor market has become a major health issue in recent years. In contrast to short-term sickness absence, rates for LTSA have been on the increase. This paper, part 1 of a two-part paper, identifies individual domain barriers to returning to work (RTW) from LTSA across the work disability timeline in the UK labor market. METHODS: This is a retrospective cohort study of 6,246 workers from an occupationally diverse Police Force within the UK using a large administrative database. A series of chi-squared analyses were conducted to analyze the between and within group associations. Next, multiple logistic regression analyses using the Enter method were performed to develop a predictive model for RTW and Absence Phase. RESULTS: Findings substantiated the presence of individual domain barriers to RTW and predictors of RTW outcome and established the absence phase specificity of a number of risk factors of prolonged work disability. In particular, injury/illness especially mental ill health (MIH), physical job demands, sex, and number of episodes of LTSA are significant individual domain barriers to RTW and represent important risk factors for prolonged work disability. CONCLUSIONS: Duration of work disability is associated with medical diagnosis, especially MIH, physical job demands, sex, and number of LTSA episodes. Findings also support the importance of using the outcome measure of absence phase of risk factors in addition to RTW outcome. PMID- 20737424 TI - Chemoprevention of a flavonoid fraction from Rhus verniciflua Stokes on aflatoxin B1-induced hepatic damage in mice. AB - Since aflatoxin B(1) (AFB(1))-mediated hepatic damage is related to the production of AFB(1)-8,9-epoxide and reactive oxygen species, bioactive compounds having antioxidant potentials are suggested to be capable of reducing AFB(1) induced toxicity. We previously purified a mixture of flavonoids that we named RCMF (Rhus verniciflua Stokes chloroform-methanol fraction), from a traditional Korean food additive and herbal medicine. RCMF exhibited various biological effects, including antioxidant and antitumor activities. In this study, we examined whether RCMF protects against AFB(1)-induced liver injury using in vitro and in vivo systems. Pretreatment of HepG2 cells with RCMF significantly reduced AFB(1)-stimulated production of ROS and malondialdehyde (MDA) to the control levels. RCMF also prevented the reduction in HepG2 cell viability caused by AFB(1). Oral administration of RCMF to mice significantly suppressed an AFB(1) induced increase in serum levels of alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. It also prevented MDA formation and blocked decreases in glutathione levels and superoxide dismutase activities in the livers of AFB(1)-treated mice. In addition, RCMF supplementation prevented an AFB(1) -induced decrease in serum titers of IgA and IgG1. Collectively, these results suggest that RCMF attenuates AFB(1)-mediated damage to the liver, and that this effect is at least partially related to the restoration of antioxidant defense systems and an increase in AFB(1)-GSH conjugate formation. PMID- 20737425 TI - Does 2,2',4,4'-tetrabromodiphenyl ether interact directly with thyroid receptor? AB - 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a flame-retardant chemical appearing at increasing concentrations and frequency in the environment and human samples. A number of health effects of exposure to BDE-47 have been observed, thyroid disruption being the most sensitive. Our objective was to examine BDE-47 interaction with thyroid receptor beta (TRbeta). We used a variety of approaches, including in vitro binding assays, luciferase reporter-gene transcriptional assays, and analysis of expression of thyroid responsive genes in rat offspring exposed perinatally to BDE-47. We found that BDE-47 alone or in mixture with 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153) does not compete with [(125)I]T(3) for TRbeta-binding even at 4000 fold higher concentrations. Also, BDE-47 does not affect thyroid responsive genes through TRbeta in in vitro studies of transcription regulation. A subset of thyroid responsive genes were significantly differentially expressed in liver and frontal lobe brain samples of exposed pups, however, the action of BDE-47 was neither agonistic or antagonistic to that of thyroid hormone. We conclude that BDE-47 does not interact directly with TRbeta1 nor does it influence its transcriptional activity. Developmental exposure of rats to BDE-47 leads to differential expression of thyroid responsive genes in liver and brain due to unknown mechanism. PMID- 20737427 TI - Improving the performance of industrial ethanol-producing yeast by expressing the aspartyl protease on the cell surface. AB - The yeasts used in fuel ethanol manufacture are unable to metabolize soluble proteins. The PEP4 gene, encoding a vacuolar aspartyl protease in Saccharomyces cerevisiae, was either secretively or cell-surface anchored expressed in industrial ethanol-producing S. cerevisiae. The obtained recombinant strains APA (expressing the protease secretively) and APB (expressing the protease on the cell wall) were studied under ethanol fermentation conditions in feed barley cultures. The effects of expression of the protease on product formation, growth and cell protein content were measured. The biomass yield of the wild-type was clearly lower than that of the recombinant strains (0.578 +/- 0.12 g biomass/g glucose for APA and 0.582 +/- 0.08 g biomass/g glucose for APB). In addition, nearly 98-99% of the theoretical maximum level of ethanol yield was achieved (relative to the amount of substrate consumed) for the recombinant strains, while limiting the nitrogen source resulted in dissatisfactory fermentation for the wild-type and more than 30 g/l residual sugar was detected at the end of fermentation. In addition, higher growth rate, viability and lower yields of byproducts such as glycerol and pyruvic acid for recombinant strains were observed. Expressing acid protease can be expected to lead to a significant increase in ethanol productivity. PMID- 20737426 TI - Biochemical and histopathological evaluation of functionalized single-walled carbon nanotubes in Swiss-Webster mice. AB - With their unique physicochemical properties, single-walled carbon nanotubes (SWCNTs) have many potential new applications in medicine and industry. A biomedical application of single-wall carbon nanotubes such as drug delivery requires a fundamental understanding of their fate and toxicological profile after administration. However, the toxicity of SWCNT is barely known when they are introduced into the blood circulation, which is especially vital for their biomedical applications. The aim of this study was to assess the effects, after intraperitoneal injection, of functionalized SWCNTs (carboxyl groups) on reactive oxygen species (ROS) induction and various hepatotoxicity markers (ALT, AST, ALP, LPO and morphology of liver) in the mouse model. We exposed mice to three different concentrations of functionalized SWCNTs (0.25, 0.5 and 0.75 mg kg-1 b.w.) and two controls (negative and positive). Samples were collected 24 h after the last treatment following standard protocols. Exposure to carboxylated functionalized SWCNT induced ROS and enhanced the activities of serum amino transferases (ALT/AST) and alkaline phosphatases (ALP) and the concentration of lipid hydroperoxide compared with control. Histopathology of the exposed liver showed a statistically significant effect in the morphological alterations of the tissue compared with controls. The cellular findings reported here do suggest that purified carboxylated functionalized SWCNT has the potential to induce hepatotoxicity in Swiss-Webster mice through activation of the mechanisms of oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies. However, more studies to clarify the role of functionalization in the in vivo toxicity of SWCNTs are required and parallel comparison is preferred. PMID- 20737428 TI - Transformation of Candida albicans with a synthetic hygromycin B resistance gene. AB - Synthetic genes that confer resistance to the antibiotic nourseothricin in the pathogenic fungus Candida albicans are available, but genes conferring resistance to other antibiotics are not. We found that multiple C. albicans strains were inhibited by hygromycin B, so we designed a 1026 bp gene (CaHygB) that encodes Escherichia coli hygromycin B phosphotransferase with C. albicans codons. CaHygB conferred hygromycin B resistance in C. albicans transformed with ars2-containing plasmids or single-copy integrating vectors. Since CaHygB did not confer nourseothricin resistance and since the nourseothricin resistance marker SAT-1 did not confer hygromycin B resistance, we reasoned that these two markers could be used for homologous gene disruptions in wild-type C. albicans. We used PCR to fuse CaHygB or SAT-1 to approximately 1 kb of 5' and 3' noncoding DNA from C. albicans ARG4, HIS1 and LEU2, and introduced the resulting amplicons into six wild-type C. albicans strains. Homologous targeting frequencies were approximately 50-70%, and disruption of ARG4, HIS1 and LEU2 alleles was verified by the respective transformants' inabilities to grow without arginine, histidine and leucine. CaHygB should be a useful tool for genetic manipulation of different C. albicans strains, including clinical isolates. PMID- 20737429 TI - Requirement of glutathione for Sod1 activation during lifespan extension. AB - It has been shown that the activation of cytosolic superoxide dismutase (Sod1) in Saccharomyces cerevisiae is only dependent on Ccs1, which is responsible for insertion of copper into the enzyme catalytic center, and that glutathione (GSH) is not necessary for this process. In this work, we addressed an important role of GSH in Sod1 activation by a Ccs1-dependent mechanism during oxidative stress and its role in yeast lifespan. Exponential cells of Saccharomyces cerevisiae, treated or not with 0.5 mM menadione for 1 h, were used for evaluation of the effect of a mild oxidative stress pre-treatment on chronological lifespan. The results showed that menadione induced a lifespan extension in the wild-type (WT) strain but this adaptive response was repressed in gsh1 and in sod1 strains. Interestingly, menadione treatment increased SOD1 and CCS1 gene expression in both WT and gsh1 strains. However, while these strains showed the same Sod1 activity before treatment, only the WT presented an increase of Sod1 activity after menadione exposure. Glutathionylation seems to be essential for Sod1 activation since no increase in activity was observed after menadione treatment in grx1 and grx2 null mutants. Our results suggest that GSH and glutathionylation are fundamental to protect Sod1 sulfhydryl residues under mild oxidative stress, enabling Sod1 activation and lifespan extension. PMID- 20737430 TI - Hairpin dsRNA does not trigger RNA interference in Candida albicans cells. AB - RNA interference/silencing mechanisms triggered by double-stranded RNA (dsRNA) have been described in many eukaryotes, including fungi. These mechanisms have in common small RNA molecules (siRNAs or microRNAs) originating from dsRNAs that, together with the effector protein Argonaute, mediate silencing. The genome of the fungal pathogen Candida albicans harbours a well-conserved Argonaute and a non-canonical Dicer, essential members of silencing pathways. Prototypical siRNAs are detected as members of the C. albicans transcriptome, which is potential evidence of RNA interference/silencing pathways in this organism. Surprisingly, expression of a dsRNA a hairpin ADE2 dsRNA molecule to interfere with the endogenous ADE2 mRNA did not result in down-regulation of the message or produce adenine auxotrophic strains. Cell free assays showed that the hairpin dsRNA was a substrate for the putative C. albicans Dicer, discounting the possibility that the nature of the dsRNA trigger affects silencing functionality. Our results suggested that unknown cellular events govern the functionality of siRNAs originating from transgenes in RNA interference/silencing pathways in C. albicans. PMID- 20737431 TI - Slt2 MAPK pathway is essential for cell integrity in the presence of arsenate. AB - Arsenate is a common toxic metalloid found in drinking water worldwide that causes several human diseases. The biochemical action underlying cellular response to arsenate, however, is not yet completely understood. Here we used Saccharomyces cerevisiae as an eukaryotic model system to identify proteins essential for adaptation to arsenate treatment. Previous studies have demonstrated a function for Hog1 MAPK in modulating the cellular response to arsenite. Our results, however, showed that cells deficient in Hog1 did not show increased sensitivity to arsenate, suggesting that perhaps other MAPKs may be involved in the response to this particular arsenic species. Here, we found that Slt2 MAPK and several of its upstream regulators are essential in modulating the response to arsenate, and that Slt2 is phosphorylated after arsenate treatment. Furthermore, whole-genome transcriptional analysis showed that Slt2 is required for the induction of several genes in response to arsenate exposure. Many of these genes are involved in the cellular response to heat, suggesting an overlap between these two stress response pathways, and pointing toward a common response to both arsenate and heat exposure in Saccharomyces cerevisiae. Furthermore, our results support the idea that cellular exposure to arsenate results in induction of cellular signalling pathways different from those induced under arsenite treatment. PMID- 20737432 TI - Retrieval analysis and in vitro assessment of strength, durability, and distraction of a modular total hip replacement. AB - We investigated a commercial Co-Cr-alloy head--Ti6Al4V alloy neck and Ti6Al4V stem modular total hip replacement. We assessed the distraction forces after in vitro cycling in bovine serum, fatigue durability, fretting corrosion damage, and load bearing capacity of new implants using fatigue-corrosion, pull-off, scanning electron microscopy, fatigue and compression investigations. In addition, we studied corrosion, fretting damage, and distraction forces on retrievals. For both retrievals and in vitro test samples, the neck-stem interface required the higher distraction force as compared with the head-neck interface. One of 12 retrievals showed strong fretting corrosion at the neck-stem interface which resulted in a high disassembly force of about 16 kN. For in vitro test samples, the neck-stem pull-off force initially increased during cycling and showed a maximum value of 5.704 kN at ~100,000 cycles, which is equivalent to gait cycles performed in approximately 36 days. Overall, assembly force, initial component settling, and interface corrosion primarily determine the force required to distract the modular components. One million cycles fatigue failure of the neck can be expected at a maximum compression load of -6.5 kN. No component failure was observed during quasistatic compression; rather the neck deformed plastically and the ultimate compression load-bearing capacity was -13 kN. PMID- 20737434 TI - Fabrication of polyvinyl alcohol/gelatin nanofiber composites and evaluation of their material properties. AB - Electrospinning of polyvinyl alcohol (PVA), gelatin (GE), and a PVA/GE blend was conducted with the aim of fabricating biodegradable scaffolds for tissue engineering. The process parameters including the concentration of GE in PVA/GE blends, electrical field, and tip-to-collector distance (TCD) were investigated. Electrospinning processes were conducted at three different GE concentrations (PVA/GE = 2/8, 6/4, and 8/2), and the voltage and TCD were varied from 18 to 24 kV and 7 to 20 cm, respectively. The average diameter of the electrospun PVA, GE, and PVA/GE blend fibers ranged from 50 to 150 nm. The TCD had significant effects on the average diameter of the PVA/GE nanofiber, while changes in the voltage did not significantly affect the diameter of the PVA/GE nanofiber. The miscibility of the PVA/GE blend fibers was examined by differential scanning calorimetry, and X ray diffraction was used to determine the crystallinity of the membrane. Tensile strength was measured to evaluate the physical properties of the membrane. Based on the combined results of this study, the PVA/GE membrane holds great promise for use in tissue engineering applications, especially in bone or drug delivery systems. PMID- 20737433 TI - Simple immersion of filter devices into an urokinase solution prevents fibrin net formation during carotid artery stenting. AB - Slow-flow phenomenon is frequently observed during carotid artery stenting (CAS) with a filter embolic protection device. It results in technical difficulties and can lead to adverse neurological events. Flow impairment is thought to be caused by plaque entrapped by the filter and/or blood coagulation on the filter. Characteristics of heparin- or urokinase-treated polyurethanes were analyzed by surface plasmon resonance, and the fibrinolytic activity of the urokinase-treated filter of Angioguard XP was estimated by the fibrin plate assay. A filter membrane of Angioguard XP protection device was treated with a heparin or urokinase solution. In clinical studies, six and nine patients were treated by CAS using Angioguard XP modified with heparin and urokinase, respectively. Filter membranes were examined by scanning electron microscopy (SEM). From in vitro studies, it appeared that urokinase adsorbed and remained on the Angioguard XP filter, and its fibrinolytic activity was demonstrated even after washing with saline; heparin, however, was easily washed out from the surface. From clinical study, some filter pores were obstructed in all six patients in the heparin group and in three patients in the urokinase group. Fibrin net was found on the filter in five of six patients in the heparin group and in one of nine patients in the urokinase group. Treatment of an Angioguard XP filter with a urokinase solution is effective in preventing pore occlusion and may reduce occurrence of the slow flow phenomenon. PMID- 20737435 TI - Subcritical crack growth behavior of dispersion oxide ceramics. AB - Zirconia (Y-TZP) is used as material for components of implants and prostheses because of its high short-term strength. The mechanical long-term reliability, however, is limited for Y-TZP because of hydrothermal aging effects and a pronounced tendency for subcritical crack growth. The hypothesis of this study was that a substantial amount of alumina in a zirconia matrix can help to significantly suppress subcritical crack growth and thereby improve the mechanical long-term reliability. The Weibull parameters as well as the parameters of the subcritical crack growth were determined for Alumina, Y-TZP, and two dispersion ceramics, that is Alumina Toughened Zirconia (ATZ, 20% alumina/80% Y-TZP), and Zirconia Toughened Alumina (ZTA, 75% alumina/25% Y-TZP). The long-term failure probability as a function of service time was predicted for the four ceramics. The parameter n of the subcritical crack growth was approx. 80% higher for ATZ compared to Y-TZP. In consequence, the estimated lifetime revealed a significant better mechanical long-term reliability for ATZ. It can be concluded that tailored dispersion oxide ceramics can address the aging problem of monolithic zirconia. This makes ATZ very interesting for components of joint replacement as well as for dental prostheses and implants. PMID- 20737436 TI - A tiny infarct on the dorsolateral pons mimicking vestibular neuritis. AB - We report a case of a tiny infarct on the left dorsolateral pons in a 50-year-old man who presented with prolonged and isolated vertigo. The clinical features mimic vestibular neuritis and can easily lead to misdiagnosis. Selective involvement of the left superior vestibular nucleus might explain the resemblance to acute peripheral vestibulopathy. PMID- 20737437 TI - Structure of a putative BenF-like porin from Pseudomonas fluorescens Pf-5 at 2.6 A resolution. PMID- 20737439 TI - Side-chain rotamer transitions at protein-protein interfaces. AB - We compare the changes in side chain conformations that accompany the formation of protein-protein complexes, in residues forming either the interface or the remainder of the solvent-accessible surface of the proteins in the Docking Benchmark 3.0. We find that the interface residues undergo significantly more changes than other surface residues, and these changes are more likely to convert them from a high-energy torsion angle state to a lower-energy one than the reverse. Moreover, in both the unbound proteins and the complexes, the interface residues are more frequently found to be in a high-energy torsion angle state than the noninterface residues. As these differences exist before the binding step, they may be relevant to specificity and help in identifying binding sites for docking predictions. PMID- 20737440 TI - The diagnosis of non-Hodgkin lymphoma using fine-needle aspiration cytopathology: a work in progress. PMID- 20737438 TI - The Abl and Arg non-receptor tyrosine kinases regulate different zones of stress fiber, focal adhesion, and contractile network localization in spreading fibroblasts. AB - Directed cell migration requires precise spatial control of F-actin-based leading edge protrusion, focal adhesion (FA) dynamics, and actomyosin contractility. In spreading fibroblasts, the Abl family kinases, Abl and Arg, primarily localize to the nucleus and cell periphery, respectively. Here we provide evidence that Abl and Arg exert different spatial regulation on cellular contractile and adhesive structures. Loss of Abl function reduces FA, F-actin, and phosphorylated myosin light chain (pMLC) staining at the cell periphery, shifting the distribution of these elements more to the center of the cell than in wild-type (WT) and arg(-/-) cells. Conversely, loss of Arg function shifts the distribution of these contractile and adhesion elements more to the cell periphery relative to WT and abl(-/-) cells. Abl/Arg-dependent phosphorylation of p190RhoGAP (p190) promotes its binding to p120RasGAP (p120) to form a functional RhoA GTPase inhibitory complex, which attenuates RhoA activity and downstream pMLC and FA formation. p120 and p190 colocalize both in the central region and at the cell periphery in WT cells. This p120:p190 colocalization redistributes to a more peripheral distribution in abl(-/-) cells and to a more centralized distribution in arg(-/-) cells, and these altered distributions can be restored to WT patterns via re expression of Abl or Arg, respectively. Thus, the altered p120:p190 distribution in the mutant cells correlates inversely with the redistribution in adhesions, actin, and pMLC staining in these cells. Our studies suggest that Abl and Arg exert different spatial regulation on actomyosin contractility and focal adhesions within cells. PMID- 20737441 TI - Protein homomers in point-group assembly: symmetry making and breaking are specific and distinctive in their codes of chemical alphabet in side chains. AB - Oligomerizing to point-group symmetry, protein oligomers need to have the symmetry broken for biologically crucial functions, such as, allosteric regulation, enzyme catalysis, and so forth. In the making of symmetry, based on self assembly, and the breaking of symmetry, based on intermolecular interactions, proteins may manifest, like their other functions, specific scripts over the coding alphabet in side chains. To address the possibility, we analyzed 82 protein homodimers in their C(2)-symmetry-related side chains across noncrystallographic interfaces, to know if they may be identical or distinct in conformation, and thus conserved or broken in symmetry. We find the propensity to conformational mismatch across interfaces correlated with side-chain chemical structure, low to very low in aromatic Trp, Tyr, His, Phe, and Arg, and high to very high in aliphatic Val, Pro, Met, Glu, Ser, Lys, Gln, Asn, and Asp, related not to polarity but, interestingly, to aromaticity of the structure. The organizational plan having aromatics embedded in a hub of aliphatic-nonpolar groups and a surrounding rim of aliphatic-polar groups, called "hotspot," has been known to direct protein-protein interaction. Finding conformational-mismatch propensities of side chains congruous with their specific chemical roles in protein-protein interaction, we propose that aromatic side chains will drive protein homomers to high symmetry, while polar- and nonpolar aliphatic side chains will drive them to the functionally-necessitated breaks of symmetry. Side chains are in their roles as protein-coding alphabet illuminated in the physics, which is discussed. PMID- 20737442 TI - Practical issues and lessons learned from multi-regional clinical trials via case examples: a Japanese perspective. AB - The multi-regional clinical trials (MRCTs) being administered in different regions of the world now play a major role in providing evidence for the efficacy and safety of new drugs amidst the simultaneous global development and worldwide registration of such drugs, in support of the expeditious availability of medical products to patients. However, such trials present considerable challenges as far as quality, design, implementation, analysis, and interpretation are concerned. In this article, we share our observations and lessons learned from the design, implementation, analysis, and interpretation of some MRCTs with case examples. Current Japanese regulatory guidance on MRCTs is introduced along with some suggestions for design, implementation, and interpretation. PMID- 20737443 TI - Precautions to improve the accuracy of quantitative determinations of biomarkers in clinical diagnostics. AB - Although protein biomarkers have a great potential as biomarkers for diagnosis of diseases, they are seldom used in hospitals. There are many reasons for this, for instance, the difficulties to (i) find a biomarker for which the concentration in body fluids clearly differs between patients and healthy subjects, (ii) attain purification of the biomarker close to 100%, which is required for production of conventional protein antibodies as well as artificial gel antibodies for selective capture of a biomarker, (iii) design a standard curve for rapid and accurate determination of the concentration of the biomarker in the body fluid because of adsorption of the biomarker onto vials, pipettes, etc., (iv) determine accurately the sample volume delivered by a pipette, (v) avoid polymerization of the biomarker upon storage and to decide whether it is in the form not only of monomers, but also of dimers, trimers, etc., in the native state, (vi) determine the degree of possible glycosylation and amidation of the biomarker and (vii) decide whether glycosylation and amidation positively or negatively affects the possibility to use the protein as a biomarker. In this article, we discuss in quantitative terms the difficulties (iii-vii) and how to overcome them, which also may help to overcome the difficulty (ii), which in turn minimizes difficulty (i). PMID- 20737444 TI - Recombinant clotting factor VIII concentrates: Heterogeneity and high-purity evaluation. AB - Factor VIII is an important glycoprotein involved in hemostasis. Insertion of expression vectors containing either the full-length cDNA sequence of human factor VIII (FLrFVIII) or B-domain deleted (BDDrFVIII) into mammalian cell lines results in the production of recombinant factor VIII (rFVIII) for therapeutic usage. Three commercially available rFVIII concentrates (Advate, Helixate NexGen and Refacto), either FLrFVIII or BDDrFVIII, were investigated by 1- and 2-DE and MS. The objective of this study was to compare the heterogeneity and the high purity of both rFVIII preparations before and after thrombin digestion. In particular, the 2-D gel was optimized to better highlight the presence of contaminants and many unexpected proteins. Recombinant strategies consisting of insertion of expression vectors containing BDDrFVIII and FLrFVIII resulted in homogeneous and heterogeneous protein products, respectively, the latter consisting in a heterogeneous mixture of various B-domain-truncated forms of the molecule. Thrombin digestion of all the three rFVIII gave similar final products, plus one unexpected fragment of A2 domain missing 11 amino acids. Regarding the contaminants, Helixate NexGen showed the presence of impurities, such as Hsp70 kDa, haptoglobin and proapolipoprotein; Refacto showed glutathione S-transferase and beta-lactamase, whereas Advate apparently did not contain any contaminants. The proteomic approach will contribute to improving the quality assurance and manufacturing processes of rFVIII concentrates. In this view, the 2-DE is mandatory for revealing the presence of contaminants. PMID- 20737445 TI - Study of electromigration effects on a pH boundary during the on-line electrokinetic preconcentration by capillary electrophoresis. AB - A contribution to the description of electrokinetic effects on the pH boundary formed by sodium borate pH 9.5 and sodium phosphate pH 2.5 electrolytes for on line preconcentration of weak acids is presented in this article. Simulations of electrokinetic injections together with experimental studies using contactless conductivity detection verified that the preconcentration is induced mainly by dissociation changes of analytes on the pH boundary and transient ITP state. Moreover, a study of the addition of organic solvent to the injection electrolyte was performed with impressive results. Subnanomolar LODs of hydroxybenzoic acids were achieved with 80% of methanol in the injection electrolyte which represents more than 70 000-fold preconcentration in comparison with classical CZE method. PMID- 20737446 TI - Parallel separations using capillary electrophoresis on a multilane microchip with multiplexed laser-induced fluorescence detection. AB - Parallel separations using CE on a multilane microchip with multiplexed LIF detection is demonstrated. The detection system was developed to simultaneously record data on all channels using an expanded laser beam for excitation, a camera lens to capture emission, and a CCD camera for detection. The detection system enables monitoring of each channel continuously and distinguishing individual lanes without significant crosstalk between adjacent lanes. Multiple analytes can be determined in parallel lanes within a single microchip in a single run, leading to increased sample throughput. The pK(a) determination of small molecule analytes is demonstrated with the multilane microchip. PMID- 20737447 TI - An ultra-high temperature flow-through capillary device for bacterial spore lysis. AB - Rapid and specific characterization of bacterial endospores is dependent on the ability to rupture the cell wall to enable analysis of the intracellular components. In particular, bacterial spores from the bacillus genus are inherently robust and very difficult to lyze or solubilize. Standard protocols for spore inactivation include chemical treatment, sonication, pressure, and thermal lysis. Although these protocols are effective for the inactivation of these agents, they are less well suited for sample preparation for analysis using proteomic and genomic approaches. To overcome this difficulty, we have designed a simple capillary device to perform thermal lysis of bacterial spores. Using this device, we were able to super heat (195 degrees C) an ethylene glycol lysis buffer to perform rapid flow-through rupture and solubilization of bacterial endospores. We demonstrated that the lysates from this preparation method are compatible with CGE as well as DNA amplification analysis. We further demonstrated the flow-through lysing device could be directly coupled to a miniaturized electrophoresis instrument for integrated sample preparation and analysis. In this arrangement, we were enabled to perform sample lysis, fluorescent dye labeling, and protein electrophoresis analysis of bacterial spores in less than 10 min. The described sample preparation device is rapid, simple, inexpensive, and easily integratable with various microfluidic devices. PMID- 20737448 TI - Conformation dependence of DNA electrophoretic mobility in a converging channel. AB - The electrophoresis of lambda-DNA is observed in a microscale converging channel where the center-of-masses trajectories of DNA molecules are tracked to measure instantaneous electrophoretic (EP) mobilities of DNA molecules of various stretch lengths and conformations. Contrary to the usual assumption that DNA mobility is a constant, independent of field and DNA length in free solution, we find DNA EP mobility varies along the axis in the contracting geometry. We correlate this mobility variation with the local stretch and conformational changes of the DNA, which are induced by the electric field gradient produced by the contraction. A "shish-kebab" model of a rigid polymer segment is developed, which consists of aligned spheres acting as charge and drag centers. The EP mobility of the shish kebab is obtained by determining the electrohydrodynamic interactions of aligned spheres driven by the electric field. Multiple shish-kebabs are then connected end-to-end to form a freely jointed chain model for a flexible DNA chain. DNA EP mobility is finally obtained as an ensemble average over the shish-kebab orientations that are biased to match the overall stretch of the DNA chain. Using physically reasonable parameters, the model agrees well with experimental results for the dependence of EP mobility on stretch and conformation. We find that the magnitude of the EP mobility increases with DNA stretch, and that this increase is more pronounced for folded conformations. PMID- 20737450 TI - Quantitative determination of sparfloxacin in rat plasma by liquid chromatography/tandem mass spectrometry. AB - Sparfloxacin, a fluoroquinolone antibiotic, is used for the treatment of bacterial infection. A quantification method using mass spectrometry was developed for the determination of sparfloxacin in rat plasma. After simple protein precipitation with acetonitrile, the analytes were chromatographed on a reversed-phase C18 column and detected by liquid chromatography/tandem mass spectrometry with electrospray ionization. The accuracy and precision of the assay were in accordance with FDA regulations for validation of bioanalytical methods. This method was applied to measure the plasma sparfloxacin concentrations after a single oral administration of sparfloxacin in rats. PMID- 20737452 TI - Gastrointestinal stromal tumors presenting as gynecological masses: usefulness of multidetector computed tomography. AB - Large extraluminal gastrointestinal tumors (GISTs) may present as pelvic masses and thus mimic gynecological neoplasms in female patients. On clinical examination and pelvic ultrasound, these tumors resemble pedunculated fibroids or ovarian tumors. Multidetector computed tomography (CT), with its ability to perform isotropic multiplanar reconstruction, is useful in differentiating GISTs from true gynecological masses by demonstrating the pedicle sign connecting a pelvic GIST to its organ of origin. This allows a preoperative diagnosis to be made, which may be helpful in guiding therapeutic options and management. We present two cases of GISTs presenting as pelvic masses in which ultrasound findings suggested a gynecological cause, but multidetector CT with multiplanar reconstruction was able to determine their true organ of origin. PMID- 20737451 TI - Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre-eclampsia. AB - OBJECTIVES: To evaluate whether the measurement of maternal serum inhibin A, activin A and placental growth factor (PlGF) at 12 + 0 to 16 + 0 weeks of gestation alone or in combination with second-trimester uterine artery Doppler pulsatility index (PI) is useful in predicting pre-eclampsia. METHODS: This was a case-control study of pre-eclampsia. From pregnant women attending their first antenatal examination at 12-16 weeks we collected serum samples and stored them at - 80 degrees C. All patients also underwent uterine artery Doppler examination to measure the PI at 22-24 weeks' gestation. We retrieved for analysis frozen samples from women who then developed pre-eclampsia, as well as three control samples per woman, matched for gestational age and storage time. Inhibin A, activin A and PlGF were measured using an enzyme-linked immunosorbent assay (ELISA) by an examiner who was blinded to the pregnancy outcome. RESULTS: There were 31 cases with pre-eclampsia and 93 controls. Second-trimester uterine artery PI and marker levels were expressed as multiples of the median (MoM). The uterine artery PI was increased in pregnancies with pre-eclampsia compared with controls (mean +/- SD, 1.45 +/- 0.31 MoM vs. 1.02 +/- 0.25 MoM, P < 0.001), as were the level of inhibin A (mean +/- SD, 1.57 +/- 0.34 MoM vs. 1.08 +/- 0.43 MoM, P < 0.001) and the level of activin A (mean +/- SD, 1.68 +/- 0.38 MoM vs. 1.06 +/- 0.42 MoM, P < 0.001). The level of PlGF was decreased in pre-eclampsia compared with controls (mean +/- SD, 0.69 +/- 0.23 MoM vs. 1.00 +/- 0.26 MoM, P < 0.001). Receiver-operating characteristics curves were analyzed for controls and cases and areas under the curve (AUC) were 0.796 (95% CI, 0.712-0.880, P < 0.001) for inhibin A, 0.823 (95% CI, 0.746-0.899, P < 0.001) for activin A, 0.831 (95% CI, 0.752-0.910, P < 0.001) for PlGF and 0.851 (95% CI, 0.783-0.920, P < 0.001) for uterine artery PI. The combination of activin A, inhibin A and PI using logistic regression analysis yielded an AUC of 0.907 (95% CI, 0.830-0.938, P < 0.001) with a sensitivity of 87% and a specificity of 80%. The combination of activin A, PlGF and PI gave an AUC of 0.925 (95% CI, 0.852-0.978, P < 0.001) with a sensitivity of 90% and a specificity of 80%. Combining all four markers gave an AUC of 0.941 (95% CI, 0.891-0.990, P < 0.001) with a sensitivity of 93% and a specificity of 80%. CONCLUSION: Early second-trimester serum inhibin A, activin A, PlGF and second-trimester uterine artery Doppler PI may add further information for the prediction of pre-eclampsia. The combination of the three serum markers and uterine artery Doppler PI has the highest prediction value for pre-eclampsia. PMID- 20737453 TI - Outcome prediction in monochorionic diamniotic twin pregnancies with moderately discordant amniotic fluid. AB - OBJECTIVE: The aim of this study was to identify predictors of twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic (MCDA) twin pregnancies with moderate amniotic fluid discordance (mAFD). METHODS: Monochorionic twins with mAFD (n = 45; gestational age, 15-29 weeks) were assessed for extent of fluid discordance, fetal growth discordance and fetal cardiac dysfunction, and were followed longitudinally. A prediction algorithm was constructed for TTTS and sIUGR and validated in an unrelated cohort (n = 52). RESULTS: Cardiac dysfunction could not predict TTTS or sIUGR. Twins below 20 weeks of gestation with a fluid discordance of >= 3.1 cm had a risk of TTTS of 85.7%. Sensitivity for TTTS was nevertheless only 55%. An intertwin weight discordance of >= 25% had 63% sensitivity and 76% specificity for sIUGR without TTTS. CONCLUSION: The outcome of MCDA twins with mAFD remains unpredictable, yet high-risk and low-risk subgroups for TTTS can be identified based on severity of fluid discordance and gestational age. PMID- 20737454 TI - Ultrasound-guided tru-cut biopsy of abdominal and pelvic tumors in gynecology. AB - OBJECTIVE: To analyze the safety, adequacy and accuracy of tru-cut biopsy and to evaluate factors potentially affecting adequacy. METHODS: We analyzed retrospectively a group of patients who had undergone tru-cut biopsy for either primary suboptimally operable tumors, recurrence or suspected non-genital or secondary tumor. Tru-cut biopsy was performed either transvaginally or transabdominally, using an automatic biopsy gun with disposable needle and needle guide attached to the probe. The adequacy, i.e. obtaining a sample sufficient for identification of the origin of the tumor and performance of immunohistochemistry; accuracy, i.e. agreement between biopsy and final postoperative histology; and safety, as determined by complication rate, were assessed. Variables potentially influencing adequacy were analyzed using the orthogonal projections to latent structure method. RESULTS: A total of 195 biopsies were performed on 190 patients. An adequate sample was obtained in 178 (91.3%) biopsies. The final histology was not in agreement with the result from tru-cut biopsy in two out of 118 patients who underwent subsequent surgery (accuracy 98.3%). There were complications in two cases out of the 195 biopsies performed (1.0%). Ascites, elevated CA 125, primary suboptimal operable tumor, serous epithelial ovarian cancer histology, carcinomatosis and vaginal approach were significant positive predictors for the achievement of an adequate sample, while recurrence as an indication, non-serous and non-ovarian histotypes and transabdominal approach were negative predictors. CONCLUSION: Ultrasound-guided tru-cut biopsy is an efficient, minimally invasive, accurate and safe diagnostic method in the management of advanced, recurrent or atypical abdominal and pelvic tumors of probable non-genital origin, where unnecessary laparotomy or laparoscopy can be avoided. The adequacy of tru-cut biopsy is mainly influenced by indication group, histology, site of biopsy and approach. Our analysis can help in counseling the patient before the procedure and helps to explain the possible causes of failure of the procedure. PMID- 20737455 TI - Early fetal growth, PAPP-A and free beta-hCG in relation to risk of delivering a small-for-gestational age infant. AB - OBJECTIVES: To examine early fetal growth, pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) in relation to the risk of delivering a small-for-gestational age (SGA) infant. METHODS: Included in the study were 9450 singleton pregnant women who attended the prenatal screening program at Aarhus University Hospital, Denmark, between January 2005 and December 2007. Maternal serum levels of PAPP-A and free beta-hCG were measured between gestational weeks 8 and 13. Two ultrasound examinations were performed, the first at 11-13 weeks and the second at 18-22 weeks, from which gestational age was estimated based on crown-rump length and biparietal diameter, respectively. Early fetal growth was expressed as an index: the ratio between the estimated number of days from the first to the second scan and the actual calendar time elapsed in days. SGA was defined as birth weight < 5(th) centile for gestational age, and the risk of SGA was evaluated according to different cut-offs of the early fetal growth index and the serum markers. RESULTS: PAPP-A < 0.4 MoM combined with an early fetal growth index < 10(th) centile resulted in an increased risk of SGA (odds ratio (OR), 5.8; 95% CI, 2.7-12.7). Low PAPP-A, low free beta-hCG and slow early fetal growth were statistically, independently associated with SGA, and the association between free beta-hCG < 0.3 MoM and SGA was as strong as that between PAPP-A < 0.3 MoM and SGA (OR, 3.1 and 3.0, respectively). CONCLUSION: The combination of slow early fetal growth and low PAPP-A resulted in a nearly six fold increased risk of delivery of an SGA infant. These findings might improve our chances of early identification of fetuses at increased risk of growth restriction. PMID- 20737456 TI - Prenatal diagnosis of fetal left pulmonary artery sling. AB - Left pulmonary artery (LPA) sling is a very rare anomaly in which the LPA arises distally, far from the right pulmonary artery on the right side of the distal trachea, turns sharply leftwards around the trachea and courses to the left lung hilum through the space between the trachea and esophagus. LPA sling is often associated with distal tracheal narrowing, due to either intrinsic stenosis or secondary compression by the anomaly itself. To our knowledge, prenatal diagnosis of LPA sling has not been reported so far. We report a case in which LPA sling was diagnosed during fetal ultrasound examination. PMID- 20737457 TI - Antenatal embolization of a large chorioangioma by percutaneous Glubran 2 injection. AB - We describe a case of a large chorioangioma diagnosed at 18 weeks' gestation. Because of advanced fetal heart failure at 23 weeks' gestation, embolization of the chorioangioma's vessels was performed by percutaneous injection of Glubran 2 surgical glue. There was no immediate secondary effect of treatment. Devascularization was complete and durable. Signs of fetal cardiac failure normalized after 1 month and a healthy infant was delivered at 38 weeks. To our knowledge this is the first reported case of perinatal survival after successful embolization of a chorioangioma using tissue glue. PMID- 20737458 TI - Fetal cardiac function between 11 and 35 weeks' gestation and nuchal translucency thickness. AB - OBJECTIVES: The pathophysiological background of an increased nuchal translucency (NT) is still poorly understood. Cardiac dysfunction has been proposed as a cause. The aim of this study was to determine if, in fetuses with normal hearts, the NT thickness is related to cardiac function throughout gestation. METHODS: The NT was measured in 191 karyotypically/phenotypically normal fetuses with structurally normal hearts and was increased (>= 95(th) centile) in 104. All fetuses had been referred for fetal echocardiography and were prospectively included between October 1 2003 and April 1 2009. Three-hundred and ten echocardiograms were performed between 11 and 35 weeks' gestation. The E- and A wave velocity, E/A velocity ratio, E/time velocity integral (TVI) ratio over the atrioventricular (AV) valves, myocardial performance index, acceleration time (AT) and peak velocity over the semilunar valves, stroke volume (SV) and cardiac output (CO) as well as the ductus venosus pulsatility index for veins at 11-14 weeks' gestation (DV-PIV), were measured. A multilevel analysis was performed using the NT multiples of the median (MoM) as a continuous variable. RESULTS: AV E- and A-wave velocities, E/A velocity ratios, semilunar valve peak velocity, SV, CO and aortic valve (AoV) AT increased significantly with advancing gestation. At 11-14 weeks' gestation, the AoV-AT, tricuspid valve (TV)-E/A, TV-E/TVI ratios and DV-PIV increased, and the pulmonary valve (PV) AT decreased, with increasing NT MoMs. After midgestation, the PV-AT increased and the AoV-AT, TV-E/A and TV-E/TVI ratios decreased with increasing NT-MoMs. CONCLUSIONS: NT thickness is related to right ventricular diastolic function and semilunar valve AT. Our findings suggest improved first-trimester, but later reduced, right ventricular relaxation and discordant ventricular afterload in fetuses with an increased NT. PMID- 20737461 TI - Reduction of a chelating bis(NHC) palladium(II) complex to [{mu-bis(NHC)}2Pd2H]+: a terminal hydride in a binuclear palladium(I) species formed under catalytically relevant conditions. PMID- 20737463 TI - Predictors of physical and emotional recovery 6 and 12 months after surgery. AB - BACKGROUND: A proportion of patients do not recover fully from surgery or they develop chronic postsurgical pain. The aim of this study was to examine the incidence and predictors of unfavourable long-term outcome after surgery using a prospective cohort design. METHODS: Some 401 patients undergoing various elective surgical procedures filled in the RAND 36-item Health Survey 1.0 health-related quality-of-life questionnaire before operation and at 6 and 12 months of follow up to assess changes in pain, physical functioning, mental health and vitality. Preoperative psychological assessment was obtained. RESULTS: Most patients showed improvement in the various aspects of health-related quality of life after surgery, but a considerable proportion (14-24 per cent) still showed deterioration at 6 and 12 months. Multivariable linear regression analysis identified acute postoperative pain, duration of the operation and preoperative physical condition as the most important predictors of long-term pain and physical functioning. Preoperative surgical fear also had a small but significant contribution. The main predictors of mental health and vitality were physical condition before surgery, surgical fear and optimism. CONCLUSION: Up to a quarter of patients experienced suboptimal recovery after surgery. Both somatic and psychological factors were associated with the long-term outcome. Optimal recovery could be promoted by effective interventions on malleable factors. PMID- 20737464 TI - Iron supply to soybean plants through the foliar application of IDHA/Fe3+: effect of plant nutritional status and adjuvants. AB - BACKGROUND: Synthetic Fe chelates are commonly used to overcome Fe deficiencies in crops, but most of them are scarcely biodegradable. Iminodisuccinic acid (IDHA) is a biodegradable chelating agent that is currently being evaluated as an alternative to EDTA. In this work, the efficacy of the foliar application of IDHA/Fe(3+) to soybean chlorotic plants under controlled conditions was studied, testing the influence of the adjuvant used and of the plant nutritional status. RESULTS: When IDHA/Fe(3+) was applied to soybean plants with severe Fe chlorosis and the foliar sprays were the sole source of Fe, this chelate behaved similarly to the EDTA/Fe(3+) and the recovery of the plants was slight in both cases. The same chelates were tested when foliar sprays were an additional source of Fe for mildly chlorotic plants, which were also being supplied with low concentrations of Fe applied to the nutrient solution. Then, plant recovery was appreciable in all cases, and the IDHA/Fe(3+) was as effective as EDTA/Fe(3+). Among the adjuvants studied, a urea-based product was the only one that did not damage the leaf surface and that could improve the efficiency of IDHA/Fe(3+) up tp the level of EDTA/Fe(3+). CONCLUSIONS: Thus, it was concluded the foliar application of IDHA/Fe(3+) can be an environmentally friendly alternative to the non biodegradable chelate EDTA/Fe(3+) when the appropriate adjuvant is used. PMID- 20737465 TI - Determination of free bilirubin and its binding capacity by HSA using a microfluidic chip-capillary electrophoresis device with a multi-segment circular ferrofluid-driven micromixing injection. AB - A PMMA microfluidic chip-CE device with a multi-segment circular-ferrofluid driven micromixing injector has been developed for the determination of free bilirubin and its binding capacity by HSA at equilibrium. The design of the device and its fabrication by a low cost CO(2) laser are discussed for intended applications. Under optimized conditions, the total binding capacity of HSA for bilirubin was determined as 16.3+/-1.4 mg/l00 mL human serum (n=3) and residual binding capacity for bilirubin 9.8 mg/100 mL (n=3) in normal infants. To assess risk of hyperbilirubinemia, free bilirubin and residual binding capacity by HSA provide a better indicator than total bilirubin, as neonates with impaired bilirubin binding capacity could be detected. In addition, residual binding capacity provides an advanced indicator to predict the onset of hyperbilirubinemia before the appearance of free bilirubin. HSA down to 94 nL is used in each titration and a full assay of four titrations takes up 376 nL HSA, sufficient for newborns with HSA in microliter range. The device has shown capable to provide adequate margin of protection to detect an early rising level of bilirubin and impaired binding capacity prior to the onset of jaundice condition. PMID- 20737466 TI - Analysis of the workforce and workplace for rheumatology and the research activities of rheumatologists early in their careers. AB - OBJECTIVE: To assess the workforce and workplace in rheumatology, and the research work of early-career rheumatologists. METHODS: Early-career rheumatologists were defined as practicing physicians who joined the American College of Rheumatology (ACR) in 1991-2005, were 49 years of age or younger when they joined, and reside in North America. This cohort participated in a Web-based survey distributed by the ACR. A total of 247 surveys (21.2% response) were used for this analysis. Survey questions were designed to obtain core insights about the workforce, workplace, research activities, funding, and the demographic profile of respondents. RESULTS: Respondents from all workplaces-clinical, academic, federal, and industry-engaged in clinical care, teaching, administration, and research. The time devoted to these tasks was employer dependent, and workplaces shaped the scale and scope of research. Patient oriented research was predominant across all workplaces. Disease, population, and translational research were intermediate, and few respondents pursued basic or prevention-oriented research in any type of workplace. Rheumatologists obtained extramural funds (21.3%) and intramural funds (78.7%) to pay portions of their salaries for time spent on research. Receiving a National Institutes of Health K08/K23 award was associated with receipt of a federal research project grant (P < 0.001). Respondents associated investigative work with reduced earnings, a perception validated by an estimated drop in pre-tax annual earnings of 2.3% for each half-day/week dedicated to research (P < 0.01). CONCLUSION: The results of this study justify interventions for closing gaps embedded in investigational rheumatology. These include improved funding for clinical research, increasing the number of K08/K23 awards, and recruiting rheumatologists from underrepresented demographic groups. PMID- 20737467 TI - Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis. AB - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This study was undertaken to investigate the ability of COMP to regulate complement, a capacity that has previously been shown for some other cartilage proteins. METHODS: Regulation of complement by COMP was studied using functional in vitro assays. Inter-actions between complement proteins and COMP were investigated by direct binding assay and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured with a novel enzyme-linked immunosorbent assay. RESULTS: We found in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not patients with OA. COMP induced activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which was attributable to direct interaction between COMP and properdin. Furthermore, COMP inhibited the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively. CONCLUSION: COMP is the first extracellular matrix protein for which an active role in inflammation has been demonstrated in vivo. It can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP fragments, which may be disease specific. PMID- 20737468 TI - Oxidative stress in systemic lupus erythematous: comment on the article by Wang et al. PMID- 20737469 TI - The research-based rheumatologist: strategies to remove the species from the endangered list. PMID- 20737470 TI - Ward's area location, physical activity, and body composition in 8- and 9-year old boys and girls. AB - Bone strength is the result of its material composition and structural design, particularly bone mass distribution. The purpose of this study was to analyze femoral neck bone mass distribution by Ward's area location and its relationship with physical activity (PA) and body composition in children 8 and 9 years of age. The proximal femur shape was defined by geometric morphometric analysis in 88 participants (48 boys and 40 girls). Using dual-energy X-ray absorptiometry (DXA) images, 18 landmarks were digitized to define the proximal femur shape and to identify Ward's area position. Body weight, lean and fat mass, and bone mineral were assessed by DXA, PA by accelerometry, and bone age by the Tanner Whitehouse III method. Warps analysis with Thin-Plate Spline software showed that the first axis explained 63% of proximal femur shape variation in boys and 58% in girls. Most of this variation was associated with differences in Ward's area location, from the central zone to the superior aspect of the femoral neck in both genders. Regression analysis demonstrated that body composition explained 4% to 7% of the proximal femur shape variation in girls. In boys, body composition variables explained a similar amount of variance, but moderate plus vigorous PA (MVPA) also accounted for 6% of proximal femur shape variation. In conclusion, proximal femur shape variation in children ages 8 and 9 was due mainly to differences in Ward's area position determined, in part, by body composition in both genders and by MVPA in boys. These variables were positively associated with a central Ward's area and thus with a more balanced femoral neck bone mass distribution. PMID- 20737471 TI - Pyridoxal-5'-phosphate phosphatase/chronophin induces astroglial apoptosis via actin-depolymerizing factor/cofilin system in the rat brain following status epilepticus. AB - Actin-depolymerizing factor (ADF)/cofilin is a small cytoskeletal protein that is a stimulus-responsive mediator of actin dynamics. ADF/cofilin also translocates into mitochondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/cofilin translocations are negatively regulated by phosphorylation. Recently, it has been reported that pyridoxal-5'-phosphate (PLP) phosphatase/chronophin (PLPP/CIN) regulates phosphorylation of ADF/cofilin levels. Therefore, we investigated whether PLPP/CIN contributes to apoptosis-like events via modulation of ADF/cofilin phosphorylation following status epilepticus (SE). In the present study, apoptosis-like astroglial damages were detected in the dentate gyrus after SE. Upregulation of ADF/cofilin and PLPP/CIN expression in the cytoplasm and nucleus were accompanied by apoptosis-like events. PLPP/CIN level showed a direct proportionality to nuclear translocation of ADF/cofilin. Moreover, nuclear accumulation of apoptosis-inducing factor was simultaneously observed with that of ADF/cofilin. Tat-PLPP/CIN pretreatment accelerated astroglial apoptosis-like degeneration following SE, although Tat-PLPP/CIN transduction alone could not induce apoptosis or necrosis in astrocytes. Therefore, our findings suggest that nuclear accumulation of ADF/cofilin itself may not induce apoptogenic events, but may play a synergic role in apoptosis-like astroglial loss following SE. PMID- 20737472 TI - Manganese-induced downregulation of astroglial glutamine transporter SNAT3 involves ubiquitin-mediated proteolytic system. AB - SNAT3 is a major facilitator of glutamine (Gln) efflux from astrocytes, supplying Gln to neurons for neurotransmitter synthesis. Our previous investigations have shown that, in primary cortical astrocyte cultures, SNAT3 protein is degraded after exposure to manganese (Mn(2+)). The present studies were performed to identify the processes responsible for this effect. One of the well-established mechanisms for protein-level regulation is posttranslational modification via ubiquitination, which leads to the rapid degradation of proteins by the 26S proteasome pathway. Here, we show that astrocytic SNAT3 directly interacts with the ubiquitin ligase, Nedd4-2 (neural precursor cells expressed developmentally downregulated 4-2), and that Mn(2+) increases both Nedd4-2 mRNA and protein levels. Additionally, we have found that Mn(2+) exposure elevates astrocytic ubiquitin B mRNA expression, free ubiquitin protein levels, and total protein ubiquitination. Furthermore, Mn(2+) effectively decreases astrocytic mRNA expression and the phosphorylation of serum and glucocorticoid-inducible kinase, a regulatory protein, which, in the active phosphorylated form, is responsible for the phosphorylation and subsequent inactivation of Nedd4-2. Additional findings establish that Mn(2+) increases astrocytic caspase-like proteolytic proteasome activity and that the Mn(2+)-dependent degradation of SNAT3 protein is blocked by the proteasome inhibitors, N-acetyl-leu-leu-norleucinal and lactacystin. Combined, these results demonstrate that Mn(2+)-induced SNAT3 protein degradation and the dysregulation of Gln homeostasis in primary astrocyte cultures proceeds through the ubiquitin-mediated proteolytic system. PMID- 20737473 TI - Physiologic role for "inducible" nitric oxide synthase: a new form of astrocytic neuronal interface. AB - Nitric oxide (NO) has been long recognized as an atypical neuronal messenger affecting excitatory synaptic transmission, but its cellular source has remained unresolved as the neuronal isoform of NO synthase (nNOS) in many brain regions is expressed only by small subsets of inhibitory neurons. It is generally believed that the glial NO-producing isoform (iNOS) is not expressed in the normal brain, but rather it undergoes a transcription-mediated up-regulation following an immunological challenge. Therefore, the involvement of iNOS in modulating normal neuronal functions has been largely ignored. Here I review evidence to the contrary: I summarize data pointing to the existence of a functioning iNOS in normal undisturbed mammalian brains, and experimental results tracing this expression to astrocytes. Finally, I review recent findings asserting that iNOS dependent NO modulates synaptic release from presynaptic terminals. Based on these data, I propose that astrocytes express basal levels of iNOS. Flanking synaptic elements, astrocytes are perfectly positioned to release NO and affect synaptic transmission. PMID- 20737474 TI - Sperm status and DNA dose play key roles in sperm/ICSI-mediated gene transfer in caprine. AB - In relation to the growing recent interest in the establishment of sperm-mediated gene transfer (SMGT) technology as a convenient and effective method for the simple production of transgenic animals, in this study the possibility of using SMGT to produce transgenic caprine embryos was investigated for the first time. Buck sperm were directly incubated with different concentrations (0-500 ng) of pcDNA/his/Lac-Z plasmid and used for IVF or ICSI. Sperm used for ICSI were categorized into motile or live-immotile group before being injected into oocytes. In a separate experiment, dead sperm prepared by repeated freezing/thawing were used for DNA-incubation before ICSI. Sham injection was carried out by intracytoplasmic injection of approximately the same volume of media containing different doses of DNA using an ICSI needle. Transgene expression and transmission were detected by X-Gal staining and PCR analysis of developed embryos, respectively. A reasonable blastocyst rate was observed in all the groups. Only embryos in the sham group were negative for transgene transmission. Transgene expression was completely dependent on the delivery technique and status of sperm, and was only observed in the live-immotile and dead ICSI groups. The results of this study showed that the technique (IVF vs. ICSI vs. sham injection), sperm status (motile vs. live-immotile vs. dead) and to some extent DNA concentration affect embryo development, transgene transmission and expression. PMID- 20737475 TI - Astrocytes contacting HIV-1-infected macrophages increase the release of CCL2 in response to the HIV-1-dependent enhancement of membrane-associated TNFalpha in macrophages. AB - The presence of human immunodeficiency virus (HIV)-infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome-related neuroinflammation. Once penetrated the blood-brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell-cell interaction between HIV-infected macrophages and astrocytes, we observed that the HIV-1 expression in macrophagic cells correlated with increased chemotactic activity in supernatants of astroglial cells. Gene array analysis revealed an impressive increase in the transcription of the gene for the CCL2/MCP-1 chemokine in astroglial cells isolated from HIV-1-infected co-cultures compared with cells from uninfected co-cultures. This phenomenon coupled with the increase in CCL2 release and depended on the cell-cell contact. In addition, it was a consequence of the HIV-1-induced enhancement of membrane-associated tumor necrosis factor alpha in macrophagic cells, and correlated with increased levels of nuclear factor kappaB activation in astroglial cells. These observations could mirror a mechanism of recruitment of leukocytes through the BBB, likely contributing to the increase in both viral load and inflammation in central nervous system of HIV infected patients. PMID- 20737476 TI - Glucosamine exerts a neuroprotective effect via suppression of inflammation in rat brain ischemia/reperfusion injury. AB - We investigated the neuroprotective effect of glucosamine (GlcN) in a rat middle cerebral artery occlusion model. At the highest dose used, intraperitoneal GlcN reduced infarct volume to 14.3% +/- 7.4% that of untreated controls and afforded a reduction in motor impairment and neurological deficits. Neuroprotective effects were not reproduced by other amine sugars or acetylated-GlcN, and GlcN suppressed postischemic microglial activation. Moreover, GlcN suppressed lipopolysaccharide (LPS)-induced upregulation of proinflammatory mediators both in vivo and in culture systems using microglial or macrophage cells. The anti inflammatory effects of GlcN were mainly attributable to its ability to inhibit nuclear factor kappaB (NF-kappaB) activation. GlcN inhibited LPS-induced nuclear translocation and DNA binding of p65 to both NF-kappaB consensus sequence and NF kappaB binding sequence of inducible nitric oxide synthase promoter. In addition, we found that GlcN strongly repressed p65 transactivation in BV2 cells using Gal4 p65 chimeras system. P65 displayed increased O-GlcNAcylation in response to LPS; this effect was also reversed by GlcN. The LPS-induced increase in p65 O GlcNAcylation was paralleled by an increase in interaction with O-GlcNAc transferase, which was reversed by GlcN. Finally, our results suggest that GlcN or its derivatives may serve as novel neuroprotective or anti-inflammatory agents. PMID- 20737478 TI - Astrocyte-derived glutathione attenuates hemin-induced apoptosis in cerebral microvascular cells. AB - Intracerebral hemorrhage (ICH) induces neurovascular injury via poorly defined mechanisms. The aim of this study was to determine whether gliovascular communication may restrict hemorrhagic vascular injury. Hemin, a hemoglobin by product, concentration- and time-dependently increased apoptotic cell death in mouse bEnd.3 cells and in primary human brain microvascular endothelial cells, at least in part, via a caspase-3 dependent pathway. Cell death was preceded by a NFkappaB-mediated increase in inflammatory gene expression, including upregulation of inducible nitric oxide synthase (iNOS) expression and activity. Functionally, inhibition of iNOS or the addition of a peroxynitrite decomposition catalyst reduced cell death. Interestingly, co-treatment with astrocyte conditioned media (ACM) reversed hemin-induced NFkappaB activation, nitrotyrosine formation, and apoptotic cell death, at least in part, via the release of the endogenous antioxidant, reduced glutathione (GSH). Prior treatment of astrocytes with the GSH-depleting agent, DL-buthionine (S,R)-sulfoximine or direct addition of diethyl maleate, a thiol-depleting agent, to ACM reversed the observed protection. In contrast, neither exogenous GSH nor the GSH precursor, N acetylcysteine, was protective in bEnd.3 cells. Together, these data support an important role for astrocyte-derived GSH in the maintenance of oxidative balance in the vasculature and suggest therapeutic targeting of the GSH system may reduce neurological injury following ICH. PMID- 20737479 TI - Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis. AB - Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25 positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, alpha synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS. PMID- 20737480 TI - Small deletions but not methylation underlie CDKN2A/p16 loss of expression in conventional osteosarcoma. AB - Conventional osteosarcoma is characterized by rapid growth, high local aggressiveness, and metastasizing potential. Patients developing lung metastases experience poor prognosis despite extensive chemotherapy regimens and surgical interventions. Previously we identified a subgroup of osteosarcoma patients with loss of CDKN2A/p16 protein expression in the primary tumor biopsies which was significantly predictive of a very poor prognosis. Here we aimed to identify the underlying mechanism(s) of this protein loss in relation to osteosarcoma behavior. The CDKN2A locus was analyzed in osteosarcoma cases with total loss of CDKN2A/p16 expression and in cases with high protein expression using melting curve analysis-methylation assay (MCA-Meth), fluorescent in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and mutation analysis. All cases with complete CDKN2A/p16 protein loss showed homozygous deletions at the CDKN2A locus. In none of the cases hyper methylation of the promoter region was seen which was confirmed by sequencing this region. Taken together we show that large or smaller deletions of the CDKN2A locus are evident in patient samples and underlie the CDKN2A/p16 protein expression loss while promoter methylation does not appear to be a mechanism of this expression loss. Genomic loss of CDKN2A instead of promoter methylation might be a plausible explanation for the rapid proliferation and high aggressiveness of osteosarcoma by simultaneous impairment CDKN2A/p14(ARF) function. PMID- 20737477 TI - Spinal injection of TNF-alpha-activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein-1. AB - Accumulating evidence suggests that spinal astrocytes play an important role in the genesis of persistent pain, by increasing the activity of spinal cord nociceptive neurons, i.e., central sensitization. However, direct evidence of whether activation of astrocytes is sufficient to induce chronic pain symptoms is lacking. We investigated whether and how spinal injection of activated astrocytes could produce mechanical allodynia, a cardinal feature of chronic pain, in naive mice. Spinal (intrathecal) injection of astrocytes, which were prepared from cerebral cortexes of neonatal mice and briefly stimulated by tumor necrosis factor-alpha (TNF-alpha), induced a substantial decrease in paw withdrawal thresholds, indicating the development of mechanical allodynia. This allodynia was prevented when the astrocyte cultures were pretreated with a peptide inhibitor of c-Jun N-terminal kinase (JNK), D-JNKI-1. Of note a short exposure of astrocytes to TNF-alpha for 15 min dramatically increased the expression and release of the chemokine monocyte chemoattractant protein-1 (MCP-1), even 3 h after TNF-alpha withdrawal, in a JNK-dependent manner. In parallel, intrathecal administration of TNF-alpha induced MCP-1 expression in spinal cord astrocytes. In particular, mechanical allodynia induced by TNF-alpha-activated astrocytes was reversed by a MCP-1 neutralizing antibody. Finally, pretreatment of astrocytes with MCP-1 siRNA attenuated astrocytes-induced mechanical allodynia. Taken together, our results suggest that activated astrocytes are sufficient to produce persistent pain symptom in naive mice by releasing MCP-1. PMID- 20737481 TI - CKS1B amplification is a frequent event in cutaneous squamous cell carcinoma with aggressive clinical behaviour. AB - Genetic mechanisms giving rise to the development of cutaneous squamous cell carcinoma (cSCC) are poorly understood and development of genomic high resolution techniques has led to a better knowledge of the genetic basis of several human cancers. In this study, 16 cSCC were analyzed using array comparative genomic hybridization (arrayCGH). The most common aberrations found were gains of 3q11q13, 1q21.3q25, 13q34, and 19p13, and losses of 1p36p31, 3p24p21, 10p15q22, and 13q11q21. We detected gains (3/16) and amplification (1/16) of the 1q21.1q21.3 region. A potential candidate gene in this region, CKS1B (1q21.2), was selected for validation in an independent cohort and correlations with clinicopathological features were carried out. CKS1B gene and protein status were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a series of 53 cSCC, 22 actinic keratoses (AK), and 10 normal skin samples. cSCC presented a higher frequency of chromosome 1 polysomy than AK (70% vs. 46%, P = 0.047). Association between CKS1B protein overexpression and both polysomy and amplification was demonstrated in cSCC (P < 0.001). Regarding amplifications, 11 cSCC patients (21%) presented CKS1B gene amplification. Interestingly, 8/11 (73%) patients who showed a CKS1B amplification had presented metastatic spread (mcSCC). Differences between the presence of CKS1B amplification and the presence or absence of mcSCC were observed (mcSCC [8/14] vs. cSCC [3/39]) (P < 0.001). Several drugs targeting CKS1B have been reported and may be useful for treating patients with cSCC and CKS1B amplifications. PMID- 20737482 TI - Identification of novel carcinogen-mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique. AB - We here report the genetic basis for susceptibility and resistance to carcinogen mediated [7,12-dimethylbenz[a]anthracene (DMBA)] mammary tumorigenesis using the full panel of SS/BN consomic rat strains, in which substitutions of individual chromosomes from the resistant BN strain onto the genomic background of the susceptible SS strain were made. Analysis of 252 consomic females identified rat mammary Quantitative Trait Loci (QTLs) affecting tumor incidence on chromosomes 3 and 5, latency on chromosomes 3, 9, 14, and 19, and multiplicity on chromosomes 13, 16, and 19. In addition, we unexpectedly identified a novel QTL on chromosome 6 controlling a lethal toxic phenotype in response to DMBA. Upon further investigation with chromosomes 6 and 13 congenic lines, in which an additional 114 rats were investigated, we mapped (1) a novel mammary tumor QTL to a region of 27.1 Mbp in the distal part of RNO6, a region that is entirely separated from the toxicity phenotype, and (2) a novel and powerful mammary tumor susceptibility locus of 4.5 Mbp that mapped to the proximal q-arm of RNO13. Comparison of genetic strain differences using existing rat genome databases enabled us to further construct priority lists containing single breast cancer candidate genes within the defined QTLs, serving as potential functional variants for future testing. PMID- 20737483 TI - CT cross-sectional imaging classification system for substernal goiter based on risk factors for an extracervical surgical approach. AB - BACKGROUND: The purpose of this study was to identify risk factors for surgical extracervical approach in patients with substernal goiter. We used a novel classification system based on CT scan cross-sectional imaging (CSI) reconstruction. METHODS: Medical records of 4297 patients with thyroid disease operated on at our department were reviewed. A CSI classification system defined substernal goiter in the cranio-caudal dimension as: grade 1 (above aortic arch), grade 2 (level of aortic arch), and grade 3 (below aortic arch); in the anteroposterior dimension as type A (prevascular), type B (retrovascular paratracheal), and type C (retrotracheal); in the latero-lateral dimension as: monolateral or bilateral. RESULTS: The prevalence of substernal goiter was 222 of 4297 cases (5.1%). Fifteen of 222 cases (6.7%) required an extracervical approach due to grade >=2 and/or type C substernal goiter (14 of 15 cases). Ten of 15 patients had malignancy. CONCLUSION: The CT-CSI classification system allows us to identify risk factors for extracervical surgical approach in substernal goiter. They are grade >=2, type C substernal goiter, and malignancy. PMID- 20737484 TI - Feasibility of submandibular gland preservation in neck dissection: A prospective anatomic-pathologic study. AB - BACKGROUND: The submandibular gland is commonly removed during neck dissection involving sublevel IB. However, removal reduces basal salivary secretion and therapeutic options for minimizing xerostomia. The purpose of this study was to determine whether all lymph nodes in sublevel IB can be extirpated without removing the submandibular gland. METHODS: Twenty consecutive patients undergoing 33 neck dissections were prospectively enrolled. Sublevel IB dissection was performed by 3 sequential steps: (1) removal of targeted lymph node groups (preglandular and postglandular, prevascular and postvascular), (2) removal of submandibular gland, and (3) removal of residual lymphoadipose tissue in the surgical bed. RESULTS: Complete removal of lymph nodes in sublevel IB was achieved before excising the submandibular gland in all of the 30 eligible neck dissections. The submandibular gland and the surgical bed contained no residual lymph nodes. CONCLUSION: In suitable cases, it is technically feasible to remove all lymph nodes in sublevel IB and preserve the submandibular gland. PMID- 20737485 TI - Retropharyngeal lymph node metastases in head and neck malignancies. AB - Retropharyngeal lymph node (RPLN) metastasis of primary head and neck cancer often receives less consideration than lymph node metastasis in the neck. With improvements in imaging techniques and reports of surgical pathology, there is an improved understanding of the risk and subsequently the need for treatment of RPLNs. The rates of RPLN metastasis from carcinomas of the nasopharynx, oropharynx, hypopharynx, postcricoid region, maxillary sinus, and cervical esophagus are sufficiently high to warrant routine treatment, either electively or therapeutically, of this region. Through improved diagnostic techniques and heightened awareness of RPLN metastasis, patients at risk of having these metastases can be treated more effectively. PMID- 20737486 TI - Evaluation of drug transporters' significance for multidrug resistance in head and neck squamous cell carcinoma. AB - BACKGROUND: Multidrug resistance (MDR) hampers chemotherapy in head and neck squamous cell carcinoma (HNSCC). There is little information about MDR mediating drug transporters in HNSCC. METHODS: Nine HNSCC cell lines were characterized concerning drug transporter expression and susceptibility to cisplatin, paclitaxel, and 5-fluorouracil (5-FU) using a DNA microarray and proliferation assays. Three cells lines were precisely investigated for transporter expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and drug resistance before and after simulated chemotherapies. RESULTS: The cell lines differed in drug resistance and transporter expression. Cisplatin and paclitaxel resistances were inversely associated. Drugs rendered HNSCC cells resistant, cross-resistant, or cross-sensitive. Sensitivity changes were accompanied by transporter mRNA expression changes. CONCLUSION: Paclitaxel was identified as a potent inducer of numerous drug transporters and phenotypic MDR in HNSCC. Thus, cytostatic susceptibility of HNSCC cannot exclusively be deduced from the expression of single transporters but more likely of the entire transportome and non-transporter modulators. PMID- 20737487 TI - Sclerotherapy of lymphangiomas of the head and neck. AB - Lymphangiomas are congenital malformations of the lymphatic system that consist of cysts of varying size. Although they are benign, they can undergo progressive growth with compression and infiltration of adjacent structures. Surgical excision has been the cornerstone of treatment, although total excision of the lymphangioma can be a major challenge and may be associated with severe complications. Therefore, a variety of nonsurgical methods have been proposed to reduce the surgical morbidity and to decrease the recurrence rate. Percutaneous sclerotherapy of lymphangioma involves the injection of sclerosing substances into the lymphangioma cysts. During the past years, different sclerosants and sclerosant techniques have been developed. This review summarizes the current knowledge on sclerotherapy of lymphangiomas of the head and neck. PMID- 20737489 TI - Survival analysis of head and neck squamous cell carcinoma: influence of smoking and drinking. AB - BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are associated with tobacco and alcohol; however, the prognostic relevance of these substances is unclear. METHODS: Univariate and multivariate survival analyses were performed for patients with (n = 1829) and without (n = 183) substance use. RESULTS: HNSCC specific survival (death due to primary-HNSCC or recurrent HNSCC) and HNSCC/second primary tumor-specific survival (death due to primary-HNSCC or recurrent HNSCC or second primary tumor) were not significantly different for patients who smoked and drank alcohol (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.86-1.85) and those who did not (HR, 1.34; 95% CI, 0.96-1.88). Overall survival was significantly affected; HR for patients who smoked and drank alcohol was 1.50 (95% CI, 1.16-1.93). CONCLUSION: Although tobacco and alcohol use are the main risk factors for development of HNSCC, disease outcome was comparable in patients who did or did not use these substances. Tobacco and alcohol use affected overall survival, which emphasizes the importance of substance use cessation. PMID- 20737490 TI - Prevalence and impact on clinicopathological characteristics of human papillomavirus-16 DNA in cervical lymph node metastases of head and neck squamous cell carcinoma. AB - BACKGROUND: Human papillomavirus (HPV) is a basic risk factor for head and neck squamous cell carcinoma (HNSCC). Little knowledge exists about the impact of HPV on clinical diagnostic and therapy of patients with HNSCC. METHODS: We evaluated the evidence of HPV16 in 131 retrospectively collected HNSCC and associated cervical lymph node metastases by HPV16 real-time polymerase chain reaction (PCR) and p16 immunohistochemistry and its impact on clinicopathological characteristics. RESULTS: HPV16-DNA and p16 overexpression were present in 27% of HNSCCs. All cervical lymph node metastases of HPV16-positive HNSCC showed HPV16 DNA. HPV16 was strongly associated with tumors arising from the oropharyngeal site (p < .000001), favorable outcome after standard therapy in univariate (p = .001) and multivariate (p = .0004) analysis, and cervical lymph node metastases before primary detection. CONCLUSION: HPV16-diagnostic in cervical lymph node metastases can predict the site of tumor origin in case of carcinoma of unknown primary (CUP) and favorable outcome and should, therefore, be included in routine diagnostic workup. PMID- 20737488 TI - Differences in history of sexual behavior between patients with oropharyngeal squamous cell carcinoma and patients with squamous cell carcinoma at other head and neck sites. AB - BACKGROUND: An emerging epidemic of human papillomavirus (HPV)-associated oropharyngeal cancer has been proposed. The purpose of this study was for us to compare the sexual behaviors of patients with squamous cell carcinoma of the oropharynx (SCCOP) and patients with squamous cell carcinoma of non-oropharyngeal (SCCNOP) head and neck sites to expand our understanding of sexual behavior as a risk factor for HPV-associated head and neck cancer. METHODS: The sexual history of 165 patients with SCCOP and 87 patients with SCCNOP was determined in a hospital-based case-to-case comparison study. RESULTS: Patients with SCCOP were significantly more likely than patients with SCCNOP to have had >9 lifetime sex partners (odds ratio [OR], 39.2; 95% confidence interval [CI], 8.2-187.3), to have engaged in oral-genital sex (OR, 3.5; 95% CI, 1.1-11.1), and to have had >4 oral-genital sex partners (OR, 8.6; 95% CI, 2.2-33.4). CONCLUSION: The findings of this study suggest that some risk factors are site-specific and provide further evidence that certain sexual behaviors increase the risk of HPV associated SCCOP. PMID- 20737491 TI - Changes in nutritional status and dietary intake during and after head and neck cancer treatment. AB - BACKGROUND: The purpose of this study was to test whether nutritional status of patients with head and neck cancer changes during and after treatment. METHODS: Nutritional status (including body weight, lean mass, and fat mass) and dietary intake were assessed in 29 patients with head and neck cancer. Patients were assessed 1 week before, and 1 and 4 months after treatment (radiotherapy, either alone or combined with chemotherapy or surgery). RESULTS: During treatment, body weight (-3.6 +/- 5.3 kg; p = .019) and lean mass (-2.43 +/- 2.81 kg; p = .001) significantly declined. Patients with sufficient intake (>=35 kcal and >=1.5 grams protein/kg body weight) lost less body weight and lean mass than patients with insufficient intake (mean difference, -4.0 +/- 1.9 kg; p = 0.048 and -2.1 +/ 1.0 kg; p = .054, respectively). After treatment, only patients with sufficient intake gained body weight (2.3 +/- 2.3 kg) and lean mass (1.2 +/- 1.3 kg). CONCLUSION: Patients with head and neck cancer fail to maintain or improve nutritional status during treatment, despite sufficient intake. PMID- 20737493 TI - Tumor growth inhibition of metastatic nasopharyngeal carcinoma cell lines by low dose of arsenic trioxide via alteration of cell cycle progression and induction of apoptosis. AB - BACKGROUND: Although arsenic trioxide (ATO) has displayed anticancer activity against primary nasopharyngeal carcinoma (NPC), its efficacy in metastatic NPC deserved further investigation because the biological/therapeutic difference in cancer cells probably exists between primary and distant sites. METHODS: Two human metastatic NPC cell lines (NPC-BM1 and NPC-BM2) were investigated. We measured cellular proliferation, cell cycle, and apoptotic extent of BM1 and BM2 cells treated with ATO in vitro. Furthermore, we evaluated the tumor growth after ATO treatment in vivo. RESULTS: Low-dose ATO treatment is sufficient to induce an antiproliferative effect, alter the cell cycle, and increase apoptosis in BM1 and BM2 cells. BM1 tumor growth in a xenograft model with low-dose and short-schedule (1 mg/kg/day, intraperitoneal injection for 5 consecutive days) of ATO treatment significantly slowed in vivo. CONCLUSION: ATO at low dose seems to be an encouraging schedule for palliative treatment of metastatic NPC. PMID- 20737492 TI - Polyethylenimine-mediated PUMA gene delivery to orthotopic oral cancer: suppression of tumor growth through apoptosis induction in situ and prolonged survival. AB - BACKGROUND: PUMA (a p53 up-regulated modulator of apoptosis) is induced by p53 tumor suppressor and other apoptotic stimuli. It was found to be a principal mediator of cell death in response to diverse apoptotic signals, implicating PUMA as a likely tumor suppressor. METHODS: In this study, we examined the efficacy of targeted PUMA gene therapy in human oral cancer (SAS) cells using polyethylenimine (PEI)-mediated transfection for gene delivery. RESULTS: Exogenous expression of PUMA in SAS cells resulted in apoptosis with cytochrome c release, activation of caspase-3 and -9, and cleavage of PARP. Gene delivery of PEI/PUMA in SAS xenografts induced apoptosis and resulted in significant reductions (~60%) of tumor growth in vivo. Furthermore, we have shown that PEI mediated PUMA gene therapy prolonged survival of animals with orthotopic SAS oral cancers. CONCLUSIONS: Taken together, these results indicated that PUMA gene therapy via PEI delivery could be a promising method for the treatment of oral squamous cell carcinoma. PMID- 20737494 TI - Osteolipoma of the parapharyngeal space mimicking liposarcoma: a case report. AB - BACKGROUND: Lipomas are the most common benign neoplasm of the head and neck. However, osteolipomas, a rare variant of lipoma, are uncommon in this location. When they occur, variations in location and radiographic presentation may obscure the diagnosis. METHODS AND RESULTS: A 68-year-old man presented with left jaw pain and numbness in the maxillary (V-1) distribution. A CT angiography of the neck revealed a possible liposarcoma. Embolization of the mass was determined to be unfeasible. Consequently, surgical resection was performed revealing a benign osteolipoma. CONCLUSION: We report a rare case of osteolipoma of the parapharyngeal space. Clinicians should be aware that the clinical and radiological features of patients with head and neck osteolipomas may mimic malignant neoplasms. When given deserved consideration, inappropriate treatment of an otherwise benign lesion may be avoided. PMID- 20737495 TI - Dexamethasone prophylaxis before thyroidectomy to reduce postoperative nausea, pain, and vocal dysfunction: a randomized clinical controlled trial. AB - BACKGROUND: The objective of this 2-arm, double-blind, randomized, controlled study was to assess the effects of a preoperative single dose steroid on postoperative nausea and vomiting (PONV), pain, and vocal function after thyroidectomy for benign disease. METHODS: We randomized 102 patients into 2 groups from January to December 2009: (1) treatment with 8 mg/2 mL of dexamethasone and (2) treatment with 2 mL NaCl 0.9%, both administered intravenously before anesthesia. RESULTS: The severity of nausea and the need for antiemetic drugs were reduced in patients receiving dexamethasone (p = .0001). Dexamethasone patients reported significantly less pain (p = .008); the need for analgesic drugs was lower in the dexamethasone group (p = .048). No differences were noted with regard to subjective voice analysis (p = .693). CONCLUSION: Dexamethasone (8 mg IV) is a safe and effective method to reduce PONV and pain after thyroid resection and should be used routinely. PMID- 20737496 TI - Relation of mucous membrane alterations to oral intake during the first year after treatment for head and neck cancer. AB - BACKGROUND: Acute oral mucositis is associated with pain and impaired swallowing. Little information is available on the effects of chronic mucositis on swallowing. METHODS: Sixty patients treated for cancer of the head and neck were examined during the first year after their cancer treatment. Oral mucosa was rated with the Oral Mucositis Assessment Scale. Stimulated whole-mouth saliva, oral pain rating, percent of oral intake, and 2 subscales of the Performance Status Scale for Head and Neck (PSS-HN) cancer were also collected. RESULTS: Mucositis scores and pain ratings decreased over time while functional measures of eating improved over time. Reduction in chronic mucositis was correlated with improved oral intake and diet. CONCLUSION: Lack of association with pain was attributed to the absence of ulcerations. Continued impairment of oral intake during the first year posttreatment may be related to oral mucosal changes and other factors. PMID- 20737497 TI - Neck dissections in the United States from 2000 to 2006: volume, indications, and regionalization. AB - BACKGROUND: The purpose of this study was to examine trends in neck dissection and regionalization. METHODS: This cross-sectional and longitudinal study used the years 2000, 2004, and 2006 data from the Nationwide Inpatient Sample. Chi square tests compared trends for total neck dissections and specific subsites. To test regionalization, we examined the distribution of procedures across hospital and procedure volume quartiles. RESULTS: From 2000 to 2006, the number of neck dissections increased from 18,112 to 22,918. Three-fourths of the total increase was associated with thyroid and parathyroid gland or skin neoplasms. There was an increase in neck dissections for upper aerodigestive tract (UADT) subsites and no decline for the oropharynx and tongue base. Regionalization occurred as high volume hospitals and providers performed a greater proportion of neck dissections over time. CONCLUSION: Neck dissections increased from the year 2000 to 2006. There were no decreases in neck dissections for certain subsites with a greater role for primary chemoradiotherapy. Regionalization has occurred. PMID- 20737498 TI - Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases. AB - BACKGROUND: In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland has not been studied extensively. We analyzed the clinicopathological features and the clinical course of all patients with parotid gland MALT lymphoma diagnosed and treated at our institution. METHODS: Patient characteristics including an underlying autoimmune disease, disease stage, genetic aberrations, treatment, and clinical course were assessed and evaluated. Twenty-eight patients (19 women, 9 men) were identified; median age at diagnosis was 49 years (interquartile range [IQR], 40-56), and 18 patients (64%) had an underlying autoimmune disease. Eleven had stage IE, 7 patients had stage IIE, and 10 had advanced disease (stage IV). RESULTS: Genetic aberrations were detected in 9 of 20 patients; 5 patients had trisomy 3, 2 patients had a t(11;18)(q21;21) translocation, 1 had trisomy 3 and 18, and 1 patient had a t(14;18)(q32;q21) translocation plus trisomy 18. After a median follow-up time of 62 months (IQR, 32-98 months), 24 patients (86%) are alive. Fifteen patients are free from lymphoma, whereas 13 patients (46%) have had a relapse. CONCLUSION: Our data suggest that MALT lymphoma of the parotid gland is often associated with autoimmune diseases and that trisomy 3 is the most common genetic feature of this disease. The high rate of relapse warrants further study on optimal therapy of such patients. PMID- 20737499 TI - Classification of papillary thyroid microcarcinoma according to size and fine needle aspiration cytology: Behavior and therapeutic implications. AB - BACKGROUND: The purpose of this study was to assess and classify cases of papillary microcarcinoma according to size (up to 0.5 cm and between 0.6 and 1.0 cm) and fine-needle aspiration cytology (FNAC). These results were then correlated with clinical and histopathologic factors of worse prognosis. METHODS: A total of 448 cases of papillary thyroid carcinoma were studied retrospectively. RESULTS: Of the 448 patients, 173 presented with carcinomas of <=0.5 cm and 275 patients presented with carcinomas sized between 0.6 and 1.0 cm (>0.5 cm). Lymph node metastasis was diagnosed in 6% of the carcinoma cases of <=0.5 cm and in 16% of the cases with tumors of >0.5 cm. A total of 281 cases tested positive for papillary carcinoma by FNAC, and in 113 cases, the carcinoma was diagnosed during the histopathologic examination. A positive FNAC for carcinoma was correlated with a higher incidence of lymph node metastasis (16% vs 5%). CONCLUSION: The diagnosis of papillary carcinoma using the preoperative biopsy enables a more precise oncological procedure with greater chance of biological cure. PMID- 20737500 TI - Contemporary management of sinonasal cancer. AB - BACKGROUND: Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinologists, and skull base surgeons. Recent innovations in surgical and nonsurgical therapeutic modalities raise the question of whether there has been any measurable improvement for treatment outcomes. METHODS: A retrospective review of data from recent studies that focus on surgery, radiation, and chemotherapy, or combinations thereof, was conducted. RESULTS: Surgery continues to be the preferred treatment and provides the best results, albeit with an inherent bias based on patient selection. For advanced disease (T4 lesions), the survival rate remains only modest. Complications of treatment, including both surgical and radiation therapy, have been reduced. CONCLUSIONS: There is a need to improve the efficacy of treatment for this disease. Recommendations for the future direction of therapeutic investigations are outlined. PMID- 20737501 TI - Long-term survival of a patient with leptomeningeal involvement by nasopharyngeal carcinoma after treatment with high-dose intravenous methotrexate. AB - BACKGROUND: Nasopharyngeal carcinoma with leptomeningeal involvement is rare and typically has poor prognosis. METHODS AND RESULTS: We present a case report of a patient with nasopharyngeal carcinoma who was treated with high-dose intravenous methotrexate and remains asymptomatic and without clinical evidence of disease 6 years later. CONCLUSIONS: Systemic high-dose methotrexate should be evaluated in the treatment of advanced nasopharyngeal carcinoma with central nervous involvement. PMID- 20737502 TI - Aspiration after supracricoid partial laryngectomy: Incidence, risk factors, management, and outcomes. AB - BACKGROUND: The aim of this study was to evaluate the incidence, risk factors, management, and outcome of postoperative aspiration in patients managed with a supracricoid partial laryngectomy (SCPL) for selected invasive squamous carcinoma of the larynx. METHODS: In all, 457 patients underwent SCPL at an academic, tertiary referral care center, 1975-2000. The incidence of aspiration defined in accord with Pearson's scale was recorded. Univariate and multivariate analyses were performed for potential statistical relation with various variables. The management and outcome of aspiration are presented. RESULTS: Normal swallowing without aspiration was noted in 259 patients (58.9%). Grades 1, 2, and 3 aspiration occurred in 87, 48, and 53 patients (19%, 10.5%, and 11.6%), respectively. A significant relationship was noted between aspiration and increased age, performing cricohyoidopexy, not repositioning the pyriform sinuses, and resecting an arytenoid cartilage. A prediction model, based on multinomial logistic regression, found that the probability that severe aspiration cases (grade 2-3) exceeded the subclinical ones (grade 0-1) occurred only when a cricohyoidopexy with partial or total arytenoid resection was performed in patients >70 years of age (p = .0000001). Management of aspiration required a temporary gastrostomy, a permanent gastrostomy, and a completion total laryngectomy in 65, 3, and 7 of 188 patients (34.5%, 1.6%, and 3.7%, respectively) who aspirated, and 65, 3, and 7 of 457 of the entire population (14.2%, 0.6%, and 1.5%, respectively). Aspiration-related death was not encountered in the current series. CONCLUSIONS: Aspiration after SCPL is a common but rarely severe event, with a low incidence for permanent gastrostomy or completion laryngectomy. Aspiration can be minimized with careful patient selection and precise surgical technique. PMID- 20737503 TI - The ziwi promoter drives germline-specific gene expression in zebrafish. AB - We describe here the characterization of the promoter activity of a 4.8-kb sequence isolated from the 5' end of the zebrafish germ cell-specific ziwi gene. We show that this fragment is sufficient to drive heterologous gene expression specifically in germ cell starting as early as 7 days post-fertilization, a time point when only mitotic germ cells are present in the gonad. In adult animals, we find that this fragment is sufficient to drive gene expression in all germ cells with stage-specific differences in expression levels. In females, EGFP expression is highest in stage IB oocytes, but appreciable expression is detected in both pre-meiotic germ cells, as well stage II-IV oocytes and mature eggs. In males, EGFP expression is highest in spermatogonial stem cells, but low levels are detected in all stages, including spermatozoa. PMID- 20737504 TI - Conservation, expression, and knockdown of zebrafish plxnb2a and plxnb2b. AB - In mice lacking Plexin B2, a receptor of the axon guidance molecules Semaphorin 4C and Semaphorin 4D, the closure of the neural tube and structural organization of the cerebellum are severely impaired. We cloned two Plexin B2 orthologs, plxnb2a and plxnb2b, in zebrafish, which is a widely used model for the development of the vertebrate central nervous system (CNS). The predicted proteins, Plexin B2a and Plexin B2b, contain all the conserved and functional domains of the plexin B-subfamily. During embryonic development, plxnb2a is expressed, e.g., in pharyngeal arches while plxnb2b expression is more confined to neuronal structures like the cerebellum. However, both plxnb2a and plxnb2b are expressed at the midbrain-hindbrain boundary, in the otic vesicles, facial ganglia, and pectoral fins. Knockdown of both plxnb2a and plxnb2b simultaneously (>95% and 45%, respectively) resulted in normal CNS structure, axon guidance and swimming performance of the morphants. PMID- 20737506 TI - Autotaxin controls caudal diencephalon-mesencephalon development in the chick. AB - The diencephalon is the embryonic anlagen of the higher integration centers of the brain. Recent studies have elucidated how the cells in the rostral diencephalon acquire their regional identities. However, the understanding of the mechanisms under which the caudal diencephalon is formed is still limited. Here we focus on the role of Autotaxin (ATX), a lysophospholipid-generating exoenzyme, whose mRNA is detected in the caudal diencephalon. RNA interference against ATX altered the expression pattern of Pax6-regualted genes, Tcf4, Lim1, and En1, implying that ATX is required for the maintenance of the regional identity of the caudal diencephalon and the diencephalon-mesencephalon boundary (DMB). Furthermore, ATX-RNAi inhibited neuroepithelial cell proliferation on both sides of the DMB. We propose a dual role of ATX in chick brain development, in which ATX not only contributes to the formation of caudal diencephalon as a short-range signal, but also regulates the growth of mesencephalon as a long-range signal. PMID- 20737507 TI - Protein tyrosine kinase 2 beta (PTK2B), but not focal adhesion kinase (FAK), is expressed in a sexually dimorphic pattern in developing mouse gonads. AB - Sexual reproduction is essential for the propagation and the maintenance of fitness of our species, and is dependent on the correct development of the bipotential genital ridges into testes and ovaries. Although several transcription factors, secreted signaling molecules, and their receptors have been found to be important for testis determination and early gonad development, comparatively little research has been carried out into intracellular signal transduction pathways activated during these processes. Focal adhesion kinase (FAK) and protein tyrosine kinase 2 beta (PTK2B) form one group of cytosolic tyrosine kinases that are known to be important for processes such as cell proliferation, differentiation, and motility. Here, we describe the temporal and spatial expression patterns of Fak and Ptk2b mRNA and protein during sex determination and early gonadogenesis in mouse embryos. Ptk2b mRNA and PTK2B protein were expressed in testes from 11.5 days post coitum onward, predominantly in developing Sertoli cells, in a SOX9-dependent manner. Fak mRNA and FAK protein were expressed in gonads of both sexes at all stages examined. Our data suggest cell type- and stage-specific roles for PTK2B during early testis development. PMID- 20737505 TI - Organogenesis and tumorigenesis: insight from the JAK/STAT pathway in the Drosophila eye. AB - The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is one of the main signaling pathways in eukaryotic cells. This pathway is used during diverse growth and developmental processes in multiple tissues to control cell proliferation, differentiation, survival, and apoptosis. In addition to its role during development, the JAK/STAT pathway has also been implicated in tumorigenesis. Drosophila melanogaster is a powerful genetic tool, and its eyes have been used extensively as a platform to study signaling pathways. Many reports have demonstrated that the JAK/STAT pathway plays pleiotropic roles in Drosophila eye development. Its functions and activation are decided by its interplay with other signal pathways and the epigenetic status. In this review, we focus on the functions and regulation of the JAK/STAT pathway during eye development and provide some insights into the study of this pathway in tumorigenesis. PMID- 20737508 TI - Developmental expression of sideroflexin family genes in Xenopus embryos. AB - Emerging evidence indicates that mitochondrial carriers are not only crucial for metabolism, but also important for embryonic development. Sideroflexin is a novel family of mitochondrial tricarboxylate carrier proteins, of which the in vivo function is largely unknown. Here, we report on the expression patterns of five sideroflexin genes in Xenopus embryos. Whole-mount in situ hybridization analysis reveals that while sideroflexin2 is expressed in the pancreas, sideroflexin1 and 3 display a complex expression in the central nervous system, somites, pronephros, liver, and pancreas. In contrast, only a weak expression of sideroflexin4 and 5 was detected in embryonic brain. Taken together, the five sideroflexin genes show both overlapping and nonoverlapping expression during Xenopus embryogenesis. As the primary structures of the five sideroflexin proteins are also quite similar, their functional redundancy should be taken into consideration for gene targeting studies. PMID- 20737509 TI - Analysis of a Hand1 hypomorphic allele reveals a critical threshold for embryonic viability. AB - Loss-of-function analysis of the basic helix-loop-helix (bHLH) transcription factor Hand1 indicates critical roles in development. In an effort to generate a Hand1 cDNA knock-in reporter mouse, we generated two hypomorphic alleles, which extend embryonic survival to between embryonic day (E) 10.5 and E12.5. Heart morphogenesis appears largely normal; however, hypomorphic mice display thin left ventricular myocardium and reduction in pharyngeal mesoderm. Caudal defects, large allantois, and thickened yolk sac are observed and consistent with systemic Hand1 gene deletion. Hand1 mRNA is expressed at 30% of wild-type littermates and known Hand1-dependent genes show intermediate expression compared with wild-type and Hand1 null mice. Interestingly, putative bHLH partners, Hand2 and Twist1, show altered expression in both Hand1 null and hypomorphic backgrounds and intercrossing the Hand1 hypomorphic mice onto the Hand2 systemic null background exacerbates the cardiac and lateral mesoderm phenotypes. Together, these data define a critical threshold of Hand1 expression that is necessary for embryonic survival. PMID- 20737510 TI - Anti-JC virus antibodies: implications for PML risk stratification. AB - OBJECTIVE: A study was undertaken to establish an enzyme-linked immunosorbent assay (ELISA) to detect JC virus (JCV)-specific antibodies in multiple sclerosis (MS) patients, and to evaluate its potential utility for identifying patients at higher or lower risk (ie, risk stratification) of developing progressive multifocal leukoencephalopathy (PML). METHODS: A 2-step assay for detecting and confirming the presence of anti-JCV antibodies in human serum and plasma was developed and demonstrated to be both sensitive and specific. ELISA cutpoints were statistically established using sera from >800 MS patients from natalizumab clinical studies. Subsequently, this assay was used to determine the presence of anti-JCV antibodies in natalizumab-treated PML patients where serum samples were collected 16-180 months prior to the diagnosis of PML. RESULTS: In our evaluation of natalizumab-treated MS patients, 53.6% tested positive for anti-JCV antibodies, with a 95% confidence interval of 49.9 to 57.3%. The false-negative rate of the ELISA was calculated to be approximately 2.5%, with an upper 1-sided confidence limit of 4.4%. Notably, we observed anti-JCV antibodies in all 17 available pre-PML sera samples, which was significantly different from the 53.6% seropositivity observed in the overall MS study population (p < 0.0001). INTERPRETATION: This 2-step assay provides a means to classify MS patients as having detectable or not detectable levels of anti-JCV antibodies. The finding that all 17 of the pre-PML samples that were available tested seropositive, and none tested seronegative, warrants further research on the clinical utility of the anti-JCV antibody assay as a potential tool for stratifying MS patients for higher or lower risk of developing PML. PMID- 20737511 TI - A transgenic zebrafish for monitoring in vivo microtubule structures. AB - The microtubule (MT) cytoskeleton plays crucial roles in brain development by regulating the proliferation of neuronal progenitor cells, neuronal migration and axon guidance. Methods for monitoring MT in the intact brain, however, have been limited in vertebrates. Here, we report a transgenic zebrafish line for monitoring MT in vivo. This reporter line carries a transgene encoding the green fluorescent protein (GFP) -tagged tubulin gene linked to the upstream activating sequence (UAS), the recognition sequence of the yeast Gal4 transcriptional activator. By crossing this reporter line with appropriate transgenic Gal4 driver lines, we induced the GFP-tagged tubulin in various cell types from the embryonic stages to the adult stage. In larvae expressing the modified tubulin, individual MT filaments and other MT structures, including the mitotic spindles in proliferating neuronal progenitor cells, were clearly visualized. Therefore, the transgenic UAS reporter line should be useful for directly monitoring MTs in the intact brain. PMID- 20737512 TI - Zebrafish cx30.3: identification and characterization of a gap junction gene highly expressed in the skin. AB - We have identified and characterized a zebrafish connexin, Cx30.3. Sequence similarity analyses suggested that Cx30.3 was orthologous to both mammalian Cx26 and Cx30, known to play important roles in the skin and inner ear of mammals. Analysis of mRNA expression showed that Cx30.3 was present in early embryos, and was highly abundant in skin, but also detected in other tissues including fins, inner ear, heart, and the retina. Injection of Cx30.3 cRNA into Xenopus oocytes elicited robust intercellular coupling with voltage gating sensitivity similar to mammalian Cx26 and Cx30. The similarities in functional properties and expression patterns suggest that Cx30.3, like mammalian Cx26 and Cx30, may play a significant role in skin development, hearing, and balance in zebrafish. Thus, zebrafish could potentially serve as an excellent model to study disorders of the skin and deafness that result from human connexin mutations. PMID- 20737514 TI - Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. AB - OBJECTIVE: Analyses were conducted to determine the clinical utility of measuring JC virus (JCV) DNA in blood or urine of natalizumab-treated multiple sclerosis (MS) patients to predict the risk of progressive multifocal leukoencephalopathy (PML). METHODS: A total of 12,850 blood and urine samples from nearly 1,400 patients participating in natalizumab clinical trials were tested for JCV DNA using a commercially available quantitative polymerase chain reaction (qPCR) assay. A subset of these samples was also tested using a more sensitive qPCR assay developed at the National Institutes of Health (NIH). RESULTS: At the time natalizumab dosing was suspended, JCV DNA was detected in plasma by the commercial assay in 4 of 1,397 (0.3%) patients; the NIH assay confirmed these positive samples and detected JCV DNA in an additional 2 of 205 (1%) patients who tested negative with the commercial assay. None of these 6 JCV DNA positive patients developed PML. In a 48-week study testing the safety of natalizumab redosing, JCV DNA was detected in plasma of 6 of 1,094 (0.3%) patients, none of whom developed PML. Urine at baseline and week 48 was assessed in 224 patients; 58 (26%) were positive at baseline, and 55 (25%) were positive after 48 weeks of natalizumab, treatment. JCV DNA was not detected in peripheral blood mononuclear cells from any of these 1,094 patients before or after natalizumab treatment. In 5 patients who developed PML, JCV DNA was not detected in blood at any time point before symptoms first occurred. INTERPRETATION: Measuring JCV DNA in blood or urine with currently available methods is unlikely to be useful for predicting PML risk in natalizumab-treated MS patients. PMID- 20737515 TI - Antioxidant and pancreas-protective effect of red mold fermented products on streptozotocin-induced diabetic rats. AB - BACKGROUND: Red mold fermented products contain various antioxidants, and were mentioned in an ancient Chinese pharmacopoeia of medicinal food and herbs. They were considered useful for the treatment of diabetes. The objective of this study was to determine the antioxidant and pancreas-protective function of red mold fermented products on streptozotocin (STZ)-induced diabetic rats. RESULTS: Throughout the experimental period (8 weeks), significantly (P < 0.05) lowered plasma glucose, amylase, triglyceride and cholesterol levels were observed in groups treated with red mold fermented products. Diabetic rats showed higher reactive oxygen species (P < 0.05) and lower activities of glutathione disulfide reductase, glutathione reductase and catalase (P < 0.05) in pancreas as compared to normal rats and those treated with red mold fermented products. There were some necrotic cells observed in the pancreas of diabetic rats and pancreatic tissue damaged by STZ in the red mold fermented products supplemented groups was ameliorated. CONCLUSION: These results indicate that red mold fermented products not only regulate hyperglycemia but also provide prevention against the effects of STZ-induced pancreatic damage. PMID- 20737516 TI - More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial. AB - OBJECTIVE: Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies. Recently, we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics (FGAs) in a 6 week randomized controlled trial (RCT). The short duration of that trial was its limitation. This study aimed to explore whether longer treatment is worthwhile. METHOD: Completers of the RCT (n = 39) received open-label add-on mirtazapine for additional 6 weeks. The Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) and several other clinical parameters were measured prospectively. RESULTS: During the open-label phase, significant improvement was achieved in all parameters, with an effect size of 0.94 (CI 95% = 0.45-1.43) on the primary outcome and an impressive additive antipsychotic effect. Patients who received mirtazapine during both phases demonstrated greater improvement in positive symptoms (29.6% versus 21.2%, p = 0.027) than those who received mirtazapine during open-label extension phase only. CONCLUSIONS: These findings support our previous data on the additive antipsychotic effect of mirtazapine in FGAs-treated schizophrenia. Mirtazapine may be effective in other symptom domains, too. Longer duration of mirtazapine treatment may yield additional benefits. If these results will be confirmed in larger studies, add-on mirtazapine may become a feasible option in difficult-to-treat schizophrenia. PMID- 20737513 TI - Endothelial cell migration during murine yolk sac vascular remodeling occurs by means of a Rac1 and FAK activation pathway in vivo. AB - The molecular mechanism(s) controlling cell migration during vascular morphogenesis in vivo remain largely undefined. To address this within a physiological context, we used retinaldehyde dehydrogenase-2 (Raldh2) null mouse embryos and demonstrate that retinoic acid (RA) deficiency results in abnormal yolk sac vascular remodeling due to decreased Rac1 activation, increased RhoA activation, and increased focal adhesions. Vinculin was increased in Raldh2-/- yolk sacs, and molecular events important for focal adhesion turnover, FAK phosphorylation (Tyr397) and FAK-paxillin association, were decreased. RA-rescue of vascular remodeling down-regulated vinculin and restored FAK phosphorylation (Tyr397) and FAK-paxillin association. Furthermore, vascular rescue with vascular endothelial growth factor-A, Indian hedgehog, and basic fibroblast growth factor restored FAK phosphorylation (Tyr397) in the endothelium of Raldh2-/- yolk sacs. Our results provide new insights into the regulation of endothelial cell migration during vascular remodeling in vivo by adding the Rac1 and FAK activation pathway as a critical mediator of focal adhesion formation and turnover during vascular remodeling. PMID- 20737517 TI - Relative association of treatment-emergent adverse events with quality of life of patients with schizophrenia: post hoc analysis from a 3-year observational study. AB - OBJECTIVE: To explore the relative association of adverse events with health related quality of life (HRQL) in patients (N = 16 091) with schizophrenia, treated with antipsychotic medication. METHODS: In this post hoc analysis of data from two 3-year observational studies, a mixed effects model with repeated measures was used to evaluate the association between HRQL (EuroQoL visual analogue scale (EQ-VAS)) and pre-specified covariates including: severity of illness, extrapyramidal symptoms, tardive dyskinesia, sexual dysfunction, and clinically significant weight gain (> 7% increase from baseline after > or = 3 months of treatment). RESULTS: Mean EQ-VAS increased from 47.8 +/- 21.7 at baseline to 72.4 +/- 18.4 after 36 months. The rank order of the negative association of adverse events with HRQL was: sexual dysfunction (effect estimate 4.04; 95% CI -4.30 to -3.79), extrapyramidal symptoms (effect estimate -2.09; 95% CI -2.43 to -1.75), and tardive dyskinesia (effect estimate -0.89; 95% CI -1.46 to -0.32). CONCLUSIONS: Differences were observed in the direction and magnitude of the association between each adverse event and HRQL. Recognition of the relative association of adverse events with HRQL may contribute to improved adherence of patients with schizophrenia to antipsychotic therapy. PMID- 20737518 TI - Effects of a multi-vitamin/mineral supplement on cognitive function and fatigue during extended multi-tasking. AB - OBJECTIVES: A significant minority of the population consume multi vitamins/minerals for their putative health benefits, including potentially beneficial effects on cognitive performance, fatigue and mood. The current study investigated the effect of supplementation with a multi-vitamin/mineral on fatigue and cognitive function in healthy females. METHODS: In this placebo controlled, double blind, randomized, parallel groups trial the effect of a multi vitamin/mineral (Supradyn) was assessed in 216 females aged 25-50 years. Participants attended the laboratory before and 9 weeks after commencing treatment. During both visits cognitive function and the modulation of task related mood/fatigue were assessed in two discrete 20-min assessment periods during which participants completed a four-module version of the Multi-Tasking Framework. RESULTS: Those in the vitamin/mineral group exhibited an attenuation of the negative effects of extended task completion on mood/fatigue. Multi tasking performance for this group was also improved in terms of accuracy across all tasks, and on two of the individual tasks (Mathematical Processing and Stroop) in terms of both faster and more accurate responses. Analysis of a subsection (N = 102) demonstrated significant reductions in homocysteine levels following the vitamins/mineral supplement. CONCLUSIONS: These findings suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation. PMID- 20737519 TI - Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults. AB - OBJECTIVE: There is a lack of research into the cognitive and mood effects of repeated ginseng ingestion. The present study assessed the effects of Panax ginseng (G115) on subjective mood and aspects of 'working' memory processes, following a single dose and following sub-chronic (7 days) ingestion, in healthy volunteers. METHODS: A placebo-controlled, double-blind, randomised, crossover was utilised. Thirty volunteers (mean age 22.87 years; SD 4.01) received each treatment (200 mg; 400 mg; placebo) for 8 days, in a counter balanced order, with a 6-day wash-out period. Testing was on days 1 and 8 of each treatment period, at pre-dose, 1, 2.5 and 4 h post-dose. RESULTS: Results revealed dose-related treatment effects (p < 0.05). Two hundred milligrams slowed a fall in mood at 2.5 and 4 h on day 1 and at 1 and 4 h on day 8, but slowed responding on a mental arithmetic task across day 1 and at 1 and 2.5 h on day 8. The 400 mg dose also improved calmness (restricted 2.5 and 4 h on day 1) and improved mental arithmetic across days 1 and 8. CONCLUSIONS: We found no evidence of additional benefits, nor attenuation of acute effects following repeated ingestion of Panax ginseng (G115). PMID- 20737520 TI - Serotonergic modulation of response inhibition and re-engagement? Results of a study in healthy human volunteers. AB - OBJECTIVE: Cognitive functions dependent on the prefrontal cortex, such as the ability to suppress behavior (response inhibition) and initiate a new one (response re-engagement) is important in the activities of daily life. Central serotonin (5-HT) function is thought to be a critical component of these cognitive functions. In recent studies, 5-HT failed to affect stop-signal reaction time (SSRT), a fundamental process in behavioral inhibition. We were interested if response inhibition and re-engagement are influenced through central 5-HT activity as mediated via the 5-HT transporter. METHODS: Here, using a stop-change task, we investigated the effects of acute and repeated treatment with 10 mg escitalopram, a selective 5-HT reuptake inhibitor, in 36 healthy human volunteers on response inhibition and re-engagement in a randomized, double blind, placebo-controlled study with cross-over design. RESULTS: Results do not show an influence of escitalopram on response inhibition or response re engagement as we did not find differences in SSRT or change reaction time (CRT). CONCLUSIONS: These findings support the results of previous studies suggesting that 5-HT is not critical in inhibition of already initiated responses and response re-engagement. We hypothesize that results are due to different forms of behavioral inhibition and 5-HT may critical to other forms. PMID- 20737521 TI - Pharmacogenetic study of serotonin 6 receptor gene with antidepressant response in major depressive disorder in the Japanese population. AB - OBJECTIVE: Several investigations have suggested that alterations in serotonin 6 (5-HT6) receptors might be associated with the pathophysiology of major depressive disorder (MDD), and that 5-HT6 receptors might be a therapeutic target for serotonin selective reuptake inhibitor (SSRI) in MDD. To evaluate the association between HTR6 and the efficacy of SSRI treatment in Japanese MDD patients, we conducted a case-control study in a Japanese population sample. METHODS: We selected five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), and performed an association analysis of HTR6 and the efficacy of SSRI treatment in 260 MDD patients. RESULTS: We did not detect an association between tagging SNPs in HTR6 and the therapeutic response to SSRI in MDD in allele/genotype or haplotype analysis. CONCLUSIONS: HTR6 may not play an important role in the pathophysiology of SSRI response in the Japanese population. Because our sample was relatively small, statistical errors were possible in the results of our association analyses. To overcome these limitations, a replication study using a larger sample may be required for conclusive results. PMID- 20737522 TI - Oral administration of 5-hydroxytryptophan (5-HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task. AB - OBJECTIVE: Although the serotonin precursor 5-hydroxytryptophan (5-HTP) is marketed as a psychoactive nutritional supplement, knowledge is limited regarding the effects of exogenous 5-HTP on brain activity. This study examined if oral administration of 5-HTP to healthy adults impacted: (1) mood states, as measured by the Profile of Mood States (POMS); and (2) performance on the Iowa Gambling Task (IGT), a measure sensitive to alterations in frontocortical serotonin levels. METHODS: A sample of 46 undergraduates participated, and each received either two 50 mg 5-HTP capsules or placebos, and completed the IGT and POMS following an absorption period. RESULTS: 5-HTP did not significantly alter mood states, but did impair performance on the IGT. Specifically, the 5-HTP group performed more poorly than the placebo group during the first 20 trials of the IGT but did not differ from the placebo group on trials 21-100. This suggests that oral 5-HTP specifically impaired decision making under ambiguity but not under risk. Males also performed more poorly on the first 20 trials of the IGT, regardless of treatment group. CONCLUSIONS: Oral 5-HTP is psychoactive at low doses. Decisions made under ambiguity may be differentially sensitive to increased serotonin release or associated reductions in frontocortical dopamine activity. PMID- 20737523 TI - A cross-sectional observation of the factors associated with deliberate self poisoning with acetaminophen: impact of gender differences and psychiatric intervention. AB - OBJECTIVES: The objectives of this study were to determine the risk factors and life stressors that are prevalent among the acetaminophen deliberate self poisoning (DSP) cases, to identify gender differences in the associated factors, and to determine the prevalence of psychiatric diagnosis and the patterns and types of psychotherapeutic interventions provided by psychiatrists. METHODS: This is a cross-sectional study, a retrospective descriptive case review of hospital admissions for acetaminophen DSP. RESULTS: There were 177 incidences of DSP during the study period. The mean age of the cases was 23.1 +/- 7.3 years and 84.1% of them were females. The risk factors were more significantly associated with males: chronic ethanol intake (p = 0.04), higher reported dose ingested (p = 0.01), higher latency time (p = 0.04) and longer hospital stay (p = 0.03). The most commonly reported psychotherapeutic interventions used by psychiatrists were psychoeducation of the patient, followed by referral to a psychiatric clinic, family psychoeducation and psychotropic medication. Sertraline (SSRI) was the most frequently prescribed antidepressant. CONCLUSIONS: Males have been shown to use more toxic doses and to delay treatment due to high latency time. Most DSP patients have different life stressors and psychiatric diagnoses that may be associated with varying degrees of suicidal intent. All patients presenting following DSP need to be carefully screened for psychiatric illness. Randomized controlled studies need to be conducted on DSP patients with psychiatric illness to determine which treatments are effective. PMID- 20737524 TI - A double-blind, placebo-controlled pilot study of ondansetron for patients with obsessive-compulsive disorder. AB - OBJECTIVE: To assess the efficacy and tolerability of ondansetron in combination with selective serotonin reuptake inhibitors (SSRIs) in patients with obsessive compulsive disorder (OCD). METHODS: The study was an 8-week pilot double-blind randomized clinical trial. Forty-two adult outpatients who met the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria for OCD based on the structured clinical interview participated in the trial. In this study, patients were randomly assigned to receive either ondansetron (4 mg) plus fluoxetine or fluoxetine (20 mg/day) plus placebo. RESULTS: The results showed a significant difference between two groups in the treatment of OCD (based on t test). There was not any significant difference between the two groups in terms of observed side effects. CONCLUSIONS: The results of this study show that ondansetron has positive effects on obsession and compulsion which start two weeks after the beginning of the treatment. PMID- 20737525 TI - Synthesis, isolation, and characterization of 1,1-diGrignard and 1,1-dizincio silanes. PMID- 20737526 TI - Controlled delivery using oligonucleotide-capped mesoporous silica nanoparticles. PMID- 20737527 TI - Cellular integration of an enzyme-loaded polymersome nanoreactor. PMID- 20737528 TI - Rhodium(II)-catalyzed one-pot four-component synthesis of functionalized polyether macrocycles at high concentration. PMID- 20737529 TI - Electrochemical probes for detection and analysis of exocytosis and vesicles. AB - Unraveling the mechanistic details of neurotransmitter exocytosis is arguably among the most important molecular problems in neuroscience today. Investigations at single cells, particularly with electrochemical methods, have given unique chemical and biological insight into this process at the fundamental level. The rapid response time (submillisecond) of microelectrodes makes them well suited for monitoring the dynamic process of exocytosis. We review here recent developments in electrochemical techniques to spatially and simultaneously detect exocytosis across a single cell and to measure the transmitter content of single vesicles removed from cells. The former method is used to demonstrate dynamic heterogeneity in release across a cell, and in the latter work comparison is made between vesicle content and release to conclude that only a fraction of the transmitter is released during full exocytosis. PMID- 20737530 TI - Structure-activity relationships and molecular docking of novel dihydropyrimidine based mitotic Eg5 inhibitors. AB - Dihydropyrimidine-based compounds belong to the first discovered inhibitors of the human mitotic kinesin Eg5. Although they are used by many research groups as model compounds for chemical genetics, considerably less emphasis has been placed on the improvement of this type of inhibitor, with the exception of two recent studies. Dihydropyrimidines can be divided into class I (analogues that bind in the S configuration) and class II type inhibitors, which bind in the R configuration. Herein we report the synthesis and optimization of novel class II type dihydropyrimidines using a combination of in vitro and docking techniques. PMID- 20737531 TI - Electrochemically assisted fabrication of metal atomic wires and molecular junctions by MCBJ and STM-BJ methods. AB - Atomic wires (point contacts) and molecular junctions are two fundamental units in the fields of nanoelectronics and devices. This Minireview introduces our recent approaches aiming to develop versatile methods to fabricate and characterize these unique metallic and molecular structures reliably. Electrochemical methods are coupled with mechanically controllable break junction (EC-MCBJ) or scanning tunneling microscopy (STM) break junction (EC-STMBJ) methods to fabricate metallic point contacts and metal/molecule/metal junctions. With the designed electrodeposition method, the metal of interest (e.g. Au, Cu, Fe or Pd) is deposited in a controlled way on the original electrode pair, on a chip for MCBJ or on the STM tip, to make the metallic contact. Then, various metal atomic wires and molecular junctions can be fabricated and characterized systematically. Herein, we measured the quantized conductance through the construction of histograms of these metal atomic point contacts and of single molecules including benzene-1,4-dithiol (BDT), ferrocene-bisvinylphenylmethyl dithiol (Fc-VPM), 4,4'-bipyridine (BPY), 1,2-di(pyridin-4-yl)ethene (BPY-EE), and 1,2-di(pyridin-4-yl)ethane (BPY-EA). Finally, we briefly discussed the future of EC-MCBJ and EC-STM for nanoelectronics and devices, for example, for the formation of heterogeneous metal-based atomic point contacts and molecular junctions. PMID- 20737533 TI - Aspects of the atmospheric chemistry of amides. AB - The gas-phase reactions of six amides, formamide, N-methyl formamide, N,N dimethyl formamide, acetamide, N-methyl acetamide and N,N-dimethyl acetamide with the atmospheric oxidants OH radicals and Cl atoms, but in a number of cases also with NO(3) radicals and ozone, are presented and discussed. Kinetic and mechanistic information available from previous experimental work is combined with new kinetic and product information from this study, obtained in a photoreactor using in situ FTIR spectrometry, to elucidate the gas-phase photooxidation mechanisms of the amides and assess potential environmental implications. PMID- 20737532 TI - Probing the hydrogen bonding structure in the Rieske protein. AB - The use of the far-infrared spectral range presents a novel approach for analysis of the hydrogen bonding in proteins. Here it is presented for the analysis of Fe- S vibrations (500-200 cm(-1)) and of the intra- and intermolecular hydrogen bonding signature (300-50 cm(-1)) in the Rieske protein from Thermus thermophilus as a function of temperature and pH. Three pH values were adequately chosen in order to study all the possible protonation states of the coordinating histidines. The Fe--S vibrations showed pH-dependent shifts in the FIR spectra in line with the change of protonation state of the histidines coordinating the [2Fe -2S] cluster. Measurements of the low-frequency signals between 300 and 30 K demonstrated the presence of a distinct overall hydrogen bonding network and a more rigid structure for a pH higher than 10. To further support the analysis, the redox-dependent shifts of the secondary structure were investigated by means of an electrochemically induced FTIR difference spectroscopic approach in the mid infrared. The results confirmed a clear pH dependency and an influence of the immediate environment of the cluster on the secondary structure. The results support the hypothesis that structure-mediated changes in the environment of iron -sulfur centers play a critical role in regulating enzymatic catalysis. The data point towards the role of the overall internal hydrogen bonding organization for the geometry and the electronic properties of the cluster. PMID- 20737534 TI - An alternative solvent-free synthesis of nopinone under ball-milling conditions: Investigation of reaction parameters. AB - A new method for the oxidative cleavage of beta-pinene (1) yielding nopinone (2) with potassium permanganate as oxidant under solvent-free conditions was established. The reaction was performed in a conventional ball mill with use of a grinding auxiliary. The auxiliary has the ability to sorb liquid reactants such as 1 on its surface to make liquid(s) accessible for mechanical impact. Different reaction parameters and technical variables were assessed concerning their influence on yield and selectivity of 2. Different chemical parameters such as oxidants, grinding auxiliaries, and quantities were investigated. Also tuning parameters including milling time, rotation frequency, and number of milling balls were explored. PMID- 20737535 TI - C--C bond formation reactions for biomass-derived molecules. PMID- 20737536 TI - Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancer: coexpression of Notch-1 and vascular endothelial growth factor-A predicts poor survival. AB - BACKGROUND: Notch signaling plays a key role in embryonic vascular development and angiogenesis. The authors aimed to study the prognostic role of the angiogenesis-related Notch ligands and receptors and investigate the prognostic impact of the coexpression of vascular endothelial growth factor-A (VEGF-A) and Notch signaling. METHODS: Tumor tissue samples from 335 resected patients with stage I to IIIA nonsmall cell lung cancer (NSCLC) were obtained, and tissue microarrays were constructed from duplicate cores of tumor cells and tumor related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers Notch-1, Notch-4, Delta-like ligand 4 (DLL4), and Jagged-1. RESULTS: There were 191 squamous cell carcinomas (SCCs), 113 adenocarcinomas (ACs), and 31 large cell carcinomas. In AC, low tumor cell Delta like ligand 4 expression was an independent negative prognostic factor (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.4-6.3 [P = .006]), whereas high tumor cell Notch-1 expression was an independent negative prognostic factor (HR, 2.2; 95% CI, 1.2-4.1 [P<.001]). In SCC, low stromal Delta-like ligand 4 expression was an independent indicator of poor prognosis (HR, 3.3; 95% CI, 1.8 6.1 [P<.001]). The coexpression of Notch-1 and VEGF-A had a significant prognostic impact (P<.001). For Notch-1 and VEGF-A, low/low (n = 142) versus high/high (n = 35) expression resulted in 5-year survival rates of 69% and 32%, respectively. CONCLUSIONS: Delta-like ligand 4 and Notch-1 are independent prognostic factors in NSCLC, but have diverse impacts in SCC and AC. The coexpression of tumor cell Notch-1/VEGF-A has a major impact on survival. PMID- 20737538 TI - Scoring system to identify patients at high risk of oesophageal cancer. AB - BACKGROUND: Identification of a patient cohort at high risk of developing oesophageal cancer might enable a greater proportion of patients with curable disease stages to be identified and permit better use of investigative resources. The aim of this study was to develop a scoring system that identifies patients with dysphagia at greatest risk of having oesophageal cancer. METHODS: Data on 435 patients with dysphagia were recorded. Univariable and multivariable analyses were performed to identify parameters predictive of cancer. These were used to create the Edinburgh Dysphagia Score (EDS), which was then validated in a second cohort of patients. RESULTS: The EDS contained six parameters: age, sex, weight loss, duration of symptoms, localization of dysphagia and acid reflux. It stratified the development cohort into a group at higher risk, containing 39 of 40 patients with cancer, and a group at lower risk, comprising 36.0 per cent of referrals (sensitivity 97.5 per cent, negative predictive value 99.3 per cent). On validation, the EDS divided the referrals into a higher-risk group identifying all 26 cancers and a lower-risk group comprising 30.0 per cent of referrals. CONCLUSION: From 574 referrals, the EDS correctly classified as higher risk all but one patient with cancer. Some 34.0 per cent of patients identified as lower risk could have been investigated less urgently. This simple scoring system permits sensitive prioritization of patients referred with dysphagia, and enables more efficient use of investigative resources. PMID- 20737537 TI - Screening for major depression in cancer outpatients: the diagnostic accuracy of the 9-item patient health questionnaire. AB - BACKGROUND: Systematic screening for depression has been recommended for patients who have medical conditions like cancer. The 9-item Patient Health Questionnaire (PHQ-9) is becoming widely used, but its diagnostic accuracy has not yet been tested in a cancer patient population. In this article, the authors report on the performance of the PHQ-9 as a screening instrument for major depressive disorder (MDD) in patients with cancer. METHODS: Data obtained from a depression screening service for patients who were attending clinics of a Regional Cancer Centre in Edinburgh, United Kingdom were used. Patients had completed both the PHQ-9 and a 2-stage procedure to identify cases of MDD. Performance of the PHQ-9 in identifying cases of MDD was determined using receiver operating characteristic (ROC) analysis. RESULTS: Data were available on 4264 patients. When scored as a continuous measure, the PHQ-9 performed well with an area under the ROC curve of 0.94 (95% confidence interval [CI], 0.93-0.95). A cutoff score of >= 8 provided a sensitivity of 93% (95% CI, 89%-95%), a specificity of 81% (95% CI, 80%-82%), a positive predictive value (PPV) of 25%, and a negative predictive value (NPV) of 99% and could be considered optimum in a screening context. The PHQ-9 did not perform as well when it was scored using an algorithm with a sensitivity of 56% (95% CI, 55%-57%), a specificity of 96% (95% CI, 95%-97%), a PPV of 52%, and an NPV of 97%. CONCLUSIONS: The PHQ-9 scored as a continuous measure with a cutoff score of >= 8 performed well in identifying MDD in cancer patients and should be considered as a screening instrument in this population. PMID- 20737539 TI - Development of efficient enzymatic production of theanine by gamma glutamyltranspeptidase from a newly isolated strain of Bacillus subtilis, SK11.004. AB - BACKGROUND: Theanine, a unique amino acid found almost exclusively in tea plants, has various favourable physiological and pharmacological functions in humans. Gamma-glutamyltranspeptidase (GGT, EC 2.3.2.2) is considered to be the most effective enzyme for the production of theanine. In fact, GGT can catalyse the transfer of gamma-glutamyl moieties from gamma-glutamyl compounds to water (hydrolysis) or to amino acids and peptides (transpeptidation). RESULTS: A novel strain, SK11.004, which produces GGT with high theanine-forming ability was isolated from fermented shrimp paste and identified as Bacillus subtilis through its physiological and biochemical properties as well as its 16S rDNA sequence analysis. Theanine (18.9 mmol L(-1)) was synthesised by GGT (0.06 U mL(-1)) through transfer reaction in the presence of glutamine (20 mmol L(-1)) as a donor and ethylamine HCl (50 mmol L(-1)) as an acceptor at pH 10 and 37 degrees C for 4 h, the conversion rate being up to 94%. CONCLUSION: The enzymatic synthesis of theanine using GGT from a newly isolated strain Bacillus subtilis SK11.004 was found to be an efficient method. Moreover, compared with others, the GGT from B. subtilis SK11.004 exhibited the highest ratio of transferring activity to hydrolytic activity using glutamine, suggesting a high potential application in the production of theanine and other functional gamma-glutamyl compounds. PMID- 20737541 TI - The actin gene family: function follows isoform. AB - Although actin is often thought of as a single protein, in mammals it actually consists of six different isoforms encoded by separate genes. Each isoform is remarkably similar to every other isoform, with only slight variations in amino acid sequence. Nevertheless, recent work indicates that actin isoforms carry out unique cellular functions. Here, we review evidence drawn from localization studies, mouse models, and biochemical characterization to suggest a model for how in vivo mixing of actin isoforms may influence cytoskeletal function in cells. PMID- 20737542 TI - Falls in Parkinson's disease: kinematic evidence for impaired head and trunk control. AB - Changes in stride characteristics and gait rhythmicity characterize gait in Parkinson's disease and are widely believed to contribute to falls in this population. However, few studies have examined gait in PD patients who fall. This study reports on the complexities of walking in PD patients who reported falling during a 12-month follow-up. Forty-nine patients clinically diagnosed with idiopathic PD and 34 controls had their gait assessed using three-dimensional motion analysis. Of the PD patients, 32 (65%) reported at least one fall during the follow-up compared with 17 (50%) controls. The results showed that PD patients had increased stride timing variability, reduced arm swing and walked with a more stooped posture than controls. Additionally, PD fallers took shorter strides, walked slower, spent more time in double-support, had poorer gait stability ratios and did not project their center of mass as far forward of their base of support when compared with controls. These stride changes were accompanied by a reduced range of angular motion for the hip and knee joints. Relative to walking velocity, PD fallers had increased mediolateral head motion compared with PD nonfallers and controls. Therefore, head motion could exceed "normal" limits, if patients increased their walking speed to match healthy individuals. This could be a limiting factor for improving gait in PD and emphasizes the importance of clinically assessing gait to facilitate the early identification of PD patients with a higher risk of falling. PMID- 20737543 TI - Incidence of Parkinson's disease among hospital patients with methamphetamine-use disorders. AB - Because methamphetamine exposure to experimental animals can damage brain dopamine neurones, we examined whether hospital patients diagnosed with methamphetamine-related disorders might have greater risk of subsequent admission with a Parkinson's disease diagnosis. This was a population-based cohort study using all statewide inpatient hospital discharge records from July 1, 1990, through June 30, 2000, in California, USA, in which subjects aged at least 50 years were followed for up to 10 years. Individuals with reported methamphetamine related conditions (n = 1,863; ICD-9 codes 304.4, 305.7, 969.7, and E854.2) were matched on demographic variables and follow-up time with those with primary appendicitis conditions (n = 9,315). The appendicitis group had a Parkinson's disease incidence rate no different than the rate found among members of a large health maintenance organization in California. Cox regression procedures were used to estimate group differences in the rates of receiving a subsequent inpatient diagnosis of Parkinson's disease (ICD-9 332.0). The methamphetamine group showed increased risk of a subsequent admission with Parkinson's disease compared with that of the matched appendicitis group (adjusted hazard ratio = 2.65, 95% CI, 1.17-5.98, P= 0.019). Study limitations include a population limited to hospital admissions, an uncertainty regarding diagnostic validity of the ICD-9 code 332.0 (Parkinson's disease), and a small number of incident cases with suspected Parkinson's disease. We strongly emphasize the preliminary nature of the findings. Nevertheless, these data, requiring replication, provide some evidence that methamphetamine users might be at greater than normal risk for developing Parkinson's disease. PMID- 20737540 TI - Dynamic regulation of sarcomeric actin filaments in striated muscle. AB - In striated muscle, the actin cytoskeleton is differentiated into myofibrils. Actin and myosin filaments are organized in sarcomeres and specialized for producing contractile forces. Regular arrangement of actin filaments with uniform length and polarity is critical for the contractile function. However, the mechanisms of assembly and maintenance of sarcomeric actin filaments in striated muscle are not completely understood. Live imaging of actin in striated muscle has revealed that actin subunits within sarcomeric actin filaments are dynamically exchanged without altering overall sarcomeric structures. A number of regulators for actin dynamics have been identified, and malfunction of these regulators often result in disorganization of myofibril structures or muscle diseases. Therefore, proper regulation of actin dynamics in striated muscle is critical for assembly and maintenance of functional myofibrils. Recent studies have suggested that both enhancers of actin dynamics and stabilizers of actin filaments are important for sarcomeric actin organization. Further investigation of the regulatory mechanism of actin dynamics in striated muscle should be a key to understanding how myofibrils develop and operate. PMID- 20737544 TI - Postmortem degradation of desmin and calpain in breast and leg and thigh muscles from Taiwan black-feathered country chickens. AB - BACKGROUND: Several studies have reported that the postmortem changes are more rapid in breast muscles (BM) than in leg and thigh muscles (LM) of chickens. However, the reasons for the differences in postmortem proteolysis of BM and LM are still uncertain. The purpose of this study was therefore to compare the postmortem degradation of desmin and calpains in BM and LM from Taiwan black feathered country chickens at 5 degrees C. RESULTS: The pH was lower (P < 0.05) in BM than in LM. Western blot indicated that postmortem desmin degradation was more rapid in BM than in LM. Casein zymograms showed that at-death u-calpain activity was higher in BM than in LM. As postmortem time proceeded, u-calpain was activated and autolyzed more extensively in BM than in LM. However, the u/m calpain activity remained stable during postmortem storage in both BM and LM. CONCLUSION: Our results suggest that the more rapid postmortem proteolysis found in BM than in LM at 5 degrees C similar with the previous study could be mainly explained by both greater amounts and faster activation and autolysis of u calpain in BM. PMID- 20737545 TI - Restless legs syndrome and Parkinson's disease in men. AB - We examined whether men with restless legs syndrome (RLS) have a higher prevalence of Parkinson's disease (PD) among 23,119 US participants of the Health Professional Follow-up Study who were free of diabetes and arthritis. RLS was assessed using a set of standardized questions recommended by the International RLS Study Group. PD cases were identified by self-reported questionnaires and confirmed by review of medical records. Compared to men without RLS, multivariate adjusted odds ratios for PD were 1.1 (95% confidence interval: 0.4, 3.0) for men with RLS symptoms 5-14 times per month and 3.09 (95% confidence interval: 1.5, 6.2; P trend = 0.003) for those with symptoms 15 times or more per month, after adjusting for age, smoking, use of antidepressant, and other covariates. In conclusion, men with RLS are more likely to have concurrent PD. Prospective studies are warranted to clarify the temporal relationship between RLS and PD. PMID- 20737546 TI - Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX(r)) across multiple indications. AB - This meta-analysis evaluated the frequency of neutralizing antibody (nAb) conversion with onabotulinumtoxinA (BOTOX(r); Allergan) across five studied indications. The analysis was based on large, controlled or prospective, open label trials (durations 4 months to >=2 years). Serum samples were analyzed for nAbs using the Mouse Protection Assay. Subjects who were antibody negative at baseline and had at least one analyzable postbaseline antibody assay result were included. The 16 clinical studies included 3,006 subjects; of these, 2,240 met the inclusion criteria for this analysis. Subjects received 1-15 treatments (mean 3.8 treatments) with onabotulinumtoxinA. Total doses per treatment cycle ranged from 10 or 20 units in glabellar lines to 20-500 units in cervical dystonia. The numbers of subjects who converted from an antibody-negative status at baseline to antibody-positive status at any post-treatment time point were: cervical dystonia 4/312 (1.28%), glabellar lines 2/718 (0.28%), overactive bladder 0/22 (0%), post stroke spasticity 1/317 (0.32%), and primary axillary hyperhidrosis 4/871 (0.46%). Across all indications, 11/2,240 subjects (0.49%) converted from antibody negative at baseline to positive at one or more post-treatment time points, but only three subjects became clinically unresponsive to onabotulinumtoxinA at some point following a positive assay. Based on these large trials, the frequency of antibody conversion after onabotulinumtoxinA treatment is very low, and infrequently leads to loss of efficacy. (c) 2010 Movement Disorder Society. PMID- 20737547 TI - Processing characteristics and flavour of full lotus root powder beverage. AB - BACKGROUND: Lotus root beverage is commonly made from raw lotus root (RLR). However, RLR production is strictly limited, because it is prone to decomposition and browning after its short harvest season. In this study an innovative beverage was prepared from full lotus root powder (FLRP) as a substitute for RLR in an attempt to solve this problem. RESULTS: The components of FLRP basically corresponded to those of RLR, but there was some loss of heat-labile compounds. Using differential scanning calorimetry, a gelatinisation temperature range of 57.08-67.80 degrees C was determined for FLRP with an average particle size distribution of 70 um. The optimal conditions for enzymatic treatment of FLRP beverage were determined by response surface methodology as an enzyme concentration of 2.2 g kg(-1) at 53 degrees C for 86 min. Turbidity decreased from 1082 to 280 nephelometric turbidity units following enzymolysis. Properties of FLRP beverage were also studied and a qualitative comparison of flavour compounds between RLR and FLRP beverages was made by electronic nose. CONCLUSION: Basic flavour compounds were consistent and flavour radar plots had approximately the same shape, area and proportion when all ingredients were identical apart from FLRP and RLR. Therefore, in terms of flavour, FLRP beverage appears to be a feasible substitute for RLR beverage. PMID- 20737548 TI - Psychiatric symptoms associated with focal hand dystonia. AB - Myoclonus dystonia and idiopathic dystonia are associated with a greater frequency of obsessive compulsive disorder (OCD) and major depression. We investigated the frequency of OCD in 39 patients with primary focal hand dystonia (FHD) using a semistructured interview. OCD and subsyndromal OCD was diagnosed in 5 of 39 (12.82%) patients with FHD, whereas OCD occurs in 2.3% of the general population. Recurrent depression occurred in (7 of 39) 17.95% of patients with FHD along with a family history of depression in (16 of 39) 41.02%. Overlapping mechanisms manifesting as FHD may also predispose to OC symptoms and likely implicates a common striatal dysfunction. PMID- 20737549 TI - Prevalence and clinical profile of restless legs syndrome in Parkinson's disease. AB - Parkinson's disease (PD) and restless legs syndrome (RLS) have a dopaminergic link. More insight in the clinical profile of RLS in patients with PD may benefit our understanding of this link. The aims of this study were to evaluate the frequency and clinical profile of RLS in a large cohort of PD patients. In 269 nondemented Caucasian PD patients, the four diagnostic criteria for RLS were administered by a RLS trained researcher. In patients with definite RLS, the severity of these symptoms was assessed. Furthermore, in all patients, relevant motor and nonmotor symptoms in PD were evaluated. Definite RLS was present in 11% of the patients. RLS patients were more often female (69% vs. 32%, P < 0.001), but no other significant differences existed between PD patients with and without RLS. Within the PD patients with RLS, severity of RLS correlated positively with PD severity, motor fluctuations, depressive symptoms, daytime sleepiness, cognitive problems, autonomic symptoms, and psychotic symptoms. This study in a large PD cohort shows that prevalence of RLS is similar to that in the general population, which might be caused by underestimation of RLS due to dopaminergic treatment. No relations were found between the presence of RLS and PD symptoms, but the severity of RLS was related to the severity of PD-related, mainly nondopaminergic, symptoms. It is hypothesized that, nondopaminergic systems, such as the noradrenergic system may play a role in the possible link between PD and RLS. PMID- 20737550 TI - ADEM presenting as a movement disorder. PMID- 20737551 TI - Long-term effects of coordinative training in degenerative cerebellar disease. AB - Few clinical studies have evaluated physiotherapeutic interventions for patients with degenerative cerebellar disease. In particular, evidence for long-term effects and transfer to activities of daily life is rare. We have recently shown that coordinative training leads to short-term improvements in motor performance. To evaluate long-term benefits and translation to real world function, we here assessed motor performance and achievements in activities of daily life 1 year after a 4 week intensive coordinative training, which was followed by a home training program. Effects were assessed by clinical rating scales, a goal attainment score and quantitative movement analysis. Despite gradual decline of motor performance and gradual increase of ataxia symptoms due to progression of disease after 1 year, improvements in motor performance and achievements in activities of daily life persisted. Thus, also in patients with degenerative cerebellar disease, continuous coordinative training leads to long-term improvements, which translate to real world function. PMID- 20737552 TI - Work-related effort thrombosis in a millwright: a case report. AB - BACKGROUND: Effort thrombosis refers to axillosubclavian vein thrombosis secondary to physical activities of the upper extremity. METHODS: This report describes the clinical presentation of effort thrombosis in a millwright and reviews the literature for occupational reports of this condition. RESULTS: While there is a paucity of literature reporting an occupational association, work related physical demands on the upper extremity appears to increase the risk of axillosubclavian impingement and thrombosis in certain patients. CONCLUSION: Effort thrombosis is a rare vascular condition of the upper extremity that may be seen in workers with repetitive, forceful, or overhead arm activities. PMID- 20737553 TI - Compound muscle action potential and motor function in children with spinal muscular atrophy. AB - Reliable outcome measures that reflect the underlying disease process and correlate with motor function in children with SMA are needed for clinical trials. Maximum ulnar compound muscle action potential (CMAP) data were collected at two visits over a 4-6-week period in children with SMA types II and III, 2-17 years of age, at four academic centers. Primary functional outcome measures included the Modified Hammersmith Functional Motor Scale (MHFMS) and MHFMS Extend. CMAP negative peak amplitude and area showed excellent discrimination between the ambulatory and non-ambulatory SMA cohorts (ROC = 0.88). CMAP had excellent test-retest reliability (ICC = 0.96-0.97, n = 64) and moderate to strong correlation with the MHFMS and MHFMS-Extend (r = 0.61-0.73, n = 68, P < 0.001). Maximum ulnar CMAP amplitude and area is a feasible, valid, and reliable outcome measure for use in pediatric multicenter clinical trials in SMA. CMAP correlates well with motor function and has potential value as a relevant surrogate for disease status. PMID- 20737554 TI - Cytocompatibility of bio-inspired silicon carbide ceramics. AB - Due to its good mechanical and biochemical properties and, also, because of its unique interconnected porosity, bio-inspired silicon carbide (bioSiC) can be considered as a promising material for biomedical applications, including controlled drug delivery devices and tissue engineering scaffolds. This innovative material is produced by molten-Si infiltration of carbon templates, obtained by controlled pyrolysis of vegetable precursors. The final SiC ceramic presents a porous-interconnected microstructure that mimics the natural hierarchical structure of bone tissue and allows the internal growth of tissue, as well as favors angiogenesis. In the present work, the in vitro cytocompatibility of the bio-inspired SiC ceramics obtained, in this case, from the tree sapelli (Entandrophragma cylindricum) was evaluated. The attachment, spreading, cytoskeleton organization, proliferation, and mineralization of the preosteoblastic cell line MC3T3-E1 were analyzed for up to 28 days of incubation by scanning electron microscopy, interferometric profilometry, confocal laser scanning microscopy, MTT assay, as well as red alizarin staining and quantification. Cells seeded onto these ceramics were able to attach, spread, and proliferate properly with the maintenance of the typical preosteoblastic morphology throughout the time of culture. A certain level of mineralization on the surface of the sapelli-based SiC ceramics is observed. These results demonstrated the cytocompatibility of this porous and hierarchical material. PMID- 20737555 TI - Characteristics and biocompatibility of a biodegradable genipin-cross-linked gelatin/beta-tricalcium phosphate reinforced nerve guide conduit. AB - To modulate the mechanical properties of nerve guide conduit for surgical manipulation, this study develops a biodegradable composite containing genipin cross-linked gelatin annexed with beta-tricalcium phosphate ceramic particles as a nerve guide material. The conduit was dark bluish and round with a rough and compact outer surface compared to the genipin cross-linked gelatin conduit (without beta-tricalcium phosphate). Water uptake and swelling tests indicate that the conduit noticeably increases the stability in water, and the hydrated conduit does not collapse and stenose. The conduit has a sufficiently high level of mechanical properties to serve as a nerve guide. After subcutaneous implantation on the dorsal side of a rat, the degraded conduit only evokes a mild tissue response, and the formation of a very thin fibrous capsule surrounds the conduit. This paper assesses the effectiveness of the conduit as a guidance channel when we use it to repair a 10 mm gap in the rat's sciatic nerve. The experimental results show no gross inflammatory reactions of the peripheral nerve tissues at the implantation site in either group. In overall gross examination, the diameter of the intratubular and newly formed nerve fibers in the conduits exceeds that of the silicone tubes during the implantation period. The quantitative results indicate the superiority of the conduits over the silicone tubes. This study microscopically observes the nerve regeneration in the tissue section at the middle region of all implanted conduits. Therefore, the histomorphometric assessment demonstrates that the conduit could be a candidate for peripheral nerve repair. PMID- 20737556 TI - Deposition of substituted apatites with anticolonizing properties onto titanium surfaces using a novel blasting process. AB - A series of doped apatites have been deposited onto titanium (V) substrates using a novel ambient temperature blasting process. The potential of these deposited doped apatites as non-colonizing osteoconductive coatings has been evaluated in vitro. XPS, EDX, and gravimetric analysis demonstrated that a high degree of coating incorporation was observed for each material. The modified surfaces were found to produce osteoblast proliferation comparable to, or better than, a hydroxyapatite finish. Promising levels of initial microbial inhibition were observed from the Sr- and Ag-doped surfaces, with the strontium showing prolonged ability to reduce bacteria numbers over a 30-day period. Ion elution profiles have been characterized and linked to the microbial response and based on the results obtained, mechanisms of kill have been suggested. In this study, the direct contact of coated substrate surfaces with microbes was observed to be a significant contributing factor to the antimicrobial performance and the anticolonizing activity. The silver substituted apatite was observed to out perform both the SrA and ZnA in terms of biofilm inhibition. PMID- 20737557 TI - Ciliary neurotrophic factor-coated polylactic-polyglycolic acid chitosan nerve conduit promotes peripheral nerve regeneration in canine tibial nerve defect repair. AB - A variety of nerve conduits incorporated with chemical and biological factors have been developed to further stimulate nerve regeneration. Although most of the nerve guides in studies are basically limited to bridge a short gap of nerve defect in rat models, it is vital to evaluate effects of conduits on nerve regeneration over distance greater than 20 mm, or more clinically relevant nerve gap lengths in higher mammals. In this study, a poly(lactide-co-glycolide) (PLGA) nerve conduit, treated with pulsed plasma and coated with ciliary neurotrophic factor (CNTF) as well as chitosan, was used to repair 25-mm-long canine tibial nerve defects in eighteen cross-bred dogs. The canines were randomly divided into three groups (n = 6), a 25-mm segment of the tibial nerve was removed and replaced by a PLGA/chitosan-CNTF nerve conduit, PLGA/chitosan conduit and autologous nerve grafts were performed as the control. The results were evaluated by general observation, electromyogram testing, S-100 histological immunostaining, and image analysis at 3 months after operation. The histological results demonstrated that the PLGA/chitosan-CNTF conduits and PLGA/chitosan conduits were capable of leading the damaged axons through the lesioned area. Through the comparison of the three groups, the results in PLGA/chitosan-CNTF conduits group were better than that of PLGA/chitosan conduits group, while they were similar to autologous nerve grafts group. Therefore, CNTF-coated PLGA/chitosan nerve conduits could be an alternative artificial nerve conduit for nerve regeneration. PMID- 20737558 TI - Clinical device-related article surface characterization of explanted endovascular stents: evidence of in vivo corrosion. AB - Limited information exists regarding the in vivo stability of endovascular stents. Nine excised human vascular segments with implanted stents (n = 16) manufactured from stainless steel, nickel-titanium, tantalum, and cobalt-based alloys were analyzed. The stent/tissue components were separated using an established tissue dissolution protocol and control and explanted stents were evaluated by digital optical and electron microscopy. Metallic content in surrounding tissues was measured by mass spectroscopy. Surface alterations, consistent with corrosion mediated by electrochemical and mechanical factors, were observed in 9 of the 16 explanted stents and were absent from control stents. Tissue dissolved from around corroded stents corresponded with a higher metallic content. The effect of these changes in the microtopography of stents on their mechanical properties (fatigue strength and fracture limit) in addition to the potential for released metallic debris contributing to the biological mechanisms of in-stent restenosis supports the need for further investigations. PMID- 20737559 TI - Management of acral myxoinflammatory fibroblastic sarcoma. AB - BACKGROUND: Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low grade sarcoma that commonly affects the distal extremities. From the published cases, therapy for AMFS to date has been comprised of excision or amputation, with limited use of radiotherapy (RT) or chemotherapy. In this report, the outcome of 17 patients with AMFS treated at the study institution was reported. METHODS: A retrospective review of all cases of AMFS identified in the Sarcoma Database in the Department of Radiation Oncology at the study institution was conducted. Treatment records and data from follow-up visits of patients were reviewed. RESULTS: Seventeen patients were identified. All the patients underwent surgical resection (15 excisions and 2 amputations). Positive surgical margins after excisions were noted in 5 patients and were widely positive in 1 patient. Of the 17 patients, 14 patients received some form of RT. The average total dose was 56.4 Gray (Gy). Eight patients received preoperative RT alone, 5 patients received preoperative RT and postoperative RT, and 1 patient received preoperative RT and intraoperative RT. Median follow-up was 24.5 months. One patient presented with recurrent disease and was treated with resection, and both pre- and postoperative RT. He was free of disease 23 months after his last treatment. No local recurrence was noted in the remaining patients. Of the 14 patients undergoing preoperative RT, complete pathologic necrosis or no tumor was noted in 1 of the patients. No metastatic disease was observed in any of the patients. There was no significant radiation toxicity observed in any of the patients. CONCLUSIONS: Data were consistent with local control of distal extremity sarcomas with resection and RT, suggesting that limb-sparing surgery with this treatment combination is an appropriate option in the limb-sparing control of patients with AMFS, even those with positive surgical margins. PMID- 20737560 TI - Cognitive impairment in men with testicular cancer prior to adjuvant therapy. AB - BACKGROUND: Cognitive dysfunction experienced by individuals with cancer represents an important survivorship issue because of its potential to affect occupational, scholastic, and social activities. Whereas early efforts to characterize cognitive dysfunction primarily focused on the effects of chemotherapy, more recent evidence indicates that impairment may exist before systemic treatment. This study characterized cognitive dysfunction before adjuvant chemotherapy in a sample of men diagnosed with nonseminomatous germ cell tumors (NSGCT) of the testis. METHODS: Men with newly diagnosed NSGCT were recruited after orchiectomy but before adjuvant chemotherapy. Patients completed neuropsychological tests to assess attention, learning, language, executive function, and motor function. Self-report measures of depression and anxiety were also administered. An overall cognitive function index was computed for participants. Cognitive impairment was defined as a z-score of less than or equal to -1.5 on 2 or more tests, or a z-score of less than or equal to -2.0 on a single test. RESULTS: Approximately 46% of patients exhibited cognitive impairment at the time of assessment, which is significantly greater than would be expected considering healthy population norms (binomial test: P < .0001). Patients exhibited impairments in motor function, verbal learning, and executive function much more frequently relative to normative expectations (binomial test: P < .0001). CONCLUSIONS: The prevalence of cognitive impairment in men with newly diagnosed NSGCT is unexpectedly high before the receipt of adjuvant chemotherapy. Efforts to track cognitive function over time and to develop effective interventions are warranted. PMID- 20737561 TI - Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. AB - BACKGROUND: The authors studied the survival and long-term morbidities of children with nasopharyngeal carcinoma (NPC). METHODS: This was a retrospective review of children with NPC who were treated at St. Jude Children's Research Hospital between 1961 and 2004. Prognostic factors and long term effects of therapy were analyzed. RESULTS: Fifty-nine patients (median age, 14.1 years) were identified. Most were male (66.1%) and black (54.2%) and had lymphoepithelioma (93.2%). Thirty-five patients had stage IV disease (59.3%), 20 patients had stage III disease (33.9%), and 4 patients had stage II disease (6.8%). All patients received radiotherapy (RT) to the primary tumor, and most received cervical RT (98.3%) and chemotherapy (88.1%). The 15-year survival and event-free survival (EFS) rates were 67.2% +/- 7.5% and 63.5% +/- 7.8%, respectively. Five patients (8.5%) developed subsequent malignancies 8.6 to 27 years after NPC diagnosis. EFS was improved in patients who were diagnosed after 1980 (74.8% +/- 10% vs 45.5% +/ 10.1%; P = .031), in patients who had stage III disease compared with patients who had stage IV disease (79.3% +/- 9.6% vs 56.2% +/- 11.8%; P = .049), in patients who received cisplatin (81% +/- 10.7% vs 45.8% +/- 9.7%; P = .013), and in patients who received >= 50 grays of RT (71.4% +/- 9.3% vs 43.8% +/- 11.6%; P = .048). White patients had higher distant failure rates than black patients (41.7% +/- 10.4% vs 15.6 +/- 6.5%; P = .045). The 15-year cumulative incidence (CI) of any morbidity was 83.7% +/- 5.4%, the CI of sensorineural hearing loss was 52.9% +/- 6.7%, the CI of primary hypothyroidism was 42.7% +/- 6.6%, and the CI of growth hormone deficiency (GHD) was 14.1% +/- 4.7%. Dose-response relations were observed between the RT dose and primary hypothyroidism and GHD. CONCLUSIONS: The outcome of children with NPC improved over the past 4 decades with the use of cisplatin-based chemotherapy and higher RT doses. However, many survivors had long-term treatment-related morbidities. PMID- 20737562 TI - Predictors of competing mortality in early breast cancer. AB - BACKGROUND: Death in the absence of disease recurrence (competing mortality) is an important determinant of disease-free survival (DFS) in early breast cancer. The authors sought to identify predictors of this event using competing risks modeling. METHODS: A cohort study was made of 1231 consecutive women with stage I to II invasive breast cancer diagnosed between 1986 and 2004, treated with breast conservation therapy. Median follow-up was 82 months. The authors used a parametric competing risks regression model to analyze factors associated with the cumulative incidence of competing mortality. They generated a risk score from the model coefficient estimates and stratified patients according to low and high risk score for analysis. RESULTS: Ten-year DFS was 69.7% (95% confidence interval [CI], 66.2%-72.9%). The 10-year cumulative incidence of locoregional recurrence (LRR) was 4.4% (95% CI, 3.0%-5.8%), distant recurrence was 7.1% (95% CI, 5.4% 8.9%), and competing mortality was 18.7% (95% CI, 15.9%-21.6%). On multivariate analysis, competing mortality was associated with increasing age (hazard ratio [HR], 1.83 per 10 years; 95% CI, 1.58-2.12), black race (HR, 1.71; 95% CI, 1.17 2.51), and comorbid disease (HR, 1.93, 95% CI, 1.40-2.65). Ten-year cumulative incidences of competing mortality, locoregional recurrence, and distant recurrence for patients at low (n=638) versus high (n=593) risk of competing mortality were 7.2% versus 30.6% (P<.001), 4.4% versus 4.4% (P=.97), and 8.6% versus 5.6% (P=.12), respectively. CONCLUSIONS: Competing mortality is an important event influencing 10-year DFS in early breast cancer and is associated with increasing age, black race, and comorbid disease. Stratifying patients according to competing mortality risk may be useful in designing clinical trials. PMID- 20737563 TI - MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of approximately 60% of all human genes. They play important roles in numerous cellular processes, including development, proliferation, and apoptosis. Currently, it is believed that miRNAs elicit their effect by silencing the expression of target genes. In this study, the authors demonstrated that miRNA 205 (miR-205) induced the expression the interleukin (IL) tumor suppressor genes IL24 and IL32 by targeting specific sites in their promoters. METHODS: The methods used in this study included transfection of small RNAs; quantitative real time polymerase chain reaction; in situ hybridization; fluorescence-labeled in situ hybridization; cell cycle, apoptosis, cell viability, migratory, clonability, and invasion assays; immunoblotting; and luciferase reporter, nuclear run-on, and chromatin immunoprecipitation assays. RESULTS: The results revealed that miR-205 was silenced in prostate cancer. Its re-expression induced apoptosis and cell cycle arrest. It also impaired cell growth, migration, clonability, and invasiveness of prostate cancer cells. Micro-RNA-205 induced the expression of tumor suppressor genes IL24 and IL32 at both the messenger RNA and protein levels. The induction of in vitro transcription and enrichment of markers for transcriptionally active promoters in the IL24 and IL32 genes was observed in response to miR-205. CONCLUSIONS: In this study, a new function for miR-205 was identified that specifically activated tumor suppressor genes by targeting specific sites in their promoters. These results corroborate a newly identified function that miRNAs have in regulating gene expression at the transcriptional level. The specific activation of tumor suppressor genes (eg, IL24, IL32) or other dysregulated genes by miRNA may contribute to a novel therapeutic approach for the treatment of prostate cancer. PMID- 20737564 TI - The expanding melanoma burden in California hispanics: Importance of socioeconomic distribution, histologic subtype, and anatomic location. AB - BACKGROUND: The incidence patterns and socioeconomic distribution of cutaneous melanoma among Hispanics are poorly understood. METHODS: The authors obtained population-based incidence data for all Hispanic and non-Hispanic white (NHW) patients who were diagnosed with invasive cutaneous melanoma from 1988 to 2007 in California. By using a neighborhood-level measure of socioeconomic status (SES), the variables investigated included incidence, thickness at diagnosis, histologic subtype, anatomic site, and the relative risk (RR) for thicker (>2 mm) versus thinner (<= 2 mm) tumors at diagnosis for groups categorized by SES. RESULTS: Age adjusted melanoma incidence rates per million were higher in NHWs (P < .0001), and tumor thickness at diagnosis was greater in Hispanics (P < .0001). Sixty-one percent of melanomas in NHWs occurred in the High SES group. Among Hispanics, only 35% occurred in the High SES group; and 22% occurred in the Low SES group. Lower SES was associated with thicker tumors (P < .0001); this association was stronger in Hispanics. The RR of thicker tumors versus thinner tumors (<= 2 mm) in the Low SES group versus the High SES group was 1.48 (95% confidence interval [CI], 1.37-1.61) for NHW men and 2.18 (95% CI, 1.73-2.74) for Hispanic men. Patients with lower SES had less of the superficial spreading melanoma subtype (especially among Hispanic men) and more of the nodular melanoma subtype. Leg/hip melanomas were associated with higher SES in NHW men but with lower SES in Hispanic men. CONCLUSIONS: The socioeconomic distribution of melanoma incidence and tumor thickness differed substantially between Hispanic and NHW Californians, particularly among men. Melanoma prevention efforts targeted to lower SES Hispanics and increased physician awareness of melanoma patterns among Hispanics are needed. PMID- 20737565 TI - Association of PAI-1 gene polymorphism with survival and chemotherapy-related vascular toxicity in testicular cancer. AB - BACKGROUND: High Plasminogen-Activator Inhibitor 1 (PAI-1) expression by tumors has been associated with poor prognosis in several cancer types, and high systemic PAI-1 levels with increased thrombosis risk. The authors investigated whether the germline 4G/5G deletion/insertion polymorphism in the PAI-1 promoter (rs1799889), which may influence PAI-1 expression, is associated with survival and chemotherapy-related vascular toxicity in testicular cancer (TC). METHODS: Data were collected on PAI-1 4G/5G polymorphism, survival, venous thromboembolism (VTE), and coronary heart disease (CHD) for 324 non-seminomatous TC patients treated with platinum-based chemotherapy. Genotypes were compared regarding survival and disease outcome. VTE and CHD incidence were compared with adjustment for cardiovascular risk factors and prothrombotic gene polymorphisms of coagulation factors II/prothrombin (G20210A) and V (G1691A). RESULTS: The 4G/4G variant of PAI-1 4G/5G polymorphism shows a higher prevalence of International Germ Cell Cancer Classification (IGCCC) poor prognosis compared with 4G/5G and 5G/5G (24% vs 8% and 15%; chi-square P = .003). In addition, the 4G/4G variant shows reduced TC-related survival with a hazard ratio of 2.69 (95% CI, 1.26-5.73; P = .010) for TC-related death (adjusted for IGCCC). This is related to an increased risk for refractory disease and early relapses (odds ratio, 3.35; 95% CI, 1.48-7.59; P = .004). PAI-1 4G/5G polymorphism is not associated with VTE and CHD risk. CONCLUSIONS: The 4G/4G variant of PAI-1 4G/5G polymorphism may be an unfavorable prognostic as well as predictive factor for response to chemotherapy in TC patients. If confirmed, it may contribute to the identification of patients with increased risk for refractory disease. PMID- 20737566 TI - Immunophenotype and intermediate-high international prognostic index score are prognostic factors for therapy in diffuse large B-cell lymphoma patients. AB - BACKGROUND: The development of gene expression profiling and tissue microarray techniques have provided more information about the heterogeneity of diffuse large B-cell lymphoma (DLBCL), enabling categorization of DLBCL patients into 3 prognostic groups according to cell origin (but independently from the International Prognostic Index [IPI] score): germinal center (GCB), activated B cell (ABC), and not classified (NC) diffuse large B-cell lymphoma. This study investigated the role of immunohistochemical discrimination between GCB and ABC&NC-DLBCL subtypes in identifying those high-risk patients who may benefit from a more aggressive first-line therapeutic approach. METHODS: From February 2003 to August 2006, 45 newly diagnosed DLBCL patients, with IPI>=2, were considered eligible for this study: 13 had a GCB, 8 an ABC, and 24 a NC-DLBCL. GCB patients received 6 courses of rituximab, cyclophophosphamide, doxorubicin, vinicristine, and prednisone (R-CHOP) chemotherapy, with a subsequent, autologous stem cell transplantation in case of partial response. All ABC and NC-DLBCL patients received 6 R-CHOP cycles and autologous stem cell transplantation. RESULTS: Complete response rate for each treatment arm was 84.6% for GCB and 89.7% for ABC&NC-DLBCL (P = .50), with a continuous complete response rate of 81.8% and 84.6%, respectively (P = .59). Projected 4-year overall survival is 100% for GCB and 82% for ABC&NC patients (P = .12). Progression-free survival is 77% and 79% (P = .7), respectively. CONCLUSIONS: The autologous stem cell transplantation consolidation in the ABC&NC-DLBCL subtypes induced the same rate of complete response (and similar progression-free survival rate) compared with GCB-DLBCL. In ABC&NC-DLBCL patients the authors observed a complete response rate of 89.7% vs. 84.6% in the GCB-DLBCL subset, without any significant difference in progression-free survival rate. PMID- 20737567 TI - Phase 1 clinical trials in 83 patients with pancreatic cancer: The M. D. Anderson Cancer Center experience. AB - BACKGROUND: The outcomes of patients with pancreatic cancer treated on early phase clinical trials have not been systematically analyzed. The purpose of this study was to report the presenting characteristics and outcomes of patients with locally advanced or metastatic pancreatic cancer treated on phase 1 clinical trials at a single institution. METHODS: The authors reviewed the records of consecutive patients with metastatic pancreatic cancer who were treated in the Phase I Clinical Trials Program at The University of Texas M. D. Anderson Cancer Center from November 2004 to March 2009. Data recorded and analyzed included survival, response, and disease characteristics. RESULTS: Eighty-three patients were identified. The median age was 62 years (range, 39-81 years). Of 78 patients evaluable for response, 2 (3%) had a partial response (PR), and 10 (13%) had stable disease (SD) for >= 4 months. With a median follow-up for survivors of 3.7 months, the median survival from presentation in the phase 1 clinic was 5.0 months (95% confidence interval [CI], 3.3-6.2). The median overall survival from diagnosis was 22.1 months (95% CI, 17.9-26.5). The median time to treatment failure was 1.5 months (95% CI, 1.3-1.8). Independent factors associated with lower rates of PR/SD were liver metastases (P = .001) and performance status >0 (P = .01). Independent factors associated with shorter survival were liver metastases (P = .007), low calcium level (P = .015), and elevated CEA level (>6 ng/mL) (P = .005). CONCLUSIONS: Our results suggest that phase 1 clinical trials offer a reasonable therapeutic approach for patients with advanced pancreatic cancer. PMID- 20737568 TI - Quality of surgical resection for nonsmall cell lung cancer in a US metropolitan area. AB - BACKGROUND: Curative treatment of early stage nonsmall cell lung cancer (NSCLC) requires good quality surgical resection (GQR). The degree of compliance with national recommendations for GQR is poorly defined. We sought to quantitatively define the degree of compliance in a consecutive series of NSCLC resections. METHODS: Medical records of patients who underwent curative-intent resection for NSCLC in the Memphis, TN metropolitan area from January 1, 2004 to December 31, 2007 were retrospectively reviewed (N = 746 patients). GQR criteria were obtained from the National Comprehensive Cancer Network (NCCN), the RADIANT adjuvant study of erlotinib, and the American College of Surgeons Oncology Group (ACOSOG) Z0030 study. Factors associated with or without achievement of GQR were evaluated. Categorical variables were compared using chi-square or Fisher exact test, and survival curves by the log-rank test. RESULTS: Twenty-three and one-half percent of patients met GQR criteria as established by RADIANT, 8.2% by NCCN, and 0.9% by ACOSOG. The most common limiting factor in achieving GQR was inadequate lymph node sampling. The only patient factor associated with GQR was race (African Americans were more likely than Caucasians to have GQR per RADIANT and NCCN criteria [P = .022 and P = .0489, respectively]). There was no significant survival difference between GQR and non-GQR patients. CONCLUSIONS: The vast majority of curative-intent resections did not achieve GQR standards. The greatest deficit is in surgical sampling of mediastinal (Level 2) lymph nodes, but evaluation of Level 1 lymph nodes is also suboptimal. Interventions are needed to improve current surgical practices and achieve minimum standards for accurate staging, prognostication, and eligibility for clinical trials. PMID- 20737569 TI - Evaluation of the seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification. AB - BACKGROUND: The seventh TNM staging system for gastric cancer of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) had a more detailed classification than the sixth TNM staging system for both the tumor (T) and lymph nodes (N). The authors compared survival rates assessed by the seventh staging system with those by the sixth system. METHODS: The authors analyzed the prospectively collected database on patients with gastric cancer who underwent surgery at Seoul National University Hospital between 1986 and 2006, and calculated the survival rates of 9998 cases with primary cancer, R0 resection, and >14 retrieved lymph nodes. RESULTS: The 5-year cumulative survival rates (5YSR) according to the seventh edition T or N classifications were significantly different. The 5YSR according to seventh edition of the TNM staging system were 95.1% (stage IA), 88.4% (stage IB), 84.0% (stage IIA), 71.7% (stage IIB), 58.4% (stage IIIA), 41.3% (stage IIIB), and 26.1% (stage IIIC), which were significantly different from each other. The 5YSR of the seventh edition T2 and T3 classifications had significant differences in patients with every N classification, and the 5YSR of seventh edition N1 and N2 classifications had significant differences in T2 patients, T3 patients, and T4 patients. Each stage in the sixth edition was divided into the seventh edition stage with different survival rates. In addition, the number of homogenous groupings in seventh edition TNM stages was increased from 1 to 2. CONCLUSIONS: The seventh system provided a more detailed classification of prognosis than the sixth system, especially between T2 and T3 tumors and N1 and N2 tumors, although further studies were found to be needed for the N3a and N3b classification. PMID- 20737570 TI - Genetic variants in one-carbon metabolism-related genes contribute to NSCLC prognosis in a Chinese population. AB - BACKGROUND: One-carbon metabolism plays a critical role in DNA methylation and DNA synthesis. Variants of genes involved in one-carbon metabolism may result in aberrant methylation and/or DNA synthesis inhibition, and ultimately modulate the initiation and progression of tumors. In this study, the authors hypothesized that polymorphisms in one-carbon metabolism-related genes may contribute to the prognosis of nonsmall cell lung cancer (NSCLC). METHODS: The authors screened 57 potentially functional single nucleotide polymorphisms (SNPs) from 11 candidate genes involved in one-carbon metabolism and genotyped them in a cohort of 568 NSCLC patients by using Illumina Golden Gate platform. The Kaplan-Meier method with log-rank test and Cox proportional hazards model were used for survival analyses. RESULTS: Variant alleles were significantly associated with favorable survivals of NSCLC for MTR rs3768160 A>G (allelic hazards ratio [HR], 0.78; 95% confidence interval [CI], 0.62-0.98), MTRR rs2966952 G>A (allelic HR, 0.84; 95% CI, 0.71-0.99) and DHFR rs1650697 G>A (allelic HR, 0.83; 95% CI, 0.70-0.99) and with unfavorable prognosis for MTHFD1 rs1950902 G>A with borderline significance (allelic HR, 1.18; 95% CI, 0.99-1.40). In addition, the combined genotypes of these four SNPs showed a locus-dosage effect on NSCLC survival (P(trend) = 6.9 * 10(-5) ). In the final multivariate Cox regression model, combined genotypes based on 3 categories may be an independent prognostic factor for NSCLC with adjusted trend HR of 0.78 (95% CI, 0.66-0.92). CONCLUSION: Genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis. PMID- 20737571 TI - Analysis of pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy and subsequent use of adjuvant radiation in a national cohort. AB - BACKGROUND: The Surveillance, Epidemiology, and End Results database was analyzed to explore the pathologic extent of disease for clinically localized prostate cancer after radical prostatectomy as well as the use of adjuvant radiation in this population. METHODS: Identified were patients from 2004 to 2006 with clinically staged T1c-2cNx-0M0 prostate adenocarcinoma who underwent radical prostatectomy. All patients had complete clinical and pathologic data. The use of postoperative radiation was recorded. Logistic regression analysis was performed to identify unadjusted and adjusted predictors for extraprostatic disease or positive surgical margins and for adjuvant radiation use. RESULTS: A total of 35,642 patients were identified. For those patients with Gleason 7 (4 + 3) and a prostate-specific antigen (PSA) level of >=10.1 ng/mL or Gleason 8 to 10 with any PSA level, the rate of organ-confined disease with negative surgical margins was found to be <50%. Of those with indications for adjuvant radiation, 11.1% received the treatment. CONCLUSIONS: This large population-based study detailed the risk of extraprostatic extension and positive surgical margins in a broad setting across multiple regions and communities, as well as the use of adjuvant radiation for these patients. As of 2006, 11.1% of patients who had indications for adjuvant radiation received this treatment, providing a useful baseline for future patterns of care studies. PMID- 20737572 TI - Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?: a Gynecologic Oncology Group ancillary data analysis. AB - BACKGROUND: This study evaluated whether progression-free interval (PFI) following primary chemotherapy (PCT) was predictive of overall survival (OS) after second-line chemotherapy in advanced/recurrent endometrial cancer (EC). METHODS: This is a pooled analysis of patients who recurred after PCT and were treated with second-line chemotherapy on Gynecologic Oncology Group trials. PFI-1 measured from initiation of PCT to recurrence or treatment-free interval (TFI) measured from completion of PCT to initiation of second-line chemotherapy was evaluated in relation to clinical outcomes. RESULTS: A total of 586 patients treated on 5 phase 3 PCT protocols were included. Baseline factors in primary setting associated with clinical outcome after PCT were also predictive of OS after second-line chemotherapy, including race, Gynecologic Oncology Group performance status, grade, and prior radiation therapy (P<.01). PFI-1 was the most significant factor predictive of survival after second-line chemotherapy, with a 30% reduction in the risk of death for PFI-1>6 months compared with <=6 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.59-0.84 [P<.0001]) and median OS after second-line chemotherapy of 10 versus 5 months. A total of 275 patients treated on 9 phase 2 second-line chemotherapy protocols were also evaluated, and TFI>3 months was associated with a 25% reduction in the risk of death (HR, 0.75; 95% CI, 0.57-0.97 [P=.030]) and median OS after second line chemotherapy of 10 versus 7 months compared with TFI<=3 months. The tumor response to second-line chemotherapy was 9.6% versus 5.8%; the difference was not statistically significant. CONCLUSIONS: Time to recurrence after PCT is predictive of survival after recurrence in advanced/recurrent EC. However, there is no evidence that this variable can be used in selecting salvage chemotherapy. PMID- 20737573 TI - Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. AB - BACKGROUND: Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival. METHODS: A retrospective, multicenter cohort study was performed in French-speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies. RESULTS: The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement. CONCLUSIONS: A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. PMID- 20737574 TI - Influence of abdominal adiposity, waist circumference, and body mass index on clinical and pathologic findings in patients treated with radiotherapy for localized prostate cancer. AB - BACKGROUND: Increased body mass index (BMI) has been associated with more aggressive prostate cancer (PC). The relation among abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), waist circumference (WC), and BMI was compared with clinical and pathologic findings in patients treated with radiotherapy for localized PC. METHODS: VAT, SAT, WC (all measured by planning abdominopelvic computed tomography scan) and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether obesity measures significantly predicted risk for secondary malignancies. RESULTS: Of 276 analyzed patients, 80 (29%) were obese (BMI >= 30 kg/m(2) ). Median BMI at baseline was 27.6 kg/m(2) (interquartile range [IQR], 25.1-30.5 kg/m(2) ). Increased SAT and VAT were associated with a higher National Comprehensive Cancer Network (NCCN) PC risk group (P = .0001 and .008, respectively). Greater SAT was associated with a higher Gleason score (GS) (P = .030). Younger age at diagnosis was significantly correlated with higher SAT and BMI, whereas increased prostate size was found in patients with higher BMI, WC, SAT, and VAT. At a median follow-up of 42.3 months (IQR, 32.3-59.9 months), 15 secondary malignancies were observed. On multivariate analysis, VAT was a significant predictor for secondary cancers (adjusted hazards ratio, 1.014; P = .0001). CONCLUSIONS: Measurements of greater abdominal adiposity were strongly associated with adverse pathologic features in patients with localized PC, including higher GS and NCCN PC risk groups. Moreover, VAT was found to be a strong risk factor for secondary malignancies. PMID- 20737575 TI - Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene. AB - BACKGROUND: Tumor suppressor microRNA miR-145 is commonly down-regulated in colon carcinoma tissues, but its specific role in tumors remains unknown. METHODS: In this study, the authors identified the Friend leukemia virus integration 1 gene (FLI1) as a novel target of miR-145. FLI1 is involved in t(11;22)(q24:q12) reciprocal chromosomal translocation in Ewing sarcoma, and its expression appears to be associated with biologically more aggressive tumors. RESULTS: The authors demonstrated that miR-145 targets a putative microRNA regulatory element in the 3'-untranslated region (UTR) of FLI1, and its abundance is reversely associated with FLI1 expression in colon cancer tissues and cell lines. By using a luciferase/FLI1 3'-UTR reporter system, they found that miR-145 down-regulated the reporter activity, and this down-regulation was reversed by anti-miR-145. Mutation of the miR-145 microRNA regulatory element sequence in the FLI1 3'-UTR abolished the activity of miR-145. miR-145 decreased FLI1 protein but not FLI1 mRNA, suggesting a mechanism of translational regulation. Furthermore, the authors demonstrated that miR-145 inhibited cell proliferation and sensitized LS174T cells to 5-fluorouracil-induced apoptosis. CONCLUSIONS: Taken together, these results suggest that miR-145 functions as a tumor suppressor by down regulating oncogenic FLI1 in colon cancer. PMID- 20737576 TI - Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration. AB - BACKGROUND: Results from salvage therapy in adult patients with acute lymphocytic leukemia (ALL) are wide-ranging and depend on several disease and patient characteristics. The objectives of this study were to define the prognosis for adult patients with ALL after first salvage through multivariate analyses of patient and disease characteristics. METHODS: Adults with ALL who had primary resistance to frontline therapy or who had a disease recurrence after a first complete response (CR) duration <1 year were analyzed. Multivariate analyses for subsequent CR and survival were conducted. RESULTS: Seventy-five of 245 patients (31%) achieved CR. The median CR duration was 5 months, the median survival was 4.7 months. In multivariate analysis, independent poor prognostic factors for not achieving CR were age >55 years, bone marrow blasts >=20%, and platelet count <75 * 10(9) /L. Variables that were associated independently with shorter survival were age >55 years, bone marrow blasts >=20%, platelet count <75 * 10(9) /L, albumin level <3 g/L, and lactic dehydrogenase level >=1000 IU/L. Patients who had >=3 of the 5 adverse factors (45%) had a median survival of 2 to 3 months and CR rates of 8% to 15%. Achieving CR was associated independently with improved survival in a landmark multivariate analysis (P < .0001; hazard ratio, 0.40; 95% confidence interval, 0.03-0.72). CONCLUSIONS: The current analyses identified a subset of adults patients ALL in first salvage for whom standard therapies were associated with an extremely poor outcome. The results also confirmed the importance of achieving CR to attain improved survival. PMID- 20737577 TI - A role for regulatory T cells in acceptance of ESC-derived tissues transplanted across an major histocompatibility complex barrier. AB - We have previously reported that ESC-derived tissues are subject to some level of immune privilege, which might facilitate induction of immune tolerance. Herein, we further demonstrate that fully allogeneic ESC-derived tissues are accepted with a regimen of coreceptor blockade even in recipients known to be relatively resistant to such a tolerizing protocol. Moreover, ESC-derived tissues could be spontaneously accepted across a class I major histocompatibility complex disparity. We further show that CD4(+)FoxP3(+) regulatory T cells (Treg) appear to be essential for this natural "privileged" state as their ablation with an anti-CD25 mAb results in rejection of ESC-derived tissue. This same treatment exposes activation of macrophages and effector CD8(+) T cells, suggesting that these cells are subject to regulatory T cell control. Thus, spontaneous acceptance of ESC-derived tissues mimics the acquired immune privilege induced by coreceptor blockade and is determined by Treg-mediated suppression. PMID- 20737578 TI - Autocatalytic maturation, physical/chemical properties, and crystal structure of group N HIV-1 protease: relevance to drug resistance. AB - The mature protease from Group N human immunodeficiency virus Type 1 (HIV-1) (PR1(N)) differs in 20 amino acids from the extensively studied Group M protease (PR1(M)) at positions corresponding to minor drug-resistance mutations (DRMs). The first crystal structure (1.09 A resolution) of PR1(N) with the clinical inhibitor darunavir (DRV) reveals the same overall structure as PR1(M), but with a slightly larger inhibitor-binding cavity. Changes in the 10s loop and the flap hinge propagate to shift one flap away from the inhibitor, whereas L89F and substitutions in the 60s loop perturb inhibitor-binding residues 29-32. However, kinetic parameters of PR1(N) closely resemble those of PR1(M), and calorimetric results are consistent with similar binding affinities for DRV and two other clinical PIs, suggesting that minor DRMs coevolve to compensate for the detrimental effects of drug-specific major DRMs. A miniprecursor (TFR 1-61 PR1(N)) comprising the transframe region (TFR) fused to the N-terminus of PR1(N) undergoes autocatalytic cleavage at the TFR/PR1(N) site concomitant with the appearance of catalytic activity characteristic of the dimeric, mature enzyme. This cleavage is inhibited at an equimolar ratio of precursor to DRV (~6 MUM), which partially stabilizes the precursor dimer from a monomer. However, cleavage at L34/W35 within the TFR, which precedes the TFR 1-61/PR1(N) cleavage at pH <= 5, is only partially inhibited. Favorable properties of PR1(N) relative to PR1(M) include its suitability for column fractionation by size under native conditions and >10-fold higher dimer dissociation constant (150 nM). Exploiting these properties may facilitate testing of potential dimerization inhibitors that perturb early precursor processing steps. PMID- 20737580 TI - Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice. AB - Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60-day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL 1beta), and interleukin-6 (IL-6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations >= 1 mg PFOS/kg TAD in a dose-dependent manner. Ex vivo IL-1beta production by peritoneal macrophages was elevated substantially at concentrations of >= 5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF-alpha, IL 1beta and IL-6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-6, and proto-oncogene, c myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action. PMID- 20737579 TI - The apicomplexan Cryptosporidium parvum possesses a single mitochondrial-type ferredoxin and ferredoxin:NADP+ reductase system. AB - We have successfully expressed recombinant mitochondrial-type ferredoxin (mtFd) and ferredoxin:NADP(+) reductase (mtFNR) from Cryptosporidium parvum and characterized their biochemical features for the first time for an apicomplexan. Both C. parvum mtFd (CpmtFd) and FNR (CpmtFNR) were obtained and purified as holo proteins, in which the correct assembly of [2Fe-2S] cluster in Fd and that of FAD in FNR were confirmed and characterized by UV/vis and electron paramagnetic resonance. These proteins were fully functional and CpmtFNR was capable of transferring electrons from NADPH to CpmtFd in a cytochrome c-coupled assay that followed a typical Michaelis-Menten kinetics. Apicomplexan mtFd and mtFNR proteins were evolutionarily divergent from their counterparts in humans and animals and could be explored as potential drug targets in Cryptosporidium and other apicomplexans. PMID- 20737581 TI - Upconversion: road to El Dorado of the fluorescence world. AB - Upconversion nanoparticles (UCNs), in the recent times have attracted attention due to their unique properties, which makes them ideal fluorophores for use in biological applications. There have been various reports on their use for targeted cell imaging, drug and gene delivery and also for diffuse optical tomography. Here we give a brief introduction on what are UCNs and the mechanism of upconversion, followed by a discussion on the biological applications of UCNs and further on what the future holds for UCNs. PMID- 20737582 TI - Environmental nitration processes enhance the mutagenic potency of aromatic compounds. AB - This work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2-Nitrophenol (2 NP), 2,4-Dinitrophenol (2,4-DNP), Pyrene (Py), 1-Nitropyrene (1-NPy), 1,3 Dinitropyrene (1,3-DNPy), 1,6-Dinitropyrene (1,6-DNPy), and 1,8-Dinitropyrene (1,8-DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1-NPy and 1,8-DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1-NPy and 1,8-DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. (c) 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012. PMID- 20737585 TI - Does stem preheating have a beneficial effect on PMMA bulk porosity in cemented THA? AB - In cemented total hip arthroplasty (THA), porosity plays a major role in the fatigue failure of bone cement. Stem preheating procedure is known to reduce the stem/cement interfacial porosity. In the literature, no information is available about the effect of such procedure on cement bulk porosity. This study helps to find out if stem preheating can have a beneficial effect on bulk porosity, thus enhancing long-term bone cement integrity. A simplified experimental model of a stem/cement/bone construct of a cemented THA is designed to reproduce the mechanical boundary conditions of polymerizing cement. Effect of stem preheating and polymethylmethacrylate prechilling and mixing method (hand mixed and vacuum mixed) on cement porosity are investigated. Bulk porosity is analysed within three zones across the cement mantle in terms of pore number, pore area, and mean pore size. The results demonstrate that bulk cement porosity is strongly influenced by stem preheating, cement precooling as well as cement composition and mixing method. Stem preheating procedure displaces the porosity away from stem/cement interface toward bone; consequently reducing the pore area within the zone near the stem and increasing it in the middle and bone/cement zone. The most pronounced beneficial effect of stem preheating before implantation is visible for vacuum mixed procedure as the cement contains few pores of very small size (<100 MUm). However, if stem is preheated, cement precooling should be avoided as it could counteract the beneficial effect of reduced porosity inside cement mantle. PMID- 20737584 TI - Dipyridamole versus verapamil for treatment of no-reflow during primary angioplasty. AB - BACKGROUND: No previous study has assessed the possible role of dipyridamole for treatment of no-reflow during acute myocardial infarction (AMI). METHODS AND RESULTS: Forty-six consecutive patients (age 64 +/- 13 years, 37 men) with no reflow during primary percutaneous coronary intervention were randomized to initial treatment with either dipyridamole (0.56 mg/kg i.c.) or verapamil (1 mg i.c.). Patients with unsuccessful response to the first drug were then switched to the second one (from dipyridamole to verapamil and vice versa). Angiographic end-points were similar in the two groups: TIMI flow was 2.9 +/- 0.3 versus 2.8 +/- 0.4 (P = 0.28), corrected TIMI frame count (cTFC) 26.4 +/- 8.8 versus 31.6 +/ 11.4 (P = 0.14) and TIMI myocardial perfusion grade (TMPG) 2.1 +/- 1.2 versus 1.7 +/- 1.2 (P = 0.12) in dipydidamole and verapamil group, respectively. Optimal myocardial perfusion (TMPG-3) was achieved by 56% of patients with dipyridamole and 39% with verapamil (P = 0.38). In patients with persistent no-reflow administration of dipyridamole on top of verapamil resulted in a significant further improvement of cTFC (from 31.6 +/- 11.4 to 24.6 +/- 5.7 P = 0.009) and of TMPG (from 1.7 +/- 1.2 to 2.6 +/- 0.7, P = 0.007). Conversely, verapamil did not induce a significant improvement in coronary flow (cTFC changed from 26.4 +/- 8.8 to 24.5 +/- 8.5, P = 0.28 and TMPG from 2.1 +/- 1.2 to 2.4 +/- 1.2, P = 0.13). There were no significant side effects induced by dipyridamole, while verapamil caused AV block in 9% of cases. CONCLUSIONS: Dipyridamole is a safe and effective first-line drug for treatment of no-reflow. Dipyridamole can also be successfully used in patients with incomplete response to verapamil. PMID- 20737587 TI - Ricky. PMID- 20737586 TI - Human bone marrow-derived stromal cells cultured with a plasma sprayed CaO-ZrO2 SiO2 coating. AB - The CaO-ZrO2-SiO2 (CZS) coating was prepared by plasma-spraying chemically synthesized CZS powder onto a Ti-6Al-4V substrate. This CZS coating has been demonstrated to have good bioactivity, high bonding strength with the substrate and a low degradation rate. However, the effect of CZS coating on the osseointegration of bone-implant is still unknown. In this study, human bone marrow-derived stromal cells (hBMSCs) were cultured on CZS coating in vitro, and cell behavior was investigated, with the classical hydroxyapatite (HA) coating as a control. Scanning electron microscopy (SEM) and immunofluorescence studies showed that the hBMSCs on the CZS coating spread well with organized cytoskeleton structure at 24 h following cell seeding. The MTT assay and the Alamar Blue assay indicated that CZS coating promoted the attachment and proliferation of hBMSCs. The results of alkaline phosphatase (ALP) activity test and the expression of osteogenic marker genes, such as ALP, collagen I (COLI), osteopontin (OPN), and osteocalcin (OCN), demonstrated that the osteoblastic differentiation of hBMSCs was enhanced more by CZS coating than by HA coating. These results suggest that CZS coating possess excellent biological properties and may have potential in biomedical applications. PMID- 20737588 TI - Studying submicrosecond protein folding kinetics using a photolabile caging strategy and time-resolved photoacoustic calorimetry. AB - Kinetic measurement of protein folding is limited by the method used to trigger folding. Traditional methods, such as stopped flow, have a long mixing dead time and cannot be used to monitor fast folding processes. Here, we report a compound, 4-(bromomethyl)-6,7-dimethoxycoumarin, that can be used as a "photolabile cage" to study the early stages of protein folding. The folding process of a protein, RD1, including kinetics, enthalpy, and volume change, was studied by the combined use of a phototriggered caging strategy and time-resolved photoacoustic calorimetry. The cage caused unfolding of the photolabile protein, and then a pulse UV laser (~10(-9) s) was used to break the cage, leaving the protein free to refold and allowing the resolving of two folding events on a nanosecond time scale. This strategy is especially good for monitoring fast folding proteins that cannot be studied by traditional methods. PMID- 20737589 TI - Testicular Leydig cell tumor diagnosed on fine needle aspiration. AB - We report on the cytopathologic findings of a Leydig cell tumor of the testis in an adult male with no evidence of endocrine dysfunction. The preoperative diagnosis was based on fine needle aspiration cytology (FNAC) and was subsequently confirmed on histomorphology. The cytologic smears were cellular and showed tumor cells arranged singly, as well as in dyscohesive clusters. The tumor cells were large, round to polygonal, with indistinct cytoplasmic margins and pale, abundant, granular to vacuolated cytoplasm. A few intranuclear Reinke's crystals that are considered pathognomonic and essential for the diagnosis were seen. The present case was of interest because of the scarcity of literature on the cytodiagnosis of this tumor. The use of FNAC for diagnosis may vitiate the need for more invasive biopsy procedures in the preoperative diagnosis of this rare testicular tumor. PMID- 20737592 TI - Complete mapping of glomeruli based on sensory nerve branching pattern in the primary olfactory center of the cockroach Periplaneta americana. AB - Glomeruli are structural and functional units in the primary olfactory center in vertebrates and insects. In the cockroach Periplaneta americana, axons of different types of sensory neurons housed in sensilla on antennae form dorsal and ventral antennal nerves and then project to a number of glomeruli. In this study, we identified all antennal lobe (AL) glomeruli based on detailed innervation patterns of sensory tracts in addition to the shape, size, and locations in the cockroach. The number of glomeruli is approximately 205, and no sex-specific difference is observed. Anterograde dye injections into the antennal nerves revealed that axons supplying the AL are divided into 10 sensory tracts (T1-T10). Each of T1-T3 innervates small, oval glomeruli in the anteroventral region of the AL, with sensory afferents invading each glomerulus from multiple directions, whereas each of T4-T10 innervates large glomeruli with various shapes in the posterodorsal region, with a bundle of sensory afferents invading each glomerulus from one direction. The topographic branching patterns of all these tracts are conserved among individuals. Sensory afferents in a sub-tract of T10 had axon terminals in the dorsal margin of the AL and the protocerebrum, where they form numerous small glomerular structures. Sensory nerve branching pattern should reflect developmental processes to determine spatial arrangement of glomeruli, and thus the complete map of glomeruli based on sensory nerve branching pattern should provide a basis for studying the functional significance of spatial arrangement of glomeruli and its developmental basis. PMID- 20737591 TI - Central respiratory chemoreception. AB - By definition central respiratory chemoreceptors (CRCs) are cells that are sensitive to changes in brain PCO(2) or pH and contribute to the stimulation of breathing elicited by hypercapnia or metabolic acidosis. CO(2) most likely works by lowering pH. The pertinent proton receptors have not been identified and may be ion channels. CRCs are probably neurons but may also include acid-sensitive glia and vascular cells that communicate with neurons via paracrine mechanisms. Retrotrapezoid nucleus (RTN) neurons are the most completely characterized CRCs. Their high sensitivity to CO(2) in vivo presumably relies on their intrinsic acid sensitivity, excitatory inputs from the carotid bodies and brain regions such as raphe and hypothalamus, and facilitating influences from neighboring astrocytes. RTN neurons are necessary for the respiratory network to respond to CO(2) during the perinatal period and under anesthesia. In conscious adults, RTN neurons contribute to an unknown degree to the pH-dependent regulation of breathing rate, inspiratory, and expiratory activity. The abnormal prenatal development of RTN neurons probably contributes to the congenital central hypoventilation syndrome. Other CRCs presumably exist, but the supportive evidence is less complete. The proposed locations of these CRCs are the medullary raphe, the nucleus tractus solitarius, the ventrolateral medulla, the fastigial nucleus, and the hypothalamus. Several wake-promoting systems (serotonergic and catecholaminergic neurons, orexinergic neurons) are also putative CRCs. Their contribution to central respiratory chemoreception may be behavior dependent or vary according to the state of vigilance. PMID- 20737593 TI - Progranulin expression in the developing and adult murine brain. AB - Frontotemporal lobar degeneration (FTLD) is a neurodegenerative condition characterized by focal degeneration of the frontal and temporal lobes of the brain. Autosomal dominantly inherited mutations of the progranulin gene (GRN) have been identified as the cause of a subset of cases of familial FTLD. In order to better understand the function of progranulin in the central nervous system (CNS), we have assessed the spatiotemporal expression pattern of both the murine progranulin gene (Grn) and the protein (Grn) by using transgenic knock-in mice expressing a reporter gene from the Grn locus and by immunohistochemistry, respectively. We compared Grn expression with a panel of established markers for distinct neuronal developmental stages and specific cell lineages at time points ranging from embryonic day 13.5 through to the mature adult. We find that Grn is expressed in both neurons and microglia within the CNS, but that it shows a different developmental expression pattern in each cell type. Grn expression in neurons increases as the cells mature, whereas expression in microglia varies with the cells' state of activation, being specifically upregulated in microglia in response to excitotoxic injury. Our results suggest that progranulin plays distinct roles in neurons and microglia, both of which likely contribute to overall neuronal health and function. PMID- 20737594 TI - Distribution of hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons in the hypothalamic paraventricular nucleus of the mouse. AB - Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons, the central regulators of the hypothalamic-pituitary-thyroid axis, are located in the hypothalamic paraventricular nucleus (PVN) in a partly overlapping distribution with non-hypophysiotropic TRH neurons. The distribution of hypophysiotropic TRH neurons in the rat PVN is well understood, but the localization of these neurons is unknown in mice. To determine the distribution and phenotype of hypophysiotropic TRH neurons in mice, double- and triple-labeling experiments were performed on sections of intact mice, and mice treated intravenously and intraperitoneally with the retrograde tracer Fluoro-Gold. TRH neurons were located in all parts of the PVN except the periventricular zone. Hypophysiotropic TRH neurons were observed only at the mid-level of the PVN, primarily in the compact part. In this part of the PVN, TRH neurons were intermingled with oxytocin and vasopressin neurons, but based on their size, the TRH neurons were parvocellular and did not contain magnocellular neuropeptides. Co-localization of TRH and cocaine- and amphetamine-regulated transcript (CART) were observed only in areas where hypophysiotropic TRH neurons were located. In accordance with the morphological observations, hypothyroidism increased TRH mRNA content of neurons only at the mid-level of the PVN. These data demonstrate that the distribution of hypophysiotropic TRH neurons in mice is vastly different from the pattern in rats, with a dominant occurrence of these neurosecretory cells in the compact part and adjacent regions at the mid-level of the PVN. Furthermore, our data demonstrate that the organization of the PVN is markedly different in mice and rats. PMID- 20737595 TI - How the primate fornix is affected by age. AB - The effects of age on nerve fibers and neuroglial cells in the fornix were examined in 25 rhesus monkeys between 4 and 33 years of age. There is no age related change in the cross-sectional area of the fornix, but there is a significant loss of myelinated nerve fibers. The loss of myelinated nerve fibers is accompanied by a significant increase in the numbers of nerve fibers that show degeneration of their axons and alterations in myelin sheaths. Aging also brings about an increase in the frequency of profiles of paranodes, indicating that some of the nerve fibers are being remyelinated. Aging also affects neuroglial cells. Each type shows inclusions in their perikarya, and in the case of astrocytes and microglial cells some of these inclusions are phagocytosed myelin. Numbers of astrocytes and microglial cells do not appear to increase with age, but there is a 20% increase in oligodendrocytes. When correlations with cognitive impairments displayed by individual monkeys are examined, the decreased packing density of nerve fibers and the increasing frequency of nerve fibers with degenerating axons and of nerve fibers with altered myelin sheaths all correlate with increasing cognitive impairment. It is suggested that these correlations result from some disconnection of the hippocampus from the thalamus, septal nuclei, and medial frontal cortex and from reductions in the conduction velocity brought about by the shorter internodal lengths of remyelinated nerve fibers in the fornix. PMID- 20737596 TI - Neuronal DNA content variation (DCV) with regional and individual differences in the human brain. AB - It is widely assumed that the human brain contains genetically identical cells through which postgenomic mechanisms contribute to its enormous diversity and complexity. The relatively recent identification of neural cells throughout the neuraxis showing somatically generated mosaic aneuploidy indicates that the vertebrate brain can be genomically heterogeneous (Rehen et al. [2001] Proc. Natl. Acad. Sci. U. S. A. 98:13361-13366; Rehen et al. [2005] J. Neurosci. 25:2176-2180; Yurov et al. [2007] PLoS ONE:e558; Westra et al. [2008] J. Comp. Neurol. 507:1944-1951). The extent of human neural aneuploidy is currently unknown because of technically limited sample sizes, but is reported to be small (Iourov et al. [2006] Int. Rev. Cytol. 249:143-191). During efforts to interrogate larger cell populations by using DNA content analyses, a surprising result was obtained: human frontal cortex brain cells were found to display "DNA content variation (DCV)" characterized by an increased range of DNA content both in cell populations and within single cells. On average, DNA content increased by approximately 250 megabases, often representing a substantial fraction of cells within a given sample. DCV within individual human brains showed regional variation, with increased prevalence in the frontal cortex and less variation in the cerebellum. Further, DCV varied between individual brains. These results identify DCV as a new feature of the human brain, encompassing and further extending genomic alterations produced by aneuploidy, which may contribute to neural diversity in normal and pathophysiological states, altered functions of normal and disease-linked genes, and differences among individuals. PMID- 20737597 TI - Retinal photoreceptors of two subterranean tuco-tuco species (Rodentia, Ctenomys): morphology, topography, and spectral sensitivity. AB - Traditionally, vision was thought to be useless for animals living in dark underground habitats, but recent studies in a range of subterranean rodent species have shown a large diversity of eye features, from small subcutaneous eyes to normal-sized functional eyes. We analyzed the retinal photoreceptors in the subterranean hystricomorph rodents Ctenomys talarum and Ctenomys magellanicus to elucidate whether adaptation was to their near-lightless burrows or rather to their occasional diurnal surface activity. Both species had normally developed eyes. Overall photoreceptor densities were comparatively low (95,000 150,000/mm(2) in C. magellanicus, 110,000-200,000/mm(2) in C. talarum), and cone proportions were rather high (10-31% and 14-31%, respectively). The majority of cones expressed the middle-to-longwave-sensitive (L) opsin, and a 6-16% minority expressed the shortwave-sensitive (S) opsin. In both species the densities of L and S cones were higher in ventral than in dorsal retina. In both species the tuning-relevant amino acids of the S opsin indicate sensitivity in the near UV rather than the blue/violet range. Photopic spectral electroretinograms were recorded. Unexpectedly, their sensitivity profiles were best fitted by the linear summation of three visual pigment templates with lambda(max) at 370 nm (S pigment, UV), at 510 nm (L pigment), and at 450 nm (an as-yet unexplained mechanism). Avoiding predators and selecting food during the brief aboveground excursions may have exerted pressure to retain robust cone-based vision in Ctenomys. UV tuning of the S cone pigment is shared with a number of other hystricomorphs. PMID- 20737598 TI - Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain. AB - Relaxin-3 (RLN3) and its native receptor, relaxin family peptide 3 receptor (RXFP3), constitute a newly identified neuropeptide system enriched in mammalian brain. The distribution of RLN3/RXFP3 networks in rat brain and recent experimental studies suggest a role for this system in modulation of arousal, stress, metabolism, and cognition. In order to facilitate exploration of the biology of RLN3/RXFP3 in complementary murine models, this study mapped the neuroanatomical distribution of the RLN3/RXFP3 system in mouse brain. Adult, male wildtype and RLN3 knock-out (KO)/LacZ knock-in (KI) mice were used to map the central distribution of RLN3 gene expression and RLN3-like immunoreactivity ( LI). The distribution of RXFP3 mRNA and protein was determined using [(35)S] oligonucleotide probes and a radiolabeled RXFP3-selective agonist ([(125)I] R3/I5), respectively. High densities of neurons expressing RLN3 mRNA, RLN3 associated beta-galactosidase activity and RLN3-LI were detected in the nucleus incertus (or nucleus O), while smaller populations of positive neurons were observed in the pontine raphe, the periaqueductal gray and a region adjacent to the lateral substantia nigra. RLN3-LI was observed in nerve fibers/terminals in nucleus incertus and broadly throughout the pons, midbrain, hypothalamus, thalamus, septum, hippocampus, and neocortex, but was absent in RLN3 KO/LacZ KI mice. This RLN3 neural network overlapped the regional distribution of RXFP3 mRNA and [(125)I]-R3/I5 binding sites in wildtype and RLN3 KO/LacZ KI mice. These findings provide further evidence for the conserved nature of RLN3/RXFP3 systems in mammalian brain and the ability of RLN3/RXFP3 signaling to modulate "behavioral state" and an array of circuits involved in arousal, stress responses, affective state, and cognition. PMID- 20737599 TI - Sympathetic innervation of the ileocecal junction in horses. AB - The distribution and chemical phenotypes of sympathetic and dorsal root ganglion (DRG) neurons innervating the equine ileocecal junction (ICJ) were studied by combining retrograde tracing and immunohistochemistry. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) was investigated. Sympathetic neurons projecting to the ICJ were distributed within the celiac (CG), cranial mesenteric (CranMG), and caudal mesenteric (CaudMG) ganglia, as well as in the last ganglia of the thoracic sympathetic chain and in the splanchnic ganglia. In the CG and CranMG 91 +/- 8% and 93 +/- 12% of the neurons innervating the ICJ expressed TH- and DBH-IR, respectively. In the CaudMG 90 +/- 15% and 94 +/- 5% of ICJ innervating neurons were TH- and DBH-IR, respectively. Sympathetic (TH-IR) fibers innervated the myenteric and submucosal ganglia, ileal blood vessels, and the muscle layers. They were more concentrated at the ICJ level and were also seen encircling myenteric plexus (MP) and submucosal plexus (SMP) descending neurons that were retrogradely labeled from the ICJ. Among the few retrogradely labeled DRG neurons, nNOS-, CGRP-, and SP-IR nerve cells were observed. Dense networks of CGRP-, nNOS-, and SP-IR varicosities were seen around retrogradely labeled prevertebral ganglia neurons. The CGRP-IR fibers are probably the endings of neurons projecting from the intestine to the prevertebral ganglia. These findings indicate that this crucial region of the intestinal tract is strongly influenced by the sympathetic system and that sensory information of visceral origin influences the sympathetic control of the ICJ. PMID- 20737600 TI - Expression of neuronal markers, synaptic proteins, and glutamine synthetase in the control and regenerating lizard visual system. AB - Spontaneous regrowth of retinal ganglion cell (RGC) axons occurs after optic nerve (ON) transection in the lizard Gallotia galloti. To gain more insight into this event we performed an immunohistochemical study on selected neuron and glial markers, which proved useful for analyzing the axonal regrowth process in different regeneration models. In the control lizards, RGCs were beta-III tubulin (Tuj1) and HuCD-positive. The vesicular glutamate transporter-1 (VGLUT1) preferentially stained RGCs and glial somata rather than synaptic layers. In contrast, SV2 and vesicular GABA/glycine transporter (VGAT) labeling was restricted to both plexiform layers. Strikingly, the strong expression of glutamine synthetase (GS) in both Muller glia processes and macroglial somata revealed a high glutamate metabolism along the visual system. Upregulation of Tuj1 and HuCD in the surviving RGCs was observed at all the timepoints studied (1, 3, 6, 9, and 12 months postlesion). The significant rise of Tuj1 in the optic nerve head and optic tract (OTr) by 1 and 6 months postlesion, respectively, suggests an increase of the beta-III tubulin transport and incorporation into newly formed axons. Persistent Tuj1(+) and SV2(+) puncta and swellings were abnormally observed in putative degenerating/dystrophic fibers. Unexpectedly, neuron-like cells of obscure significance were identified in the control and regenerating ON-OTr. We conclude that: 1) the persistent upregulation of Tuj1 and HuCD favors the long-lasting axonal regrowth process; 2) the latter succeeded despite the ectopia and dystrophy of some regrowing fibers; and 3) maintenance of the glutamate-glutamine cycle contributes to the homeostasis and plasticity of the system. PMID- 20737602 TI - Molecular characterization of sickle cell anemia in the Northern Brazilian state of Para. AB - To assess alpha+-thalassemia deletion alleles, beta-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belem, Para State, for their possible effects on the patients' survival. -alpha(3.7), -alpha(42), -alpha(20.5), and (MED) alpha+-thalassemia deletion alleles were investigated using multiplex gap PCR method. Characterization of beta-thalassemia mutations was made by direct genomic sequencing of the beta-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5'gammaG, (2) HindIII-gammaG, (3) HindIII-gammaA, (4) HincII-psibeta, (5) HincII-3'psibeta, and (6) HinfI-5'beta] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -alpha3.7 thalassemia. Sixteen of those (76%) were heterozygous ( alpha3.7/alphaalpha) and 5 (24%) were homozygous (-alpha3.7/-alpha3.7). Alpha(4.2), -alpha(20.5) and -(MED) deletions were not found. Nine cases of sickle cell-beta thalassemia were found and four different beta-thal mutations were identified: beta(+) -88 (C>T), 3.8%; beta(+) codon 24 (T > A), 1.5%; beta(+) IVSI-110 (G > A), 0.7% and beta (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -alpha(3.7) deletion, beta-thalassemia and HHB*S haplotypes distribution. Our results suggest that although alpha- and beta thalassemia and betaS haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival. PMID- 20737603 TI - Socioeconomic status, education, and reproduction in modern women: an evolutionary perspective. AB - Although associations between status or resources and reproduction are positive in premodern societies and also in men in modern societies, in modern women the associations are typically negative. We investigated how the association between socioeconomic status and reproductive output varies with the source of status and resources, the woman's education, and her age at reproductive onset (proxied by age at marriage). By using a large sample of US women, we examined the association between a woman's reproductive output and her own and her husband's income and education. Education, income, and age at marriage are negatively associated with a woman's number of children and increase her chances of childlessness. Among the most highly educated two-thirds of the sample of women, husband's income predicts the number of children. The association between a woman's number of children and her husband's income turns from positive to negative when her education and age at marriage is low (even though her mean offspring number rises at the same time). The association between a woman's own income and her number of children is negative, regardless of education. Rather than maximizing the offspring number, these modern women seem to adjust investment in children based on their family size and resource availability. Striving for resources seems to be part of a modern female reproductive strategy- but, owing to costs of resource acquisition, especially higher education, it may lead to lower birthrates: a possible evolutionary explanation of the demographic transition, and a complement to the human capital theory of net reproductive output. PMID- 20737604 TI - Genetic characterization of uniparental lineages in populations from Southwest Iberia with past malaria endemicity. AB - Malaria endemicity in Southwest Iberia afforded conditions for an increase of sickle cell disease (SCD), which in the region follows a clinal pattern toward the south, where foci of high prevalence were found. SCD distribution is associated with specific geographical areas, and therefore, its introduction into Iberia may be related to the migration of different populations. We have analyzed the variation of uniparental markers in Portuguese populations with high frequency of SCD--Coruche, Pias, and Alcacer do Sal--to evaluate if their present day pattern of neutral diversity could provide evidence about people inhabiting the area over different time periods. Two hundred and eighty-five individuals were sampled in Coruche, Pias, and Alcacer do Sal. All were analyzed for the control region of mitochondrial DNA (mtDNA); males were additionally examined for Y-chromosome markers. Results were then compared with data from other Portuguese and non-Portuguese populations. In Coruche, the genetic profile was similar to the profile usually found in Portugal. In Alcacer do Sal, the frequency of sub Saharan mtDNA L lineages was the highest ever reported (22%) in Europe. In Pias, mtDNA diversity revealed higher frequencies of Mediterranean haplogroups I, J, and T than usually found in surrounding populations. The presence of Sub-Saharan maternal lineages in Alcacer do Sal is likely associated with the influx of African slaves between the 15th and 19th centuries, whereas in Pias, the Mediterranean influence might be traced to ancient contacts with Greeks, Phoenicians, and Carthaginians, who established important trading networks in southern Iberia. PMID- 20737605 TI - Lumbar ontogenetic growth and sexual dimorphism in modern humans. AB - To detect and differentiate between possible heterochronic processes in the ontogenetic growth pattern of the human lumbar region, in relationship with sexual dimorphism. We measured the growth trajectories of average length and width, length/width ratio, posterior projected surface area, and bone mineral density using dual energy X-ray absorptiometry, in a sample group of 1718 modern humans. These growth patterns were analyzed using the Gompertz model. In adult lumbar region, only surface area and width were significantly higher in men. Regarding the ontogenetic growth pattern leading to the dimorphic states, all values obtained for women were significantly higher than those obtained for men. Maximum initial growth rates occurred for surface area and density in women. Width scaled faster than length in both sexes. The lumbar region followed patterns similar to those of other skeletal elements when compared with a previous classification of growth patterns in the human skeleton; however, in this study, the growth rate was slower. With regard to the effect of dimorphism, sexual differences in growth rate accounted for only a small proportion of the variation in lumbar length, mineral density, and surface area. Nevertheless, these sexual differences played an important role in the increase of the length/width ratio, which was reflected in the ages at which sexual dimorphism developed. The sexual dimorphism found in the lumbar region of human adults is not caused by any heterochronic process. The lower values of bone mineral density in adult women could explain the origin of some pathologies related. PMID- 20737606 TI - Digit ratio (2D:4D), sex differences, allometry, and finger length of 12-30-year olds: evidence from the British Broadcasting Corporation (BBC) Internet study. AB - Many studies have reported digit ratio (2D:4D) to be sexually dimorphic, (males lower 2D:4D than females). However, Kratochvil and Flegr ([2009]: Biol Lett 5:643 646) have suggested that 2D regressed on 4D has an allometric regression line with nonzero Y-intercept that is shared by males and females. Thus, 2D is shorter than expected when 4D is long, and males have lower 2D:4D than females because they have longer fingers. In this study, it is shown that this suggestion may be incorrect because sex differences in slope were not considered. Participants were recruited in an Internet study and had an age range of 12-30 years. The expected sex difference in 2D:4D was found, and the regression of 2D on 4D showed a significant sex difference in slope (males lower than females). A comparison of 10 age groups (12 years, 13 years..., 21-30 years) showed that sexual dimorphism for fingers was age dependent, varying from monomorphic to very dimorphic. Changes in sexual dimorphism of 2D:4D were much less marked, but there was a significant reduction in mean 2D:4D with age. The tendency for slopes of 2D regressed on 4D to be lower in males compared with females was significant in eight age groups. Sex difference in 2D:4D varied across the age groups and was positively related to the magnitude of the difference in female and male slopes. In contrast to the report of Kratochvil and Flegr, it was found that the regression of 2D on 4D showed sex differences in slope, and such differences gave rise to the sexual dimorphism in 2D:4D. PMID- 20737607 TI - Relationships between adiponectin, leptin, and blood lipids in physically active postmenopausal females. AB - The aim of this study was to investigate the possible relationships between adiponectin and leptin with blood lipids (CHOL, HDL-C, LDL-C, and TG) in physically active postmenopausal women. One hundred and thirty-four physically active practicing gymnastics (2-3 times per week) women between the ages of 51 to 85 years participated in this cross-sectional study. Body height, body mass, waist-to-hip circumference ratio (WHR), and BMI were used as anthropometrical parameters. Body composition parameters (fat%, fat mass, fat free mass) were measured by DXA. The fasting adiponectin, leptin, CHOL, HDL-C, LDL-C, and TG were measured. From the anthropometrical and body composition parameters, only WHR correlated significantly with adiponectin (r = -0.306). In addition, adiponectin correlated with TG (r = -0.277) and leptin (r = -0.381). Leptin was positively related to body mass (r = 0.261), and BMI (r = 0.274) from anthropometrical parameters and body fat% (r = 0.288) and fat mass (r = 0.298) from body composition variables. No relationships emerged between leptin and blood lipids. We found that there are some significant relationships between adiponectin, leptin and anthropometrical and body composition parameters in physically active postmenopausal females. From blood lipids, only TG correlated significantly with adiponectin. PMID- 20737608 TI - Do mobile phone base stations affect sleep of residents? Results from an experimental double-blind sham-controlled field study. AB - OBJECTIVES: The aim of the present double-blind, sham-controlled, balanced randomized cross-over study was to disentangle effects of electromagnetic fields (EMF) and non-EMF effects of mobile phone base stations on objective and subjective sleep quality. METHODS: In total 397 residents aged 18-81 years (50.9% female) from 10 German sites, where no mobile phone service was available, were exposed to sham and GSM (Global System for Mobile Communications, 900 MHz and 1,800 MHz) base station signals by an experimental base station while their sleep was monitored at their homes during 12 nights. Participants were randomly exposed to real (GSM) or sham exposure for five nights each. Individual measurement of EMF exposure, questionnaires on sleep disorders, overall sleep quality, attitude towards mobile communication, and on subjective sleep quality (morning and evening protocols) as well as objective sleep data (frontal EEG and EOG recordings) were gathered. RESULTS: Analysis of the subjective and objective sleep data did not reveal any significant differences between the real and sham condition. During sham exposure nights, objective and subjective sleep efficiency, wake after sleep onset, and subjective sleep latency were significantly worse in participants with concerns about possible health risks resulting from base stations than in participants who were not concerned. CONCLUSIONS: The study did not provide any evidence for short-term physiological effects of EMF emitted by mobile phone base stations on objective and subjective sleep quality. However, the results indicate that mobile phone base stations as such (not the electromagnetic fields) may have a significant negative impact on sleep quality. PMID- 20737609 TI - Meta-analysis of digit ratio 2D:4D shows greater sex difference in the right hand. AB - OBJECTIVES: Our aims are, first, to describe the sex difference in the length ratio of the second and fourth digits (2D:4D), which likely reflects prenatal testosterone levels in humans. Second, to infer the loss of reliability observed in 2D:4D based on self-measured finger lengths. METHODS: We used random-effects meta-analysis of 2D:4D based on expert-measured finger lengths (116 samples with 13,260 females and 11,789 males). RESULTS: We find a moderate sex difference (with lower 2D:4D for males), which shows substantial heterogeneity (which is unrelated to age). The sex difference is moderated by the type of finger length measurement and by hand. Measurement involving the distortion of soft tissue leads to a significantly larger sex difference than finger length measurement avoiding this. The sex difference in 2D:4D is larger in the right hand than in the left. The reliability of self-measured 2D:4D in the BBC internet study, by far the largest study on 2D:4D, is estimated to be 46% of that of expert-measured 2D:4D. CONCLUSIONS: Right-hand 2D:4D might be a better indicator of prenatal androgenisation than left-hand 2D:4D. The view that 2D:4D has allometric properties (Kratochvil L, Flegr J. 2009. Differences in 2nd to 4th digit length ratio in humans reflect shifts along the common allometric line. Biol Lett 5:643 646.) is not supported. Bone lengths contribute to the sex difference in 2D:4D. In addition, there might be a sex difference in fingers' soft tissue, which should be investigated. Because of measurement unreliability, correlations between 2D:4D and variables of interest are about one-third smaller in the BBC internet study than in studies in which 2D:4D is based on expert-measured finger lengths. PMID- 20737610 TI - The trend of mean BMI values of US adults, birth cohorts 1882-1986 indicates that the obesity epidemic began earlier than hitherto thought. AB - BACKGROUND: The trend in the body mass index (BMI) values of the US population has not been estimated accurately because the time series data are unavailable and the focus has been on calculating period effects. OBJECTIVES: To estimate the trend and rate of change of BMI values by birth cohorts stratified by gender and ethnicity born 1882-1986. METHODS: We use loess additive regression models to estimate age and trend effects of BMI values of US-born black and white adults measured between 1959 and 2006. We use all the National Health Examination Survey and National Health and Nutrition Examination Survey data. RESULTS: The increase in BMI was already underway among the birth cohorts of the early 20th century. The rate of increase was fastest among black females; for the three other groups under consideration, the rates of increase were similar. The generally persistent upward trend was punctuated by upsurges, particularly after each of the two world wars. The estimated rate of change of BMI values increased by 71% among black females between the birth cohorts 1955 and those of 1965 is indicative of the rapid increases in their weight. CONCLUSIONS: We infer that transition to postindustrial weights was a gradual process and began considerably earlier than hitherto supposed. PMID- 20737611 TI - The role of fat mass index in determining obesity. AB - OBJECTIVES: The objective of this study is to compare body mass index (BMI), percent body fat (PBF), and fat mass index (FMI) and to investigate the accuracy of FMI as a convenient tool for assessing obesity. DESIGN: Anthropometric measurements and bioelectrical impedance analyses were performed on 538 Mexican Americans (373 women and 165 men). Correlations between BMI and PBF and between FMI and PBF were investigated. The percentage of persons misclassified as obese using different classifications was calculated. Multiple linear regression analysis was performed to generate predictive models of FMI for males and females separately. RESULTS: BMI and PBF were correlated in men (rho = 0.877; P < 0.0001) and women (rho = 0.966; P < 0.0001); however, 20 and 67.2% of the men and 9.2 and 84.2% of women, classified as normal weight and overweight by BMI, respectively, were diagnosed as obese by PBF. FMI and PBF were also correlated in men (rho = 0.975; P < 0.0001) and women (rho = 0.992; P < 0.0001). Four percent of the men classified as normal weight and 65.5% classified as overweight by BMI were obese by FMI, while 71.3% of women classified as overweight by BMI were obese by FMI. Misclassification of obesity between FMI and PBF categories was observed in 5.4% of men and 7.8% of women. CONCLUSIONS: The discrepancy observed between BMI and PBF reflects a limitation of BMI. Conversely, FMI accurately assessed obesity in our study of Mexican Americans, but further studies are necessary to confirm our findings in different ethnic groups. PMID- 20737612 TI - Bayesian longitudinal plateau model of adult grip strength. AB - OBJECTIVES: This article illustrates the use of applied Bayesian statistical methods in modeling the trajectory of adult grip strength and in evaluating potential risk factors that may influence that trajectory. METHODS: The data consist of from 1 to 11 repeated grip strength measurements from each of 498 men and 533 women age 18-96 years in the Fels Longitudinal Study (Roche AF. 1992. Growth, maturation and body composition: the Fels longitudinal study 1929-1991. Cambridge: Cambridge University Press). In this analysis, the Bayesian framework was particularly useful for fitting a nonlinear mixed effects plateau model with two unknown change points and for the joint modeling of a time-varying covariate. Multiple imputation (MI) was used to handle missing values with posterior inferences appropriately adjusted to account for between-imputation variability. RESULTS: On average, men and women attain peak grip strength at the same age (36 years), women begin to decline in grip strength sooner (age 50 years for women and 56 years for men), and men lose grip strength at a faster rate relative to their peak; there is an increasing secular trend in peak grip strength that is not attributable to concurrent secular trends in body size, and the grip strength trajectory varies with birth weight (men only), smoking (men only), alcohol consumption (men and women), and sports activity (women only). CONCLUSIONS: Longitudinal data analysis requires handling not only serial correlation but often also time-varying covariates, missing data, and unknown change points. Bayesian methods, combined with MI, are useful in handling these issues. PMID- 20737613 TI - Sex differences in child nutritional and immunological status 5-9 years post contact in fringe highland Papua New Guinea. AB - OBJECTIVES: This study examines sex differences in vulnerability among children experiencing rapid culture change that may reflect distinct microecologies driven by differential parental investment and/or sex-specific life history strategies. Apparent female growth canalization may be a life history strategy favoring growth over maintenance but also may reflect sex-differentiated selection for resilience based on unequal treatment during early life. METHODS: Stature, weight, and serum measures of C-reactive protein (CRP, an inflammation marker) and Epstein-Barr Virus antibodies (EBV, a humoral immune response marker) were collected longitudinally among children/adolescents ages 5-20 years (N = 65), 5-9 years after sustained contact in a fringe highland hunter-horticulturalist group from the Schrader Range in Papua New Guinea exhibiting male preference and sex biased survival. It was hypothesized that girls would exhibit canalization, with better nutritional status than boys; lower maintenance investment would yield lower female immune activation; and because of differential survivorship, females would appear increasingly canalized as early conditions for girls worsened relative to boys. RESULTS: Girls had greater arm circumference z-scores than boys, less frequent stunting, and lower CRP despite high pathogen load. Average nutritional status for girls improved over time as the sex ratio became increasingly male biased and the condition of female infants reportedly worsened. CONCLUSIONS: Both canalization and survivorship effects were found. Although a life history perspective on female canalization can help explain developmental outcomes in populations undergoing rapid culture change amid adversity, possible sex differences in the strength of survivorship effects that select for resiliency should not be ignored. PMID- 20737614 TI - Chronic radiation exposure in the Rivne-Polissia region of Ukraine: implications for birth defects. AB - OBJECTIVES: The health effects of chronic low-dose radiation exposure remains a controversial question. Monitoring after the Chernobyl nuclear accident in Ukraine suggested that chronic low-dose radiation exposure was not linked to cancer mortality among the general population. However, elevated rates of birth defects in contaminated compared to uncontaminated regions suggest that exposure to radiation in utero might impact development and that chronic radiation exposure might represent an underestimated risk to human health. METHODS: We sought to determine current radiation exposure routes in Rivne-Polissia, a region of Ukraine contaminated by the Chernobyl accident. This represents a first step toward comprehensive studies of the effects of chronic radiation exposure on human health. We designed and administered a dietary and activity survey to 344 women in Polissia. We assessed types and sources of food consumed, types of outdoor activities, and alcohol intake. RESULTS: Alcohol intake was low and alone does not account for the observed high rates of birth defects. Wild foods, especially mushrooms and berries, and locally produced foods, especially milk related, were major radiation exposure routes. Additionally, women were exposed to radiation through inhalation while burning grasses and potato vines in fields, and wood for cooking and heating. CONCLUSIONS: Twenty four years after the Chernobyl accident, women continue to be chronically exposed to low-dose radiation at levels exceeding current recommendations. This might contribute (especially synergistically with alcohol consumption and micronutrient deficiencies) to higher prevalence of birth defects in areas of Ukraine with high levels of radiation contamination compared to uncontaminated areas. PMID- 20737616 TI - Sex influence on myocardial function with exercise in adolescents. AB - OBJECTIVES: Ventricular systolic functional response to exercise has been reported to be superior in adult men compared to women. This study explored myocardial responses to maximal upright progressive exercise in late pubertal males and females. METHODS: Doppler echocardiographic techniques were utilized to estimate myocardial function response to a bout of progressive cycle exercise. RESULTS: Systolic functional capacity, as indicated by ejection rate (12.5 +/- 2.8 and 13.1 +/- 1.0 [x10(-2)] ml s(-1) cm(-2) for boys and girls, respectively) and peak aortic velocity (208 +/- 45 and 196 +/- 12 cm s(-1), respectively) at maximal exercise, did not differ between the two groups. Similarly, peak values as well as increases in transmitral pressure gradient (mitral E flow velocity), ventricular relaxation (tissue Doppler imaging E'), and left ventricular filling pressure (E/E' ratio) as estimates of diastolic function were similar in males and females. CONCLUSIONS: This study failed to reveal qualitative or quantitative differences between adolescent boys and girls in ventricular systolic or diastolic functional responses to maximal cycle exercise. PMID- 20737615 TI - Relation between C-reactive protein levels and body composition in a multiethnic sample of school children in Hawaii. AB - OBJECTIVES: Adipose cells secrete proinflammatory cytokines that stimulate hepatic production of C-reactive protein (CRP). CRP levels are associated with adiposity levels in adults, adolescents, and older children but not in young children (age 2-3). This study examined the relation between CRP, adiposity, and cardiovascular and metabolic variables including blood pressure, glucose, and blood lipids in two young cohorts of children, averaging approximately 5.5 and 8.5 years, respectively. METHODS: Children (N = 125) from eight elementary schools in the multiethnic community of Hilo Hawaii were recruited to fill out questionnaires, undergo anthropometrics and air displacement plethysmography, have resting blood pressure measured, and provide a finger stick blood sample for analysis of CRP, glucose, and blood lipids. RESULTS: There were no significant differences between the cohorts in ethnic make up, household income, or parents' educational attainment. No significant relation was found between CRP and either adiposity or cardiovascular/metabolic variables in the younger cohort. However, significant correlations were found between CRP and adiposity measures and blood pressure in the older cohort. There was no marked difference in association of CRP with BMI versus waist circumference or waist-to-hip ratio. In neither cohort was CRP significantly related to glucose or blood lipids. CONCLUSIONS: Both amount of fat mass and time duration for possessing the adipose tissue may be important factors in determining the relation between CRP and both adiposity and blood pressure. PMID- 20737617 TI - Leg length and age of puberty among men and women from a developing population: the Guangzhou Biobank Cohort study. AB - OBJECTIVES: Leg length and relative leg length are considered to be reliable markers of prepubertal living conditions. Cessation of leg growth, driven by estrogen, occurs earlier in puberty in girls than boys. We hypothesized that leg length and relative leg length, as sitting height to leg ratio, might have sex specific associations with age of puberty. METHODS: We used multivariable linear regression in 10,046 older (>or=50 years) Chinese from the Guangzhou Biobank Cohort Study (Phase 3) to examine the associations of recalled age of puberty (women: age of menarche, and men: mean age of first nocturnal emission, voice breaking, and first pubic hair) with subischeal leg length, sitting height to leg ratio, and sitting height. RESULTS: Leg length and sitting height to leg ratio had different associations with age of puberty in men and women (P-values for interaction <0.001), but sitting height did not. Per year earlier puberty, legs were longer among men by 0.09 cm (95% confidence interval (CI) 0.01-0.18) and shorter among women by -0.16 cm (95% CI -0.20 to -0.12). Further adjustment for age, hip size (as a marker of buttock fat), and several markers of childhood conditions did not obviate the difference in association by sex. CONCLUSIONS: Adult leg length and relative leg length (sitting height to leg ratio) may be biomarkers of different exposures in men and women, with corresponding implications for their interpretation as a biomarker of early life exposures. PMID- 20737618 TI - Secular trend in age at menarche in indigenous and nonindigenous women in Chile. AB - OBJECTIVES: To estimate the secular trend in age at menarche, comparing indigenous and nonindigenous women, and its relationship with socio-demographic, family and nutritional factors. METHODS: A study (historical cohorts) of 688 indigenous and nonindigenous women, divided into four birth cohorts (1960-69, 1970-79, 1980-89, and 1990-96) in an area in central southern Chile was carried out. Data and measurements were collected by health professionals using a previously validated questionnaire. Age at menarche was self-reported (recall). Adjusted differences among cohorts were estimated using a multivariate regression model. RESULTS: A secular trend (P < 0.001) in age at menarche was found in both ethnic groups, with no significant differences between them (P > 0.05). In an adjusted model, a reduction in age at menarche was estimated at 3.7 months per decade between 1960 and 1990. This trend was moderated by higher socio-economic level, smaller number of siblings, and cohabitation with a single parent during infancy. CONCLUSIONS: The trend has occurred in a steady progression over time in indigenous women, whereas in nonindigenous women, it was slow initially but has accelerated in recent years. Nonindigenous women have maintained a slightly lower age of menarche than their indigenous counterparts. PMID- 20737620 TI - Why does head form change in children of immigrants? A reappraisal. AB - OBJECTIVES: We test two specific hypotheses that explain the cranial changes Boas observed in Hebrews and Sicilians, namely that Hebrew change results from abandoning cradling of infants in America, while in Sicilians it results from impaired growth in America. METHODS: Boas's (1928) data were used to test these hypotheses. The role of cradling in cranial shape was examined by comparing cranial indices of U.S.-born and foreign children between 1.5 and 5 years of age. Age changes in cranial index of Hebrew and Sicilian children ages five to eighteen were examined to demonstrate differing patterns of age changes, which could be explained by environmental differences. Statistical methods employed were t-tests, least squares, and loess regression. RESULTS: The difference between American and foreign-born Hebrew children arose prior to five years of age, after which it remained constant. American and foreign-born Sicilians, on the other hand, had similar cranial indices at age five, and diverged during the growing years, primarily because American-born children did not exhibit the reduction in cranial index with age seen in the other groups. CONCLUSIONS: The results support the two hypotheses tested. Change in Hebrew cranial indices resulted from abandoning the practice of cradling infants in America. U.S.-born Sicilian children experienced an environment worse than the one in Europe, and consequently experienced impaired growth. We conclude that the changes Boas observed resulted from specific behavioral and economic conditions unique to each group, rather than a homogeneous American environment. PMID- 20737619 TI - Comparison of body fat estimates using 3D digital laser scans, direct manual anthropometry, and DXA in men. AB - OBJECTIVES: The purpose of this study was to assess the feasibility of utilizing three dimensional whole body laser surface scanning (3DS) to obtain specific anthropometric measurements to estimate percent body fat (BF). METHODS: Percent BF estimates from 37 male volunteers, of age 18-62 yr, were determined by inputting manual anthropometric (MA) and 3DS anthropometric measurements into the current Army BF prediction equation for males. The results were compared with each other and to BF values from Dual Energy X-ray Absorptiometry (DXA), employed as a reference method. RESULTS: Mean percent BF estimates (+/-SD) derived from MA, 3DS and from DXA were 18.4(+/-3.8), 18.8(+/-3.9), and 18.9(+/-4.7), respectively. Analysis of Variance tests revealed no statistical difference between the mean values. Correlation analysis comparing MA and 3DS derived percent BF estimates to each other and to those measured by DXA revealed moderate to strong Pearson correlation coefficients (r), small to moderate standard errors of the estimate (SEE), and were statistically significant (p < 0.05). CONCLUSIONS: Correlation coefficients and SEE results for this sample were: (1) DXA vs 3DS; r = 0.74, SEE = 3.2, (2) MA vs DXA; r = 0.82, SEE = 2.8, and (3) MA vs 3DS; r = 0.96, SEE = 1.0. Lin's concordance analysis, including Bland-Altman limits of agreement (LOA), revealed statistically significant measurement agreement among the three measurement modalities (p < 0.05). The application of 3DS scanning to estimate percent BF from commonly used anthropometric measurements are in close agreement with BF estimates derived from analogous MA measurements and from DXA scanning. PMID- 20737621 TI - Influence of the mother's preceding pregnancies on fetal development and postnatal survival of the neonate, in normal pregnancy. An immunological phenomenon? AB - OBJECTIVES: The objective of this study is to test for an association between the sex of conceptuses of the mother's preceding pregnancies and fetal development and early neonatal survival in normal pregnancy. METHODS: A population of 27,243 neonates, including a subsample of 7,773 "newborn/mother/placenta units" were divided into cohorts according to the sex of the neonate and the sex and number of conceptuses of the mother's preceding pregnancies. The average birth weight, placenta weight and early neonatal mortality rate were measured for each cohort and compared. The "dose effect" of preceding pregnancy was tested by linear and quadratic regression analysis, and by chi-square trend test for linearity of proportions. RESULTS: The results have shown an association between these three variables and the preceding pregnancies of the mother. Fetal development and early survival of the neonate are positively associated with the mother's preceding pregnancies of same sex as the neonate, and negatively associated with the preceding pregnancies of opposite sex to the neonate. The strength of the phenomenon increases with parity, at least for the first three parities. The association is statistically significant. CONCLUSIONS: The association between fetal development and neonatal survival and preceding pregnancies of the mother would be compatible with the action of male and female specific antigens capable of affecting selective implantation of blastocysts, which commands subsequent fetal development as well as early neonatal survival. PMID- 20737622 TI - Inbreeding and PKU allele frequency: Estimating by microsatellite approaches. AB - Estimates of allele frequencies for recessive diseases are generally based on the frequency of affected individuals (q(2)). However, these estimates can be strongly biased due to inbreeding in the population. OBJECTIVES: The purpose of this study was to gain a better understanding of how inbreeding in the Minas Gerais State population affects phenylketonuria (PKU) incidence in the state and to determine the inbreeding coefficient based on microsatellites. METHODS: Inbreeding coefficients of samples of 104 controls and 76 patients with PKU were estimated through a microsatellite approach. Besides, the amount and distribution of genetic variation within and among patients with PKU and control samples were characterized. RESULTS: No genetic differentiation was observed between the samples. However, the Fis value found for samples of patients with PKU (0.042) was almost 15 times higher than that found among controls (0.003). When corrected by the inbreeding coefficient found among the controls, the PKU allele frequency decreased to 0.0057. CONCLUSIONS: The results enables us to infer that at least 35% of the PKU recessive homozygotes from the Minas Gerais population could be due to consanguineous marriages and suggest that microsatellites can be an useful approach to estimate inbreeding coefficients. PMID- 20737623 TI - Cancer-preventive activities of secondary metabolites from leaves of the bilberry Vaccinium smallii A. Gray. AB - Ten secondary metabolites including flavonoids (1-8), caffeic (9) and chlorogenic (10) acids were structurally identified from the extract of Sakhalin bilberry Vaccinium smallii leaves and studied in vitro as potential cancer-preventive agents. The results showed that compounds 1-10 inhibited EGF-induced neoplastic transformation of mouse JB6 Cl 41 P+ cells in soft agar with an inhibition concentration (INCC50) of 20-80 um. Moreover, all these natural products were non toxic against JB6 Cl 41 P+ cells up to a concentration of 200 um. PMID- 20737624 TI - Soft gelatin capsules (softgels). AB - It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds. PMID- 20737625 TI - Kinetics of aspartic acid isomerization and enantiomerization in model aspartyl tripeptides under forced conditions. AB - The aim of the present study was the determination of the isomerization and enantiomerization of aspartic acid (Asp) in tripeptides. Capillary electrophoresis (CE) assays were developed and validated allowing the simultaneous determination of the diastereomeric alpha-D/L-Asp and beta-D/L-Asp peptides. Rapid isomerization and enantiomerization were noted for peptides with the Phe-Asp-GlyOH sequence at pH 10 and 80 degrees C while Gly-Asp-PheOH proved to be more stable due to the steric influence of the phenyl side chain. A kinetic model assuming a central role of the succinimide intermediate was used to fit the concentration versus time data. In incubations of L-Phe-alpha-L-Asp-GlyOH the ratio of alpha-Asp/beta-Asp peptides was about 1:4 in agreement with literature data. With regard to L-Asp and D-Asp peptides an alpha-Asp/beta-Asp ratio of about 1:3 and 1:5, respectively, was observed. The stereochemistry of Phe at the X-1 position affected the ratio of L-Asp/D-Asp implying an effect of the stereochemistry of neighboring amino acids on Asp enantiomerization. Modeling only overall Asp enantiomerization rate constants in accordance to literature data were observed for Asp peptides. In case of the asparagine (Asn) peptide the data could only be fitted to the models considering a direct conversion of L-Asn to a D-configured succinimide via an alternative pathway. PMID- 20737626 TI - Application of Monte Carlo simulation-based photon migration for enhanced understanding of near-infrared (NIR) diffuse reflectance. Part II: Photon radial diffusion in NIR chemical images. AB - This is the second of a series of articles applying Monte Carlo simulation-based photon migration as a means of enhancing understanding of near-infrared (NIR) diffuse reflectance in pharmaceutical analysis. This work utilizes Monte Carlo simulation to explore photon movement along the radial direction, as a means of investigating the potential 2-D spatial distortion in NIR chemical images caused by photon radial diffusion. Simulations indicate that the physical sample represented by an observed pixel in an image contributes 17% of the spectral information, while the remaining contribution comes from a radial area around the observed pixel about 500 microm wide. Empirical measurements on a two-medium sample (i.e., Teflon films with different thicknesses laid on the top of a pure theophylline compact) were used to confirm the effect of photon radial movement on a physical feature in an NIR chemical image, that is, edge blurring. As a means of edge clarification, a preliminary Monte Carlo simulation-based deconvolution filter was developed and tested for its efficacy on sharpening the physical feature and maintaining the original chemical information in a measured NIR chemical image. The initial success of the deconvolution filter highlights the potential to develop a filter for practical applications. PMID- 20737627 TI - Factors affecting calcium precipitation during neutralisation in a simulated intestinal environment. AB - Maintaining soluble calcium in the gastrointestinal tract after administration of a calcium supplement is essential for intestinal absorption. Due to the low solubility of calcium carbonate, calcium may precipitate as the carbonate salt during intestinal neutralisation with bicarbonate. The influence of neutralising solution, calcium salt and the presence of amino acids and bile components were determined in an in vitro system. After dissolution of calcium citrate or chloride salt in 0.1 N HCl, the mixture was neutralised to pH 7 with either HCO3( ) or OH(-). For further investigation, amino acids or bile components were added to the initial solution to simulate the effect of digested protein and bile, respectively. The pH and PCO2 were monitored, and samples were analysed for calcium during neutralisation. Precipitation of calcium occurred with the citrate salt, while the chloride salt only precipitated at a high secretion rate of HCO3( ), where no calcium remained in solution at pH 7 and PCO2 was at saturation. There was a buffering effect by amino acids, and bile components maintained calcium in solution. The total soluble calcium under the different physiological conditions in vitro may be used to further understand calcium solubility in vivo, a contributing factor of calcium absorption. PMID- 20737628 TI - Salicylic acid/gamma-cyclodextrin 2:1 and 4:1 complex formation by sealed-heating method. AB - A novel complex of salicylic acid (SA) and gamma-cyclodextrin (gamma-CD) was obtained via the sealed-heating method. The influence of the water content of gamma-CD on the complex formation with SA by sealed-heating process was investigated. Quantitative determination of SA revealed that sealed-heated samples of SA and gamma-CD with low water content (0.8-5.4%) formed the SA/gamma CD = 2:1 complex, while the samples with high water content (8.5-11.5%) formed the SA/gamma-CD = 4:1 complex. The molecular arrangements of gamma-CD in 2:1 and 4:1 complexes were determined by powder X-ray diffraction measurements to be in monoclinic-columnar and tetragonal-columnar forms, respectively. The results of infrared spectroscopy and (13)C solid-state NMR measurements showed that two types of SA molecules resided in the 4:1 complex, whereas only one type of SA molecules existed in the 2:1 complex. The obtained 2:1 complex was assumed to contain two SA molecules per one gamma-CD, with the SA molecules existing in the intermolecular spaces formed by the gamma-CD columns. In the case of the 4:1 complex, two SA molecules were incorporated into the intermolecular spaces while the other two SA molecules were included within the gamma-CD cavity. PMID- 20737629 TI - In vivo study of a polymeric glucose-sensitive insulin delivery system using a rat model. AB - This study assesses the feasibility of an intraperitoneal (IP) implantable closed loop insulin delivery device in rats, that delivers insulin via a glucose sensitive material such that blood glucose (BG) levels are adjusted automatically to within normal tolerances. A gateway layer of this gel governs the output of insulin from an insulin reservoir device for IP implant. The performance of the system was compared over time in diabetic rats with a control system using oral glucose challenges and daily assessments of BG and body weight. The automated response of the active system was quantified using IP multiple dose injection (MDI) results in the same rat model. Successful control was found for the device containing active gel when assessed daily and when challenged with large glucose doses. This was not found when comparing an inactive gel analog as a control. The regimen was quantified by comparison with the informative MDI study. The device was well tolerated and might operate to further advantage when vascular omentum grows into the perforated front of the device. The successful device must have been outputting approximately 0.5 U/kg/h basal with 2 U/kg boosts in order to match the demand of the challenges. However, the device eventually exhausts and a refill mechanism needs to be devised in future models. PMID- 20737630 TI - Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs. AB - Dissolving microneedle patches offer promise as a simple, minimally invasive method of drug and vaccine delivery to the skin that avoids the need for hypodermic needles. However, it can be difficult to control the amount and localization of drug within microneedles. In this study, we developed novel microneedle designs to improve control of drug encapsulation and delivery using dissolving microneedles by (i) localizing drug in the microneedle tip, (ii) increasing the amount of drug loaded in microneedles while minimizing wastage, and (iii) inserting microneedles more fully into the skin. Localization of our model drug, sulforhodamine B in the microneedle tip by either casting a highly concentrated polymer solution as the needle matrix or incorporating an air bubble at the base of the microneedle achieved approximately 80% delivery within 10 min compared to 20% delivery achieved by the microneedles encapsulating nonlocalized drug. As another approach, a pedestal was introduced to elevate each microneedle for more complete insertion into the skin and to increase its drug loading capacity by threefold from 0.018 to 0.053 microL per needle. Altogether, these novel microneedle designs provide a new set of tools to fabricate dissolving polymer microneedles with improved control over drug encapsulation, loading, and delivery. PMID- 20737631 TI - Comparative evaluation of disodium edetate and diethylenetriaminepentaacetic acid as iron chelators to prevent metal-catalyzed destabilization of a therapeutic monoclonal antibody. AB - Understanding the effect of metal chelators with respect to their ability to inhibit metal-catalyzed degradation in biologic products is a critical component for solution formulation development. Two metal chelators, disodium edetate (Na(2)EDTA) and diethylenetriaminepentaacetic acid (DTPA), were evaluated for their ability to stabilize IgG2 mAb in solution formulations spiked with various levels of iron. Real-time stability attributes such as oxidation, soluble aggregate formation, deamidation, and fragmentation demonstrated that DTPA was equivalent to Na(2)EDTA with respect to inhibiting iron-induced degradation over the range of iron concentrations studied. When sufficient chelator was present to stoichiometrically complex trace iron contamination, both Na(2)EDTA and DTPA exhibited the capacity to reduce protein degradation. However, substoichiometric ratios of both chelators were unable to inhibit the degradation induced by free iron ions, which were found to bind weakly to the mAb. This bound iron did not measurably alter the secondary or the tertiary structure of the mAb but appeared to decrease its intrinsic thermodynamic stability, probably by causing subtle perturbations in the tertiary structure. These destabilization effects were not observed when the chelators were present at stoichiometric ratios highlighting the feasibility of using DTPA as an alternate trace metal chelator to Na(2)EDTA in biologic protein formulations. PMID- 20737632 TI - Bimodal release of olanzapine from lipid microspheres. AB - Olanzapine was formulated as 10% (w/w) mixture with cutina to which stearic acid was added, ranging from 10% to 90% (w/w) of the total mass to control the drug release. The molten mixtures were processed by ultrasound-assisted spray congealing technique, obtaining solid microspheres. The drug is stable under these conditions and only a partial miscibility in the solid state was observed by DSC between the two fatty materials with two separated melting endotherms in the thermograms: this can be due to the presence of two phases inside the solid dispersion. Olanzapine is distributed into the two phases according to its partition coefficient: two phases make the system less suitable to crystallization of the drug; the loading of the drug could reach saturation with difficulty and the rate of the olanzapine release is differentiated, since the drug is released from two different carriers. Dissolution profiles suggest occurrence of a bimodal release, where each portion of the release profile is linear and the slope increases with a higher content of stearic acid in the carrier mixture, that behaves as a release promoter. Tests were also carried out with palmitic and lauric acids for comparison and also for systems in the absence of ultrasound. PMID- 20737633 TI - Biodegradable nanoparticles with sustained release of functional siRNA in skin. AB - A key challenge in developing RNAi-based therapeutics is efficient delivery of functional short interfering RNA (siRNA) to target cells. To address this need, we have used a supercritical CO(2) process to incorporate siRNA in biodegradable polymer nanoparticles (NPs) for in vivo sustained release. By this means we have obtained complete encapsulation of the siRNA with minimal initial burst effect from the surface of the NPs. The slow release of a fluorescently labeled siRNA mimic (siGLO Red) was observed for up to 80 days in vivo after intradermal injection into mouse footpads. In vivo gene silencing experiments were also performed, showing reduction of GFP signal in the epidermis of a reporter transgenic mouse model, which demonstrates that the siRNA retained activity following release from the polymer NPs. PMID- 20737634 TI - Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosis. AB - The present study aimed to develop bilayered nail lacquer of terbinafine hydrochloride (TH) for treatment of onychomycosis. The composite nail lacquer formed an underlying drug-loaded hydrophilic layer and overlying hydrophobic vinyl layer. The hydrophilic lacquer made of hydroxylpropyl methylcellulose E-15 contained polyethylene glycol 400 (PEG 400) as a drug permeation enhancer. The vinyl lacquer was composed of poly (4-vinyl phenol) as a water-resistant film former. In vitro permeation studies in Franz diffusion cells indicated that the amount of TH permeated across the human cadaver nail in 6 days was 0.32 +/- 0.14, 1.12 +/- 0.42, and 1.42 +/- 0.53 microg/cm(2) from control (hydrophilic lacquer devoid of PEG 400), monolayer (hydrophilic lacquer alone), and bilayered nail lacquers, respectively. A higher nail drug load was seen in vitro with the bilayered lacquer (0.59 +/- 0.13 microg/mg) as compared to monolayer (0.36 +/- 0.09 microg/mg) and control (0.28 +/- 0.07 microg/mg) lacquers. The drug loss despite multiple washing was significantly low (p < 0.001) for the bilayered lacquer owing to the protective vinyl coating. Clinical studies demonstrated the efficacy of bilayered lacquer to achieve better drug load in the nail plate (1.27 +/- 0.184 microg/mg) compared to monolayer (0.67 +/- 0.18 microg/mg) and control (0.21 +/- 0.04 microg/mg) lacquers. PMID- 20737635 TI - Single layer transdermal film containing lidocaine: water and lidocaine mobility determined using neutron scattering. AB - The diffusivity of lidocaine through a polymer film developed for transdermal drug administration has been characterized by macroscopic permeation experiments and by neutron quasielastic spectroscopy that provides information on microscopic diffusivity parameters. It turns out that film hydration plays a key role on the performance and efficiency of the investigated system. Diffusion of lidocaine, at the microscopic level, is triggered by the presence of "mobile water." At hydration levels below 15% (weight water/weight hydrated film) neither lidocaine nor water show any appreciable long-range diffusion. At higher hydration levels, the onset of water long-range diffusion triggers diffusion of lidocaine through the film. The use of neutron quasielastic scattering makes it possible to measure lidocaine mobility within the film without the need of any additional physical barrier. PMID- 20737636 TI - Enhancement of the aqueous solubility and masking the bitter taste of famotidine using drug/SBE-beta-CyD/povidone K30 complexation approach. AB - The objective of the present study was to evaluate the potential of ternary system (comprised of famotidine, beta-cyclodextrin (beta-CyD) or its derivatives and a hydrophilic polymer) as an approach for enhancing the aqueous solubility and masking the bitter taste of famotidine. The aqueous solubility of famotidine increased in the presence of beta-CyDs, particularly sulfobutyl ether beta-CyD (SBE-beta-CyD), and it was further enhanced by the combination of SBE-beta-CyD and polyvinyl pyrrolidone (Povidone) K30. The solid binary (drug-beta-CyDs) and ternary (drug-beta-CyDs-Povidone K30) systems were prepared by the kneading and freeze-drying methods. The dissolution rates of these solid systems were much faster than that of the drug alone. A taste perception study was carried out, initially using a taste sensory machine and subsequently on human volunteers to evaluate the taste masking ability of the ternary complexation. Our results indicated that the combination of SBE-beta-CyD and Povidone K30 is effective not only in the enhancement of the solubility and dissolution rate of famotidine, but also in masking of the bitter taste of the drug. This technique may be of value for the pharmaceutical industries, especially in preparation of rapidly disintegrating tablets dealing with bitter drugs to improve patient compliance and thus effective pharmacotherapy. PMID- 20737637 TI - Spinning disc processing technology: potential for large-scale manufacture of chitosan nanoparticles. AB - Mass production of nanoparticles using a reliable cost-effective approach is a challenge in the pharmaceutical industry. In this study, the spinning disc processing (SDP) technology was used to fabricate chitosan nanoparticles, with a view to commercially produce chitosan nanoparticle-based drug delivery platforms. Chitosan solution (0.25%, w/v, in dilute acid, 27.5 mL, 1.5 mL/s) was intensely mixed with sodium tripolyphosphate solution (0.10%, w/v, in water, 20 mL, 1.1 mL/s) on the spinning disc (1000 rpm). Transmission electron microscopy and dynamic light scattering data confirmed that the nanoparticles (20 +/- 3 nm) were comparable in size and shape to those synthesised using a beaker and magnetic stirrer (31 +/- 13 nm). Larger nanoparticles (131 +/- 5 nm) were produced by increasing the chitosan and TPP feed concentrations to 0.5% and 0.125%, respectively. Drug loading further increased the size of the nanoparticles, with N-acetyl cysteine (NAC) having a greater effect (403 +/- 4 nm) than paracetamol (165 +/- 4 nm). Co-loading of both drugs increased the size of the particles to the micron range. In conclusion, the SDP is a robust technology capable of expanding the production of blank and drug-loaded chitosan nanoparticles for the biomedical and pharmaceutical industries. PMID- 20737638 TI - Asymmetry effect of particle size distribution on content uniformity and over potency risk in low-dose solid drugs. AB - Most active pharmaceutical ingredients (API) exhibit particle size distributions with some degrees of asymmetry deviating from log-normality. A new log-skew normal (L-S-N) distribution model is proposed for a systematic comparison of the asymmetry effect on content uniformity. The new model originated from the S-N model used by Azzalini gives a close approximation to real API particle size distribution. Monte-Carlo method was employed to simulate the dosage potency distribution. A high risk of over potency is uncovered when either the dose is low or API particle size distribution is positively skewed. This is due to the formation of pseudo heavy tail in potency distribution that decays slower than exponentially. Nomographs of API particle size versus dosage strength were constructed with a range of geometric standard deviations and asymmetry parameters with and without particle size cut-off (sieving) for a combined 99% pass rate against USP <905> Uniformity of Dosage Units. It was found that for a given specification of volume median and 90% diameters (d(50) and d(90)), the dosage strength must increase by 10 times if the API asymmetry parameter changes from 1 (log-normal) to 1.1. PMID- 20737639 TI - The effect of dryer load on freeze drying process design. AB - Freeze-drying using a partial load is a common occurrence during the early manufacturing stages when insufficient amounts of active pharmaceutical ingredient (API) are available. In such cases, the immediate production needs are met by performing lyophilization with less than a full freeze dryer load. However, it is not obvious at what fractional load significant deviations from full load behavior begin. The objective of this research was to systematically study the effects of variation in product load on freeze drying behavior in laboratory, pilot and clinical scale freeze-dryers. Experiments were conducted with 5% mannitol (high heat and mass flux) and 5% sucrose (low heat and mass flux) at different product loads (100%, 50%, 10%, and 2%). Product temperature was measured in edge as well as center vials with thermocouples. Specific surface area (SSA) was measured by BET gas adsorption analysis and residual moisture was measured by Karl Fischer. In the lab scale freeze-dryer, the molar flux of inert gas was determined by direct flow measurement using a flowmeter and the molar flux of water vapor was determined by manometric temperature measurement (MTM) and tunable diode laser absorption spectroscopy (TDLAS) techniques. Comparative pressure measurement (capacitance manometer vs. Pirani) was used to determine primary drying time. For both 5% mannitol and 5% sucrose, primary drying time decreases and product temperature increases as the load on the shelves decreases. No systematic variation was observed in residual moisture and vapor composition as load decreased. Further, SSA data suggests that there are no significant freezing differences under different load conditions. Independent of dryer scale, among all the effects, variation in radiation heat transfer from the chamber walls to the product seems to be the dominant effect resulting in shorter primary drying time as the load on the shelf decreases (i.e., the fraction of edge vials increases). PMID- 20737640 TI - Variations in compaction behaviour for tablets of different size and shape, revealed by small-angle X-ray scattering. AB - Local variations in compaction behaviour were investigated, for specimens of different shapes and thickness, comparing predictions from finite element (FE) modelling and results from a recently developed method using small-angle X-ray scattering (SAXS). Good agreement was generally obtained between these methods, in terms of the variations of density, compaction strain and principal strain direction within the specimens examined. The combination of SAXS and FE methods appeared particularly suitable for studying pharmaceutical tablets, revealing effects (such as nano-strain of intragranular morphology and strain direction) that are not easily observed by other methods, and which may have significant effects on tablet integrity or swelling and drug delivery characteristics. PMID- 20737641 TI - On the possibility of self-induction of drug protein binding. AB - The equilibrium unbound drug fraction (f(u)) is an important pharmacokinetic parameter, which influences drug elimination and distribution in the body. Commonly the drug plasma concentration is substantially less then that of drug binding proteins, so that f(u) can be assumed constant independent of drug concentration. A general consideration of protein binding based on the mass action law provides that the unbound drug fraction increases with the increase of drug concentration, which is also a usual experimental observation. For several drugs, though, a seemingly unusual sharp decrease of the unbound drug fraction with the increase of total drug concentration (R(o)) in the interval 0 < R(o) less, similar 5 microM was experimentally observed. A possible explanation of this apparently strange phenomenon is presented. The explanation is based on the consideration of a two-step mechanism of drug protein binding. The first step occurs as a drug binding to the site with relatively low affinity. Consequently this binding leads to the activation of a high affinity site, which otherwise is not available for binding. The suggested binding scheme yields the curves for f(u) dependence on the total drug concentration that are in good agreement with experimental measurements. The interpretation of pharmacokinetic data for the drugs with such unusual concentration dependence of f(u) appears to be a formidable problem. PMID- 20737642 TI - IVIVC for fenofibrate immediate release tablets using solubility and permeability as in vitro predictors for pharmacokinetics. AB - The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose-technique. The in vitro determined drug solubility and permeability data were related to the C(max) values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation data were combined and compared with the C(max) values for the fenofibrate formulations, assuming a 50 mL in vivo dissolution volume. A good IVIVC was observed for five fenofibrate formulations (R(2) = 0.94). The in vitro studies revealed that the formulation compositions containing sodium lauryl sulfate (SLS) interfered with the vesicular drug solubilizing system of the biorelevant medium and antagonized its solubilization capacity. The opposing interaction of surfactants with the emulsifying physiological constituents in intestinal juice should be taken into consideration in order to prevent unsatisfactory in vivo performance of orally administered formulations with low soluble active pharmaceutical ingredients. PMID- 20737644 TI - Prognostic value of health-related quality-of-life parameters in early-stage breast cancer: an 8-year follow-up study. AB - OBJECTIVE: The purpose was to investigate whether self-reported health-related quality-of-life (HRQOL) parameters at time of diagnosis and/or 1-year follow-up are prognostic for disease-free survival (DFS) in early-stage breast cancer patients. METHODS: Data from 195 women, diagnosed with early-stage breast cancer, who had filled in the EORTC QLQ-C30 and the Hospital Anxiety and Depression Scale (HADS) at time of diagnosis and 1 year after surgery, were analyzed. RESULTS: After a median follow-up of 8.2 years (range 0.09-9.45), 27 (14.1%) deaths and 22 (11.5%) recurrences were observed. Using Cox multivariate regression analysis, appetite loss reported 1-year following surgery (HR 2.92, 95% CI 1.50-5.66), p=0.002) was significantly predictive for shorter DFS, even after controlling for age and depression. None of the clinical or biological prognostic factors was found to have a confounding effect. CONCLUSION: The findings indicate that loss of appetite probably is of prognostic value in addition to well-recognized clinical and biological data, in early-stage breast cancer. PMID- 20737643 TI - Effect of patient and patient-oncologist relationship characteristics on communication about health-related quality of life. AB - OBJECTIVE: To test the effects of patient and patient-oncologist relationship factors on the time spent communicating about health-related quality of life (HRQOL) during outpatient clinic encounters between oncologists and their patients with advanced cancer. METHODS: Using mixed methods, we coded for duration of HRQOL talk in a subset of audio-recorded conversations from the Study of Communication in Oncologist-Patient Encounters (SCOPE) Trial. Multivariable linear regression modeling was used to investigate the relationship between duration of HRQOL talk and gender concordance, race concordance, patient education status, patient marital status, and length of the patient-oncologist relationship (i.e. number of previous visits). RESULTS: Sixty-six encounters were analyzed that involved 63 patients and 34 oncologists. Patients were more likely to be female (51%), white (86%), married (78%), and possess a college or more advanced degree (33%). Most oncologists were male (82%) and white (82%). Mean ages were 58.8 years for patients and 44.9 years for oncologists. Regression results showed that the number of a patient's previous visits with their oncologist was significantly associated with a longer duration of HRQOL talk during their audio-recorded clinic visit. The remaining independent variables, gender concordance, race concordance, patient education status, and patient marital status were not significant predictors of duration of HRQOL talk. CONCLUSIONS: Our findings suggest that length of the patient-oncologist relationship is related to duration of HRQOL talk. Improvements in HRQOL communication may best be achieved through efforts directed at those in earlier stages of the doctor-patient relationship. PMID- 20737645 TI - Gender differences in re-offending among psychiatrically examined Swedish offenders. AB - BACKGROUND: The gender gap for violent offending is narrowing in the general population. Substance abuse and mental health problems are known risk factors for criminality. While substance abuse treatment has been associated with reduced risk of re-offending, women seem less likely to engage than men. People misusing substances tend to be high users of emergency room (ER) services. Such use may be an indicator both of treatment failure for substance misuse and offending. Little is known about gender differences in this respect. AIMS: This study aims to test for gender differences in re-offending, use of substance abuse treatment, and hospital ER visits among offenders referred for forensic psychiatric assessment in Sweden. METHOD: The study used a longitudinal retrospective design. Data on all 31 women from a 2-year (2000-2001) cohort of serious offenders referred for forensic psychiatric assessment in Stockholm county, and 31 men from the same cohort, were extracted from forensic service and national records. Selection of the men was by initial random sampling followed by matching on age and substance misuse. The two resulting samples were compared on health service use and re offending data between release and the census date (30 April 2004). RESULTS: There were no gender differences for violent re-offending or for engagement in planned substance abuse treatment, in spite of longer time at risk for the men. Re-offending was reduced for women but not men who did not present in the ER with physical health problems. CONCLUSIONS: Our study is limited by sample size, although it included all women referred to the specialist forensic psychiatric service over 2 years, but it does indicate that differences between men and women in this situation are likely, and worthy of further study. The only way of achieving adequate sample sizes is likely to be through multi-centre collaboration. PMID- 20737646 TI - Personality structure among prisoners: how valid is the five-factor model, and can it offer support for Eysenck's theory of criminality? AB - BACKGROUND: Research with offenders has tended to use a categorical system of diagnosis or a three-factor model. There is growing evidence among non-offending groups that a five-factor model (FFM), which is more holistic and emphasises strengths as well as limitations, may be more clinically useful. AIM: The purpose of this study was to test the validity of the FFM of personality in a sample of adult male prisoners. It was predicted that they would show higher scores for extraversion (E) and lower scores for emotional stability (ES) [the equivalent of higher neuroticism (N)], that E would be predicted by prison experience and age and that the FFM would be confirmed as a better fit to the data over Eysenck's three-factor [P(psychoticism)EN] model. METHODS: Two independent samples of adult male prisoners were asked to complete the International Personality Item Pool while locked in their cells over the lunchtime period. Parallel and confirmatory factor analyses were used to test the hypotheses. RESULTS: There was a 65 and 75% response rate across the independent samples, resulting in samples of 259 and 183, respectively. Overall, more positive personality traits were evidenced across both samples. E was not predicted by prison experience or age, with increased ES related to increased age in only one sample. The best-fitting model comprised five factors, but represented a variant of the FFM. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The value of applying broad conceptualisations of personality to special samples is discussed, with the importance of accounting for positive, as well as negative, traits acknowledged. The presence of increased positive traits in comparison to negative traits is not in keeping with Eysenck's original personality theory of criminal behaviour, with the study highlighting value in accounting more for environmental factors. PMID- 20737647 TI - Triply troubled: criminal behaviour and mental health in a cohort of teenage pregnant substance misusers in treatment. AB - BACKGROUND: Teenage substance misuse and pregnancy are major public health problems in the UK, where the most recent figures on maternal deaths suggest that they have doubled among young substance misusers. In general, little is known about their pregnancy outcomes. AIMS: The aims of this study were to describe the characteristics of a sample of teenage pregnant drug users in the UK, to examine their psychosocial risk and complicating factors at presentation, to evaluate adherence to current national guidelines and to assess the adequacy of guidelines in relation to identified characteristics. METHODS: A six-year records survey of young people attending a specialist adolescent drug misuse service in the west midlands of the UK. RESULTS: Ten pregnant adolescents were identified from records. These girls have had unstable or abusive experiences through childhood, half having other substance misusers in the family. All were with substantially older partners, who were also substance misusers. All had required a mental health assessment and 90% had a history of self-harm. There were no maternal or neonatal deaths, and only one girl had a miscarriage, but in four cases, the child had to be fostered. CONCLUSIONS: To our knowledge, this is the first analysis of this kind in the UK. Available guidelines were followed, but our findings suggest that more detailed and comprehensive guidelines are required. Preventive measures through education are likely to be hampered by the early age at which these girls cease attending school. PMID- 20737648 TI - A new Pr3+-activated molybdate-based phosphor for application to white LEDs with blue excitation. AB - The novel red-emitting phosphors K(x)Sr(1-2x)MoO4:Pr3+(x) (0.00 <= x <= 0.04) were prepared by solid-state reaction. The crystallization and particle sizes of samples were investigated by powder X-ray diffraction (XRD) and transmission electron microscopy (TEM). TEM images were in good agreement with the theoretical calculation data from the XRD patterns. Photoluminescence analysis indicated that there were three excitation peaks under 430-500 nm, and all samples showed the intensely red emission at 648 nm corresponding to the 3P0 -> 3F2 transition of Pr3+. The concentrations of doping ions, temperature and polyethylene glycol in the phosphor system can significantly influence the intensity of the red emission. The photoluminescence spectral intensity reached its maximum at x = 0.02. The results showed that the investigated phosphor is a potential red phosphor for white light-emitting diodes. PMID- 20737649 TI - Simple and sensitive spectrofluorimetric method for the determination of pregabalin in capsules through derivatization with fluorescamine. AB - A new, simple and sensitive spectrofluorimetric method has been developed for the determination of pregabalin (PG) in capsules. The method is based on the reaction between pregabalin and fluorescamine in borate buffer solution of pH 10 to give a highly fluorescent derivative that is measured at 487 nm after excitation at 390 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence intensity concentration plot was rectilinear over the range of 0.01-0.3 ug mL-1 with a lower detection limit of 0.0017 ug mL-1 and limit of quantitation of 0.005 ug mL-1. The developed method was successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recovery of PG in its capsule was 99.93+/-1.24 (n = 3). Statistical comparison of the results with those of the comparison method revealed good agreement and proved that there was no significant difference in the accuracy and precision of the two methods. A proposed reaction pathway was postulated. PMID- 20737650 TI - Determination of ketotifen fumarate by capillary electrophoresis with tris(2,2' bipyridyl) ruthenium(II) electrochemiluminescence detection. AB - On the basis of an europium (III)-doped Prussian blue analog film modifying platinum electrode as the working electrode, a Ru(bpy)32+-based electrochemiluminescence (ECL) assay coupled with capillary electrophoresis has been first established for the determination of ketotifen fumarate (KTF). Analytes were injected onto a separation capillary of 50 cm length (50 MUm i.d., 360 MUm o.d.) by electrokinetic injection for 10 s at 10 kV. Parameters related to the separation and detection were discussed and optimized. It was proved that 15 mM phosphate buffer at pH 8.0 could achieve the most favorable resolution, and the highest sensitivity of detection was obtained using the detection potential at 1.25 V and 5 mM Ru(bpy)32+ in 100 mM phosphate buffer at pH 8.0 in the detection reservoir. Under the optimized conditions, the ECL intensity was in proportion to KTF concentration over the range from 3.0 * 10-8 to 5.0 * 10-6 g mL 1 with a detection limit of 2.1 * 10-8 g mL-1 (3sigma). The relative standard deviations of the ECL intensity and the migration time were 0.95 and 0.26%, respectively. The developed method was successfully applied to determine KTF contents in pharmaceuticals and human urine with recoveries between 99.5 and 107.0%. PMID- 20737651 TI - Characteristics of rare earth (RE = Eu, Tb, Tm)-doped Y2O3 phosphors for thermometry. AB - The temperature-dependent photoluminescences of Y(2)O(3) : Eu (6% Eu), Y(2)O(3) : Tb (4% Tb) and Y(2)O(3) : Tm (1% Tm) were investigated for high-temperature phosphor thermometry. Two different phases, the monoclinic phase and cubic phase, were considered because the fluorescence spectra vary with the phase. To employ the intensity ratio method, we investigated their photoluminescence spectra under the excitation light of an Hg-Xe lamp as the temperature was elevated from room temperature to more than 1200 K. As a result, it was confirmed that the luminescence intensity of all of the phosphors varied with elevating temperature, i.e. thermal quenching, with the variations depending on the type of rare earth impurity and their phases. The results indicate that Y(2)O(3) : Eu phosphors are applicable to the intensity ratio method because they show appropriate variations in the intensity ratio of two emission lines, and they also have strong and sharp peak intensities without excessive optical noise or black body radiation over a wide range of temperatures. The intensity ratios for Y(2)O(3) : Tb provide such small variations with temperature that the temperature resolution is low, despite the strong emission intensities. As for Y(2) O(3) :Tm, the intensity ratios also have a low temperature resolution and their emission intensities are weak. Therefore, Y(2)O(3) : Tb and Y(2)O(3) : Tm are not appropriate for the intensity ratio method for phosphor thermometry. PMID- 20737653 TI - Simultaneous quantification of total eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid in plasma by high-performance liquid chromatography-tandem mass spectrometry. AB - A method for the simultaneous quantification of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in human plasma by HPLC tandem mass spectrometry (HPLC-MS/MS) was developed and validated. Free and esterified forms of fatty acids were hydrolysed from plasma samples in the presence of an internal standard and subjected to liquid-liquid extraction. The chromatographic run time was 3.5 min per sample. The assay was linear from 0.5 to 300 mg/L (r(2) > 0.997, n = 18). Based on matrix addition, accuracy deviation was <15%, except for AA at 10 mg/L (30-90%), whereas precision was <8% for all fatty acids studied. The method was applied to the measurement of these omega-3 fatty acids in a fish oil supplement study with healthy volunteers. Healthy males (n = 4) were administered a supplement containing 465 mg EPA and 375 mg DHA per capsule (Omacor(r)). A dose of two capsules was given daily over a 4 week period. Pre-treatment concentrations varied between subjects for EPA (17-68 mg/L), DHA (36-63 mg/L) and AA (121-248 mg/L). During the dosing period EPA increased 460 480% from the baseline concentration, while DHA increased 150-160%. The EPA-AA ratio increased from 0.07-0.56 to 0.3-3.1 after 4 weeks of dosing. In conclusion, the method described could be suitable for monitoring EPA, DHA and AA in clinical studies that may aid in achieving optimal concentrations of these fatty acids in patients who could be at risk of sudden cardiac death. PMID- 20737652 TI - Spectroscopy characterization of the interaction between brevifolin carboxylic acid and bovine serum albumin. AB - Themechanism of binding of the antivirus drug, brevifolin carboxylic acid (BCA) with bovine serum albumin (BSA) was investigated by steady-state and time resolved fluorescence, circular dichroism (CD), Fourier transform infrared (FT IR) and Raman spectroscopy under pseudo-physiological conditions for the first time. A strong fluorescence quenching was observed and the quenching mechanism was considered as static quenching. Various binding parameters were evaluated. The quantitative analysis of CD spectral data revealed that the a-helical content of BSA increased from 48.91% (in free BSA) to 52.46% (in bound form) in the presence of BCA. Based on the Forster's theory of non-radiation energy transfer, the relation of the binding average distance r between the donor (BSA) and acceptor (BCA) and acceptor concentration was determined. The changes in association constants of BCA-BSA in the presence of the common ions are also discussed. From the CD, FT-IR, time-resolved fluorescence and Raman spectroscopic results, it is apparent that the interaction of BCA with BSA causes a conformational change in the protein, and the Trp and Tyr residues are buried in more hydrophobic surroundings. BCA mainly binds to residue Trp 212 located in domain II of BSA by hydrophobic interaction and hydrogen bond. PMID- 20737654 TI - Simultaneous determination of five active hydrolysis ingredients from Panax quinquefolium L. by HPLC-ELSD. AB - An effective method for simultaneous determination of five hydrolysis products of 20 (R)-dammarane-3beta,6alpha,12beta,20,25-pentol, 24(R)-ocotillol, 20(R) protopanaxatriol, 20(S)-panaxatriol and 20(R)-dammarane-3beta,12beta,20,25-tetrol was developed using high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD). The hydrolysis products from Panax quinquefolium L. in the stems and leaves, berries, flower buds and roots components were successfully separated on a Kromasil C(18) column using methanol and water (83:17, v/v) as mobile phase in 18 min. The parameter for the ELSD was set to a probe temperature of 40 degrees C and the nebulizer for nitrogen gas was adjusted to 3 L/min. All calibration curves showed good linear regression (r > 0.9975) within test ranges. The validation of the method included recovery, linearity, accuracy and precision (intra- and inter-day variation). The accuracy and precision were satisfactory, with the overall intra- and inter-day variation being less than 3.11%, and recoveries of this method were greater than 95.0%. This study developed an effective and rapid method for simultaneous determination of multiple hydrolysis components from Panax quinquefolium L. PMID- 20737655 TI - Indirect reversed-phase high-performance liquid chromatographic and direct thin layer chromatographic enantioresolution of (R,S)-Cinacalcet. AB - Enantioresolution of the calcimimetic drug (R,S)-Cinacalcet was achieved using both indirect and direct approaches. Six chiral variants of Marfey's reagent having L-Ala-NH(2), L-Phe-NH(2), L-Val-NH(2), L-Leu-NH(2), L-Met-NH(2) and D-Phg NH(2) as chiral auxiliaries were used as derivatizing reagents under microwave irradiation. Derivatization conditions were optimized. Reversed-phase high performance liquid chromatography was successful using binary mixtures of aqueous trifluoroacetic acid and acetonitrile for separation of diastereomeric pairs with detection at 340 nm. Thin silica gel layers impregnated with optically pure L histidine and L-arginine were used for direct resolution of enantiomers. The limit of detection was found to be 60 pmol in HPLC while in TLC it was found to be in the range of 0.26-0.28 ug for each enantiomers. PMID- 20737656 TI - Anxiolytic-like effects of standardized extract of Justicia pectoralis (SEJP) in mice: Involvement of GABA/benzodiazepine in receptor. AB - Justicia pectoralis (Acanthaceae) is used as an antiinflammatory, antimicrobial and bronchodilator, and its extract exerts an anxiolytic-like effect profile in animal models. This work presents the behavioral effects of an aqueous standardized extract of Justicia pectoralis (SEJP) in animal models, such as the elevated plus maze (EPM), light/dark, open field, rota rod and pentobarbital sleep time. The extract was administered intragastrically to male mice at single doses of 50, 100 and 200 mg/kg, while diazepam 1 or 2 mg/kg was used as a standard drug and flumazenil 2.5 mg/kg was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg/kg), SEJP significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field, rota rod and pentobarbital sleep time tests. Flumazenil reversed not only the diazepam effect but also the SEJP effect. In the same way, all doses of SEJP increased the time of permanence in the light box in the light/dark test. The results showed that SEJP presented an anxiolytic-like effect, disproving sedative effects. PMID- 20737657 TI - The link between value motives, value success, and well-being among people diagnosed with cancer. AB - OBJECTIVE: This study investigated the relationship between cancer patient's values and cancer related distress. METHOD: A total of 107 patients with cancer diagnoses completed an anonymous questionnaire. RESULTS: Less self-regulating motivation for health values was significantly related to poorer well-being. Greater success at living one's values was significantly related to improved well being and distress-related outcomes. Sex difference analysis suggested that success at friendship values was linked to less cancer-related distress among women, but not men, whereas success at romantic relationship values was linked to less distress among men, but not women. CONCLUSION: The results have important implications for values focused interventions, highlighting the importance of facilitating success at valued living and attending to sex differences among cancer patients. PMID- 20737658 TI - Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats. AB - Several recent preliminary clinical studies have suggested that artichoke (Cynara scolymus L., Asteraceae family) preparations may be capable of lowering post prandial glycemia. The present study was designed to test this hypothesis in laboratory rats. To this aim, non-selected Wistar and genetically obese Zucker rats were treated acutely with a purified extract of Cynara scolymus flowering heads (500-1500 mg/kg by gavage) immediately prior to 1 h access to a fixed amount of food. Glycemia was recorded 60, 120 and 360 min after food presentation. Treatment with Cynara scolymus flowering head extract resulted in a significant decrease of post-prandial glycemia in both rat strains. The lack of any fiber content in this Cynara scolymus flowering head extract excludes the involvement of dietary fibers in glycemia reduction. The results obtained constitute the first evidence of a hypoglycemic effect of an artichoke preparation in laboratory rodents and confirm previous observations made in humans. PMID- 20737659 TI - Fructus ligustri lucidi extracts induce human glioma cell death through regulation of Akt/mTOR pathway in vitro and reduce glioma tumor growth in U87MG xenograft mouse model. AB - The present study was undertaken to examine the effect of Fructus ligustri lucidi (FLL) extracts on glioma cell growth and to determine the underlying mechanism by which FLL extracts exert anticancer properties in human U87MG glioma cells. The FLL extracts resulted in cell death in a dose- and time-dependent manner. Western blot analysis showed that treatment with FLL extracts caused down-regulation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Overexpression of Akt prevented the cell death induced by the FLL extracts. The FLL extracts caused a decrease in the expression of mammalian target of rapamycin (mTOR) and the FLL extract-induced cell death was increased by the mTOR inhibitor rapamycin. The FLL extracts decreased the expression of survivin. Oral administration of FLL extracts in subcutaneous U87MG xenograft models reduced the glioma tumor volume. These findings indicate that the FLL extracts resulted in glioma cell death through regulation of the Akt/mTOR/survivin pathway in vitro and inhibited glioma tumor growth in vivo. These data suggest that the FLL extracts may serve as a potential therapeutic agent for malignant human gliomas. PMID- 20737660 TI - Should routine peripheral blood glucose testing be done for all newborns at birth? AB - PURPOSE: To determine the (1) incidence of peripheral blood glucose (PBG < 40 mg/dL) in infants within 2 hours of birth and (2) validity of using maternal and infant risk factors and/or infant signs/symptoms of hypoglycemia as a screen for PBG < 40 mg/dL. STUDY DESIGN: Descriptive study with a convenience sample of 220 mother-infant dyads admitted to a mother-baby unit. Maternal and infant risk factors and infant signs/symptoms of hypoglycemia were assessed, and a PBG value was obtained within 2 hours of birth from the infant. Data were analyzed with descriptive statistics, multiple regression analysis, and sensitivity and specificity testing. RESULTS: The incidence of PBG < 40 mg/dL was 5.1% (N = 10 of 198). Fifteen maternal/infant risk factors were found; 2 of the 23 risk factors predicted PBG values within 2 hours of birth at a statistically significant level (jitteriness [p = .011] and tachypnea [p = .033]). Sensitivity was 71.9% and specificity 44.7% for using the presence of at least one maternal/infant risk factor and/or infant signs/symptoms of hypoglycemia to correctly identify PBG < 40 mg/dL within 2 hours of birth. CLINICAL IMPLICATIONS: Nurses working with mothers and infants can use the data from our study along with the recommendations from professional organizations such as American Academy of Pediatrics to begin a conversation at their institutions about revising protocols for routine PBG testing. Screening infants for maternal/infant risk factors and infant signs/symptoms of hypoglycemia could be used instead to safely decrease by 45% the number of infants who would need to have a PBG sample obtained within 2 hours of birth. PMID- 20737661 TI - Festschrift to honor Edward J. McGuire. October 23-24, 2008. Ann Arbor, Michigan, USA. PMID- 20737662 TI - The Plasmodium stage manager. PMID- 20737663 TI - eDNA limits biofilm attachment. PMID- 20737664 TI - Baculoviruses 'ride' actin. PMID- 20737666 TI - Chlamydia gets a NUE look. PMID- 20737665 TI - PD1 turns down the heat. PMID- 20737667 TI - Proceedings of the 17th International Conference on Radionuclide Metrology and its Applications (ICRM 2009). September 7-11, 2009. Bratislava, Slovak Republic. PMID- 20737668 TI - TCA signals a switch. PMID- 20737669 TI - Retraction notice to "Characterization and mechanistic analysis of the visible light response of cerium and nitrogen co-doped TiO2 nano-photocatalyst synthesized using a one-step technique" [Journal of Hazardous Materials 176 (2010) 829-835]. PMID- 20737670 TI - Retraction notice to "Study of the filtration performance of a plain wave fabric filter using response surface methodology" [J. Hazard. Mater. 176 (2010) 559 568]. PMID- 20737671 TI - A rare case of horseshoe lung presenting in adulthood and associated with a pulmonary sling: case report and review of the literature. AB - Horseshoe lung is a rare congenital malformation in which the pulmonary parenchyma connects in the midline posterior to the pericardium and anterior to the aorta and esophagus. There have been 51 case reports in the world literature. About 80% of these have been associated with Scimitar syndrome, and most cases are diagnosed in infancy due to pulmonary symptoms. To our knowledge, this is the first case report of horseshoe lung presenting in an adult and associated with a pulmonary sling, complete bowel malrotation, and renal ectopia. PMID- 20737672 TI - Weak at the knees. PMID- 20737673 TI - A large cystic intrasellar and suprasellar tumor. PMID- 20737674 TI - [Diagnostic value of the determination of salivary acute-phase proteins in patients with myocardial infarction]. AB - The salivary and plasma levels of acute phase proteins were determined in 59 patients with myocardial infarction (MI). In acute and subacute MI, the content of ceruloplasmin, orosomucoid, and alpha1-antitrypsin increased not only in the plasma, but also in the saliva. A noninvasive procedure was devised to diagnose the termination of an inflammatory process in the necrotic process in MI, which implies the determination of salivary ceruloplasmin, if the latter is less than 106 mg/l, inflammation completeness in the necrotic area is diagnosed. The procedure is simple, reliable, and usable in clinical laboratories. PMID- 20737675 TI - [Methods for determining the activity of lysosomal hydrolases used in diagnosis of hereditary lysosomal diseases]. AB - The paper describes biochemical methods for determining the activity of a number of lysosomal hydrolases, deficiency of which underlies hereditary lysosomal storage diseases. The methods permit the precise diagnosis of the diseases in a patient and the prenatal diagnosis of a disease in a fetus in at-risk families. PMID- 20737676 TI - [Methylglyoxal--a test for impaired biological functions of exotrophy and endoecology, low glucose level in the cytosol and gluconeogenesis from fatty acids (a lecture)]. AB - In philogenesis, due to the failure to store a great deal of carbohydrates in vivo as glycogen, all animal species began synthesizing from glucose palminitic fatty acid and depositing it as triglycerides. During biological dysfunction of exotrophy (long starvation, early postnatality, hibernation), cells also accomplish a reverse synthesis of glucose from fatty acids under aerobic conditions. Under physiological conditions, acetyl-CoA that is converted to malate and pyruvate in the glyoxalate cycle is a substrate of glyconeogenesis. Under pathological conditions of hypoxia and deficiency of macroerges, gluconeogenesis occurs without ATP consumption through the methylglyoxal pathway when used as a substrate of ketone bodies via the pathway: butyric acid (butyrate) --> beta-hydroxybutyrate --> acetoacetate --> acetone --> acetol --> methylglyoxal --> S-D-lactol-glutathione --> D-lactate --> pyruvate --> D lactate. Under physiological conditions, this gluconeogenesis pathway does not function. We believe that with low glucose levels in the cell cytosole (glycopenia), under pathological conditions of hypoxia and due to failure to mitochondria to oxidize fatty acids, gene expression and gluconeogenesis occur through the methylglyoxal pathway. At the same time, the cytosol, intercellular environment, and plasma shows the elevated levels of methylglyoxal and D-lactate that it is converted to by the action of glyoxalases I and II. Under pathological conditions, glycopenia develops in starvation, diabetes, and metabolic acidosis, neoplasms, renal failure, and possibly, metabolic syndrome. The chemical interaction of methylglyoxal with the amino acid residues of lysine and arginine results in the denaturation of circulating and structurized proteins via carbonylation--glycosylation. PMID- 20737677 TI - [Urgent problems in the diagnosis of acute respiratory viral infections]. PMID- 20737678 TI - [Domestic chromogenic nutrient medium for differentiation of Klebsiella]. AB - Studies to design a dry chromogenic nutrient medium for the diferentiation of Klebsiella were under way, by detecting the intracellular Klebsiella genus specific enzyme of human potential pathogenicity--5-aminosalicylate decarboxylase. The composition of the proposed medium that ensured its high sensitivity and improved its differentiating properties as compared with the known traditional media was worked through. Klebsiella are isolated and identified on the proposed medium in one step, which substantially reduces diagnosis time and material costs and takes some burden from microbiologists. PMID- 20737679 TI - [The biofilm formation in Yersinia pestis strains isolated in Astrakhan region]. AB - AIM: To study biofilm formation in strains of Yersinia pestis isolated in 2009 in Astrakhan region. MATERIALS AND METHODS: Study of biofilm formation was performed on abiotic surfaces as well as on cuticle of nematode Caenorhabditis elegans. Detection of genes was performed by PCR with specific primers. RESULTS: Study of phenotypic (fermentation of sugars and alcohols) as well as genetic (presence of plasmids, genes of chromosome region of pigmentation) characteristics of Y. pestis strains showed that they are typical for strains isolated in Astrakhan region. All isolated in 2009 strains formed well developed biofilm on abiotic surfaces and cuticle of C. elegans nematode. They contained genes of hms operon and regulatory genes hmsT and hmsP, which are necessary for formation of pigmented colonies on Congo red medium as well as biofilm on abiotic and biotic surfaces. CONCLUSION: Strains of Y. pestis isolated in 2009 in Astrakhan region formed well developed biofilm on different types of surfaces, which could facilitate their survival in complex parasitic biocenosis of plague natural focus. PMID- 20737680 TI - [Issues of optimization of legislation concerning prevention of spread of infection caused by human immunodeficiency virus]. PMID- 20737681 TI - [Epidemiological and molecular biological analysis of causes of rise of hepatitis A incidence in Republic of Tuva in 2008]. AB - AIM: Analysis of hepatitis A (HA) incidence in Tyva Republic in 2008 exploiting traditional epidemiological and molecular methods. MATERIALS AND METHODS: Epidemiological analysis of HA cases and contact persons in Erzinsky and Kyzyl regions of Tyva Republic was performed. Class M and G antibodies to HAV were determined in serum samples (n = 28), and HAV RNA--in stool samples (n = 16). Phylogenetic analysis of HAV RNA sequence was performed for VP1/2A region of the HAV genome with length 394 nucleotides. RESULTS: Cases of HA were registered during 3.5 months. Water supply sources did not have deviations from established standards. According to results of interviews, common food factor, which was able to cause the rise of HA incidence, was not determined. Signs of fecal contamination were revealed on environmental objects in preschool institutions and schools that demonstrate the low level of hygienic behaviour. It was shown that all cases of HA are related with different variants of the virus belonged to genotype IA that points to the absence of common source of infection. CONCLUSION: Results of epidemiological and genetic analysis of HAV demonstrate that observed rise in HA incidence in Tyva Republic are connected with phase of seasonal rise of HA incidence, which is characteristic for its perennial dynamics with active realization of contact route of virus transmission. PMID- 20737682 TI - [Results of preclinical study of inactivated subunit adsorbed monovalent influenza vaccine "PANDEFLU"]. AB - AIM: To perform preclinical study of subunit monovalent adsorbed inactivated influenza vaccine "PANDEFLU" [strains A/California/7/2009 (HIN1)v]. MATERIALS AND METHODS: Preclinical study of acute toxicity on experimental animals (assessment of vaccine's toxic effects on organs and body systems; pathomorphologic study of organs and tissues after administration of the vaccine; assessment of its influence on hematologic indicators). RESULTS: It was shown that administration of the vaccine did not lead to death of animals as well as to decrease of body mass or development of pathologic, focal sclerotic changes in parenchymal cells and visceral stroma; the vaccine did not negatively change hematologic and biochemical indicators of blood. Results of necropsy and histological study after acute administration of the vaccine in standard dose did not lead to irritation, inflammation or destruction of tissues in the place of inoculation. The vaccine was apyrogenic and did not have local irritating and allergenic effects. Status of animals after acute inoculation of the vaccine demonstrated its good tolerability and safety in doses exceeding standard human doses more than tenfold. CONCLUSION. Performed research demonstrated absence of contraindications for conduction of clinical trials of "PANDEFLU" vaccine on limited contingent of volunteers. PMID- 20737683 TI - [Study of tolerability and reactogenicity of pandemic vaccines against influenza type A/H1N1]. AB - AIM: To study tolerability and safety of pandemic vaccines against influenza A/H1N1 "INFLUVIR" and "PANDEFLU" on limited group of volunteers during phase I clinical trial. MATERIALS AND METHODS: Thirty healthy volunteers were participated in phase I clinical trial. Clinical and laboratory tests of volunteers randomized to 2 groups (20 persons received vaccine and 10 persons - placebo) were performed. "INFLUVIR" vaccine was administered by intranasal route. Volunteers were hospitalized and followed up for development of local and systemic adverse events during 7 days after vaccination. "PANDEFLU" was administered intramuscularly; vaccinees were followed for 7 days in outpatient settings. RESULTS. Phase I clinical trial showed good tolerability and low reactogenicity of "INFLUVIR" and "PANDEFLU" vaccines. There were no moderate and severe local and systemic adverse events registered. CONCLUSION: On the basis of performed phase I clinical trial, phase II trial was recommended to perform in order to assess the reactogenicity, safety and immunogenicity of studied vaccines. PMID- 20737684 TI - [Effect of methods of application of bacterial ligands on activation of lymphoid organs' effectors in mice]. AB - AIM: Evaluation of differentiation dynamics and localization of various populations of lymphocytes as well as their expression of TLRs during different methods of administration (intranasal, oral, and subcutaneous) of bacterial ligands of opportunistic microorganisms (Immunovac-VP-4 vaccine) in experiment on mice. MATERIALS AND METHODS: Polycomponent vaccine Immunovac-VP-4 consisting of ligands of 4 opportunistic bacteria was administered to CBA line mice. Groups of mice were immunized orally, subcutaneously, or intranasally. Number of mononuclear leukocytes, as well as levels of cytokines, lymphocytic antigens, and cytotoxic activity of cells were measured. RESULTS: It was demonstrated that modification of immunophenotype of lymphocytes and cytotoxic activity of NK cells depends from route of administration of Immunovac-VP-4 because the most intensive activation of cells occurred in organs proximal to place of vaccine application. However, already 1 day after administration of vaccine there was intensive exchange between lymphoid cells not only in nasal associated lymphoid tissue, bronchial associated lymphoid tissue, and gut associated lymphoid tissue but also in spleen that points to integration of fine mechanisms of mucosal and systemic immune response regulation. CONCLUSION: Development of noninvasive methods of vaccination is an optimal way of safe and mass prevention of infectious diseases. PMID- 20737685 TI - [Bacillus genus bacteria are producers of biologically active compounds with antimicrobial effect]. AB - Biologically active compounds of spore-forming bacteria of Bacillus genus, which have antagonistic effect on opportunistic and pathogenic microorganisms, are characterized in the review. Information about known to date antibiotics and bacteriocins produced by Bacillus species is presented. PMID- 20737687 TI - [Hygienic assessment of large-size hole type storages for low-to-moderate activity radioactive waste]. AB - Analysis of the design features of radioactive waste (RAW) storages of large-size hole type, geological and hydrogeological conditions of their location, a multi barrier system for environmental protection, and the reliability of a computer aided geomonitoring system allows one assess these facilities as meeting the current International Atomic Energy Agency recommendations for RAW storages. PMID- 20737686 TI - [The status and measures to secure safe household water supply in the Russian Federation]. AB - To preserve the health of our nation, to reduce mortality rates, and to increase longevity are the most important conditions for solving the problem of national security. The Russian Federation completely supports the world community's efforts to conserve water bodies and to prevent the spread water-borne diseases. Despite the fact that Russia is the largest water country and has one fifth of the worldwide resources, the situation in this sphere is serious as before. Portable water deficiency in a number of the Russian Federation's subjects, such as the Kostroma, Kaluga, and Pskov Republics, the Republic of North-Alania, etc., is one of the poor factors of household water supply. To improve the provision of our country's population with good-quality drinking water, the Russian Inspectorate for the Protection of Consumer Rights and Human Welfare, continuously does work to improve the legal and regulatory basis that stipulates sanitary-and-epidemiological standards for portable water and drinking water supply. PMID- 20737688 TI - [Microbial risk assessment to establish water quality-enteric infection morbidity relationships]. AB - The authors have constructed a mathematical model for the cause-and-effect relationship between acute enteric infection (AEI) morbidity and the levels of water bacterial contamination and the properties of microorganisms. New procedures were proposed to calculate a risk for water-borne AEI depending on the sanitary-and hygienic conditions of water use and the degree of water contamination in the direct isolation of the causative agents of pathogenic and opportunistic infections, which allow the calculation and prediction of the occurrence of AEI at the individual and population levels. PMID- 20737689 TI - [Use of controlled respiratory rhythm to enhance stress resistance in pupils]. AB - To enhance stress resistance in pupils is now a very urgent problem. The influence of a method affecting the central nervous system as acquisition of the averaged value of intrinsic respiratory rhythm has been studied. There has been a positive result of using the procedure to increase working capacity during performance by pupils and positive changes in electroencephalographic readings, by optimizing the autonomic provision for their activity. PMID- 20737690 TI - [Changes in the anthropometric characteristics of neonatal infants and in the reproductive behavior of the indigenous population of Chukotka]. AB - The anthropometric characteristics of neonatal infants from the Chukotka indigenous population, age of onset of sexual behavior, and maternal age at first birth were assessed from the records available in 257 labor histories. According to the WHO criteria, physical development was rated as satisfactory in a 2000 2003 neonatal cohort. Birth weight and head and chest circumferences in the neonates were significantly lower than those in a 1967-1970 one. The proportion of babies who had birth weight less than 2500 was 97 per thousand, which was higher than the average value in the Russian Federation and than that of the indigenous population of Alaska and Canada. By the early 2000s versus 1990, reproductive behavioral changes in the native women of Chukotka were exhibited by an average 17-month decrease in age of onset of sexual behavior to 16.9 and 17.26 years in females living in the settlements and villages, respectively. In the meantime, the mean female age at first birth did not differ from that for a group of traditional lifestyle (18-19 years), but the dispersion of the indicator was on the rise. As a result, the proportion of parturients among the Chukchi girls aged 17 years or younger was 2-4 times (according to the place of residence) greater than the total Russian value. PMID- 20737691 TI - [Autonomic cardiac rhythm regulation in adolescents during simulation of conflict inducing medium]. AB - Autonomic balance shifts were studied from the parameters of cardiac rhythm variability in subjects of both sexes with a varying conflict potential under the influence of a conflict-inducing factor. There was autonomic balance displacement towards a reduced sympathotonus in conflict subjects irrespective of gender and in non-conflict girls during simulation of a conflict-inducing medium, which suggests their favorable response to presented loads. The sympathetic part of the autonomic nervous system was found to play an increased role in the regulation of cardiac performance in examined non-conflict boys during simulation of a conflict inducing medium, suggesting the development of psychogenic emotional tension by the negative psychosomatic type. PMID- 20737692 TI - [Biologically active additives in health prophylaxis of medical workers]. AB - The aim of the investigation was to use the biologically active additive (BAD) Kalifen to prevent metabolic disturbances in medical workers during their occupational activity. Female physicians aged 40-50 years were examined. Group 1 (control) included 20 age-matched healthy female donors. Group 2 comprised 27 female physicians (anesthesiologists and surgeons) daily exposed to stresses (chemical, psychoemotional, work-related, etc.) who were asked after blood biochemical tests to daily take the BAD Kalifen in a dose of 2.5 ml after a meal (they made up Group 3), which is equal to the daily prophylactic dose in 100 mg of total polyphenols. The plasma tested before an experiment showed hypertriglyceridemia and hypercholesterolemia, suppressed hepatic etherifying function, imbalance of the fractional content of phospholipids, exhaustion of the antioxidative system, increased lipid peroxidation, and impaired erythrocytic membrane permeability. The prophylactic use of the BAD Kalifen eliminates stress induced metabolic disturbances and increases occupational and biological longevity in the able-bodied population. PMID- 20737693 TI - [Consideration of a potential death risk in the methodology of assessing the population's health]. AB - It has been shown that when calculating the summarized population's health index and the significance (weight) of partial signs, it is expedient to use the calculation from the potential death risk index rather than an expert judgment. The results of calculation examples using morbidity and mortality rates suggest that public health can be assessed on this methodic ground. It is advisable to apply the proposed method for assessing the population's health during sanitary and-epidemiological surveillance (sociohygienic monitoring) when decisions are taken on the lines of health-promotion measures to reduce morbidity and mortality mainly by circulatory diseases, neoplasms, injuries, and intoxications. PMID- 20737694 TI - [Synthetic materials used in surgery and their transformation in organism]. AB - Our experience of elaboration and introduction of various synthetic materials proves trustworthily the necessity of conduction of a long-term complex investigations by various scientific centers with the objective of creation and application in Ukrainian surgical practice a medical materials of own production as accessible, safe and qualitative preparations. And more, the Ukraine may implement such programs, taking into account a great scientific-technical power she owes. PMID- 20737695 TI - [Experimental investigation of intra-abdominal pressure influence on multiple organ insufficiency and bacterial translocation]. AB - The influence of intraabdominal hypertension on polyorgan insufficiency and bacterial translocation formation was studied in experiment on 40 white male rats owing mass about 250-300 g. Intraabdominal pressure (IAP) raising in the rats causes abdominal ischemia and consequent early changes in anterior abdominal wall muscles, small intestine and large bowel, kidneys, spleen, liver, and bacterial.translocation as well. The results of investigation trusts the necessity of monitoring and IAP effective control conduction in surgical patients. PMID- 20737696 TI - [Treatment of nonparasitic hepatic cyst in experiment]. AB - Experimental investigation was conducted in two stages. During the first stage there was planned to create a nonparasitic hepatic cyst simulation and during a second one--various methods of physical processing of the cyst residual cavity with the objective to estimate their efficacy and traumaticity. After fulfillment of the second stage of experiment euthanasia of the laboratory animals was performed during the determined term, histological investigation of preparations was conducted. PMID- 20737697 TI - [Hepatic tissue regeneration after electrothermocoagulation in experimental pathology of local blood circulation]. AB - The regeneration processes course in the liver, occurring after its wedge resection performance using electrothermoadhesion method, were studied on two simulating models: the stress model of atherosclerosis and experimental hyperglycemia. The dynamics of morphological changes in the liver observed have had witnessed a tendency preservation towards formation of elastic linear cicatrix of collagen and a full-fledged morphofunctional restoration of liver after the operation. Peculiarities of the restoration processes course were connected with the disorder severity. PMID- 20737698 TI - [Surgical treatment of anal sphincter insufficiency using the flaps of the gluteus maximus muscle]. AB - The anal sphincter insufficiency stage III, caused by inborn developmental disorders and traumatic affection of its vast portions, may be successfully eliminated using plasty performance with application of a long flap of muscle gluteus maximus. Various ants of the operation were applied in 29 patients. Electrostimulation of muscles and curative exercises were conducted before and after the operation. Good and satisfactory results were achieved in 21 patients. PMID- 20737699 TI - [Role of an anesthesiologist-resuscitation specialist in organ donation for transplantation]. AB - There is an annual reduction in the number of donors worldwide. An anesthesiologist-resuscitation specialist is a key figure in the whole system of organ donation. The so-called transplantation, i.e., the organization of the whole process of interaction between a healthy care facility, a local organ donation center, and ancillary laboratory and diagnostic services is one of his/her primary roles in organ donation. The organizational, legal, and ethic issues of organ donation for transplantation are discussed from the viewpoint of an anesthesiologist-resuscitation specialist. There is a parallel between the treatment of a patient with multiple organ dysfunction and the management of a donor with brain death. PMID- 20737700 TI - [Chronic pain management in non-cancer patients]. AB - Chronic non-cancer pain management is an urgent global problem. To set up pain clinics is a promising and economically sound approach. There are pain clinics operating in Russia; however, there are no unified approaches to solving their organizational, therapeutic, and educational-and-methodological problems. An antipain care model is proposed for patients with chronic non-cancer pain, which makes it possible to optimize the treatment of the patients, to train pain specialists, and to enhance the economic efficiency of management. PMID- 20737701 TI - [Using noninvasive positive pressure (mask) pulmonary ventilation in patients with acute myocardial infarction]. AB - As of now, medical therapy for acute heart failure has achieved considerable clinical results. Nevertheless, the treatment of cardiogenic pulmonary edema (CPE) and respiratory failure remain unsolved problems, complicate the course of disease, and increase mortality among patients with acute myocardial infarction (AMI). Hospital mortality due to acute heart failure ranges from 4% and runs up to 36% in artificial ventilation-requiring situations. Noninvasive respiratory support in various modes, such as continuous positive airway pressure, pressure support ventilation (PSV), and PSV + positive end-expiratory pressure (PEEP), is an effective method for the treatment of standard medical therapy-refractory CPE in patients with AMI. Noninvasive ventilation (NV) shows clinical improvement and positive changes in the parameters of not only hemodynamics, but also gas exchange. The efficiency of various NV modes and the nature of their action on such indices, such as respiratory movement rate, heart rate, mean pulmonary artery pressure, pulmonary artery wedge pressure, peripheral tissue oxygen delivery index, pO2a, pulmonary artery pO2, and Qs/Qt, have proved similar. There is a difference in the impact of PSV and PSV+PEEP on the increase in the left ventricular stroke output index and on the reduction in arterial blood CO2 tension. PMID- 20737702 TI - [Role of an educational-and-methodological complex in the optimization of teaching at the stage of additional professional education of physicians in the specialty "anesthesiology and reanimatology"]. AB - An educational-and-methodological complex (EMC) in the specialty 'Anesthesiology and Reanimatology", which promotes manageability, flexibility, and dynamism of an educational process, is of great importance in solving the problem in the systematization of knowledge and its best learning by physicians at a stage of additional professional education (APE). EMC is a set of educational-and methodological materials required to organize and hold an educational process for the advanced training of anesthesiologists and resuscitation specialists at the stage of APE. EMC includes a syllabus for training in the area "Anesthesiology and Reanimatology" by the appropriate training pattern (certification cycles, topical advanced training cycles); a work program for training in the specialty "Anesthesiology and Reanimatology"; a work curriculums for training in allied specialties (surgery, traumatology and orthopedics, obstetrics and gynecology, and pediatrics); work programs on basic disciplines (pharmacology, normal and pathological physiology, normal anatomy, chemistry and biology); working programs on the area "Public health care and health care service", guidelines for the teacher; educational-and-methodological materials for the student; and quiz programs. The main point of EMC in the specialty "Anesthesiology and Reanimatology" is a work program. Thus, educational-and-methodological and teaching materials included into the EMC in the specialty 'Anesthesiology and Reanimatology" should envisage the logically successive exposition of a teaching material, the use of currently available methods and educational facilities, which facilitates the optimization of training of anesthesiologists and resuscitation specialists at the stage of APE. PMID- 20737703 TI - [Quality and efficiency of medical care for workers exposed to conditions violating sanitary and hygienic rules]. AB - The authors analyzed results of organizing and performing preliminary and periodic medical examinations of workers exposed to conditions violating sanitary and hygienic rules, exemplified by Bashkortostan Republic. The analysis also covered some parameters of occupational morbidity changes since 1968 to 2008. To increase diagnostic efficiency for occupational diseases, according to the authors, one needs a whole system of evaluation and management of occuupational risks on basis of continuous development of compatible information databases concerning work conditions and workers' health parameters. PMID- 20737704 TI - [Psychologic and educational conditions to preserve psychologic health in medical college students]. AB - Psychologic counselling program was designed for medical college students to preserve and strengthen the psychologic health. Comparative analysis of psychologic health parameters in main (experimental) group of students subjected to the program vs. the reference group who did not participate in the experiment proved the program efficient. PMID- 20737705 TI - [Phylogeny, development of processes of cellular fatty acid transfer and absorption, biological locomotion function, and insulin function. Pathogenesis of insulin resistance syndrome]. AB - Passive cellular absorption of first glucose (Glu) and then fatty acids (FA) as substrate for energy generation formed during phylogeny. Glucose transporters ensure Glu absorption; the cells absorb FA as polar unetherified FA from the associates with albumin and oxidize them at once. Later there was an active cell absorption of saturated and unsaturated (with one-three double bonds) FAs as nonpolar triglycerides as part of very low-density lipoproteins via apoB-100 receptor-mediated endocytosis. When the biological function of locomotion was established, there was an insulin (Ins) system; the latter initiated apoE vector synthesis and targeted FA transfer mainly to skeletal myocytes and formed apoE/B 100 endocytosis. The major role of Ins is energy provision for the biological function of locomotion. Ins blocks the lipolysis and oxidation of FA in the myocytes until the cytosol contains sufficient Glu, and activates its absorption from the intercellular medium. FA lipolysis and oxidation begin only in glycopenia. Activation of myocytic FA oxidation with normal Glu levels and blocked lipolysis underlies Ins resistance. This occurs with: a) activated biological function of adaptation, a biological stress reaction, and the elevated intercellular levels of unetherified FAs that are passively absorbed and oxidized by cells; b) impaired biological function in exotrophy--high dietary palmitinic FA levels, a biological reaction of FA transfer to the cells, and blockade of apoE/B-100 endocytosis; c) impaired biological function of endoecology, purity of the intercellular medium, biological function of inflammation, and synthesis of lipid transfer C-reactive protein that as a vector redirects a flux of FA from myocytes to interstitial cells that realize the systemic inflammatory response syndrome. Since the formation of biological functions of adaptation, exotrophy, and endoecology occurred earlier than that of biological function of locomotion, Ins resistance is the enhanced passive cell absorption of FA, as this took place before the function of locomotion was formed. According to our described principle of biological subordination, phylogenetically later Ins cannot regulate the processes formed in earlier steps of phylogeny. PMID- 20737706 TI - [Modulation of afferent nerve impulsation by certain physical factors (experimental study)]. AB - Effects of different therapeutic physical factors of electromagnetic (millimeter wavelengths waves, polychromatic light) and mechanical (high- and low-frequency ultrasound) nature on the pulsed electrical activity of afferent somatic fibers in n. saphenus were evaluated in acute experiments using anesthetized rats. It was shown that the action of these factors on the afferent nerve impulsation frequency (its increase or decrease) depends on the choice of dosimetric parameters. PMID- 20737707 TI - [The role of therapeutic exercises in the combined treatment and rehabilitation of patients with pain syndrome associated with the dysfunction of temporomandibular joint]. AB - In a group of patients with pain syndrome associated with the dysfunction of temporomandibular joint positive results of combined therapy and rehabilitative treatment including remedial gymnastics persisted significantly longer than in controls (p < 0.01). Results of long-term follow-up confirmed the desirability of rehabilitation based on therapeutic exercises. This approach permits to enhance the effectiveness of therapy and rehabilitation of patients with pain syndrome associated with the dysfunction of temporomandibular joint, reduce the number of the patients' visits for repeated treatment and its total duration during a year. PMID- 20737708 TI - [The study of expression of apoptosis receptors (CD95+) on the surface of neutrophils from cervical secretion of women with chlamydial infection and the possibility of its correction by magnetic laser radiation]. AB - The present work was designed to study the expression of CD95 antigen (Fas/APO-1) at the surface of neutrophil granulocytes from the cervical secretion. Sixty five female patients with Chlamydia infection available for observation exhibited enhanced CD95+ expression following basic therapy. It was found that combined treatment with the use of magnetic laser radiation normalized the level of CD95+ surface receptors on neutrophils. PMID- 20737709 TI - [Correction of immune and mediator characteristics by low-frequency magnetotherapy in children who frequently fall ill]. AB - The objective of this work was to compare characteristics of clinical condition and immune status of children with repeated respiratory diseases of different clinical and nosological forms after standard treatment and magnetotherapy. It was shown that magnetotherapy produces well-apparent immunocorrective effects in children with the affected upper and lower respiratory tracts including patients with bronchial obstruction syndrome. Positive changes of both cellular and humoral immunity characteristics were documented coupled to the improvement of serum cortisol levels. Results of the study give reason to recommend inclusion of magneotherapy in the combined treatment of children with repeated respiratory diseases. PMID- 20737710 TI - [A chronobiological approach to the treatment of obesity in children based at a sanatorium and spa facility]. AB - The objective of the study was to evaluate results of non-medicamental treatment of 167 children with obesity taking into account dynamics of annual rhythms of their clinical, hormonal, metabolic, and psychological characteristics. The period from August till November was shown to be especially favourable in terms of body weight loss, improvement of hormonal, metabolic, and psychic status. Analysis of these changes permitted to correct the proposed mode of combined therapy of obesity during the period from December till July. PMID- 20737711 TI - [The problem of specificity in physiotherapy]. PMID- 20737713 TI - [Choice of an upper urinary tract drainage method in urolithiasis]. AB - We made a retrospective (290) and a prospective (131) analysis of the evidence obtained on 421 patients with nephrostomic drainage (251) and an ureteral stent (170) treated for urolithiasis in the urological department of the Moscow Regional Research Clinical Institute from 1995 to 2008. Assessment of clinical and laboratory characteristics of the patients with nephrostomic drainage and an ureteral stent allowed the following conclusions: puncture nephrostomy (p < 0.05) for upper urinary tract drainage is preferable in a solitary functioning kidney, acute obstructive pyelonephritis, anuria, hyperthermia 380 and higher, marked supravesical urodynamic disorder, renal failure, plasmic creatinine level over 200 mcmol/l, azotemia over 10 mmol/l, blood potassium over 5.0 mmol/l, uric acid over 380 mcmol/l and leukocytosis over 8.0 x 10(9)/l. In the other cases a drainage method can be chosen by a physician. Cephalosporines, aminoglycosides, fluoroquinolones and carbapenems in standard doses are recommended in active inflammation when antibioticograms are not obtained yet. Significant differences are seen in drainage with nephrostoma and ureteral stent. Recommendations on nephrostomic drain and ureteral stent installation depending on clinical and laboratory findings are presented. PMID- 20737712 TI - [Endothelial dysfunction in urolithiasis patients]. AB - To characterize endothelial dysfunction in operated nephrolithiasis patients, we studied NO, VEGF, ET-1, IL-6 concentration in the blood serum and NO in the urine of nephrolithiasis patients divided into three groups by the type of surgical treatment before operation, 7-10 days and 1 month after it. We used beta-2 microglobulin as an indicator of tubular dysfunction. We found a significant rise of a concentration of the endothelial dysfunction markers ET-1, IL-6 and VEGF in the blood serum (p < 0.05), showing endothelial dysfunction in nephrolithiasis patients, especially in early postoperative period after multiple exposure to short-wave lithotripsy. One month after open surgery or lithotripsy a complete recovery of endothelial function was not recorded. PMID- 20737714 TI - [Ruptures of orthotopic ileoneocystis]. AB - Urgent surgical treatment was conducted in 3 patients admitted to hospital with neocystic rupture which occurred 6, 10 and 22 months after removal of the bladder with orthotopic cystoplasty. Two patients have undergone laparotomy, neocystic defect repair and drainage. In the third patient mobilization of the reservoir was accompanied with accidental cut of the ureters. Relaparotomy was made with bilateral ureterocutaneostomy. Intestinal plastic reconstruction of both ureters followed after stabilization of the patients' condition. Thus, all the patients with ileoneocystis rupture were successfully rehabilitated. PMID- 20737715 TI - [Nephrolithiasis: choice of optimal treatment]. AB - As shown by the results of 113 percutaneous operations for nephrolithiasis, percutaneous nephrolithotomy with lithoextraction is effective in dense, large, multiple, and in some cases, in stag-horn concrements. This operation is a method of choice. Mean duration of the operation is 38.3 +/- 3.8 min, hospital stay is 9.4 +/- 1.6 days. PMID- 20737716 TI - [Treatment of chronic prostatitis caused by chlamydial and ureaplasmic infection and complicated with male infertility]. AB - Etiologically, chronic prostatitis can result from urogenital latent infections caused by chlamydia, ureaplasma and others. First of all, such patients should be examined for urethritis. We examined 306 patients aged 23-45 years with chronic prostatitis caused by chlamydial and ureaplasmic infection. The samples were taken from the urethra, urine, prostatic secretion, ejaculate and were examined using direct immunofluorescence, polymerase chain reaction, culturing. We found spermatogenetic disorders in 50% patients, 35 (11.4%) patients had a deferent duct obstruction. The patients had also immunointerferon deficiency and alterations in prostatic echostructure. In chronic prostatitis caused by chlamydial-ureaplasmic infection the treatment must combine antibacterial drugs (vilprophen, unidox, solutab) with interferons (lavomax, genferon). Male infertility treatment should be started only after elimination of the bacterial infection. PMID- 20737718 TI - Considering robotics? Plan for a program, not just procedures. PMID- 20737717 TI - [Priapism: current understanding]. PMID- 20737719 TI - A "theatre of rule?" Domestic service in aristocratic households under the Third Republic. AB - E. P. Thompson developed the notion of "cultural hegemony" to analyse the power of the ruling class over the working class in eighteenth-century England. This article examines the aristocracy's endeavour to maintain its cultural hegemony in the France of the Third Republic. Drawing on the private archives of noble families, it documents servants' roles in supporting the "conspicuous consumption" of their employers, the hierarchy and wages of male and female servants and the language and gestures used in employer-servant interaction. It then looks at working-class responses to nobles' hegemonic ritual of hunting and concludes with discussion of the post-war socio-economic climate in which the distinctive features of domestic service in aristocratic households were gradually abandoned. PMID- 20737720 TI - Sorcery and publicity: the Cadiere-Girard scandal of 1730-1731. AB - The Cadiere-Girard trial of 1730-1731 is an early example of a sensational, nationally publicized French trial in which the major parties were private individuals. Cadiere, a female penitent, accused Girard, her Jesuit confessor, of bewitching and raping her; Girard claimed that Cadiere was guilty of slander. It was to be the last witchcraft trial in the francophone world. Another notable feature of the trial was its publicity, in which the contesting parties almost immediately became stand-ins for the Society of Jesus and for its Jansenist adversaries. This paper argues that certain anti-Jesuits, particularly Cadiere's defence team and in the Parlement of Aix-en-Provence, acted to prolong the trial with the aim of creating as much bad publicity as possible for the Society of Jesus; it also shows how Jansenist publicists took advantage of the lengthy process, creating literature that "burned Girard in spirit," and with him, the Jesuits as a whole. PMID- 20737721 TI - Innocence and experience: sexuality among young people in modern France, c. 1750 1950. AB - Prying into the sex lives of young people in the past has always proved a challenging exercise. Historians have often ended up relying on the testimony from adult observers or on the quantitative evidence provided by illegitimacy rates. This article adopts a more direct route by drawing on first-hand accounts of early sexual experiences written by French people in diaries, childhood reminiscences and autobiographies. As a preliminary, it analyses the way various authorities depicted young people as sexual (or non-sexual) beings, and the state of sex education in France before the mid-twentieth century. It then considers the way people depicted their first stirrings of sexuality during childhood and adolescence. Finally, it examines evidence from the "ego documents" on sexual relations in the run-up to marriage. PMID- 20737722 TI - "New Sport" in the street: self-defence, security and space in belle epoque Paris. AB - Near the turn of the twentieth century, traditional self-defence methods (for example, jiu-jitsu) were revamped into a more accessible and practical set of techniques and tactics for everyday use in urban public space. Framed as a "new sport" with broad public utility, early urban self-defence developed against the backdrop of heightening fears of violent crime and a burgeoning politics of security, as well as tensions provoked by the increasingly common appearance of unchaperoned, middle-class women in public. Self-defence masters pitched their innovations in an inclusive rhetoric, always with separate lessons for men and women and their respective spaces of risk. This article places modern self defence practices in tension with historical transformations in the urban landscape, arguing that urban self-defence posited a certain subjective relation to the city that tapped simultaneously into the desire for empowerment, fantasies of criminal danger and a law-and-order tone that shaded into urban vigilantism. PMID- 20737723 TI - The Pasteurization of Algeria? AB - This essay focuses on the anti-malarial campaigns of Edmond and Etienne Sergent in colonial Algeria during the period from 1900 to 1930. This Pasteur Institute of Algeria was part of an elaborate, global network of men and institutions that constituted the scientific empire of Third Republic France. It was deeply indebted to the methods pioneered by Pasteur and to the shared foundational myth that connected the overseas Pasteur Institutes to Paris. But the Sergent brothers' work operated within a dynamic context of international public health too. Algeria's European settlers had also worked out a creolized identity that was both dependent upon and distinct from metropolitan practices. Ultimately, the Pasteur Institute of Algeria bore the mark of the settler colonialism that had given rise to it. PMID- 20737725 TI - Cake And Conversation: the women's jour in Parisian high society, 1880-1914. AB - At the end of the nineteenth century an upper-class Parisian hostess invited guests into her home on a fixed afternoon of her choice each week. Was this tradition, known as the jour, merely an occasion to partake of refreshments and chat? Or did it serve broader purposes for the women of High Society? This article investigates the process of invitation to a jour, the subtle nuances of etiquette at these gatherings, conversation between men and women, and what was consumed in the way of food and drink. By documenting social interaction in the space of the salon, this article analyses the way in which "power" was constituted through bodily practices. It then goes on to show what the exercise of this power reveals about gender roles, and the structure of social relationships among the Parisian upper class, in the decades before the First World War. PMID- 20737727 TI - Neuroblastoma--a model disease for childhood cancer. PMID- 20737728 TI - Emergency preparedness committees need biomedical expertise. PMID- 20737729 TI - Building interoperable healthcare systems through IHE. PMID- 20737730 TI - The government of chronic poverty: from exclusion to citizenship? AB - Development trustees have increasingly sought to challenge chronic poverty by promoting citizenship amongst poor people, a move that frames citizenship formation as central to overcoming the exclusions and inequalities associated with uneven development. For sceptics, this move within inclusive neoliberalism is inevitably depoliticising and disempowering, and our cases do suggest that citizenship-based strategies rarely alter the underlying basis of poverty. However, our evidence also offers some support to those optimists who suggest that progressive moves towards poverty reduction and citizenship formation have become more rather than less likely at the current juncture. The promotion of citizenship emerges here as a significant but incomplete effort to challenge poverty that persists over time. PMID- 20737731 TI - A relational approach to durable poverty, inequality and power. AB - The article argues for what can be called a 'relational' approach to poverty: one that first views persistent poverty as the consequence of historically developed economic and political relations, and second, that emphasises poverty and inequality as an effect of social categorisation and identity, drawing in particular on the experience of adivasis ("tribals") and dalits ("untouchables") subordinated in Indian society. The approach follows Charles Tilly's Durable Inequality in combining Marxian ideas of exploitation and dispossession with Weberian notions of social closure. The article then draws on the work of Steven Lukes, Pierre Bourdieu and Arjun Appadurai to argue for the need to incorporate a multidimensional conception of power; including not only power as the direct assertion of will but also 'agenda-setting power' that sets the terms in which poverty becomes (or fails to become) politicised, and closely related to power as political representation. This sets the basis for discussion of the politics of poverty and exclusion. PMID- 20737732 TI - Increases in primary care physician income due to the Patient Protection and Affordable Care Act of 2010 - continued tweaking of physician payment. AB - The Patient Protection and Affordable Care Act (ACA) authorizes several changes to the Resource-Based Relative Value Scale (RBRVS) system that are designed to increase primary care physician personal income and reduce geographic variation in primary care payment. In this brief, the ACA-authorized primary care payment adjustments are modeled in a prototypical rural primary care practice to assess both the potential impact on physician personal income and the likelihood that the changes will achieve the desired policy outcome. Key Findings. (1) The Patient Protection and Affordable Care Act (ACA) increases physician personal income in a prototypical primary care practice an average of $3,537 (1.9%) in 2010 compared to baseline income as if the ACA were not enacted. In 2011, physician personal income in a prototypical primary care practice increases by an average of $12,013 (9.3%) compared to baseline. (2) Due to Geographic Practice Cost Index (GPCI) changes legislated by the ACA, physician personal income increases are greater in entire-state Medicare payment localities than in states with multiple Medicare payment localities. (3) The requirement that at least 60% of a practice's furnished services must be specific "primary care services" to receive the ACA primary care bonus may eliminate eligibility for rural primary care practices that tend to offer more procedures (thus proportionally fewer primary care services) than urban/suburban practices. (4) The ACA primary care payment increases may be too small to have a significant impact on primary care and rural physician shortages. Targeted and significant primary care payment bonuses may be a more effective policy to reduce specific physician shortages. PMID- 20737733 TI - All bleeding stops eventually. PMID- 20737734 TI - The need for sustainability in contemporary global health efforts: missions vs mission. PMID- 20737735 TI - Bile leaks and sepsis: drain now, fix later. PMID- 20737736 TI - Mom is not permitted to be ill. PMID- 20737737 TI - Rural Medicare Advantage: modest enrollment growth in 2010. PMID- 20737739 TI - School exclusion as social exclusion: the practices and effects of a conditional cash transfer programme for the poor in Bangladesh. AB - Evidence indicates that a much-feted conditional cash transfer programme designed to widen access to basic education in Bangladesh has failed in its aims. The programme is analysed here as an instance of the effort to govern chronic poverty. For the state, education fits within a national project of poverty reduction and creating governable citizens. For the poor, education signals social inclusion and access to the state. Yet class and social distinctions through which state actors 'see' poor children result in beneficiary selection practices that routinely exclude the poorest from school, with longer-term adverse effects for their social inclusion and citizenship. PMID- 20737738 TI - Governing chronic poverty under inclusive liberalism: the case of the Northern Uganda Social Action Fund. AB - The paradigm of 'inclusive neoliberalism' that currently characterises international development places a particular emphasis on community-based responses to the often structural problems of poverty and exclusion. Such approaches have become increasingly controversial: celebrated by optimists as the most empowering way forward for marginal citizens on the one hand, and derided as an abrogation of responsibility by development trustees by sceptics on the other. Uganda provides a particularly interesting context to explore these debates, not least because it has become a standard bearer for inclusive neoliberalism at the same time that regional inequalities within it have become increasingly apparent. Our investigation of the flagship response to deep impoverishment in its northern region, the World Bank-funded Northern Uganda Social Action Fund, offers greater support to the sceptics, not least because of the ways in which the more pernicious tendencies within inclusive neoliberalism have converged with the contemporary politics of development in Uganda. PMID- 20737740 TI - "We have always lived here": indigenous movements, citizenship and poverty in Argentina. AB - This article explores the nexus between indigenous mobilisation, citizenship, and poverty in Argentina. A subnational comparison of land struggles among the Diaguita Calchaqu in Tucumn and the Mbya Guaran in Misiones shows that changing global and national opportunity structures, most prominently a new multicultural citizenship regime, set the stage for indigenous mobilisation. In turn, local transformations of capitalist development motivate indigenous mobilising efforts, whereas leadership patterns and state-movement relations shape the capacity to mobilise. Diaguita and Mbya mobilisation reveals that indigenous movements play a central role in the activation of formal citizenship rights and the contestation of dominant notions of poverty. At the same time, the current design of multicultural citizenship and the adverse socioeconomic incorporation of indigenous communities also counteract indigenous mobilising efforts in Argentina. PMID- 20737741 TI - Decentring poverty, reworking government: social movements and states in the government of poverty. AB - The significance of social movements for pro-poor political and social change is widely acknowledged. Poverty reduction has assumed increasing significance within development debates, discourses and programmes - how do social movement leaders and activists respond? This paper explores this question through the mapping of social movement organisations in Peru and South Africa. We conclude that for movement activists 'poverty' is rarely a central concern. Instead, they represent their actions as challenging injustice, inequality and/or development models with which they disagree, and reject the simplifying and sectoral orientation of poverty reduction interventions. In today's engagement with the poverty-reducing state, their challenge is to secure resources and influence without becoming themselves subject to, or even the subjects of, the practices of government. PMID- 20737742 TI - The global household: toward a feminist postcapitalist international political economy. AB - The goal of this article is to introduce a new category into international political economy-the global household-and to begin to widen the focus of international political economy to include nonmarket transactions and noncapitalist production. As an economic institution composed of transnational extended families and codwellers (including international migrants and family members left behind in countries of origin), the global household is engaged in coordinating international migration, sending and receiving billions of dollars in remittances, and organizing and conducting market- and non-market-oriented production on an international scale. We first trace the discursive antecedents of the global household concept to theories of the household as a site of noncapitalist production and to feminist ethnographies of transnational families. In order to demonstrate the potential significance and effect of this newly recognized institution, we estimate the aggregate population of global households, the size and distribution of remittances, and the magnitude and sectoral scope of global household production. We then examine the implications of the global household concept for three areas of inquiry: globalization, economic development, and the household politics of economic transformation. Finally, we briefly explore the possibilities for research and activism opened up by a feminist, postcapitalist international political economy centered on the global household. PMID- 20737743 TI - Hegemonic developments: the new Indian middle class, gendered subalterns, and diasporic returnees in the event of neoliberalism. AB - The "new middle class" as a political construct is valuable for feminist theorizations of international political economy, particularly those concerned with development. The rise of the new middle class is usually juxtaposed with neoliberalism, so we offer a new theorization of neoliberalism-as-event and analyze an array of new-middle-class signs and subjects in India. Questioning the repetition of the figure of the new Indian woman in resolving the sociotemporal and spatiotemporal paradoxes of the nation, we argue, first, that the figure of the subaltern woman is a necessary counter to the new Indian woman. The arrival of the gendered subaltern on the national stage is celebrated through discourses that articulate and disarticulate the subaltern woman and bear the traces of subaltern struggles. Her gendered body constitutes the line between who can be new middle class and at the vanguard of neoliberal development and who cannot. Second, we argue that new-middle-class formation is taking place in the households of diasporic returnees through class practices that involve speaking to and for domestic servants. Returnees hold in tension urges to encourage class mobility and to discipline their servants through neoliberal governmentalities that draw on global discourses of corporate responsibility, professionalism, and empowerment. These development scripts are interspersed with reflections on the poor material conditions of domestic service work. The implications of this article for feminist theorizations of international political economy are methodological, analytical, and political. PMID- 20737744 TI - "Marking" of cancer: the road to clinical decision making. PMID- 20737745 TI - Opening and continuing the discussion on influenza vaccination timing. PMID- 20737746 TI - Biomolecular markers as determinants of patients selection for adjuvant chemotherapy of sporadic colorectal cancers. AB - Colorectal cancer (CRC) is a disease classified and based on genetic alteration resulting from interaction of environmental factors, individual cancer susceptibility and accumulated somatic changes of the colorectal epithelium. Advanced knowledge in genetics and epigenetics of colorectal cancer develops a hypothesis that various clinical manifestations of colorectal cancer are caused by different carcinogenesis pathways. Different carcinogenesis pathways and types of colorectal cancer appear to bring effects on different response against chemotherapy and prognosis. Chemotherapy is mainly provided for patients with stage III CRC which are also the largest proportion of CRC patients in Indonesia. However, it is also provided for some patients with high risk stage II CRC. Classically, clinical factors have been generally accepted as prognostic factors including depth of tumor invasion, regional nodal metastasis, vascular invasion, poor differentiation, and serologic tumor marker such as carcinoembryonic antigen (CEA). However, clinical and histopathological factors themselves do not provide accurate prediction for colorectal cancer prognosis and treatment. A biomolecular marker is necessary to provide such prediction. Numerous studies have been conducted to evaluate the molecular biological markers in order to determine either the possibility of successful treatment for colorectal cancer (predictive factor) or life-expectancy (prognostic factor). Results of several studies demonstrate different status of some molecular markers to determine successful treatment between stage II and stage III colorectal cancer. Certainly, such finding should be followed up but it shall be accepted that there will be a shift of paradigm of CRC treatment. Therefore, the success of colorectal cancer, excluding the patient's socioeconomic factors and the surgeon's skill, will depend extremely on molecular parameter and not only the stage. PMID- 20737747 TI - [Embolic materials and technique]. PMID- 20737748 TI - [IVR: Puncture technique]. PMID- 20737749 TI - [Radiological catheter placement for hepatic arterial infusion chemotherapy]. PMID- 20737750 TI - Diabetes unresolved health issues. PMID- 20737751 TI - [Applied technology for interventional radiology using blood flow dynamics]. PMID- 20737752 TI - [Radiation exposure protection in IVR]. PMID- 20737753 TI - The role of incretin on diabetes mellitus. AB - Beta cell dysfunction in type-2 diabetes mellitus holds an important role not just on its pathogenesis, but also on the progression of the disease. Until now, diabetes treatment cannot restore the reduced function of pancreatic beta cell. McIntyre et al stated that there is a factor from the intestine which stimulates insulin secretion as a response on glucose.This factor is known as incretin. It is a hormone which is released by the intestine due to ingested food especially those which contain carbohydrate and fat. Currently, there are 2 types of incretin hormones which have been identified, i.e.Glucose dependent insulinotropic polypeptide (GIP) and Glucagon like peptide-1 (GLP-1). These two hormones act by triggering insulin release immediately after food ingestion, inhibiting glucagon secretion, delaying stomach emptying, and suppressing hunger sensation. Several in vitro studies have demonstrated that these two incretin hormones may increase the proliferation of pancreatic beta cell.There is a decrease of GIP function and GLP-1 amount in type-2 diabetes mellitus; thus the attempt to increase both incretin hormones - in this case by using GLP-1 agonist and DPP-IV inhibitor - is one of treatment modalities to control the glucose blood level, either as a monotherapy or a combination therapy. Currently, there are two approaches of incretin utilization as one of type-2 diabetes mellitus treatment, which is the utilization of incretin mimetic/agonist and DPP-IV inhibitor. PMID- 20737754 TI - Dyspepsia and gastroesophageal reflux disease (GERD): is there any correlation? AB - Dyspepsia is a syndrome characterized by symptoms and signs of upper gastrointestinal tract and the adjacent organs. It is estimated that 25% of the community have symptoms of dyspepsia syndrome. One-third of patients who visit general physician practices are patients with dyspepsia syndrome; and half of patients who visit gastroenterologists are also patients with dyspepsia syndrome. Dyspepsia syndrome and gastroesophageal reflux disease (GERD) are very prevalent in the community throughout the world.Gastroesophageal reflux disease (GERD) is more and more commonly found in daily medical practice. Until now,the natural history of disease on GERD and dyspepsia is hardly understood, even though many scientists studied both conditions and there are frequently overlapping. In an individual, GERD and dyspepsia may occur simultaneously and therefore they are hardly to be discriminated.The management of GERD is performed in keeping with Indonesia and Asia Pacific consensus, life-style modification and administering the acid suppression agents (Proton pump inhibitor (drug of choice), H2-receptor antagonist, etc),prokinetic agents (Cisapride, domperidone, etc). Life-style modification shall be performed as follows, i.e. sleep with 30-45 degree elevated head or upper chest, do not avoid sour beverages, chocolate, coffee or alcohol, avoid fat and various fried foods, sour food, less stress, stop smoking, small but frequent feeding, etc. There is a correlation between dyspepsia syndrome and gastroesophageal reflux disease(GERD), particularly between the functional dyspepsia and non-erosive gastroesophageal reflux (NERD). More appropriate definition is necessary to differentiate the dyspepsia syndrome and GERD. Further studies are needed to establish distinct definition and criteria between dyspepsia syndrome and GERD. PMID- 20737755 TI - Healthy communities: new opportunities for promoting health. PMID- 20737756 TI - Planning for end-of-life care. PMID- 20737757 TI - Fighting colorectal cancer. PMID- 20737758 TI - [Q & A: peritonitis resistant to treatment with antitubercular agents]. PMID- 20737759 TI - Fixing a broken Michigan. PMID- 20737760 TI - The attack on Social Security. PMID- 20737761 TI - Getting out of the recession. PMID- 20737762 TI - Clinical practice corner. Patient advocacy. PMID- 20737763 TI - New developments in orthopedic surgery. AB - Several examples of newly developed concepts and techniques have been described. Better results in congenital dislocation of the hip are being achieved by early diagnosis in the infant and the Salter innominate osteotomy in the older child. Halo-femoral traction has been developed as an adjunct in the treatment of severe scoliosis. Compression stress applied to fractures provokes rapid healing. Early active exercises in joint fractures enhance the functional result. New approaches to the intervertebral disk are being used. The externally powered prosthesis is an example of collective effort from diverse scientific areas. Research activities tend to relate more directly to clinical problems. These and many advances not mentioned are manifestations of the continuing maturation of orthopedic surgery as a surgical specialty. PMID- 20737764 TI - The emergency care and treatment of hand injuries. AB - 1. Evaluate the wound. Don't be fooled by simple lacerations. 2. The wound should be cleaned and covered with a sterile dressing as soon as possible-No probing. No antiseptics. 3. Protect the wound from added contamination or additional damage, using a large pressure dressing. PMID- 20737765 TI - Recent trends in lower extremity amputation. Surgery and rehabilitation. AB - With the use of modern prosthetic appliances and the initiation of early ambulation, satisfactory function can be expected in the vast majority of below knee amputees. The rehabilitation of the above-knee amputee is more difficult and the performance of these patients does not compare favorably with that of the below-the-knee amputee. Immediate postsurgical fitting appears to have resulted in a higher percentage of successful below-knee amputations in patients with peripheral vascular disease. The rigid dressing provided by the temporary prosthesis applied to the stump immediately after the amputation seems to control excessive edema and places the severed tissues in an environment more conducive to uneventful healing. Myoplastic techniques and early ambulation are not necessary prerequisites for the use of the immediate postsurgical fitting technique. Below-knee myoplasty should not be performed in patients with peripheral vascular disease because of its questionable value and the undesirable additional surgical trauma that this technique requires. Early weight-bearing ambulation is not a prerequisite for the use of the immediate postsurgical fitting technique and may be instituted only in cases in which the patients' general condition, balance, and coordination are sufficiently intact to permit supervised instructions. The application of the temporary pylon requires wide prosthetic experience and extreme care. PMID- 20737766 TI - Treatment of scoliosis. AB - We do not know the etiology of the great majority of cases of structural scoliosis with which we are confronted today, namely, the 80 to 90 per cent classified as "idiopathic." Treatment of these cases, once the lateral curvature has developed, must be directed by one knowledgeable in the pathogenesis of scoliosis, the potentialities of these curves in terms of etiology and degree of maturation of the individual, and an awareness of the various methods of treatment. The basic principles of obtaining correction are distraction and the application of corrective forces to the convex side of the curve, by external or internal fixation. Ironically, while our present-day methods are somewhat more refined and sophisticated, these are the same principles that have been utilized since the fifteenth century. We have in the past fifty years added the innovation of fusion of the vertebral segments involved, to maintain the correction that has been attained. Needless to say, we are striving through basic and clinical research to ascertain the cause of idiopathic scoliosis and, at the same time, evolving better methods of efficient and effective correction, and maintaining correction of these deformities, once they have developed. PMID- 20737767 TI - Organization and administration of the orthopedic nursing unit. AB - Sociologic and economic factors, as well as developments in science, in medical practice, and in nursing, have coincided to make the hospital orthopedic nursing unit one of relatively short-term, intensive patient care and intensive preparation for the rehabilitation period to follow. Some administrative arrangements which hold promise for the furthering of patient care objectives are found in the areas of physical plant, personnel, supply and equipment, and communications. PMID- 20737769 TI - Nursing care of the patient with a laminectomy. PMID- 20737768 TI - Therapeutic nursing care of orthopedic patients. PMID- 20737770 TI - Nursing care of the patient with spinal cord injury. AB - The rehabilitation process must begin at the onset of illness and include not only a cure for the immediate disorders but methods of preventing further disability, the general management of convalescence, and the ultimate return of the individual to his maximum health and efficiency. As a member of the rehabilitation team the nurse must recognize the patient as a human being and emotionally accept him, maintain good interpersonal relations with other team members, know what resources are available, and help to provide continuity of care when the patient is discharged. She must counsel and guide the patient and family, know and apply good general nursing care, and understand the emotional factors in long-term care. When deformities and other complications are prevented and the patient keeps up his strength through early activities, the confinement will be shorter, the cost will be less, and the patient will return more quickly to independence. PMID- 20737771 TI - Nursing care of patients with cancer of the bone. PMID- 20737772 TI - Nursing care in surgery of the head and neck. PMID- 20737773 TI - Nursing care of the patient with cleft lip and palate. PMID- 20737774 TI - The use of silicone implants in plastic surgery. AB - Cooperation between chemists and physicians has created a whole new family of materials to enrich our lives. They have endless industrial applications, and a glimpse has been presented of what they offer the field of surgery. Silicones persist indefinitely as substitutes for bone, cartilage, and soft tissue of all shapes and sizes. Their future in surgery is as exciting and boundless as human imagination. PMID- 20737775 TI - Emotional support of patients with head and neck surgery. PMID- 20737776 TI - Nursing care of patients with surgery of the chest. AB - In summary, care of the thoracic patient encompasses three major periods: the preoperative phase in which diagnostic evaluation of the patient is the important concern of the physician but in which patient education, establishment of rapport, and anxiety alleviation or "morale boosting" become the chief responsibility of the nursing staff; the operative period, in which technical skill and operative efficiency by all members of the thoracic team functioning as a unit become the most important considerations; and the postoperative period in which careful and vigilant monitoring of vital signs becomes the most important function of the nursing staff. The major portion of responsibility for effective action in the face of pathological alteration of patient physiology depends, of course, on the physician, but he is heavily dependent upon the data on the patient's physiological state obtained by the nursing staff during this period. PMID- 20737777 TI - Removing bronchial secretions. Intratracheal suction and related measures. AB - Intratracheal suction is a proved adjunct in the maintenance of normal homeostasis of the tracheobronchial tree after major abdominal and thoracic operations. A sound understanding of the principles and techniques of intratracheal suction and intelligent use at appropriate intervals are primarily the responsibility of the nursing staff. If intratracheal suction is ineffective, other measures must be employed, including bronchoscopy or tracheostomy. PMID- 20737778 TI - Coarctation of the aorta. AB - A review of the congenital anomaly of coarctation of the aorta has been presented. The salient features in diagnosis are the differential pressures and pulses between the upper and lower extremities. Also, the features of left ventricular hypertrophy and pulsating intercostal vessels are significant. The essential complications are those of sustained hypertension. In most cases surgical correction can be accomplished with excision of the coarcted segment and an end-to-end anastomosis. In some instances, particularly in adults, a graft may be necessary. The surgical results have been gratifying with a mortality rate of less than 5 per cent and in general a reduction of the blood pressure to normal. PMID- 20737779 TI - Surgery for coronary artery disease. PMID- 20737780 TI - The nursing care of the open heart patient. AB - The recovery of the open heart patient depends on good nursing care and is often very rapid. In a very successful case the patient will be sitting up the evening of surgery, dangling the first postoperative day, out of bed in a chair the second, and walking the third. He may be discharged as soon as a week following surgery. The patient's rate of recovery is an individual matter. He will determine his own activity by his condition. We usually let the patient be the guide in determining his limitations and progress. It is both thrilling and rewarding to see this type of progress in a patient. To quote Dr. James Jude, chief of cardiovascular surgery at Jackson Memorial Hospital, "The future of cardiac nursing is bright. It calls for those who desire to give their hearts to the healing of hearts of others." PMID- 20737781 TI - The insertion of cardiac implants and the nursing care problems involved. PMID- 20737782 TI - Care of the infant with exstrophy of the bladder. AB - In summary, there is one major principle in the care of the child with exstrophy of the bladder; it is to prevent infection. It is not the exstrophied bladder but the serious infection that causes most of the related deaths. To prevent infection, the child must be kept clean and dry, have a blanced diet with special attention to vitamin A and proteins, have rest, be protected from trauma, take antibiotics, and have a good mental outlook. Even babies can sense when they are rejected or unloved. Parents must learn to control their emotions, understand and accept the baby, and give him the love and care that he needs and deserves as their own child. PMID- 20737783 TI - The way it was Croupous pneumonia. PMID- 20737784 TI - Identification of cholinergic synaptic transmission in the insect nervous system. AB - A major criteria initially used to localize cholinergic neuronal elements in nervous systems tissues that involve acetylcholine (ACh) as neurotransmitter is mainly based on immunochemical studies using choline acetyltransferase (ChAT), an enzyme which catalyzes ACh biosynthesis and the ACh degradative enzyme named acetylcholinesterase (AChE). Immunochemical studies using anti-ChAT monoclonal antibody have allowed the identification of neuronal processes and few types of cell somata that contain ChAT protein. In situ hybridization using cRNA probes to ChAT or AChE messenger RNA have brought new approaches to further identify cell bodies transcribing the ChAT or AChE genes. Combined application of all these techniques reveals a widespread expression of ChAT and AChE activities in the insect central nervous system and peripheral sensory neurons which implicates ACh as a key neurotransmitter. The discovery of the snake toxin alpha-bungatoxin has helped to identify nicotinic acetylcholine receptors (nAChRs). In fact, nicotine when applied to insect neurons, resulted in the generation of an inward current through the activation of nicotinic receptors which were blocked by alpha bungarotoxin. Thus, insect nAChRs have been divided into two categories, sensitive and insensitive to this snake toxin. Up to now, the recent characterization and distribution pattern of insect nAChR subunits and the biochemical evidence that the insect central nervous system contains different classes of cholinergic receptors indicated that ACh is involved in several sensory pathways. PMID- 20737785 TI - The evolution of pentameric ligand-gated ion channels. AB - Fast, ionotropic neurotransmission mediated by ligand-gated ion channels is essential for timely behavioral responses in multicellular organisms. Metazoa employ more ionotropic neurotransmitters in more types of synapses, inhibitory or excitatory, than is generally appreciated. It is becoming increasingly clear that the adaptability of a single neurotransmitter receptor superfamily, the pentameric ligand-gated ion channels (pLGICs), makes the diversity in ionotropic neurotransmission possible. Modification ofa common pLGIC structure generates channels that are gated by ligands as different as protons, histamine or zinc and that pair common neurotransmitters with both cation and anion permeability. A phylogeny of the pLGIC gene family from representative metazoa suggests that pLGIC diversity is ancient and evolution of contemporary phyla was characterized by a surprising loss of pLGIC diversity. The pLGIC superfamily reveals aspects of early metazoan evolution, may help us identify novel neurotransmitters and can inform our exploration of structure/function relationships. PMID- 20737786 TI - Diversity of insect nicotinic acetylcholine receptor subunits. AB - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate fast synaptic transmission in the insect nervous system and are targets of a major group of insecticides, the neonicotinoids. They consist of five subunits arranged around a central ion channeL Since the subunit composition determines the functional and pharmacological properties of the receptor the presence of nAChR families comprising several subunit-encodinggenes provides a molecular basis for broad functional diversity. Analyses of genome sequences have shown that nAChR gene families remain compact in diverse insect species, when compared to their nematode andvertebrate counterparts. Thus, the fruit fly (Drosophila melanogaster), malaria mosquito (Anopheles gambiae), honey bee (Apis mellifera), silk worm (Bombyx mon) and the red flour beetle (Tribolium castaneum) possess 10-12 nAChR genes while human and the nematode Caenorhabditis elegans have 16 and 29 respectively. Although insect nAChRgene families are amongst the smallest known, receptor diversity can be considerably increased by the posttranscriptional processes alternative splicing and mRNA A-to-I editingwhich can potentially generate protein products which far outnumber the nAChR genes. These two processes can also generate species-specific subunit isoforms. In addition, each insect possesses at least one highly divergent nAChR subunit which may perform species-specific functions. Species-specific subunit diversification may offer promising targets for future rational design of insecticides that target specific pest insects while sparing beneficial species. PMID- 20737787 TI - Identification of critical elements determining toxins and insecticide affinity, ligand binding domains and channel properties. AB - Insect nicotinic acetylcholine receptors have been objects of attention since the discovery of neonicotinoid insecticides. Mutagenesis studies have revealed that, although the detailed subunit composition of insect nicotinic acetylcholine receptors subtypes eludes us, the framework provided by mutagenesis analysis makes a picture of the subunits involved in the ligand binding and channel properties. In fact, many residues that line the channel or bind to the ligand seemed to be strongly conserved in particular in the N-terminal extracellular region and the second transmembrane domain which constitutes the ion-conducting pathway supporting the flux of ions as well as their discrimination. In fact, the positions are carried by loops B and C, respectively, which contain amino acids directly contributing to the acetylcholine binding site. Mutation ofthese residues accounts for insect resistance to neonicotinoid insecticides such as imidacloprid or a loss ofspecific binding. The discovery of the same mutation at homologous residues in different insect species or its conservation raises the intriguing question of whether a single mutation is essential to generate a resistance phenotype or whether some subunit confer insensitivity to ligand. Consequently, recent finding using information from Torpedo marmorata al subunit and soluble Aplysia californica and Lymnae stagnalis acetylcholine bindingproteins from crystallization suggest that insect nAChR subunits had contributing amino acids in the agonist site structure which participate to affinity and pharmacological properties of these receptors. These new range of data greatly facilitate the understanding of toxin-nAChR interactions and the neonicotinoid binding and selectivity. PMID- 20737788 TI - Electrophysiological studies and pharmacological properties of insect native nicotinic acetylcholine receptors. AB - The existence of several nicotinic acetylcholine receptor genes in insects suggests that many nicotinic receptor subtypes are present, but the identification and characterization of these subtypes in native neurons has been limited. Their pharmacological properties came from electrophysiological studies in which variations in the sensitivity of insect neurons were correlated with time course, current amplitudes, desensitization rates occurring in varying proportions in different cells. Thus pressure application of agonists on cultured cells induced inward currents showing that acetylcholine and nicotine were partial agonists of some cells with a lower efficacy while they were full agonists in other neurons. The variation in kinetics appeared to be due to differential expression of distinct nicotinic receptor subtypes as corroborated by the blocking activity induced by antagonists. In fact, the alpha-bungarotoxin sensitive nicotinic receptor subtypes described as homomeric could be also heteromeric receptors. Interestingly, some receptors mediating nicotinic responses have been termed 'mixed' receptors because they were blocked by a range of nicotinic and muscarinic antagonists. Following electrophysiological studies, it has been also demonstrated that insect nicotinic receptors were modulated by Ca2+ pathways. Ca2+ permeability through insect nicotinic receptors, voltage gated Ca2+ channels or released from intracellular stores represents an important indication of insect native nicotinic acetylcholine receptor modulation. The Ca2+ flow may trigger a variety of cytosolic Ca2+ pathways underlying many cellular processes such Calmodulin kinase, PKA and PKC. Most of the studies suggested that the effect of phosphorylation mechanism was dependent on the receptor subtype. PMID- 20737789 TI - Characterisation of insect nicotinic acetylcholine receptors by heterologous expression. AB - As with other neurotransmitter receptors and ion channels, characterisation ofnicotinic acetylcholine receptors (nAChRs) has relied heavily on studies conducted with cloned receptors expressed in artificial expression systems. Although much has been achieved in recent years by such studies, considerable problems have been encountered in the heterologous expression of several nAChR subtypes; problems that have been particularly pronounced for insect nAChRs. Here we will review studies that have been conducted with nAChRs cloned from insects, with emphasis on experimental strategies that have been employed in an attempt to circumvent the problems associated with inefficient heterologous expression of insect nAChRs. These approaches include the expression of hybrid nAChRs (containing insect nAChR subunit co-expressed with vertebrate subunits), artificial subunit chimeras and the co-expression of molecular chaperones such as RIC-3. PMID- 20737790 TI - Neonicotinoid insecticides: historical evolution and resistance mechanisms. AB - The use ofneonicotinoid insecticides has grown considerably since their introduction in 1990s. They are used extensively for the control of agriculturally important crop pests and also in the control of cat and dog fleas. Imidacloprid exploited through an elaborated structural and substituent optimization of nithiazine was launched to market in 1990. The selectivity ofneonicotinoid compounds for insect species has been attributed to their binding on nicotinic acetylcholine receptors in which the negatively charged nitro- or cyano-groups of neonicotinoid compounds interact with a cationic subsite within insect nicotinic acetylcholine receptors. The first example of a pest evolving resistance to field use of neonicotinoids was Bemisia tabaci. Resistance to neonicotinoids can arise either through nAChR subtypes expression, detoxification mechanisms and/or structural alterations of target-site proteins. Consequently, a number of derivatives and analogues ofimidacloprid have been generated to date. In 1992, a new neonicotinoid using acetylcholine as the lead compound has been found. This was dinotefuran, which has a characteristic tetrahydro-3-furylmethyl group instead of the pyridine-like rings of others neonicotinoids. PMID- 20737791 TI - Ecotoxicity of neonicotinoid insecticides to bees. AB - This chapter reviews the available data on the toxicity of neonicotinoid insecticides to bees that are the prominent and the most economically important group of pollinators worldwide. Classical and new methods developed to take into account the characteristics and different types of effects of the neonicotinoid insecticides to bees are described. The available toxicity results are critically analyzed. Thus, the nitro-substituted compounds (clothianidin, dinotefuran, imidacloprid and its metabolites, thiamethoxam, nitenpyram) appear the most toxic to bees. The cyano-substituted neonicotinoids seem to exhibit a much lower toxicity (acetamiprid and thiacloprid). The chapter ends with suggestions for additional studies aiming at better assess the hazard of this important insecticide family to bees. PMID- 20737792 TI - State of the art on insect nicotinic acetylcholine receptor function in learning and memory. AB - Acetylcholine is the most abundant excitatory neurotransmitter in the insect brain and the most numerous acetylcholine receptors are the nicotinic ones (nAChRs). The genome sequencing of diverse insect species has demonstrated the existence of at least 10 nAChR genes coding for alpha and beta subunits, suggesting the existence in the insect CNS of several subtypes ofnAChRs whose molecular composition and pharmacological properties are still unknown. Insect nAChRs have given rise to an abundance of literature about their sensitivity to neonicotinoid insecticides but only limited data are available on the functional role of nAChRs in insect cognitive functions. The data we have collected on honeybees are the only data that shed light on the role of nAChRs in learning and memory processes. The behavioral response of proboscis extension (PER), which appears when the honeybee perceives sugar, was used to quantify learning and memory performances in associative and non-associative learning procedures. Habituation of the PER, which consists in ceasing to respond to sucrose upon repetitive antennal sucrose stimulation, was facilitated by the injection into the brain of one of the nicotinic antagonists mecamylamine, alpha-bungarotoxin (alpha-BGT) or methyllycaconitine (MLA). Pavlovian associative protocol was used to condition the PER to olfactory or tactile stimulus after single- or multiple trial training. Localized brain injections of the nicotinic antagonist mecamylamine were performed before or after one-trial olfactory learning in the mushroom bodies (MB), the integrative structures of the insect brain. The results showed that the calical input structures of the MB are necessary for the acquisition processes and the output a-lobe regions are involved in retrieval processes. Brain injection of one of the three nicotinic antagonists mecamylamine, alpha-BGT and MLA was combined with single- and multiple-trial olfactory and tactile learning and memory performances were evaluated at long- or short-term intervals. Mecamylamine impaired the acquisition of one-trial learning and the retrieval of information, regardless of the number of trials during training and the learning modality (olfactory or tactile cues used as conditioned stimulus). Memory performance evaluated at long-term intervals was decreased by injection of alpha-BGT and MLA in multiple-trial olfactory and tactile experiments. We conclude from these results that at least two subtypes of nAChRs exist in the honeybee brain. The alpha-BGT-sensitive nAChRs are necessary for the formation of long-term memory and the alpha-BGT-insensitive nAChRs are involved in one-trial acquisition and in retrieval processes. The hypothesis is put forward that multiple-trial associative learning triggers activation of the alpha BGT-sensitive nAChRs that, in turn, activate intracellular events leading to LTM formation. PMID- 20737793 TI - Influence of season, ethnicity, and chronicity on vitamin D deficiency in traumatic spinal cord injury. AB - BACKGROUND: Inadequate levels of vitamin D increase the risk of osteoporosis, a highly prevalent condition in patients with traumatic spinal cord injury (SCI). Reduced sunlight and dark skin further contribute to low vitamin D levels. OBJECTIVES: To compare serum 25-hydroxy vitamin D [vitamin D25(OH)] levels in acute and chronic SCI and to explore seasonal and ethnic differences among patients with acute and chronic SCI. PATIENTS/METHODS: Patients (N=96) aged 19 to 55 years with C3-T10 motor complete SCI participated. Acute SCI was 2 to 6 months after injury, whereas chronic SCI was at least 1 year from injury. Serum vitamin D25(OH), calcium, and parathyroid hormone were drawn dUring summer or winter months. Vitamin D deficiency (<13 ng/mL), insufficiency (<20 ng/mL), and subtherapeutic (<32 ng/mL) levels were compared for all groups. A 3-way analysis of covariance was adopted to determine significant main effects of season, chronicity, and ethnicity. Interactions between season and chronicity, season and ethnicity, and chronicity and ethnicity were evaluated. Evaluation of a 3-way interaction among season, chronicity, and ethnicity was completed. RESULTS: In summer, 65% of patients with acute SCI and 81% of patients with chronic SCI had subtherapeutic vitamin D levels, whereas in winter, 84% with acute SCI and 96% with chronic SCI had vitamin D25(OH) (<32 ng/mL). Lower vitamin D25(OH) levels were observed in African Americans relative to whites. Significant main effects were noted for season (P = 0.017), chronicity (P = 0.003), and ethnicity (P < 0.001). However, interactions between 2 or more factors were not found. CONCLUSIONS: Vitamin D insufficiency and deficiency are found in the majority of patients with chronic SCI and in many with acute SCI. Initial screening for serum vitamin D25(OH) levels should be performed early in rehabilitation. Periodic monitoring in the chronic setting is highly recommended. PMID- 20737794 TI - Underestimation of bone loss of the spine with posterior-anterior dual-energy X ray absorptiometry in patients with spinal cord injury. AB - BACKGROUND: Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal by routine posterior-anterior (PA) bone density imaging in patients with chronic spinal cord injury (SCI). OBJECTIVE: To determine BMD of the L-spine by PA and lateral (LAT) dual-energy radiographic absorptiometry (DXA) in patients with chronic SCI. DESIGN: Prospective study. SETTING: Veterans Affairs Medical Center and a private rehabilitation facility. METHODS: Measurements of the PA and LAT L-spine and hip were performed in 15 patients with SCI: 9 with tetraplegia and 6 with paraplegia. The DXA (GE Lunar Advance DXA) images were obtained using standard software. Results are reported as mean +/- SD. RESULTS: The mean age was 35 +/- 15 years (range = 20-62 years), and the duration of injury was 57 +/- 74 months (range = 3-240 months). T- and Z-scores were lower for the LAT L-spine than those for PA L-spine (T-scores L2: -0.7 +/- 1.2 vs. 0.0 +/- 1.4, P < 0.01; L3: -0.9 +/- 1.6 vs. 0.3 +/- 1.3, P < 0.002; L2 L3: -0.8 +/- 1.3 vs. 0.2 1.3 vs. 0.2 +/- P < 0.001; Z-scores Z-0.3 +/- 1.1 vs. 0.2 +/- 1.2, P < 0.05; L3: -0.6 +/- 1.3 vs. 0.5 +/- 1.3, P < 0.01; L2-L3: -0.4 +/ 1.1 vs. 0.4 +/- 1.2, P < 0.005). The T- and Z-scores for the total hip (-1.1 +/- 1.0 and -1.0 +/- 1.0, respectively) and L2-L3 LAT L-spine demonstrated remarkable similarity, whereas the L2-L3 PA L-spine scores were not reduced. Bone mineral density of the LAT L-spine, but not the PA L-spine, was significantly reduced with increasing duration of injury. CONCLUSIONS: Individuals with SCI may have bone loss of the L-spine that is evident on LAT DXA that may be misdiagnosed by PA DXA, underestimating the potential risk of fracture. PMID- 20737795 TI - Statewide investigation of medically attended adverse health conditions of persons with spinal cord injury. AB - BACKGROUND/OBJECTIVE: To report over a 10-year period the statewide prevalence and incidence of medically attended adverse health conditions in people with new traumatic spinal cord injury (TSCI). DESIGN: Retrospective cohort study. METHODS: (a) Identified all new TSCI cases discharged alive from statewide acute care hospitals, 1996 to 2000, using ICD-9-CM methodology. (b) Followed cases from 1996 to 2005 to quantify medically attended health conditions documented during emergency department visits, acute care hospitalizations, and outpatient hospital visits. (c) Used the life table method to calculate the prevalence and incidence of health conditions. (d) Examined Cox proportional hazard ratio of mortality by gender controlling for age and TSCI severity. RESULTS: Nine hundred eighty-eight residents (257 women, 731 men) with TSCI were alive 90 days after discharge from acute care hospitalization from 1996 to 2000. Nine hundred twenty-three (251 female, 672 male) (93.4%) residents had an observed medically attended adverse health condition in the 10-year followup period. The most prevalent classes of diseases and disorders were (a) muscle and connective tissue, (b) renal and urinary, (c) digestive, (d) circulatory, (e) respiratory, (f) endocrine/nutritional/metabolic, and (g) infectious. Incidence of new injury was 29.0% for males and 26.9% for females. During the follow-up period, 49 women (19%) and 104 men (14%) died. CONCLUSIONS: People with TSCI experience diverse adverse health conditions in the 10 years after initial injury. An interdisciplinary health care provider team approach to allocating resources and implementing countermeasures to prevent or limit occurrence of these conditions is vital to these patient's continuum of care. PMID- 20737796 TI - Comparing quantification of pain severity by verbal rating and numeric rating scales. AB - BACKGROUND: Researchers have reported widely varying correlations among the 3 main instruments used to quantify pain severity, Visual Analog Scale (VAS), Verbal Rating Scale (VRS), and Numeric Rating Scale (NRS), both at the level of groups and at the level of individuals. OBJECTIVE: To assess the comparability of reports of pain severity using a VRS and a NRS in a spinal cord injury (SCI) sample. METHODS: Data were taken from a longitudinal observational study. Patients were 168 individuals with new traumatic SCI admitted for inpatient rehabilitation who completed the VRS and NRS multiple times, each time for multiple pains as appropriate. RESULTS: For 1114 ratings of pain, VRS and corresponding NRS ratings were correlated weakly (Spearman correlation, rho = 0.38). For 36 individuals with at least 10 completions of paired VRS and NRS, rho ranged from -0.55 to 0.76. Variation in NRS rating for each VRS adjective was reduced by about 25% when between-patient variation was eliminated. Mean NRS ratings by VRS adjective, for patients who had used each of at least 2 adjectives at least 5 times each, showed large differences in mean NRS scores between individuals using the same VRS adjective. CONCLUSION: There are considerable differences between individuals in how NRS and VRS are used; there also seem to be individuals whose understanding of the meaning of the VRS adjectives is completely different from what was assumed by the creators of this VRS. Both VRS and NRS data must be used with extreme caution by SCI clinicians and researchers. PMID- 20737797 TI - Fever during rehabilitation in patients with traumatic spinal cord injury: analysis of 392 cases from a national rehabilitation hospital in Turkey. AB - OBJECTIVE: To determine the incidence and etiology of fever and the risk factors related to fever in adults with spinal cord injury (SCI) at the rehabilitation stage. DESIGN/SUBJECTS: A retrospective examination of records of 392 consecutive adult patients with traumatic SCI who received inpatient rehabilitation program. SETTING: A national rehabilitation center in Turkey. OUTCOME MEASURES: Incidence and etiology of fever, period of hospitalization (days). RESULTS: A total of 187 patients (47.7%) had fever at least once during their rehabilitation program. The most common etiology was urinary tract infection. The rate of fever occurrence was significantly higher in patients with complete SCI (P = 0.001). In patients with fever, the use of an indwelling catheter was significantly higher compared with clean intermittent catheterization and spontaneous voiding (P = 0.001). The hospitalization period of patients with fever was significantly longer than that of patients without fever (P = 0.006). CONCLUSIONS: A high rate of fever was seen in patients with SCI during rehabilitation. Fever was caused by various infections, of which urinary tract infection was the most common. Patients with motor complete injuries and those with permanent catheters constituted higher risk groups. Fever prolonged the length of rehabilitation stay and hindered active participation in the rehabilitation program. PMID- 20737798 TI - Age, gender, and side differences of cutaneous electrical perceptual threshold testing in an able-bodied population. AB - OBJECTIVE: To investigate age, gender, and left-right differences in cutaneous electrical perceptual threshold (EPT) testing in an able-bodied, Australian sample. STUDY DESIGN: Prospective experimental. SETTING: Hospital-based spinal cord injuries unit. METHODS: Cutaneous electrical stimulation of the 28 dermatomes at ASIA sensory key points (C2-S4/S5) was performed on 29 female and 16 male healthy volunteers aged 21 to 76 years. Mean EPTs for each dermatome were compared (repeated measures ANOVA) for left-right, gender-related, and age related (50 years of age) differences. RESULTS: There was no group difference between sides (repeated measures ANOVA, P = 0.934). Women across all ages had lower group mean EPTs than men (P < 0.0001). Women younger than age 50 years had lower mean EPTs than those older than age 50 years (P = 0.008). There was no group difference between younger and older men (P = 0.371). Analysis of individual dermatomes revealed no significant differences in thoracic dermatomes between genders or age groups, contrary to the limb dermatomes. CONCLUSION: There were gender differences in EPT values across all ages. Women had higher EPTs as they advanced in age, but this was less clear in men. There was considerable somatotopic variability in EPTs, especially in the lower limbs. If EPT testing is to be applied to detect subclinical changes within a dermatome, establishment of age- and gender-specific somatotopic normograms is a prerequisite. PMID- 20737799 TI - Spinal schistosomiasis: differential diagnosis for acute paraparesis in a U.S. resident. AB - BACKGROUND: Spinal schistosomiasis is a severe presentation of Schistosoma mansoni infection, which is endemic in South America, the Middle East, and sub Saharan Africa. With increasing international travel, a disease can spread from an endemic area to another part of the world easily. OBJECTIVES: To present a case of a US resident who developed acute paraparesis due to spinal schistosomiasis after traveling to sub-Saharan Africa. PARTICIPANT: A 45-year-old woman presented with abdominal pain radiating into the bilateral lower extremities. She was diagnosed with a pelvic mass and underwent an urgent hysterectomy with right salpingo-oopherectomy. Postoperatively, she developed progressive weakness with worsening pain in her bilateral lower extremities and neurogenic bladder. Magnetic resonance imaging showed an abnormal T2 hyperintense signal in the entire spinal cord below the T3 level with abnormal contrast enhancement from T9 through the conus medullaris. Spinal fluid analysis showed lymphocytic pleocytosis and elevated protein. The patient was diagnosed with transverse myelitis. Subsequently, a detailed history revealed a visit to Ethiopia 2 years earlier. Tests for S mansoni were positive. After treatment with praziquantel and prednisone, her neurologic function began to improve. CONCLUSIONS: An increasing incidence of international travel is increasing the likelihood of US physicians' encountering this treatable condition. Travelers with spinal schistosomiasis may not have symptoms of systemic infection. Therefore, it is important to include spinal schistosomiasis in the differential diagnosis of acute inflammatory myelopathy, particularly with a history of travel to endemic areas. PMID- 20737800 TI - Electrical stimulation of the urethra evokes bladder contractions in a woman with spinal cord injury. AB - OBJECTIVE: Electrical stimulation of pudendal urethral afferents generates coordinated micturition in animals and bladder contractions in men after spinal cord injury (SCI), but there is no evidence of an analogous excitatory urethra spinal-bladder reflex in women. The objective of this study was to determine whether electrical stimulation of the urethra could evoke bladder contractions in a woman with SCI. CASE REPORT: A 38-year-old woman with a C6 ASIA A SCI who managed her bladder with clean intermittent catheterization and oxybutynin demonstrated neurogenic detrusor overactivity on urodynamics. Oxybutynin was discontinued 2 days prior to urodynamic testing with a custom 12F balloon catheter mounted with ring-shaped electrodes located in the bladder neck, mid urethra, and distal urethra. The inflated balloon was placed against the bladder neck to stabilize the catheter electrodes in place along the urethra. However, the balloon limited emptying during contractions. Urodynamics were performed at a filling rate of 25 mL/minute until a distention-evoked bladder contraction was observed. The urethra was stimulated over a range of bladder volumes and stimulus parameters to determine whether electrical stimulation could evoke a bladder contraction. FINDINGS: Electrical stimulation via urethral electrodes evoked bladder contractions that were dependent on bladder volume (>70% capacity) and the intensity of stimulation. CONCLUSIONS: This is the first report of an excitatory urethra-spinal-bladder reflex in a woman with SCI. Future studies will determine whether this reflex can produce bladder emptying. PMID- 20737801 TI - Autonomic dysreflexia as a complication of a fecal management system in a man with tetraplegia. AB - BACKGROUND/OBJECTIVE: To present a case of autonomic dysreflexia caused by the use of a fecal management system in a patient with tetraplegia. DESIGN: Case report. SETTING: Military rehabilitation center. RESULTS: A man with tetraplegia had a fecal management system inserted to divert stool away from his sacral pressure ulcer to reduce contamination and infection risk. Two days later, he developed severe autonomic dysreflexia that improved after removal of the system. CONCLUSIONS: Autonomic dysreflexia, a life-threatening complication, has not been reported before as a side effect of a fecal management system. These systems should be used with caution in patients with high-level spinal cord injury. PMID- 20737802 TI - Dorsal epidural intervertebral disk herniation with atypical radiographic findings: case report and literature review. AB - BACKGROUND/OBJECTIVE: Intervertebral disk herniation is relatively common. Migration usually occurs in the ventral epidural space; rarely, disks migrate to the dorsal epidural space due to the natural anatomical barriers of the thecal sac. DESIGN: Case report. FINDINGS: A 49-year-old man presented with 1 week of severe back pain with bilateral radiculopathy to the lateral aspect of his lower extremities and weakness of the ankle dorsiflexors and toe extensors. Lumbar spine magnetic resonance imaging with gadolinium revealed a peripheral enhancing dorsal epidural lesion with severe compression of the thecal sac. Initial differential diagnosis included spontaneous hematoma, synovial cyst, and epidural abscess. Posterior lumbar decompression was performed; intraoperatively, the lesion was identified as a large herniated disk fragment. CONCLUSIONS: Dorsal migration of a herniated intervertebral disk is rare and may be difficult to definitively diagnose preoperatively. Dorsal disk migration may present in a variety of clinical scenarios and, as in this case, may mimic other epidural lesions on magnetic resonance imaging. PMID- 20737803 TI - Pilomatrix carcinoma of the thoracic spine: case report and review of the literature. AB - CONTEXT: Pilomatrixoma is a common head and neck neoplasm in children. Its malignant counterpart, pilomatrix carcinoma, is rare and found more often in men. METHOD: Case report of a 21-year-old man with pilomatrixoma of the thoracic spine that underwent malignant degeneration to pilomatrix carcinoma. FINDINGS: The appearance of a painless mobile axillary mass was followed by severe back pain 1 year later. Imaging revealed a compression fracture at the T5 level. The patient underwent resection of the axillary mass and spinal reconstruction of the fracture; the pathology was consistent with synchronous benign pilomatrixomas. Three months later he presented with a recurrence of the spinal lesion and underwent further surgical resection; the pathology was consistent with pilomatrix carcinoma. He received adjuvant radiotherapy and at his 1-year follow up examination had no sign of recurrence. CONCLUSION/CLINICAL RELEVANCE: Pilomatrix carcinoma involving the spine is a rare occurrence. It has a high incidence of local recurrence, and wide excision may be necessary to reduce this risk. Radiotherapy may be a helpful adjuvant therapy. Clinicians should be aware of this entity because of its potential for distant metastasis. PMID- 20737804 TI - Steroid-responsive myeloneuropathy associated with antithyroid antibodies. AB - BACKGROUND/OBJECTIVE: To present information about 2 steroid-responsive, antithyroid antibody-positive patients with myeloneuropathy and myelopathy. METHODS: Case reports. RESULTS: A 48-year-old woman and a 42-year-old man presented with acute onset tetraparesis and magnetic resonance imaging studies showing cervical spinal lesions. Nerve conduction and biopsy studies of the woman were suggestive of a demyelinating polyradiculoneuropathy. Detailed diagnostic workup turned out to be negative for both patients, except for highly elevated antithyroid antibodies with normal thyroid functions and imaging. Both patients responded remarkably well to high-dose steroid treatment, and their symptoms disappeared in a few months. Both patients' antithyroid antibody levels were reduced shortly after steroid treatment and in parallel with the amelioration of symptoms. CONCLUSIONS: Antithyroid antibodies might be associated with acute demyelinating myeloneuropathy or myelopathy pathogenesis and might indicate a good response to steroid treatment in these syndromes. PMID- 20737806 TI - Gun control redux. PMID- 20737807 TI - [Expensive drugs and intergenerational justice]. AB - Among all categories of health expenditure in Canada, spending on drugs is the fastest growing. The factors at play in the increase in expenditure on drugs are essentially those related to the volume of use and the arrival of new drugs on the market. Some of these new drugs are very expensive. In fact, the costs of certain drugs threaten the continued existence of the Quebec Prescription Drug Insurance Plan. In Quebec, the Conseil du medicament (Drug Board) is responsible for recommending drugs to the Ministry of Health and Social Services to be put on the formulary of drugs covered by the public plan. In spite of pressure by various stakeholders, we believe that the rationing of drugs that are too expensive can achieve political legitimacy if it is based on a transparent justification that includes not only evidence-based criteria, but also ethical principles and values. For egalitarians, fairness in the supply of health care should be accomplished as a function of health care needs. But this concept of justice should also be extended to future generations. The balance of current and future needs should be achieved by determining what would be "reasonable access" through public consultations among experts and citizens. PMID- 20737805 TI - Sexuality and reproductive health in adults with spinal cord injury: a clinical practice guideline for health-care professionals. PMID- 20737808 TI - Food insecurity among Inuit women exacerbated by socioeconomic stresses and climate change. AB - OBJECTIVES: To identify and characterize the determinants of food insecurity among Inuit women. METHODS: A community-based study in Igloolik, Nunavut, using semi-structured interviews (n = 36) and focus groups (n = 5) with Inuit women, and key informants interviews with health professionals (n = 13). RESULTS: There is a high prevalence of food insecurity among Inuit females in Igloolik, with women in the study reporting skipping meals and reducing food intake on a regular basis. Food insecurity is largely transitory in nature and influenced by food affordability and budgeting; food knowledge; education and preferences; food quality and availability; absence of a full-time hunter in the household; cost of harvesting; poverty; and addiction. These determinants are operating in the context of changing livelihoods and climate-related stresses. CONCLUSION: Inuit women's food insecurity in Igloolik is the outcome of multiple determinants operating at different spatial-temporal scales. Climate change and external socio economic stresses are exacerbating difficulties in obtaining sufficient food. Coping strategies currently utilized to manage food insecurity are largely reactive and short-term in nature, and could increase food system vulnerability to future stresses. Intervention by local, territorial and federal governments is required to implement, coordinate and monitor strategies to enhance women's food security, strengthen the food system, and reduce vulnerability to future stressors. PMID- 20737809 TI - High HIV-TB co-infection rates in marginalized populations: evidence from Alberta in support of screening TB patients for HIV. AB - Heretofore we have not seen strong evidence of synergy between HIV and tuberculosis (TB) in Canada. This may simply reflect a lack of concurrent surveillance for the two diseases. To date, the goal of universal HIV testing of TB patients (> 80% tested) in Canada has not been achieved, despite the existence of two national advisories recommending universal HIV testing of TB patients. In response to these advisories, we recently undertook to demonstrate the feasibility of using an 'opt-out' approach to achieve universal HIV testing of TB patients in Alberta--see the Canadian Journal of Public Health 2009;100(2):116 20. In the present commentary, we add two more years of data (2007-2008) to our earlier report and demonstrate for the first time that HIV co-infection is significantly greater in middle-aged (35-64 years) compared to young adult (15-34 years) TB patients and in Aboriginal and sub-Saharan African, compared to Canadian-born non-Aboriginal and foreign-born 'other' TB patients. Our findings underscore the need for universal concurrent testing as well as greater interaction between TB and HIV programs. PMID- 20737810 TI - Sustained intra- and inter-jurisdictional transmission of tuberculosis within a mobile, multi-ethnic social network: lessons for tuberculosis elimination. AB - BACKGROUND: A context-specific, spatial-temporal understanding of a chain of tuberculosis (TB) transmission can inform TB elimination strategy. METHODS: Clinical, public health and molecular epidemiologic data were used to: 1) identify and describe a complex cluster of TB cases in Alberta, 2) elucidate transmission sequences, and 3) assess case-patient mobility. Socio-economic indicators in loci of transmission and the province at large were described. Factors seen to be fostering or hampering TB elimination were identified. RESULTS: Over a 15-year period, 18 TB cases in Alberta and multiple cases in the Northwest Territories were determined to be due to the same strain. One patient was diagnosed at death; all others completed directly-observed therapy (DOT). Case-level analysis revealed that patients were highly mobile with transmission of the strain over 26,569 km2, an average of 2.8 different places of residence per patient during treatment, and contacts of sputum smear-positive cases spanning 9 of 17 regional health authorities. The majority of the contacts (57%) were attached to a single infectious case living in a homeless shelter. The three loci of transmission in Alberta were separated geographically but similar in terms of median incomes, rates of unemployment, levels of post-secondary education, and rates of population mobility (p < 0.0001). CONCLUSION: Upon review of the experience, central oversight, intra- and inter-jurisdictional coordination and DOT were seen as fostering, and the absence of 'real-time' DNA fingerprinting, social network analysis, engineering controls in shelters and better determinants of health in loci of transmission were seen as hampering TB elimination. PMID- 20737811 TI - Characteristics and response to treatment among Aboriginal people receiving heroin-assisted treatment. AB - BACKGROUND: Medically prescribed diacetylmorphine, the active ingredient of heroin, has been shown to be effective for the treatment of severe opioid addiction. However, there are no data regarding its effectiveness among Aboriginal heroin injectors. METHODS: The present analyses were performed using data from the NAOMI study (North American Opiate Maintenance Initiative), an open label randomized controlled trial that compared the effectiveness of injectable diacetylmorphine (45.8%) and hydromorphone (10%) vs. oral methadone (44.2%) among long-term treatment-refractory opioid-dependent individuals. Rates of retention and response to treatment were analyzed among participants from the Vancouver site (n = 192). RESULTS: Baseline profiles were similar among Aboriginal (n = 60) and non-Aboriginal (n = 132) participants except for higher HIV positive rates among Aboriginal people (23.3% vs. 8.3%). Among Aboriginal participants in the injection and methadone groups, retention rates at 12 months were 84.4% vs. 57.1% and response rates were 68.8% vs. 53.4%, respectively. Aboriginal and non Aboriginal rates were not significantly different. DISCUSSION: Offering treatment assisted with medically prescribed diacetylmorphine or hydromorphone to long-term treatment-refractory opioid-dependent Aboriginal people could be an effective way to attract them into and retain them in treatment as well as dramatically reduce the risk of HIV infection. PMID- 20737812 TI - A systematic literature review on response rates across racial and ethnic populations. AB - OBJECTIVE: To conduct a systematic review examining whether minority ethnic populations participate in surveys as actively as the majority ethnic population. METHODS: A literature and grey literature search was conducted using five online databases as well as government databases and reports, including the search terms: survey response rates or non-response rates and racial or ethnic populations (White, African American, Asian, and Hispanic); survey modes or methods (mail, telephone, face to face, e-mail); and response bias (non-response bias, response bias or social desirability). The search was limited to English language and articles published from January 1990 to June 2009. Article exclusions were based on further inclusion and exclusion criteria. SYNTHESIS: Thirty-five articles were identified on ethnicities and response rates to survey modes. Six articles compared survey mode and response rate for multiple ethnic populations. Response rates ranged from 22.0% to 68.8% in Whites, and in other ethnic groups ranged from 15.4% in African Americans to 70.9% in Latino Americans. Among the 29 articles that presented survey mode and response rate for a specific ethnicity, the highest response rate reported was from African Americans (92.5%) and the lowest was from Cambodian Americans (30.3%). CONCLUSION: Response rate varied across studies but was similar across ethnicities. Response rate may be related to many factors, including survey mode, length of questionnaire, survey language and cultural sensitivity to content. Our review indicates that ethnic populations who participate in surveys are as likely to participate in research as Whites. In literature, data validity across ethnicity is still unknown and should be studied in the future. PMID- 20737813 TI - Cost-effectiveness of high-risk human papillomavirus testing for cervical cancer screening in Quebec, Canada. AB - OBJECTIVES: Human papillomavirus (HPV) testing is not widely used for triage of equivocal Pap smears or primary screening in Quebec, Canada. Our objective was to evaluate the cost-effectiveness of cervical cancer screening strategies utilizing HPV testing. METHODS: We used a lifetime Markov model to estimate costs, quality of life, and survival associated with the following strategies: 1) cytology; 2) cytology with HPV testing to triage equivocal Pap smears; 3) HPV testing followed by colposcopy for HPV-positive women; 4) HPV testing with cytology to triage HPV positive women; and 5) simultaneous HPV testing and cytology. Cytology was used in all strategies prior to age 30. Outcome measures included disease incidence, quality-adjusted life-years saved (QALYs), lifetime risk of cervical cancer, and incremental cost-effectiveness ratios. RESULTS: All strategies incorporating HPV testing as a primary screening test were more effective and less expensive than annual cytology alone, while HPV testing to triage equivocal Pap smears annually was very cost-effective ($2,991 per QALY gained compared to annual cytology alone). When compared to cytology every three years, HPV-based strategies cost an additional $8,200 to $13,400 per QALY gained. CONCLUSION: Strategies incorporating HPV testing are not only more effective than screening based on cytology alone but are also highly cost-effective. Provincial policy-makers should evaluate incorporating HPV-based strategies into current cervical cancer screening guidelines. PMID- 20737814 TI - Noise-induced hearing loss in construction workers being assessed for hand-arm vibration syndrome. AB - BACKGROUND: Construction workers are at risk of noise-induced hearing loss (NIHL) but often have no periodic audiometric testing. METHODS: The participants were construction workers assessed for Hand-Arm Vibration Syndrome (HAVS) at the Occupational Health Clinic, St. Michael's Hospital, Toronto, Ontario. Audiometry was offered and 169 of the 191 workers assessed for HAVS agreed to have the audiometric test. The objective was to examine the prevalence of hearing loss in these 169 workers and to determine the effect on hearing of duration of work in construction (as a proxy for noise exposure) and the severity of vibration white finger (VWF) which previous studies have suggested is a marker for increased individual susceptibility for NIHL. VWF was measured by the Stockholm vascular scale. RESULTS: All participants were men, median age of 57 (range: 28-75), median number of years worked in construction of 35 (range: 4-52). All of the Spearman rank correlations between years worked in construction and the hearing levels at each audiometric frequency were statistically significant (p < 0.001). Overall, 31 (18.3%) participants had hearing loss at or above the level at which a workers' compensation pension would be granted in Ontario and the prevalence of this auditory outcome had a statistically significant increase as years worked in construction increased. Multivariate linear regression indicated that VWF also had a statistically significant effect on hearing loss for all audiometric frequencies combined after controlling for years worked in construction. CONCLUSION: Improved prevention of hearing loss in construction workers is needed. PMID- 20737815 TI - Rates of congenital anomalies and other adverse birth outcomes in an offspring cohort of registered nurses from British Columbia, Canada. AB - OBJECTIVES: Although there is concern that occupational exposures in some nursing professions may confer reproductive risks, there are few relevant studies. Our objective is to determine if a cohort of female registered nurses (RN) from British Columbia (BC), in comparison to BC women in general, have elevated rates of congenital anomalies, stillbirths, low birth weight, or prematurity in their offspring. METHODS: A cohort of RNs from BC was linked to Vital Statistics birth records and the BC Health Status Registry (HSR) between the years 1986 and 2000. The RN offspring cohort included 23,222 births. For each outcome, odds ratios (OR) with 95% confidence intervals (CI) were determined by comparing rates in the nurses' cohort with the rates in the general population standardized for the year of birth. RESULTS: Apart from chromosomal anomalies, for each of the ICD-9 congenital anomaly categories there were fewer congenital anomalies than expected, resulting in an overall prevalence of congenital anomaly cases (with at least one anomaly) that was significantly lower in the RN cohort (1,567 observed vs. 1,846 expected; OR 0.84, 95% CI 0.78-0.90) in comparison to the general population. Low birth weight (1,138 observed vs. 1,260 expected; OR 0.90, 95% CI 0.83-0.98) was also significantly lower, while prevalence of prematurity and stillbirths were not significantly different than among the general population. CONCLUSION: Offspring of RNs in BC had a lower prevalence of congenital anomalies and low birth weight compared to the rates found among the general population. Further studies are underway to determine if subpopulations within the RN cohort are at risk. PMID- 20737816 TI - Pascal's Wager: from science to policy on early childhood development. AB - Evidence suggests that our brains are shaped profoundly by experiences in early life, with long-lasting implications for development. This science has yet to make the leap to policy on early childhood development in Canada--a shortcoming that has left this country well behind other developed nations. The Pascal Report, released in June 2009, marks an historic opportunity to enact comprehensive early childhood education and care policy in Ontario. Properly implemented, it could serve as a model for such policy across the country. Its successful adoption will require sustained advocacy and ongoing research by the Canadian medical community. PMID- 20737817 TI - Barriers to optimizing investments in the built environment to reduce youth obesity: policy-maker perspectives. AB - OBJECTIVE: To identify factors which limit the ability of local governments to make appropriate investments in the built environment to promote youth health and reduce obesity outcomes in Atlantic Canada. METHOD: Policy-makers and professionals participated in focus groups to discuss the receptiveness of local governments to introducing health considerations into decision-making. Seven facilitated focus groups involved 44 participants from Atlantic Canada. Thematic discourse analysis of the meeting transcripts identified systemic barriers to creating a built environment that fosters health for youth aged 12-15 years. RESULTS: Participants consistently identified four categories of barriers. Financial barriers limit the capacities of local government to build, maintain and operate appropriate facilities. Legacy issues mean that communities inherit a built environment designed to facilitate car use, with inadequate zoning authority to control fast food outlets, and without the means to determine where schools are built or how they are used. Governance barriers derive from government departments with distinct and competing mandates, with a professional structure that privileges engineering, and with funding programs that encourage competition between municipalities. Cultural factors and values affect outcomes: people have adapted to car-oriented living; poverty reduces options for many families; parental fears limit children's mobility; youth receive limited priority in built environment investments. CONCLUSION: Participants indicated that health issues have increasing profile within local government, making this an opportune time to discuss strategies for optimizing investments in the built environment. The focus group method can foster mutual learning among professionals within government in ways that could advance health promotion. PMID- 20737818 TI - The unmet health needs of East Asian high school students: are homestay students at risk? AB - OBJECTIVES: Most "homestay" high school students come to Canada from East Asian countries such as China, Korea and Japan to attend school while living with another family. Our objectives were to examine: 1) the characteristics of homestay youth compared to immigrant and Canadian-born East Asian youth and 2) whether their health risk behaviours are similar to immigrant or Canadian-born East Asian youth. METHODS: We used the 2003 British Columbia Adolescent Health Survey to examine characteristics of East Asian youth and their health risk behaviours, including sexual behaviours, substance abuse, abuse history, and health status. Homestay students were those not born or raised in Canada and not living with their parent(s) or in foster care. Multivariate models tested for the independent association of student group, controlling for age. RESULTS: Homestay students (weighted n = 3,085) were older, on average, than immigrant or Canadian born youth and spoke a language other than English at home (p < 0.001). Multivariate analyses showed that homestay students were more likely to engage in sexual behaviours than other youth and over 4 times more likely to have used cocaine. Female homestay students were 3 times more likely to be a victim of sexual abuse and were also 3 times more likely to use a substance prior to sex. CONCLUSION: Homestay students remain a forgotten and extremely vulnerable group of youth, in part because they have special living arrangements. No one is currently held accountable for their health or safety. In the absence of health policy about homestay students, public health officials and providers have a central role in ensuring the former's health is not threatened. PMID- 20737819 TI - The majority of older British Columbians take vitamin D-containing supplements. AB - OBJECTIVES: Health Canada recommends vitamin D supplements (10 microg/d) for Canadians aged > or = 50 years, but no data are available on adoption of this recommendation. Accordingly, this study was conducted to determine the current use of vitamin D supplements among British Columbian adults 50 years and over, and to explore relationships among vitamin D supplement use, socio-demographic variables, and knowledge, attitudes and beliefs about vitamin supplementation. METHODS: A population-representative stratified sample, recruited by random-digit dialling, completed a telephone-administered survey in late fall of 2008. Respondents provided details on supplements used in the past month (dosage, frequency, etc.) and demographic data, and responded to statements reflecting health beliefs about supplements, from which a Supplement Health Belief score was calculated. Eligible non-respondents indicated their age, sex, and whether they had used a supplement within the past month. RESULTS: Similar proportions of participants (n = 969) and non-respondents (n = 1,027) reported any supplement use in the past month. Among participants, 60% had used a vitamin D supplement (median intake among supplement users was 10 microg/d) and 3% exceeded the Tolerable Upper Intake Level of 50 microg/d. In multivariate analysis, vitamin D supplementation was significantly associated with female sex, not smoking, higher educational attainment, having a health care professional recommend supplement use, and a higher Supplement Health Belief score. CONCLUSION: Although most older adults used a vitamin D supplement, further dissemination of this recommendation is needed. PMID- 20737820 TI - The effect of cash lottery on response rates to an online health survey among members of the Canadian Association of Retired Persons: a randomized experiment. AB - OBJECTIVES: The objectives of the study were 1) to assess the effect of cash lottery on participation rates in a web-based study of physical activity and joint health and 2) to compare recruitment via direct e-mail versus advertisement in an online newsletter. METHODS: A sample of 1,150 individuals, randomly selected from a database of members of the Canadian Association of Retired Persons (CARP), was e-mailed a request to participate in an online survey, with follow-up e-mails after 1 and 2 weeks. The sample was randomly split into two groups. Half the sample was offered entry into a cash draw with a $500 grand prize and five $100 prizes, whereas the other half was not offered any incentive. In addition, a brief advertisement about the survey (without an incentive) was placed in an online newsletter that was circulated to 14,000 randomly selected CARP members. RESULTS: In the incentive group, 305 (53.0%) clicked on the hyperlink and visited the website and 84 (14.6%) completed the survey. In the group who received no incentive, 280 (48.7%) clicked on the link and 59 (10.3%) completed the survey. Of those who received the online newsletter, 492 (3.5%) visited the website and 106 (0.76%) completed the survey. CONCLUSION: A relatively modest financial incentive in the form of a cash lottery significantly increased participation rates in an online health survey. Recruitment through a newsletter advertisement had a very low yield compared to direct e-mail. PMID- 20737821 TI - Men's sexual orientation and health in Canada. AB - OBJECTIVES: Previous large-scale population studies have reported that gay and bisexual men may be at increased risk for health disparities. This study was conducted to determine whether health status and health risk behaviours of Canadian men vary based on sexual orientation identity. METHODS: Utilizing the Canadian Community Health Survey data (Cycle 2.1, 2003; n = 49,901), we conducted multivariable logistic regression to assess the independent effects of sexual orientation on health status and health risk behaviours. For all multivariate models, we calculated odds ratios, p-values, standard errors, and 95% confidence intervals (CIs) using the bootstrap re-sampling procedure recommended by Statistics Canada. RESULTS: When compared to heterosexual men, gay and bisexual men did not report more respiratory conditions; had lower rates of obesity and overweight BMI; and reported more mood/anxiety disorders, and a history of lifetime suicidality. Gay and bisexual men did not report higher rates of daily smoking or risky drinking, however, gay men reported an almost six-fold increase in STD diagnoses when compared to heterosexual men. CONCLUSION: This study represents the largest-known population-based data analysis on health risks and behaviours among men of varying sexual orientations. These findings raise important concerns regarding the impact of sexual orientation on mental and sexual health. Limitations of this data set, including those associated with measurement of sexual orientation, are discussed. Further research is required to understand the mechanisms that influence these health resiliencies and disparities. PMID- 20737822 TI - Igniting an agenda for health promotion for women: critical perspectives, evidence-based practice, and innovative knowledge translation. AB - Health promotion is a set of strategies for positively influencing health through a range of individual, community-based, and population interventions. Despite international recognition that gender is a primary determinant of health and that gender roles can negatively affect health, the health promotion field has not yet articulated how to integrate gender theoretically or practically into its vision. For example, interventions often fail to critically consider women's or men's diverse social locations, gender-based power relations, or sex-based differences in health status. Yet without such analyses, interventions can result in the accommodation or exploitation of gender relations that disadvantage women and compromise their health. In this paper, we seek to ignite an agenda for health promotion for women. We discuss the need for a conceptual framework that includes a sex-gender-diversity analysis and critically considers 'what counts' as health promotion to guide the development and implementation of evidence-based practice. We also consider how innovative knowledge translation practices, technology developments and action research can advance this agenda in ways that foster the participation of a wide range of stakeholders. PMID- 20737823 TI - Future challenges to health and public health services in Canada. PMID- 20737824 TI - Prevalence of overweight and obesity among children aged 6-12 years in Dodoma and Kinondoni municipalities, Tanzania. AB - A cross-sectional comparison study was conducted to determine the prevalence of overweight and obesity among schoolchildren 428 children aged 6 -12 years in Dodoma and Kinondoni municipalities in Tanzania. Anthropometric and body composition measurements were taken for all respondents. A total of 428 children were involved in the study. The prevalence of obesity among children aged 6 - 9 years in Dodoma and Kinondoni were 5.6% (n = 118) and 6.3% (n = 87), respectively. Likewise, 4.2% (n = 118) of children aged 6-9 years in Dodoma were overweight while 8.6% (n = 87) of their counterparts in Kinondoni municipality were overweight. For children aged 10-12 years, 3.9% (n= 118) in Dodoma were obese compared to 5.8% (n = 87) of their peers in Kinondoni. Some 4.9% of the children aged 10-12 years in Dodoma were overweight compared to 5.8% of their counterparts in Kinondoni. The average body fat mass of children aged 6 - 9 years in Dodoma ranged from 21.42-21.81%, while that of their peers in Kinondoni ranged from 21.66-21.98%. The average body fat mass of children aged 10-12 years ranged between 23.95-24.10% in Dodoma and 23.65-24.95% in Kinondoni. There were gender and age differences in body fat mass distribution, with girls and the older children having significantly (P < 0.05) higher proportion of body fat mass. In conclusion, although the prevalence of overweight and obesity among children in this study were lower than those reported elsewhere, there is an imminent danger because the trend of the conditions is rising swiftly with urbanization, changes in lifestyles and socio-economic transition. It is recommended that, children should be educated on good nutrition practices and trained to develop healthy eating behaviours. Parents should encourage lifestyle behaviours that promote high level of physical activities. Physical education and organized sports at schools should be revived. PMID- 20737825 TI - Thyroid hormones profile in students of Makerere College of Health Sciences in Kampala Uganda. AB - Serum concentrations of thyroxine (T4), triiodothyronine (T3) and Thyroid Stimulating Hormone (TSH) are used to assess thyroid function. It is recommended that each laboratory or hospital should establish its own reference values of T4, T3 and TSH for their clients because these hormones vary with ethnicity, geographical and climatic conditions of a population. There is no documented study which has been done to determine the Thyroid hormones profile in Ugandan general population. This study is one of the first attempts to determine Thyroid hormones profile in healthy Ugandans. The main objective of this study was to determine the thyroid hormones profile of students of the Makerere College of Health Sciences in Kampala, Uganda. A cross sectional descriptive study was done involving 72 students, with the mean age of 24.17 +/- 4.48 years. Subjects who volunteered to participate in the study were interviewed; their height and body weight measured, 5 ml of blood withdrawn, and sera harvested. FT4 and T3 Radioimmuno Assay (RIA) were done and TSH was assayed using Immunoradiometric Assay (IRMA) technique. The mean serum concentration of FT4 was 17.016 +/- 3.847 mol/L. For T3, mean serum concentration was 1.43 +/- 0.825 nmol/L, and mean serum TSH level was 2.412 +/- 2.284 microIU/ml. Variations of serum concentrations of FT4, T3 and TSH with sex, age, or region of origin were not statistically significant. Serum concentration of TSH increased with increased body mass index (BMI). It was 2.073 +/- 1.907 microIU/ml for subjects with BMI of < or = 24.9 Kg/m2, 3.588 +/- 1.495 microIU/ml for subjects with BMI of 25 - 29.9 kg/m2 and 4.450 +/- 0.593 microIU/ml for subjects with BMI > or = 30 kg/m2 (P=0.009). However, BMI had no effect on serum concentrations of FT4 and T3. Serum concentrations of T4, T3 and TSH obtained from this study all differ with the values which are currently used as reference ranges in the country. We recommend a similar study involving a population representative of Ugandans to be conducted so as to establish normal reference values of T4, T3 and TSH for Ugandans. We also recommend BMI of patients to be taken into consideration during interpretation of serum TSH concentrations results. PMID- 20737826 TI - Socio-economic and partner relationship factors associated with antenatal depressive morbidity among pregnant women in Dar es Salaam, Tanzania. AB - Depression during pregnancy may negatively influence social functioning, birth outcomes and postnatal mental health. A cross-sectional analysis of the baseline survey of a prospective study was undertaken with an objective of determining the prevalence and socio-demographic factors associated with depressive morbidity during pregnancy in a Tanzanian peri-urban setting. Seven hundred and eighty seven second to third trimester pregnant women were recruited at booking for antenatal care at two primary health care clinics. Prenatal structured interviews assessed socio-economic, quality of partner relationships and selected physical health measures. Depressive symptoms were measured at recruitment and three and eight months postpartum using the Kiswahili version of the Hopkins Symptom Checklist. Completed antenatal measures available for 76.2% participants, showed a 39.5% prevalence of depression. Having a previous depressive episode (OR 4.35, P<0.01), low (OR 2.18, P<0.01) or moderate (OR 1.86, P=0.04) satisfaction with ability to access basic needs, conflicts with the current partner (OR 1.89, P<0.01), or booking earlier for antenatal care (OR 1.87, P=0.02) were independent predictors of antenatal depression in the logistic regression model; together explaining 21% of variance in depression scores. Attenuation of strength of multivariate associations suggests confounding between the independent risk factors and socio-demographic and economic measures. In conclusion, clinically significant depressive symptoms are common in mid and late trimester antenatal clinic attendees. Interventions for early recognition of depression should target women with a history of previous depressive episodes or low satisfaction with ability to access basic needs, conflict in partner relationships and relatively earlier booking for antenatal care. Findings support a recommendation that antenatal services consider integrating screening for depression in routine antenatal care. PMID- 20737827 TI - Understanding women's experiences of distress during pregnancy in Dar es Salaam, Tanzania. AB - Several studies show depression is common during pregnancy. However, there is limited information in Tanzania on the magnitude of perceived distress during pregnancy and meanings ascribed to such distress. A descriptive survey collected data using unstructured interviews from 12 traditional practitioners and 10 peri urban women with previous pregnancy related mental health concerns identified using a depression vignette. The objectives were to describe the sources and characteristics of distress during pregnancy, and idioms of distress that could inform cultural adaptation of depression screening tools. Narrative analysis showed an emergent category of "problematic pregnancies" framed women's recollections of prolonged periods of sadness. This experience was qualified using various idioms of distress that were differentially emphasized depending on informant's perceived causes of health concern. The idiom kusononeka was consistently used to describe extreme sadness across causal categories and clustered with at least two typical features of major depression. This suggested existence of a construct with similarities to biomedical criteria for depression. "Thinking too much" emerged as a distinctive expression associated with prolonged sadness. Distinctive expressions of social functioning impairments were identified that can inform depression severity assessments. In conclusion, contextual inquiry into experiences of psychological distress showed distinct local idioms that clustered in patterns similar to symptoms of biomedical depressive episodes. Further studies to assess the utility of local idioms of distress and distress related functional impairment in depression assessment tools are warranted. PMID- 20737828 TI - Knowledge and perception of mothers and caregivers on childhood diarrhoea and its management in Temeke municipality, Tanzania. AB - Diarrhoea is an increase in volume of stool or frequency of defecation. It is one of the most common clinical signs of gastrointestinal diseases, but also can reflect primary disorders outside of the digestive system. This cross-sectional descriptive survey was conducted in Temeke Municipality, Dar es Salaam over a 4 month period to investigate on knowledge and perception of mothers/caregivers of underfives on childhood diarrhoea. Specifically, the study focused on frequency of diarrhoeal episodes and their risk factors as well as effectiveness of traditional remedies used for its management prior to seeking medical attention. A semi-structured questionnaire was used for data collection, through which a total of 161 mothers were interviewed. Of those, 74 (46%) had female and 87 (54%) had male underfives with median age of 2-years. Frequency of diarrhoeal episodes was high among the underfives and was comparable between females and males (87 vs 74; P<0.05). Medicinal plants were the most common traditional remedies employed by majority (71%) of the interviewees, which have been purported to be effective in management of childhood diarrhoea. Guava (leaves and fruits) was the most commonly used remedy in the treatment of diarrhoea. Mothers' knowledge on predisposing factors of childhood diarrhoea was poor, which was directly correlated with education level. Only about one-third of the respondents (31%) were aware of risk factors for childhood diarrhoea that cited poor sanitation and water as the main factors. Diarrhoeal episodes were perceived wrongly as normal growth stage and that were caused by several other "illnesses". It is important that further studies on traditional remedies should be carried out to validate their usefulness in the treatment of childhood diarrhoea. PMID- 20737829 TI - Perspectives of patients towards medical students' at the Queen Elizabeth Central Hospital, Blantyre, Malawi. AB - Medical students gaining experience in outpatient's clinics and admission wards are exposed to clinical clerkship as this is an important part of their training. There is paucity of reported patients' experiences and perceptions of medical students in low-income settings. The present study was conducted at the Queen Elizabeth Central Hospital (QECH), Malawi to describe patients' and perceptions of, and experience with medical students being present when patients are seen by a medical doctor or students' individual clerking. Participants mostly felt that medical students were compassionate, enthusiastic and helpful to them. The participants' who had been ever clerked by students felt motivated to be present for student learning for altruistic reasons as well as for mutual benefit between student and patient. Patients attending the QECH in Blantyre, Malawi are generally satisfied with the attention and support they obtain from students. Balancing the need for appropriate supervision of students, and facilitating the retention of this patient-cantered approach to care should be maintained. PMID- 20737830 TI - Brine shrimp toxicity of some plants used as traditional medicines in Kagera Region, north western Tanzania. AB - Dichloromethane and/or ethanol extracts of 30 plants used as traditional medicines in Bukoba district, northwestern Tanzania were evaluated for brine shrimp toxicity. Among the 50 extracts tested, 32 extracts (64%) showed very low toxicity with LC50 values above 100 microg/ml. Among these 12 (24%) which had LC50 >500 microg/ml can be categorized as being practically non-toxic. Among the remaining extracts 19 (38%) which showed LC50 > 100 < 500 microg/ml are also considered to be non-toxic. Extracts that showed LC50 results between 30-100 microg/ml have been categorized as mildly toxic; these include ethanol extracts of Lantana trifolia (LC50 32.3 microg/ml), Vernonia bradycalyx (LC50 33.9 microg/ml), Antiaris toxicaria (LC50 38.2 microg/ml) and Rubus rigidus (LC50 41.7 microg/ml) and the dichloromethane extracts of Gynura scandens (LC50 36.5 microg/ml) and Bridelia micrantha (LC50 32.0 microg/ml). The dichloromethane extracts of Picralima nitida (LC50 18.3 microg/ml) and Rubus rigidus (LC50 19.8 microg/ml), were only moderately toxic. Picralima nitida and Rubus rigidus extracts are only 1.1 and 1.2 less toxic than the standard drug, cyclophosphamide (LC50 16.3 microg/ml). In conclusion, the results indicate that among the 30 plants used as traditional medicines, 28 are safe for short term use. Picralima nitida and Rubus rigidus extracts are mildly toxic, but by comparison have a remote possibility to yield active anticancer compounds. PMID- 20737831 TI - Diversity, spatial and temporal abundance of Anopheles gambiae complex in the Rufiji River basin, south-eastern Tanzania. AB - The Anopheles gambiae complex contains the most efficient malaria vectors in the world. Identification of the species and the concomitant distribution are vital for effective malaria control. The objective of the study was to establish the diversity, spatial and seasonal abundance of malaria vectors in the Rufiji River Basin in Tanzania and the implications on malaria vector control. Mosquitoes were collected using CDC light-traps. Anopheles mosquitoes were identified by conventional keys. Anopheles gambiae complex were speciated using standard PCR method. Of the 562 specimens analysed by PCR 69% produced fragments equivalent to An. gambiae s.s. (390 bp), 23% equivalent to An. arabiensis (315 bp), and 7% as An. merus (464 bp). An. gambiae s.s. and An. merus were more abundant on the plateau than on the flood plain (Fisher's exact test, P < 0001), whereas An. arabiensis was equally abundant between the two sites (Fisher's exact test, P=1656). The density of the three sibling species of An. gambiae complex also varied with the seasons. An. gambiae s.s. and An. arabiensis were most predominant species during the start of the rainy season, but as season progresses, An. gambiae s.s. predominated. An. merus was only recorded during the short rainy season. In conclusion, both An. gambiae s.s., An. arabiensis and An. merus are malaria vectors in the Rufiji River basin and that An. merus is recorded for the first time in the south-eastern coast of Tanzania. These findings are important in the planning and implementation of malaria vector control activities in the Rufiji River basin, south-eastern Tanzania. PMID- 20737832 TI - In vitro susceptibility of Plasmodium falciparum isolates from Abidjan, Cote d'Ivoire, to artemisinin, chloroquine, dihydroartemisinin and pyronaridine. AB - Cote d'Ivoire is an endemic area for Plasmodium falciparum malaria, with perennial transmission in the southern forest and seasonal transmission in the northern savannah. Change of first-line treatment of uncomplicated malaria to artemisinin-combination therapy (ACT) is widespread in the country as elsewhere in Africa. The present study was conducted to assess the in vitro response of Plasmodium falciparum to antimalarial drugs currently used in the country (chloroquine, artemisinin and dihydroartemisinin) and new drugs that could be used in the near future (pyronaridine) and to analyse the pattern of cross resistance between these drugs. The standard in vitro drug sensitivity microtechnique recommended by the World Health Organization was used to assess the sensitivity of Plasmodium falciparum isolates collected in Abidjan (Cote d'Ivoire) between April and December 2006. Of 128 in vitro tests performed, 112 (87.5%) were successful. Among them, 32, 27, 25, and 28 P. falciparum isolates grew satisfactorily and yield interpretable results for chloroquine, pyronaridine, artemisinin, and dihydroartemisinin respectively. The proportions of resistant isolates were 56.2% for chloroquine, 48% for pyronaridine, 36% for artemisinin and 3.6% for dihydroartemisinin. The most potent drug was dihydroartemisinin with a geometric mean IC50 of 2.72 nM ranged from 1.45 to 3.99 nM. No multi-resistant isolates (showing resistance to more than three drugs) were found. A positive correlation was found between the IC50 values for the following drugs: chloroquine and pyronaridine (r=0.45), pyronaridine and dihydroartemisinin (r=0.40), chloroquine and artemisinin (r=0.68), artemisinin and dihydroartemisinin (r=0.62). Data suggested cross-resistance between these drugs and warrant an improved surveillance programme for drug resistance to malaria in Cote d'Ivoire. PMID- 20737833 TI - Spatial and temporal distribution of rabies in northern Tanzania in the period of 1993-2002. AB - A retrospective study was carried out to investigate the occurrence and distribution patterns of rabies cases in northern Tanzania. Data on laboratory confirmed brain samples and associated case reports submitted to the Arusha Veterinary Investigation Centre, for a period of ten years (1993-2002) was retrieved and reviewed. A total of 98 suspected rabies brain specimens from different animal species and geographical areas were submitted and processed during the period under review. Rabies was confirmed using Fluorescent Antibody Technique test. Of the 98 brain specimens processed, 65 (66.3%) were confirmed to be rabies cases. Canine rabies accounted for 73.8% of the cases and was diagnosed in dogs (43), jackals (4) and hyenas (1). Rabies in wildlife accounted for 5 out of 48 canine confirmed cases. Most of the cases were from Arusha Municipality (20) followed by Arumeru (19), Ngorongoro (9) and Moshi (8) districts. Rabies positive cases in other animal species were in the following order of frequencies: bovine (9 out of 11); feline (5 out of 10); equine (1 out of 2); caprine (2 out of 2). One porcine brain specimen was rabies negative. The high proportion of rabies positive cases confirmed suggests the level of their endemicity in the northern regions of Tanzania. Moreover, the findings highlights the need for sustained surveillance and institution of control measures among dog population and awareness creation particularly among general public and children whom are at high risk of contracting rabies because of their close contact with dogs. PMID- 20737834 TI - Soil transmitted helminth infections and schistosomiasis in school age children in sub-Saharan Africa: efficacy of chemotherapeutic intervention since World Health Assembly Resolution 2001. AB - Soil transmitted helminth infections (STH) and schistosomiasis constitute major public health challenges among school-age children in sub-Saharan Africa. This review assessed the efficacy of chemotherapeutic intervention in line with the World Health Assembly (WHA) resolution since the passage in 2001. Using the Medline Entrez-Pubmed search, relevant publications were identified via combinations of key words such as helminth infection, school children, chemotherapy, Africa. Albendazole, mebendazole, and praziquantel were the antihelminthic drugs most commonly evaluated. Cure rates >80% and egg reduction rates >90% were recorded in most cases of schistosomiasis using praziquantel. Albendazole was very effective against A. lumbricoides and hookworm infections with majority of the studies recording cure rates >75%, but the efficacy of the drug was poor against T. trichiura. To ensure the realization of the WHA resolution, there is need for regular treatment of school children, development of alternative antihelminthic drugs and vaccines, environmental control measures and health education. PMID- 20737836 TI - Redesign and operation of the National Home And Hospice Care Survey, 2007. AB - OBJECTIVES: This methods report provides an overview of the redesigned National Home and Hospice Care Survey (NHHCS) conducted in 2007. NHHCS is a national probability sample survey that collects data on U.S. home health and hospice care agencies, their staffs and services, and the people they serve. The redesigned survey included computerized data collection, greater survey content, increased sample sizes for current home health care patients and hospice care discharges, and a first-ever supplemental survey called the National Home Health Aide Survey. METHODS: The 2007 NHHCS was conducted between August 2007 and February 2008. NHHCS used a two-stage probability sampling design in which agencies providing home health and/or hospice care were sampled. Then, up to 10 current patients were sampled from each home health care agency, up to 10 discharges from each hospice care agency, and a combination of up to 10 patients/discharges from each agency that provided both home health and hospice care services. In-person interviews were conducted with agency directors and their designated staff; no interviews were conducted directly with patients. The survey instrument contained agency- and person-level modules, sampling modules, and a self-administered staffing questionnaire. RESULTS: Data were collected on 1036 agencies, 4683 current home health care patients, and 4733 hospice care discharges. The first stage agency weighted response rate (for differential probabilities of selection) was 59%. The second-stage patient/discharge weighted response rate was 96%. Three public-use files were released: an agency-level file, a patient/discharge-level file, and a medication file. The files include sampling weights, which are necessary to generate national estimates, and design variables to enable users to calculate accurate standard errors. PMID- 20737835 TI - Role of microscopic examination of stool specimens in the diagnosis of campylobacter infection from children with acute diarrhoea in Kampala, Uganda. AB - Campylobacter species are a frequent cause of enteritis and less often of extraintestinal infections in humans. The diagnosis of campylobacter infection depends mainly on culture which is difficult and expensive to be done as routine in most clinical microbiology laboratories in the developing countries. This study was conducted to determine the sensitivity and specificity of Gram-stain of the stool in diagnosis of campylobacter infection, using culture as the gold standard. A total of 226 stool specimens were obtained from children with acute diarrhoea, attending Mulago Hospital in Kampala, Uganda. Stool smears were made and conventional Gram stain done using 0.3% carbol-fuschin as counter stain for 5 minutes. Mucous part of the stool was cultured in Charcoal Ceferaperazone Deoxycholate Agar and blood contained selective media. A total of 21 stool samples (9.3%) were positive by culture and 17 (7.5%) by Gram stain. Sensitivity and specificity of Gram stain in the diagnosis of campylobacter infection was 76% and 99.5%, respectively with positive predictive value of 94.1%. A total of 127 (56.2%) had white blood cells (WBC) in stool and there was strong association between WBC in stool and the presence of campylobacter infection (P=0.001). Gram stain is a good alternative in diagnosis of campylobacter infection in place where facilities for culture are limited. PMID- 20737838 TI - Reproduction of the fish Lutjanus analis (mutton snapper; Perciformes: Lutjanidae) from Northeastern Brazil. AB - The mutton snapper Lutjanus analis is an overexploited species of economic importance for the Northeast region of Brazil. To determine the reproductive aspects of the mutton snapper, biological data were sampled from Bahia, Pernambuco, Paraiba, Rio Grande do Norte and Ceara States, between 7 and 200m depth, from February 1997 to December 1999, performed in the Brazilian Economic Exclusive Zone Study Program (REVIZEE-NE Program). Data on total length (TL), fork length (FL), standard length (SL), total weight (TW) and gutted weight (GW) were measured. The gonads were collected and fixed in FAACC for histological analysis on maturational stage and calculation of the gonadosomatic index (GSI). A total of 135 fishes were collected; from these, 74 were females and 61 were males. Females were between 28.0 and 69.0cm (TL) and the males between 35.0 and 75.0cm (TL). Mutton snapper are gonochorists, and the spawning season, determined by the maturity stages frequency and the GSI, occurred between November and April, with peak spawning in March. The mature females' minimum length was 28.0cm fork length, smaller than the minimum maturation length previously reported for the species in Cuba. The exploitation status of the species and the biological traits enhances the importance of establishing spatial and seasonal protection measures such as protected areas both in nursery and spawning sites. PMID- 20737837 TI - Design and operation of the National Survey of Adoptive Parents, 2007. AB - OBJECTIVE: This report presents the development, plan, and operation of the National Survey of Adoptive Parents (NSAP), a module of the State and Local Area Integrated Telephone Survey conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics. NSAP was designed to produce national estimates of the characteristics, health, and well-being of adopted children and their families, the preadoption experiences of the adoptive parents, and their access to and utilization of postadoption supports and services. Funding for the survey was provided by the Office of the Assistant Secretary for Planning and Evaluation and the Administration for Children and Families, both of the Department of Health and Human Services. METHODS: The National Survey of Children's Health, 2007 (NSCH) was a random-digit-dial telephone survey of households with children under age 18 years. In households with more than one child, one child was randomly selected to be the subject of the interview. Children identified as adopted, who did not live with a biological parent and who lived in households where English was spoken, were eligible for the NSAP follow up interview. The NSAP interview was a call-back scheduled at the end of the NSCH telephone interview. Sampled children included those adopted from other countries, from the U.S. foster care system, and from private domestic sources. Respondents were either the adoptive mother or the adoptive father. RESULTS: A total of 2,089 NSAP interviews were completed from April 2007 to July 2008. The interview completion rate (i.e., cooperation rate) for eligible respondents was 74.4%. The overall response rate, taking into account nonresponse to NSCH, was 34.6%. PMID- 20737839 TI - [Morphogeometry of fishes in the genus Hyphessobrycon (Characiformes: Characidae), heterorhabdus group, from Venezuela]. AB - Hyphessobrycon is the most numerous and morphologically complex genus of Characidae, that includes 122 valid species, 17 of which are present in Venezuela. Different methods have been proposed for species identification within this genus. We present a morphometric analysis for the species Hyphessobrycon, heterorhabdus group. A total number of 310 individuals were photographed and analyzed by means of Box Truss method. The combination of 16 homologous landmarks and the design of Box Truss yielded 28 measurements. The Principal Components Analysis (PCA) indicated that the differences between the species are related to the distance between snout and the supraoccipital (81.7%), and between the supraoccipital and the base of the pectoral fin (11.87%). All species showed allometric growth except for Hyphessobrycon tuyensis, which resulted isometric in the Box Truss I. The partial deformations describe the form differences related to the cephalic region and the body depth. The great body form similarity is related to the phylogeny and biogeography of these species. PMID- 20737840 TI - [Redescription of Parodon caliensis and Saccodon dariensis (Characiformes: Parodontidae)]. AB - Redescription of Parodon caliensis and Saccodon dariensis (Characiformes: Parodontidae). Parodontidae family is a group of Characiformes fishes distributed throughout South America and parts of Panama, except in the basins of the southern Bahia state in Brasil on the Atlantic coast, Patagonia and the Amazon river channel. The family includes three genera: Apareiodon Eigenmann 1916, Parodon Valenciennes 1849 y Saccodon Kner 1863, 28 recognized species and two valid genera: Parodon and Saccodon. Redescription of Parodon caliensis and Saccodon dariensis is carried out based on type, and topotypic material from Colombia. Significant differences were found in morphometric, meristic, osteologic and color characters. S. dariensis is widely distributed but P. caliensis is restricted to the upper Cauca River drainage. Three species are considered herein as synonyms of S. dariensis: Apareiodon dariensis, A. compressus and S. caucae. Sexual dimorphism is described for both species. PMID- 20737841 TI - Hydrochemistry and phytoplankton composition of two tidal creeks in South-Western Nigeria. AB - As in other countries, the effects of human stressors on coastal areas and waters in Nigeria are increasing, and management strategies are urgent. In order to assess this, studies on phytoplankton composition in relation to physico-chemical characteristic of two tidal creeks in Lagos were conducted for six months (October 2007 to March 2008). Variations in some of the physical and chemical parameters such as rainfall, temperature, salinity, nitrate-nitrogen, phosphate phosphorus, sulphate, salinity, biological oxygen demand and chemical oxygen demand influenced the phytoplankton abundance. Three major divisions were recorded for the two creeks: Bacillariophyta, Chlorophyta and Cyanophyta. Among these, diatoms were the most abundant group observed. Water quality characteristics reflected the effect of tidal influence and consequent salt water inflow, fresh water incursion and the pollution status of one of the creeks, as a result of industrial and commercial activities in the area. PMID- 20737842 TI - [Lipids in the amphipod Talorchestia margaritae (Amphipoda: Talitridae) and its relationship with the ecology of the species]. AB - T. margaritae, an endemic species inhabiting Venezuelan coasts, plays an important ecological role in plant and animal decomposition. To understand this issue in some animal groups, especially small ones, lipid composition analysis has been an interesting tool to describe their trophic relationships and food preferences. In order to assess this and visualize the components of their diet, we determined the lipid composition differences between males and females and among age classes in this species. Two sandy beaches were selected: Mangle Quemao and Las Mercedes de Paparo, from which sand samples of known volume were collected at the supralittoral area in 2007. Organisms were separated by age and sex classes, and their size, weight, density, biomass, total lipids (TL), lipid classes and fatty acid markers present in their tissues were determined. The sizes were similar for all age classes between the two locations, while the weights were higher for Mangle Quemao. The TL and lipid classes showed similar proportions between sexes, age classes and locations (TL: 3-5%; Phospholipids: 20 30%; Glycolipids: <1%; sterols: 4%). On the other hand, Triglycerides (TAG) were higher in Mangle Quemao, which may be related to the difference between the weights of two locations. The most abundant fatty acid biomarkers in the two studied sites were 16:0 and 18:1(n-9); this last one is characteristic of a carnivorous diet. The other nine markers were identified with changes in their distribution in organisms at Mangle Quemao and between males and females of both populations. Based on observed fatty acids markers we can assume T. margaritae as a generalist carnivore. Those populations were influenced by available food; inducing differences in weight, TAG proportion and markers diversity. PMID- 20737843 TI - Mangrove forest composition and structure in Las Perlas Archipelago, Pacific Panama. AB - Mangrove forest is an important ecosystem that provides many services, but in Panama, as in other countries, they are under threat due to a variety of human activities. Nowadays, large areas of mangroves continue to be lost without been described and lack of management strategies. This study focused on the mangrove structure in the two largest islands, Isla del Rey and Isla San Jose, of Las Perlas Archipelago (LPA), Pacific Panama. Assessment of Landsat satellite imagery revealed loss of mangroves in the LPA of 965ha in the period 1974-1986, and 248ha in the period 1986-2000. The majority of the loss (>77%) from the two study islands was due to timber extraction and agricultural development. In May 2006, permanent plots following the CARICOMP protocol were established at two sites on Isla del Rey (R1 and R2) and one site on Isla San Jose (SJ) where standardized metrics such as species, height and diameter at breast height of adult trees and seedlings were recorded. Forest structure differed at the three sites, although R1 and R2 were most similar. At R1, Laguncularia racemosa was the important species and R2 was dominated by Pelliciera rhizophorae. Examination of the forest structure and classified imagery indicated that these sites are spatially dynamic and appear to be rejuvenating. The forest structure would indicate that the sites have been growth-limited previously by human activities and possibly by other factors. SJ was dominated by Rhizophora mangle and appears to have a mature forest with large adult trees and few seedlings. It does not appear to have shown the same extent of spatial regrowth as the other two sites between 1986 and 2000 and is relatively static. The establishment of permanent plots and monitoring will be useful as part of the management plan, as the LPA shows a variety of mangrove structures and could be subject to further coastal development. PMID- 20737844 TI - Extant freshwater ostracodes (Crustacea: Ostracoda) from Lago Peten Itza, Guatemala. AB - Ostracode taxonomy has been of great interest because of their possible use as indicator species in climate and ecosystem changes. In Central and South America, few studies have been carried out and this study includes a contribution to the group. Eleven ostracode species were collected in Lago Peten Itza (approximately 100km2), the second largest lowland lake in Guatemala, and from its inflow tributary, Rio Ixlu in November 2005 and February 2008. Twenty-seven surface sediment samples were retrieved at water depths from the littoral zone to the lake's maximum depth (>160m). Hard and soft parts of ostracodes were analyzed, and each ostracode species was described for taxonomy, size, ecology, biology and geographic distribution. Species recorded include: Candonocypris serratomarginata?, Cypretta brevisaepta?, Cypridopsis okeechobei, Cytheridella ilosvayi, Darwinula stevensoni, Heterocypris punctata, Limnocythere opesta, Physocypria globula, Pseudocandona sp., Stenocypris major and Strandesia intrepida. Most of the species have a neotropical distribution, two are distributed world-wide (D. stevensoni and S. major), and C. okeechobei and P. globula display nearctic and neotropical distributions. We present new records of C. brevisaepta?, C. serratomarginata?, S. major, and S. intrepida in Guatemala. Physocypria globula was misidentified previously in Lago Peten Itza as Cypria petenensis, Pseudocandona sp. was misidentified as Candona sp., and C. okeechobei was identified the past as C. vidua. Limnocythere opesta is the only endemic species of the Peten Lake District, Guatemala. The most abundant and widely distributed species in the lake are P. globula, C. okeechobei, and Pseudocandona sp. Species restricted to the littoral zones and water depths <15 m are C. brevisaepta?, D. stevensoni, H. punctata, and S. intrepida. Limnocythere opesta, C. ilosvayi, C. okeechobei, and Pseudocandona sp. are distributed from the littoral zone to a depth of 40m. Species collected only in the Ixlu tributary and in a littoral zone on the west side of the lake were C. serratomarginata? and S. major. During November, live adult L. opesta and C. okeechobei were abundant, but no C. brevisaepta? or C. serratomarginata? adults were found. Adult specimens of C. ilosvayi were more abundant in February. In general, ostracodes collected were smaller than those reported in the literature. An accurate taxonomy will improve the use of ostracode fossil assemblages in long sediment cores when reconstructing past climatic and environmental changes in the northern lowland Neotropics. PMID- 20737845 TI - Taxonomy and distribution of aquatic and semiaquatic Heteroptera (Insecta) from Cuba. AB - Heteroptera is a worldwide distributed group of insects inhabiting both terrestrial and aquatic habitats and has an important ecological role. A survey of aquatic and semiaquatic Heteroptera from Cuba is provided based on literature reports and field collections. General data on species geographical distribution are given, along with altitude and collection season. Representatives of 86 species and morphospecies of the infraorders Dipsocoromorpha, Leptopodomorpha, Gerromorpha and Nepomorpha are listed, distributed in 35 genera and 16 families were found. Based on distributional data, a preference for habitats of stagnant water or slow current and lower altitudes is inferred. Fifteen species are distributed throughout the entire island. A higher species diversity was found in the Eastern sector, with 53 species (61.63%), 16 of which (18.60%) are confined to this area. The strongest biological similarity was found between Eastern and Western sectors (25%), and the weakest between Western and Central sectors (14%). PMID- 20737846 TI - The invasion of five alien species in the Delta do Parnaiba Environmental Protection Area, Northeastern Brazil. AB - Marine biological invasions have been regarded as one of the major causes of native biodiversity loss, with shipping and aquaculture being the leading contributors for the introductions of alien species in aquatic ecosystems. In the present study, five aquatic alien species (one mollusk, three crustaceans and one fish species) were detected during dives, shore searches and from the fisheries on the coast of the Delta do Parnaiba Environmental Protection Area, in the States of Piaui and Maranhao, Northeastern Brazil. The species were the bicolor purse-oyster Isognomon bicolor, the whiteleg shrimp Litopenaeus vannamei, the giant river prawn Macrobrachium rosenbergii, the Indo-Pacific swimming crab Charybdis hellerii and, the muzzled blenny Omobranchus punctatus. Ballast water (I. bicolor, C. hellerii, and O. punctatus) and aquaculture activities (L. vannamei and M. rosenbergii) in adjacent areas are the most likely vectors of introduction. All exotic species found have potential impact risks to the environment because they are able to compete against native species for resources (food and habitat). Isognomon bicolor share the same habitat and food items with the native bivalve species of mussels and barnacles. Litopenaeus vannamei share the same habitat and food items with the native penaeids such as the pinkspot shrimp Farfantepenaeus brasiliensis, the Southern brown shrimp Farfantepenaeus subtilis, and the Southern white shrimp Litopenaeus schmitti, and in the past few years L. vannamei was responsible for a viral epidemics in the cultivation tanks that could be transmitted to native penaeid shrimps. Charybdis hellerii is also able to cause impacts on the local fisheries as the species can decrease the populations of native portunid crabs which are commercialized in the studied region. Macrobrachium rosenbergii may be sharing natural resources with the Amazon River prawn Macrobrachium amazonicum. Omobranchus punctatus shares habit with the native redlip blenny Ophioblennius atlanticus and other fishes, such as the frillfin goby Bathigobius soporator Some immediate remedial measures to prevent further introductions from ballast water and shrimp farm ponds should be: (i) to prevent the release of ballast water by ship/vessels in the region; (ii) to reroute all effluent waters from shrimp rearing facilities through an underground or above-ground dry well; (iii) to install adequate sand and gravel filter which will allow passage of water but not livestock; (iv) outdoor shrimp pounds located on floodable land should be diked, and; (v) to promote environmental awareness of those directly involved with ballast water (crews of ship/vessels) and shrimp farms in the region. PMID- 20737847 TI - [Bycatch fish species from shrimp industrial fishery in the Gulf of California, Mexico]. AB - Bycatch fish species from shrimp industrial fishery in the Gulf of California, Mexico. The shrimp fishery in the Gulf of California is one the most important activities of revenue and employment for communities. Nevertheless, this fishery has also created a large bycatch problem, principally fish. To asses this issue, a group of observers were placed on board the industrial shrimp fleet and evaluated the Eastern side of the Gulf during 2004 and 2005. Studies consisted on 20kg samples of the capture for each trawl, and made possible a systematic list of species for this geographic area. Fish represented 70% of the capture. A total of 51 101 fish were collected, belonging to two classes, 20 orders, 65 families, 127 genera, and 241 species. The order Perciformes was the most diverse with 31 families, 78 genera, and 158 species. The best represented families by number of species were: Sciaenidae (34) and Paralichthyidae (18) and Haemulidae and Carangidae (16 each). The best represented genera in number of species were Symphurus (nine) and Diplectrum and Cynoscion (six); other important genera were Larimus and Porichthys with five species each. The best represented species in number were Syacium ovale, Pseudupeneus grandisquamis, Haemulopsis nitidos, Diplectrum pacificum, Synodus scituliceps, Balistes polylepis, Eucinostomus currani, Eucinostomus gracilis, Porichthys analis, Chloroscombrus orqueta, Selene peruviana, Orthopristis reddingi, Etropus crossotus, Scorpaena sonorae and Urobatis halleri. The number of recorded species is notably high, compared with demersal fauna of other areas of the Mexican Pacific, such as Gulf of Tehuantepec (178), Nayarit, Michoacan, Guerrero (174, 120 and 166), Jalisco and Colima (161 species), and those of the Western coast of the Baja California Peninsula (220 species). PMID- 20737848 TI - [False eggs (SAGs) facilitate social post-hatching emergence behaviour in Leatherback turtles Dermochelys coriacea (Testudines: Dermochelyidae) nests]. AB - Hatchling emergence to the beach surface from deep sand nests occurs without parental care. Social behaviour among siblings is crucial to overcome this first challenge in sea turtles life. This study, carried out at the Caribbean coast of Colombia, describes the emergence social behaviour of hatchlings from eight nests, and assess the nests translocation effects on temporal patterns of emergence. For the first time, we propose that space released by dehydration of shelled albumen globes (SAGs) at the top of the clutch, might be a reproductive advantage, while facilitating neonates to group together in a very limited space, and favouring the synchrony of emergence. The mean time of groups emergence was of 3.3 days, varying between 1 and 6 days. We found that relocation of the nests did not significantly affect the temporal pattern of emergence, which was mainly nocturnal (77.7% of natural nests and 81.7% of translocated ones). The maximum number of emergences to the surface occurred at the lowest air temperatures (22:00h-06:00h). The selective advantage of this pattern is probably related to the greater rate of predation and mortality by hyperthermia observed during the day. PMID- 20737849 TI - [Architecture and leaf anatomy of the Polypodium plesiosorum sensu Moran complex (Polypodiaceae)]. AB - Architecture and leaf anatomy of the Polypodium plesiosorum sensu Moran complex (Polypodiaceae). The Polypodium plesisorum complex is a heterogeneous morphology group. We studied leaf architecture and anatomy of 12 species of this group, in addition to other 23 species of Polypodium (P. dulce, P. polypodioides and P. vulgare complex sensu Moran) and related genera (Goniophlebium, Phlebodium, Pleopeltis, Serpocaulon, Synammia), for comparative purposes. Two homogeneous groups of species were established in P. plesiosorum complex. One of them is recognized based on the type of anastomosis of the veins (Type III): Polypodium conterminans (originally considered in the group of P. dulce with free venation by Moran), P. hispidulum, P. plesiosorum and P. rhodopleuron. The second group with Polypodium arcanum, P. castaneum, P. colpodes, P. eatonii, and P. flagellare were recognized based on the type of anastomosis of the veins (Type IV) and how vascular strands fuse along the petiole-leaf rachis. Characters studied helped to group the remaining species with other groups outside the complex under study. PMID- 20737850 TI - [Fungal and bacterial biomass as indicators of soil C sequestration in savannas soils substituted by pine plantations]. AB - A transformation of any natural ecosystem to an agricultural or forest system leads to an important soil modification, not only in the total carbon pool, but also in the carbon associated to the microbial biomass. This way, carbon quantification on soil quality is important for the determination of impacts of agricultural practices and land use changes. The aim of this study was to the determine, through the selective inhibition technique, the fungal and bacterial biomass, and fungal-to-bacterial ratio (F:B) in pine plantations (Pinus caribaea var. hondurensis), to establish if these parameters are sensible indicators of changes in the carbon content in Uverito soils (Venezuela). Furthermore, the inhibitor additivity ratio (IAR) and total combined inhibition (TCI) were carried out to determine if the antibiotics caused non-target inhibition. The quantification of fungal and bacterial biomass was carried out by using of cyloheximide as fungal inhibitor, and streptomycin and chloranphenicol as specific bacterial inhibitors. This research evidences that this land use change exerted a significant effect on soil microbial biomass, and shows that in pine plantations there is a dominance of the fungal component, in contrast to the native savanna, in which the bacterial biomass dominates. The substitution of native savanna by pine plantation in Uverito promotes a major soil carbon sequestration. The values of the inhibitor additivity ratio (IAR) as for native savanna as pine system, were both >1.0. The total combined inhibition (TCI) was smaller in the pine systems, from which it is possible to infer that a high proportion of microbial biomass was affected by the combination of the inhibitors. PMID- 20737851 TI - Ecological consequences of primary and secondary seed dispersal on seed and seedling fate of Dipteryx oleifera (Fabaceae). AB - The relative contributions of primary and secondary seed dispersal to plant demography have received little investigation. Evidence on these seed dispersal types, on seed fate and seedling recruitment of the tropical rain forest tree Dipteryx oleifera, is presented. The study was conducted in a 6.37ha permanent plot where seeds and seedlings were located and tagged for the 2007 cohort. A total of 2 814 seeds were threaded and their fate was followed one year after germination. Primary seed dispersal by bats protected seeds from insect larval predation below the adult tree. Bats congregated seeds in bat seed piles located at a mean distance of 40.94 +/- 1.48m from the nearest adult individual of D. oleifera. Terrestrial vertebrates congregated seeds in caches located 41.90 +/- 2.43m from the nearest adult individual of D. oleifera. The results of the fitted proportional hazard model suggested that primary seed dispersal decreased seed hazard probability by 1.12% for each meter from the adult conspecific (p<0.001) and that secondary seed dispersal decreased it by 23.97% (p<0.001). Besides, the odds ratio regression models results showed that the overall effect of unviable seeds was a reduction in viable seed predation rate. For each unviable seed deposited by bats into the seed piles, the rate of seed predation by terrestrial vertebrates decreased 6% (p<0.001). For each damaged seed by terrestrial vertebrates in the seed piles, the rate of germination decreased 4% (p<0.001). For each germinated seed in the seed piles, the rate of recruitment increased 16% (p=0.001). Seedling survival of seeds that emerged after secondary seed dispersal events, showed no statistically significant difference in arthropod herbivory, in relation to seedlings that came from seeds that were dispersed only primarily by bats (F=0.153, p=0.697, df=1.98). Thus both primary and secondary dispersal contributed to higher seedling survival away from the nearest adult D. oleifera (r2=0.713, n=578, p=0.004). The distribution of D. oleifera seedlings is consistent with the Janzen-Connell Hypothesis and depends on primary dispersal by bats, secondary dispersal by terrestrial vertebrates, a seed masking effect and, the constant threat of insect herbivores on seedlings. PMID- 20737852 TI - [Biodiversity of land gastropods (Mollusca) in Sierra de San Javier Park, Tucuman, Argentina]. AB - Studies related to land mollusk diversity in tropical and subtropical forests are scarce. To assess this, a study on land snail diversity of subtropical cloudforest (Yungas) and dry forest (Chaco) areas of Sierra de San Javier Park, Tucuman, Argentina, was carried out. Taxonomic identifications were performed to species level and built a species per stations data matrix to analyze diversity patterns on qualitative and quantitative samples processed from 10x10m quadrates in altitudinal transects. Non parametric analysis (ICE, ACE, Chao 1 and Chao 2) were used to estimate the true diversity of the area, as well as the degree of undersampling and spatial aggregation of the data. Diversity was also calculated using Shannon, Simpson, Whittaker and Jaccard indices. The richness of the San Javier Park was estimated to be 32 species distributed into 13 families and 21 genera. From the total number of species collected, a single one belongs to Caenogastropoda, while the rest of the species are classified into Pulmonata Stylommatophora and Systellommatophora. The most representative family was the micromollusc Charopidae, while the most relatively abundant species was another micromollusc snail, Adelopoma tucma. Richness and diversity were slightly more elevated in dry forest areas of the Chacoan Ecoregion than in cloud forest areas of Yungas. Non parametric estimators showed that the inventory was complete. Diversity values obtained were high in comparison to previously studied areas of Northwestern Argentina. The total number of specimen collected (22 169 specimens), was higher than other published studies. PMID- 20737853 TI - [Effect of pine plantations on soil arthropods in a high Andean forest]. AB - One of the most common problems in the Colombian mountains has been the replacement of native vegetation by pine plantations. Soil arthropods are a fundamental component of forest ecosystem, since they participate in the organic matter fragmentation, previous to decomposition. This role is more valuable in high altitude environments, where low temperatures limit the dynamics of biological processes, where the effects of pine plantations on soil arthropods are still not well-known. In a remnant of high-andean forest (Neusa - Colombia) and a pine plantation of about 50 years-old, it was evaluated the composition, richness and abundance of arthropods at surface (S), organic horizon (O) and mineral horizon (A) of soil, to establish the differences associated to the soil use transformation. It was used "Pitfall" sampling to register the movement of the epigeous fauna, and extraction by funnel Berlese for determining the fauna density from O and A horizons. The Shannon and Simpson indexes estimated the diversity at different places and horizons, and the trophic structure of the community was evaluated. Overall, there were collected 38 306 individuals from forest and 17 386 individuals from pine plantation, mainly distributed in Collembola (42.4%), Acari (27%), Diptera (17.6%) and Coleoptera (4.6%). The most important differences were given in the surface, where the mobilization in forest (86 individuals/day) almost triplicates the one in pine plantation (33 individuals/day). The differences in composition were given in Collembola, Araneae, Hemiptera, Homoptera and Hymenoptera. The dynamics of richness and abundance along the year had significant high values in the native forest than in the pine plantation. The general trophic structure was dominated by saprophagous (75%), followed by predators (14%) and phytophagous (9%), but in two layers of the pine plantation soil (S and O) this structural pattern was not given. Based on the results, it was concluded that pine plantations affect the diversity, composition, community dynamic and trophic structure of soil arthropods. Also, some estimators of soil stability give signals that these effects are reducing the ecosystem function in the region. PMID- 20737854 TI - [Genetic methods for the reintroduction of primates Saguinus, Aotus and Cebus (Primates: Cebidae) seized in Bogota, Colombia]. AB - Primates are one of more confiscated taxa by the environmental authorities in Bogota, Colombia. During 2008, 133 monkeys were confiscated; samples from 115 of them were sequenced by the mitochondrial cythocrome oxidase II gene (mtCOII) and 112 sequences obtained were of high quality. These sequences were compared with those obtained by our research group from individuals directly sampled in the field, with precise geographic origin. So, a more specific geographic area of the Colombian territory could be considered for a correct rehabilitation treatment during the reintroduction of these confiscated animals. The main results with five primate species were: 1--For all the specimens analyzed of Saguinus leucopus, they could be liberated in any geographical area of its distribution range, since only one gene pool was found. 2--For the 14 Aotus sp. individuals sequenced from the SDA (Environmental District Secretariat), one of them (A. vociferans) was coming from the Amazon, seven exemplars belonged to A. griseimembra from the Magdalena Valley and the Colombian Caribbean coasts, four individuals represented to A. brumbacki from the Colombian Eastern Llanos, and two were associated to A. azarae azarae from Northern Argentina and Paraguay (which means that illegal traffic of animals is arriving to Colombia from other South-American countries). 3--Out 14 Cebus albifrons sequenced, two belonged to the geographical area of C. a. versicolor, one to C. a. pleei, 10 to C a. leucocephalus and one could be not assigned because its sequence yielded a great genetic divergence with respect to the other specimens sequenced of this species. 4--The two Cebus capucinus sequenced showed to be associated to a gene pool found in the Northern of Choco, Sucre and Cordoba Departments. 5--Out 11 Cebus apella sequenced, 10 showed to belong to the gene pool presented in the Colombian Eastern Llanos and highly related (but differentiable) to Cebus apella apella from the French Guyana. It could be named C. a. fatuellus sensu Groves (2001). One exemplar sequenced could be not related with the other C. apella analyzed, nor the related taxa to the aforementioned species (C. a. paraguayanus = C. cay; C. xanthosternos; C. nigritus). PMID- 20737855 TI - Habitat use and home range of brown-nosed coati, Nasua nasua (Carnivora: Procyonidae) in the Brazilian Cerrado biome. AB - The brown-nosed coati (Nasua nasua) is a carnivorous species found in all the Brazilian biomes, some of which are endangered areas. The aim of this work was to determine the habitat use and selection, home range and core area of N. nasua in the Cerrado biome, central region of Tocantins, Brazil. The study was carried out in an area of approximately 20 000ha from May 2000 to July 2002. A total of seven box traps were placed in the area for 13 months, three of 11 captured animals were followed and monitored by radio-tracking during 13 months. The monitoring was conducted once a day, three times a week using a car and walking through the study area (radio-tracking and visual contact). The results demonstrate that these three males used more frequently the gallery forest formation, followed by cerrado and wetlands. The use of gallery forest by these animals indicated an habitat selection (Proportion test, z=12.98, p<0.01). Besides, adult males used the gallery forest more frequently (Fisher's exact test, p<0.01) and wetlands less frequently (Fisher's exact test, p<0.01) than juvenile males, without significant differences between animal ages for cerrado percentage of habitat use. Besides, results also showed a gallery forest selection by adult (Proportion test z=13.62, p<0.01) and juvenile (Proportion test z=2.68, p<0.01) males, and a wetland selection by the juvenile male (Proportion test z=3.90, p<0.01). The home ranges varied from 2.20 to 7.55km2 for the Minimum Convex Polygon 100% (MCP 100%) and from 4.38 to 13.32km2 for the Harmonic Mean 95% (HM 95%). The smallest home range overlap occurred between the adult males (Nm1 and Nm3), and the greatest between the juvenile Njm2 and the adult Nm1. The average of the core area (HM 75%) for the three monitored animals represented 21.29% of the home range calculated with HM 95%. No overlap between core areas was observed for adult males, but, it was an overlap between the core area of the juvenile male and its band with that of the two adult males. The present study provides new data on core area size and frequency habitat use by adult and juvenile males of N. nasua in the Brazilian Cerrado, that may support conservation efforts. PMID- 20737856 TI - Non-legalized commerce in game meat in the Brazilian Amazon: a case study. AB - In tropical forests, wild game meat represents an option or the only protein source for some human populations. This study analyzed the wildlife meat trade destined to human consumption in an open market of the Amazon rainforest, Brazil. Wildlife meat trade was monitored during 2005 through interviews to vendors and consumers in order to evaluate the socioeconomic profile of the sellers, the main species and byproducts sold, their geographical origin, commercial value, frequency of sale and product demand. Data indicated that vendors were financially highly dependant of this activity, getting a monthly income up to US$271.49. During the survey, the amount of wildlife meat on sale added a total of 5 970kg, as follows: 63.2% capybara (Hydrochoerus hydrochaeris), 34.4% cayman (Melanosuchus niger and/or Caiman crocodilus crocodilus), 1.1% paca (Cuniculus paca); 0.6% armadillo (Dasypus novemcinctus), 0.5% deer (Mazama americana), 0.2% matamata (Chelus fimbriatus), and 0.1% opossum (Didelphis marsupialis). Most of the commercialized species were not slaughtered locally. The consumption of wildlife meat was admitted by 94% of the interviewed, consisting of 27 ethno species: 19 mammals, 6 reptiles, and 2 birds. The same percentage of the interviewed (94%) already bought wildlife meat of 18 species: 12 mammals and 6 reptiles. The great amount of wildlife meat traded and the important demand for these products by the local population, point out the necessity to adopt policies for a sustainable management of cinegetic species, guaranteeing the conservation of the environment, the improvement of living standards, and the maintenance of the local culture. PMID- 20737857 TI - The development of social security in America. AB - This article examines the historical origins and legislative development of the U.S. Social Security program. Focusing on the contributory social insurance program introduced in title II of the Social Security Act of 1935, the article traces the major amendments to the original program and provides an up-to-date description of the major provisions of the system. The article concludes with a brief overview of the debate over the future of the program, and it provides a summary assessment of the impact and importance of Social Security as a central pillar of the U.S. social welfare system. PMID- 20737858 TI - Administering social security: challenges yesterday and today. AB - In 2010, the Social Security Administration (SSA) celebrates the 75th anniversary of the passage of the Social Security Act. In those 75 years, SSA has been responsible for programs providing unemployment insurance, child welfare, and supervision of credit unions, among other duties. This article focuses on the administration of the Old-Age, Survivors, and Disability Insurance program, although it also covers some of the other major programs SSA has been tasked with administering over the years-in particular, Medicare, Black Lung benefits, and Supplemental Security Income. The article depicts some of the challenges that have accompanied administering these programs and the steps that SSA has taken to meet those challenges. Whether implementing complex legislation in short timeframes or coping with natural disasters, SSA has found innovative ways to overcome problems and has evolved to meet society's changing needs. PMID- 20737859 TI - U.S. Social Security at 75 years: an international perspective. AB - Is the historical development of the Old-Age, Survivors, and Disability Insurance (OASDI) program unique or similar to the development of social security programs in other industrialized countries? The U.S. Social Security program was adopted some 40 to 50 years after those of most Western European nations. The United States thus had the opportunity to choose from a number of models and clearly chose to follow the classic social insurance path of such countries as Austria, France, and Germany, which in 1935 already had considerable experience administering earnings-related, employer/worker-financed old-age pension programs. Although based on the traditional social insurance model, OASDI evolved in certain unique ways, including the rejection over the course of succeeding decades of any reliance on general revenue financing, the importance attached to long-range (75-year) actuarial projections, and the relative generosity of benefits for survivors and dependents. PMID- 20737860 TI - Widows and social security. AB - This article provides policymakers with context for understanding past and future policy discussions regarding Social Security widow benefits. Using data from surveys, projections from a microsimulation model, and recent research, it examines three types of benefits-those for aged widows, widows caring for children, and disabled widows. The economic well-being of aged widows has shifted from one of widespread hardship to one in which above-poverty, but still modest, income typically prevails. Many aged widows experience a decline in their standard of living upon widowhood, a pattern which is pronounced among those with limited education. Widows caring for children have been a sizeable beneficiary group historically, but policy changes and demographic trends have sharply reduced the size of this group. Family Social Security benefits ensure a modest level of household income for widows caring for children. Disabled widows differ from the other groups because they are at higher risk for poverty. PMID- 20737861 TI - The future financial status of the Social Security program. AB - The concepts of solvency, sustainability, and budget impact are common in discussions of Social Security, but are not well understood. Currently, the Social Security Board of Trustees projects program cost to rise by 2035 so that taxes will be enough to pay for only 75 percent of scheduled benefits. This increase in cost results from population aging, not because we are living longer, but because birth rates dropped from three to two children per woman. Importantly, this shortfall is basically stable after 2035; adjustments to taxes or benefits that offset the effects of the lower birth rate may restore solvency for the Social Security program on a sustainable basis for the foreseeable future. Finally, as Treasury debt securities (trust fund assets) are redeemed in the future, they will just be replaced with public debt. If trust fund assets are exhausted without reform, benefits will necessarily be lowered with no effect on budget deficits. PMID- 20737862 TI - Metabolic stabilization of acetylcholine receptors at newly formed neuromuscular junctions in rat. AB - The turnover of acetylcholine receptors (AChRs) was studied at developing motor endplates in embryonic rat diaphragm and at newly formed ectopic endplates in soleus muscles of adult rats. After the receptors were labeled in situ with 125I alpha-bungarotoxin, the rate of loss of bound toxin was determined by autoradiography of single muscle fibers and was used to calculate the turnover time of AChRs. A new, convenient method for preparing large numbers of single muscle fibers is described. AChRs in extrajunctional regions of embryonic diaphragms turn over with a short half-time (24 hr) similar to that of AChRs in cultured myotubes and of extrajunctional AChRs in denervated adult muscle. AChRs in newly formed clusters in developing muscle and in ectopically innervated adult muscle also turn over with short half-times. Within a few days, however, the turnover time increases to values characteristic of adult junctional receptors (6 10 days). Transection of the nerve at newly formed ectopic endplates prevents the change. The metabolic stabilization of AChRs at motor endplates in rat muscles is thus a relatively early event in synapse formation; it coincides neither with the clustering of receptors, which precedes it, nor with the decrease in AChR channel open time which has been shown to occur postnatally. PMID- 20737863 TI - Formation of neuromuscular junctions in adult rats: accumulation of acetylcholine receptors, acetylcholinesterase, and components of synaptic basal lamina. AB - We describe the appearance and accumulation of four specialized molecular components of the adult neuromuscular junction during ectopic endplate formation in adult rat soleus muscles. One component, the acetylcholine receptor (AChR), is a major constituent of the postsynaptic muscle membrane. The other three, acetylcholinesterase (AChE) and two extracellular synapse-specific antigens, are associated, at least in part, with the basal lamina in the synaptic cleft. The accumulation of each component was studied by immunocytochemistry. In addition, the accumulation of AChRs was measured by autoradiography after reaction with 125I-alpha-bungarotoxin, and AChE was examined by histochemistry and by sedimentation analysis. Endplate formation was initiated by cutting the original nerve to a muscle in which a foreign nerve had been previously implanted. Within 2 days, clusters of AChRs appeared in the new endplate zone. The density of AChRs in these clusters increased from 1 x 10(4) sites/microm2 to nearly the final value of 2 x 10(4) sites/ microm2 by 4 days. The cluster continued to grow in size and receptor number over the next month. AChE was not detected on the surface of the muscle fiber until after 1 week, when it was present at some, but not all ectopic endplates. Its appearance coincided with a rapid accumulation of the endplate-specific, 16 S form of AChE (A12) in the portion of the muscle containing new endplates. By 2 weeks virtually all endplates stained for AChE and by 1 month both immunochemical and histochemical staining resembled that of normal adult endplates. The synapse-specific basal lamina antigens that we studied were detected at some endplates by Day 6, and their further appearance followed a time course similar to, or slightly ahead of, that of AChE. Thus maturation of the synaptic basal lamina occurs after the AChRs have formed clusters and achieved nearly their final density. PMID- 20737864 TI - Developmental changes in acetylcholine receptor aggregates at rat skeletal neuromuscular junctions. AB - The development of acetylcholine (ACh) receptor aggregates at the neuromuscular junction was studied in rat sternomastoid muscles. The first junctional clusters of ACh receptors were loose aggregates of small receptor patches (15 1/2 to 16 1/2 days of gestation). These clusters coalesced to more compact but simple plaques (18 days of gestation to 3 days postnatal). During the first 2 weeks postnatal several changes occurred: the receptor plaque was modified to the adult junctional receptor distribution, multiple innervation was eliminated, and extrajunctional ACh receptors were lost. At the time of birth the receptors in the junctional receptor plaque were already degraded more slowly than were extrajunctional receptors. The junction increased in length most rapidly during the period when the muscle increased most rapidly in mass, from 15 to 100 days postnatal. It is concluded that the junction goes through several stages during development. PMID- 20737865 TI - Temporal regulation of cuticle synthesis during development of Caenorhabditis elegans. AB - The pattern of cuticle protein synthesis during development of the nematode Caenorhabditis elegans has been studied using NaH14CO3. Both pulse-labeling and pulse-chase-labeling experiments indicate that synthesis of cuticle components occurs at high levels during the molting periods and at much reduced rates during the intermolt periods. No such discontinuous pattern is observed for the synthesis of total noncuticle macromolecules during development. The soluble and insoluble proteins of the cuticle, which comprise the inner and outer cuticle layers, respectively, follow similar patterns of synthesis during the two molts examined. At each molt the structural components of the cuticle account for approximately 10% of the total macromolecules labeled by NaH14CO3. No evidence is found for reuse of cuticle material between successive developmental stages of C. elegans. PMID- 20737866 TI - Species- and age-dependent changes in the relative amounts of cardiac myosin isoenzymes in mammals. AB - In mice, rabbits, and pigs, two basic types of cardiac myosin isoenzymes were found by electrophoresis of native molecules: a fast-migrating form with high Ca(2+)-dependent ATPase activity and a slow-migrating form with low activity. According to the nomenclature of J. F. Y. Hoh, P. A. McGrath, and P. T. Hale (1978, J. Mol. Cell. Cardiol. 10, 1053-1076) these forms are called, respectively, V1 and V3. In all species, myosin was essentially V3 during fetal life, while V1 appeared around the time of birth. There were species differences in adults: mice remained V1, while rabbits and pigs returned to V3 after 3 weeks of age. Adult dog, beef, and human myosins were also composed of the V3 form only. PMID- 20737867 TI - Sea urchin egg and embryo ribosomes: differences in translational activity in a cell-free system. AB - To determine whether ribosomes have a role in the postfertilization activation of protein synthesis in sea urchin eggs, we measured the translational activity of ribosomes isolated from unfertilized eggs and embryos of Strongylocentrotus purpuratus. Numerous previous studies have indicated few if any differences in the activity of such ribosomes. However, by using improved physiological isolation and in vitro conditions, we have found important differences in the activities of egg and embryo ribosomes. Ribosomes obtained from blastula polyribosomes were active in translating reticulocyte mRNA in a ribosome dependent cell-free translation system, whereas ribosomes obtained from unfertilized eggs became fully active only after a characteristic, reproducible delay of up to 15 min at 26 degrees C. The extent of this delay varied with incubation pH, but not with concentrations of K+, Mg2+, initiation factors, or mRNA. However, at incubation pH between 6.90 and 7.65, the egg ribosomes were always less active than blastula ribosomes. PMID- 20737868 TI - Sperm isolation and biochemical analysis of the major sperm protein from Caenorhabditis elegans. AB - In order to facilitate the biochemical analysis of spermatogenesis in the nematode Caenorhabditis elegans methods have been developed for obtaining large quantities of males and for the isolation of sperm. Males are isolated by a passive filtration method from strains producing high proportions of males and sperm are isolated by physical pressure followed by filtration and differential centrifugation. Biochemical analyses show that sperm contain a major protein component that represents 17% of the total sperm protein. This protein has a molecular weight of 15,600, an isoelectric pH of 8.6, and exists as a dimer. It is shown by immunocytochemical techniques to be a specific product of spermatogenesis. It is localized in the proximal arm of the male gonad and in the sperm of both the male and hermaphrodite but it is not detected in other tissues of the nematode. It is not a nuclear binding protein. Pulse-labeling studies show that this major sperm protein is first synthesized in the proximal arm of the male gonad beginning at 39-42 hr after hatching at 20 degrees C. Poly(A) mRNA coding for this protein is first detected in a translatable form just before synthesis of this sperm protein suggesting transcriptional control. PMID- 20737869 TI - Cyclic AMP inhibits dedifferentiation in the cellular slime mold Dictyostelium discoideum. AB - When aggregating amoebas of the cellular slime mold Dictyostelium discoideum are disaggregated and morphogenesis is reinitiated, the amoebas will reaggregate in less than 1/10th the original time. When aggregating amoebas are disaggregated and resuspended either in full nutrient medium or in buffered salts solution containing dextrose, they retain this developmentally acquired capacity to rapidly reaggregate for approximately 1 hr and then lose it completely in a synchronous and discrete step which we have referred to as the "erasure event." In this report, it is demonstrated that micromolar concentrations of cAMP completely block this transition from the developmental to vegetative state, and that other cyclic nucleotides also inhibit it, but they do so at 20-fold higher concentrations. Neither the hydrolysis products of cAMP nor the vegetative chemoattractant folic acid inhibit dedifferentiation at concentrations as high as 10(-3) M, demonstrating a specificity for cyclic nucleotides and cAMP in particular. The addition of cAMP at any time during the lag period preceding the erasure event inhibits it and addition immediately after the erasure event reverses it. Since cAMP may inhibit the transition from the developmental to vegetative state intracellularly or extracellularly, we have also examined the intracellular concentration of cAMP and the levels of cAMP binding sites on the cell surface during the erasure process. Evidence is presented that the majority of cAMP binding sites on the cell surface are not necessary for the inhibition of erasure by cAMP. The results of these latter studies are discussed in terms of alternative models for the involvement of cAMP in the transition from the developing to vegetative state. PMID- 20737870 TI - Localization of a single sperm membrane autoantigen (RSA-1) on spermatogenic cells and spermatozoa. AB - The rabbit sperm membrane autoantigen RSA-1 is a sialoglycoprotein of 13,000 daltons which first appears on the surface of pachytene spermatocytes. Using specific antiserum to RSA-1 the antigen has been localized by immunofluorescence and immunoperoxidase staining. On testicular cells labeled at 37 degrees C, RSA-1 is seen in patches on the surfaces of pachytene spermatocytes, round spermatids, and over the acrosomal area of later spermatids and spermatozoa. Over the postacrosomal and middle-piece regions of late spermatids and spermatozoa the labeling appears uniform. The uniformity can be seen to stop abruptly at the equatorial segment-postacrosomal border. Labeling cells after fixation gives a uniform distribution of label over the surface where patches were seen at 37 degrees C. The polypeptides recognized by the antiserum used for labeling were identified by immunoadsorbent chromatography and subsequent SDS-PAGE. In testicular cells anti-RSA-1 recognizes the 13,000-dalton form and another component which migrates with the dye front. In ejaculated spermatozoa anti-RSA-1 recognizes a distinct ejaculate complex of higher-molecular-weight proteins containing an 84,000-dalton major band and five minor components. PMID- 20737871 TI - Effects of alpha-amanitin on programming of mouse blastocyst development. AB - We have investigated the effect of alpha-amanitin treatment of mouse blastocysts on their further development. Twenty-four-hour treatments with alpha-amanitin at 1 microg/ml do not interfere with embryo survival or gross morphological development over the next few days although the rate of synthesis of polyA containing RNA is dramatically reduced during exposure to the antimetabolite. Effects upon rates of protein synthesis are not observed initially, but incorporation of (35S)methionine into acid-insoluble material is ultimately inhibited by approximately 50% in all the treated samples. Developmental markers do not all respond in the same way to the alpha-amanitin treatments used. Whereas levels of beta-glucuronidase and plasminogen activator are virtually unaffected by the antimetabolite, alpha-amanitin treatment interferes with delta5,3beta hydroxysteroid dehydrogenase activity in trophoblast cells and formation of a bilayered inner cell mass. The effects upon the latter markers differ quantitatively with the various exposure periods to alpha-amanitin. On the basis of these observations, we propose that mRNAs for at least some developmental markers in mouse blastocysts are synthesized long before they are translated. PMID- 20737872 TI - Ultrastructure of sites of cholinesterase activity on amphibian embryonic muscle cells cultured without nerve. AB - Muscle cells, derived from 1-day-old embryos of Xenopus laevis, were cultured in the absence of nerve and then examined histochemically for cholinesterase activity. Virtually all of the cells exhibited one or more discrete patches of cholinesterase activity on their surface. The patches were located not only on the lower cell surface which was apposed to the floor of the culture dish but also on the lateral and upper surfaces which were not apposed to any solid substrate. At many of the cholinesterase patches the cell surface was invaginated and the invaginations also became filled with the histochemical reaction product. Surface sites of cholinesterase activity were often associated with a thickened plasma membrane and overlying basal lamina-like material. Regions of the cell surface without cholinesterase were typically smooth and ultrastructurally unspecialized. The cholinesterase patches and their associated ultrastructural features developed in the absence of electrical and contractile activity. The similarities between the muscle specializations at cholinesterase sites on cultured, noninnervated, Xenopus muscle cells and those at the neuromuscular and myotendinous junctions of normal skeletal muscle are discussed. PMID- 20737873 TI - Variation of DNA polymerase activities of rat giant trophoblast cells in mid gestation. AB - The activities of the DNA polymerases alpha, beta, and gamma were determined in rat giant trophoblast cells during mid-gestation. Trophoblasts at this period of time have ceased to divide but continue to carry out DNA endoreduplication resulting in polyploidy. DNA polymerase-alpha activity in extracts was found to drop sharply from a high level at Day 11 to 1/10 of that level at Day 12 and to continue at a constant level thereafter. A similar pattern of activity was observed for polymerase-gamma, however, in this case the drop represented 50% of the activity at 11 days. Polymerase-beta showed no significant change in activity during this period of development. Endoreduplication (polyploidy) continued during this period as measured by a linear increase in chromosomal DNA content. The sharp drop in alpha-polymerase activity from Day 11 to Day 12 appears to result from the loss of a protein(s) which specifically stimulate(s) alpha polymerase. PMID- 20737874 TI - Galactose and glucose metabolism by cultured hepatocytes: responsiveness to insulin and the effect of age. AB - Age changes in utilization of glucose and galactose were studied in primary cultures of rat hepatocytes. (1) With increasing age of donor from 2 to 10 weeks, the rate of galactose utilization fell while that of glucose utilization increased from a negative value (net production) to a level approximately double that of galactose. Glucose production could account for about 80% of the galactose taken up by cells from 2- to 3-week-old rats. (2) With increasing time of culture there was a fall in galactose utilization and an increase in glucose utilization comparable to the changes with increasing age in vivo. (3) The change in utilization of each sugar was independent of the change in utilization or availability of the other. It is suggested that the switch from galactose to glucose as the preferred substrate in vivo is not determined by dietary availability of these hexoses. (4) The increased utilization of glucose by cells of older animals was associated with a decrease in responsiveness to the glycogenic action of insulin. The change in responsiveness was not due to a decrease in insulin binding capacity of the cells. PMID- 20737875 TI - Program of early development in the mammal: synthesis and intracellular migration of histone H4 during oogenesis in the mouse. AB - Synthesis of histone H4 by mouse oocytes and unfertilized eggs has been examined by using a modified high-resolution two-dimensional gel electrophoresis procedure capable of resolving basic proteins (M. J. LaMarca and P. M. Wassarman, 1979, Develop. Biol. 73, 103-119). Histones were separated on such gels and observed rates of incorporation of [35S]methionine into histone H4 were converted into absolute rates of synthesis by using previously determined values for the absolute rates of total protein synthesis in mouse oocytes and unfertilized eggs (R. M. Schultz, G. E. Letourneau, and P. M. Wassarman, 1979, Develop. Biol. 68, 341-359; 73, 120-133). Histone H4 was synthesized at all stages of oogenesis examined, and accounted for 0.07, 0.05, and 0.04% of total protein synthesis in growing oocytes, fully grown oocytes, and unfertilized eggs, respectively. During oocyte maturation the absolute rate of histone H4 synthesis decreased by about 40%, as compared to a 23% decrease in the rate of total protein synthesis during the same period. These measurements indicate that enough histone is synthesized during oogenesis in the mouse to support two to three cell divisions. Examination of the intracellular location of newly synthesized proteins in fully grown oocytes revealed that histone H4 was highly concentrated in the nucleus (germinal vesicle), whereas total protein and tubulin were not. Nearly 50% of the histone H4 synthesized during a 5-hr period was located in the oocyte's germinal vesicle, as compared to 1.9 and 0.9% for total protein and tubulin, respectively. These results are compared with those obtained using oocytes and eggs from nonmammalian animal species. PMID- 20737876 TI - Anterior and posterior compartments in the proboscis of Drosophila. AB - Genetic techniques for marking single cells and their descendents are used to study the development of the Drosophila proboscis. The proboscis develops from a pair of imaginal discs which form the left and right halves of the adult organ. Each half of the proboscis is subdivided into two compartments, one positioned anterior to the other. The homeotic mutation proboscipedia transforms the distal proboscis into a pair of distal first legs or antennae. Clones of this mutation are restricted to one or the other of the two proboscis compartments and reveal a precise homology between these compartments and the anterior and posterior compartments of the thorax and eye-antenna. These results provide strong support for the hypothesis that anterior and posterior compartments reflect basic subunits of segment development in Drosophila. PMID- 20737877 TI - A blastoderm fate map of compartments and segments of the Drosophila head. AB - The epidermis of the adult head of Drosophila is composed of the derivatives of three pairs of imaginal discs: the labial discs which form the proboscis, the cibarial discs which form the clypeolabrum, and the eye-antennal discs which form all of the remaining head structures (i.e., the eyes, antennae, head capsule, and maxillary palps). Both the proboscis and the eye-antenna are known to be subdivided into anterior and posterior compartments. This paper reports a gynandromorph fate map of the blastoderm primordia forming the compartments and segments of the adult head. The major results are: (1) For both the proboscis and eye-antenna, blastoderm cells giving rise to the anterior compartment are positioned anterior to cells giving rise to the posterior compartment. This result suggests that the relative anteroposterior position of blastoderm cells constitutes the positional basis for the segregation of anterior and posterior polyclones in different segments. (2) The clypeolabral primordium is adjacent and anterior to the eye-antennal primordium; the proboscis primordium is adjacent and anterior to the prothoracic primordium. Assuming that all segment primordia are of equal length in the blastoderm, the proboscis and eye-antennal primordia are separated by a gap in which three other segment primordia might fit. These results suggest that at the blastoderm stage, the Drosophila head consists of a series of six segment primordia of similar size. PMID- 20737878 TI - Studies on the interactions of sperm with the surface of the sea urchin egg. AB - We have examined the relationship between sperm adhesion and fertilization in the cross species insemination of Arbacia punctulata eggs by Strongylocentrotus purpuratus sperm. As previously reported (Kinsey et al., 1980) the addition of S. purpuratus egg jelly results in induction of the acrosome reaction in sperm and significant numbers of S. purpuratus sperm adhere to A. punctulata eggs. However, in the absence of S. purpuratus egg jelly, S. purpuratus sperm fail to bind to A. punctulata eggs. Although at least 200 S. purpuratus sperm bind to an A. punctulata egg in the presence of S. purpuratus jelly, less than 8% of the eggs are fertilized. The adhesion of S. purpuratus sperm meets the same functional criteria as homologous A. punctulata sperm-egg adhesion. Electron microscopy shows that S. purpuratus sperm that have undergone the acrosome reaction adhere to A. punctulata eggs by their bindin-coated acrosomal process in a manner that is morphologically identical to that observed with homologous A. punctulata sperm. We have also compared the ability of S. purpuratus and A. punctulata sperm to fuse and fertilize with A. punctulata eggs after removal of the vitelline layer. Using high levels of sperm of either species, heterologous as well as homologous fertilization is readily detectable. Under these conditions, where stable binding is not demonstrable, there is no difference in the ability of S. purpuratus and A. punctulata sperm to fertilize A. punctulata eggs. These observations suggest that the failure of S. purpuratus sperm to fertilize A. punctulata eggs under normal conditions may be due to their inability to penetrate the vitelline layer so that they can fuse with the egg plasma membrane. In relation to the possible mechanism of vitelline layer penetration, we have also investigated the mode of action of chymostatin, an inhibitor of chymotrypsin that has been reported to inhibit fertilization of sea urchin eggs (Hoshi et al., 1979). Our findings suggest that the fertilization inhibitory activity of chymostatin is not related to its antichymotrypsin activity. Rather, it appears that this inhibition is due to the induction of an abnormal acrosome reaction in sperm that precludes formation of the acrosome process. PMID- 20737879 TI - Regulation and secretion of early developmentally controlled enzymes during axenic growth in Dictyostelium discoideum. AB - The four earliest developmentally controlled enzymes in the cellular slime mold, Dictyostelium discoideum, accumulate during axenic growth in rich media. We have shown that at low cell titers the specific activities of N-acetylglucosaminidase, alpha-mannosidase, leucine aminopeptidase, and alanine transaminase are each at very low or vegetative levels comparable to amoebae which have been grown on bacteria as the food source. During the exponential phase of growth all four enzymes accumulate dramatically reaching cellular specific activities at least as high as during development. The magnitude of this accumulation is influenced by alterations in the growth medium. We suggest that these results, combined with those of prior investigations, indicate that a restricted segment of early development is initiated during axenic growth. This means that growth and early development are not mutually exclusive events in this organism. The secretion of lysosomal enzymes is also affected by the composition of the growth media. In all media, including growth in bacterial suspensions, lysosomal enzymes are secreted in significant quantities. There is a correspondence in the effects of media composition on the secretion of these enzymes and on the regulation of developmentally controlled enzymes during axenic growth. The secretion of lysosomal enzymes that are not developmentally regulated is affected in these media, suggesting that the regulation and secretion of these enzymes are under separate control. It is clear that studies of the regulation of lysosomal enzymes in this organism must take into account the secretion of the enzymes as well as their cellular specific activities to properly reflect levels of gene expression. PMID- 20737880 TI - Characterization and regulation of insulin binding by embryonic chick heart cells. AB - We have compared insulin binding by heart cells at 7 and 14 days of development. Species specificity, optimum pH, temperature relationships, and time to equilibrium for binding of insulin were the same in both 7 and 14-day systems. Curvilinear Scatchard plots for chicken insulin binding were demonstrated. Binding affinities and capacities were calculated based on a two-receptor model including a specific high-affinity receptor and a less specific low-affinity receptor that bound insulin and other growth peptides. Apparent association constants (K(A)) were 4.0 and 0.05 nM(-1) and binding capacities were 600 and 9000 sites per cell for high- and low affinity receptors, respectively. We have also investigated the ability of insulin to regulate binding to its own receptors. Chick heart cells from 7- and 14-day embryos, cultured for 44 hr in insulin-enriched medium (3.4 microM), bound 50% less insulin (down-regulated) than control cells. At both developmental stages, down regulation was primarily a reduction in binding to the high-affinity receptor. The low-affinity receptor was less susceptible to down regulation and retained its ability to mediate maximal insulin stimulation of amino acid transport. PMID- 20737881 TI - DNA synthesis during the change to pupal commitment of Manduca epidermis. AB - Cytophotometric and cell sorter analysis of Feulgen-stained nuclei of the dorsal abdominal epidermis of the tobacco hornworm Manduca sexta through the final larval instar showed that both 2C and 4C populations were present. A transient population of octaploid cells (30%) was seen on Day 3 at the time of the ecdysteroid-directed reprogramming of the cells for metamorphosis. This specific replication was found to occur in vitro, irrespective of whether the cells were incubated in 20-hydroxyecdysone to induce the change to pupal commitment or in hormone-free media during which they retain their commitment to make larval cuticle. Cytosine arabinoside (1 and 10 microg/ml) inhibited cell cycling during the time of the change of commitment but did not prevent the ecdysteroid-directed change. Thus, DNA synthesis is coincident with, but not necessary for, the genetic reprogramming of Manduca larval epidermis. PMID- 20737882 TI - Activation of protein synthesis in a sea urchin cell-free system. PMID- 20737883 TI - Ontogeny and localization of the alpha, beta, and gamma crystallins in newt eye lens development. AB - The alpha-, beta-, and gamma-crystallins, proteins characteristic for the vertebrate eye lens, have been localized in the developing lens of Notophthalmus viridescens, the eastern spotted newt. Using the immunofluorescence technique, antibodies to the alpha-, beta-, and gamma-crystallin classes were applied to tissue sections through the eye region of developing N. viridescens embryos, Harrison (external) Stages 30 to 46+. beta-Crystallins were the first of the crystallins to appear in a few cells of the lens vesicle even before the lengthening of the prospective primary fiber cells. gamma-Crystallins were first detectable at a slightly more advanced stage in the prospective primary fibers, and alpha-crystallins in a few cells of the beginning primary fiber area. The external layer/epithelium was negative for beta-crystallins until late in lens morphogenesis, and alpha- and gamma-crystallins could not be detected in these cells at any time. This, the first use in amphibia of homologous antibodies specific for the crystallin classes, makes clear that phylogenetic differences exist as to the primacy and relevance of specific crystallins to events during morphogenesis of the eye lens. PMID- 20737884 TI - Biochemical studies of mammalian oogenesis: metabolic cooperativity between granulosa cells and growing mouse oocytes. AB - Freeze fracture and lanthanum tracer experiments have shown that gap junctions exist throughout folliculogenesis between granulosa cells and growing mouse oocytes (Anderson and Albertini, J. Cell Biol. 71, 680-686, 1976). The following lines of experimentation in the present study suggest that metabolic cooperativity exists between granulosa cells and their enclosed oocytes, i.e., gap junctions are functional, and that in most cases examined, greater than 85% of the metabolites present in follicle-enclosed oocytes were originally taken up by the granulosa cells and transferred to the oocyte via gap junctions: (1) When incubated with various radiolabeled compounds, follicle-enclosed oocytes contained more intracellular radioactivity than did oocytes with no attached granulosa cells (denuded oocytes); (2) for two radiolabeled ribonucleosides examined, the distribution of phosphorylated metabolites in follicle-enclosed oocytes resembled that of granulosa cells and differed significantly from that in denuded oocytes; (3) pulse-chase experiments with radiolabeled ribonucleosides revealed that during the chase period more radioactivity became associated with the follicle-enclosed oocyte; (4) treatments known to disrupt gap junctions in other cell types were effective in reversibly uncoupling metabolic cooperativity between granulosa cells and oocytes; and (5) a series of control experiments using (a) medium conditioned by granulosa cells and (b) cocultures of denuded oocytes and granulosa cells in which physical contact between the two cell types was not permitted demonstrated that contact between follicle cells and oocytes was necessary for observing metabolic cooperativity. Metabolic cooperativity was also found between follicle cells and oocytes in the two culture systems which support growth of mouse oocytes in vitro. The fact that oocytes do not grow well, if at all, in the absence of follicle cells and the large contribution of nutrients apparently furnished to the oocyte by the granulosa cells is consistent with the concept that gap junction mediated metabolic cooperativity between follicle cells and their enclosed oocytes is vital for mammalian oocyte growth. PMID- 20737885 TI - The shibire(ts) mutant of Drosophila: a probe for the study of embryonic development. AB - A temperature-sensitive mutant strain (shibire) has been used to probe the normal developmental process in Drosophila melanogaster. At high temperatures lethality occurs during embryonic development. Heat pulses given early disrupt cellular blastoderm formation in these mutants. Even in the absence of cells, the embryo begins morphogenetic movements characteristic of gastrulation. With heat pulses given later, the embryonic cells proliferate without normal differentiation. PMID- 20737886 TI - Electrical membrane properties of the Xenopus laevis oocyte during progesterone induced meiotic maturation. AB - The membrane input resistance (R(m)), potential (E(m)), and capacitance (C(m)) of fully grown Xenopus oocytes removed from their follicles have been measured. Before hormonal maturation, R(m), E(m), and C(m) were found to be: 1.86 +/- 0.63 Momega, -49 +/- 17 mV, and 11.9 +/- 4.8 microF/cm2 of apparent surface area. Long term recording from oocytes in the presence of 1 microM progesterone reveal that during early GVBD (germinal vesicle breakdown) the membrane potential depolarized to about -10 mV, the apparent specific capacitance decreased to 1.5 to 3 microF/cm2, and the membrane resistance transiently increased by a factor of about 3. These results indicate that a decrease in surface area, a transient increase in membrane resistance, and a change in the ionic mechanisms for the membrane potential occur during progesterone-induced meiotic maturation. The continuous monitoring of these parameters has further shown that the major changes occur at about 50 to 60% of the time from progesterone application to GVBD, and that at the sensitivities used, generally 1.25 mV/mm, no changes are seen immediately upon application of the hormone. PMID- 20737887 TI - Cytogeometrical determination of ciliary pattern formation in the hypotrich ciliate Stylonychia mytilus. II. Stability and field regulation. AB - The first regeneration sequence after folding of right fragments of Stylonychia mytilus results in formation of mirror-imaged incomplete doublets illustrating independent determination of polar and lateralaxes. Analysis of the second morphogenetic sequence illustrates that the independent determination of polar and lateral axes is stable through a subsequent cellular reorganization and confirms that cytogeometry participates in determination of ciliary pattern. The morphogenetic inversion of cirral row primordia in this type of fragment is reflected in the structure of the individual cirri. These data not only extend and confirm our earlier study on this type of fragment, but also are consistent with the conclusion derived from data on a different type of mirror-imaged doublet, that global patterning and assembly of ciliature are independently determined. PMID- 20737888 TI - The ferritin content of human red blood cells during the replacement of embryonic cells by fetal cells. AB - Mature human embryonic erythrocytes (hemoglobin is > or = 90% of the cellular protein) contained at least 20 times as much ferritin as human adult erythrocytes, suggesting the possibility that the embryonic red cells participate in iron storage as they do in other embryonic or larval vertebrates. The ferritin content of mature red cells in the circulation declined when fetal red cells replaced embryonic red cells; the cell replacement was monitored by the disappearance of embryonic epsilon-chains and the appearance of the fetal globin chains, gammaA and gammaG. A constant ratio of 0.67 was obtained for gammaG/gammaA + gammaG from the first detectable appearance (4 weeks after conception) until 13 weeks, a value which is similar to the value previously obtained at 20 weeks gestation and birth but higher than that observable in adults; thus, both gammaG and gammaA chains are produced in similar amounts throughout gestation. The high levels of ferritin in normal human embryonic erythrocytes emphasize the similarity of erythropoiesis in human embryos and other vertebrates. In addition, the results show that red cell ferritin can be used as a marker for studying the mechanism of induction of embryonic erythropoiesis in cultured cell lines, such as K562 from human chronic myelocytic leukemia, and that ferritin content may also serve as a marker for cellular transformations involving reversions to embryonic erythropoiesis. PMID- 20737889 TI - [Mesocorticolimbic dopaminergic system in adaptive behavior]. AB - A review. The midbrain dopaminergic system is traditionally considered as a 'common neural currency' for rewards of most kinds. There are several competing hypotheses of its precise contribution in behavior: 1) dopamine mediates the pleasure of rewards; 2) dopamine signals a reward prediction error and, thus, is involved in associative learning; 3) dopamine motivates the pursuit of rewards. However, some investigations have questioned the role of the midbrain dopamine in all these processes. Considerable evidence has illustrated that dopamine system is crucially involved in learning and prediction processes, in estimation of the results of activity, in novel stimulus salience attributions, in decision-making processes and, the most important, in estimation of uncertainty. Such mysterious modulation provides our spontaneity and protects against high reactivity. PMID- 20737890 TI - [The possible mechanisms of acetylcholine receptor desensitization]. AB - The postsynaptic mechanisms initiating the development of two acetylcholine receptor states (I and D) which determine the desensitization are discussed. Attention is focused on the processes of receptor endocytosis as the major mechanism of desensitization. General processes and differences in the development of the D state during the desensitization and long-term depression are analyzed. A mathematical model taking into account the membrane and intracellular receptor states is used. This model makes it possible to analyze the influence of some intracellular substances on the receptor internalization and recycling. PMID- 20737891 TI - [Reference system for representation of the subjective "straight ahead" position]. AB - Representation of space by the neural system is supposed to be carried out by neural networks which describe space in different reference frames fixed relative to body segments or external objects. This study focuses on finding a reference frame for representation of the subjective "straight ahead" position. An experiment is described where deflections of the subjectively defined "straight ahead" position from the objective position in front of the trunk are measured when the subject's head is deviated to the right or to the left. Individual preferences for either the head-fixed reference frame or the trunk-fixed frame are revealed. It was shown that there are differences in subjective representation of the "straight ahead" position depending on the left or right turn of the head, which is supposed to be connected with brain asymmetry in spatial perception. PMID- 20737892 TI - [Buildup of echo suppression for the high frequency signal]. AB - The buildup of echo suppression for noise bursts in the band of 5-18 kHz was studied. Durations of the bursts were 5, 10, 20 and 100 ms. Test stimulus were preceded by a train of stimuli. The stimulus was a noise burst pair, in which the lead burst was presented from either the left (+45 deg) or right (-45 deg) side, and the lag burst was presented from the opposite side. The train consisted of 10 stimuli. The echo delays were 1, 2, 4, 8, 16, 32, 64 and 125ms. The echo threshold was measured as the minimum echo delay at which subjects reported hearing one sound rather than two sounds. The average echo thresholds were significantly elevated for all durations of bursts for buildup condition. However, despite the fact that the average threshold was slightly higher in case of the right-side lead signal presentation than that in case of its left-side presentation, there was no significant difference for the signals of 5, 10, 20, and 100 ms in duration (p > 0.05). PMID- 20737893 TI - [Effects of blokade of the dopaminergic D1/D2 receptors on the single and network neuronal activity in the frontal and visual cortices and behavior of cats]. AB - The results obtained at the levels of single and network neuronal activity in the frontal and visual cortices of cats with different types of behavior revealed features of activity of these structures in normal conditions and after local introductions of antagonists of DI/D2 receptors (SCH23390 and raclopride) into the n. accumbens and frontal cortex. Under the influence of the antagonists, long latency reactions were characterized by a significant increase in the average frequency of neuronal activity in the frontal cortex, whereas in the visual cortex the average frequency decreased as compared to norm. At the same time, the network activity of the same neurons in the frontal cortex did not change but weakened in the visual cortex, which was expressed in a reduction of the number of neuronal interactions within the visual cortex and between the neurons of the frontal and visual cortices. Normally, during the long-latency conditioned reactions, the average frequency of single neuronal activity and the rate of neuronal interactions in the structures under study were significantly higher as compared to the loss of conditioned reactions. Administration of the dopamine antagonists did not change these features. The results suggest different dopamine modulations of the network activity of the cortical zones under study during the conditioned performance, which is expressed in responsiveness of the cortical projection of a trigger signal (the visual cortex) and visual-frontal networks generated in the course of training. PMID- 20737894 TI - [Comparative study of the ability to solve a string-pulling task in Corvidae]. AB - The ability of hooded crows (Corvus cornix L.) and common ravens (Corvus corax L.) to pull up a bait suspended from a horizontal perch by a string was tested. It was shown that some birds of both species successfully solved the string pulling task. Considerable inter-individual and inter-species differences in task performance are discussed. PMID- 20737895 TI - [Activation of tectofugal visual system of the pied flycatcher nestlings at early developmental stages of feeding behavior guided by diffuse photosensitivity]. AB - Immunohistochemical detection of c-Fos in serial frontal sections of the brain of Pied flycatcher nestlings was used to map the sensory structures involved in early forms of feeding behavior. The c-Fos content was quantitatively analyzed in the higher structures of thalamofugal (Wulst area) and tectofugal (entopallium) visual pathways during visually-guided feeding behavior in 6-day-old nestlings at the stage of diffuse photosensitivity. Induction of c-Fos was not observed in the Wulst area which is known to be involved in the feeding integration in adult bifoveal birds. Induction of c-Fos was detected in the ventral area of entopallium containing neurons that are, according to literature, sensitive to a luminosity change. In the entopallium of 6-day-old nestlings, asymmetry in the evoked c-Fos expression was observed, probably reflecting the asymmetry of the visual projections originating in the embryonic period. PMID- 20737896 TI - [Genotype-related changes in the reproductive function under social hierarchy in laboratory male mice]. AB - The study was designed to investigate genetic differences in reproductive consequences of social hierarchy using inbred mice strains BALB/cLac, PT and CBA/Lac. Two adult males of different genotypes were housed together for 5 days. Hierarchical status of both partners was determined by asymmetry in agonistic behavior. The number of epididymal sperm and a proportion of abnormal sperm, weights of reproductive organs, serum concentration and testicular content of testosterone, and the testosterone response to introduction of a receptive female were determined. The testosterone measures were significantly decreased in the PT strain, the epididymal sperm number was significantly decreased in the BALB/cLac strain and a proportion of abnormal sperm heads was significantly increase in the CBA/Lac (in both dominants and subordinates) as compared to control mice. The testicular testosterone response to a receptive female and precopulatory behavior was unchanged in dominants and suppressed in subordinates of the BALB/cLac strain. The results indicate that in laboratory mice the pattern of reproductive response to social hierarchy is determined by genetic background. PMID- 20737897 TI - [Changes in the high-frequency electrical brain activity in the animal hypnosis state in rabbits]. AB - The EEG spectral analysis applied to electrical brain activity of rabbits in the state of animal hypnosis revealed a 2-4-fold increase in the power of the sigma frequency band (12-17 Hz) and a 1.5-2-fold decrease in the gamma frequency (especially 40-70 Hz) in addition to well-known growth of delta (0.3-3 Hz) and reduction of theta activity (4-8 Hz). The changes were more prominent in the frontal cortex areas. The influence of hypnotic state on cortical gamma activity pharmacologically augmented by ketamine injection was analyzed. Administration of subanesthetic ketamine doses led to behavioral locomotor excitation of an animal accompanied by a long-lasting (up to 2 h) increase in the gamma electrical activity. If the animal hypnosis was induced after the ketamine injection, it resulted in an almost instant reorganization of the spectral power. The slow-wave power increased and the gamma-power decreased to the baseline levels. Thus, the animal hypnosis eliminated the reorganization of cortical rhythmicity produced by ketamine, which suggests a stabilizing and, to a certain extent, protective function of this kind of hypnosis in the states of behavioral locomotion and stress. PMID- 20737898 TI - [Pinch-induced catalepsy in rats of various genetic groups with different predisposition to audiogenic epilepsy]. AB - Proportion of animals which developed pinch-induced catalepsy and the duration of this state were analyzed in rats of several genotypes which differed in audiogenic epilepsy proneness and compared with "audiogenic" catalepsy after a sound-induced seizure fit. The following genotypes were studied: Wistar, KM (Krushinsky-Molodkina) strain and substrains "4" and "0" (selected from KM and Wistar hybrid population for high "4" and low "0" audiogenic epilepsy proneness). Adult KM and substrain "4" rats developed the most intense pinch induced catalepsy, whereas Wistar and 2-month-old KM showed practically no catalepsy. After a single sound exposure pinch-induced catalepsy developed in all animals which demonstrated an audiogenic seizure fit--in KM, substrain "4", part of Wistar rats and several animals of substrain "0", latency of the fit onset in all rats being shorter than initially. After sound exposure pinch-induced catalepsy was revealed even in those substrain "0" rats, which demonstrated no audiogenic fits. It is suggested that despite the phenomenological similarity between cataleptic states of different origin (pinch-induced, "audiogenic") their neurophysiologic substrates overlap only partially. The findings are considered as presenting genetic model for further analysis of catalepsy. PMID- 20737899 TI - [Maternal behavior of WAG/Rij strain rats in normal conditions and during intervention in the activity of dopaminergic brain system]. AB - Lactating dams of WAG/Rij and Wistar rat strains were repeatedly placed on the "open field" arena with their pups (4-9 postnatal days). In these conditions WAG/Rij rats showed significantly poorer maternal behavior and were slower in forming pup location response. These results add to the notion of disorders in the activity of the nervous system of WAG/Rij rats (as genetic models for absence epilepsy). Administration of Haloperidol in a low dose (0.1 mg/kg, i.p.) reduced the motor activity ofdams of both strains and maternal behavior under conditions of bright illumination. Under conditions of red-light illumination, haloperidol increased the number of approaches to the pups and the number of their transportations in WAG/Rij (but not Wistar) rats and reduced the latencies of the behavioral reactions. It is suggested that dopaminergic regulation of maternal behavior depends on both genetic (strain differences) and environmental (illumination conditions) factors. PMID- 20737900 TI - [Optimization of counting process of dopaminergic neurons in substantia nigra of parkinsonian mice]. AB - Parkinson's disease (PD) results from degeneration of dopaminergic (DA-ergic) neurons of sunstantia nigra pars compacta (SNc). In experimental studies, this condition is modelled by administration of neurotoxin's precursor 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). The followed degeneration of DA ergic neurons is estimated by cell counting. Cell counting with serial sections is exceedingly hard and expensive. Therefore this method is not used extensively in spite of its high precision. Widely known Konigsmark's formula (KF) allows not to count cells in all serial section, but only in sections selected at regular interval. However, its precision decreases with increasing the interval and other parameters. In given work we have developed mathematical method of approximation (MA) by improving of KF. MA allows reducing the time and chemical products expenses for processing and analysis of the material with maintenance of necessary counting precision. Two groups of C56/BL mice were used in this study. The first group received MPTP in a dose of 8 mg/kg with 1 week interval and showed 20% decrease in DA-ergic neurons in SNc. The second group received MPTP in a dose of 12 mg/kg four times with 2-h interval and showed 40 % decrease in DA ergic neurons in SNc. Degeneration took place mostly in the middle part of SNc within rostra-caudal direction and led to rise of sharp differences in the number of neurons from section to section. These differences substantially decreased precision of FK (6 % error with counting in every 5th section), whereas precision of MA was sufficiently good (4% error with counting in every 7th section). Thus, we have developed MA, that allows us to decrease expenses of the time and chemicals for estimation of DA-ergic cells number in SNc of parkinsonian mice. PMID- 20737901 TI - [Agglutination and phagocytosis of foreign abiotic particles by bluebottle Calliphora vicina haemocytes in vivo. II. Influence of the previous septic immune induction on haemocytic activity]. AB - The rate of Calliphora vicina haemocytic defense reaction to foreign particles injection depends on the larval age and on the previous bacterial immunization. Immunization of crop-empting larvae induces an evident increase in particles phagocytosis by juvenile plasmatocytes in 24 h after injection. Both the hemogram and the pattern of cellular defense reaction change significantly after crop empting. Immunized larvae start intensive adhesion of foreign particles to plasmatocytes surface and formation of great aggregations of plasmatocytes (morules) no longer than in 34 min after injection. The period of particle haemocyte adhesion is short-termed and no more than after 30 min cell aggregates dissociate and adhered charcoal particles pass to thrombocydoidal agglutinates. Unimmunized control larvae of the same age have shown no adhesion and morules formation. In immunized wadering and diapausing larvae, formation of capsules consisting of central thrombocydoidal agglutinate filled with alien particles and adherent plasmatocytes I is intensified. In contrast to moru-les, this capsule formation is not accompanied by charcoal particles adhesion to plasmatocytes. Immunization of mature larvae of C. vicina shown no prominent influence on both the rate of phagocytosis and the hyaline cells differentiation. It might be supposed that the receptors system is complex and the immunization both the mechanisms of foreigners recognition (adhesion, morulation and incapsulation) and the far more lately occurring phagocytosis. PMID- 20737903 TI - [Light- and electron-microscopical study of Pelomyxa stagnalis Sp. n. (Archamoebae, Pelobiontida)]. AB - The structure of a new pelomyxa species was investigated with the use of light- and electron-microscope technique. Motile individuals reach 800 microm in length. There is a thin layer of amorphous glycocalix on the cell surface. Many non motile flagellae are found mainly in the uroidal zone. The axoneme has a non stable set of microtubules. There are no any special elements in the transition zone. A short kinetosome is about 150 nm long. A bundle of 15-20 microtubules starts from the one side of kinetosome and pass below the cell surface. Structure vacuoles are one of the main cytoplasm components of Pelomyxa stagnalis. Glycogen bodies are surrounded with flattened reticulum cisterns often containing electron dense material. Two morphological distinct species if prokaryote endobionts were found in the cells of P. stagnalis. The number of nuclei in the cells of P. stagnalis reaches 50 or more. The nuclei are rounded by a two-layer envelope including a multilaminar layer and outer layer, which is formed by small vesicles often containing electron-dense material. One nucleolus is situated at the center of a nucleus. In the nuclei, often in connection with the nucleolus, there are bodies formed by electron-dense threads. PMID- 20737902 TI - [Effect of immunization on the in vivo immunocytes reaction to foreign particles in the larvae of the flesh fly Calliphora vomitoria]. AB - Bacterial immunization of Calliphora vomitoria larvae induces hemocytic defense reaction in response to abiotic foreign particles injections. This reaction depends on the larval age and, consequently, the immunocytes composition. The juvenile plasmatocytes which are abundantly present in the end feeding and crop emptying larvae are initially very active and their reaction rate does not depend on the immunization. The plasmatocytes I appear after crop emptying. Immunization has a positive effect on their differentiation rate and, correspondently, the rapid progress in the defense response. The proportion of competent plasmatocytes in immunized larvae increases. The stable hyaline cells formation also depends on immunization, although elements of this response vary at different age steps. immunization of the end feeding and crop emptying larvae induces an increase in the percentage of hyaline cells, but alien particles injection does not provide additional stimulating effect. After crop emptying, immunization of wandering larvae ceases to exert an obvious direct influence, but significantly increases the sensitivity to charcoal injection. The emergence of foreign particles in the hemolymph of immunized wandering larvae causes a rapid increase in the number of hyaline cells due to prohemocytes and undifferentiated plasmatocytes differentiation. PMID- 20737904 TI - [Nucleosome remodeling on the regulatory region of the rat tryptophan dioxygenase (tdo) gene during transcription in vivo]. AB - Two DNase I-hypersensitive regions are identified on the regulatory region of the rat tryptophan dioxygenase (tdo) gene which is expressed tissue-specifically under control ofglucocorticoid hormones. DNase I-hypersensitive regions are identified in position -470 and in the vicinity of the first upstream gene. Micrococcal nuclease digestion pattern of this region shows disturbances in the regular cleavage and appearance of shorter DNA molecules than nucleosomal DNA. However the control experiments demonstrate that the same DNA region could be involved in the regular nucleosome core particles under in vitro reconstitution. Taken together, these data show that the nucleosome array in the regulatory region of the actively transcribed tdo gene in vivo is disturbed. PMID- 20737905 TI - [Acetylation of microtubules during endocytosis of epidermal growth factor receptor (c-ErbB1) in interphase HeLa cells]. AB - Acetylation of microtubules (MT) during endocytosis of epidermal growth factor receptor, c-ErbB1, was studied by confocal immunofluorescence microscopy. It was found that stimulation of endocytosis of c-ErbB1 complexed with the epidermal growth factor (EGF), resulted in continuous raising of MT acetylation that reached its maximum at 60-90 min and then went down to the control level. Simultaneously, the receptor-containing endosomes grew in size and were redistributed into juxtranuclear region. Enlarged endosomes formed dense clusters around MTOC in 60-90 min. Another native c-ErbB1 ligand, transforming growth factor-alpha (TGF-alpha) and unlike EGF causing the receptor recycling, also initiated a wave of MT acetylation, but the effect was expressed more poorly. In this case, endosomes did not grow in size and did not form dense clusters near the MTOC. Cell treatment with deacetylase inhibitor trichostatin A (TSA) caused acetylation of the whole cellular MT population. Under these conditions, translocations of EGF-c-ErbB1-containing endosomes had the same pattern as in the cells untreated with the inhibitor, but the size of endosomes didn't increase during their redistribution into juxtranuclear region. Acetylation was especially pronounced in strongly bent MT regions positioned proximally to MTOC and forming there a dense meshwork whereas peripheral MT plus-ends were basically straight and not modified. We assume that MT acetylation is not so much crucial for preferential interaction with dynein or kinesin and, accordingly, for organization of endosome translocations in a certain direction. It is rather the result of stabilization of some MT pool which supports homotypic fusion of endosomes at early stage of their maturation. PMID- 20737906 TI - [Localization and composition of renal immunodeposits in mice developing HgCl2 induced autoimmune process]. AB - A characteristic feature of systemic autoimmune diseases along with appearance of autoantibodies targeting self-antigenes is deposition of immunoglobulins and components of the complement system in kidneys. However, mechanisms of the deposit formation and their cytotoxic effects still remain poorly studied. To elucidate these questions, we used SJL/J mice which are known to develop autoimmune process accompanied by the appearance of anti-fibrillarin antibodies following regular administrations of sublethal dozes of HgCl2. Using antibodies to the total murine ummunoglobulins we showed that immunodeposits were present in glomeruli of autoimmune and control (not-autoimmune) animals, but their intensity was directly correlated with the titer of anti-fibrillarin autoantibodies and was minimal in control mice. By confocal microscopy and conventional fluorescence microscopy it was defined that immunodeposits deeply penetrate glomeruli and are the most likely located within mesangial cells. In autoimmune animals, ummunoglobulins completely colocolized with the C3--component of complement, but not with the major autoantigen--the protein fibrillarin. We failed to determine the signs of cell proliferation or death in glomeruli. The most prominent difference between control and autoimmune mice was the presence if immunodeposits in renal blood vessels. These observations argue in favor of the idea that destructive and disfunctional renal lesions accompanying development of autoimmune diseases can be caused, in part, by accumulation of immunodeposits in blood vessels. PMID- 20737907 TI - [Change in the distribution of transposable elements in isogenic strain--cause or consequence in Drosophila melanogaster selection for quantitative traits?]. AB - The distribution patterns pf hobo transposon and Dm412 retrotransposon hybridization sites on the salivary gland polytene chromosomes from the larvae of Drosophila melanogaster isogenic strain 51, used for analyzing the effect of transposable element (TE) transposition on the selection for quantitative traits, were studied, It was demonstrated that at least half Dm412 hybridization sites were retained 15 years after isogenization; the frequency of Dm412 transposition varied from 2.0 x 10(-4) to 8.8 x 10(-5) depending on whether the appearance of the same hybridization sites in some individuals were regarded as independent events or as a manifestation of the sample heterogeneity. The distribution patterns of hobo hybridization sites in two isofemale strains derived from isogenic strain 51 differed more noticeably: the number of hobo sites in one of the derivative strains was threefold smaller than in another and only a fraction of the sites was common. Within each derivative strain, the TE distribution was uniform, suggesting that inbreeding had no effect on the Dm412 activity in this strain. The rates of change in the distribution patterns of various TEs in strain 51 corresponded to their spontaneous transposition rates. As isogenic strain accumulates the polymorphism in TE distribution without selection, the TEs are more likely to be the markers of selection events than their inducers. Thus, when studying the effects of various environmental factors on TE transposition even in isogenic strains, it is necessary to perform rounds of close inbreeding to reduce the potential polymorphism. PMID- 20737908 TI - Characterization of calcium oxalate biominerals in some (non-Cactaceae) succulent plant species. AB - The water-accumulating leaves of crassulacean acid metabolism plants belonging to five different families were investigated for the presence of biominerals by infrared spectroscopic and microscopic analyses. Spectroscopic results revealed that the mineral present in succulent species of Agavaceae, Aizoaceae, and Asphodelaceae was calcium oxalate monohydrate (whewellite, CaC2O4 x H2O). Crystals were predominantly found as raphides or solitary crystals of various morphologies. However, representative Crassulaceae members and a succulent species of Asteraceae did not show the presence of biominerals. Overall, these results suggest no correlation between calcium oxalate generation and crassulacean acid metabolism in succulent plants. PMID- 20737909 TI - Synthesis and antifungal activities of some 2,6-bis-(un)substituted phenoxymethylpyridines. AB - Several 2,6-bis-(un)substituted phenoxymethylpyridines were synthesized and evaluated in vitro against Fusarium graminearum, Helminthosporium sorokinianum, Alternaria brassicae, Alternaria alternata, and Fusarium oxysporum f. sp. vasinfectum. Among all derivatives, compound 3a exhibited a broad-spectrum antifungal activity against the five phytopathogenic fungi. PMID- 20737910 TI - Antifungal activities of some indole derivatives. AB - Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide. PMID- 20737911 TI - Acetylcholinesterase inhibitory activity of uleine from Himatanthus lancifolius. AB - Application of acetylcholinesterase (AChE) inhibitors is the primary treatment for Alzheimer's disease. Alkaloids, such as physostigmine, galanthamine, and huperzine A, play an important role as AChE inhibitors. The aim of this work was to evaluate Himatanthus lancifolius (Muell. Arg.) Woodson, a Brazilian species of Apocynaceae, and its main indole alkaloid uleine, in order to identify new AChE inhibitors. The plant fluid extract, fractions, and uleine were tested for AChE inhibitory activity using Ellman's colorimetric method for thin-layer chromatography (TLC), 96-well microplates, and also Marston's TLC colorimetric method. Both TLC assays showed similar results. At 5 mg/mL, the fluid extract inhibited the AChE enzyme by (50.71 +/- 8.2)%. The ethyl acetate fraction exhibited the highest level of AChE inhibition, followed by the dichloromethane fraction. The isolated alkaloid uleine displayed an IC50 value of 0.45 microM. PMID- 20737912 TI - Investigation of aminomethyl indole derivatives as hyaluronidase inhibitors. AB - Hyaluronidase inhibitors are of potential therapeutic value for the treatment of a variety of diseases, such as cancer, arthrosis, or bacterial infections. Potent and selective hyaluronidase inhibitors are not known so far, and current approaches to the development of hyaluronidase inhibitors are limited. Elevated levels of hyaluronan (HA) are connected with most malignant tumours. Therefore, the search for drugs modulating the hyaluronidase activity became very important. In the present study, a new series of aminomethyl indole derivatives (AMIDs) were tested for inhibition of bovine testes hyaluronidase (BTH). In vitro assays were performed using stains-all at pH 7 and Morgan-Elson reaction at pH 3.5. Among the AMIDs, 3-[(4-methylpiperazin-1-yl)methyl]-5-phenyl-1H-indole (9) was found to be active with 23% inhibition at 50 microM and pH 7. All the other inhibitors showed less activity at pH 3.5 and pH 7. These activity results demonstrated that compounds with phenyl substitution at position 5 have higher activity. The results confirmed that more lipophilic compounds have better inhibition against the hyaluronidase enzyme. PMID- 20737914 TI - Alkaloid accumulation in different parts and ages of Lycoris chinensis. AB - The galanthamine, lycorine, and lycoramine content of Lycoris chinensis was researched during development from young to old plants, i.e. in seeds, ten-day old seedlings, three-month-old seedlings, one-year-old seedlings, and perennial seedlings. Notably the alkaloid level reduced to its lowest content 10 days after seed germinating. Then the accumulation of galanthamine tended to increase with age, reaching a higher value in perennial seedlings. The production pattern of lycorine and lycoramine was found similar to that of galanthamine. Different plant organs were also evaluated for their galanthamine, lycorine, and lycoramine contents. Mature seeds had the highest content of galanthamine (671.33 microg/g DW). Kernels, seed capsules, and root-hairs were the main repository sites for galanthamine, lycorine, and lycoramine. The leaves were the least productive organs. PMID- 20737913 TI - Vasorelaxant action of N-p-nitrophenylmaleimide in the isolated rat mesenteric artery. AB - The vasorelaxant response of N-p-nitrophenylmaleimide (4-NO2-NPM) was evaluated. The mesenteric rings (1-2 mm i.d.) were suspended by cotton thread for isometric tension recordings in a Tyrode's solution at 37 degrees C and gassed with a mixture of 95% O2 and 5% CO2, under a resting tension of 0.75 g. 4-NO2-NPM induced relaxation in mesenteric rings pre-contracted with phenylephrine (Phe; 10 microM, pD2 = 6.7 +/- 0.3) or KCl (80 mM, pD2 = 3.9 +/- 0.2). This effect was significantly attenuated after removal of the vascular endothelium, N(G)-nitro L arginine methyl ester (L-NAME; 100 microM), atropine (1 microM), indomethacin (10 microM), L-NAME + indomethacin or 1H-[1,2,3]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM). L-Arginine (1 mM) reversed the inhibitory effect of L-NAME. In endothelium-intact preparations pre-incubated with 20 mM KCl, tetraethylammonium bromide (TEA; 1 mM) or glibenclamide (Glib; 10 microM), the vasorelaxant effect was significantly attenuated when compared to controls (endothelium intact). In denuded rings, separate incubation with 20 mM KCl, TEA or Glib did not change the relaxation when compared with that obtained in denuded rings. 4-NO2-NPM inhibited in a concentration-dependent and non-competitive manner the concentration response curves induced by CaCl2. In calcium-free medium, the transient contractions induced by Phe (10 microM) or caffeine (20 mM) were inhibited. The relaxant effect induced by 4-NO2-NPM appeared to be due to endothelial muscarinic receptors activation, NO and prostacyclin release and K(ATP) and BK(Ca) (Ca(2+) activated K+ channels) endothelium-dependent activation. Inhibition of the Ca2+ influx and inhibition of the Ca2+ release from intracellular IP3- and caffeine sensitive stores are also involved in the vasorelaxation. PMID- 20737916 TI - Devil's claw hairy root culture in flasks and in a 3-L bioreactor: bioactive metabolite accumulation and flow cytometry. AB - Phenylethanoids are a group of natural water-soluble compounds with high biological value, which could potentially be commercially produced by hairy root cultures. Thus, we have examined the capacity of transformed root cultures of Devil's claw (Harpagophytum procumbens) to accumulate four phenylethanoid glycosides -beta-OH-verbascoside, verbascoside, leucosceptoside A, and martynoside--in shake-flasks and a 3-L stirred tank reactor. Verbascoside was found to be the major phenylethanoid, and its maximal contents were the same (1.12 mg/g dry weight) in both kinds of culture. However, peak leucosceptoside A contents were 1.6-times higher in bioreactor cultures than in shake-flask cultures. Flow cytometry analysis revealed that G0 + G1-phase cells predominated throughout the growth of the cultures, which was in accordance with the very high proportion of quiescent cells in the transformed roots. The results provide the first demonstration of the potential utility of Devil's claw hairy roots as biofactories for producing high-value phenylethanoid glycosides. PMID- 20737915 TI - Effects of hydrogen sulfide on alternative pathway respiration and induction of alternative oxidase gene expression in rice suspension cells. AB - The toxic effects of H2S on plants are well documented. However, the molecular mechanisms reponsible for inhibition of plants by H2S are still not completely understood. We determined the effects of NaHS in the range of 0.5-10 mM on the growth of rice suspension culture cells, as well as on the expression of the alternative oxidase (AOX) gene. AOX is the terminal oxidase of the alternative pathway (AP) and exists in plant mitochondria. The results showed that H2S treatment enhanced the AP activity. During the process of H2S treatment for 4 h, the AP activity increased dramatically and achieved the peak value at a concentration of 2 mM NaHS. Then it declined at higher concentrations of NaHS (5 10 mM) and maintained a steady level. The AOX1 gene transcript level also showed a similar change as the AP activity. Interestingly, different NaHS concentrations seemed to have different effects on the expression of AOX1a, AOX1b, and AOX1c. The induction of AOX expression by low concentrations of NaHS was inferred through a reactive oxygen species (ROS)-independent pathway. At the same time, rice cells grown in culture were very sensitive to H2S, different H2S concentrations induced an increase in the cell viability. These results indicate that the H2S-induced AOX induction might play a role in inhibiting the ROS production and have an influence on cell viability. PMID- 20737917 TI - A new laboratory cultivation of Paramecium bursaria using non-pathogenic bacteria strains. AB - In most studies dealing with the laboratory cultivation of paramecia (Paramecium bursaria), Klebsiella pneumoniae bacteria are used to inoculate the medium. However, Klebsiella pneumoniae is a typical pathogen, and its use is always associated with a risk of infection. The aim of the present research was to examine non-pathogenic bacteria strains as components of the medium for Paramecium bursaria. The paramecia were incubated on lettuce infusions bacterized with different bacteria strains: Bacillus subtilis DSM 10, Bacillus megaterium DSM 32, Escherichia coli DSM 498, Micrococcus luteus DSM 348. A strain derived from the natural habitat of Paramecium bursaria was used as the control one. Experiments were conducted under constant light and in the dark. Paramecia cells were counted under a stereomicroscope on consecutive days of incubation. The obtained results show that the most intensive growth of Paramecium bursaria occurs in the presence of Escherichia coli DSM 498. The use of this strain as a component of the medium allows one to obtain a high number of ciliates regardless of the light conditions. It can be concluded that the Paramecium bursaria cultivation procedure can be modified by using the non-pathogenic bacteria strain Escherichia coli DSM 498 instead of Klebsiella pneumoniae. PMID- 20737918 TI - Selection of lipase-producing microorganisms through submerged fermentation. AB - Lipases are enzymes used in various industrial sectors such as food, pharmaceutical and chemical synthesis industries. The selection of microorganisms isolated from soil or wastewater is an alternative to the discovery of new species with high enzymes productivity and with different catalytic activities. In this study, the selection of lipolytic fungi was carried out by submerged fermentation. A total of 27 fungi were used, of which 20 were isolated from dairy effluent and 7 from soil contaminated with diesel oil. The largest producers were the fungi Penicillium E-3 with maximum lipolytic activity of 2.81 U, Trichoderma E-19 and Aspergillus O-8 with maximum activities of 2.34 and 2.03 U where U is the amount of enzyme that releases 1 micromol of fatty acid per min per mL of enzyme extract. The fungi had maximum lipolytic activities on the 4th day of fermentation. PMID- 20737919 TI - Analysis and identification of astaxanthin and its carotenoid precursors from Xanthophyllomyces dendrorhous by high-performance liquid chromatography. AB - This study presents an HPLC method for simultaneous analysis of astaxanthin and its carotenoid precursors from Xanthophyllomyces dendrorhous. The HPLC method is accomplished by employing a C18 column and the mobile phase methanol/water/acetonitrile/ dichloromethane (70:4:13:13, v/v/v/v). Astaxanthin is quantified by detection at 480 nm. The carotenoid precursors are identified by LC-APCI-MS and UV-vis absorption spectra. Peaks showed in the HPLC chromatogram are identified as carotenoids in the monocyclic biosynthetic pathway or their derivatives. In the monocyclic carotenoid pathway, 3,3'-dihydroxy-beta,psi carotene-4,4'-dione (DCD) is produced through gamma-carotene and torulene. PMID- 20737920 TI - Analysis of genetic relationships in germplasms of Mugua in China revealed by internal transcribed spacer and its taxonomic significance. AB - Genetic relationships were studied among eight species of three taxa in the genus Chaenomeles by nuclear ribosomal internal transcribed spacer (ITS) analysis. A genetic distance matrix based on ITS sequences was estimated according to the formula of Kimura-2 parameter and a neighbour-joining phenogram, which were obtained with Clustalx4.1 software. The results showed that the germplasms of Mugua originate from Ch. speciosa (Sweet) Nakai, not including Ch. sinensis (Thouin) Kochne and Ch. cathayensis (Hemsl.) Schneid. The results also showed that 'Yao Mugua' and 'Ornamental Mugua' are the most distantly related species in germplasms. PMID- 20737921 TI - Cloning and expression analysis of 1 L-myo-inositol-1-phosphate synthase gene from Ricinus communis L. AB - A novel 1 L-myo-inositol-1-phosphate synthase (MIPS, EC 5.5.1.4) gene, designate rcMIPS, was cloned from Ricinus communis. It contained an open reading frame (ORF) of 1669 bp coding for a peptide of 510 amino acids with a molecular mass of 56 kDa. Sequence anaylsis showed high homology compared to other plant MIPS genes, because it contained typical domains owned by MIPS enzymes. The transcript levels of the rcMIPS gene in leaves, stems, and roots were examined after drought stress for 24, 48, and 72 h. The transcript levels in the leaves, stems, and roots increased significantly compared to the control. Results of the enzyme assay showed a significant correlation between the changes of enzyme activity and the transcript levels of the rcMIPS gene in different organs. Decreased relative water contents (RWC) and increased malondialdehyde (MDA) contents in the leaves represented a stress response against drought stress. Our findings suggest that MIPS plays an important role in the defensive mechanisms of R. communis against drought stress. PMID- 20737922 TI - Characterization of a late expression gene of Bombyx mori nucleopolyhedrovirus. AB - Bombyx mori nucleopolyhedrovirus (BmNPV) ORF5 (Bm5) is a gene present in many lepidopteran nucleopolyhedroviruses (NPVs), but its function is unknown. In this study, Bm5 was characterized. The transcript of Bm5 was detected 12-72 h post infection (p.i.). Polyclonal antiserum raised to a His-BM5 fusion protein recognized BM5 in infected cell lysates from 24 to 72 h p.i., suggesting that Bm5 is a late gene. Immunofluorescence analysis by confocal microscopy showed that the BM5 protein is localized primarily in the cytoplasm. Localization of BM5 in budded virion (BV) and occlusion-derived virion (ODV) by Western analyses demonstrated that BM5 is not a structural protein associated with BV or ODV. PMID- 20737923 TI - Changes in liver gene expression of Azin1 knock-out mice. AB - The ornithine decarboxylase antizyme inhibitor (AZI) was discovered as a protein that binds to the regulatory protein antizyme and inhibits the ability of antizyme to interact with the enzyme ornithine decarboxylase (ODC). Several studies showed that the AZI protein is important for cell growth in vitro. However, the function of this gene in vivo remained unclear. In our study, we analyzed the transcriptional profiles of livers on the 19th day of pregnancy of Azin1 knock-out mice and wild-type mice using the Agilent oligonucleotide array. Compared to the wild-type mice, in the liver of Azin1 knock-out mice 1812 upregulated genes (fold change > or = 2) and 1466 downregulated genes (fold change < or = 0.5) were showed in the microarray data. Altered genes were then assigned to functional categories and mapped to signaling pathways. These genes have functions such as regulation of the metabolism, transcription and translation, polyamine biosynthesis, embryonic morphogenesis, regulation of cell cycle and proliferation signal transduction cascades, immune response and apoptosis. Real-time PCR was used to confirm the differential expression of some selected genes. Overall, our study provides novel understanding of the biological functions of AZI in vivo. PMID- 20737924 TI - Optimization and purification of L-asparaginase produced by Streptomyces tendae TK-VL_333. AB - Cultural factors affecting the production of L-asparaginase by Streptomyces tendae isolated from laterite soil samples of Guntur region were investigated on glycerol-asparagine-salts (modified ISP-5) broth. Optimal yields of L asparaginase were recorded in the culture medium with the initial pH 7.0 incubated at 30 degrees C for 72 h. The strain utilized sucrose (2%) and yeast (2%) extract as carbon and nitrogen sources for L-asparaginase production. The productivity of L-asparaginase was slightly enhanced when the strain was treated with cell-disrupting agents like EDTA. The crude enzyme was purified to homogeneity by ammonium sulfate precipitation, Sephadex G-100 and CM-Sephadex G 50 gel filtration. By employing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular weight of the enzyme was recorded as 97.4 kDa. This is the first report on production and purification of L-asparaginase from S. tendae. PMID- 20737925 TI - Compressed-air work is entering the field of high pressures. AB - Since 1850, compressed-air work has been used to prevent shafts or tunnels under construction from flooding. Until the 1980s, workers were digging in compressed air environments. Since the introduction of tunnel boring machines (TBMs), very little digging under pressure is needed. However, the wearing out of cutter-head tools requires inspection and repair. Compressed-air workers enter the pressurized working chamber only occasionally to perform such repairs. Pressures between 3.5 and 4.5 bar, that stand outside a reasonable range for air breathing, were reached by 2002. Offshore deep diving technology had to be adapted to TBM work. Several sites have used mixed gases: in Japan for deep shaft sinking (4.8 bar), in The Netherlands at Western Scheldt Tunnels (6.9 bar), in Russia for St. Petersburg Metro (5.8 bar) and in the United States at Seattle (5.8 bar). Several tunnel projects are in progress that may involve higher pressures: Hallandsas (Sweden) interventions in heliox saturation up to 13 bar, and Lake Mead (U.S.) interventions to about 12 bar (2010). Research on TBMs and grouting technologies tries to reduce the requirements for hyperbaric works. Adapted international rules, expertise and services for saturation work, shuttles and trained personnel matching industrial requirements are the challenges. PMID- 20737926 TI - Spontaneous hydrocele resolution after hyperbaric oxygen treatment: a clinical case report. AB - Hyperbaric oxygen is considered an adjunctive treatment to medical and surgical care. We present a unique case in which a male patient with decompression illness affecting inner ear and spinal cord presented a worsened unilateral hydrocele synchronously with the neurological pathology. At the Diving and Hyperbaric Medicine Department, the patient was initially recompressed using a modified United States Navy Treatment Table 6A; on the following days he was treated for decompression illness using hyperbaric oxygen. Hyperbaric oxygen treatment has not been used for the treatment of hydrocele, but disappearance of the hydrocele occurred during the time he was treated with hyperbaric oxygen for decompression illness. He was discharged on Day 8, free of symptoms, having a normal neurological examination. PMID- 20737927 TI - Middle-ear barotrauma after hyperbaric oxygen therapy. AB - BACKGROUND: Middle-ear barotrauma (MEB) is one of the most common side effects of hyperbaric oxygen therapy (HBO2). The incidence of MEB has been shown to vary between treatment centers and patients. This study was aimed to determine which patients are at high risk of MEB. MATERIALS AND METHODS: Prospective study including all the patients treated in a multiplace HBO2 chamber between January and December 2005. Scoring of MEB before and after HBO2 by otoscopy was performed using the Haines and Harris classification. RESULTS: We included 130 patients: 53 Males, 37.5 +/- 20.5 years old; 76% were treated for CO poisoning, 11% for iatrogenic gas embolism, 12% for decompression sickness and 4% for necrotizing soft tissue infection. 13% were intubated. MEB occurred in 13.6% of the patients (12.4% of the conscious and 24.4% of the intubated patients, p = 0.26). Risk factors for MEB were: repetitive treatments and difficulties with pressure equalization. There was no influence of age, sex or mechanical ventilation on the occurrence of MEB. CONCLUSIONS: MEB induced by HBO2 occurred in 13.6% of the patients. There is no difference in incidence when comparing intubated and non intubated patients. In non-comatose patients, difficulties with equalizing pressure were predictive of MEB. PMID- 20737928 TI - A survey of neurological decompression illness in commercial breath-hold divers (Ama) of Japan. AB - A survey was conducted in the northern district of Yamaguchi, Japan to determine the relationship between neurological diving accidents and risk factors among commercial breath-hold divers (Ama). A questionnaire was distributed to 381 Ama divers who are members of the Ama diving union. We sought information on their dive practices (depth of single dive, single dive time, surface interval, length of dive shifts, lunch break) and the presence or absence of medical problems, such as hypertension, cardiac arrhythmia, diabetic mellitus and other issues. Of the 381 Ama divers, 173 responded (45%): 29 were Funado (assisted-descent using weights) and 144 Cachido (unassisted) divers. Twelve had experienced strokelike symptoms during or after repetitive breath-hold diving; 11 were assisted and one unassisted (Funado vs. Cachido). Only two of 12 divers with neurological diving accidents had musculoskeletal symptoms. Neurological events were significantly correlated with dive depth, dive time, and surface interval; however, they were not related to medical history. Neurological diving accidents are more likely to happen among assisted Ama divers than unassisted ones. Repetitive breath-hold diving with a deep dive depth, long dive time, and short surface interval predisposes divers to decompression illness, which characteristically manifests as cerebral stroke. PMID- 20737929 TI - Hyperbaric stress in divers and non-divers: neuroendocrine and psychomotor responses. AB - This study compared neuroendocrine and psychomotor responses in divers (D, n = 11) and non-divers (ND, n = 9) following 30-minute hyperbaric and decompression stress to 180, 300 and 450 kPa. Venous blood was drawn pre-dive and at 20 and 60 minutes post-dive and analyzed for norepinephrine (NE), epinephrine (E), tryptophan (TRP), cortisol (COR), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and prolactin (PRL). Reaction time was assessed using a psychomotor vigilance task. There was no difference between groups, across time or among levels of hyperbaric stress, for NE, E, TRP or GH. Small decreases over time in COR were noted. ACTH was significantly higher for ND at 20 minutes following 180 kPa and after 60 minutes for 450 kPa exposure. PRL increased significantly more for ND, and changes from baseline following 450 kPa exposure were moderately related (r = 0.52) to the significant slowing of reaction time at 20 minutes (296 +/- 55 msec) and 60 minutes (277 +/- 35 msec) compared with baseline (247 +/- 22 msec), although PRL returned to baseline levels faster than reaction time. It was concluded that for the stress hormones measured, PRL may provide some indication of the adaptation involved with repeated hyperbaric stress, but its relationship to changes in reaction time was weak. PMID- 20737930 TI - Identification of bacteria in scuba divers' rinse tanks. AB - Scuba divers typically rinse equipment in communal tanks. Studies show these tanks are contaminated with bacteria, but the types of bacteria have not been studied. We sought to identify bacteria in rinse tanks at a dive facility at San Pedro, Belize, to determine the origin of the bacteria and determine whether the bacteria represented potential threats to human health. The identity of bacteria was investigated using reverse line blot (RLB) assays based on 28 different rDNA probes designed to detect known pathogens of sepsis, as well as by sequencing 23S rDNA from isolates and performing VITEK identification of several isolates. Based on the identities of bacteria in divers' rinse tanks, many likely originate from the ocean, and others likely originate from the divers themselves. None of the bacteria identified would be considered overt human pathogens. However, some of the bacteria found in the tanks are known to be associated with unsanitary conditions and can cause opportunistic infections, which may pose health problems to some individuals. Rinsing scuba equipment in communal tanks has the potential to transmit disease among some divers. Equipment, especially regulators and masks, should be rinsed/cleaned individually and not be placed in communal tanks. PMID- 20737931 TI - Transplantation of cryopreserved teeth: a systematic review. AB - The aim of this article was to examine the research articles regarding biological and mechanical properties of cryopreserved teeth for potential use in tooth transplantation. A systematic review of literatures was performed by Pubmed searching with assigned key words from January 1, 1990 to June 8, 2009. All articles were examined for inclusion criteria. Secondary search was conducted by hand-search through references of included articles from primary search. A total of 24 articles were obtained from both primary and secondary search and used as fundamental articles in this review. Periodontal ligament tissues of cryopreserved teeth were able to maintain their biological properties resulted in a satisfactory healing of periodontium. Dental pulp tissues, however, may be compromised by limitation of permeability of cryopreservative agent into pulp cavity. Therefore, an endodontic treatment of transplanted cryopreserved teeth was recommended. Cryopreserved teeth had comparable mechanical properties to those of normal teeth. Importantly, the success of cryopreserved tooth transplantation treatment in orthodontic patients was reported. The cryopreserved teeth for tooth banking have a potential clinical application for treatment of missing teeth. Case selection, however, is critical for treatment success. More studies and data regarding masticatory function and periodontal healing of transplanted cryopreserved teeth are needed. PMID- 20737933 TI - Interaction between Schwann cells and osteoblasts in vitro. AB - AIM: Given the well-known properties of Schwann cells in promoting nerve regeneration, transplanting Schwann cells into implant sockets might be an effective method to promote sensory responses of osseointegrated implants. The aim of this study was to evaluate the interaction between Schwann cells and osteoblasts. METHODOLOGY: Schwann cells derived from the sciatic nerves of neonatal rat were co-culured with osteoblasts using Transwell inserts. The proliferation of Schwann cells in the co-culture system was evaluated using methylthiazol tetrazolium (MTT) colorimetric method. Moreover, the secretions and mRNA levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR, respectively. In order to test the effect of Schwann cells on osteoblasts, alkaline phosphatase (ALP) staining and Alizerin red staining were performed as well. RESULTS: Schwann cells, which were co-cultured with the osteoblasts, showed an intact proliferation during the observation period. Moreover, the gene expression and synthesis of BDNF and NGF were not impaired by the osteoblasts. Meanwhile, co-cultured osteoblasts exhibited a significant increase in the proliferation on day 3 and 6 (P< 0.05). Co-culture of these two types of cells also led to a more intense staining of ALP and an elevated number of calcified nodules. CONCLUSION: These findings demonstrate that, in the in vitro indirect co-culture environment, Schwann cells can maintain their normal ability to synthesize neurotrophins, which then enhance the proliferation and differentiation of osteoblasts. PMID- 20737932 TI - Targeted antimicrobial therapy against Streptococcus mutans establishes protective non-cariogenic oral biofilms and reduces subsequent infection. AB - AIM: Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans (S. mutans) can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. METHODOLOGY: Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically targeted antimicrobial peptides (STAMPs) against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. RESULTS: S. mutans colonization was considerably reduced ( +/- 0.4 fold reduction, P=0.01) when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization (5 minutes treatment: 38 +/- 13 fold reduction P=0.01; 16 hours treatment: 96 +/- 28 fold reduction P=0.07). CONCLUSION: S. mutans infection is reduced by the presence of existing biofilms. Thus maintaining a healthy or "normal" biofilm through targeted antimicrobial therapy (such as the STAMPs) could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression. PMID- 20737934 TI - Association between diabetes mellitus and oral health status in Japanese adults. AB - AIM: The objective of this study was to analyze the oral health among Japanese adults, with and without diabetes mellitus. METHODOLOGY: The subjects were 518 community residents aged 20 to 91 years in Japan, who participated in the "Akita health and nutrition survey" and the "Akita dental disease survey", conducted in 2006. The surveys comprised a self-administered questionnaire, along with medical and dental examinations. RESULTS: Using the community periodontal index (CPI), the mean numbers of sextants presenting codes 0, 1 and 2 were significantly lower in diabetics than non-diabetics among the 59 years or younger age group. Although the mean numbers of sextants with codes 0, 1 and 2 among the 60 to 69 years age group were lower, and sextants with a code X among the 59 years or younger age group were higher in diabetics than non-diabetics, no statistically significant differences were detected. The tendency of lower mean numbers of natural teeth and functional tooth units in diabetics than non-diabetics was observed, however no differences were statistically significant. CONCLUSION: The outcome of periodontal disease seemed to be influenced by the diabetic state to some degree, but a clear association between diabetes and oral health status was not found. PMID- 20737935 TI - The prevalence of hepatitis C virus infection in oral lichen planus in an ethnic Chinese cohort of 232 patients. AB - AIM: Oral lichen planush (OLP) is a chronic inflammatory disease, and has been reported to have a correlation with hepatitis C virus (HCV) infection in some regional investigations. In this study, we investigated the prevalence of HCV in patients with oral lichen planus in an ethnic Chinese METHODOLOGY: The antibody of HCV infection was detected by using enzyme-linked immunosorbent assay. Moreover, the clinical characteristics of whole the cohort have also been studied, such as the gender, age, clinical type, habits and social factors. RESULTS: Of all 232 patients, the antibody of HCV infection was detected positive in 4 patients (1.72%) using enzyme-linked immunosorbent assay. It was lower than that in control group of 2.5%, but not significant (P=0.309). The positive rate of HCV antibody in the erosive type ones (4.2%) was higher than that in the reticular type ones (1.0%), but this difference was proved to be not significant (P=0.389). The clinical characteristics of whole cohort, such as the gender, age, clinical type, habits and social factors, showed the outcome obtained in the present study were similar to thao of our previous study. CONCLUSION: HCV may play no etiological role in oral lichen planus in ethnic Chinese OLP patients. PMID- 20737936 TI - Applied anatomic site study of palatal anchorage implants using cone beam computed tomography. AB - AIM: The purpose of this study was to conduct quantitative research on bone height and bone mineral density of palatal implant sites for implantation, and to provide reference sites for safe and stable palatal implants. METHODOLOGY: Three dimensional reformatting images were reconstructed by cone beam computed tomography (CBCT) in 34 patients, aged 18 to 35 years, using EZ Implant software. Bone height was measured at 20 sites of interest on the palate. Bone mineral density was measured at the 10 sites with the highest implantation rate, classified using K-mean cluster analysis based on bone height and bone mineral density. RESULTS: According to the cluster analysis, 10 sites were classified into three clusters. Significant differences in bone height and bone mineral density were detected between these three clusters (P<0.05). The greatest bone height was obtained in cluster 2, followed by cluster 1 and cluster 3. The highest bone mineral density was found in cluster 3, followed by cluster 1 and cluster 2. CONCLUSION: CBCT plays an important role in pre-surgical treatment planning. CBCT is helpful in identifying safe and stable implantation sites for palatal anchorage. PMID- 20737937 TI - Fixed bicortical screw and blade implants as a non-standard solution to an edentulous (toothless) mandible. AB - AIM: This paper deals with the treatment of an atrophied toothless mandible with a fixing bridge carried by two nonstandard implant systems. METHODOLOGY: Four bicortical screws were implanted into the frontal part of the mandible and one implant on each side was placed into the distal area of the mandible as a support for a fixing bridge. RESULTS: During the years 2002 - 2007 the authors placed a total of 256 bicortical screw and 84 blade implants. During this period only four bicortical screws and one blade implant failed. The primary and secondary surgical success rate was therefore above 98%, while the prosthetic success rate was 100%. (Bridges which had to be re-fabricated due to implant failure were not taken into account.) CONCLUSION: This approach is recommended as a highly successful and affordable option for a wide range of patients. PMID- 20737938 TI - Pyoderma gangrenosum with oral involvement - case report and review of the literature. AB - Pyoderma gangrenosum (PG) is a rare, noninfectious neutrophilic dermatosis. Clinically, it begins with sterile pustules that rapidly progress into painful ulcers of variable depth and size with undermined violaceous borders. The diagnosis of PG is based on the history of an underlying disease, a typical clinical presentation, histopathology, and exclusion of other diseases. The peak incidence occurs between the ages of 20 to 50 years with women being more often affected than men. There have been very few reports of pyoderma gangrenosum with oral mucosal involvement. Oral lesions in previously reported cases have included ulcers of varying sizes from a few mm to several cm and have been reported to have been found on the tongue, soft and hard palate, buccal mucosa, and gingiva. Some of these oral lesions have been associated with ulcerative colitis, inflammatory bowel disease, and polycythemia rubra vera. A few cases were reported with biopsy findings, the histological picture being nonspecific, showing ulceration, and necrosis with inflammatory cell infiltrate. A peculiar case of pyoderma gangrenosum with an oral lesion is presented here, and the differential diagnosis is discussed. PMID- 20737940 TI - [Correction of minor exophthalmos by enlargement of orbital volume through conjunctive approach]. AB - OBJECTIVE: To investigate the treatment of minor exophthalmos by enlargement of orbital volume through conjunctive approach. METHODS: Through the conjunctive approach medial to the eye ball, the dissection was performed subperiosteally to expose the ethmoid bone at the medial orbital wall. The exposure bone was 2.5-3.0 cm in length and 2.0-2.5 cm in width. Then the ethmoid bone was fractured to enlarge the orbital volume. From June 2006 to April 2008, 3 cases were treated. RESULTS: The patients recovered in a short time with no visible skin scar. The technique was mini-invasive, and didn't affect the function of eyeball. CONCLUSION: It is easy and effective way to correct the minor exophthalmos by enlargement of orbital volume through conjunctive approach. PMID- 20737939 TI - [Fabricated expanded thoracodorsal artery perforator flap to repair cervical scar in children]. AB - OBJECTIVE: To investigate ideal methods to repair cervical cicatricial contracture in children. METHODS: The expanders were implanted subcutaneously around the cervical scar and above the latissimus. After expansion was completed, the cervical cicatricial contracture was released and the wound was covered with local expanded flaps and free expanded prefabricated thoracodorsal artery perforator flap, leaving no injury to thoracodorsal nerves and latissimus. The wound at the donor site was closed directly. RESULTS: From July 2007 to October 2009, 10 patients were treated. All the flaps survived completely. All the wounds were repaired totally and the deformities were corrected completely. The patients were followed up for 3-30 months. When the patients grew up, the flaps enlarged simultaneously. The flaps were not bulky and had a good color match. The scar at the donor site was inconspicuous with no functional morbidity. CONCLUSION: The fabricated expanded thoracodorsal artery perforator flaps is an ideal method for severe cervical cicatricial contracture in children. PMID- 20737941 TI - [The treatment of lower eyelid retraction at the different degree]. AB - OBJECTIVE: To explore the effective methods for the correction of lower eyelid retraction at different degree. METHODS: 258 patients with lower eyelid retraction were treated in our department since 1999. The lower eyelid retraction could be divided into mild, moderate and severe degree. The lateral canthal anchoring (n = 150), Hamra's lower eyelid blepharoplasty (n = 80) and translid cheek lifting (n = 28) were adopted according to the severity. The therapeutic effect for different degree of lower eyelid retraction was compared. RESULTS: 98 patients were followed up for 3-12 months, including 51 patients of mild degree, 29 patients of moderate degree, and 18 patients of severe degree. The retraction were corrected completely in 91 patients. The lower eyelid was repositioned to the level of inferior limbus without inferior scleral show when eyes opened. The palpebral fissure could close completely. The blunt lateral canthus turned to be acute and the scar was inconspicious. The retraction was improved, but not corrected completely in 3 patients of moderate degree and 4 patients of severe degree. The complications included petechiae, chemosis, and so on. CONCLUSIONS: The lower eyelid retraction can be corrected effectively if the appropriate techniques are performed according to the degree of retraction. PMID- 20737942 TI - [Repairing finger's penetrating soft tissue defects with "dumbbell" fascial metacarpal flap pedicled with skin perforator of dorsal metacarpal artery]. AB - OBJECTIVE: To assess the effect of "dumbbell" fascial metacarpal flap pedicled with skin perforator of dorsal metacarpal artery in treating the finger's penetrating soft tissue defect. METHODS: From February 2006 to August 2009, according to the courses, branches and distributions of the dorsal metacarpal artery, a "dumbbell" fascial metacarpal flap was designed and transposed to cover the penetrating soft tissue defects in 9 fingers. RESULTS: All of 9 flaps survived and got primary healing. The shape and function of the fingers were satisfied after 1-18 months period of follow-up. CONCLUSION: The "dumbbell" fascial metacarpal flap pedicled with skin perforator of dorsal metacarpal artery is an ideal donor site for repairing the finger's penetrating soft tissue defect. PMID- 20737943 TI - [The reverse flap based on two dorsal metacarpal artery for reconstruction of degloved fingertip avulsion]. AB - OBJECTIVE: To discuss the application of reverse flap based on two dorsal metacarpal artery for reconstruction of degloved fingertip avulsion. METHODS: From Jan. 2005 to Mar. 2008, 28 cases with degloved fingertip avulsion were treated with reverse flaps based on two dorsal metacarpal artery. The defects were located distal to the distant interphalangeal joints and were 0.8-2.2 cm in length. 10 defects was in the index fingers, 13 in the middle fingers and 5 in the ring fingers. 24 fingers were treated in an emergency surgery. 4 fingers were treated due to skin necrosis. RESULTS: Epidermal necrosis happened at the distal end of flaps in 3 cases. All the other flaps survived completely. 25 cases were followed up for 4-27 months with satisfactory cosmetic and functional results. The 2-points discrimination distance was 6.0-9.0 mm (average, 7.6 mm). CONCLUSIONS: The reverse flap based on two dorsal metacarpal artery is easily performed and reliable for degloved fingertip avulsion with satisfactory results. PMID- 20737944 TI - [Integrated autologous fat graft in face recontouring]. AB - OBJECTIVE: To discuss the integrated autologous fat graft technique in face recontouring. METHODS: In this study we treated 83 cases of face recontouring with 3L3M technique (low pressure suction, low speed centrifugation, low volume, multi-plane, multi-tunnel, multi-point injection). Each case was treated 1-3 times and the interval period is 3-6 months. The result was based on comparing the photos taken from pre-operation and post operation, observing the expression recovery, cysts, local absorption, and patients self evaluation. RESULTS: Long time follow up showed that fat graft can be alive in the recipient site for long time after 1-3 times autologous fat injection. More than 73.5% patients were satisfactory with the curative effect while less than 4.8% patients were unsatisfactory. CONCLUSION: 3L3M integrated fat graft technique is an effective and safe treatment in face recontouring. PMID- 20737945 TI - [Application of fractional laser resurfacing in the treatment of superficial scar]. AB - OBJECTIVE: To study the therapeutic effect, safety and risk of fractional resurfacing with ablative laser in the treatment of superficial scar. METHODS: 88 cases of superficial scar, including 66 cases of acne scar, 12 cases of burn scar and 10 cases of other scar, were treated. All the patients were treated with Pixel (Er:YAG 2940 nm, > or = 3 times), or Encore (Ultrapulse CO2 10600 nm, > or = 2 times), or a combination of Pixel and Encore( > or = 3 times). RESULTS: The therapeutic effect of treatment was graded as medium when the scar was improved > 25%, as good when the scar was improved > 50%. The effective result was achieved in 80% of the patients. Good effect was achieved in 50% of the patients. There were 244 treatments of Pixel and 86 treatments of Encore. Persistent hyperpigmentation was happened in one case with Encore treatment, which relieved four months later. No other complication was happened. CONCLUSIONS: The fractional resurfacing with ablative laser is an effective method for superficial scar, especially acne scar. It is mini-invasive with low risk. The key mechanism is the ability of enhancing the tissue remodeling induced by heat effect of laser. PMID- 20737946 TI - [Finite element study of maxillary Le Fort-I osteotomy with rigid internal fixation]. AB - OBJECTIVE: To study the biomechanical characteristic of maxillary Le fort- I osteotomy with rigid internal fixation (RIF) , so as to choose best fixation method. METHODS: The 3-dimensional finite element models of maxillary Le Fort-I osteotomy with 9 kinds of RIF methods were established. Then the models were divided into three groups to calculate the stress distribution of the maxilla and the displacement of bone segment under 3 kinds of occlusion condition. The fixation stability of the different RIF methods was evaluated. RESULTS: Under the incisor occlusion condition, the stress of the cranio maxillary complex transmits mainly along the nasal-maxillary buttress. Under the premolar and molar occlusion condition, the stress transmits along the alveolar process first, then turns to the nasal-maxillary and zygomatic-maxillary buttress. The focused stress position of the internal fixation system is at the connection between the screws and the plate and at the plate near the osteotomy line. Under the premolar occlusion condition, the displacement of bone segment with different RIF methods was (in a decreasing order) 0.396509 mm (with bio-absorbable plate), 0.148393 mm (with micro-plate ), 0.078436 mm (with mini-plate) in group 1; 0.188791 mm (fixing at the nasal-maxillary buttress), 0.121718 mm (fixing at the zygomatic-maxillary buttress), 0.078436 mm (fixing at the both buttress) in group 2; 0.091023 mm (with straight plate), 0.078436 mm (with L shape plate), 0.072450 mm (with Y shape plate), 0.065617 mm (with T shape plate) in group 3. CONCLUSIONS: The fixation stability of using the bio-absorbable plate in Le Fort-I osteotomy is less stable than using the titanium plate. Fixing at the zygomatic-maxillary buttress is more stable than at the naso-maxillary buttress. The fixation stability is different by using different shapes of plates. PMID- 20737947 TI - [Diagnosis of peripheral lymph circulation disorders with contrast MR lymphangiography]. AB - OBJECTIVE: To evaluate anatomical and functional images of contrast MR lymphangiography in the diagnosis of limb lymphatic circulation disorders. METHODS: 30 patients with limb lymphedema were enrolled in the study. There were 27 patients of primary lymphedema and 3 of secondary lymphedema. Contrast enhanced lymphangiography was performed with 3.0 T MR Unit after intracutaneous injection of gadobenate dimeglumine into the interdigital webs of the dorsal foot and hand. The kinetics of enhanced lymph flow within the lymphatics were calculated using the formula: Speed (cm) = total length of visualized lymph vessel (cm)/ inspection time (minutes) and by comparing dynamic nodal enhancement and time-signal intensity curves between edematous and contralateral limbs. Morphological abnormalities of the lymphatic system were also evaluated. RESULTS: Following injection of the contrast agent enhanced lymphatic channels were consistently visualized in all clinical lymphedematous limbs and five contralateral limbs of unilateral lymphedema cases. The speed of enhanced flow within the lymphatics of lymphedematous limbs ranged from 0.30 to 1.48 cm/min. The contrast enhancement in inguinal nodes of edematous limbs was significantly lower than that of contralateral limbs (P < 0.01). Dynamic measurement of contrast enhancement showed a remarkable lowering of peak time (P < 0.01) and peak enhancement (P < 0.01) and a delay in outflow in inguinal nodes of affected limbs compared with that of control limbs. Post-contrast MR imaging also depicted varied distribution patterns of lymphatics and abnormal lymph flow pathways within lymph nodes in the limbs with lymphatic circulation disorders. CONCLUSIONS: Contrast MR lymphangiography with gadobenate dimeglumine was able to visualize the precise anatomy of lymphatic vessels and lymph nodes in lymphedematous limbs. It also provided comprehensive information about the functional status of lymph flow transportation in lymphatics and lymph nodes. PMID- 20737949 TI - [Influence on costal cartilage reparative regeneration by replanting the small blocks of autogeneic cartilage]. AB - OBJECTIVE: To investigate the influence on costal cartilage reparative regeneration by replanting the small blocks of autogeneic cartilage into the perichondrial pocket at the donor-site. METHODS: 16 rabbits (8-10 weeks old, 1.8 2.2 kg) were randomly divided into four groups as three experimental groups and one control group. The 1.5 cm in length of costal cartilage defect was made in experimental groups with the perichondrium and costochondral junction left completely intact. The cartilage defect was closed by 3 methods as saturation directly, or replanting the small blocks of autogeneic cartilage, or plugging bio protein jelly after cartilage replanting. Each experimental group was handled with two methods in two sides of costal cartilage. No operation was performed in control group. All the rabbits were sacrificed 16 weeks after operation. The appearance of thoracic cage and new-formed tissue at the defect site were examined grossly. Haematoxylin-eosin staining was performed to evaluate the characteristics of new-formed tissues and biomechanical detection was used to measure intension of new-formed tissues. RESULTS: The appearance of thoracic cage was normal in every experimental group. Histological study showed that the defect was filled with abundant fibrous tissue in each group. The chipping of cartilage survived effectively with little proliferation. Biomechanical detection showed that the intension of new-formed tissue in the non-replanted group [(193.92 +/- 41.41) N] was obviously less than that in the replanted group [(318.88 +/- 28.28) N], or bio-protein jelly group [(301.00 +/- 39.52) N], or control group [(300.54 +/- 38.35) N] (P < 0.01). Furthermore, there was no statistical difference between the latter three groups (P > 0.05). CONCLUSIONS: Although replanting the chipping of cartilage can't promote reparative regeneration of hyaline cartilage, it can definitively strengthen the intensity of new-formed tissue, reinforce thoracic stability. It may also indirectly decrease the incidence rate of postoperative chest wall deformity. PMID- 20737948 TI - [The expression of CEACAM-1 and CXCL-14 in infantile hemangioma]. AB - OBJECTIVE: To examine the expression of CEACAM-land CXCL-14 in the different stages of infantile hemangioma and to explore the role of CEACAM-1 and CXCL-14 in the occurrence and development of infantile hemangioma. METHODS: The expression of CEACAM-1 and CXCL-14 was detected by immunohistochemical technique and Western Blot in cases of proliferating hemangiomas, involuting hemangiomas, involuted hemangiomas. The mean optical density was measured by image analysis system. RESULTS: The expression of CEACAM-1 in early stage of proliferating hemangiomas was weak or negative, while it was strong in involuting hemangiomas and positive in the involuted stage. The differences between different stages had a statistically significance (P < 0.05). The expression of CXCL-14 was weak or negative in stage of proliferating hemangiomas, positive in involuting hemangiomas and strong in the involuted stage. The differences between different stages had a statistically significance (P < 0.05). CONCLUSIONS: CEACAM-1 and CXCL-14 are involved in the occurrence and development of infantile hemangioma. PMID- 20737950 TI - [The expression of melatonin receptor in human hypertrophic scar]. AB - OBJECTIVE: To investigate the expression and its significance of melatonin receptor in human hypertrophic scarring. METHODS: The expression of melatonin receptor GPR50 was detected with immunohistochemistry and the melatonin receptors (MT1, MT2) mRNA were assessed with RT-PCR method in 10 cases of human hypertrophic scar and normal skin. The positive production was sequenced with auto sequencing instrument. RESULTS: Positive signals of melatonin receptor could be found in the cell membrane and cytoplasm. The melatonin receptor GPR50 was located in the epithelial basal cells,sweat gland cells and hair follicle in both hypertrophic scar and normal skin. The melatonin receptor GPR50 was extensively expressed in fibroblasts of hypertrophic scar, but not in fibroblasts in normal skin. RT-PCR showed that the expression of melatonin receptor (MT1, MT2) mRNA in hypertrophic scar was significantly higher than that in normal skin (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was higher than MT2 mRNA (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was 0.99081 +/- 0.26485 and 1.16584 +/- 0.21829 copy number/microl cDNA, respectively; the expression of MT2 mRNA was 0.77083 +/- 0.15927 and 0.99550 +/- 0.14624 copy number/ microl cDNA, respectively. Sequencing results indicated that the positive product coincided with cDNA of human melatonin receptor in GeneBank. CONCLUSIONS: Positive expression of melatonin receptor can be found in human hypertrophic scar and normal skin, but it is higher in scar. The over expression of melatonin receptor in hypertrophic scar may be related to the development of hypertrophic scar. PMID- 20737951 TI - [The effect of electroporation mediated gene therapy on bone mineral density and strength of new-formed bone in mandibular distraction gap in rabbit]. AB - OBJECTIVE: To explore the effect of electroporation mediated gene therapy on bone mineral density and strength of new-formed bone in mandibular distraction gap, so as to enhance the osteogenesis and shorten the distraction term. METHODS: New Zealand rabbits were employed. The distraction began after 3 days of latency period at the rate of 0. 8 mm per day for 7 days. After distraction, the rabbits were randomly divided into 5 groups to receive injection in the distraction gap with recombinant plasmid 2 microg (0.1 microg/microl) pIRES-hVEGF165-hBMP2 in group A, with recombinant plasmid pIRES-hBMP2 in group B, with recombinant plasmid pIRES-hVEGF165 in group C, with pIRES in group D, and with normal saline (NS) in group E. After injection, electroporation was performed in all the groups. After 1 week, 2 weeks, 4 weeks and 8 weeks of consolidation, all the animals underwent X-ray and quantitative computed tomography (QCT). The new formed bone in distraction gap was selected as regions of interest (ROI) to measure the bone mineral density(BMD). Then the rabbits were sacrificed and the new-formed bone samples were harvested to detect 3-point crushing strength. RESULTS: BMD of newly formed bone in group A, B and C was markedly higher than that in group D and E (P < 0.01). After 2 weeks of consolidation, BMD in group A was much higher than that in the other groups, but there was no difference between group B and C. After 4 weeks of consolidation, BMD in group A and B was markedly higher than that in group C, D and E (P < 0.01). After 8 weeks of consolidation, BMD in group A was markedly higher than that in the other groups. While the BMD was not significantly different between group B and C, but the BMD in group B and C was higher than that in group D and E (P < 0.01). After 4 weeks of consolidation, the 3-point crushing strength of newly formed bone in group A was markedly higher than that in group B,C, D and E (P < 0.01), which was still the same after 8 weeks of consolidation. And the crushing strength in group B was higher than that in group C, D and E (P < 0. 05). CONCLUSIONS: Electroporation mediated transfection of recombinant plasmid pIRES-hVEGF165-hBMP2 could greatly enhance osteogenesis and calcification. A combination of VEGF and BMP may promote osteogenesis and angiogenesis simultaneously, so as to magnify the effect of each growth factor, resulting a synergetic effect. PMID- 20737952 TI - [Effect of photodynamic therapy on the proliferation and cell distribution of hypertrophic scar fibroblast]. AB - OBJECTIVE: To investigate the effect of HMME-PDT on the proliferation and cell distribution of hypertrophic scar fibroblast (HSF). METHODS: HSF were cultured and only 4-6th passages were used in this study. Argyrophilic protein in nucleolar organizer regions(AgNORs) were calculated by I. S% after argyrophilic staining. Flow cytometry was applied to analyze the cell cycle and proliferation index (PI). RESULTS: 1) I. S% of HSF after HMME-PDT was reduced markedly. 2) HMME PDT inhibited HSF entering S stage from G, stage, cell percentage in S stage was decreased to (11.2 +/- 2.3)%. 3) PI in HMME-PDT group was less than that in control group [(35.0 +/- 3.4)% vs (27.2 +/- 3.1)%, P < 0.05]. CONCLUSIONS: HMME PDT can inhibit proliferation of HSF, and chang cell distribution. PMID- 20737953 TI - [The study on the role of the soluble factors secreted by engineered cartilage in inducing bone marrow stromal cells chondrogenesis]. AB - OBJECTIVE: To study the role of the soluble factors secreted by tissue engineered cartilage in promoting bone marrow stromal cells (BMSCs) chondrogenesis as an important aspect. METHODS: Porcine BMSCs, chondrocytes and dermal fibroblasts were respectively in vitro expanded and then seeded onto the polyglycolic acid/polylactic acid (PGA/PLA) scaffold. After 3 days, they were indirectly co cultured by transwell. BMSCs-scaffold constructs were co-cultured with chondrocytes-scaffold constructs as experiment group (Exp), while co-cultured with fibroblasts-scaffold constructs as control group. BMSCs with the same cell number were seeded onto the scaffolds as another control group. There were 3 specimens in each group. All specimens were harvested after in vitro indirect co culture for 8 weeks. Gross observation, histology, immunohistochemistry and RT PCR were used to evaluate the results. RESULTS: The BMSCs-scaffold constructs co cultured with chondrocytes-scaffold shrunk gradually during in vitro culture, but formed the mature lacuna structures and metachromatic matrices, collagen II expression could be observed by immunohistochemistry and RT-PCR examination. In the control group, the constructs shrunk greatly during in vitro culture and showed mainly fibrous tissue. CONCLUSIONS: The soluble factors secreted by chondrocytes can solely induce chondrogenic differentiation of BMSCs and thus promote the in vitro chondrogenesis of BMSCs. PMID- 20737954 TI - [Angular nerve of facial nerve: anatomic research]. AB - OBJECTIVE: To study the anatomy of angular nerve (AN), so as to provide safe approach for the denervation surgery of corrugator supercilii, depressor supercilii and procerus. METHODS: 10 fresh cadaver (20 sides)were perfused and fixed with formalin. Dissection was performed in the 10 x operating microscope. The plexus of the zygomatic branch and the buccal branch were detected to confirm the AN. The relationship of AN with the surrounding blood vessels was observed. We tracked AN until it entered corrugator supercilii, depressor supercilii and procerus. RESULTS: (1) AN was classified into I, II, III type according to its formation pattern. Type I (20%, 4/20 sides) AN is single, which is mainly from the plexus of buccal branch plus the zygomatic branch from the orbicularis oculi muscle. In type II (20%, 4/20 sides), the single AN was formed by buccal branch plexus and zygomatic branch plexus in the "Four Muscle Gap". In type III (60%, 12/20 sides), the AN had two branches in the "Four Muscle Gap". (2) The three types AN passed inferior to the support ligament at the suborbital part, and then transversed medial to the support ligament at the medial canthus, along the vessels of medial canthus. (3) The branch of AN enters the depressor supercilii or procerus 2.19 to 4.28 mm above the medial canthus ligament. The backward branch enters the levator labii superioris alaeque nasi 6.89 to 9.38 mm below the medial canthus ligament. CONCLUSIONS: The approach of denervation surgery for AN should be performed medial to the support ligation, between 2.19 mm above the medial canthus and 6.89 mm below the medial canthus. PMID- 20737955 TI - [Rectification of nasal deviation with open operation]. AB - OBJECTIVE: To investigate the quantitative classification and measuring method of nasal deviation and effectiveness of Septo-rhinoplasty for nasal deviation. METHOD: Fourteen selected cases of nasal deviation were rectified by Septo rhinoplasty. The deviated parameters were measured both before and after operation. RESULT: The deviated parameter after operation was (2.75 +/- 1.67) mm in 14 cases. The preoperative parameter was (5.05 +/- 2.03) mm. The difference in changes of deviated parameters before and after operation was significant (P < 0.01). Satisfactory results were achieved after operation in 12 cases. The rate of good cosmetic outcome was 85.71%. CONCLUSION: Both quantitative grading standard of nasal deviation and measurement of deviation value contribute to clinical diagnosis and medical records. The Septo-rhinoplasty is effective for nasal deviation. PMID- 20737956 TI - [Therapy for olfactory disorder associated with URTI along with nasal and accessory nasal diseases]. AB - OBJECTIVE: To observe the effect of intranasal jet nebulizing inhalation with budesonide suspension on 20 patients with olfactory disorder due to upper respiratory tract infections (URTI) or nasal and accessory nasal diseases. METHOD: We tested the twenty patients with upper respiratory infection, naso sinusitis, allergic rhinitis, olfactory cleft disease induced olfactory loss by medical history, physical examination, olfactory tests and medical imaging. Budesonide suspension doses of 1 mg daily was administered by means of intranasal nebulization for 15 days. Olfactory function was assessed by T&T Olfactometry and olfactory event-related potentials before and after treatment, and only T&T Olfactometry was used after every 5 times for inhalation of budesonide. RESULT: Of the patients with olfactory disorder, olfactory function was recovered in 90% after the course of treatment, including cured in 25%, improved in 50%, and slightly improved in 15%. And apparent effect was observed to appeared mostly after nebulizing inhalation for 10 times. CONCLUSION: The above findings suggest that intranasal nebulizing inhalation with budesonide may be an effective therapy in the treatment of URTI-related or nasal and accessory nasal diseases related olfactory disorder. It is worth using the therapy. PMID- 20737957 TI - [Clinical analysis of chronic rhinosinusitis in children]. AB - OBJECTIVE: To determine the ideal treatment for the pediatric patients with chronic rhinosinusitis. METHOD: Eighty-eight patients (aged 5-14 years) were divided into group A, B, C. In group A, 30 cases (60 sides) who had chronic rhinosinusitis without nasal polyps were treated systemically with medicine. In group B, 31 cases (62 sides) were chronic rhinosinusitis without nasal polyps and accompanied by adenoid vegetation and/or chronic tonsillitis,and were systemically treated with a combined therapy of medicine and adenoidectomy and/or tonsillectomy. In group C, 27 cases (54 sides) were chronic rhinosinusitis with nasal polyps,and were treated systemically with medicine and endoscopic sinus surgery. RESULT: All patients were followed up for 12-18 months, with an average of 16 months. In group A, 48 sides were cured, 8 sides improved and 4 sides showed no effect. In group B, 46 sides were cured, 10 sides improved and 6 sides showed no effect. In group C, 40 sides were cured, 8 sides improved and 6 sides showed no effect. There were no significant differences in the efficacy among the three groups (P > 0.05). CONCLUSION: Systemic medical treatment should be the first choice for chronic rhinosinusitis in children. Children with adenoid vegetation and/or chronic tonsillitis are basically treated with systemic medicine combined with adenoidectomy and/or tonsillectomy. Administration of medicine before and after the endoscopic surgery is more efficient for chronic rhinosinusitis with nasal polyps in children. PMID- 20737958 TI - [Study of phosphorylated ERK1/2 on nasal polyps]. AB - OBJECTIVE: To study the expression of phosphorylated extracellular regulator kinase (ERK1/2) on nasal polyps. METHOD: The immunohistochemistry and Western blot were used to study the phosphorylation of ERK1/2 on the normal nasal mucosa and nasal polyps. RESULT: The phosphorylated ERK1/2 was mainly expressed on the hyperplastic epithelium, inflammatory cells, glandular epithelium and endothelium of nasal polyps by immunohistochemistry, which was much stronger on nasal polyps than that of normal mucosa. The expression of phosphorylated ERK1/2 was 4.2 times than that of normal mucosa. CONCLUSION: The study indicated that the phosphorylation of ERK1/2 might play an important role on the occurrence and progression of nasal polyps. PMID- 20737959 TI - [Allergic fungal rhinosinusitis: one case and literature review]. AB - OBJECTIVE: To investigate the presentation and the management of allergic fungal rhinosinusitis (AFRS). METHOD: One case of AFRS was reported and the relevant literatures were reviewed. CT scan showed high-attenuation like "cloud and mist", Charcot-Leyden crystals and fungal hyphae were found in nasal smear. RESULT: The patient removed after a combined therapy of endoscopic sinus surgery, steroids and local antifungal drugs. CONCLUSION: The diagnosis of AFRS depends on history, the characteristics of CT scanning, pathology, mycologic and immunologic test. The management of surgery, systemic immunotherapy, local antifungal drugs and longer follow up is very important. PMID- 20737960 TI - [Expression and DNA binding activity of NF-kappaB p50 in nasal mucosal tissue of seasonal allergic rhinitis]. AB - OBJECTIVE: To study the expression and activation of p50 subunit of nuclear factor-kappa B(NF-kappaB) in mucosa of seasonal allergic rhinitis. METHOD: The expression of p50 subunit of NF-kappaB in the mucosa from 16 patients (6 patients with symptom, 10 patients without symptom)and 10 normal subjects were detected by immunohistochemistry. The activation of DNA-binding proteins which was labeled with 32P-radiolabeled oligonucleotide probe for NF-kappaB was detected with electrophoretic mobility shift assays(EMSA) in mucosa. RESULT: The expression of p50 subunit of NF-kappaB was observed in the nasal mucosa of SAR and normal samples. The expression of p50 subunit of NF-kappaB was positive in the cytoplasm and some nuclei of the mucosal epithelia, inflammatory cells, glandular epithelia, and vascular endothelia in nasal mucosa. The Rate of nucleus positive staining of p50 was (41.83 +/- 4.43)% and(37.19 +/- 3.93)% in SAR with symptom and SAR without symptom patients,respectively. There was no significant difference (P > 0.05). The Rate of nucleus positive staining of p50 in nasal mucosa of normal samples was (8.89 +/- 1.32)%. The difference of p50 subunit of NF-kappaB expression between SAR group and normal group was statistically significant (P < 0.01). The DNA-binding proteins activity of samples from patients with seasonal allergic rhinitis was stronger than that in normal subjects (P < 0.05). CONCLUSION: p50 subunit of NF-kappaB was activated in healthy nasal mucosa to some extent. The expression and DNA-binding proteins activity of p50 subunit of NF-kappaB was enhanced in seasonal allergic rhinitis. It indicated that p50 subunit of NF-kappaB may be involved in nasal mucosa physiological function and may have an important role in maintaining the chronic inflammation in seasonal allergic rhinitis. PMID- 20737961 TI - [Relationship between adult craniofacial structures and development of obstructive sleep apnea-hypopnea syndrome]. AB - OBJECTIVE: To explore the influence of adult craniofacial structures on obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: This study compared the measurements of the height, body weight,neck circumference, the mallampati oropharyngeal score grading, thyromental distance, thyromental angle, lobule mental distance, mental-lower lip distance of 50 patients with OSAHS with those of 50 controls. RESULT: Statistical findings showed that OSAHS patients were different from controls in the following ways: (1) higher neck circumference; (2) larger thyromental angle; (3) higher Mallampati scores; (4) higher body mass index; (5) shorter mental-lower lip distance. CONCLUSION: A crowded posterior oropharynx and a steep thyromental plane are associated with OSAHS. The adult craniofacial structures of bony and soft tissue determine the dimension of upper airway during sleep andpaly an important role in the development of OSAHS. PMID- 20737962 TI - [Nasal endoscopic-assisted surgery for adults cleft palate repair]. AB - OBJECTIVE: To evaluate the efficacy of nasal endoscopic-assisted surgery for adults cleft palate repair. METHOD: We designed and made two suitable nasal mucoperiosteal flaps in nasal cavities, then released the nasal mucoperiosteal flaps to the level of hard palate and sewed up two flaps on the midline of oral cavity to repair the nasal side of cleft palate. RESULT: Nine of 11 patients were healed after three months following-up. The bilateral palatal mucoperiosteal flap were separated in the front of hard palate in 2 patients, however they were not perforated due to well-healing of nasal mucoperiosteal flaps and second stage surgery was not necessary. CONCLUSION: The cleft palate could be repaired using the tensionless nasal mucoperiosteal flap with good blood supply, and'procedures could be carried out under nasal endoscopy. Endoscopic-assisted surgery for cleft palate repair was simple to perform, and its effect was satisfactory. PMID- 20737963 TI - [Clinicopathologic features of respiratory epithelial adenomatoid hamartoma of bilateral olfactory clefts]. AB - OBJECTIVE: To describe five rare cases of bilateral olfactory clefts respiratory epithelial adenomatoid hamartoma (REAH), and investigate the clinicopathologic features in REAH. METHOD: Five cases with REAH were reported and the relevant literatures were reviewed. All the cases were confirmed by pathology. RESULT: The chief complaint in 4 cases when visited was nasal obstruction and rhinorrhea, with or without hyposmia and headache. Another was discomfortable of head-facial region, sometimes with pus discharge and blood in nasal discharge. Polypoid neoplasms can be seen in nasal meatus of the 5 cases. Endoscopic sinus surgery was utilized to eliminate foci in 5 cases. All REAH foci located in bilateral olfactory clefts areas, four of which appeared polypoid changes,one appeared obvious inflammatory edema. All of them presented as wide-based lesion with tenacious quality compared to polyps. Histologically, these lesions were characterized by a glandular proliferation lined by ciliated respiratory epithelium originated from the surface epithelium, and the glands surround into round or oval, with various sizes and separated by stromal tissue. CONCLUSION: It is possible to continue developing after operation, if REAH is not completely resected. Complete resection of lesions is the key to treatment success for this entity in endoscopic sinus surgery. Although REAH arising from the rhino sinusal region is very rare, rhinolaryngologists must know this entity in order to differentiate it from inverted papilloma and adenocarcinoma. PMID- 20737964 TI - [Comparison of the nasal sinus development of children with or without sinusitis in Yunnan province]. AB - OBJECTIVE: To investigate the nasal sinus development and discuss the relation between sinusitis and nasal development. METHOD: One thousand seven hundred and five healthy children and 1424 children with sinusitis were selected randomly. All children underwent naso sinus computer tomography. Sagittal, coronal and transverse diameters of all sinuses were measured and statistically analyzed. RESULT: The measured sinus diameters of children with sinusitis were longer than that of healthy children (P < 0.01). Pearson analyses revealed a low correlation of age and the history of sinusitis (P < 0.01), and no correlation of gender and the history of sinusitis. There was moderate to high consistency between clinical diagnosis and nasal CT results about sinusitis (P < 0.01). CONCLUSION: These results demonstrated that the differences of sinus development exist between the healthy children and children with sinusitis, and the sinus development in children with sinusitis were better than that of healthy children. PMID- 20737965 TI - The nature and objectives of intensive care nursing. PMID- 20737966 TI - The intensive care unit: its characteristics and social relationship. PMID- 20737967 TI - Planning and administering the intensive care unit. PMID- 20737968 TI - The multiphasic human-to-human monitor (ICU model). Nursing observation in the intensive care unit. PMID- 20737969 TI - Psychological hazards of the intensive care unit. Nursing care aspects. AB - The intensive care unit provides a variety of psychiatric complications. Their physiologic concomitants can endanger life. The special environment of these units can be quite stressful to patients and staff. Patients in the open-heart recovery room have a high incidence of delirium thought to be related to the sleep deprivation and sensory monotony of these rooms. Suggestions are made to improve rooming and nursing procedures to reduce these hazards. A preoperative orientation will also help to reduce anxiety postoperatively. The coronary care unit has similar problems. Nurses must learn to reduce the anxiety produced by frequent emergencies and deaths. The nursing staffs in these units have special problems produced by the unique responsibilities they must assume there. The charge nurse and medical staff must make special provision to reduce tension and maintain morale. PMID- 20737970 TI - Nursing assessment of circulatory function. AB - Assessment of circulatory function demands of the nurse skilled observation integrated with knowledge and understanding. Appreciation of normal physiology allows the nurse to make sound evaluations and judgments. Because of her increased understanding, the nurse brings security to the patient, family, and physician, as well as herself, by her ability to anticipate and often prevent catastrbphic circulatory events, and thus actively contributes to the survival of patients. PMID- 20737971 TI - Assessment and maintenance of adequate respiration. AB - In order to make an adequate assessment of and to maintain respiratory function in patients in the intensive care unit, the nursing responsibilities include: (1) Recognition of physiologic and psychologic changes related to respiratory disease. (2) Appreciation of individual reactions to respiratory stressful situations, particularly during periods of hypoxemia and hypercapnia. (3) Awareness that behavioral changes related to changes in respiratory physiology are reversible with corrective respiratory therapy. (4) Skill in implementing the prescribed medical therapy quickly and efficiently and ability to evaluate the patient's response. (5) Assessment and appropriate involvement of the family as an essential factor in the plan for care. PMID- 20737972 TI - Nursing observations of fluid imbalance. PMID- 20737973 TI - A program for inservice education in an intensive coronary care unit. AB - Education of the nurse for coronary care includes training in external cardiac massage, proper ventilation techniques, monitoring techniques, a working knowledge of electrocardiographic arrhythmias, artifacts and precatastrophic situations. An intensive care unit nurse must keep in mind that the monitoring equipment only enhances her power of observation, and that no degree of electronic superiority can ever replace a nurse's interpretation of her observation or her vigilance and skill. She must be the ever faithful sentinel constantly alert to the slightest change in these critically ill patients. The development and activation of an educational program that provides an adequate background of knowledge and an opportunity for the mastery of the techniques utilized in the medical therapy are essential for the achievement of the goal of intensive care-the reduction of morbidity and mortality and the preservation of a functional human life. PMID- 20737974 TI - What the nursing service director expects. AB - Nursing education has been taking some progressive steps in preparing new graduates. The young graduate can give good physical care and sensitive emotional support, particularly if she is encouraged to do so. We need more effective leadership on many of our nursing units and new approaches to providing continuity of nursing care among all personnel on various shifts. The high turnover rates are exhausting to those who are trying to maintain the continuity of nursing care. Short-term employment makes it very difficult and costly to provide the guidance, encouragement, and assistance that new graduates have the right to expect. I believe, however, that the employer also has the right to expect employees to select a position carefully and then plan to invest of themselves in the position for a minimum of one year. Nursing administrators need to be better prepared educationally to provide the organization and climate for effective nursing care. Nursing service and nursing education need each other and must explore every means of communicating with each other about our common goal of improved nursing care. PMID- 20737975 TI - Expectations of the staff nurse in nursing practice. PMID- 20737977 TI - The nurse-patient relationship. A monologue. PMID- 20737976 TI - Strains in the nurse-doctor relationship. AB - Many problems and conflicts between nurses and doctors in the hospital stem from the organizational structure of the hospital rather than from the personalities of the individuals involved. Nurses often assert the latter. Understanding these conflicts requires that they be examined in terms of the organizational context within which they occur. To understand the modern American hospital it is useful to view its development. Private practitioners who at one time had cared for patients in their homes shifted the locus of care to the hospital as medical care became more complex in the latter half of the nineteenth century. Three selected aspects of hospital structure that are seen as sources of strain for nurses in their relationship with doctors are: (1) Doctors do not see themselves as full fledged members of the hospital organization. While nurses, who do, feel bound by the operating rules of the hospital, doctors tend to operate as free agents. There is probably little that nurses can do to reduce this source of strain. (2) The hospital has two lines of authority, administrative and medical, unlike most large-scale organizations which have only one. Nurses are in the former while doctors are in the latter hierarchy. The "influence relationship" between nurses and doctors is largely unarticulated; informally "negotiated" patterns prevail. Nurses can be more aggressive in attempting to develop institutional patterns that are mutually satisfactory to themselves and to doctors and that meet the needs of the hospital as a whole. (3) In the absence of a functioning health team nurses have assumed responsibility, without the requisite authority, for the coordination of patient care. Although this action is for the immediate benefit of patients nurses should realize that it also tends to retard the development of needed organizational changes in the hospital. Nurses generally accept the possibility of changing the personality structure of an individual. They should be aware that in an analogous fashion organizations can change their structure. There is a dire need for hospital nurses to participate more actively and creatively in activities that can alter the existing hospital structures so that health personnel can more effectively bring the benefits of modern medical science and technology to their patients. PMID- 20737978 TI - Nursing practice: a student's perspective. PMID- 20737979 TI - Preparing for unexpected responsibilities. PMID- 20737980 TI - The supportive role of the nurse in relation to health service workers. PMID- 20737981 TI - Emerging nursing techniques: venipuncture. AB - Venipuncture is a medical function delegated to professional nurses in some states. Each nurse must ascertain if the state in which she practices considers this a legal nursing function, and if the institution in which she is employed permits nurses to perform venipunctures. Adequate instruction and supervised practice in the technique is mandatory before a nurse performs the procedure on a patient. Psychological and physical preparation of the patient is necessary prior to a venipuncture as it is usually attended by some degree of anxiety and some restriction of activity if an infusion is ordered. Knowledge of the location, structure, and characteristics of arteries and veins is essential for patient safety. Aberrant arteries increase the hazard of venipunctures. Recognition of pathologic conditions that would preclude the use of a vein or extremity for needle insertion is imperative. The best site for a venipuncture if an infusion is to be administered is in the forearm; the least desirable site is the foot and ankle. Thrombophlebitis invariably develops to some degree whenever a needle remains in a vein for many hours, but its severity increases when a foot or ankle vein is used. The patient receiving an infusion requires nursing care determined by his particular condition, his reaction to the therapy, and the degree of immobility effected by the presence of the needle in his vein. Frequent observation of the patient and the infusion setup is essential. Many hours of practice are needed before one feels confident in performing a venipuncture. Success is contingent upon the triad of skill, knowledge, and a sensitivity to the patient who is to receive the venipuncture. PMID- 20737982 TI - Two new diuretics. PMID- 20737983 TI - Infectiousness of tuberculosis. PMID- 20737984 TI - Pulmonary consumption: its dietetic management. 1892. PMID- 20737985 TI - Wealth and happiness never seem to add up. PMID- 20737986 TI - Current development of saliva/oral fluid-based diagnostics. AB - Saliva can be easily obtained in medical and non-medical settings, and contains numerous bio-molecules, including those typically found in serum for disease detection and monitoring. In the past two decades, the achievements of high throughput approaches afforded by biotechnology and nanotechnology allow for disease-specific salivary biomarker discovery and establishment of rapid, multiplex, and miniaturized analytical assays. These developments have dramatically advanced saliva-based diagnostics. In this review, we discuss the current consensus on development of saliva/oral fluid-based diagnostics and provide a summary of recent research advancements of the Texas-Kentucky Saliva Diagnostics Consortium. In the foreseeable future, current research on saliva based diagnostic methods could revolutionize health care. PMID- 20737987 TI - Weekly monitoring of the water fluoride content in a fluoridated metropolitan city--results after 1 year. AB - It continues to be the goal of the United States Department of Health and Human Services to fluoridate community water supplies to prevent dental caries. In Houston, Texas, where community water is assumed to contain in the range of 0.7 1.2 ppm fluoride, water samples were taken from the same source on approximately a weekly basis over a period of 52 weeks. The purpose of this study was to determine the extent of fluctuation of water fluoride concentration in these samples. Water fluoride analysis with an ion-specific electrode and millivolt meter of the data set showed a range of 0.33 to 1.00 ppm fluoride, with a mean of 0.70 ppm and a standard deviation of 0.15. This wide range of fluoride concentrations may create a risk for fluorosis in pediatric patients who are prescribed dietary fluoride supplements. PMID- 20737989 TI - Value for your profession. Get the best deal on your office lease. PMID- 20737988 TI - Dental unit waterline contamination--a review. AB - Manufacturers of dental units have responded positively to the challenge from the American Dental Association (ADA) and the subsequent guidelines issued by the Centers for Disease Control and Prevention (CDC) to deliver patient treatment water that is at least as pure as drinking water. Dental units are now routinely manufactured with anti-retraction devices that are designed to control oral fluids from being aspirated into the lines during treatment and many units have water systems that isolate source water from municipal water supply. The dental industry has also produced an array of devices and cleaning/disinfectant products to further facilitate the use of clean patient treatment water. Products that claim disinfectant efficacy must be registered with the Environmental Protection Agency (EPA). If they are not EPA-registered, they can be labeled as waterline cleaners only. Waterline treatment devices that are sold separately and require connection to dental units must be registered with the Food and Drug Administration (FDA) as medical devices. Patient treatment water quality can be monitored by using in-office chairside kits or through commercial laboratory services. PMID- 20737990 TI - Oral and maxillofacial pathology case of the month. Atypical histiocytic granuloma (pseudolymphoma). PMID- 20737991 TI - The Clark revolving dental cabinet. PMID- 20737992 TI - The 2010 SDSMA alliance quality of service award. PMID- 20737993 TI - Health system reform and the SDSMA's work for better health. PMID- 20737994 TI - The sharp point of care: quality, safety and Creutzfeldt-Jakob disease. PMID- 20737995 TI - Systemic affects of methamphetamine use. AB - Methamphetamine (meth) is the most widely used illegal stimulant in the United States and is especially prevalent in Midwestern states. The sense of euphoria caused by the drug, the ease of manufacturing and the relatively low cost make it a drug of choice for many. The broad range of systemic effects potentially caused by the use of this drug is wide reaching and can vary in degree and presentation from patient to patient. Abnormalities include cardiac and pulmonary disorders as well as observable integumentary problems, psychoses, CNS disturbances, problems associated with immunity and constitutional signs and symptoms. Health care providers need to be vigilant in their efforts to identify patients who may be users of meth and to identify any subtle abnormal findings that may be indicative of significant underlying systemic pathology. Questionnaires like the RAFFT (Relax, Alone, Forget, Friends, Trouble) and the MINI (Mini-International Neuropsychiatric Interview) can be helpful in identifying substance abuse disorders in patients. PMID- 20737996 TI - Dronedarone: where does it fit in the treatment of atrial fibrillation? PMID- 20737997 TI - Quality focus: physician consortium for performance improvement. PMID- 20737998 TI - Chemo fog: cancer chemotherapy-related cognitive impairment. Preface. PMID- 20737999 TI - Short introduction and history. AB - If one does a MEDLINE search using as keywords chemo fog or chemo brain or their hyphenated equivalents, fewer than 30 'hits' appear. The oldest dates back to 2003. This small number of hits in some way captures one aspect of the current state of the phenomenon (or phenomena). In contrast, if one does the search using 'cognitive x cancer x chemotherapy', hundreds more hits appear. This in some way captures another aspect of the phenomenon.It is both little-known and well-known. To go a step further, some data suggest that it is one of the most common adverse effects of chemotherapy, other data suggest that it does not exist. Even its name (or lack thereof) is still unsettled. Yet, patients consistently report it. This chapter introduces the reader to the fascinating and complex challenges-to patients, healthcare providers, basic scientists, employers, insurers and others inherent in this topic and the current state of knowledge about it. PMID- 20738000 TI - Patient's perspective. AB - An unknown, but significant subgroup (perhaps the majority), of patients who have undergone chemotherapy treatment for their cancer report a subsequent decline in cognitive performance (e.g., difficulty in balancing a checkbook; forgetting or mixing up names of friends or relatives, etc.). The condition has been termed chemo fog, chemo brain, or some similar term to reflect the fact that the symptoms are usually difficult to describe and involve domains of cognition such as attention, concentration, memory, speed of information processing, multitasking, or ability to organize information. The deficits are reported to persist. The magnitude of the negative impact on quality of life depends, as does the condition itself, on multiple and varied factors. This chapter relates the experience of one patient. PMID- 20738001 TI - Oncology nurse's perspective. AB - Oncology nurses are increasingly recognizing the importance of chemotherapy related cognitive impairment (CRCI) in the lives of their patients and are contributing to the state of the knowledge in this field of study. The Oncology Nursing Society has included treatment related changes in cognitive function as a priority in the 2009-2013 "Oncology Nursing Society Research Agenda and Priorities". Related educational programming has been included at national nursing symposia. A brief review of some research conducted by oncology nurses is described. PMID- 20738002 TI - Oncology pharmacist's perspective. AB - The pharmacist's role places them squarely on the front line of the benefit-risk analysis of drug administration. They are often the ones who explain the drugs to the patients and, in the process, supply part of the information about which patients must make an informed decision about their chemotherapy. This chapter presents the reflections of one oncology/pain specialty pharmacist. PMID- 20738003 TI - The impact of chemo brain on the patient with a high-grade glioma. AB - Health-related quality of life for patients with high-grade gliomas has always been poor. The multiple insults to the brain-tumor existence and surgical procedures, irradiation, the level of stress and anxiety suffered and the adjuvant medications--steroids and anti-convulsants, all combine to diminish their health-related quality of life. Prior to the development of chemotherapy agents capable of penetrating the blood brain barrier, prognosis was 6 to 18 months. Life expectancy was short and there was little time to address the health related quality of life. The newer agents have served to extend life, but have added another condition to the existing poor health-related quality of life, i.e., chemo brain. Chemo brain affects all cognitive function. The patients have great difficulty processing information. They have reduced attentional and concentration capability and cannot learn new information. The overall impact on their lives renders them unemployable and places a great burden on their families and on society. This chapter provides an overview of the patient experience and the burden placed on their families and on society. PMID- 20738004 TI - Neurocognitive effects of childhood cancer treatment. AB - With changes in the approach to treatment of childhood leukemia and brain tumors, more children are surviving into adulthood. With this increase in long-term survivorship, long-term neurocognitive side effects have emerged. Research has shown that these survivors suffer a variety of neurocognitive effects including changes in attention span, concentration, school performance and executive functioning. Researchers continue to study changes in therapy with the hopes of decreasing these long-term side effects without compromising overall survival rates. Others have focused on developing adaptations to how these children learn, equipping them with tools to better cope with learning deficits. Still, others have looked into pharmacological interventions. This chapter will discuss the historical course of therapy for both leukemia and brain tumors. In addition, it will highlight how late effect studies guided changes in therapeutic approach for both childhood leukemias and brain tumors. This chapter will also discuss specific neurocognitive effects from childhood cancer treatment, challenges in research methodologies as well as current pharmacological and nonpharmacological interventions for affected childhood cancer survivors. PMID- 20738005 TI - The economic burden. AB - Not only is chemo fog a troublesome medical problem for the sufferers, but in addition it is the source of nearly $300 million in direct and indirect expense in the United States alone each year. And since it often persists for extended periods of time, the indirect costs, which stem mainly from lost productivity, continue to accumulate with another nearly $250 million added to the overall cost each year. This is not the highest economic burden for common diseases, but it is a significant amount that could be mostly avoided if biomedical scientists were to find a means to employ safer chemotherapeutic agents. PMID- 20738006 TI - Designing conceptual model-based research in chemotherapy-related changes in cognitive function. AB - Any well-designed biobehavioral research will begin with a comprehensive understanding and stated conceptual approach to the issue to be studied and the hypotheses to be tested. Following this conceptual orientation, the research protocol can be designed. This chapter reviews these factors to guide conceptual model-based research of chemotherapy-related changes in cognitive function. PMID- 20738007 TI - Neuropsychologic testing for chemotherapy-related cognitive impairment. AB - No standard has been established for neuropsychologic testing to identify and quantify chemotherapy-related cognitive impairment (CRCI). A number of issues exist related to the complexity of the phenomenon and lack of correlation between standardized objective tests and subjective tests by patient self-report. Review of the issues related to current neuropsychologic tests used to evaluate CRCI provides support for qualitative examination of patients' lived experience in order to guide the development of more accurate tests. PMID- 20738008 TI - Imaging as a means of studying chemotherapy-related cognitive impairment. AB - The chemotherapy-related cognitive impairment (chemo fog/chemo brain) that is reported by many cancer patients is supported to varying degrees primarily by evidence from prospective and retrospective clinical studies. However, the inherent difficulty in conducting such trials (including ethical issues of placebo-controlled designs), the fact that the cognitive impairment is characteristically subtle and that the patients might be able to compensate for their deficits during testing, gives rise to questions about the degree and the extent of the problem-and indeed even if there is a problem. Neuroimaging techniques might offer additional insight. This chapter is a succinct summary of a more expanded review of the relatively few such studies. PMID- 20738009 TI - Chemotherapy associated central nervous system damage. AB - Chemotherapy is commonly associated with harmful effects to multiple organ systems, including the central nervous system (CNS). Neurotoxicity may manifest as both acute and delayed complications, which is particularly a concern for long term survivors. Patients may experience a wide range of neurotoxic syndromes, ranging from neuro-vascular complications and focal neurological deficits to generalized neurological decline with cognitive impairment, cortical atrophy and white matter abnormalities. Along with the use of more aggressive and combined treatment modalities and prolonged survival of cancer patients, neurological complications have been observed with increasing frequency. The mechanisms by which cancer therapy, including chemotherapy and radiation, result in neurological complications, have been poorly understood. Recent studies have now started to unravel the cell-biological basis for commonly seen neurotoxic syndromes and have provided compelling explanations for delayed neurological complications, such as cognitive decline, progressive myelin disruption and brain atrophy. PMID- 20738010 TI - Is systemic anti-cancer therapy neurotoxic? Does chemo brain exist? And should we rename it? AB - The existence of chemo brain has become almost universally accepted, although many details of the concept are controversial. Data about the different types of cognitive impairment and their duration are not always consistent in the literature. We still do not know which cytotoxic agents are responsible, which characteristics make patients vulnerableand which biologic mechanisms are involved. This chapter reviews the recent literature and provides an actualized definition of chemo brain, including recent functional imaging data and discusses its controversial aspects. Potential underlying mechanisms and their future possible clinical applications in the prevention and treatment of chemo brain are also discussed. These issues are of clinical importance given the prevalence of breast carcinoma, the increased use of chemotherapy as adjuvant therapy, the increasing use of more aggressive dosing schedules and the increasing survival rates. Better-designed future trials should lead to a better definition and understanding of chemo brain and to future therapies. PMID- 20738011 TI - Evaluation of multiple neurotoxic outcomes in cancer chemotherapy. AB - Although it is now clear that cognitive dysfunction is a common accompaniment of cancer chemotherapy, its implications await further research and direction. Most of the clinical research relies on standard neuropsychological tests that were developed to diagnose stable traits. Cognitive dysfunction in patients undergoing treatment varies with time, however. Its dimensions will vary during the course of treatment, which generally consists of cycles of drug administration followed by recovery periods. To effectively determine the connection between chemotherapy and cognitive function requires neuropsychological tests based on performance, so that they can be administered repeatedly at specified times during the entire course of treatment and beyond. A number of computerized test batteries, many of which have been developed for environmental neurotoxicology, are now available that fit such criteria. Moreover, cognitive impairment is only one aspect of chemotherapy-induced neurotoxicity. A full appreciation of its scope requires assessment of sensory functions such as vision, audition and somatosensory properties and assessment of motor function. A program of research based on animal models is also essential. Only with animal models is it possible to determine dose-response relationships and to couple behavioral with mechanistic indices such as neuroplasticity. Animal behavior models play a vital role in environmental toxicology because, from them, it is possible to derive some index of exposure that limits adverse effects. However, as in human testing, it is critical to choose situations whose properties remain stable over long periods of time so as to trace the time course of neurotoxicity. Schedule-controlled operant behavior offers the most promising source of animal models. PMID- 20738012 TI - Chemotherapy-related visual system toxicity. AB - Most, if not all, of the studies that report cognitive impairments in patients who have been treated with cancer chemotherapy also report deficits involving the visual system (e.g., visual-spatial function or visual memory). The visual system seems like a likely susceptible target of cytotoxic drugs. Therefore, some portion of the vision-related cognitive deficits ofchemo fog/chemo brain might result from a direct action of the drugs or from site/site interaction between effects on the visual system and other critical brain regions. This chapter is a succint summary of a more expanded review. PMID- 20738013 TI - The possible role of cytokines in chemotherapy-induced cognitive deficits. AB - roinflammatory cytokines play a significant role in the body's immune response to pathogens, including malignant cells. Proinflammatory cytokines are associated with tumor invasion and progressive disease and are released in response to many antineoplastic agents. Exogenous administration and endogenous production ofcytokines is related to a pattern of behaviors known as sickness behavior that has a significant impact on patients' quality of life. The behavioral patterns associated with sickness behavior include inability to concentrate and impaired learning. Identification of sequelae specific to individual cytokine activity provides novel targets for investigation. PMID- 20738014 TI - Pharmacokinetics of anti-cancer drugs used in breast cancer chemotherapy. AB - Pharmacokinetics of anticancer drugs used in breast cancer therapy are well established. This chapter reviews preclinical and clinical pharmacokinetics of the following drugs: cyclophosphamide, docetaxel, doxorubicin, 5-fluorouracil, methotrexate and tamoxifen. The absorption, distribution, metabolism and elimination of drugs are discussed in the context of breast cancer. The effect of age and menopause status on drug pharmacokinetics is evaluated. The important role of pharmacokinetic-pharmacodynamic modeling in understanding the phenomenon of chemo fog, memory deficit in breast cancer chemotherapy, is explored. PMID- 20738015 TI - Combination analysis. AB - This chapter describes quantitative methodology that is directed toward assessing interactions between a combination of agonist drugs that individually produce overtly similar effects. Drugs administered in combination may show exaggerated, reduced or predictable effects that are dependent on the specific drug pair and the doses of t h e constituents. The basisfor quantitating these unusual interactions is the concept of dose equivalence which, in turn, is determined from the individual drug dose-effect relations. A common analytical procedure that follows from dose equivalence uses a graph termed an isobologram. We present here an overview of the isobologram, its use and certain related methods that apply to classifying various drug interactions. PMID- 20738016 TI - Animal models. AB - As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits. PMID- 20738017 TI - Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. AB - Doxorubicin (ADRIAMYCIN, RUBEX) is a chemotherapeutic agent that is commonly administered to breast cancer patients in standard chemotherapy regimens. As true of all such therapeutic cytotoxic agents, it can damage normal, noncancerous cells and might affect biochemical processes in a manner that might lead to, or contribute to, chemotherapy-induced cognitive deficits when administered either alone or in combination with other agents. PMID- 20738018 TI - Effects of 5-FU. AB - 5-fluorouracil (5-FU) is a chemotherapeutical agent used to treat cancers including breast and colorectal. Working as an antimetabolite to prevent cell proliferation, it primarily inhibits the enzyme thymidylate synthase blocking the thymidine formation required for DNA synthesis. Although having a relatively short half-life (< 30 mins) it readily enters the brain by passive diffusion. Clinically, it is used both as a single agent or in combination with other chemotherapies and has been associated with the long-term side effects of cognitive impairment, known as "chemo brain" or "chemo fog" These accounts have come primarily from patients undergoing treatment for breast cancer who report symptoms including confusion and memory impairment, which can last for months to years. Psychometric studies of patients have suffered from confounding variables, which has led to the use of rodent models to assess the cognitive effects of this drug. Researchers have used behavioral and physiological tests including the Morris water maze, novel object location/recognition tests, shock motivated T maze, sensory gating and conditioning, to investigate the effect of this drug on cognition. The variety of cognitive tests and the difference in dosing and administration of 5-FU has led to varied results, possibly due to the different brain regions associated with each test and the subtlety of the drug's effect, but overall these studies indicates that 5-FU has a negative effect on memory, executive function and sensory gating. 5-FU has also been demonstrated to have biochemical and structural changes on specific regions of the brain. Evidence shows it can induce apoptosis and depress cell proliferation in the neurogenic regions of the adult brain including the sub granular zone (SGZ) within the hippocampus and in oligodendrocyte precursor populations within white matter tracts. Furthermore, investigations indicate levels ofdoublecortin, a marker for newly formed neurons and brain derived neurotrophic factor, a cell survival modulator, are also reduced by 5-FU in the SGZ. Thus, 5-FU appears to have a lasting negative impact on cognition and to affect cellular and biochemical markers in various brain regions. Further work is needed to understand the exact mechanisms involved and to devise strategies for the prevention or recovery from these symptoms. PMID- 20738019 TI - Future directions. AB - The chapters of this book summarize much of what has been done and reported regarding cancer chemotherapy-related cognitive impairment. In this chapter, we point out some future directions for investigation. PMID- 20738020 TI - [Mitochondrial arteriopathy as a cause of spontaneous dissection of cerebral arteries]. AB - The vascular wall weakness caused by dysplastic alterations predisposes to the spontaneous dissection of cerebral arteries. The authors hypothesized for the first time that dysplasia might be the result of mitochondrial cytopathy. To test this hypothesis, the muscle biopsy was conducted in 3 male patients, aged 30-38 years, with the spontaneous dissection of the internal carotid (2) and posterior cerebral (1) arteries. Clinically dissections manifested by ischemic stroke (2) or the peripheral paresis of the hypoglossal nerve (1). The morphological study of fresh frozen sections of muscle by modified Gomori trichrome method revealed ragged-red fibers The histochemical study showed the severe decrease of the stain on succinate dehydrogenase and cytochrome-c-oxidase as well as the focal intensive staining of peripheral regions of muscle fibers. The complex of found changes is characteristic for a mitochondrial pathology. No patients had A3243G tRNA gene mutation, the most common mutation for MELAS. The serum lactate level was elevated only in one patient. We suggest that the mitochondrial disorder occurs not only in muscle, but also in cerebral artery wall--mitochondrial arteriopathy, which predisposes to spontaneous cerebral artery dissection. PMID- 20738021 TI - [Algorithm of management of patients in the acute period of ischemic stroke]. AB - On the basis of the research on clinical and prognostic characteristics of the acute period of ischemic stroke, the author has created an algorithm of activities during the first 24 h of the disease. It allows to manage the relocation of the patient in a hospital and to carry out consultative, medical and preventive measures. A software package for optimization the process of decision taking in the management of these patients is suggested. PMID- 20738022 TI - [Computer tomographic and laboratory predictors of clinical outcomes of acute ischemic stroke patients after the systemic thrombolytic therapy]. AB - Today the systemic thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is the most effective treatment of ischemic stroke. We included 116 patients with stroke, 82 received rt-PA, 34 were enrolled to the control group. Median NIHSS score was 16,2 +/- 5,4 in the main group and 16,2 +/- 5,4 in the control group. The trial revealed the prognostic significance of some early CT sings of ischemic brain damage for the hemorrhagic transformation and functional outcomes to the 90th day. It was shown that hyperfibrinogenemia (over 450 mg/dl) might be a risk factor of the hemorrhagic transformation. The excess of segmental leukocytes over 78% might be a predictor of the lethal outcome. The initial activity of tissue plasminogen inhibitor (first type) over 11,65 IU/L might be a risk factor of the vascular reocclusion after successful thrombolysis. The analysis of characteristic curves of leukocyte elastase revealed the informativeness of its initial values in the prognosis of reocclusion and hemorrhagic transformation. PMID- 20738023 TI - [Passive tilting in patients in the acute period of cerebral stroke]. AB - Passive tilt table test is one of the methods of early rehabilitation in the most acute and acute periods of stroke. We included 36 patients with stroke: 17 patients underwent passive tilting using "Lojer 1445YH" (a main group), 19 patients underwent changing position with a functional bed (a control group) on days 1, 2, 3, 5, 7, 14 and 21 after the onset of disease. Some patients were intolerant to passive tilting due to decreasing of systolic blood pressure to more than 20 mm Hg in the first 48 h after stroke. Such patients presented inadequate autonomic tests, had severe neurological deficit on the NIHSS and low heart rate variability (SDNN (standart deviation NN intervals): 19,4 +/- 4,3 ms vs 31,8 +/- 12,6 ms; TP (total power): 483,4 +/- 177,7 ms2 vs 1227,1 +/- 865,8 ms2; p< or =0,05). At the end of the first week after stroke, patients from the main group had higher indices of heart rate variability compared with the control group. Functional outcomes on the Barthel Index and the modified Rankin Scale were better in the main group as well at the 14th day, the between-group difference being the most marked at the 21st day. Passive tilting may be used as one of the methods of early rehabilitation that facilitates abilities of patients and improves functional outcomes provided a careful monitoring of health condition and blood pressure of a patient during the session. PMID- 20738024 TI - [Endogenous intoxication and compensatory reactions in the restoration period of ischemic stroke]. AB - An aim of the study was to assess the severity of the syndrome of nonspecific metabolic endogenous intoxication (EI) and characteristics of compensatory reaction of serum albumin (SA) in patients in the early restoration period (4-5 months) of ischemic stroke (II). We measured levels of middle-sized molecules (MSM) and malonic dialdehyde (MDA) and determined parameters of functional activity of SA in 30 patients (mean age 69 +/- 8 years) after the first II and in 17 age- and sex-matched healthy people. Neurological deficit and functional restoration of patients were assessed with the NIHSS and Barthel index. The increase of MSM and MDA concentrations was found in 98% and 88% patients, respectively, as compared to healthy people (p<0,01). These metabolic disturbances were associated with the formation of EI and caused functional structural changes of SA molecules. The correlation between changes of effective concentrations of SA and MDA was characteristic of the group of patients with II. The increase of total SA concentration was found in 87% of cases compared to controls (p<0,01) that indicated the manifestation of compensatory reaction of SA in response to EI. The decrease of all SA parameters, including the total concentration, was noted in 13% of patients and was associated with the decompensatory reaction to SA. The rehabilitation of CNS dysfunctions was associated with the undamaged SA compensatory reaction. The functional-structural changes of SA molecules in patients in the restoration period of II may lead to the changes in drug disposition, i.e. pharmacokinetics and pharmacodynamics, thus reducing possibilities of rehabilitation therapy. PMID- 20738025 TI - [Interaction effect of serotonin transporter gene and brain-derived neurotrophic factor on the platelet serotonin content in stroke patients]. AB - Platelet serotonin content in patients in the acute period of stroke is an important index of clinical changes during the post stroke period as well as a predictor of development of mental disorders. We studied the association between two polymorphisms (5-HTTLPR and Val66Met BDNF) and the platelet serotonin content in 47 patients with stroke. We also investigated the moderating effect of genetic variants on the association between platelet serotonin content and development of affective and anxiety disorders in stroke patients in the acute period of stroke. The interaction effect of two polymorphisms on levels of platelet serotonin was found. The lowest level was observed in patients with the diplotype LL*ValVal, the highest level--in the group of patients with the LL genotype and genotypes containing at least one copy of a Met allele. No moderating effect of genetic variants on the relationship between serotonin content and affective or anxiety disorder was found. PMID- 20738026 TI - [The new MRI pulse sequence: experience in emergency neuroradiology]. AB - The new pulse sequence (PS) has been obtained on MRI tomography Ellipse, B=0,15 and Biospec 70/30, B=7 T. The new pulse images of the brain combine features of FLAIR and its sensitivity to magnetic field heterogeneity. We named its PS as the T2 Fluid Attenuation Gradient Echo (T2 FLAGE). The T2 FLAGE characteristics of tissue contrast as well as its efficacy in detection of ICH have been assessed in 57 patients with acute stroke and in 16 experimental rats. The analysis of tissue contrast of lesions and normal brain structure has revealed the greater visibility of T2 FLAGE images compared to FLAIR. At the same time, the images sensitivity of magnetic field heterogeneity is retained. The ROC-analysis has shown that T2 FLAGE images are more effective in differential diagnosis of stroke type compared to FLAIR. PMID- 20738027 TI - [Poststroke fatigue]. PMID- 20738028 TI - Independence is essential. PMID- 20738029 TI - Sapropterin. Phenylketonuria: for a minority of patients. AB - Phenylketonuria and tetrahydrobiopterin deficiency are rare congenital disorders involving phenylalanine metabolism. If left untreated, they lead to severe mental retardation and neuropsychological problems. Management is based on a diet low in phenylalanine, started as early as possible. Sapropterin is a synthetic analogue of tetrahydrobiopterin, a cofactor for the enzyme that metabolises phenylalanine into tyrosine. Sapropterin is authorised in the European Union for some patients with phenylketonuria or tetrahydrobiopterin deficiency. In patients with phenylketonuria, the clinical evaluation of sapropterin is based on two randomised placebo-controlled trials lasting 6 to 10 weeks. One trial included 133 "responders" (about 20% of the patients initially enrolled). No data on clinical complications or better acceptance of the diet were reported. In the second placebo-controlled trial, 45 "responders" (about half of the children initially enrolled) aged 4 to 12 years who were on a low-phenylalanine diet were able to tolerate an increase in phenylalanine (dry powder) supplementation when treated with sapropterin. In late 2009, the clinical evaluation of sapropterin in tetrahydrobiopterin deficiency was based on non-comparative data in about forty patients, showing a decline in phenylalanine concentrations. No signs of serious adverse effects have emerged so far. Sapropterin has not been studied in pregnant women, but animal data call for caution. In summary, sapropterin seems to make it possible to relax some dietary restrictions in a minority of children with phenylketonuria (moderate relaxation of dietary control, on average). No data are available on the impact of sapropterin on clinical complications. Evaluation is inadequate in patients with tetrahydrobiopterin deficiency and a register should be established for all treated patients. PMID- 20738031 TI - Triptorelin and sex offenders. Limited clinical data. PMID- 20738030 TI - Sevelamer carbonate. No better than sevelamer hydrochloride. PMID- 20738032 TI - Degarelix. More rapid medical castration, nothing more. AB - In patients with non-localised prostate cancer, medical castration is generally achieved with a GnRH agonist such as triptorelin. A peripheral antiandrogen can be added during the first weeks of treatment to counteract the initial testosterone surge. Degarelix is the first GnRH antagonist to be authorised in this setting in the European Union. A randomised unblinded trial compared subcutaneous degarelix versus intramuscular leuprorelin, without the addition of a peripheral antiandrogen. Castration was achieved in almost all patients after the first month of treatment. Testosterone levels decreased within a few days with degarelix and more slowly with leuprorelin, after an initial surge, and these levels were maintained in both groups throughout the one-year study period. The more rapid fall in testosterone obtained with degarelix, without an initial surge, did not translate into lower mortality (there were only 2 cancer deaths) or fewer adverse effects during the first month of treatment. The main adverse effects in this trial were linked to castration: hot flushes and weight gain. Reactions at the injection site (pain, erythema) were far more frequent with degarelix than with leuprorelin, affecting respectively about 40% and fewer than 1% of patients. The large volume of the degarelix subcutaneous solution (3 to 4 mi) is not very practical to administer. In practice, degarelix has no tangible advantages over a GnRH agonist such as triptorelin. It is better to continue to use triptorelin, possibly with addition of an antiandrogen at the beginning of treatment. PMID- 20738033 TI - Liraglutide. Type 2 diabetes: more prudent to continue using exenatide. AB - When patients with type 2 diabetes fail to achieve strict HbA1c control with oral glucose-lowering drugs, insulin is the standard recourse. Exenatide, an injectable incretin analogue, should only be used when weight gain is a major problem. Liraglutide is another injectable incretin analogue recently authorised for use in this setting. Two randomised unblinded trials, one versus insulin glargine in 581 patients and the other versus exenatide in 464 patients, suggest that liraglutide has a slightly more potent effect on glycaemia. Weight loss was similar in the liraglutide and exenatide groups. In a trial including 1091 patients, liraglutide was not more or less effective than glimepiride on glycaemia. Like exenatide, liraglutide can cause pancreatitis. In the trial comparing liraglutide versus exenatide, one-quarter of patients experienced nausea. There is more evidence of a risk of thyroid cancer with liraglutide than with exenatide. Liraglutide is administered as a single daily subcutaneous injection, whereas exenatide requires two daily injections. In practice, when prescribing an incretin analogue seems justified, it is more prudent to continue using exenatide, while closely monitoring patients for adverse effects. PMID- 20738034 TI - Gefitinib. Still no convincing results in non-small cell lung cancer. PMID- 20738035 TI - Long-acting injectable olanzaoine. Inadequate assessment and a risk of overdose. PMID- 20738036 TI - Ezetimibe. The French authorities gradually confirm the lack of benefit. PMID- 20738037 TI - Drug-induced myopia, hyperopia and accommodation disorders. AB - Myopia, hyperopia and accommodation disorders are common refractive disorders, usually due to anatomical abnormalities or to physiological aging. They can also be functional, however, particularly when provoked by drugs. Drug-induced refractive disorders resolve after treatment cessation. All drugs acting on the autonomic nervous system can affect vision. Other drugs have unpredictable effects: the mechanism is not always known but sometimes appears to involve changes in the hydration of various ocular structures. PMID- 20738038 TI - Neuropsychological effects of macrolides. AB - Pharmacovigilance data collected from several European countries show that macrolides can provoke neuropsychological adverse effects such as hallucinations, delirium, manic episodes and sometimes depression, in both adults and children. These effects seem to be rare and are reversible on macrolide withdrawal. In practice, keep in mind that if neuropsychological disorders can be attributed to macrolides, treatment should be halted. PMID- 20738039 TI - Postmenopausal hormone replacement therapy and meningioma. AB - A retrospective study including more than 350,000 women, about 1400 of whom had developed meningioma, showed that the risk of meningioma was about twice as high in users of postmenopausal hormone replacement therapy as in non-users. Hormone replacement therapy should be discontinued if meningioma is diagnosed. PMID- 20738040 TI - Lung cancer associated with beta-carotene supplementation in smokers. AB - A meta-analysis of four randomised trials in a total of 109 394 subjects showed a statistically significant increase in the risk of lung cancer among smokers who used dietary supplements containing beta-carotene, at a mean dose of 20 to 30 mg/day. This contradicts the results of observational studies conducted in the 1990s. PMID- 20738041 TI - Inhaled antimuscarinic drugs: cardiovascular toxicity. AB - Inhaled antimuscarinic drugs have modest symptomatic efficacy in patients with chronic obstructive pulmonary disease (COPD). They also have several atropinic adverse effects, including mydriasis, visual disorders, dry mouth, constipation, micturition difficulties and tachycardia. In March 2008, the US Food and Drug Administration reported an increased frequency of stroke in COPD patients receiving tiotropium in clinical trials. A metaanalysis of 17 double-blind randomised trials in 13 645 patients with COPD showed a statistically significant increase in the risk of myocardial infarction, stroke and cardiovascular death associated with inhaled antimuscarinic drugs (ipratropium or tiotropium). A trial published after this metaanalysis, the Uplift study, including 5993 COPD patients followed for 4 years, showed no statistically significant difference in the frequency of cardiovascular death, myocardial infarction or stroke in the inhaled tiotropium group compared with the placebo group. However, these results are not sufficient to dispel the strong suspicion of an increased risk of cardiovascular adverse effects. In practice, the use of an inhaled antimuscarinic drug should be discussed on a case by case basis, weighing the only modest benefits against the worrisome risk of cardiovascular events. PMID- 20738042 TI - Psoriasis due to TNF alpha antagonists. PMID- 20738043 TI - Adverse effects of papillomavirus vaccination: 2009 data. PMID- 20738044 TI - Macular oedema linked to latanoprost and rosiglitazone. PMID- 20738045 TI - Automated external defibrillation by first-responders. AB - This review examines whether the use of automated external defibrillators by first-responders improves the survival of adults who suffer cardiopulmonary arrest. We also examined the risks associated with these devices, based on a review of the literature using the standard Prescrire methodology. Automated external defibrillators detect ventricular fibrillation with almost perfect sensitivity and specificity. Several studies showed that the use of automated external defibrillators by trained first-responders is associated with increased survival among patients who suffer out-of-hospital cardiac arrest in public places. A retrospective study suggests that installing automated external defibrillators in public places would only allow about one-fifth of all victims of cardiac arrest to be treated; this would increase the average survival rate after cardiac arrest from about 5% to 6.5%. The main risks associated with these devices are burns to the patient's skin at the electrode contact points, and inappropriate shock to the user--a rare occurrence. Interactions between automated external defibrillators and implantable defibrillators have been described. Drug delivery patches on the patient's chest can prevent electrode skin contact and may block delivery of the electric discharge. In the United States, about 1 in 5 functioned over a 10-year period, mainly due to electrical or software problems. In summary, automated external defibrillators have a favourable risk-benefit balance, at least in trained hands. Specific training helps first-responders to act purposefully and without delay, and to implement the chain of survival until medical help arrives. PMID- 20738046 TI - INR self-monitoring and oral anticoagulants. AB - The international normalised ratio (INR) must be measured regularly in order to maximise the benefit's and minimise the risks of oral articoagulant therapy. Devices are now available for INR measurement at home, by the patient or a caregiver. We examined whether these devices help to prevent bleeding or thromboembolism by reviewing the relevant literature using the standard Prescrire methodology. INR self-measurement is reproducible and consistent with values obtained in medical laboratories. Three meta-analyses of randomised trials show that a strategy based on patient training, INR self-measurement all mortality and the number of thromboembolic events compared with conventional laboratory monitoring. In contrast, there was no impact on the frequency of serious bleeding.The INR was measured once every one or two weeks in the self-measurement groups. This benefit probably resulted from a combination of several factors, such as better patient awareness of the importance of regular INR measurement, easier access to INR measurement, more rapid treatment adjustment, and more frequent INR measurement. It remains to be seen whether a similar benefit will be observed in France, a country with a dense network of medical laboratories. nique and, if necessary, to interpret the results and adjust the dose regimen. Depending on the trial, between 10% and 95% of eligible patients agreed to be trained in self-measurement and to adopt it in practice. However, in a British trial only half of the patients who agreed to be trained were actually capable of INR self-measurement and dose adjustment for at least one year. In practice, it appears that oral anticoagulant therapy can be optimised by INR measurement at least every two weeks, with immediate dose adjustment, whether the INR is measured in a laboratory or by the patients at home. INR self-measurement can help to ensure that these conditions are respected. PMID- 20738047 TI - Gestational diabetes: too many uncertainties to recommend routine screening. AB - Three trials comparing the effect of diabetes screening during pregnancy failed to show whether the benefits outweigh the risks, The British, U.S. and French authorities have not recommended widespread screening, The information available should be provided to pregnant women, and screening tests should be considered on a case-by-case basis, mainly for women with risk factors. PMID- 20738048 TI - Artesunate suppositories: an option for severe malaria. PMID- 20738049 TI - Drug packaging in 2009: a few advances. AB - Once again, in 2009, most of the packaging that Prescrire analysed did not meet our quality criteria. Labelling information was too often ambiguous or clumsily expressed. The quality of dosing devices and the safety of multidose bottles were not guaranteed. Patient information leaflets were more legible on the whole, but once again rather uninformative. All of these shortcomings put patients at risk. European measures concerning drug labelling have finally been transposed into French law, and have led to some improvements: the international nonproprietary name (INN) is more frequently displayed on primary packaging. The use of Braille on boxes and access to Braille package leaflets are increasing. The improved legibility of the labelling of ampoules containing certain dangerous injectable drugs, as recommended by the French drug regulatory agency (Afssaps), has become more widespread. In practice, healthcare professionals need to take action on packaging issues: by choosing the best packaging, reporting potential sources of confusion and error and informing patients. PMID- 20738050 TI - The finances of Association Mieux Prescrire 2009: Prescrire annual report. PMID- 20738051 TI - Drug companies monitor prescriptions and sales to fine-tune their marketing strategies. AB - Market research companies analyse drug prescriptions and sales in community and hospital pharmacies, thus enabling drug companies to refine their marketing strategies. Some information of interest to drug companies is provided directly by healthcare professionals, sometimes unwittingly, and sometimes in return for small "favours". PMID- 20738053 TI - Direct-to-consumer advertising: the European Commission's plan. PMID- 20738052 TI - Pharmacovigilance: an opportunity for the European Commission to put patients' interests first. PMID- 20738054 TI - Nurses addressing the challenges of chronic illness: from primary to palliative care. PMID- 20738055 TI - Cancer as a chronic disease. AB - BACKGROUND: Over the past two decades the number of people Living with cancer has increased. Many cancer survivors end up with long term disabilities requiring ongoing care and support. For many people, cancer survival now means Living with a chronic and complex condition. AIM: The purpose of this paper is to provide an overview of the long term management issues for cancer survivors and strategies to enhance their care. DISCUSSION: Cancer survivors require ongoing support in four key areas: prevention; surveillance; intervention for consequences of cancer and its treatment; and coordination between specialist and generalist providers. CONCLUSION: Cancer survivors experience significant physical and psychological morbidity which makes minimising their burden of disability and distress an important priority. Survivors require ongoing care that is well co-ordinated, focuses on prevention, provides going surveillance whilst minimising and managing the long term effects of treatment and other co-morbidities. PMID- 20738056 TI - The Healthy Ageing Model: health behaviour change for older adults. AB - Proposed is a model of primary care for older adults with chronic health conditions that focuses on active engagement in health care. The Healthy Ageing Model is anchored in established theory on motivation and health behaviour change. The model draws on empirical and applied clinical underpinnings in such diverse areas as health promotion and education, treatment of addictions or obesity, management of chronic diseases, goal-setting, and coaching techniques. The conceptual foundation for the Healthy Ageing Model is described first, followed by a brief description of the key characteristics of the model. In conclusion, suggestions are offered for the clinical application and for further developing the model. PMID- 20738057 TI - Uptake of Medicare chronic disease items in Australia by general practice nurses and Aboriginal health workers. AB - The Australian health care system is currently in a state of reform and there is increasing pressure to provide care in community settings. Rising costs, demands and population ageing underscore the importance of adopting models of health care delivery to address changing epidemiological patterns. Population ageing and the increase of chronic conditions challenge models based on acute care. Changes to the Medicare benefits schedule have facilitated the development of a range of expanded nursing services in the general practice setting. In particular, item number 10997 was introduced to reimburse practice nurses and Aboriginal health workers (AHWs) for providing monitoring and support to people with a chronic disease for and on behalf of a general practitioner (GP). The uptake of Medicare Item 100997 from 2007 to 2009, to monitor chronic disease interventions provided by general practice nurses has increased dramatically. The rate of uptake of Item 100997 has not been consistent across States and Territories, even allowing for population distributions. Exploring reasons for these regional variations and linking uptake of Medicare Item numbers to patient outcomes is important in developing the nursing role in Australian general practice. PMID- 20738058 TI - Can principles of the Chronic Care Model be used to improve care of the older person in the acute care sector? AB - BACKGROUND: There is increasing evidence that hospitals are failing to meet the needs of older people. As a consequence acute care needs to be adapted to meet the needs of older people. Although initially developed for chronic conditions the Chronic Care Model (CCM) provides useful strategies for improving continuity and quality of care. METHOD/AIM: This paper describes the elements of the CCM and discusses how a chronic care approach can improve models of care delivery for older persons in the acute care hospital settings. DISCUSSION: The CCM provides a potentially useful approach to improve health care for older people in the acute care setting. Positive policy environments, interdisciplinary care collaboration, evidence-based practice, an emphasis on self-management strategies and empowered communities are essential elements for driving development of effective models of care. CONCLUSION: Models of care require a multifaceted collaborative approach for sustainability. Implementing elements of the CCM in developing models of acute care may improve patient outcomes and decrease unnecessary admissions to hospital for older people. IMPLICATIONS FOR PRACTICE: This paper provides suggestions for models of care to improve care of the older person in the acute care setting. PMID- 20738059 TI - The role of parents in managing asthma in middle childhood: an important consideration in chronic care. AB - Asthma is a significant illness for Australian children and their families. In childhood, parents have the primary responsibility for managing asthma on a day to-day basis, and therefore understanding the management of asthma by parents is important to nursing practice. Middle childhood (5-12 years) is an important time in the lives of children and families with asthma, as children commence school and spend increasing amounts of time away from direct parental care. In order to manage asthma during middle childhood, parents need to understand asthma as an illness, understand the treatment of asthma, be able to monitor and respond to changes in condition, manage other carers, manage asthma in the context of family life and guide the development of self-management responsibility in their child with asthma. While the scope of parent management in terms of asthma knowledge and treatment has been well explored in the literature, less is known about the process by which parents support the development of self-management responsibility in children with asthma. PMID- 20738060 TI - The nurse educator role in Australian hospitals: implications for health policy. AB - To date, the nurse educator role in the Australian hospital setting has been poorly described. Current pressures for health care reform have prompted reviews of nursing roles. This paper discusses the literature pertaining to the nurse educator role within the context of the Australian health care environment and current health care policy. Building on this synthesis, barriers and facilitators impacting on the nurse educator role are identified and strategic directions for policy, role clarification and advanced practice role development are highlighted. Further research identifying the impact of the hospital-based nurse educator on patient outcomes and professional nursing practice are proposed. PMID- 20738061 TI - Integrating palliative care content into a new undergraduate nursing curriculum: the University of Notre Dame, Australia--Sydney experience. AB - BACKGROUND: The majority of society's deaths occur in a health care environment. Regardless of whether a death occurs in acute care, hospice, residential aged care or community settings, nurses are the health professionals that will spend the largest proportion of time with the patient who has a terminal condition and their families. As few nurses have specialist palliative care qualifications it is essential that nursing education prepares graduates to achieve the core capabilities required for the delivery of best evidenced based palliative care. This reality makes the integration of palliative care content into the undergraduate nursing curricula an important priority. AIM: This paper aims to describe how palliative care content has been embedded throughout the three-year University of Notre Dame Australia, Sydney (UNDA) undergraduate nursing degree. METHOD: The School of Nursing at the University of Notre Dame Australia, Sydney campus is committed to ensuring that students graduate with the capabilities to deliver appropriate care to people with requiring end-of-life care. The establishment of this new School of Nursing coincided with the release of the 'The Palliative Care Curricula for Undergraduates Program' (PCC4U) learning resources. These resources have been integrated into relevant units across the three-year nursing curricula. DISCUSSION: The nursing curriculum has been design to supports the integration of palliative care knowledge into clinical practice. The Palliative Care Curricula for Undergraduates Program Learning resources offer engaging palliative care case studies and scenarios for academics to utilise. Adopting an iterative approach where palliative care content is spiralled across multiple units provides opportunities for undergraduate nursing students to sequentially build and consolidate their palliative care capabilities. CONCLUSION: Developing a new curricular provided an ideal opportunity to integrate and embed palliative care content into the undergraduate nursing degree. The next stage of the curriculum development is to explore inter professional palliative care education opportunities. Evaluating the palliative care capabilities of our nursing graduates is also an important consideration. IMPLICATIONS FOR PRACTICE: This paper provides practical suggestions for integrating palliative care education into an undergraduate nursing curriculum. PMID- 20738062 TI - Meeting the challenges of chronic illness: a nurse-led collaborative community care program in Thailand. AB - BACKGROUND: Chronic illness is of concern to health care systems globally. Although a significant evidence base supports the concept of nurse-led interventions, less data is available to address unique features of health care systems in the developing world. AIM: The purpose of this study aimed to undertake preliminary testing of an intervention of nurse-led community care program, the Network Collaborative Action Plan (N-CAP), to assess the impact on disease severity and patient satisfaction. METHOD: A quasi-experimental study, using historical controls, evaluated a collaborative nurse-led intervention to promote coordination and continuity of care for patients with chronic illness. RESULTS: Participants, diagnosed with chronic obstructive lung disease (COPD), coronary heart disease (CHD) and chronic heart failure (CHF) were recruited. Prospective consecutive patient meeting the study criteria (n=47) were assigned into the control group and following development and implementation of the intervention eligible consenting patients were enrolled in the experimental group (n=44). Participants in the experimental group had significantly tower scores on severity of disease measurements during the third week (F = 4.61, p = 0.035) and the eighth week hospital (F = 4.30, p = .041) following hospital discharge than those in the control group. Participants in the experimental group expressed significantly higher scores on satisfaction with community care than those in the control group. CONCLUSIONS: A nurse-led, collaboratively developed program has potential to improve satisfaction and decrease symptom development in people with chronic illnesses in Thailand. PMID- 20738063 TI - Aptasensors: a review. AB - Aptamers are a promising class of agents for biomolecules detection due to their small size, chemical stability and cost effectiveness over conventional bioreceptors such as antibodies. Recent advances in micro/nano-fabrication and biotechnology have driven active participation of engineers and molecular biologists in the development of aptasensors. This review examines aptasensors from a developer standpoint discussing surface immobilization techniques and mechanisms used to detect biomolecular interactions in the context of biotechnology and nanomedicine. The factors that affect accuracy, sensitivity and stability of aptasensors are also addressed. PMID- 20738065 TI - Formation of nanosized phosphonic acid self assembled monolayers on cobalt chromium alloy for potential biomedical applications. AB - Formation of nanosized self assembled monolayers (SAMs) of carboxyl terminated 16 Phosphonohexadecanoic acid (16-PA) and methyl terminated Octadecylphosphonic acid (ODPA) on Cobalt-Chromium (Co-Cr) alloy have been successfully demonstrated. Nanosized monolayers were formed by adsorption of these phosphonic acid SAMs on bare Co-Cr alloy by solution deposition technique. The formation of the nanosized monolayers was confirmed by using characterization techniques like Fourier Transform Infrared Spectroscopy (FTIR) with Attenuated Total Reflectance (ATR) attachment, Atomic Force Microscopy (AFM), X-ray Photoelectron Spectroscopy (XPS), Ellipsometry and Contact Angle measurements. FTIR confirmed the SAM formation due to the presence of characteristic stretching vibration of SAM functional groups. FTIR studies suggest the binding of the phosphonic SAMs to be a combination of mono and bidentate binding. XPS showed presence of phosphorous peak and an increase in carbon peak intensity after SAM deposition, while it consequently showed decrease in peak intensity of the metal alloy (Co and Cr) peaks. AFM images gave good understanding of the topography, surface roughness and uniformity of SAM formation. Ellipsometric studies indicate nanosized thickness of the SAMs formed, while contact angle measurements showed changes in surface hydrophilicity/hydrophobicity after SAM formation. By tailoring the terminal functional group of these SAMs on Co-Cr alloy these nanosized monolayers could be potentially used for various biomedical applications such as localized drug delivery, biocompatibility, tissue integration etc. PMID- 20738064 TI - Controlled release carriers of growth factors FGF-2 and TGFbeta1: synthesis, characterization and kinetic modelling. AB - The purpose of this work is to produce microspheres loaded with transforming growth factor beta1 TGFbeta1 and basic fibroblast growth factor FGF-2; to ensure the protein protection from degradation during the encapsulation and storage steps, to evaluate the release rate and the microspheres toxicity. The water in oil in water double emulsion technique was adapted to avoid the protein degradation during the encapsulation. The obtained microspheres were deeply characterized to evaluate their size, morphology, toxicity, the way of degradation, the protein stability and release rate. The microspheres were found to be biocompatible and the encapsulation efficiency was about 35%. It was observed that the obtained microspheres increase the shelf life of the growth factors. The diffusion coefficient was quantified using Fick's law of diffusion that was combined to an empirical equation representing the decrease in the protein stability. Such modelling helped to give indirect information about the microspheres morphology and drug distribution within the microspheres. The main conclusion consists of the formation of a higher compact polymer matrix when smaller particles are produced, which has different distinct effects: the encapsulation efficiency and the stability of the encapsulated growth factor are enhanced while both the growth factor diffusion and the polymer degradation rates decrease. PMID- 20738066 TI - Antimicrobial and anticancer efficacy of antineoplastic agent capped gold nanoparticles. AB - Synthesis of thioguanine (TG)-capped Au nanoparticles (Au@TG) and their enhanced in vitro antimicrobial and anticancer efficacy against Micrococcus luteus, Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Aspergillus fumigatus, Aspergillus niger and Hep2 cancer cell (Human epidermiod cell) have been reported. The nature of binding between 6-TG and the gold nanoparticles via complexation is investigated using ultraviolet-visible spectrum, cyclic voltammetry, transmission electron microscopy, fluorescence and Fourier transform infrared (FT-IR) spectroscopy. The present experimental studies suggests that Au@TG are more potential than TG towards antimicrobial and anticancer activities. Hence, gold nanoparticles have the potential to be used as effective carriers for anticancer drug. PMID- 20738067 TI - Antibacterial effect of lanthanum calcium manganate (La0.67Ca0.33MnO3) nanoparticles against Pseudomonas aeruginosa ATCC 27853. AB - Nanotechnology based water purification system and treatment of human diseases are of higher priority in the immediate future for economic and undetermined health purpose. Nanoparticles offer the possibility of an efficient removal of pollutants and microbes in water treatment. Here we have used colossal magnetoresistance (CMR) materials, lanthanum calcium manganate (LCMO) and Eu3+ doped lanthanum calcium manganate (LECMO) nanoparticles, to determine the antibacterial efficacy against Pseudomonas aeruginosa-ATCC 27853, a soil and water born pathogenic bacteria. The average size of the synthesized nanoparticles was varied from 50 nm to 200 nm and X-ray diffraction pattern showed the formation of a single phase LCMO or LECMO of an orthorhombic crystal structure after annealing the precursor at 1000 degrees C for 2 h in air. The data revealed that LCMO nanoparticle have higher antibacterial activity compared to LECMO nanoparticle. Thus, LCMO nanoparticles can offer future applications as antimicrobial drug and in water purification technology. PMID- 20738068 TI - Real-time imaging of interactions between dipalmitoylphosphatidylcholine monolayers and gelatin based nanoparticles using Brewster angle microscopy. AB - Given the current interest in the pulmonary route for targeted drug delivery, assessing the impact of drug delivery vehicles on the surfactant layer lining the surface of the lung alveoli is critical. As gelatin-based nanoparticles are one such vehicle, this study addresses their interaction with the major saturated phospholipid component of native lung surfactant, dipalmitoylphosphatidylcholine (DPPC). Nanoparticles are colloidal particles in the size range of 1 to 1000 nm that are presently investigated for site-specific drug delivery in the emerging field of nanomedicine. Monolayer studies of DPPC films were performed both in the presence and absence of nanoparticles in order to assess the interaction in terms of average molecular areas occupied at given surface pressures. In Brewster angle microscopy experiments, nanoparticles significantly changed the shape and reduced the size of DPPC domains suggesting a considerable interaction of the two systems. For safe pulmonary drug delivery, understanding this interaction is a prerequisite so nanoparticles can be a feasible alternative to more conventional therapies in the future. PMID- 20738069 TI - Auger-mediated cytotoxicity of cancer cells in culture by an 125I-antisense oligomer delivered as a three-component streptavidin nanoparticle. AB - We reported recently that a three-component nanoparticle, consisting of a targeting antibody, a transfecting peptide and an 111In-antiRIalpha MORF antisense oligomer, provided Auger electron-mediated, antisense-mediated, cytotoxicity of cells in culture. We have now measured the cytotoxicity of the nanoparticle in culture with the 111In replaced by 125I, another attractive Auger electron emitter. The nanoparticle consisted of streptavidin linking the 125I labeled antiRIalpha mRNA antisense MORF oligomer, the tat transfecting peptide and the anti-Her2 Trastuzumab antibody. Cytotoxicity was evaluated by a clonogenic survival assay in BT-474 (Her2+) human breast cancer cells. In a dose escalation study, as measured by the surviving fraction, the cytotoxicity of tumor cells to the 125I-labeled antisense nanoparticle was significantly higher than that for the identical sense control. When compared with our previous study with 111In as label, a similar level of cytotoxicity was achieved but the observed minimal therapeutic dose for the 125I-labeled nanoparticle in BT-474 cells was lower than that for 111In-labeled nanoparticle in SK-BR-3 cells. Thus, a radiolabeled antisense MORF oligomer delivered into cells by a three-component nanoparticle is an effective vehicle for Auger radiotherapy when radiolabeled with 111In or 125I. PMID- 20738070 TI - Effect of hydroxyapatite and beta-tricalcium phosphate nanoparticles on promonocytic U937 cells. AB - OBJECTIVES: Nanoparticles from implanted materials are reported as the main cause of implant failure. Monocytes are among the first cells to colonize the inflammatory site. We evaluated the biological effects of bone substitutes presented to U937 cells in vitro as micron- or nanometer-sized particles. METHODS: The HA (550 nm) and beta-TCP (550 nm) nanoparticles were incubated with U937 cells. Cell cycle modification, specific antigens expression, and the extent of cell death were determined. RESULTS: Firstly, by using the sulforhodamine B (SRB) test and the annexin V-FITC analysis by flow cytometry, our results provide evidence of the absence of cytotoxicity, and show that nanoparticles do not induce more apoptosis than microparticles in U937 cells. Secondly, although morphologic evidence of stimulation of U937-cells was found by confocal microscopy, neither bone substitute altered the distribution of the cells into different phases of the cell cycle (Kit Cycle Test Plus DNA). These results suggest that nanoparticles do not cause promonocyte maturation in macrophages. Thirdly, the flow cytometry results showed no differences in the expression of the adherence and activation markers. SIGNIFICANCE: The results suggest that nanoparticles do not promote the differentiation of promonocytic U937 cells into macrophages and do not induce an enhanced inflammatory response. PMID- 20738071 TI - Biocompatibility of nanostructured chitosan/ poly(vinyl alcohol) blends chemically crosslinked with genipin for biomedical applications. AB - In the present research it is reported the development and characterization of novel polymer blends based on chitosan and poly(vinyl alcohol) (PVA). The hybrid polymeric network was synthesized and modified by chemical crosslinking using genipin for potential use in a variety of biomedical applications. The micro and nanostructures of the blended hydrogels and hybrids were characterized through Fourier Transform Infrared spectroscopy (FTIR) and swelling test analysis. Moreover, cytotoxicity and cell viability were also performed by MTT assay with cell culture. The chemical crosslinking was achieved via the relative intensity of the band at 1650 cm(-1) which is mostly associated with the reaction of genipin carboxymethyl group with the amino group of chitosan forming amides. It was found that by increasing the chitosan content relative to PVA the swelling index of the blend has decreased, reflecting the reduction on the mobility of polymer network and the hydrophilic behavior of the blend. The tested hydrogels have clearly presented adequate cell viability, non-toxicity and suitable properties which can be tailored for potential use in bioengineering applications. PMID- 20738072 TI - Folic acid-targeted mesoporous silica nanoparticles for two-photon fluorescence. AB - New nanotools for the imaging of cancer cells have been synthesized. Two-photon dye-doped 3-aminopropyltriethoxysilane-grafted mesoporous silica nanoparticles (MSN) have been grafted with folic acid (FA) functionalized PEG groups. Amine-PEG groups were first reacted with an activated ester derivative of FA. A mixture of FA- and hydroxyl-PEG has then been reacted with the amino groups at the surface of the particles. Cell culture experiments performed with MCF7 and HeLa cancer cells demonstrated that these functionalized MSN showed a low cytotoxicity even after a 24 hours incubation time at high concentrations. These modified MSN are promising for applications in the field of two-photon imaging and their potentiality for photodynamic therapy is currently being investigated. PMID- 20738073 TI - Nanoencapsulation of quercetin via miniemulsion polymerization. AB - The nanoencapsulation of quercetin, a strong antioxidant and radical scavenger, via methyl methacrylate miniemulsion polymerization, using miglyol 812 as costabilizer and lecithin as surfactant was studied and the effect of the monomer/co-stabilizer ratio and different types of initiator, 2,2'azobisisobutyronitrile (AIBN) and redox pair composed of hydrogen peroxide and ascorbic acid, was investigated. Reactions conducted in the presence of quercetin showed lower polymerization rates, indicating that the presence of quercetin inhibits (redox pair) and/or retards (AIBN) the polymerization reaction. The increment of the concentration of ascorbic acid in the reactions initiated by a redox pair resulted in a considerable increase of the reaction rate without influencing other properties as average particle diameter, due to the fact that ascorbic acid acts as a reducing agent minimizing the oxidation of quercetin. Higher quercetin recovery was obtained for nanocapsules when compared with nanospheres. PMID- 20738074 TI - Gold nanoparticle mediated detection of prostate cancer cells using photoacoustic flowmetry with optical reflectance. AB - The presence of circulating tumor cells in the bloodstream has been correlated with disease state in cancer patients. While we have successfully exploited melanin, the natural light absorber in melanoma cells, to induce photoacoustic waves for tumor cell detection, non-pigmented tumor cells do not have sufficient optical contrast for such a method. For example, breast, prostate and lung cancers lack intrinsic pigmentation and thus do not generate photoacoustic waves. In order to induce optical contrast in non-pigmented cancer cells, we have attached gold nanoparticles to a prostate cancer cell line. This optical absorption will enable us to detect such cells in a photoacoustic flowmeter designed to find circulating tumor cells in blood samples. We tested a prostate cancer cell line, PC-3, by tagging them with gold nanoparticles. We determined the photoacoustic response over the wavelengths 470-570 nm to identify the absorption peak. We then determined the response from serial dilutions of PC-3 cells suspended in saline. Finally, we showed photoacoustic response from PC-3 cells suspended among white blood cells in the flow meter to demonstrate our ability to detect single cells under flow. PMID- 20738075 TI - Hair follicles stimulation effects of gelatin nanofibers containing silver nanoparticles. AB - In the present work we studied gelatin nanofibers containing silver nanoparticles of 14 +/- 6 nm mean diameter, prepared by electrospinning. The electrospinnable solution was obtained by drop-wise adding a AgNO3/acetic acid solution to gelatin which had previously been dissolved in a mixture of formic acid and acetic acid. The silver metallic nanoparticles were formed due to the reducing action of the formic acid. The resulted material was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Subcutaneous implants in rabbits demonstrated that the gelatin nanofibers containing silver nanoparticles were resorbed with no inflammatory reactions. An increased number of secondary hair follicles developed in tissue regions close to implants, suggesting the existence of a stimulation effect of silver nanoparticles on hair follicles. PMID- 20738076 TI - Extraction issues of paclitaxel in nanocrystals. AB - Nano-carrier systems have become an attractive alternative in the formulation of hydrophobic drugs, and the number of scientific and patent publications per year on nanoparticles has experienced exponential growth since 2000. As these drugs are carried by different nano-carriers, their pharmacokinetics (PK) and biodistribution will be greatly affected. Therefore, PK and biodistribution have become important parameters to evaluate the nano-systems, which are commonly performed by HPLC. This study looks at certain issues in extraction and HPLC analysis encountered in conducting biodistribution studies for paclitaxel (PTX) nanocrystals. We report here for the first time that the extraction efficiency of PTX depends on the nano-carriers, i.e., nanocrystals and nanomicelles. A selected solvent had to be added prior to extraction to totally destruct the nano-carrier structure to resolve this difference. It was also found that the extraction recovery of PTX carried by the nanocrystals was organ specific. Therefore, it will be critical to consider this difference when studying the distribution of drugs in nano-carriers. We hope that our findings would highlight certain issues to be aware of when conducting PK and biodistribution studies for nano-drug carriers. PMID- 20738077 TI - Increases in scopes of practice and authorized acts for regulated health professionals relating to drugs and substances. PMID- 20738078 TI - Governance control: over regulated health professional colleges. PMID- 20738079 TI - Bill 179: a missed opportunity for collaborative care in Ontario. PMID- 20738080 TI - The application of the Canadian Charter of Rights and Freedoms to the regulation of health professionals: anaemic rights and prescriptions for change. PMID- 20738081 TI - Reinstatement applications under S. 72 of the Health Professions Procedural Code: a faint hope clause? PMID- 20738082 TI - The Health Professions Regulatory Advisory Council (HPRAC): its evolution from the introduction of the Regulated Health Professions Act, 1991 to the introduction of Bill 179. PMID- 20738083 TI - Amendments to the Regulated Health Professions Act, 1991: major implications for health care professionals. PMID- 20738084 TI - pH-dependent mutarotation of 1-thioaldoses in water. Unexpected behavior of (2s) D-aldopyranoses. AB - The pH-dependent mutarotation of 1-thioaldopyranoses in aqueous media has been investigated. Anomerization readily occurred at lower and neutral pH for all aldopyranoses studied, whereas mainly for (2S)-D-aldopyranoses at higher pH. 1 Thio-D-mannopyranose and 1-thio-D-altropyranose showed very strong pH dependence where the anomeric equilibrium ratios changed dramatically from a preference for the beta-anomer at lower pH to the alpha-anomer at higher pH. PMID- 20738085 TI - Mechanism and activity of photocatalytic oxygen evolution on titania anatase in aqueous surroundings. AB - Due to its high overpotential and low efficiency, the conversion of water to O(2) using solar energy remains a bottleneck for photocatalytic water splitting. Here the microscopic mechanisms of the oxygen evolution reaction (OER) on differently structured anatase surfaces in aqueous surroundings, namely, (101), (001), and (102), are determined and compared systematically by combining first-principles density functional theory calculations and a parallel periodic continuum solvation model. We show that OER involves the sequential removal of protons from surface oxidative species, forming surface peroxo and superoxo intermediates. The initiating step, the first proton removal, dictates the high overpotential. Only at an overpotential of 0.7 V (1.93 V vs SHE) does this rate-controlling step become surmountable at room temperature: the free energy change of the step is 0.69, 0.63, and 0.61 eV for (101), (102), and (001) surfaces, respectively. We therefore conclude that (i) OER is not sensitive to the local surface structure of anatase and (ii) visible light (<~590 nm) is, in principle, capable of driving the photocatatlytic OER on anatase kinetically. By co-doping high-valent elements into the anatase subsurface, we demonstrate that the high overpotential of the OER can be significantly reduced, with extra occupied levels above the valence band. PMID- 20738086 TI - Ultrafast vibrational Stark-effect spectroscopy: exploring charge-transfer reactions by directly monitoring the solvation shell response. AB - We present the first implementation of transient vibrational Stark-effect spectroscopy as an ultrafast probe of solvation dynamics. The method is applied to the phototriggered intramolecular charge-transfer reaction of Betaine-30, where the vibrational Stark shifts of the nearby solvent molecules--arising from the change in the electrostatic environment--are measured using a three-pulse photon echo probe. This new experiment provides a direct subpicosecond measure of the chromophore's excited-state dynamics and back electron transfer as viewed from the solvent's perspective. We develop a simple ab initio model that offers semiquantitative prediction of the experimental Stark shifts. PMID- 20738087 TI - Mechanism of selective halogenation by SyrB2: a computational study. AB - The mechanism of the chlorination reaction of SyrB2, a representative alpha ketoglutarate dependent halogenase, was studied with computational methods. First, a macromolecular model of the Michaelis complex was constructed using molecular docking procedures. Based on this structure, a smaller model comprising the first- and some of the second-shell residues of iron and a model substrate was constructed and used in DFT investigations on the reaction mechanism. Computed relative energies and Mossbauer isomer shifts as well as quadrupole splittings indicate that the two oxoferryl species observed experimentally are two stereoisomers resulting from an exchange of the coordination sites occupied by the oxo and chloro ligands. In principle both Fe(IV)?O species are reactive and decay to Fe(III)Cl (OH)/carbon radical intermediates via C-H bond cleavage. In the final rebound step, which is very fast and thus precluding equilibration between the two forms of the radical intermediate, the ligand (oxo or chloro) placed closest to the carbon radical (trans to His235) is transferred to the carbon. For the native substrate (L-Thr) the lowest barrier for C-H cleavage was found for an isomer of the oxoferryl species favoring chlorination in the rebound step. CASPT2 calculations for the spin state splittings in the oxoferryl species support the conclusion that once the Fe(IV)?O intermediate is formed, the reaction proceeds on the quintet potential energy surface. PMID- 20738088 TI - Efficient macrocyclization achieved via conformational control using intermolecular noncovalent pi-cation/arene interactions. AB - Quinolinium salt 3 is an effective additive that acts as a conformation control element (CCE) to promote macrocyclization to form rigid cyclophanes via olefin metathesis or Glaser-Hay coupling, which do not cyclize in the absence of the additive. The additives are easily synthesized and highly modifiable and have solubility profiles which allow for simple recovery via filtration. PMID- 20738089 TI - Michael acceptor-containing coenzyme A analogues as inhibitors of the atypical coenzyme A disulfide reductase from Staphylococcus aureus. AB - Coenzyme A (CoA) analogues containing alpha,beta-unsaturated ester, ketone, and sulfone moieties were prepared by chemo-enzymatic synthesis as inhibitors of coenzyme A disulfide reductase (CoADR), a proven and as yet unexploited drug target in Staphylococcus aureus. Among these Michael acceptor-containing CoA analogues, which were designed to target CoADR's single essential active site cysteine for conjugate addition, a phenyl vinyl sulfone-containing analogue showed the most potent inhibition with a competitive K(i) of ~40 nM, and time dependent inactivation with a second-order rate of inactivation constant of ~40,000 s(-1).M(-1). Our results suggest that electrophilic substrate analogues should be considered as potential inhibitors of other medicinally relevant disulfide reductase enzymes. PMID- 20738090 TI - Protecting polymers in space with atomic layer deposition coatings. AB - Polymers in space may be subjected to a barrage of incident atoms, photons, and/or ions. Atomic layer deposition (ALD) techniques can produce films that mitigate many of the current challenges for space polymers. We have studied the efficacy of various ALD coatings to protect Kapton polyimide, FEP Teflon, and poly(methyl methacrylate) films from atomic-oxygen and vacuum ultraviolet (VUV) attack. Atomic-oxygen and VUV studies were conducted with the use of a laser detonation source for hyperthermal O atoms and a D2 lamp as a source of VUV light. These studies used a quartz crystal microbalance (QCM) to monitor mass loss in situ, as well as surface profilometry and scanning electron microscopy to study the surface recession and morphology changes ex situ. Al2O3 ALD coatings protected the underlying substrates from atomic-oxygen attack, and the addition of TiO2 coatings protected the substrates from VUV-induced damage. The results indicate that ALD coatings can simultaneously protect polymers from oxygen-atom erosion and VUV radiation damage. PMID- 20738091 TI - Label-free detection of DNA hybridization using surface enhanced Raman spectroscopy. AB - The SERS spectrum of DNA is strongly dominated by the strong spectral feature of adenine at 736 cm(-1); the presence of adenine can serve as an endogenous marker for the label-free SERS-based detection of DNA hybridization when the probe DNA sequence is adenine-free. The substitution of 2-aminopurine for adenine on the probe DNA sequence enables the detection of a target sequence using SERS, upon hybridization of the target with the 2-AP-substituted probe DNA sequence. PMID- 20738092 TI - Mechanistic study of gold(I)-catalyzed intermolecular hydroamination of allenes. AB - The intermolecular hydroamination of allenes occurs readily with hydrazide nucleophiles, in the presence of 3-12% Ph(3)PAuNTf(2). Mechanistic studies have been conducted to establish the resting state of the gold catalyst, the kinetic order of the reaction, the effect of ligand electronics on the overall rate, and the reversibility of the last steps in the catalytic cycle. We have found the overall reaction to be first order in gold and allene and zero order in nucleophile. Our studies suggest that the rate-limiting transition state for the reaction does not involve the nucleophile and that the active catalyst is monomeric in gold(I). Computational studies support an "outersphere" mechanism and predict that a two-step, no intermediate mechanism may be operative. In accord with this mechanistic proposal, the reaction can be accelerated with the use of more electron-deficient phosphine ligands on the gold(I) catalyst. PMID- 20738093 TI - Extraction of copper(II) ions from aqueous solutions with a methimazole-based ionic liquid. AB - The recently synthesized ionic liquid (IL) 2-butylthiolonium bis(trifluoromethanesulfonyl)amide, [mimSBu][NTf(2)], has been used for the extraction of copper(II) from aqueous solution. The pH of the aqueous phase decreases upon addition of [mimSBu](+), which is attributed to partial release of the hydrogen attached to the N(3) nitrogen atom of the imidazolium ring. The presence of sparingly soluble water in [mimSBu][NTf(2)] also is required in solvent extraction studies to promote the incorporation of Cu(II) into the [mimSBu][NTf(2)] ionic liquid phase. The labile copper(II) system formed by interacting with both the water and the IL cation component has been characterized by cyclic voltammetry as well as UV-vis, Raman, and (1)H, (13)C, and (15)N NMR spectroscopies. The extraction process does not require the addition of a complexing agent or pH control of the aqueous phase. [mimSBu][NTf(2)] can be recovered from the labile copper-water-IL interacting system by washing with a strong acid. High selectivity of copper(II) extraction is achieved relative to that of other divalent cobalt(II), iron(II), and nickel(II) transition-metal cations. The course of microextraction of Cu(2+) from aqueous media into the [mimSBu][NTf(2)] IL phase was monitored in situ by cyclic voltammetry using a well-defined process in which specific interaction with copper is believed to switch from the ionic liquid cation component, [mimSBu], to the [NTf(2)] anion during the course of electrochemical reduction from Cu(II) to Cu(I). The microextraction-voltammetry technique provides a fast and convenient method to determine whether an IL is able to extract electroactive metal ions from an aqueous solution. PMID- 20738094 TI - Potential biomarkers for Turner in maternal plasma: possibility for noninvasive prenatal diagnosis. AB - Turner syndrome (TS) is the most common sex chromosome abnormality in females, caused by the complete or partial absence of one X chromosome. To identify biomarkers for TS, we compared the protein composition of maternal plasma samples from pregnant women with normal and TS fetuses, using a proteomic approach consisting of 2D-E separation and MS analysis for the identification of the differentially expressed proteins. Samples were routinely obtained in the second trimester of pregnancy, stored, and used after prenatal determination of the fetal karyotype. Nine proteins (C1S, CO3, CLUS, AFAM, HABP2, IGHA1, HPT, SHBG, and CD5L) were significantly increased in the plasma of women carrying TS fetuses, whereas KNG1, IGJ, and TTHY were decreased. Identified proteins were further evaluated by immunoblot analysis while functional network association was carried out to asses significance. The identification of specific biomarkers may facilitate the development of noninvasive prenatal diagnosis and improve our understanding of the pathology of TS. Nevertheless, testing a larger cohort of pregnant women is necessary to evaluate the relevance of the reported findings. PMID- 20738095 TI - Utilization of aldoses as a carbonyl source in cyclocarbonylation of enynes. AB - The reaction of enynes with acetyl-masked aldoses in the presence of a rhodium(I) catalyst resulted in cyclocarbonylation, thus avoiding the direct use of carbon monoxide, to afford bicyclic cyclopentenones. In rhodium catalysis, aldoses serve as a carbon monoxide equivalent by donating their carbonyl moieties on the acyclic aldehyde form to enynes. A variety of aldoses, including D-glucose, D mannose, D-galactose, D-xylose, and D-ribose, can be used as a carbonyl source. Using the method, a wide variety of enynes were cyclocarbonylated in 22-67% yields. An asymmetric variant also proceeded with moderate to high enantioselectivity. PMID- 20738096 TI - Activation of dinitrogen by solid and liquid aluminum nanoclusters: a combined experimental and theoretical study. AB - Cross sections for chemisorption of N2 onto Al44(+/-) cluster ions have been measured as a function of relative kinetic energy and the temperature of the metal cluster. There is a kinetic energy threshold for chemisorption, indicating that it is an activated process. The threshold energies are around 3.5 eV when the clusters are in their solid phase and drop to around 2.5 eV when the clusters melt, indicating that the liquid clusters are much more reactive than the solid. Below the melting temperature the threshold for Al44(-) is smaller than for Al44(+), but for the liquid clusters the anion and cation have similar thresholds. At high cluster temperatures and high collision energies the Al44N2(+/-) chemisorption product dissociates through several channels, including loss of Al, N2, and Al3N. Density functional calculations are employed to understand the thermodynamics and the dynamics of the reaction. The theoretical results suggest that the lowest energy pathway for activation of dinitrogen is not dynamically accessible under the experimental conditions, so that an explicit account of dynamical effects, via molecular dynamics simulations, is necessary in order to interpret the experimental measurements. The calculations reproduce all of the main features of the experimental results, including the kinetic energy thresholds of the anion and cation and the dissociation energies of the liquid Al44N2(+/-) product. The strong increase in reactivity on melting appears to be due to the volume change of melting and to atomic disorder. PMID- 20738097 TI - Strong micro-dielectric environment effect on the band gaps of (n,m)single-walled carbon nanotubes. AB - The electronic states of carbon nanotubes are one of the most fundamental properties of the nanotubes. We now describe the finding that the band gaps of (n,m)SWNTs are strongly affected by the change in microdielectric environments around the isolated nanotubes. In situ photoluminescence (PL) spectroelectrochemistry of the films containing 15 isolated (n,m)single-walled carbon nanotubes (SWNTs) cast on ITO electrodes in organic solvents including DMSO, acetonitirile, DMF, THF, and chloroform was completed and then the oxidation and reduction potentials, and band gaps (DeltaE(electr)) of the (n,m)SWNTs in the solvents were determined. We have discovered that the DeltaE(electr) of the (n,m)SWNTs become greater as the solvent dielectric constants decreased, which is in sharp contrast to the optical band gaps (DeltaE(opt)) that show virtually no solvent dependence. Such a strong solvent dependence of the electrochemical band gaps is due to the difference in the solvation energy of the charged SWNTs produced during the electrochemical processes. The DeltaE(electr) of both mod types of the SWNTs, mod = 1 and mod = 2, linearly increased versus the reciprocal of the tube diameter, which agrees with the theory. Moreover, the states of the pi-electrons in the SWNTs were evaluated from the dependence of the band gaps on the diameter of the SWNTs. Furthermore, the states of the pi-electrons on the sidewalls of the SWNTs were evaluated using the gamma(0) values, a parameter representing the measure of the stability or the degree of delocalization of pi-electrons in the sidewall of the SWNTs, and revealed that the gamma(0) values of the mod = 1 and mod = 2 SWNTs increased with a decrease in the dielectric constants of the solvents in the range of 38-79. This study has enabled us to understand the essential electronic properties of the carbon nanotubes. PMID- 20738099 TI - Effects of dispersion conditions of single-walled carbon nanotubes on the electrical characteristics of thin film network transistors. AB - To facilitate solution deposition of single-walled carbon nanotubes (SWNTs) for integration into electronic devices they need to be purified and dispersed into solutions. The vigorous sonication process for preparing these dispersions leads to large variations in the length and defect density of SWNTs, affecting the resulting electronic properties. Understanding the effects of solution processing steps can have important implications in the design of SWNT films for electronic applications. Here, we alter the SWNTs by varying the sonication time, followed by deposition of sub-monolayer SWNT network films onto functionalized substrates. The corresponding electrical performance characteristics of the resulting field effect transistors (FETs) are correlated with SWNT network sorting and morphology. As sonication exposure increases, the SWNTs shorten, which not only affects electrical current by increasing the number of junctions but also presumably leads to more defects. The off current of the resulting transistors initially increased with sonication exposure, presumably due to less efficient sorting of semiconducting SWNTs as the defect density increases. After extended sonication, the on and off current decreased because of increased bundling and fewer percolation pathways. The final transistor properties are influenced by the nanotube solution concentration, density, alignment, and the selectivity of surface sorting of the SWNT networks. These results show that in addition to chirality, careful consideration of SWNT dispersion conditions that affect SWNT length, bundle diameter, and defect density is critical for optimal SWNT-FET performance and potentially other SWNT-based electronic devices. PMID- 20738098 TI - Biogenic amines in microdissected brain regions of Drosophila melanogaster measured with micellar electrokinetic capillary chromatography-electrochemical detection. AB - Micellar electrokinetic chromatography with electrochemical detection has been used to quantify biogenic amines in microdissected Drosophila melanogaster brains and brain regions. The effects of pigment from the relatively large fly eyes on the separation have been examined to find that the red pigment from the compound eye masks much of the signal from biogenic amines. The brains of white mutant flies, which have characteristically low pigment in the eyes, have a significantly simplified separation profile in comparison to the red-eyed, wild type, Canton S fly. Yet, the white mutant flies were found to have significantly less amounts of dopamine, l-3,4-dihydroxyphenylalanine (L-DOPA), salsolinol, and N-acetyltyramine in their dissected brains when compared to dissected brains of Canton S flies. In addition, significant variation has been observed in the dissected brains between individual flies that might be related to changes in neurotransmitter turnover. The transgenic GFP fly line (TH-GFP), for which the overall profile of biogenic amines is not found to be significantly different from Canton S, can be used to visualize the location of dopamine neurons. Biogenic amines were then quantified in three brain regions observed to have dopamine levels, the central brain, optic lobes, and posterior superiormedial protocerebrum (PPM1) region. PMID- 20738100 TI - Electrostatic bending of lipid membranes: how are lipid and electrostatic properties interrelated? AB - Electrostatic modification of lipid headgroups and its effect on membrane curvature are not only relevant in a variety of contexts such as cell shape transformation and membrane tubulation but also are intriguingly implicated in membrane functions. For instance, the gating (open vs closed) properties of mechanosensitive channels can be influenced by membrane curvature and ion valence. However, a full theoretical description of membrane electrostatics is still lacking; in the past, membrane bending has often been considered under a few assumptions about how bending modifies lipid arrangements and surface charges. Here, we present a unified theoretical approach to spontaneous membrane curvature, C(0), in which lipid properties (e.g., packing shape) and electrostatic effects are self-consistently integrated. For the description of electrostatic interactions, especially between a lipid charge and a divalent counterion, we implement the Poisson-Boltzmann (PB) approach by incorporation of finite ionic sizes, so as to capture both lateral and transverse charge correlations on the membrane surface. Our results show that C(0) is sensitive to the way lipid rearrangements and divalent counterions are modeled. Interestingly, it can change its sign in the presence of divalent counterions, thus stabilizing reverse hexagonal (H(II)) phases. Our results show how electrostatic modification of headgroups influences the preferred structure of lipid aggregates (inverted micelles vs bilayers). PMID- 20738101 TI - Bioassay-guided isolation of the antidiabetic principle from Sorbus decora (Rosaceae) used traditionally by the Eeyou Istchee Cree First Nations. AB - Bioassay-guided fractionation of a crude extract (80% EtOH in H(2)O) of stem bark of Sorbus decora led the isolation of three new pentacycle triterpenes (compounds 1-3). The structures of 1-3 were established on the basis of spectroscopic methods (IR, HREIMS, 1D and 2D NMR) as 23,28-dihydroxyursan-12-ene-3beta caffeate, 23,28-dihydroxylupan-20(29)-ene-3beta-caffeate, and 3beta,23,28 trihydroxy-12-ursene, respectively. Compound 2 significantly enhanced glucose uptake in C2C12 cells, but compounds 1 and 3 did not. In addition, triterpenoids 4-8, catechin, and epicatechin were also isolated. This is the first comprehensive report of the phytochemical constituents of S. decora since the initial study by Narashmachari and von Rudloff (1962) and includes evaluation of their antidiabetic activity. PMID- 20738102 TI - Chemical constituents of the deep reef caribbean sponges Plakortis angulospiculatus and Plakortis halichondrioides and their anti-inflammatory activities. AB - Chemical investigations of two collections of the deep reef Caribbean sponge Plakortis angulospiculatus resulted in the isolation of a new compound (1) along with the known compound spiculoic acid B (2) belonging to the spiculoic acid class and four other new compounds (3-6) belonging to the zyggomphic acid class. Three new aromatic compounds (7-9) were isolated from the Caribbean sponge Plakortis halichondrioides. The structural determination of the compounds was based on extensive NMR and mass spectroscopic analysis. The isolated compounds 1 7 were tested for their anti-inflammatory activity using in vitro assays for inhibition of inducible nitric oxide synthase and nuclear factor kappa B (NFkappaB) activity, as well as inhibition of intracellular reactive oxygen species generation as a result of oxidative stress. The cytotoxicity of these compounds was also evaluated to determine the selectivity index of their bioactivity with respect to cytotoxicity. Compounds 1 and 4 were more potent than the positive control in inhibiting NFkappaB activity and had IC(50) values of 0.47 and 2.28 MUM, respectively. PMID- 20738104 TI - Aziridinomitosanes via lactam cyclization. AB - Aziridinomitosane ketones 4 and 24 are accessed by internal acyl anion equivalent lactam cyclization of 29 in a convergent route. The key aziridinolactam 6 is prepared by tin-lithium exchange via the lithiated aziridine 11. PMID- 20738103 TI - Antitumor Agents. 282. 2'-(R)-O-acetylglaucarubinone, a quassinoid from Odyendyea gabonensis as a potential anti-breast and anti-ovarian cancer agent. AB - A new quassinoid, designated 2'-(R)-O-acetylglaucarubinone (1), and seven known quassinoids (2-8) were isolated, using bioactivity-guided separation, from the bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre]. The structure of 1 was determined by spectroscopic analysis and by semisynthesis from glaucarubolone. Complete (1)H and (13)C NMR assignments of compounds 1-8 were also established from detailed analysis of two-dimensional NMR spectra, and the reported configurations in odyendene (7) and odyendane (8) were corrected. Compound 1 showed potent cytotoxicity against multiple cancer cell lines. Further investigation using various types of breast and ovarian cancer cell lines suggested that 1 does not target the estrogen receptor or progesterone receptor. When tested against mammary epithelial proliferation in vivo using a Brca1/p53 deficient mice model, 1 also caused significant reduction in mammary duct branching. PMID- 20738106 TI - Sampling from nanoliter plugs via asymmetrical splitting of segmented flow. AB - A microfluidic device is developed to sample from oil-segmented fluid plugs of nanoliter volume by passive splitting. In the device, plugs are pumped into a loop where they split according to the flow resistance of each arm of the loop. The loop structure prevents changes in flow resistance over time, caused by accumulation of plugs in downstream collector capillaries, from interfering with the split ratio. To prevent plugs from recombining at the downstream junction of the loop, a series of posts is fabricated into the junction. This structure allows oil to cross, enabling pressure equalization, but not the aqueous plugs allowing them to be collected into separate capillaries or channels. The split ratio depended on both dimensions of the loop channels and frequency of plugs entering the loop. Split ratios from 1:1 to 34:1 were achieved for samples from 1.7 to 3.3 nL. Long-term stability was demonstrated by splitting over 7000 plugs with 6.3% relative standard deviation of the daughter plug size. The system will have application to high-throughput chemical analysis on a nanoliter scale by enabling several applications including performing multiple assays on a single sample, preserving sample while some is removed for analysis, and splitting reagents or test compounds for use in multiple assays. PMID- 20738105 TI - Sulfate radical anion as a new reagent for fast photochemical oxidation of proteins. AB - The focus is to expand the original design of fast photochemical oxidation of proteins (FPOP) and introduce SO(4)(-*), generated by 248 nm homolysis of low millimolar levels of persulfate, as a radical reactant in protein footprinting. FPOP is a chemical approach to footprinting proteins and protein complexes by "snapshot" reaction with free radicals. The radical used until now is the OH radical, and it provides a measure of residue-resolved solvent accessibility of the native protein. We show that FPOP can accommodate other reagents, increasing its versatility. The new persulfate FPOP system is a potent, nonspecific, and tunable footprinting method; 3-5 times less persulfate is needed to give the same global levels of modification as seen with OH radicals. Although solvent-exposed His and Tyr residues are more reactive with SO(4)(-*) than with (*)OH, oxidation of apomyoglobin and calmodulin shows that (*)OH probes smaller accessible areas than SO(4)(-*), with the possible exception of histidine. His64, an axial ligand in the heme-binding pocket of apomyoglobin, is substantially up-labeled by SO(4)( *) relative to (*)OH. Nevertheless, the kinds of modification and residue selectivity for both reagent radicals are strikingly similar. Thus, the choice of these reagents relies on the physical properties, particularly the membrane permeability, of the radical precursors. PMID- 20738107 TI - Potentiometric detection of model bioaerosol particles. AB - A new technique for the detection of bioaerosols is presented, utilizing particle combustion/ionization in a premixed hydrogen/oxygen/nitrogen flame plasma, followed by gas phase electrochemical detection. Bermuda grass pollen (Cynodon dactylon, one of the most common causes of pollen allergy) and black walnut pollen (Juglans nigra) were used as model bioaerosol particles. We demonstrate that single particle detection can be comfortably achieved by zero current potential measurements between two platinum electrodes, giving potential signals of over 800 mV and unique fragmentation features which may be used for differentiating between species. The high sensitivity is due to the inherent amplification through flame fragmentation, gasification and ionization; a single pollen grain of 25 MUm diameter can give a plume of combustion products measuring 4 mm in diameter. The physical basis of the potential difference is a mixed interfacial potential with an additive diffusion/junction potential due to the increase in ionization from the pollen combustion. The results suggest this methodology may be applied to the detection of particulates composed of ionizable species (organic or inorganic) in gaseous environments, such as bacteria, viruses, pollen grains, and dust. Its effectiveness will depend on the propensity of the target particle to combust and generate voltages under specific flame and electrode conditions. PMID- 20738108 TI - Sugar-mediated acclimation: the importance of sucrose metabolism in meristems. AB - We have designed an in vitro experimental setup to study the role of sucrose in sugar-mediated acclimation of banana meristems using established highly proliferating meristem cultures. It is a first step toward the systems biology of a meristem and the understanding of how it can survive severe abiotic stress. Using the 2D-DIGE proteomic approach and a meristem-specific EST library, we describe the long-term acclimation response of banana meristems (after 2, 4, 8, and 14 days) and analyze the role of sucrose in this acclimation by setting up a control, a sorbitol, and a sucrose acclimation treatment over time. Sucrose synthase is the dominant enzyme for sucrose breakdown in meristem tissue, which is most likely related to its lower energy consumption. Metabolizing sucrose is of paramount importance to survive, but the uptake of sugar and its metabolism also drive respiration, which may result in limited oxygen levels. According to our data, a successful acclimation is correlated to an initial efficient uptake of sucrose and subsequently a reduced breakdown of sucrose and an induction of fermentation likely by a lack of oxygen. PMID- 20738109 TI - On the nature of the "dark S*" excited state of beta-carotene. AB - Femtosecond transient absorption spectroscopy has been applied to the isolated carotenoid beta-carotene under a large variety of experimental conditions regarding solvent, temperature, excitation wavelength, and intensity to study the excited state relaxation dynamics in order to elucidate the origin of the so called "dark S* state", which has been discussed very controversially in the literature. The results are analyzed in terms of lifetime density maps, and various kinetic models are tested on the data. The sample purification was found to be critical. The appearance of a component with a lifetime longer than that of the relaxed S(1) state (i.e., tau > 10 ps), which has been associated previously with the S* (or S(?)) state is due to the presence of an impurity. For pure samples, four lifetimes are typically observed (all <=10 ps at room temperature). Consideration of the large body of experimental data leads us to exclude relaxation schemes implying a separate "dark S* state" in beta-carotene formed in parallel to the normal S(2) -> S(1) relaxation scheme. Vibrational cooling in the S(1) state can explain fully all the features of the transient spectra on the picosecond time scale within a S(2) -> S(1v) -> S(1v') -> S(1) -> S(0) relaxation scheme without invoking any additional electronic or distinctly different conformational states. Thus, we exclude assignments of the previously reported "S* state" signals in beta-carotene (i) to require the postulate of a separate electronic state, (ii) to require the postulate of a large conformational change and/or a partial cis configuration formed in the relaxation pathway, or (iii) to require a vibrationally excited ground state (GS) species. High intensity excitation leads in part to a two-photon excitation to the S(2N) state which upon relaxation gives rise to a different vibrational excitation pattern in the initially created hot S(1) state(s). The spectral changes in the S(1v) state observed upon both short wave excitation as well as high intensity excitation can be explained well by such a modified vibrational excitation pattern. In contrast, the variations in the difference spectra of the partially (S(1v')) and fully vibrationally relaxed S(1) states (S(1)) are minor. The data do not provide any evidence that would require one to postulate the existence of a separate "S* state". PMID- 20738110 TI - Conformer-specific ionization spectroscopy of bromocyclohexane: equatorial versus axial conformers. AB - Ionization of equatorial and axial conformational isomers of the chair bromocyclohexane is investigated with use of the vacuum ultraviolet mass-analyzed threshold ionization (MATI) spectroscopic technique. Two distinct ionization energies of 9.8308 +/- 0.0025 and 9.8409 +/- 0.0025 eV are determined for equatorial or axial conformers, respectively. From the conformer-selective vibrational analysis, it is found that the equatorial conformer undergoes a drastic structural change upon ionization especially along the C-Br distortion mode, whereas the axial conformer shows the modest change along the ring puckering mode with ionization, corresponding to the reaction coordinate for the conformational interconversion. Density functional theory (DFT) calculations with and without considering the spin-orbit coupling provide the appropriate mode assignments for the vibrational bands active in the ionization spectra. Natural bond orbital (NBO) analysis is carried out to give insights into the contribution of the anomeric effect to the structure-energy relationship in each conformational isomer. PMID- 20738111 TI - (Me3Si)3SiH-mediated intermolecular radical perfluoroalkylation reactions of olefins in water. AB - Perfluoroalkyl-substituted compounds are regarded as important components of fluorophors and for the introduction of fluorous tags into organic substrates. Their syntheses in organic solvents are achieved through different methods, among which, the addition of perfluoroalkyl radicals to unsaturated bonds represents a convenient choice. On the other hand, intermolecular radical reactions in water have attracted the attention of synthetic chemists as a strategic route to carbon carbon bond formation reactions. In this paper we undertook the intermolecular addition of perfluoroalkyl radicals on electron rich alkenes and alkenes with electron withdrawing groups in water, mediated by silyl radicals, and obtained perfluoroalkyl-substituted compounds in fairly good yields. The radical triggering events employed consist of the thermal decomposition of an azo compound and the dioxygen initiation. Our results indicate that for intermolecular carbon-carbon bond formation reactions mediated by (Me(3)Si)(3)SiH, the decomposition of the azo compound 1,1' azobis(cyclohexanecarbonitrile) (ACCN) is the best radical initiator. We also found that water exerts a relevant solvent effect on the rates of perfluoroalkyl radical additions onto double bonds and the H atom abstraction from the silane. Our account provides a versatile and convenient method to achieve perfluoroalkylation reactions of alkenes in water to render perfluoroalkylated alkanes as key intermediates in the synthesis of fluorophors and other fluorinated materials. This is the first report where perfluoroalkyl-substituted alkanes are synthesized through intermolecular radical carbon-carbon bond formation reactions in water, mediated by silyl radicals. PMID- 20738112 TI - Influence of confinement on hydrogen bond energy. The case of the FH...NCH dimer. AB - The influence of the external pressure on the energy of the intermolecular hydrogen bond is investigated by modeling the pressure effects with helium atoms located at fixed points in space around the hydrogen bonded dimer. Several methods of estimating the energy of the H...N hydrogen bond in the He...FH...NCH...He model system are proposed. They show that the energy of the H...N hydrogen bond in this confined dimer decreases continuously with the reduction of the He...He distance, thus with the increase of the pressure effect exerted on the confined dimer. PMID- 20738113 TI - Achieving the theoretical depairing current limit in superconducting nanomesh films. AB - We show the theoretical depairing current limit can be achieved in a robust fashion in highly ordered superconductor nanomesh films having spatial periodicities smaller than both the superconducting coherence length and the magnetic penetration depth. For a niobium nanomesh film with 34 nm spatial periodicity, the experimental critical current density is enhanced by more than 17 times over the continuous film and is in good agreement with the depairing limit over the entire measured temperature range. The nanomesh superconductors are also less susceptible to thermal fluctuations when compared to nanowire superconductors. T(c) values similar to the bulk film are achieved, and the nanomeshes are capable of retaining superconductivity to higher fields relative to the bulk. In addition, periodic oscillations in T(c) are observed as a function of field, reflecting the highly ordered nanomesh structure. PMID- 20738114 TI - Spectroscopy of covalently functionalized graphene. AB - In order to engineer a band gap into graphene, covalent bond-forming reactions can be used to change the hybridization of the graphitic atoms from sp(2) to sp(3), thereby modifying the conjugation length of the delocalized carbon lattice; similar side-wall chemistry has been shown to introduce a band gap into metallic single-walled carbon nanotubes. Here we demonstrate that the application of such covalent bond-forming chemistry modifies the periodicity of the graphene network thereby introducing a band gap (~0.4 eV), which is observable in the angle-resolved photoelectron spectroscopy of aryl-functionalized graphene. We further show that the chemically-induced changes can be detected by Raman spectroscopy; the in-plane vibrations of the conjugated pi-bonds exhibit characteristic Raman spectra and we find that the changes in D, G, and 2D-bands as a result of chemical functionalization of the graphene basal plane are quite distinct from that due to localized, physical defects in sp(2)-conjugated carbon. PMID- 20738115 TI - Electrospun metal nanofiber webs as high-performance transparent electrode. AB - Transparent electrodes, indespensible in displays and solar cells, are currently dominated by indium tin oxide (ITO) films although the high price of indium, brittleness of films, and high vacuum deposition are limiting their applications. Recently, solution-processed networks of nanostructures such as carbon nanotubes (CNTs), graphene, and silver nanowires have attracted great attention as replacements. A low junction resistance between nanostructures is important for decreasing the sheet resistance. However, the junction resistances between CNTs and boundry resistances between graphene nanostructures are too high. The aspect ratios of silver nanowires are limited to ~100, and silver is relatively expensive. Here, we show high-performance transparent electrodes with copper nanofiber networks by a low-cost and scalable electrospinning process. Copper nanofibers have ultrahigh aspect ratios of up to 100000 and fused crossing points with ultralow junction resistances, which result in high transmitance at low sheet resistance, e.g., 90% at 50 Omega/sq. The copper nanofiber networks also show great flexibility and stretchabilty. Organic solar cells using copper nanowire networks as transparent electrodes have a power efficiency of 3.0%, comparable to devices made with ITO electrodes. PMID- 20738116 TI - Assessing the role of moment of inertia in optical Kerr effect spectroscopy. AB - Optical Kerr effect (OKE) spectroscopy allows for the acquisition of high quality, Bose-Einstein-corrected, low-frequency Raman spectra in liquids. However, the assignment of a molecular interpretation to these spectra remains an open problem. To address this issue, here we present an OKE study of benzene and four of its isotopologues. Our results indicate that hindered rotations are the major contributor to the OKE reduced spectral density (RSD) over the entire intermolecular spectral region (0-250 cm(-1)). We also have found that isotopologues with six (13)C atoms have RSDs that are enhanced at frequencies below 30 cm(-1). We further demonstrate that the collective orientational correlation time of these liquids scales with the inverse square root of the tumbling moment of inertia, indicating that there is strong translation-rotation coupling in benzene. PMID- 20738117 TI - SERS-active gold lace nanoshells with built-in hotspots. AB - Development of multifunctional drug delivery vehicles with therapeutic and imaging capabilities as well as in situ methods of monitoring of intracellular processes will greatly benefit from a simple method of preparation of plasmonic Au structures with nanometer scale gaps between sharp metallic elements where the so-called SERS hot spots can be formed. Here the synthesis of gold lace capsules with average diameters ca. 100 nm made of a network of metallic branches 3-5 nm wide and separated by 1-3 nm gaps is reported. Biocompatible amphiphilic polyurethanes (PUs) were used as template for these particles. The unusual topology of the produced gold lace shells somewhat reminiscent of Faberge eggs is likely to reflect the network of hydrophobic and hydrophilic domains of PU globules. The gold lace develops from initial open weblike structures by gradual enveloping the PU template. The diameter of gold lace shell is determined by the size of PUs in water and can be adjusted by the molecular mass of PUs. The close proximity between branches makes them excellent supports for surface-enhanced Raman spectroscopy (SERS), which was demonstrated using 1-naphthalenethiol upon excitation with photons with different wavelengths. The loading and releasing of pyrene as a model of hydrophobic drugs and the use of SERS to monitor it were demonstrated. PMID- 20738119 TI - Light-emitting polymer single nanofibers via waveguiding excitation. AB - We report a general approach to light-emitting polymer nanofibers (PNFs) based on waveguiding excitation. By waveguiding excitation light along the PNFs, we demonstrated that the interaction of light with PNFs is enhanced over 3 orders of magnitude compared with the currently used irradiating excitation. Intriguing advantages such as enhanced excitation efficiency, low excitation power operation down to nW levels, tightly confined excitation with low cross talk, and high photostability of the light-emitting PNFs are obtained. The waveguiding excitation allows incorporation of various fluorescent dyes into PNFs to generate multicolor emitting sources covering the entire visible spectrum. The light emitting single PNFs via waveguiding excitation may find widespread nanophotonic applications in chemical and biological sensors, multicolor emitting sources, and lasers. PMID- 20738118 TI - Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy. AB - A series of doxorubicin-loaded polymer-caged nanobins (PCN(DXR)) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCN(DXR) offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCN(DXR), and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCN(DXR) can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCN(DXR) was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy. PMID- 20738121 TI - Organic photovoltaic devices using highly flexible reduced graphene oxide films as transparent electrodes. AB - The chemically reduced graphene oxide (rGO) was transferred onto polyethylene terephthalate (PET) substrates and then used as transparent and conductive electrodes for flexible organic photovoltaic (OPV) devices. The performance of the OPV devices mainly depends on the charge transport efficiency through rGO electrodes when the optical transmittance of rGO is above 65%. However, if the transmittance of rGO is less than 65%, the performance of the OPV device is dominated by the light transmission efficiency, that is, the transparency of rGO films. After the tensile strain (~2.9%) was applied on the fabricated OPV device, it can sustain a thousand cycles of bending. Our work demonstrates the highly flexible property of rGO films, which provide the potential applications in flexible optoelectronics. PMID- 20738120 TI - Biocompatible magnetofluorescent probes: luminescent silicon quantum dots coupled with superparamagnetic iron(III) oxide. AB - Luminescent silicon quantum dots (SiQDs) are gaining momentum in bioimaging applications, based on their unique combination of optical properties and biocompatibility. Here, we report the development of a multimodal probe that combines the optical properties of silicon quantum dots with the superparamagnetic properties of iron oxide nanoparticles to create biocompatible magnetofluorescent nanoprobes. Multiple nanoparticles of each type are coencapsulated within the hydrophobic core of biocompatible phospholipid polyethyleneglycol (DSPE-PEG) micelles. The size distribution and composition of the magnetofluorescent nanoprobes were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Enhanced cellular uptake of these probes in the presence of a magnetic field was demonstrated in vitro. Their luminescence stability in a prostate cancer tumor model microenvironment was demonstrated in vivo. This paves the way for multimodal silicon quantum-dot-based nanoplatforms for a variety of imaging and delivery applications. PMID- 20738122 TI - Quantum spin transport in carbon chains. AB - First-principles and non-equilibrium Green's function approaches are used to predict spin-polarized electronic transport in monatomic carbon chains covalently connected to graphene nanoribbons, as recently synthetized experimentally (Jin, C.; et al. Phys. Rev. Lett. 2009, 102, 205501-205504). Quantum electron conductances exhibit narrow resonant states resulting from the simultaneous presence of open conductance channels in the contact region and on the chain atoms. Odd-numbered chains, which acquire metallic or semiconducting character depending on the nature of the edge at the graphene contact, always display a net spin polarization. The combination of electrical and magnetic properties of chains and contacts results in nanodevices with intriguing spintronic properties such as the coexistence of magnetic and semiconducting behaviors. PMID- 20738123 TI - Diastereoselective cycloadditions and transformations of N-alkyl and N-aryl maleimides with chiral 9-anthrylethanol derivatives. AB - Thermal Diels-Alder reactions of chiral 9-methoxyethyl and 9-hydroxyethyl anthracene have been investigated both experimentally and computationally with a range of N-substituted maleimides. Whereas cycloadditions with 9-methoxyethyl anthracene proceeded with almost complete diastereselectivity, those with 1 anthracene-9-yl-ethanol resulted in essentially no diastereoselectivity. Subsequent regio- and stereoselective transformations with reducing agents and carbon nucleophiles demonstrated the synthetic utility of this methodology, which was applied to the enantioselective synthesis of pyrrolo[2,1-a]isoquinolines and an attempted synthesis of the alkaloid crispine A. Computational studies supported the proposed hypotheses for the stereoselectivity observed in the transformations described. PMID- 20738124 TI - Plasmon-mediated radiative energy transfer across a silver nanowire array via resonant transmission and subwavelength imaging. AB - Efficient plasmon-mediated excitation energy transfer between the CdSe/ZnS semiconductor quantum dots (QDs) across the silver nanowire array up to 560 nm in length is observed. The subwavelength imaging and spectral response of the silver nanowire arrays with near-field point-source excitations are revealed by theoretical simulations. Our studies demonstrate three advantages of the nanosystem: efficient exciton-plasmon conversion at the input side of the array through near-field strong coupling, directional waveguidance and resonant transmission via half-wave plasmon modes of the nanowire array, and subwavelength imaging at the output side of the array. These advantages allow a long-range radiative excitation energy transfer with a high efficiency and a good directionality. PMID- 20738125 TI - Surface energy modification by spin-cast, large-area graphene film for block copolymer lithography. AB - We demonstrate a surface energy modification method exploiting graphene film. Spin-cast, atomic layer thick, large-area reduced graphene film successfully played the role of surface energy modifier for arbitrary surfaces. The degree of reduction enabled the tuning of the surface energy. Sufficiently reduced graphene served as a neutral surface modifier to induce surface perpendicular lamellae or cylinders in a block copolymer nanotemplate. Our approach integrating large-area graphene film preparation with block copolymer lithography is potentially advantageous in creating semiconducting graphene nanoribbons and nanoporous graphene. PMID- 20738127 TI - Selective synthesis of either isoindole- or isoindoline-1-carboxylic acid esters by Pd(0)-catalyzed enolate arylation. AB - Two efficient palladium-catalyzed intramolecular alpha-arylation reactions of alpha-amino acid esters have been developed that allow either 1 isoindolecarboxylic acid esters or the corresponding isoindolines to be selectively synthesized simply by a slight change of reaction conditions. PMID- 20738128 TI - New homotrinuclear lanthanide complexes: synthesis, characterization and spectroscopic study. AB - This work presents the synthesis and spectroscopic study of new homotrinuclear (TRI) systems for photonics applications. The luminescence spectroscopy shows characteristics transitions of Eu(III) and Tb(III) ions. For the Gd(III) complexes, the triplets states were determined by phosphorescence measurement. The complexes' coordination geometries were calculated using the Sparkle/AM1 model. For the europium systems, the Sparkle/AM1 geometries were used to calculate all details involved in the energy transfer process, and the theoretical quantum yields were determined. From an energy diagram, that estimates triplet levels, it was possible to understand some experimental phenomenon, such as weak luminescence for precursor complex (without heterocyclics ligands), and ligands emission in terbium complexes. Some of these observations can also be explained by the Jablonski diagrams that describe, based on theoretical calculations, all luminescent process. The synthesized complexes showed high values of quantum yield in ethanolic environment: 50% for EuTRIDipy, 26% EuTRITerpy, and 56% for EuTRIPhen complexes. PMID- 20738129 TI - Corrosive microenvironments at lead solder surfaces arising from galvanic corrosion with copper pipe. AB - As stagnant water contacts copper pipe and lead solder (simulated soldered joints), a corrosion cell is formed between the metals in solder (Pb, Sn) and the copper. If the resulting galvanic current exceeds about 2 MUA/cm(2), a highly corrosive microenvironment can form at the solder surface, with pH < 2.5 and chloride concentrations at least 11 times higher than bulk water levels. Waters with relatively high chloride tend to sustain high galvanic currents, preventing passivation of the solder surface, and contributing to lead contamination of potable water supplies. The total mass of lead corroded was consistent with predictions based on the galvanic current, and lead leaching to water was correlated with galvanic current. If the concentration of sulfate in the water increased relative to chloride, galvanic currents and associated lead contamination could be greatly reduced, and solder surfaces were readily passivated. PMID- 20738130 TI - Mechanisms of boron tolerance and accumulation in plants: a physiological comparison of the extremely boron-tolerant plant species, Puccinellia distans, with the moderately boron-tolerant Gypsophila arrostil. AB - The physiological characteristics of the extremely boron (B)-tolerant plant species, Puccinellia distans, were compared with those of the moderately tolerant Gypsophila arrostil, two species collected from a B-mining area of Eskisehir, Turkey. Boron was supplied to plants hydroponically at B concentrations ranging from 0.5 to 50 mg B/L for G. arrostil, and from 0.5 to 2000 mg B/L for P. distans. The results show that P. distans has a strikingly greater tolerance to B than G. arrostil. While G. arrostil was unable to survive B supply concentrations greater than 50 mg B/L, P. distans grew at B supply concentrations exceeding 1250 mg B/L. Our research supports the conclusion that from 0.5 to 50 mg B/L, P. distans is better able to restrict the accumulation of B in the whole plant, and the transport of B from root to shoot, than G. arrostil. We propose that P. distans uses several strategies to achieve B tolerance including the ability to restrict the accumulation of B relative to its accumulation of biomass, the ability to restrict the transport of B from root to shoot, and, to a lesser extent, the ability to tolerate high concentrations of B in its shoot and root tissues. PMID- 20738131 TI - Correlating nanorod structure with experimentally measured and theoretically predicted surface plasmon resonance. AB - The extinction spectra of Au nanorods electrochemically synthesized using anodic aluminum oxide templates are reported. Homogeneous suspensions of nanorods with average diameters of 35, 55, 80, and 100 nm and varying lengths were synthesized, and their resultant surface plasmon resonances were probed by experimental and theoretical methods. Experimental extinction spectra of the nanoparticles exhibit good overall agreement with those calculated using the discrete dipole approximation. We determine the dependence of the dipole plasmon wavelength on both rod length and diameter, and we then utilize these results to derive an equation for predicting longitudinal dipole resonance wavelength for nanorod dimensions beyond the quasistatic limit. On average, the equation allows one to predict plasmon resonance maxima within 25 nm of the experimentally measured values. An analysis of factors that are important in determining the plasmon width is also provided. For long rods, the width decreases with increasing length in spite of increased radiative damping due to increased frequency dispersion in the real part of the metal dielectric function. PMID- 20738133 TI - Pb2B5O9I: an iodide borate with strong second harmonic generation. AB - The combination of lone-pair effects on Pb(2+) cations and the smaller electronegativity of I(-) anions into the pentaborate framework generates a phase matchable material, Pb(2)B(5)O(9)I, with the largest powder SHG response among borates, about 13.5 times that of KDP (KH(2)PO(4)), and transparency over the near-UV to middle-IR region. DFT calculations on electronic structure and cutoff energy-dependent SHG coefficients confirm these origins. PMID- 20738132 TI - Improvement of total lipid and glycerophospholipid recoveries from various food matrices using pressurized liquid extraction. AB - The extraction of three major phospholipid (PL) classes contained in soybean, egg yolk, calf brain, and ox liver was investigated by means of two methods. The PL amounts were evaluated. A new method, based on pressurized liquid extraction (PLE), was applied for total lipids (TL), including PL, extraction and compared with a standard liquid extraction method, a modified Folch method. The three PL classes (phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylcholine (PC)) that were recovered in the obtained TL extracts were quantified using HPLC with an evaporative light-scattering detector (ELSD). Using the PLE method, a single extraction allowed a recovery of more than 94% of TL and 96% of each PL class. Two successive extractions could achieve a total recovery of the three studied PL classes. With the modified Folch method, 77-83% of TL, 80 91% of PE, 82-94% of PC, and no more than 78% of PI could be achieved from various food matrices after one extraction. Four successive extractions were necessary to recover the whole TL content and each PL class. Results indicate that PLE is a rapid and efficient lipid extraction system for the broad range of plant and animal tissues. PMID- 20738134 TI - Tunneling in a simple bond scission: the surprising Barrier in the H loss from HCOOH(+). AB - The dissociation dynamics of gas phase formic acid ions (HCOOH(+), DCOOD(+), HCOOD(+), DCOOH(+)) are investigated by threshold photoelectron-photoion coincidence (TPEPICO) spectroscopy and high level ab initio calculations. The slow rate constants for this seemingly simple H loss reaction and the large onset energy shifts due to isotopic substitution point to a substantial exit barrier through which the H or D atoms tunnel. Modeling of the HCOOH(+) experimental data using RRKM theory with tunneling through an Eckart potential are best fitted with a barrier of about 17 kJ mol(-1). High level ab initio calculations support the experimental findings with a computed barrier of 15.9 kJ mol(-1), which is associated with the substantial geometry change between the product HOCO(+) cation and the corresponding HCOOH(+) molecular ion. Because of this exit channel barrier, the formic acid ion dissociation does not provide a route for determination of the HOCO(+) heat of formation. Rather, the most accurate value comes from the calculations employing the high accuracy extrapolated ab initio thermochemistry (HEAT) scheme, which yields a Delta(f)H(o)(0K)[HOCO(+)] = 600.3 +/- 1.0 kJ mol(-1) (Delta(f)H(o)(298K)[HOCO(+)] = 597.3 +/- 1.0 kJ mol(-1)). The calculated proton affinity of CO(2) is thus 534.7 +/- 1.0 kJ mol(-1) at 0 K and 539.3 +/- 1.0 kJ mol(-1) at 298.15 K. PMID- 20738135 TI - Updated Abraham solvation parameters for polychlorinated biphenyls. AB - This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air-n-hexadecane and n-octanol-water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was derived from four PCB properties and associated Abraham solvation equations. Additionally, the influence of ortho-chlorination on PCB solvent accessible volume and surface area was investigated. The updated PCB solvation parameters were tested on partitioning between five other phase combinations. Compared to the original PCB solvation parameter set, the updated PCB solvation parameters resulted in substantially improved estimates from Abraham solvation equations for (subcooled) liquid vapor pressures, aqueous solubilities, HPLC capacity factors, and for coefficients of air-n-hexadecane, air-water, organic carbon-water, and n-octanol water partitioning. For water to polydimethyl siloxane and sodium dodecylsulphate (SDS) partitioning, the updated PCB solvation parameters yielded no improvement compared to the original data set. The main difference between the updated and the original parameter set is that updated PCB McGowan specific volumes depend on the degree of ortho-chlorination, which is qualitatively confirmed by trends in the PCB solvent accessible volumes and surface areas. The use of the updated PCB solvation parameters instead of the original values is therefore recommended. PMID- 20738136 TI - Chemiluminescence arising from the decomposition of peroxymonocarbonate and enhanced by CdTe quantum dots. AB - CdTe quantum dots (QDs) capped with mercaptoacetic acid were applied to the hydrogen peroxide-sodium hydrogen carbonate chemiluminescence (CL) system. The CL emission intensity was significantly enhanced by different sizes of CdTe QDs. Peroxymonocarbonate (HCO(4)(-)) was formed in the reaction of hydrogen peroxide and sodium hydrogen carbonate, which was a reactive oxygen species. Decomposition of HCO(4)(-) generated superoxide ion radical (.O(2)(-)) and hydroxide radical (.OH). The enhanced CL was induced by the excited CdTe QDs, which could be produced from the combination of hole (oxidized QDs (h(+))) and electron (reduced QDs (e(-))) injected QDs. Radical scavengers and organic reagents such as nitro blue tetrazolium chloride (NBT), cytochrome c, sodium azide, ascorbic acid, thiourea, tert-butanol, and dimethyl sulphoxide were used to study the emitting species. The intermediate hydroxide radical and superoxide ion were key species for producing hole and electron-injected QDs. Four emitters such as (1)O(2), (O(2))(2)*, (CO(2))(2)* and CdTe* were detected in the CL system. The mechanism was discussed based on the CL emission spectra, electron spin resonance spectra, fluorescence spectra, and UV-vis absorption spectra. The CL properties of CdTe QDs will be helpful to study semiconductor nanocrystals and will open new avenues for the application of QDs in many fields, such as chemistry, biology, microbiology, and biochemistry. PMID- 20738137 TI - Incorporation of boron, aluminum, and gallium derivatives into [{Ti(eta(5) C5Me5)(MU-O)}3(MU3-CR)] (R = H, Me). AB - The synthesis and characterization of a family of alkyl and halide adducts of group 13 elements (B, Al, Ga), containing the MU(3)-alkylidyne oxo derivative ligands [{Ti(eta(5)-C(5)Me(5))(MU-O)}(3)(MU(3)-CR)] [R = H (1), Me (2)], are presented. The compounds are synthesized by Lewis acid-base reactions involving equimolecular amounts of 1 or 2 and alkyl [AlR'(3)] (R' = Me, Et, Ph) or halide derivatives [MX(3)] (M = B, X = Br; M = Al, X = Cl, Br, I; M = Ga, X = Cl, Br). The novel species [{E(3)M}(MU(3)-O)(MU-O)(2){Ti(eta(5)-C(5)Me(5))}(3)(MU(3)-CR)] (3-8 and 11-21; R = H, Me; M = B, Al, Ga; E = alkyl, halide) exhibit coordination of 1 or 2 through one of the three oxygen atoms of the Ti(3)O(3) ring to the metal center. In the case of the reaction of 2 with 2 equiv of [AlMe(3)], the complex [{MeAl}(MU(3)-O)(3){Ti(eta(5)-C(5)Me(5))}(3)(MU(3)-CCH(2-))] (9) containing the naked carbanion MU(3)-CCH(2-) was isolated with methane elimination. On the other hand, the derivative [{Br(3)B}(MU(3)-O)(MU O)(2){Ti(eta(5)-C(5)Me(5))}(3)(MU(3)-CMe)] (11) undergoes cleavage of the trinuclear structure to give [TiBr(eta(5)-C(5)Me(5))}(MU-O){Ti(eta(5) C(5)Me(5))}(MeCBO(2)){TiBr(2)(eta(5)-C(5)Me(5))}] (22). The crystalline structures of some of these products are also included in this paper. PMID- 20738138 TI - A detailed study of the electronic structure of Fe3 cluster and associative adsorption of N2 to this cluster: a natural bond orbital analysis. AB - To develop a detailed picture of the bare Fe3 cluster structure, the nature of chemical bonding in this metal cluster is investigated by natural bond orbital (NBO) and natural resonance theory (NRT) analyses. The first part of the study clearly shows that the main factor governing the ground-state geometry of this cluster is the delocalized nature of the valence electrons. Highly unsaturated structure and the charge transfer list of Omegai -> Omegaj* NBO interactions of the parent reference Fe3 structure draw one's attention to the possible candidate structures presenting the correct electronic structure consistent with the observed optimized geometry of Fe3. In the other part of the study, different established modes of nitrogen coordination on Fe3 cluster are investigated. It is found that the most favored adsorption site for the associative attachment of N2 is the bridge site, with the binding energy of -17.6 kcal/mol. NBO analysis is also applied to present a detailed discussion of the metal-ligand interactions and the predominate role of the delocalized valence electrons. PMID- 20738139 TI - Confinement effects on monosaccharide transport in nanochannels. AB - Transport theories based on the continuum hypothesis may not be appropriate at the nanoscale in view of surface effects. We employed molecular dynamics simulations to study the effects of confinement and concentration on diffusive transport of glucose in silica nanochannels (10 nm or smaller). We found that glucose modifies the electrical properties of nanochannels and that, below 5 nm in channel height, glucose adsorption and diffusivity are significantly reduced. With increasing concentration, the diffusivity is reduced linearly in the bulk, while it is reduced nonlinearly at the interface. The effective diffusivity reduction is related to the interface thickness, which can be 2-4 nm depending on concentration, and has an unexpected reduction at low concentrations. Results suggest that nanochannels present a one-dimensional cage environment that affects diffusivity in a fashion similar to cage-breaking diffusion. Our simulation results, consistent with the experimental observations presented here, suggest that nanoconfinement is the essential cause of the observed altered fluid diffusive transport, not accounted for by classical theories, because of coupling of confinement and concentration effects. PMID- 20738140 TI - TAMkin: a versatile package for vibrational analysis and chemical kinetics. AB - TAMkin is a program for the calculation and analysis of normal modes, thermochemical properties and chemical reaction rates. At present, the output from the frequently applied software programs ADF, CHARMM, CPMD, CP2K, Gaussian, Q-Chem, and VASP can be analyzed. The normal-mode analysis can be performed using a broad variety of advanced models, including the standard full Hessian, the Mobile Block Hessian, the Partial Hessian Vibrational approach, the Vibrational Subsystem Analysis with or without mass matrix correction, the Elastic Network Model, and other combinations. TAMkin is readily extensible because of its modular structure. Chemical kinetics of unimolecular and bimolecular reactions can be analyzed in a straightforward way using conventional transition state theory, including tunneling corrections and internal rotor refinements. A sensitivity analysis can also be performed, providing important insight into the theoretical error margins on the kinetic parameters. Two extensive examples demonstrate the capabilities of TAMkin: the conformational change of the biological system adenylate kinase is studied, as well as the reaction kinetics of the addition of ethene to the ethyl radical. The important feature of batch processing large amounts of data is highlighted by performing an extended level of theory study, which TAMkin can automate significantly. PMID- 20738141 TI - Synthesis of dibenzo[b,f][1,4]oxazepin-11(10H)-ones via intramolecular cyclocarbonylation reactions using PdI(2)/Cytop 292 as the catalytic system. AB - The intramolecular cyclocarbonylation of substituted 2-(2-iodophenoxy)anilines was catalyzed by PdI(2) and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phospha adamantane (Cytop 292) in an efficient manner. A series of substituted dibenzo[b,f][1,4]oxazepin-11(10H)-ones were prepared in good yields under mild reaction conditions. PMID- 20738142 TI - Synthesis and optical properties of trioxatriangulenium dyes with one and two peripheral amino substituents. AB - Several derivatives of two new dye systems, with one or two dialkylamino donor groups attached to resonant positions at the periphery of a trioxatriangulenium ion, were synthesized. The mono- and bis-dialkylamino trioxatriangulenium salts (A(1)-TOTA(+) and A(2)-TOTA(+)) were prepared from methoxy-substituted triphenylmethylium (TPM) compounds by aromatic nucleophilic substitution with secondary amines and subsequent intramolecular ring closure. The optical properties of the new triangulenium dyes and their TPM precursors were investigated and compared to those of known TPM and xanthenium dyes. The optical properties were found to be dependent on symmetry and charge localization in the conjugated framework. The trioxatriangulenium dye with two amino groups (A(2) TOTA(+)) was found to be a strong fluorophore with properties as a blue-shifted rhodamine B. The mono-substituted compound (A(1)-TOTA(+)) was found to be only weakly fluorescent. We assign the weak fluorescence of A(1)-TOTA(+) to an efficient but reversible formation of a nonfluorescent conformation in the excited state, favored by the large degree of charge localization in this dye with only one donor group. PMID- 20738143 TI - Synthesis of geminal difluorides by oxidative desulfurization-difluorination of alkyl aryl thioethers with halonium electrophiles in the presence of fluorinating reagents and its application for 18F-radiolabeling. AB - Various omega-substituted 1,1-difluoroalkanes are synthesized in good yields from alkyl aryl thioethers by a new oxidative desulfurization-difluorination protocol with the reagents combination of 1,3-dibromo-5,5-dimethylhydantoin (DBH) as an oxidizer and pyridine.9HF (Py.9HF) as a fluoride source. The reaction proceeds via a fluoro-Pummerer-type rearrangement followed by an oxidative desulfurization fluorination step. Starting from alpha-fluorinated thioethers, this reaction is promising for (18)F-labeling (tau(1/2) = 110 min) of ligands applicable for positron emission tomography (PET). Using the combination of DBH and carrier added Py.9H[(18)F]F, an (18)F-labeled difluoride was synthesized from the corresponding alpha-fluoro thioether with a radiochemical yield of 9%. PMID- 20738144 TI - Base-promoted one-pot tandem reaction of 3-(1-alkynyl)chromones under microwave irradiation to functionalized amino-substituted xanthones. AB - A base-promoted one-pot tandem reaction has been developed from 3-(1 alkynyl)chromones with various acetonitriles to afford functionalized amino substituted xanthones 3 under microwave irradiation. This tandem process involves multiple reactions, such as Michael addition/cyclization/1,2-addition, without a transition metal catalyst. This method provides an efficient approach to build up natural product-like diversified amino-substituted xanthone scaffolds rapidly. PMID- 20738145 TI - Synthesis, structure, and electronic and photophysical properties of two- and three-layered [3.3]paracyclophane-based donor-acceptor systems. AB - The synthesis, structural, redox, and photophysical properties of the two- and three-layered donor-acceptor (D-A) type [3.3]paracyclophanes ([3.3]PCPs) are described. The synthesis of the two- and three-layered [3.3]PCPs 1 and 2 containing 2,1,3-benzothiadiazole (BTD) as an acceptor was achieved by the (p ethylbenzenesulfonyl)methyl isocyanide coupling method. The cyclic voltammograms of 1 and 2 along with those of respective dione precursors 5 and 7 clearly indicate that the presence of the -CH(2)COCH(2)- bridge interferes with the electronic interactions between the BTD and the benzene rings, suggesting the importance of the through-bond interaction in the ground state. In sharp contrast, the UV/vis spectra of 1 and 5 as well as those of 2 and 7 exhibit similar bands regardless of the presence of the -CH(2)COCH(2)- or CH(2)CH(2)CH(2)- bridges, indicating that the charge-transfer (CT) interaction is mainly responsible for the through-space interaction. The two-layered PCPs, 5 and 1, show broad structureless fluorescence bands at the same position of 468 nm, while those of the three-layered PCPs, 7 and 2, appear at 501 and 496 nm, respectively, with lower quantum yields compared to those of the two-layered PCPs probably due to the stronger intramolecular CT interaction of the three-layered PCPs in the ground state. PMID- 20738146 TI - Palladium-catalyzed alkoxyamination of alkenes with use of N fluorobenzenesulfonimide as oxidant. AB - A Pd-catalyzed alkoxyamination of protected aminoalkenes promoted by N fluorobenzenesulfonimide is described. This mild transformation allows the direct formation of ethers from carbon-carbon double bonds. An unusual switch from exo to endo selectivity in polar solvents was discovered, allowing the selective formation of either regioisomer by careful choice of reaction conditions. PMID- 20738147 TI - Free-radical ring closure to conformationally locked alpha-L-carba-LNAs and synthesis of their oligos: nuclease stability, target RNA specificity, and elicitation of RNase H. AB - A new class of conformationally constrained nucleosides, alpha-L-ribo-carbocyclic LNA thymidine (alpha-L-carba-LNA-T, LNA is an abbreviation of locked nucleic acid) analogues and a novel "double-locked" alpha-L-ribo-configured tetracyclic thymidine (6,7'-methylene-bridged-alpha-L-carba-LNA-T) in which both the sugar puckering and glycosidic torsion are simultaneously constrained, have been synthesized through a key step involving 5-exo free-radical intramolecular cyclization. These alpha-L-carba-LNA analogues have been subsequently transformed to corresponding phosphoramidites and incorporated into isosequential antisense oligonucleotides (AONs), which have then been examined for the thermal denaturation of their duplexes, nuclease stability, and RNase H recruitment capabilities. Introduction of a single 6',7'-substituted alpha-L-carba-LNA-T modification in the AON strand of AON/RNA heteroduplex led to T(m) reduction by 2 3 degrees C as compared to the native heteroduplex, whereas the parent 2'-oxa alpha-L-LNA-T modification at the identical position in the AON strand has been found to lead to an increase in the T(m) by 3-5 degrees C. This suggests that the 6' and 7' substitutions lead to much reduced thermal stability for the modified heteroduplex, especially the hydrophobic 7'-methyl on alpha-L-carba-LNA, which is located in the major groove of the duplex. All of the AONs incorporating 6',7'-substituted alpha-L-carba-LNA-T have, however, showed considerably improved nuclease stability toward 3'-exonuclease (SVPDE) and in human blood serum compared to the 2'-oxa-alpha-L-LNA-T incorporated AONs. The hybrid duplexes that are formed by 6',7'-substituted alpha-L-carba-LNA-T-modified AONs with complementary RNA have been found to recruit RNase H with higher efficiency than those of the beta-D-LNA-T or beta-D-carba-LNA-T-modified counterparts. These greatly improved nuclease resistances and efficient RNase H recruitment capabilities elevate the alpha-L-carba-LNA-modified nucleotides into a new class of locked nucleic acids for potential RNA targeting therapeutics. PMID- 20738148 TI - Improved iterative synthesis of linearly disassembling dendrons. AB - We report a significant improvement in the synthesis of disassembling dendritic structures by using 4-hydroxy-3-nitrobenzoic acid as the building block. We have prepared multigram quantities of first- through third-generation linearly disassembling dendrons containing a [3-N,4-O]-benzylaryl ether disassembly pathway, capped by a vanillin-derived phenyl allyl ether trigger, and a p nitrophenoxy (PNP) reporter group. The disassembly process of these materials was initiated by allyl deprotection and monitored by the absorbance of the PNP reporter unit in the UV-vis. Modification of the disassembly conditions for the allyl trigger resulted in decreased disassembly times, decreased incubation time for onset of disassembly from minutes to seconds, and allowed observation of indicative rate differences between generations not seen with the previously reported conditions. PMID- 20738149 TI - Antimicrobial and antioxidant effects of phenolic constituents from Klainedoxa gabonensis. AB - Bioassay-guided fractionation of the methanol extract of the stem bark of Klainedoxa gabonensis Pierre ex Engl. (Irvingiaceae) afforded 12 compounds, namely, ellagic acid (1), ellagic acid 3,3'-dimethylether (2), gallic acid (3), methyl gallate (4), lupeol (5), beta-amyrin (7), erythrodiol (8), oleanolic acid (9), betulinic acid (6), hederagenin (10), bayogenin acid (11), and stigmasterol 3-O-beta-d-glucopyranoside (12). Compounds 1-3 and 7-12 were isolated for the first time from this genus. The structures were established on the basis of 1D/2D NMR experiments and mass spectrometric data. Crude extract, fractions (A, B, C and D) and pure compounds were tested for their antimicrobial activity using paper disk agar diffusion assay. The test delivered a range of low to high activities for phenolic compounds 1-4, low or missing activities for terpenoid compounds 5-11, and impressive very high antibacterial/antifungal values for two fractions C and D probably due to synergistic effects of compounds. The broth microdilution assay revealed MICs of 15.4-115.1 MUg/mL for phenolic compounds, MICs higher than 1 mg/mL for terpenoids and MICs of 4.5-30.3 MUg/mL for fractions C and D. The determination of the radical scavenging activity using 1,1-diphenyl 2-picrylhydrazyl (DPPH) assay gave high antioxidant values for the methanol extract and fraction D (IC(50) 10.45 and 5.50 MUg/mL) as well as for the phenolic compounds 1-4 (IC(50) 45.50-48.25 mM) compared to the standard 3-t-butyl-4 hydroxyanisole (BHA) (IC(50) 44.20 mM). PMID- 20738150 TI - Design of a Pep-1 peptide-modified liposomal nanocarrier system for intracellular drug delivery: Conformational characterization and cellular uptake evaluation. AB - In order to facilitate the intracellular delivery of macromolecules, Pep-1 peptide-modified liposomal (Pep1-Lipo) nanocarriers were designed and examined for their in vitro cell translocation capability. Pep-1 peptides were coupled via thiol-maleimide linkage to small unilamellar vesicles composed of phosphatidylcholine, Tween 80, and N-[4-(p-maleimidophenyl)butyryl] phosphatidylethanolamine (MPB-PE). The amount of Pep-1 peptide conjugated to the vesicle was effectively controlled by the amounts of maleimide groups on the vesicular surface, ranging from 70 to 700 molecules per vesicle. Systems were evaluated for cell uptake capacity by monitoring entrapped fluorescence-labeled bevacizumab, a model protein for poorly permeable macromolecule, using confocal microscopy. The novel carriers rapidly bound to the cell membrane and migrated into the cells within 1 h, exhibiting better translocation of macromolecules compared to that of conventional liposomes. Cellular uptake of Pep1-Lipo was proportional to the amount of Pep-1 peptide on the liposomal surface. In conclusion, we found that the Pep1-Lipo formulation was a promising nanocarrier system for intracellular delivery of macromolecules. PMID- 20738152 TI - Mite and insect pests of cassava. PMID- 20738151 TI - Immunotoxic sesquiterpene lactone from Carpesium rosulatum Miq. AB - The whole plants of Carpesium rosulatum were chloroform extracted and the isolated sesquiterpene lactones and immunotoxicity effects were studied. The structures and stereochemistry of these compounds were established on the basis of analysis of spectra including mp, [alpha](D)(25), IR, UV, EI-MS, MS, (1)H-NMR, (13)C-NMR and some chemical transformations as follows: 1 (4beta,10alpha dihydroxy-guaia-8alpha,12-olide), 2 (4beta,10alpha-dihydroxy-1(2),11 (13) guaiadien -8alpha,12-olide), 3 (3beta,8beta-dihydroxy-1alpha,5alpha-guaian-10(14) ene-6alpha,12-olide). 4 (2beta,5-epoxy-5,10-dihydroxy-6alpha,9beta-diangeloyloxy germacran-8alpha,12-olide) The chloroform extracted had a significant toxic effect against early fourth-stage larvae of Aedes aegypti L with an LC(50) value of 13.11 ppm and an LC(90) value of 20.33 ppm. The results could be useful in search for newer, safer, and more effective natural immunotoxicity agents against A. aegypti. PMID- 20738153 TI - Potential endocrine causes of some placental pathologies and their associated offspring sex ratios. PMID- 20738154 TI - Antioxidant activity and total phenolic content of methanol extracts of Ixora coccinea. AB - OBJECTIVE: To investigate the in vitro antioxidant activity of methanol extracts of Ixora coccinea L. (Rubiaceae) flower, leaf and stem. MATERIALS AND METHODS: The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity (TAC) and xanthine oxidase inhibition assay were carried out to evaluate the antioxidant potential of the extract. The IC(50) values were calculated for the DPPH and xanthine oxidase assays in order to evaluate the antioxidant efficiency of each of the I. coccinea extracts. The phenol contents were also determined. RESULTS: I. coccinea flowers revealed the best antioxidant property, presenting much lower IC(50) value (6.6 mg/mL for DPPH assay). The flower extract showed a significantly higher antioxidant capacity compared to the other extracts. Furthermore, the highest phenolic content (polyphenols) was found in the flower extract (210.55 +/- 6.31 ug GAE/mg extract). Moreover, I. coccinea extracts scavenged the superoxide radical generated by the xanthine/xanthine oxidase system. The xanthine oxidase inhibition activity was in the order of allopurinol > leaf > flower > stem with the percentage of inhibition ranged from 39.7% to 77.3% for the plant parts investigated. The highest phenolic contents (polyphenols) were found in the flower extracts (210.55 +/- 6.31 ug GAE/mg extract). CONCLUSIONS: I. coccinea could be considered as a potential source of natural antioxidant. PMID- 20738155 TI - Tracking of specific integrant clones in dogs treated with foamy virus vectors. AB - Vector integration can lead to proto-oncogene activation and malignancies during hematopoietic stem cell gene therapy. We previously used foamy virus vectors to deliver the CD18 gene under the control of an internal murine stem cell virus promoter and successfully treated dogs with canine leukocyte adhesion deficiency. Here we have tracked the copy numbers of 11 specific proviruses found in these animals for 36-42 months after transplantation, including examples within or near proto-oncogenes, tumor suppressor genes, and genes unrelated to cancer. We found no evidence for clonal expansion of any of the clones, including those with proviruses in the MECOM gene (MDS1-EVI1 complex). These results suggest that although foamy virus vectors may integrate near proto-oncogenes, this does not necessarily lead to clonal expansion and malignancies. Additionally, we show that copy number estimates of these specific proviruses based on linker-mediated PCR results are different from those obtained by quantitative PCR, but can provide a qualitative assessment of provirus levels. PMID- 20738156 TI - A comparison of the ability of newly-developed bispyridinium oxime K203 and currently available oximes (trimedoxime, obidoxime, HI-6) to counteract the acute neurotoxicity of soman in rats. AB - The neuroprotective effects of newly-developed oxime K203 and currently available oximes (trimedoxime, obidoxime, HI-6) in combination with atropine in rats poisoned with soman were studied. The soman-induced neurotoxicity was monitored using a functional observational battery at 24 h following soman challenge. The results indicate that the potency of a newly-developed oxime K203 to counteract soman-induced neurotoxicity is very low and roughly corresponds to the neuroprotective efficacy of currently available oximes. Among tested oximes, the oxime HI-6 seems to be the most efficacious to counteract acute neurotoxicity of soman, although the differences in neuroprotective efficacy of chosen oximes are not significant. Thus, the oxime K203 does not provide any beneficial effect for the antidotal treatment of acute poisoning with soman and the oxime HI-6 should be still considered to be the best oxime for antidotal treatment of acute soman poisonings. PMID- 20738157 TI - West Nile virus--neutralizing antibodies in humans in Greece. AB - Serum samples collected during March-May 2007 from 392 residents of Imathia prefecture, Northern Greece, were tested by indirect immunofluorescence assay and enzyme-linked immunosorbent assay for IgG antibodies against West Nile virus (WNV). Microneutralization assay was applied in six positive samples. Four (4/392, 1.02%) were found positive for WNV-neutralizing antibodies. None of the positive individuals had a history of travel in endemic area or flavivirus vaccination, suggesting that WNV, or an antigenically related flavivirus, circulates in an endemic sylvatic cycle, at least locally, in rural areas in Greece. Human, animal, and vector surveillance systems have to be implemented to provide an early detection of WNV activity in Greece. PMID- 20738158 TI - Assessment of antinociceptive, anti-inflammatory and antioxidant properties of Cymbopogon winterianus leaf essential oil. AB - The present study investigated the antinociceptive, anti-inflammatory and antioxidant effects of the leaf essential oil (LEO) of Cymbopogon winterianus Jowitt (Poaceae). In the acetic acid-induced writhing and formalin tests, the LEO (50, 100, and 200 mg/kg, p.o.) significantly reduced (p < 0.05) the number of writhings and paw licking times in the first (0-5 min) and second (15-30 min) phases, respectively. In contrast, the LEO did not alter the latency time for mice licking the rear paws in hot-plate test. The LEO inhibited the carrageenan induced neutrophil migration to the peritoneal cavity in a dose-dependent manner (35.5%, 42.8%, and 66.1% at doses of 50, 100, and 200 mg/kg, respectively, p < 0.001). Moreover, LEO exhibited higher scavenging activity toward 1,1-diphenyl-2 picrylhydrazyl (DPPH) radicals with an IC(50) (12.66 +/- 0.56 MUg/mL). Our present results demonstrated that the LEO has antinociceptive, anti-inflammatory, and antioxidant properties. PMID- 20738159 TI - Association between polymorphisms at small ubiquitin-like modifier 1 and nonsyndromic orofacial clefts in Western China. AB - Small ubiquitin-like modifier 1 (SUMO1) has been shown to be associated with cleft lip and palate in animal models. However, rarely studies have linked SUMO1 to nonsyndromic cleft lip with or without cleft palate in humans. The purpose of this study was to confirm the contribution of SUMO1 to nonsyndromic orofacial clefts in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 246 case trios in western China using conditional logistic regression, transmission disequilibrium test, and case-parent trio design. Strong evidence of linkage disequilibrium was found between these markers and the disease in both single-nucleotide polymorphism analysis (G allele at rs6761131 [p=0.0008, odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.31-2.81], C allele at rs7580433 [p<0.0001, OR=2.79, 95% CI: 1.93-4.03], and G allele at rs10185956 [p=0.0069, OR=1.61, 95% CI: 1.14-2.27]) and haplotype analysis (A-C for rs6709162-rs7580433 [p=0.00024], C-G for rs7580433-rs10185956 [p=0.00091], and A-C-A for rs6709162-rs7580433-rs10185956 [p=0.004], among others). The risk factors identified in this study may provide a better understanding of the etiological role of SUMO1 in nonsyndromic cleft lip with or without cleft palate incidence. PMID- 20738161 TI - Counseling psychology: career interventions, research, and theory. PMID- 20738160 TI - Association analysis between the rs11136000 single nucleotide polymorphism in clusterin gene, rs3851179 single nucleotide polymorphism in clathrin assembly lymphoid myeloid protein gene and the patients with schizophrenia in the Chinese population. AB - Clusterin (CLU) and clathrin assembly lymphoid myeloid (CALM) protein are implicated in the function of neuronal synapses. However, to our knowledge, whether they play roles in the maldevelopment of synaptic pathways in schizophrenia has not been studied. The purpose of this study was to examine whether single nucleotide polymorphisms rs11136000 within the CLU gene and rs3851179 within the CALM gene, were associated with schizophrenia. Polymorphisms rs11136000 and rs3851179 were analyzed among 184 Chinese patients with schizophrenia and 162 healthy controls. The high-resolution melting method was used to genotype the two loci. Patients with schizophrenia and with family history showed a significant increase of allele C frequency in rs11136000 in comparison to normal controls (p = 0.03). In addition, the C allele frequency was also higher in patients with negative symptoms (p = 0.04). In contrast, allele and genotype frequencies of rs3851179 did not show significant differences between patients and normal subjects or between patients with different symptoms. The results of this study show that polymorphism of the CLU gene may confer symptomatic specificity in schizophrenia, whereas polymorphism of the CALM gene does not affect susceptibility to schizophrenia. PMID- 20738162 TI - Extended longevity of Drosophila melanogaster by water and ethanol extracts of Stachys lavandulifolia. AB - CONTEXT: Stachyss species have been used as a medicine for centuries throughout the world. Stachys lavandulifolia Vahl. var. lavandulifolia (Lamiaceae) is of interest to researchers because the constituents such as betulinic acid, oleanolic acid, rosmarinic acid, and ursolic acid are similar to other Stachys species commonly used as an alterative in medicinal preparations. OBJECTIVE: The present study investigated the effects of water extract (SLE(w)) and ethanol extract (SLE(e)) obtained from S. lavandulifolia (SLE) on the longevity of Drosophila melanogaster Meigen. MATERIALS AND METHODS: The effects of different concentrations of SLE (Control+DMSO; 4.0; 12.0 and 20.0 uL/100 mL medium) were administered separately to female and male populations of D. melanogaster for control and SLE groups. RESULTS: In all application groups, each population's longevity increased, depending on the concentration of SLE. The mean life-span of the extract groups which are applied with SLE((w)) was determined to be shorter than the extract groups which are applied with SLE((e)). For example, the maximum mean life-span applied with SLE((w)) increased from 31.86 +/- 0.92 days to 43.21 +/- 1.33 days and the maximum mean life-span applied with SLE((e)) increased from 31.86 +/- 0.92 days to 49.62 +/- 1.62 days in females. CONCLUSION: These findings demonstrate that the constituents of S. lavandulifolia have great potential as a source for natural health products for D. melanogaster management. PMID- 20738163 TI - Concern with meta-analysis of acupuncture for neck pain. PMID- 20738164 TI - Relationship between complementary/alternative treatment use and illicit drug use among a cohort of women with, or at risk for, HIV infection. AB - OBJECTIVES: Two of the most pressing public health challenges in the United States are treating human immunodeficiency virus (HIV) infection and illegal substance use. High rates of complementary and alternative medicine (CAM) use have been reported by individuals who suffer from both of these diseases. The goal of this study was to examine the relationship between CAM use and illegal substance use in a cohort of women with HIV or at risk for HIV disease. Based on previous research, it was hypothesized that CAM use may decrease substance use. DESIGN: This was a longitudinal cohort study. SUBJECTS: The subjects comprised Women in the Women's Interagency HIV Study. OUTCOME MEASURES: The role of CAM use in illegal substance use was examined. Due to the hierarchical structure of the dataset, logistic regression analysis adjusting for repeated measurements (generalized estimating equation model) was carried out to assess associations of CAM use and illicit drug use. RESULTS: There were 2176 women included in the analysis. After excluding for marijuana use, CAM use was associated with less drug use (odds ratio 0.82; 95% confidence interval: 0.73, 0.90). CONCLUSIONS: The results supported our hypothesis that CAM users are more health conscious and thus less likely to use illicit drugs. Future studies should target both specific drugs and CAM modalities to help finalize this association. PMID- 20738165 TI - Effects of scheduled qigong exercise on pupils' well-being, self-image, distress, and stress. AB - OBJECTIVES: Psychologic problems is increasing among pupils and has become a major problem in Sweden as well as in other Western countries. The aim of this study was to explore whether scheduled qigong exercise could have an effect on well-being at school, psychologic distress, self-image, and general stress. SUBJECTS: Pupils, 13-14 years, were assigned to either a qigong group or a control group. INTERVENTION: The qigong group had scheduled qigong 2 times a week for 8 weeks. MEASURES: Self-reported well-being at school, psychologic distress, self-image, and stress were measured pre- and postintervention. RESULTS: The control group had reduced well-being at school during the semester and the qigong group was stable. The qigong group reduced psychologic distress and stress, and had a tendency to improved self-image, whereas no changes were found in the control group. Self-image explains 47% (R(2) = 0.47) of well-being at school, and stress explains 29% (R(2) = 0.29) of psychologic distress. CONCLUSIONS: Scheduled qigong, meditative movement, is a possible way to improve well-being at school. PMID- 20738166 TI - The mechanisms of action of Tianhua(TM) on antitumor activity in lung cancer cells. AB - CONTEXT: Tianhua (TH-R) is extracted from Trichosanthes kirilowii Maxim (Cucurbitaceae) containing trichosanthin, a traditional Chinese medicine, which has been locally reported to have good anticancer effects in vivo in both animal and human models. However, there have been several reports that trichosanthin has an anticancer effect involving apoptosis. OBJECTIVE: To investigate other anticancer effects of TH-R, various tumorigenesis parameters were verified. MATERIALS AND METHODS: Telomerase activity, anti-apoptosis, anti-migration and immunomodulatory activity were estimated by telomeric repeat amplification protocol assay (TRAP), flow cytometry, Boyden chamber assay and ELISA assay, respectively. RESULTS: In our studies, we are the first to find that TH-R had a cytotoxic effect on lung cancer cells in MTS assays; it could change the cell cycle distribution of human lung cancer cells (A549 cell line) and induce apoptosis. Further anti-telomerase effects in human lung adenocarcinoma A549 cells using the TRAP assay were noted. TH-R also had an aggregation effect on peripheral blood lymphocytes, but no effect on stimulating peripheral lymphocytes to produce human interferon-gamma(IFN-gamma). TH-R could inhibit the migration, or metastatic ability, of A549 cells by Boyden chamber assay. In the oral feeding therapy of an in vivo mouse model, there was an initial inhibition of A549 cancer cell growth, but no statistical difference after one month of therapy. DISCUSSION AND CONCLUSION: It has been proven that medicinal herbs such as Tianhua have positive effects against cancer through preventing or inhibiting the process of lung tumorigenesis. PMID- 20738167 TI - Acupuncture benefits a pregnant patient who has Bell's palsy: a case study. AB - Here we report the complete recovery from Bell's palsy (BP) of a 27-year-old woman, 27 weeks pregnant, after 2 weeks of acupuncture treatment. BP in pregnancy is an acute idiopathic peripheral facial paralysis of unknown etiology. Treatment and management have not been well evaluated or documented in the literature. The patient was exposed to wind and cold weather before the rapid onset of BP on December 26, 2008. She was treated with acupuncture without co-intervention. During the first week, needles were gently manipulated at local and distal acupoints to induce the qi sensation, and direct moxibustion with moxa sticks was performed at two points, Yangbai (GB14) and Dicang (ST4). During the second week, needles were manipulated without inducing the qi sensation, and moxibustion was performed as previously explained. To document progress, the patient was videotaped before, during, and after each treatment. Outcome assessments included the House-Brackmann facial nerve grading system (HBS), the Nottingham facial nerve grading system, and the Facial Disability Indexes (FDIP). Prior to treatment, her HBS was II, Nottingham was 50.88%, and FDIP was 90. After 2 weeks, her symptoms had disappeared, her face was restored to normal, HBS was I, Nottingham was 96.46%, and FDIP was 100. These results suggest that acupuncture may be a safe, alternative treatment for BP in pregnancy. PMID- 20738168 TI - Electrospun poly(E-caprolactone) scaffold for suture-free solder-mediated laser assisted vessel repair. AB - BACKGROUND AND OBJECTIVE: The addition of poly(lactic-co-glycolic) acid (PLGA) scaffolds to liquid solder-mediated laser-assisted vascular repair (sLAVR) has been shown to increase soldering strength significantly. Unfortunately, the fast degradation of PLGA is associated with adverse effects such as acidity of the degradation products. This study investigated the possibility of using electrospun poly(E-caprolactone) (PCL) as reinforcement material in scaffold and solder-mediated LAVR (ssLAVR). MATERIALS AND METHODS: In vitro sLAVR of 10-mm arteriotomies (n = 62) was performed on 0.3- to 0.6-cm diameter porcine carotid arteries with a 670-nm diode laser. The solder contained 50% bovine serum albumin (BSA) and 0.1-0.7% methylene blue (MB) as a chromophore. The soldering strength was studied as a function of PCL-scaffold thickness, scaffold-fiber diameter, MB concentration, number of laser passes, and different sLAVR techniques. Leaking point pressures (LPPs) were measured with a fluid-infusion technique. RESULTS: The highest mean +/- SD LPP (749 +/- 171 mm Hg) was produced by the ssLAVR modality that included the sheathing of the arteriotomy with 30 MUL solder containing 50% BSA and 0.5% MB, followed by application of the PCL scaffold (mean +/- SD thickness of 187 +/- 9 MUm and 14-MUm fiber diameter) and irradiation with two consecutive continuous-wave laser passes. CONCLUSIONS: The study demonstrated the potential applicability of an electrospun PCL scaffold as reinforcement material in ssLAVR. Soldering strength was dependent on the scaffold physical properties, chromophore concentration, the number of laser passes, and the ssLAVR technique. PMID- 20738169 TI - Effect of low-level laser irradiation on unresponsive oral lichen planus: early preliminary results in 13 patients. AB - OBJECTIVE: To detail the efficacy of low-level laser therapy (LLLT) for the management of oral lichen planus (OLP) unresponsive to standard therapy. BACKGROUND: OLP is an inflammatory disease that can be painful, mainly in the atrophic and erosive forms. Numerous drugs have been used with dissimilar results, but most treatments are empiric. However, to date, the most commonly used and useful agents for the treatment of OLP are topical corticosteroids. MATERIALS AND METHODS: The investigators studied a prospective cohort of 13 patients affected by OLP, who received biostimulation with a pulsed diode laser (GaAs). Patients were exposed to a 904-nm pulsed infrared laser (4 J/cm(2) energy density per minute; spot size, 0.8 cm). Outcome variables, statistically evaluated, were as follows: the size of lesions, visual analogue score of pain, and stability of the obtained result in the follow-up period. RESULTS: We detailed significant reduction in lesion size and in reported pain. No reported complications or therapy side effects were observed in any of the patients treated. CONCLUSION: This study suggests that LLLT could be a possible treatment for patients with unresponsive OLP. These results, although not conclusive, are a step forward for enhanced management of this quite common condition; however, it would be interesting to the results would be the same with a greater number of patients or in a different clinical setting. PMID- 20738170 TI - Bactericidal effect of Nd:YAG and Er:YAG lasers in experimentally infected curved root canals. AB - OBJECTIVE: The purpose of this study was to evaluate the bactericidal efficacy of Nd:YAG and Er:YAG laser in the experimentally infected curved root canals. BACKGROUND DATA: Previous studies revealed that laser systems have a significant bactericidal effect in both human and bovine infected straight root canals. MATERIALS AND METHODS: Sixty extracted single-rooted teeth with single root canals were selected and then instrumented with endodontic files to a size 60 (K type file). The degree of root curvature was determined according to modified Schneider's method. Each of the specimens was incubated in a sterile centrifuge tube with 1 mL of the Enterococcus faecalis suspension at 37 degrees C for 2 weeks under aerobic conditions. After laser irradiation at each of the two settings, 50 mJ, 10 pps (0.5 W) or 100 mJ, 10 pps (1.0 W), the number of E. faecalis in each root canal was examined. RESULTS: In the straight root canals, the Er:YAG laser showed higher bactericidal effects by 6.4-10.8% than did the Nd:YAG laser. Conversely, the bactericidal effect of Er:YAG laser in the curved root canals was higher by 1.5-3.1% than was that with the Nd:YAG laser. The bactericidal effect of the Er:YAG laser in the curved root canal is significantly lower than that in the straight root canal (p < 0.05). CONCLUSION: These results suggest that further development in the endodontic laser tip and technique is required to ensure its success in curved root canals sterilization. PMID- 20738171 TI - Effect of chlorhexidine gluconate, Clearfil Protect Bond, and KTP laser on microleakage under metal orthodontic brackets with thermocycling. AB - OBJECTIVE: The purpose of this study was to evaluate the effects of antimicrobial pretreatments [chlorhexidine gluconate (CHX), Clearfil Protect Bond (CPB), and potassium-titanyl-phosphate (KTP) laser] on microleakage under metal orthodontic brackets. MATERIALS AND METHODS: Sixty freshly-extracted human premolars were randomly assigned to four equal groups: group 1, 37% phosphoric acid; group 2, 37% phosphoric acid + 2% CHX; group 3, 37% phosphoric acid + KTP laser; and group 4, CPB. The teeth were kept in distilled water for 24 h, and thereafter subjected to 500 thermal cycles. Then specimens were sealed with nail varnish, stained with 0.5% basic fuchsin for 24 h, sectioned, and evaluated under a stereomicroscope. Microleakage was scored with regard to the adhesive-tooth interface and the bracket-adhesive interface at both incisal and gingival margins by the same person. Statistical analysis was accomplished by one-way ANOVA and the Kruskal Wallis test, with significance set at p = 0.05. RESULTS: Microleakage was observed in all groups. No statistically significant difference was observed among all groups in terms of microleakage when bracket-adhesive and bracket enamel interface along both gingival and incisal margins was evaluated (p > 0.05). CONCLUSIONS: The lowest microleakage scores were observed in the control group. CPB, KTP, and CHX groups did not show significant differences with the control group (p > 0.05), but the mean scores of the CHX group were higher than those of the other two experimental groups. PMID- 20738172 TI - The role of the DNA damage response mechanisms after low-dose radiation exposure and a consideration of potentially sensitive individuals. AB - Here I consider whether radiation-sensitive individuals might exist in the population and the potential impact of low-dose/dose-rate radiation exposure. Radiation induces DNA double-strand breaks (DSBs), which cause lethality if they are unrepaired and enhance genomic instability if they are misrepaired. DNA damage response (DDR) mechanisms play a vital role in protecting cells from the harmful effects of DSB formation. The DDR encompasses DSB repair pathways, of which DNA nonhomologous end joining is the most significant, and a signal transduction process involving ATM. Patients defective in DDR proteins have been described, and some have shown clinical radiosensitivity. However, such patients are rare and belong to defined syndromes. The critical question is whether heterozygosity or mild defects in DDR proteins confer low-dose radiosensitivity. While it is unlikely that low-dose radiation will dramatically enhance cell killing in such patients, it is possible that there could be an impact on stem cell turnover, leading to stem cell depletion with age. More importantly, it is likely that such patients could have increased misrepair of radiation damage and hence an elevated risk of radiation-induced carcinogenesis. Evidence in support of this and the potentially important genes in this context are discussed. PMID- 20738174 TI - Antidiarrheal activity, chemical and toxicity profile of Berberis aristata. AB - CONTEXT: This study evaluated the in vitro and in vivo antidiarrheal activity, oral acute toxicological profile, and developed a chemical fingerprint of Berberis aristata Linn. (Berberidaceae). MATERIALS AND METHODS: The ethanol (by maceration) and aqueous (by Soxhlet) extracts of Berberis aristata bark were used for the study. The study involved the antimicrobial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) by micro dilution) and antidiarrheal (castor oil induced diarrhea, charcoal motility) tests. The active principle, berberine was characterized by different spectroscopic and chromatographic techniques. RESULTS: The MIC and MBC (of both extracts) against all strains of Shigella were recorded between 125 to 500 ug/mL and 300 to 600 ug/mL, respectively. The MIC and MBC values of berberine are almost comparable to standard ciprofloxacin. UV and IR spectroscopy along with HPTLC and HPLC studies showed presence of berberine in the extracts. The onset of castor oil induced diarrhea was delayed and number of diarrheal episodes was reduced by both the extracts in a dose dependent manner. Similarly, the length of intestine traveled by the feed was also significantly reduced in the charcoal motility test by both the extracts. LD(50) of >5000 mg/kg body weight was observed for both extracts in the acute oral toxicity studies with Swiss albino mice. CONCLUSION: The results validate in vivo and in vitro antidiarrheal activity of Berberis aristata extracts and provide its chemical fingerprint. PMID- 20738175 TI - Dichloromethane fraction from Gardenia jasminoides: DNA topoisomerase 1 inhibition and oral cancer cell death induction. AB - CONTEXT: A growing body of evidence shows that compounds of plant origin have the ability to prevent cancer. The fruit of gardenia, Gardenia jasminoides Ellis (Rubiaceae), has long been used as a food additive and herbal medicine, and its pharmacological actions, such as protective activity against oxidative damage, cytotoxic effect, and anti-inflammatory and anti-tumor activity, have already been reported. OBJECTIVE: The purpose of the present study was to investigate the presence of DNA topoisomerase 1 inhibitor in various solvent fractions of Gardenia extract and examine the induction of oral cancer cell death upon treatment with Gardenia extract. MATERIALS AND METHODS: The methanol extract of Gardenia was partitioned with n-hexane, dichloromethane, ethyl acetate, n butanol, and water. RESULTS: In the DNA topoisomerase 1 assay, n-hexane and dichloromethane fractions inhibited topoisomerase 1 and led to a decrease in the cell viability of KB cells. The dichloromethane fraction (0.1 mg/mL) also showed 77% inhibition of cell viability in KB cells compared with HaCaT cells. Treatment with dichloromethane fraction led to apoptotic cell death as evidenced by flow cytometric analysis and morphological changes. In addition, treatment with Gardenia extract dichloromethane fraction led to the partial increase of caspase 3, caspase-8 and caspase-9 activities and the cleavage of poly (ADP-ribose) polymerase. CONCLUSION: Taken together, these results suggest that the dichloromethane fraction from Gardenia extract induces apoptotic cell death by DNA topoisomerase 1 inhibition in KB cells. These findings suggest the possibility that Gardenia extract could be developed as an anticancer modality. PMID- 20738173 TI - Deficiency in Bre1 impairs homologous recombination repair and cell cycle checkpoint response to radiation damage in mammalian cells. AB - The pathway involving Bre1-dependent monoubiquitination of histone H2B lysine 123, which leads to Dot1-dependent methylation of histone H3 lysine 79 (H3K79me2), has been implicated in survival after exposure to ionizing radiation in Saccharomyces cerevisiae. We found that depletion of mammalian homologs of Bre1 compromises the response to ionizing radiation, leading to increased radiosensitivity and a G(2)/M checkpoint defect. The deficiency in Bre1a/b function was also associated with increased sensitivity to crosslinking drugs and defective formation of Rad51 foci in mouse cells, suggesting a defect in homologous recombinational repair analogous to that seen in Saccharomyces. In budding yeast, H3K79me2 is important for the recruitment of the checkpoint signaling protein Rad9 to sites of double-strand breaks (DSBs). However, in mammalian cells, 53BP1 (the Rad9 ortholog) in addition to H3K79me2 recognizes a different residue, H4K20me2, and some studies argue that it is H4K20me2 and not H3K79me2 that is the preferred target for 53BP1. We show here that depletion of Bre1b specifically reduced dimethylation of H3K79 without affecting dimethylation of H4K20. Thus our data suggest that the observed defects in the radiation response of Bre1a/b-deficient cells are associated with reduced H3K79me2 and not with H4K20me2. PMID- 20738176 TI - Preventive effect of Sphaeranthus indicus during progression of glucocorticoid induced insulin resistance in mice. AB - CONTEXT: The whole plant of Sphaeranthus indicus Linn. (Asteraceae) is traditionally used in the treatment of diabetes mellitus. OBJECTIVE: The present study investigated the effect of the methanol extract of Sphaeranthus indicus whole plant in dexamethasone-induced insulin resistance in mice. MATERIALS AND METHODS: The mice were treated with dexamethasone for 22 days and effects on plasma glucose level, serum triglyceride level, glucose uptake, levels of hepatic enzymes like glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidase (LPO), and body weight was observed. RESULTS: The Sphaeranthus indicus extract (SI) showed significant decrease in plasma glucose and serum triglyceride levels (p <0.01) at doses, of 400 and 800 mg/kg, p.o., and stimulated insulin assisted and non-insulin assisted glucose uptake in skeletal muscle. The levels of antioxidant enzymes GSH, SOD, and CAT were significantly increased (p <0.01) and there was a significant decrease in level of LPO (p <0.01). SI significantly restored (p <0.01) dexamethasone induced body weight loss. DISCUSSION AND CONCLUSION: Sphaeranthus indicus may prove to be effective in the treatment of type II diabetes mellitus owing to its ability to decrease insulin resistance. PMID- 20738177 TI - Antioxidant, antihyperuricemic and xanthine oxidase inhibitory activities of Hyoscyamus reticulatus. AB - CONTEXT: Xanthine oxidase (XO) is a key enzyme in the pathophysiological homeostasis of hyperuricemia. It catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid, the reaction involves the formation of free radical intermediates and superoxide byproducts. OBJECTIVES: This study was undertaken to investigate the antioxidant, antihyperuricemic, and xanthine oxidase inhibitory potentials of Hyoscyamus reticulatus L. (Solanaceae) extract. MATERIALS AND METHODS: The antioxidant potency was measured using the ABTS*+ scavenging capacity system, which includes Trolox as a standard. The xanthine oxidase inhibitory activity of the extract was quantitated in vitro by measuring the decline in the catalytic rate of xanthine oxidase following incubations with the plant extracts and using xanthine as a substrate. The hypouricemic potential of the extract was evaluated using an in vivo model for hyperuricemia. We tested three different doses of the extract and allopurinol was used as standard antihyperuricemic positive control. RESULTS: H. reticulatus aqueous extract exhibited significant antioxidant scavenging properties (533.26 MUmol TE/g dry extract weight) and inhibitory effect on xanthine oxidase activity (IC50 12.8 MUg/mL). Furthermore, oral administration of the aqueous extract significantly reduced serum urate levels in oxonate-induced hyperuricemic mice in a dose dependent manner. DISCUSSION AND CONCLUSION: Our results suggest that the aqueous extract of H. reticulatus aerial parts might have great potential as an antioxidant and a hypouricemic agent. Our lab is currently identifying the active compounds in the extract to which the biological activities could be attributed. PMID- 20738178 TI - Protective effect of partially purified 35 kDa protein from silk worm (Bombyx mori) fecal matter against carbon tetrachloride induced hepatotoxicity and in vitro anti-viral properties. AB - CONTEXT: It has been found that many proteins from silkworm (Bombyx mori L.) fecal matter have been active against human immunodeficiency virus, Sendai virus, herpes simplex virus type-1, and nuclear polyhedrosis virus. OBJECTIVE: A partially purified 35 kDa protein from silkworm was screened for its hepatoprotective activity, and in vitro antioxidant, and antiviral properties against camelpox and goatpox viruses. MATERIALS AND METHODS: The study investigated the efficiency of the partially purified 35 kDa protein from silk worm fecal matter against CCl4-induced liver damage measured in terms of enzyme levels such as aspartate aminotransferase (AST), alanine amino transferase(ALT), alkaline phosphatase (ALP) and total bilirubin, which maintain liver integrity. In vitro antioxidant potential of this protein was determined based on its ability to scavenge 2, 2-diphenylpicrylhydrazyl (DPPH) and superoxide anions scavenging activity. Further, in vitro cytotoxic effect on Vero cells and antiviral activity against goatpox and camelpox viruses were also studied. RESULTS: The protein had significant hepatoprotection against CCl4-induced liver damage and scavenging of DPPH radical and superoxide anion activity. However, the protein did not inhibit the multiplication of either virus tested at its maximum non-toxic concentration (MNTC) in vitro. DISCUSSION AND CONCLUSION: The partially purified 35 kDa protein from silk worm Bombyx mori L fecal matter possessed protective effect against CCl4-induced oxidative stress in rat model. The protein was found to be ineffective against camelpox and goatpox viruses at its MNTC in vitro. PMID- 20738179 TI - Beneficial effect of chyawanprash on cognitive function in aged mice. AB - OBJECTIVE: Chyawanprash is an Ayurvedic formulation which is used traditionally to increase vitality, vigor and for delaying the aging process. The present study sought to explore the beneficial effects of chyawanprash on cognitive function of aged mice. METHOD: In the present study, chyawanprash (CHY) was administered orally in two concentrations (1 and 2% w/w of the diet) for 15 successive days to 17 different groups of young (8 groups) and aged (9 groups) mice. After 15 days of chyawanprash administration, the memory of the animals was assessed using Morris water maze and elevated plus maze. The brain acetylcholinesterase activity (AChE), the levels of brain thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) were also estimated. RESULTS: The administration of chyawanprash (1 and 2% w/w) for 15 consecutive days significantly improved the memory of aged mice when compared to young mice. This Ayurvedic formulation decreased the acetylcholinesterase activity in aged mice, consequently leading to increased cholinergic transmission. Furthermore, there was a significant decrease in brain TBARS and increase in GSH levels of aged animals after chyawanprash administration, thereby indicating decreased free radical generation and increased scavenging of free radicals respectively. CONCLUSION: Chyawanprash may be looked upon as a useful memory enhancer in aged animals by virtue of its antioxidant effect, pro-cholinergic action, improved learning ability, and increased retention capacity. PMID- 20738180 TI - Low powder mass filling of dry powder inhalation formulations. AB - CONTEXT: The successful accurate dosing and filling of powders at fill masses of <10 mg is considered to be challenging for the pharmaceutical industry. This is mainly due to the limitations of current powder volumetric dosing technologies, which rely on formulations having 'good' flow properties. This is especially true for dry powder inhaler (DPI) applications where, together with good manufacturability, powders must also exhibit properties that allow acceptable product performance. OBJECTIVE: In this study, the OMNIDOSE(r) filling technology was investigated for its capability to accurately fill powders suitable for DPI applications, to masses as low as 1 mg. RESULTS: Several lactose monohydrate based powders were successfully dosed at target fill masses of 1 and 5 mg using the current technology at laboratory scale. The filling behavior of the excipients could be related to various aspects of their physical properties. DPI formulations were dosed at masses of 4 and 25 mg at pilot scale to produce capsules that exhibited aerosolization fine particle fractions of ~30% based on label claim. CONCLUSIONS: Initial studies suggest that the OMNIDOSE(((r))) technology is readily adaptable for the dosing of low masses of DPI excipients and formulations and demonstrate the value of thoroughly evaluating powder performance at laboratory scale prior to pilot scale. PMID- 20738181 TI - Self-microemulsifying drug delivery system improves curcumin dissolution and bioavailability. AB - BACKGROUND: Curcumin has a wide spectrum of biological and pharmacological activities, but it has not yet been approved as a therapeutic agent because of its low solubility and stability in aqueous solution, and the relatively low bioavailability in vivo. To overcome these limitations, self-microemulsifying drug delivery system (SMEDDS) of curcumin was developed. METHOD: Various oils, surfactants, and cosurfactants were selected to optimize the formulation. Pseudoternary phase diagrams were constructed and orthogonal design was used to compare the oil-in-water (o/w) microemulsion-forming capacity of different oils/surfactants/cosurfactants. The solubility of curcumin in various oils and cosurfactants was determined to find suitable ingredients with a good solubilizing capacity. Droplet size was measured to obtain the concentration of oil, surfactant, and cosurfactant for forming stable microemulsion. Furthermore, its quality and bioavailability in mice were assessed. RESULTS: Pseudoternary phase diagrams and solubility test showed that the formulation of SMEDDS composed of 20% ethanol, 60% Cremophor RH40(r), and 20% isopropyl myristate, in which the concentration of curcumin reached 50 mg/mL. Curcumin was released completely from SMEDDS at 10 minutes. The developed SMEDDS formulation improved the oral bioavailability of curcumin significantly, and the relative oral bioavailability of SMEDDS compared with curcumin suspension was 1213%. CONCLUSION: The SMEDDS can significantly increase curcumin dissolution in vitro and bioavailability in vivo. PMID- 20738182 TI - Mees' lines. PMID- 20738183 TI - Death on the doorstep of a border community - intentional self-poisoning with veterinary pentobarbital. AB - INTRODUCTION: "Suicide tourism," the practice of traveling to a foreign destination to commit suicide, has been described in the medical literature. Additionally, committing suicide by self-administering veterinary medications has been previously described. CASE DESCRIPTIONS: We report two successful and one unsuccessful suicide attempts involving border-town travelers utilizing self administered veterinary pentobarbital over a 1-year period. DISCUSSION/CONCLUSION: Health care practitioners should be aware of and informed about this phenomenon. PMID- 20738185 TI - iAIDS: HIV-related internet resources for the practicing clinician. AB - In this review, we collate 25 clinically useful human immunodeficiency virus (HIV)-related Web sites to facilitate efficient access to online resources according to themes of clinical inquiry: (1) comprehensive clinical information, (2) opportunistic infections, (3) antiretroviral drug interactions, (4) care of HIV-infected women and children, and (5) continuing medical education. We evaluated these Web sites for clinical content and quality using criteria including the currency of information, inclusion of references, sponsors, whether the site is useful in resource-limited settings, ease of navigation, and content specific for each theme. Using the specified criteria, we provided overall ratings for each Web site. We conclude that the Web sites listed in this review can help extend knowledge about best practices and provide real-time patient care support to clinicians. PMID- 20738186 TI - Successful eradication of a monoclonal strain of Klebsiella pneumoniae during a K. pneumoniae carbapenemase-producing K. pneumoniae outbreak in a surgical intensive care unit in Miami, Florida. AB - We describe the investigation and control of a Klebsiella pneumoniae carbapenemase-producing K. pneumoniae outbreak in a 20-bed surgical intensive care unit during the period from January 1, 2009 through January 1, 2010. Nine patients were either colonized or infected with a monoclonal strain of K. pneumoniae. The implementation of a bundle of interventions on July 2009 successfully controlled the further horizontal spread of this organism. PMID- 20738187 TI - Universal influenza vaccination: an optimal goal--but how and when? PMID- 20738188 TI - Counseling psychology. PMID- 20738189 TI - Individual differences in cognitive abilities. PMID- 20738192 TI - Antithrombotic medications and recurrent miscarriage. PMID- 20738193 TI - Cost consciousness and medical education. PMID- 20738197 TI - A new genus and species of gyrodactylid (Monogenea) from silver hake, Merluccius bilinearis, in the Bay of Fundy, New Brunswick, Canada. AB - Gyrocerviceanseris passamaquoddyensis n. gen., n. sp. is described from the gills of silver hake, Merluccius bilinearis , in Passamaquoddy Bay, southwestern New Brunswick, Canada. Diagnostic features include an oval haptor with asymmetrically distributed marginal hooks (3 pairs anterior, 5 pairs posterior) and a prominent muscular flange on the lateral margins, between the anterior and posterior groups of hooks. The hamuli are well developed, with a straight point, a short shaft, and an elongate, blade-like ventral root having a ventrally directed, gooseneck shaped tip. The ventral bar is rectangular, with a small, hourglass-shaped posterior membrane. There is no dorsal bar. The marginal hook sickle is sharply curved, with a long fine point, an upturned toe, a small heel, and a straight handle. A partial DNA sequence from 18S rDNA was generated and found to be over 11% divergent from its closest matches in GenBank. However, it was less divergent (7.8%) from a previously unpublished sequence of Gyrodactylus emembranatus Malmberg, 1970 , suggesting this species is its closest known relative. Interestingly, both species have almost identical marginal hook sickles and a male copulatory organ (MCO) with small spines in multiple arched rows. Gyrocerviceanseris n. gen. is the sixth genus of viviparous monogeneans to be described from marine and estuarine fishes of the northwestern Atlantic Ocean. PMID- 20738198 TI - Neospora caninum tachyzoite- and antigen-stimulated cytokine production by bone marrow-derived dendritic cells and spleen cells of naive BALB/c mice. AB - Neospora caninum is an intracellular protozoan pathogen that causes abortion in cattle. This parasite elicits a typical type 1 immune response in host animals, and it is widely believed that the strong type 1 immune response during pregnancy may result in fetal death. Pro-inflammatory and/or inflammatory cytokines produced during either primary or secondary pathogen exposure are supposed to be the mediators of abortion. The present study defined cytokine production by murine naive dendritic cells and spleen cells in response to whole Neospora tachyzoites (live, heat-killed, freeze-killed) or whole-cell tachyzoite lysate in the form of total (NcAg), soluble (sNcAg), or insoluble antigen (isNcAg). All tachyzoite and antigen preparations at high doses stimulated high levels of interleukin (IL) -12, interferon (IFN) -gamma, and tumor necrosis factor (TNF) alpha, except for heat-killed tachyzoites and sNcAg, which induced moderate level of IL-12 and very low levels of IFN-gamma and TNF-alpha. In general, whole N. caninum tachyzoites were more effective in inducing IL-12, IFN-gamma, and TNF alpha than the lysate antigen preparations. It appears that the heat-killed N. caninum tachyzoites were less potent in eliciting IFN-gamma or IL-10, but more effective in inducing IL-4. Thus, heat-inactivated tachyzoites or sNcAg alone may not be powerful enough to elicit strong type 1 immune responses against the disease. The present study comprehensively studied the production of critical cytokine by the murine dendritic cells and spleen cells in response to N. caninum; these results may facilitate a better understanding of antigen priming and aid in the design of vaccines/adjuvants against neosporosis. PMID- 20738199 TI - The role of damselflies (Odonata: Zygoptera) as paratenic hosts in the transmission of Halipegus eccentricus (Digenea: Hemiuridae) to anurans. AB - Halipegus eccentricus is a common hemiurid trematode in the eustachian tubes of North America frogs. However, the life cycle of this species has never been completely elucidated. Studies on H. eccentricus suggest that it has a 3-host life cycle. Here, we show through fieldwork and host specificity experimental infections that the life cycle of Halipegus eccentricus utilizes 4 hosts. Metamorphosed anurans become infected with H. eccentricus by feeding on infected damselflies; worms reside in the stomach of anurans, migrate to the eustachian tubes within 32-39 days post-exposure (DPE), and release eggs 50-60 DPE. Cystophorous cercariae develop in Physa gyrina snails within 32-35 DPE, infect ostracod ( Cypridopsis sp.) second intermediate hosts, and develop to metacercariae. Fifteen- to 19-day-old metacercariae from ostracods are infective to both damselfly larvae and metamorphosed anurans. Field surveys of damselflies and tadpoles, along with laboratory exposure of damselfly larvae, metamorphosed anurans, and tadpoles with infected ostracods, indicated that only metamorphosed anurans and damselflies become infected with H. eccentricus , whereas field collected tadpoles and laboratory-exposed tadpoles were never infected with H. eccentricus . Because little morphological change occurred in the metacercaria stage of H. eccentricus between the ostracod second intermediate host and damselfly host, and metamorphosed anurans became infected with H. eccentricus metacercariae recovered from both host groups, we suggest that odonates serve as paratenic hosts in this life cycle. Additionally, our field work and experimental infections provide data on the use of odonates as the route of infection by another North American Halipegus sp. that matures in the stomach of frogs. Our data indicate that when the life cycles are known, the use of odonates as the route of infection to anurans is common in the life cycles of Halipegus spp., and all species exhibit remarkable infection site fidelity in their amphibian hosts. PMID- 20738200 TI - ECG detection of murine chagasic cardiomyopathy. AB - Chagas' disease, induced by Trypanosoma cruzi , is a common cause of infectious myocarditis. Recent clinical treatment trials and vaccine studies indicate that chagasic immunopathology is directed against the parasite and not self-antigens. Therefore, vaccines may have the potential to protect against disease progression. Certain combinations of mouse and parasite strains produce significant histopathology and can be used for safety analyses of new vaccination strategies. The goals of this study were to determine (1) whether the development of chagasic cardiomyopathy in the murine model could be identified by electrocardiogram (ECG); and (2) whether these potential chagasic ECG changes would correlate with histopathologic findings. Groups of BALB/c, C57BL/6, and C3H mice were infected with different parasite strains (Tulahuen, Brazil, or Sylvio X10/4) and evaluated weekly by ECG. Selected tissues from subsets of mice were harvested periodically for blinded histologic evaluation. Significantly increased proportions of BALB/c mice infected with Brazil and Tulahuen strain parasites displayed prolonged QT intervals. Prolonged mean QT intervals detected in infected BALB/c mice significantly correlated with chagasic histopathologic changes. These results indicate that ECG can be used as a non-invasive method to screen for immune-mediated damage resulting in chagasic cardiomyopathy in the murine model. PMID- 20738201 TI - A new species of Capillaria (Nematoda: Capillariidae) from the intestine of the marine fish Acanthopagrus schlegelii schlegelii (Sparidae) from Japan. AB - A new nematode species, Capillaria acanthopagri n. sp. (Capillariidae), is described from the intestine of the marine fish (black porgy) Acanthopagrus schlegelii schlegelii (Bleeker) from coastal waters of the western north Pacific Ocean off Kochi, Shikoku Island, Japan. The new species, belonging to the subgenus Neocapillaria Moravec, 1987 , differs from other congeneric species of this subgenus from marine fishes (with the exception of C. navonae Timi, Rossin and Lanfranchi, 2006 ) mainly in the length (204-285 microm), shape, and structure of the spicule; and except for C. cooperi Johnston and Mawson, 1945, in markedly small body measurements (males and females 3-4 and 6-10 mm long, respectively). It is characterized by the presence of 33-43 elongate stichocytes; a heavily sclerotized spicule with rough transverse grooves; a spinous spicular sheath; and by eggs measuring 27-30 x 57-60 microm, without protruding polar plugs. Capillaria acanthopagri n. sp. is the first known species of Neocapillaria parasitizing fishes of the perciform Sparidae and the second species of this subgenus recorded from fishes of the Pacific Ocean. PMID- 20738202 TI - Litomosoides (Nemata: Filarioidea) of bats from Bolivia with records for three known species and the description of a new species. AB - Herein, we describe Litomosoides salazari n. sp. collected from the body cavity of the yellow bat, Lasiurus ega , from Bolivia. This new species of filarioid nematode is most closely related to the carinii group and is characterized by its relatively small size with the vulva located slightly posterior to the esophago intestinal junction; an arrow-shaped buccal capsule; and a short, rounded tail. New host and locality records for both Litomosoides hamletti and L. chandleri in phyllostomid bats, and L. brasiliensis occurring in both phyllostomid and vespertilionid bats, are provided. The morphological variability of the specimens is documented by providing comparative measurements of 3 known species. Litomosoides brasiliensis occurs in 6 species of bats from Bolivia and was the most common species of filarioid nematode encountered. All 4 species of nematodes, including the new species, were found in sympatry at Chijchijpa, a locality in the Yungas of Bolivia. PMID- 20738203 TI - Within- and among-family variation in parasite load and parasite-induced mortality in the land snail Arianta arbustorum, a host of parasitic mites. AB - Variation in host susceptibility and parasite-induced mortality are preconditions for parasite-related selection on host populations. In terrestrial gastropods, variation in resistance against ectoparasite infection is poorly understood. We examined the within- and among-family variation in parasite load in full-siblings of the land snail Arianta arbustorum experimentally infected with Riccardoella limacum , a mite living in the mantle cavity of helicid land snails. We also quantified the influence of family origin and host size on parasite load and calculated its heritability (h(2)). Furthermore, we examined the influence of parasite load, snail size, and family origin on host winter mortality, an important life-history trait of A. arbustorum . Parasite load was heritable (h(2) = 0.63). In infected snails, parasite load was affected by family origin and increased with increasing shell size. Host mortality during hibernation increased with increasing parasite load and differed among families, but was not affected by snail size. Our results show high among-family variation both in resistance against ectoparasite infection and in host winter mortality. Furthermore, we show that parasite load is linked to snail size, which suggests that the proliferation of R. limacum is limited by resources provided by A. arbustorum . PMID- 20738204 TI - Asymptomatic Strongyloides stercoralis hyperinfection in an alcoholic patient with intense anemia. AB - Strongyloides stercoralis infection is endemic in many tropical and subtropical areas. The parasite has the unusual ability to multiply inside the host due to the transformation of rhabditiform larvae into infective filariforms. Several studies have shown that chronic alcoholism is an important factor that predisposes to strongyloidiasis. The increased susceptibility to S. stercoralis infections seen in alcoholic individuals could be explained by their increased exposure to the parasite, malnutrition, breakdown of local immune responses, and/or alterations in intestinal barriers. Moreover, ethanol intoxication can elevate human endogenous corticosterone, which, in turn, suppresses T cell function and increases the fecundity and survival of the parasite, mimicking the effect of worm ecdysteroides. Although chronic alcoholism is a risk factor for nematode infection, most cases of hyperinfection or dissemination are associated with the presence of hepatic cirrhosis or strongyloidiasis-related symptoms. The present study describes a case of S. stercoralis hyperinfection in a 51-yr-old male patient without gastrointestinal or pulmonary symptoms and with previous anemia and chronic alcoholism. He was not receiving glucocorticoid therapy and tested negative for HTLV and human immunodeficiency virus (HIV), but he had a history of alcohol addiction for more than 20 yr. Laboratory test results showed increased eosinophilia and a high immunoglobulin E (IgE) level, which may have temporarily protected the patient from dissemination of infection, but not prevented proliferation of the parasite, as shown by the large number of S. stercoralis larvae recovered using the Baermann method. Evaluation for strongyloidiasis should occur in alcoholics, especially in endemic areas, to prevent occult asymptomatic infections from progressing to life-threatening cases. PMID- 20738205 TI - Inferring the serotype associated with dengue virus infections on the basis of pre- and postinfection neutralizing antibody titers. AB - BACKGROUND: Currently, the only tests capable of determining the serotype associated with dengue virus (DENV) infection require sampling during the period of acute viremia. No test can accurately detect the serotype associated with past DENV infections. The standard assay for determination of serotype-specific antibody against DENV is the plaque reduction neutralization test (PRNT), although performance of this test continues to be evaluated. METHODS: From a cohort study among schoolchildren in Thailand, PRNT values were determined in serum samples collected before and after infection. A multinomial logistic regression model was used to infer the serotype associated with intercurrent DENV infections. Models were validated based on polymerase chain reaction identification of DENV serotypes. RESULTS: The serotype associated with DENV infection inferred by the model corresponded with polymerase chain reaction in 67.6% of cases, and the kappa statistic was 0.479. A model for 35 cases with primary seroconversion correctly identified the DENV serotypes causing infection in 77.1% of cases, compared with 66.9%, using a model for 169 cases with secondary seroconversion. The best model using only postinfection PRNT values correctly inferred the DENV serotype causing infection in 60.3% of cases. CONCLUSIONS: A statistical model based on both pre- and postinfection PRNT values can be used to infer the serotype associated with DENV infections in prospective studies and vaccine trials. PMID- 20738206 TI - How demography, life history, and kinship shape the evolution of genomic imprinting. AB - How phenomena like helping, dispersal, or the sex ratio evolve depends critically on demographic and life-history factors. One phenotype that is of particular interest to biologists is genomic imprinting, which results in parent-of-origin specific gene expression and thus deviates from the predictions of Mendel's rules. The most prominent explanation for the evolution of genomic imprinting, the kinship theory, originally specified that multiple paternity can cause the evolution of imprinting when offspring affect maternal resource provisioning. Most models of the kinship theory do not detail how population subdivision, demography, and life history affect the evolution of imprinting. In this work, we embed the classic kinship theory within an island model of population structure and allow for diverse demographic and life-history features to affect the direction of selection on imprinting. We find that population structure does not change how multiple paternity affects the evolution of imprinting under the classic kinship theory. However, if the degree of multiple paternity is not too large, we find that sex-specific migration and survival and generation overlap are the primary factors determining which allele is silenced. This indicates that imprinting can evolve purely as a result of sex-related asymmetries in the demographic structure or life history of a species. PMID- 20738207 TI - Dispersal-dormancy relationships in annual plants: putting model predictions to the test. AB - Bet hedging is a means to increase fitness in environments that vary unpredictably in space and time. In such environments, models predict a trade-off between the bet-hedging strategies dispersal and dormancy, while the increasing importance of risk reduction with decreasing predictability should lead to an increase in dispersal and dormancy along gradients of environmental predictability. However, so far there has been no experimental study to test these predictions in the field. Here, we used a set of novel field experiments that enabled us to quantify and separate seedling recruitment from three sources: local reproduction, dormancy, and dispersal. The study included the entire plant community from five environments differing considerably in predictability. Evidence for both the existence of a trade-off between dispersal and dormancy within environments and their increased use in unpredictable environments was very weak. The importance of dispersal for population and community dynamics in our system was extremely low relative to dormancy and local reproduction. This indicates that the role of dispersal for buffering environmental variation may be negligible compared with other risk-reducing strategies. Our findings highlight the urgent need for multispecies and multisite experiments in empirical tests of theoretical predictions. PMID- 20738208 TI - Ultrasound findings in rheumatoid wrist arthritis highly correlate with function. AB - PURPOSE: The wrist is almost invariably affected in rheumatoid arthritis (RA) and inflammation of the wrist can lead to impaired function and eventually to severe destruction. Classical signs of inflammation, pain, swelling and heat may often be observed in clinical examination of wrist arthritis and in ultrasound (US) investigation. We described the relation between clinical and ultrasound parameters of wrist arthritis and secondly their relation to function. PATIENTS AND METHODS: In 33 RA patients with wrist arthritis, clinical and US parameters were measured. Function was evaluated with the SODA-S (Sequential Occupational Dexterity Assessment-Short) and the DASH-DLV (Disabilities of the Arm, Shoulder and Hand-Dutch Language Version). Correlation coefficients were calculated and factor analysis was performed to describe the relation between the aforementioned measures. RESULTS: Correlation coefficients between clinical and ultrasound parameters of RA wrist inflammation in this study were fair to moderate. We found a good correlation between ultrasound and observed function. CONCLUSION: The classical signs of inflammation (pain, swelling, redness, heat and impaired function) seem to reflect different aspects of arthritis. Ultrasound correlates well with function, thus can give paramount information on wrist function, and might therefore be a valuable complementary tool in measuring wrist arthritis in RA. PMID- 20738209 TI - Self-concept in children with cerebral palsy: is there something in the wind? AB - PURPOSE: The aim of this study was to compare self-concept in four groups of children distinguished by the presence/absence of either a motor impairment (with and without cerebral palsy, CP) or social adjustment problems (victimisation). METHOD: Four groups were formed: a victimised CP group (n=17), a non-victimised CP group (n=41), a victimised comparison group (n=10) and a non-victimised comparison group (n=46). Self-concept was measured using the Self-Perception Profile for Children (SPPC, Harter The Self-Perception Profile for Children. Unpublished manual. Denver, CO: University of Denver; 1985) during the school visit. Victimisation was obtained by conducting a classwide sociometric interview in the class of the target child. RESULTS: The results indicate that the groups differ depending on the domain measured. CONCLUSIONS: By identifying factors that may influence self-concept in children with CP, this study contributes new information to this subject. PMID- 20738210 TI - Role of neuropeptides in skin inflammation and its involvement in diabetic wound healing. AB - IMPORTANCE OF THE FIELD: In 2010, the world prevalence of diabetes is 6.4%, affecting 285 million adults. Diabetic patients are at risk of developing neuropathy and delayed wound healing that can culminate in incurable diabetic foot ulcerations (DFUs) or even foot amputation. AREAS COVERED IN THIS REVIEW: The contrast between cellular and molecular events of wound healing and diabetic wound healing processes is characterized. Neuropeptides released from the autonomous nervous system and skin cells reveal a major role in the immunity of wound healing. Therefore, the signaling pathways that induce pro/anti inflammatory cytokines expression and its involvement in diabetic wound healing are discussed. The involvement of neuropeptides in the activation, growth, migration and maturation of skin cells, like keratinocytes, Langerhans cells, macrophages and mast cells, are described. WHAT THE READER WILL GAIN: This review attempts to address the role of neuropeptides in skin inflammation, focusing on signal transduction, inflammatory mediators and pro/anti-inflammatory function, occurring in each cell type, as well as, its connection with diabetic wound healing. TAKE HOME MESSAGE: Understanding the role of neuropeptides in the skin, their application on skin wounds could be a potential therapy for skin pathologies, like the problematic and prevalent DFUs. PMID- 20738211 TI - Towards a targeted multi-drug delivery approach to improve therapeutic efficacy in breast cancer. AB - IMPORTANCE OF THE FIELD: Significant improvements in breast cancer treatments have resulted in a significant decrease in mortality. However, current breast cancer therapies, for example, chemotherapy, often result in high toxicity and nonspecific side effects. Other treatments, such as hormonal and antiangiogenic therapies, often have low treatment efficacy if used alone. In addition, acquired drug resistance decreases further the treatment efficacy of these therapies. Intra-tumor heterogeneity of the tumor tissue may be a major reason for the low treatment efficacy and the development of chemoresistance. Therefore, targeted multi-drug therapy is a valuable option for addressing the multiple mechanisms that may be responsible for reduced efficacy of current therapies. AREAS COVERED IN THIS REVIEW: In this article, different classes of drugs for treating breast cancer, the possible reasons for the drug resistance in breast cancer, as well as different targeted drug delivery systems are summarized. The current targeting strategies used in cancer treatment are discussed. WHAT THE READER WILL GAIN: This article considers the current state of breast cancer therapy and the possible future directions in targeted multi-drug delivery for treating breast cancer. TAKE HOME MESSAGE: A better understanding of tumor biology and physiological responses to nanoparticles, as well as advanced nanoparticle design, are needed to improve the therapeutic outcomes for treating breast cancer using nanoparticle-based targeted drug delivery systems. Moreover, selective delivery of multi-drugs to tumor tissue using targeted drug delivery systems may reduce systemic toxicity further, overcome drug resistances, and improve therapeutic efficacy in treating breast cancer. PMID- 20738212 TI - Protective effect of gan mai da zao decoction in unpredictable chronic mild stress-induced behavioral and biochemical alterations. AB - AIM: Growing evidence indicates that the glutamatergic system, especially the abnormalities of glutamate and N-methyl-D-aspartate (NMDA) receptors contribute to the pathophysiology and possibly the pathogenesis of major depressive disorders. This study is to evaluate the effect of gan mai da zao (GMDZ) decoction on glutamate and NMDA receptor in unpredictable chronic mild stress (UCMS) rats. MATERIALS AND METHODS: Sucrose preference test and open field test were used to estimate the depressive-like behaviors of UCMS rats. Glutamate levels and NMDA receptor subunits (NR1, NR2A and NR2B) in the frontal cortex and hippocampus were determined by HPLC-FLD and by western-blot respectively. RESULTS: 32 days UCMS induced depressive-like behaviors, increased glutamate concentration and decreased NMDA receptor subunits NR2A and NR2B in the frontal cortex and hippocampus of rats. However, NR1 expression remained constant in stressed rats compared with normal. The GMDZ decoction alleviated the depressive like behavior, decreased glutamate level, and increased expression of NMDA receptor subunit NR2A and NR2B in the frontal cortex and hippocampus of stressed rats. CONCLUSIONS: These results suggest that GMDZ treatment reversed chronic unpredictable stress-induced depressive-like behaviors in UCMS rats, possibly via reducing glutamate levels and increasing the NMDA receptor subunits NR2A and NR2B in frontal cortex and hippocampus. PMID- 20738213 TI - Toxicological studies on aqueous extract of Gmelina arborea in rodents. AB - CONTEXT: Gmelina arborea Roxb. (Verbenaceae) is an important medicinal plant in the traditional system of medicine of India. The plant is used in the treatment of snake-bites, fever, piles, and diabetes. However, there is little toxicological information available regarding its safety after exposure. The present study was designed to evaluate acute and repeated dose toxicity of the aqueous extract of Gmelina arborea stem bark. MATERIALS AND METHODS: In the acute toxicity test, Swiss albino mice were treated with aqueous extract (300, 2000, and 5000 mg/kg), orally. Animals were observed periodically during the first 24 h after administration of the extract, and daily thereafter for 14 days. In the repeated dose toxicity study, the aqueous extract of Gmelina arborea (300, 1000, and 2000 mg/kg per day) was administered orally for a period of 28 days in Wistar rats. The effects on body weight, food and water consumption, organ weight, hematology, clinical biochemistry, as well as histology, were studied. RESULTS AND CONCLUSION: Aqueous extract did not produce mortality, changes in behavior or any other physiological activities in mice, for any of the selected doses. There were no significant differences in the body weight, organ weights and feeding habits between control and treated animals. Hematological and biochemical analysis showed no marked differences in any of the parameters examined in either the control or treated groups. Pathologically, neither gross abnormalities nor histopathological changes were observed. The aqueous extract of Gmelina arborea was found safe in acute and repeated dose toxicity studies when tested in rodents. PMID- 20738214 TI - Chemical composition and analgesic activity of Senecio rufinervis essential oil. AB - CONTEXT: Senecio rufinervis D.C (Asteraceae) is a tall aromatic herb, commonly found in Uttarakhand, India. No investigations on the biological activity of this plant have been published so far. Hence, this plant species became a subject of our scientific interest. OBJECTIVE: The aim of the study was to investigate the chemical composition and analgesic activity of Senecio rufinervis essential oil in mice using both thermal and chemical models of pain. MATERIALS AND METHODS: Essential oil from dried leaves of Senecio rufinervis was extracted by steam distillation and then subjected to GC-MS analysis. Varying doses of essential oil were given to mice, 30 min prior to the induction of abdominal constrictions and determination of mean reaction time in hot-plate maintained at 55 degrees +/- 0.5 degrees C. RESULTS: The main component detected in the essential oil of Senecio rufinervis was germacrene D (40.19%) followed by beta-pinene (12.23%), beta-caryophyllene (6.21%) and beta-longipinene (4.15%). Essential oil exhibited significant and dose-dependent analgesic activity against acetic acid-induced writhing in mice. The percentage inhibition in number of writhes produced by 25, 50 and 75 mg/kg doses was, respectively, 69, 80 and 85%. The oil, at doses 50 and 75 mg/kg, significantly increased the mean latency in the hot-plate after 15 and 30 min of drug administration as compared to the control group. DISCUSSION AND CONCLUSION: The results depicted both central and peripheral analgesic activity of S. rufinervis essential oil which was attributed to the presence of terpenes. PMID- 20738216 TI - Chemical and biological investigation of some Clerodendrum species cultivated in Egypt. AB - CONTEXT: Phytochemical investigation of Clerodendrum chinense (Osbeck) Mabberley (Lamiaceae) cultivated in Egypt and evaluation for anti-inflammatory, analgesic, and antipyretic effects of the methanol and chloroform extracts of Clerodendrum chinense, Clerodendrum indicum (L.) Kuntze, Clerodendrum glabrum E. Meyer. OBJECTIVE: The objective of this study was to investigate the anti-inflammatory, analgesic, and antipyretic effects of the methanol and chloroform extracts of Clerodendrum species under investigation. MATERIALS AND METHODS: Air-dried powdered leaves of C. chinense were extracted with MeOH 80%. This extract was fractionated with successive portions of chloroform, ethyl acetate and n-butanol. By further fractionation through silica gel, polyamide and reversed phase column chromatography several compounds were isolated which were elucidated by nuclear magnetic resonance (NMR) and mass spectroscopy. For biological study, the powdered leaves of C. chinense, C. indicum and C. glabrum were extracted by chloroform and then extracted with methanol. The acute anti-inflammatory effect of tested extracts of the leaves of Clerodendrum species under investigation was estimated by carrageenan-induced rat paw edema. Antipyretic effect was evaluated and compared with that of paracetamol as standard using the yeast-induced hyperthermia method on female albino rats. Analgesic effect was evaluated and compared with that of Novalgin (metamizol sodium) as standard using an electric current anxious stimulus. RESULTS: Verbascoside, isoverbascoside, decaffeoylverbascoside, hispidulin, lupeol and icariside B5 were isolated from the leaves of C. chinense for the first time. Cornoside and rengyolone were also isolated. The methanol extract of the leaves of C. chinense and verbascoside showed significant analgesic, anti-inflammatory and antipyretic effects. CONCLUSION: The present study provided a scientific validation of the traditional claims suggested for C. chinense. PMID- 20738215 TI - Pharmacological studies on Hypericum perforatum fractions and constituents. AB - CONTEXT: This study describes the antispasmodic, bronchodilator, and cardiovascular-modulatory activities of Hypericum perforatum Linn. (Hypericaceae) fractions and constituents. AIM OF STUDY: Pharmacological investigation of H. perforatum fractions and active principles. MATERIALS AND METHODS: H. perforatum extract fractions [petroleum spirit (HpPet), chloroform (HpCHCl(3)), ethyl acetate (HpEtAc), and aqueous (HpAq)] and its compounds (hyperforin, hypericin, and hyperoside) were studied in various isolated tissue preparations. RESULTS: In rabbit jejunum, HpCHCl(3), HpEtAc and HpAq, like papaverine, inhibited both spontaneous and K(+) (80 mM)-induced contractions at similar concentrations, whereas HpPet was relatively potent against K(+), as verapamil. All fractions caused rightward of Ca(2+) concentration-response curves (CRCs), similar to verapamil. HpCHCl(3), HpEtAc, and HpAq shifted isoprenaline-inhibitory CRCs to left, like papaverine, while HpPet was devoid of any such effect, as verapamil. In guinea-pig trachea, HpCHCl(3), HpEtAc, and HpAq equipotently relaxed carbachol and K(+)-induced contractions and shifted the isoprenaline-curves to the left, whereas HpPet was more effective against K(+), without potentiating isoprenaline effect. When tested in rabbit aorta, all fractions exhibited vasoconstrictor and vasodilator effects, except HpEtAc, which did not produce vasoconstriction. In guinea-pig atria HpCHCl(3), HpEtAc, and HpAq initially caused cardiac stimulation, followed by inhibition, similar to papaverine, whereas HpPet, like verapamil, caused only cardiac suppression. Hyperforin, hypericin, and hyperoside showed a similar pattern of spasmolytic effect to verapamil. DISCUSSION AND CONCLUSION: Thus, all tested fractions of H. perforatum exhibit a combination of Ca(2+) antagonist and phosphodiesterase-inhibition, except petroleum spirit which was devoid of later mechanism. The compounds tested showed only Ca(2+) channel blocking effect. PMID- 20738217 TI - Antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of ethanol extract and pure flavonoids from Adinandra nitida leaves. AB - CONTEXT: Adinandra nitida Merr. ex. H.L. Li (Theaceae) is an indigenous plant in south China. Its leaves have been reported to have many curative effects such as reducing blood pressure, as well as antibacterial, antioxidant, and analgesic properties, which could be used in foods and medicines. OBJECTIVE: The antioxidant and angiotensin converting enzyme (ACE) inhibitory activities of the main flavonoids and ethanol extract (EE) of A. nitida leaves were investigated for the first time. MATERIALS AND METHODS: The main flavonoids of A. nitida leaves (camellianin A, camellianin B) were prepared and their contents in EE were determined by HPLC. The antioxidant activities of the samples were measured by DPPH radical scavenging assay and Rancimat test. The ACE inhibitory activities of the samples were carried out by using an assay kit with hippuryl-glycyl-glycine as substrate. RESULTS: The contents of camellianin A, camellianin B and apigenin in EE were determined as 41.98, 2.67, and 1.73%, respectively. The antioxidant activities of the flavonoids were far lower than that of EE in DPPH radical scavenging and Rancimat assays. However, the ACE-inhibitory activities of camellianin A, camellianin B and apigenin were higher than that of EE. DISCUSSION AND CONCLUSION: The flavonoid content of EE was more than 45%. The high activities of EE in DPPH scavenging and Rancimat assay could be mainly attributed to compounds other than flavonoids. However, the ACE-inhibitory activity of EE could be mainly attributed to the presence of the flavonoids. PMID- 20738218 TI - In vitro antiplasmodial activity and toxicity assessment of some plants from Nigerian ethnomedicine. AB - CONTEXT: The emergence and spread of Plasmodium falciparum-resistant parasites to nearly all available antimalarial drugs pose a threat to malaria control and necessitates the need to continue the search for new effective and affordable drugs. Ethnomedicine has been shown to be a potential source of antimalarial compounds or source of template for the synthesis of novel antimalarial molecules. OBJECTIVE: The antiplasmodial activity and toxicity assessment of 30 plant extracts from eight medicinal plants identified in Nigerian ethnomedicine for the treatment of febrile illnesses were evaluated. MATERIALS AND METHODS: In vitro antimalarial activity was evaluated using Plasmodium falciparum NF54 (sensitive to all antimalarial drugs) and K1 (chloroquine/pyrimethamine resistant) strains in the [(3)H]-hypoxanthine incorporation assay. Toxicity was determined against mammalian L6 cells using Alamar blue assay. RESULTS: The ethyl acetate extract of leaves of Ocimum gratissimum Linn. (Labiatae) and hexane extract of stem bark of Trema orientalis (L.) Blume (Ulmaceae) showed the highest antiplasmodial activity (IC(50) 1.8-1.93 ug/mL) against P. falciparum K1 strain but elicited low cytotoxicity (selective index >10). However, hexane, ethyl acetate or methanol extracts of leaves of Terminalia catappa Linn. (Combretaceae), Jatropha curcas Linn. (Euphorbiaceae), Vitex doniana Sweet. (Verbenaceae) and stem bark of Vitex doniana displayed antiplasmodial activity (IC(50) 2.3-16.9 ug/mL) with good selectivity (21-120) for malaria parasites. DISCUSSION AND CONCLUSION: The antiplasmodial activity of Terminalia catappa and Vitex doniana against P. falciparum K1 is being reported for the first time in Nigerian ethnomedicine and these plants could be potential source of antimalarial agents. PMID- 20738219 TI - Volatile constituents and biological activities of Pycnostachys abyssinica and Pycnostachys eminii extracts. AB - CONTEXT: Pycnostachys abyssinica Fresen and Pycnostachys eminii Gurke (Lamiaceae) are used in traditional Ethiopian medicine against eye and skin infections, "Mitch disease", and dysentery. OBJECTIVE: Our study was aimed at characterizing essential oil (EO), phytochemical groups, and antimicrobial and anthelmintic activity of extracts to underscore the species' indigenous medicinal use. MATERIALS AND METHODS: Plant organs of Pycnostachys species were subjected to hydrodistillation, and essential oils (EO) analyzed by GC-MS. Phytochemical compounds, antimicrobial (diffusion assay) and anthelmintic activity (bioassay) of gradient solvent extracts of different polarity were studied. RESULTS: In the stem and root EO of P. abyssinica, 25 (99%) and 30 (99.79%) compounds were detected respectively, with estragole (70.4%) (stem) and exo-fenchyl acetate (30.6%) (root) as the most abundant compounds. In leaf, stem and root EO of P. eminii, 30 (90.66%), 27 (90.59%) and 27 (99.96%) compounds were detected, respectively, with high levels of beta-caryophyllene (from 18.08% to 28.85%) and germacrene D (from 15.1% to 22.06%). Alkaloids, saponins, phytosterols, flavonoids, polyphenols, diterpenoids and carotenoids were detected in Pycnostachys. Petroleum ether, chloroform and methanol extracts showed distinct antimicrobial effects with generally higher potential activity of lipophilic and semi-lipophilic fractions. Leaf and root methanol extracts of both species showed lethal activity against earthworms. DISCUSSION: Identified EO constituents and phytochemical groups underscore the observed antifungal, antibacterial and anthelmintic activity of Pycnostachys gradient solvent extracts. CONCLUSION: EO analysis, phytochemical screening, and antimicrobial and anthelmintic assays indicate the biological potential of Pycnostachys species from Ethiopia, and emphasize their pharmacological and indigenous applications. PMID- 20738220 TI - Psychopharmacological effects of Artemisia copa aqueous extract in mice. AB - OBJECTIVE: To evaluate the aqueous extract from aerial parts of Artemisia copa Phil. (Asteraceae) administered orallyfor its psychopharmacological activities in several experimental models. METHODS: The extract was administered p.o. in Swiss albino mice and tested on pentobarbital-induced hypnosis, locomotor activity, exploration in the hole-board, anxiolytic like profile evaluated in the marble burying test and anticonvulsant activity on convulsions induced by pentylenetetrazol. RESULTS: Artemisia copa at doses up to 1.5 g/kg produced a dose-dependent sleep induction and potentiation of sub-hypnotic and hypnotic doses of pentobarbital. The extract also produced a dose-dependent increase and decrease in the spontaneous motor activity (0.5-1.5 g/kg, respectively), no disruption or a decrease on exploratory (hole-board) behavioral profiles (0.5-1.5 g/kg respectively) and a dose-related anxiolytic-like activity as indicated by increases in the percentage of marbles they left uncovered in the marble-burying test at doses (0.5 g/kg) that do not disrupt the motor activity. In addition, the extract (1.5 g/kg) produced a significant increase in the latency time and a decrease in the duration of seizures and mortality induced by PTZ 75 mg/kg in mice. CONCLUSION: These results suggest that the aqueous extract of Artemisia copa may contain sedative principles with potential anxiolytic and anticonvulsant activities. PMID- 20738221 TI - Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil. AB - The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol) poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo. PMID- 20738222 TI - Antioxidant, antitumor and antimicrobial activities of the crude extract and compounds of the root bark of Allanblackia floribunda. AB - CONTEXT: Allanblackia floribunda Oliver (Guttiferae) is an African medicinal plant used traditionally to treat a variety of ailments. OBJECTIVE: We investigated the antitumor, radical scavenging, antimycobacterial, antibacterial and antifungal activities of the root bark extract of A. floribunda and three isolated phenolics, namely 1,7-dihydroxyxanthone (1), morelloflavone (2) and 7'-O glucoside of morelloflavone (3). MATERIALS AND METHODS: The 2,2-diphenyl-1 picryl-hydrazyl-hydrate (DPPH) radical scavenging assay was used for antioxidant tests, while crown gall tumor assay was used for assay of antitumor activity. The p-iodonitrotetrazolium chloride (INT) colorimetry and Microplate Alamar Blue Assay (MABA) were used for antimicrobial investigations. RESULTS: Moderate tumor reducing activity was observed with the extract, while better activities were recorded with compounds 2 and 3. The antimycobacterial and antitumor activities of the extract are being reported for the first time. The DPPH radical scavenging test showed that all the studied samples were able to scavenge more than 50% of the free radical, with compound 3 showing the best inhibitory activity (IC(50) of 49.08 ug/mL). Compounds 1 to 3 prevented the growth of Mycobacterium smegmatis and both extract and compound 2 were active on M. tuberculosis. The lowest MIC value for the extract (9.76 MUg/mL) was recorded against Enterobacter aerogenes while the corresponding value for the compounds (4.88 ug/mL) was obtained with compound 2 on Trichophyton rubrum. DISCUSSION AND CONCLUSION: The overall results of the present work provide baseline information for the potential use of the root bark extract of A. floribunda as an antimicrobial, antitumor and antioxidant phytomedicine. PMID- 20738223 TI - Xanthine oxidase inhibitory activities of extracts and flavonoids of the leaves of Blumea balsamifera. AB - CONTEXT: Blumea balsamifera DC (Compositae) leaves have been recommended for use as a folk medicine in the treatment of various diseases related to urolithiasis in southeast Asia. Phytochemical studies of this plant revealed it contains four classes of flavonoids (e.g., flavonols, flavones, flavanones, and dihydroflavonol derivatives). OBJECTIVE: In view of the broad pharmacological activity of flavonoids, this study was carried out to determine the xanthine oxidase (XO) inhibitory and enzymatically produced superoxide radical scavenging activity of different organic extracts and that of the isolated flavonoids from B. balsamifera leaves. MATERIALS AND METHODS: The inhibitory activity of XO was assayed spectrophotometrically at 295 nm. The superoxide radicals scavenging activity was assessed by NBT reduction method, spectrophotometrically at 560 nm. A dose response curve was plotted for determining IC50 values. RESULTS: The methanol extract (IC50 = 0.111 mg/mL) showed higher XO inhibitory activity than the chloroform (0.138 mg/mL) and pet-ether extracts (0.516 mg/mL). IC50 values of scavenging of superoxide radicals for extracts decreased in the order of: methanol (0.063 mg/mL) > chloroform (0.092 mg/mL) > pet-ether (0.321 mg/mL). The XO inhibitory activity of the isolated flavonoids and reference compounds tested decreased in the order of: allopurinol > luteolin > quercetin > tamarixetin > 5,7,3',5'-tetrahydroxyflavanone > rhamnetin > luteolin-7-methyl ether > blumeatin > dihydroquercetin-4'-methyl ether > dihydroquercetin-7,4'-dimethyl ether > L ascorbic acid. DISCUSSION AND CONCLUSION: The results indicated that the flavone derivatives were more active than the flavonol derivatives. The flavanone derivatives were moderately active and the dihydroflavonol derivatives were the least. The higher flavonoid content of extracts contributed to their higher XO inhibitory activity. PMID- 20738224 TI - Evaluation of anti-inflammatory and antinociceptive activities of Murraya exotica. AB - CONTEXT: Leaves of Murraya exotica L. (Rutaceae) are used for the treatment of various disorders such as cough, fever, and infectious wounds, as well as alleviating pains in folk medicine in southern China. OBJECTIVE: The objectives of this study were to investigate the in vivo antinociceptive and anti inflammatory activities of ethanol (70%) extracts and isolated compounds obtained from the dried leaves of M. exotica. MATERIALS AND METHODS: The antinociceptive activities were evaluated with the methods of acetic acid-induced writhing response and hot-plate latent pain response test. Carrageenan induced hind paw edema, xylene induced ear edema, and a rat knee osteoarthritis model were employed to measure the anti-inflammatory activities. The compounds were isolated using column chromatography and thin-layer chromatography, and the structures identified by 1H NMR, 13C NMR, MS, and IR. RESULTS: The ethanol (70%) extracts significantly decreased in the acetic acid-induced writhing response; increased in hot-plate latency; suppressed xylene induced ear swelling and the carrageenan induced paw edema effectively. In the rat knee osteoarthritis model, the treatment of the ethanol (70%) extracts resulted in a significant increase in the activity of superoxide dismutase, an inhibition on inducible nitric oxide synthase activity, and a decrease in the contents of interleukin-1beta and tumor necrosis factor-alpha of the rat serum. Following this, we explored the components of the ethanol (70%) extracts and isolated six known coumarins, including murracarpin, which exhibited the most potential in antinociceptive and anti-inflammatory activities. DISCUSSION AND CONCLUSION: M. exotica displayed remarkable antinociceptive and anti-inflammatory activities. PMID- 20738225 TI - ABCB1 and ABCG2 expression in the placenta and fetus: an interspecies comparison. AB - IMPORTANCE OF THE FIELD: ABCB1 and ABCG2 are efflux transporters which have a major impact on the pharmacological behavior of numerous drugs. They are expressed, for example, in the intestine, liver, kidney, BBB and placenta. It has become evident that ABCB1 and ABCG2 modify the pharmaco/toxicokinetics in the placenta and fetus and may consequently affect the outcome of pregnancy. AREAS COVERED IN THIS REVIEW: Comprehensive literature searches were done using PubMed (until June 2010) to identify publications on ABCB1 and ABCG2 expression in placenta and fetal tissues in human, mouse, rat, guinea-pig and rabbit. WHAT THE READER WILL GAIN: In this review, we aim to provide an overview of the current knowledge on the ABCB1 and ABCG2 transporter expression profiles in the placenta and fetal tissues in humans relative to other species. TAKE HOME MESSAGE: The available information on ABCB1 and ABCG2 temporal expression profiles in placenta and fetus indicates rather good correlation among human, mouse and rat although some specific differences have been reported. However, at this point no detailed comparisons or comparative functional data are available. Detailed knowledge on the expression patterns and functional activity of ABCB1 and ABCG2 transporters placenta and developing embryo/fetus in different species could possibly help the interspecies extrapolation. PMID- 20738226 TI - The acute toxicity of local anesthetics. AB - IMPORTANCE OF THE FIELD: Systemic toxicity, usually from overdose or intravascular dose, is feared because it mainly affects the heart and brain, and may be acutely life-threatening. AREAS COVERED IN THIS REVIEW: Pharmacological studies of local anesthetic toxicity have largely been reviewed primarily relating to the evaluation of ropivacaine and levobupivacaine during the past decade. This review/opinion focuses more on the principles and concepts underlying the main models used, from chemical pharmacological and pharmacokinetic perspectives. WHAT THE READER WILL GAIN: Research models required to produce pivotal toxicity data are discussed. The potencies for neural blockade and systemic toxicity are associated across virtually all models, with some deviations through molecular stereochemistry. These models show that all local anesthetics can produce direct cardiovascular system toxicity and CNS excitotoxicity that may further affect the cardiovascular system response. Whereas the longer-acting local anesthetics are more likely to cause cardiac death by malignant arrhythmias, the shorter-acting agents are more likely to cause cardiac contraction failure. In most models, equi-anesthetic doses of ropivacaine and levobupivacaine are less likely to produce serious toxicity than bupivacaine. TAKE HOME MESSAGE: Of the various models, this reviewer favors a whole-body large animal preparation because of the comprehensive data collection possible. The conscious sheep preparation has contributed more than any other, and may be regarded as the de facto 'standard' experimental model for concurrent study of local anesthetic toxicity +/- pharmacokinetics, using experimental designs that can reproduce the toxicity seen in clinical accidents. PMID- 20738227 TI - No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin. AB - OBJECTIVES: Dalcetrapib, which targets cholesteryl ester transfer protein, is in clinical development for prevention of cardiovascular events and is likely to be used concomitantly with statins. Two studies investigated co-administration of dalcetrapib with atorvastatin and any effects of the timing of atorvastatin on the pharmacokinetics of dalcetrapib. RESEARCH DESIGN AND METHODS: Two crossover studies were performed in healthy subjects: a two-period study of dalcetrapib 900 mg concurrently with atorvastatin (concurrent dosing study) and a three-period study of dalcetrapib 600 mg (dose chosen for Phase III) with atorvastatin concurrently or serially 4 h after dalcetrapib (interval dosing study). MAIN OUTCOME MEASURES: The primary pharmacokinetic end points were AUC(0 - 24) and C(max); lipid effects and tolerability were secondary end points. RESULTS: In the concurrent study (n = 26), co-administration reduced dalcetrapib AUC(0 - 24) and C(max) and caused small changes in AUC(0 - 24) and C(max) of atorvastatin and its active metabolites. In the interval study (n = 52), serial and concurrent co administration of atorvastatin resulted in similar reductions in dalcetrapib exposure that were comparable to those observed in the concurrent dosing study. Co-administration did not decrease the efficacy of dalcetrapib or atorvastatin and was generally well tolerated. CONCLUSIONS: These results indicate no clinically relevant interactions for co-administration of dalcetrapib with atorvastatin. PMID- 20738229 TI - Challenges in lower-limb orthotic research. PMID- 20738228 TI - Potential economic impact of increasing low dose aspirin usage on CVD in the US. AB - BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in the US and Western Europe, but regular use of preventive low-dose aspirin has proven effective in preventing CVD events. The purpose of this study was to explore the potential economic impact in the US if preventive aspirin usage were to be increased in line with clinical guidelines for primary and secondary prevention. METHODS: The risk profile of the US population was characterized using NHANES data, and Framingham cardiovascular risk equations were applied to calculate risk for myocardial infarction, angina and ischemic stroke according to age and gender. Primary and secondary patients were considered separately. Using publicly available unit costs, a budget impact model calculated the annual impact of increased preventive aspirin usage considering gastrointestinal bleeding and hemorrhagic stroke adverse events and diminishing aspirin adherence over a 10 year time horizon. RESULTS: In a base population of 1,000,000 patients, full implementation of clinical guidelines would potentially prevent an additional 1273 myocardial infarctions, 2184 angina episodes and 565 ischemic strokes in primary prevention patients and an additional 578 myocardial infarctions, and 607 ischemic strokes in secondary prevention patients. This represents a total savings of $79.6 million for primary prevention and $32.2 million for secondary and additional out-of-pocket expense to patients of $29.0 million for primary prevention and $2.6 million for secondary prevention for the cost of aspirin. CONCLUSIONS: This budgetary model suggests that there is a strong economic case, both for payers and society, to encourage aspirin use for patients at appropriate risk and per clinical guidelines. It also provides an example of how minimizing costs do not necessarily have to imply a rationing of care. Limitations include the exclusion of other CVD interventions in the analysis. PMID- 20738230 TI - The importance of being earnest about shank and thigh kinematics especially when using ankle-foot orthoses. AB - This paper reviews and summarizes the evidence for important observations of normal and pathological gait and presents an approach to rehabilitation and orthotic management, which is based on the significance of shank and thigh kinematics for standing and gait. It discusses normal gait biomechanics, challenging some traditional beliefs, the interrelationship between segment kinematics, joint kinematics and kinetics and their relationship to orthotic design, alignment and tuning. It proposes a description of four rather than three rockers in gait; a simple categorization of pathological gait based on shank kinematics abnormality; an algorithm for the designing, aligning and tuning of AFO-Footwear Combinations; and an algorithm for determining the sagittal angle of the ankle in an AFO. It reports the results of research on Shank to Vertical Angle alignment of tuned AFO-Footwear Combinations and on the use of 'point loading' rocker soles. PMID- 20738231 TI - The effects of tuning an ankle-foot orthosis footwear combination on kinematics and kinetics of the knee joint of an adult with hemiplegia. AB - The effects of tuning the AFO footwear combination (AFOFC) for an adult with post stroke hemiplegia were investigated. Gait analysis and tuning were carried out using a Vicon 3D motion analysis system and two force plates. Tuning of the AFOFC was accomplished by gradually modifying its design over a number of gait trials, to achieve optimal (i.e., as close as possible to normal, within the capability of the patient) knee kinematics and alignment of the Ground Reaction Force vector (GRF) relative to the knee joint. Heel wedges and a stiff rocker were used to tune mid-stance and terminal stance, respectively. Temporal-spatial parameters and selected kinetic and kinematic variables were compared between the non-tuned AFOFC, the tuned AFOFC immediately after tuning, and the tuned AFOFC after three months. There were several changes after three months compared to the non-tuned AFOFC, including improvement in stride length and a reduction in knee hyperextension. A subjective reduction in knee pain and improvement in function were also reported. The feasibility and the lack of objective evidence of tuning AFOFCs as a part of a clinical service need to be addressed in future research. PMID- 20738232 TI - Effect of AFO design on walking after stroke: impact of ankle plantar flexion contracture. AB - This study was conducted to compare the effects of three ankle-foot orthosis (AFO) designs on walking after stroke and determine whether an ankle plantar flexion contracture impacts response to the AFOs. A total of 30 individuals, ranging from 6-215 months post-stroke, were tested in four conditions: shoes only (SH), dorsi-assist/dorsi-stop AFO (DA-DS), plantar stop/free dorsiflexion AFO (PS), and rigid AFO (Rigid). Kinematics, kinetics, and electromyographic (EMG) activity were recorded from the hemiparetic lower extremity while participants walked at a self-selected pace. Gait parameters were compared between conditions and between participants with and without a moderate ankle plantar flexion contracture. All AFOs increased ankle dorsiflexion in swing and early stance. Anterior tibialis EMG was reduced only in the PS AFO. Both PS and Rigid AFOs restricted ankle plantar flexion and increased knee flexion in loading. Peak ankle dorsiflexion in stance and soleus EMG intensity were greatest in the PS AFO. The Rigid AFO tended to restrict dorsiflexion in stance and knee flexion in swing only in participants without a plantar flexion contracture. Individuals without a contracture benefit from an AFO that permits dorsiflexion mobility in stance and those with quadriceps weakness may more easily tolerate an AFO with plantar flexion mobility in loading. PMID- 20738233 TI - Polypropylene ankle foot orthoses to overcome drop-foot gait in central neurological patients: a mechanical and functional evaluation. AB - The aim of this study was to assess the functional effects and mechanical contribution of Ankle Foot Orthoses (AFO) prescribed to overcome drop-foot gait. We hypothesized that poor functional effects of the AFO relate to insufficient mechanical contribution of the AFO during the swing phase, or unwanted constraining of the ankle during the stance phase. In seven patients with Stroke or Multiple Sclerosis, we determined changes in energy cost of walking resulting from wearing an AFO, as a measure of the functional effects. In addition, an instrumented gait analysis was performed, and the mechanical AFO properties were measured, to calculate the mechanical contribution of the AFO. The AFO was sufficiently stiff to effectively support the foot in swing, without hampering the ankle during stance. For the whole group, there was a significant improvement in walking speed and energy cost (12%). However, the AFO had no functional benefit in terms of a reduced energy cost of walking for three patients, who coherently demonstrated no pathological plantar flexion during swing without their AFO. We conclude that functional benefit from the AFO was only found when the mechanical AFO characteristics met the need to support the patients' mechanical deficiencies. PMID- 20738234 TI - Early observations of the effects of lateral wedge orthoses on lower limb muscle length and potential for exacerbating spasticity. AB - Lateral wedge orthoses are often prescribed to correct varus deformity after stroke. Spasticity is implicated in varus deformity and is caused by velocity related muscle length changes, so a lateral wedge may affect spasticity by manipulating foot and ankle kinematics which, in turn, may alter the length of these muscles. We sought to test this theory in healthy participants. Eight volunteers walked with no wedge and with lateral wedges of 5 and 8.5 degrees in both shoes. Qualysis motion capture system collected kinematic data and SIMM musculoskeletal modeling software calculated muscle tendon length of plantarflexor and peroneal muscle groups using 3-D ankle and knee joint angle data. The wedges increased ankle eversion (p < 0.0001) and total excursion of tibialis posterior, peroneus longus and brevis by 13-29% (p < 0.05). Muscle length of peroneus longus and brevis increased by <1% (p < 0.005). Potentially clinical meaningful effects were found for tibialis posterior (15%), peroneus brevis (23%) and peroneus tertius (13%). Further research is required to be conclusive and to explore the effects of lateral wedge orthoses in patients with stroke. If such changes are seen in people with stroke, a change in orthotic prescription practice could be indicated as lateral wedge orthoses may exacerbate spasticity. PMID- 20738235 TI - Studies examining the efficacy of ankle foot orthoses should report activity level and mechanical evidence. AB - Ankle Foot Orthoses (AFOs) to promote walking ability are a common treatment in patients with neurological or muscular diseases. However, guidelines on the prescription of AFOs are currently based on a low level of evidence regarding their efficacy. Recent studies aiming to demonstrate the efficacy of wearing an AFO in respect to walking ability are not always conclusive. In this paper it is argued to recognize two levels of evidence related to the ICF levels. Activity level evidence expresses the gain in walking ability for the patient, while mechanical evidence expresses the correct functioning of the AFO. Used in combination for the purpose of evaluating the efficacy of orthotic treatment, a conjunct improvement at both levels reinforces the treatment algorithm that is used. Conversely, conflicting outcomes will challenge current treatment algorithms and the supposed working mechanism of the AFO. A treatment algorithm must use relevant information as an input, derived from measurements with a high precision. Its result will be a specific AFO that matches the patient's needs, specified by the mechanical characterization of the AFO footwear combination. It is concluded that research on the efficacy of AFOs should use parameters from two levels of evidence, to prove the efficacy of a treatment algorithm, i.e., how to prescribe a well-matched AFO. PMID- 20738236 TI - Statins in women for primary prevention--is there evidence to back up their use?? PMID- 20738237 TI - Hormone replacement therapy in breast cancer survivors. PMID- 20738238 TI - Climacteric commentaries. Menopause management revisited. PMID- 20738239 TI - Two branched polar groups and polar linker moieties of thiophene amide derivatives are essential for MRP2/ABCC2 recognition. AB - Previously we demonstrated that the torsion angle between two biphenyl rings forming a three-dimensional conformation is the determinant factor for multi-drug resistance protein 2 (Mrp2/Abcc2) interaction [1]. More recently, we reported a heterocyclic compound, 1-(1-(4-bromophenyl)-3-carbamoyl-1H-pyrazol-4-yl) urea that shares the polar head groups with the biphenyl-substituted heterocycles, is highly secreted from bile by Mrp2/Abcc2, [2]. Collectively we hypothesized that the two branched polar groups and linkers might be essential with proposed Mrp2/Abcc2 recognition fitting in two primarily positive regions deep in the binding site. To test the hypothesis, a discovery lead compound (Compound 1) was examined to confirm the Mrp2/Abcc2 involvement resulting in hepatobiliary secretion in rats. The structural requirement of Mrp2/Abcc2 recognition was further explored in a series of thiophene amides derivatives divided into eight structural classes, with structural changes focused on the amide linker orientation or substitution from amide and sulfonamide to alkene, alkane, or alkyne linkers. In Caco-2 cell bidirectional transport assays and Mrp2/Abcc2 membrane vesicle uptake assays, the involvement of Mrp2/Abcc2 mediated transport was confirmed in structural classes 1 - 5, which contains polar amide or sulfonamide linker, but not in classes 6 - 8 with non-polar aliphatic linker. The Mrp2/Abcc2 recognition showed strong correlation with structural descriptors in predictive Bayesian model, as well as with polar surface area and lipophilicity (LogP). The result provided valuable information for predicting transporter recognition in silico, for improved predictions of transporter involved ADME in early drug discovery. PMID- 20738240 TI - Recent patents on nucleic acid-based antiviral therapeutics. AB - The concept of using nucleic acids as a prospective antiviral therapeutics has been one of the major areas of study for researchers since the last three decades. Among the many proposed technologies for specifically perturbing gene expression, four potent nucleic acids based technologies such as Antisense (AS), Ribozyme, Aptamer and RNA Interference (RNAi) have emerged. Though being technically different from each other, these technologies share among themselves the features of conceptual simplicity, straightforward designing and quick drug identification methods, which enable them to be pre-clinically and clinically tested at a rapid pace. The scale of growth, in the level of scientific interest and in the number of patents claimed based on these technologies, is not surprising considering the aforementioned factors. As more and more drugs continue to appear with the promise of actually curing the disease, instead of merely offering temporary symptomatic relief, this study is becoming even more intriguing, both scientifically and commercially. This review article puts together and discusses the latest patents filed based on the above mentioned technologies with an objective to provide an insight into the latest developments in this field of study that projects these technologies as a prospective antiviral therapeutics. The listed patents have been classified technology wise and further sub-classified on the basis of their target disease. PMID- 20738241 TI - Patent landscape of countermeasures against smallpox and estimation of grant attraction capability through patent landscape data. AB - The study was concerned with countermeasures against a possible smallpox outbreak. In the process of assessment 18 landscaping sectors were defined and described, the advantages and drawbacks of the corresponding countermeasures being reviewed. The data of the previously published influenza landscape were revisited. The current economic climate of deficit cutting (austerity) also puts emphasis on the optimization of capital investment. We used the materials of the landscape to define and analyze metrics of capital placement optimization. Value score was obtained by fitting patent landscape internals to the sale price of individual patents. Success score was obtained as a product of a-priori parameters that measure likelihood of emergence of a marketable product in a technological sector. Both scores were combined in a qualitative metric. Our methodology defined weight as a product of the sector size by the success score. We hypothesized - based on the material of two landscapes- that a life cycle of a technology begins in IP space with a high patent quality low volume "bud" of low weight, reaches maximum weight and then weight falls again when the technology becomes outdated. The weight and the annual dynamic of weight can serve a measure of investment risk and return. In this report we modeled investment by issue of government grants or purchase of patents by government. In the smallpox landscape the number of patents purchased by government agencies was the highest in the sectors with the highest weight and the trend was confirmed by the count of NIH grants issued in support of the technological sectors. In the influenza landscape only grant issue count was statistically meaningful and the trend was also confirmed. To better fit the grant support levels, the weight expression was optimized by using training coefficients. We propose to use value scores for evaluation of individual patent publications/company portfolios and to use weights for assessment of technological sectors. Such a combination of automated analytical tools may lead to optimized allocation of capital and is intended to support the decisions taken by human experts. PMID- 20738242 TI - Malaria chemotherapy: recent advances in drug development. AB - Malaria is a disease caused by parasitic protozoa of the genus Plasmodium. Despite significant advances in understanding the disease and the parasite biology, malaria still remains one of the leading causes of morbidity and mortality, particularly in malaria-endemic regions of the world. The main factor hampering malaria control is the high degree of resistance developed by Plasmodium species against several classes of drugs. Artemisinin-based Combination Therapy (ACT) is the most rapidly acting antimalarial treatment effective against multi-drug resistant strains, and is, at present, the only group of antimalarial drugs to which resistance by Plasmodium falciparum has not developed yet in the field, even though the isolation of artemisinin-resistant strains is raising concern. As a result, discovering and developing novel antimalarial agents is one of the greatest challenges facing malaria control today. This review covers patent literature from 2007 to date regarding small molecules or natural compounds targeting the asexual forms of the parasite. Recent patents filed and issued for ameliorating conventional antimalarial treatment methods by non-conventional dosage forms are also reviewed. PMID- 20738243 TI - Oxidative stress in the cochlea: an update. AB - This paper will focus on understanding the role and action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the molecular and biochemical pathways responsible for the regulation of the survival of hair cells and spiral ganglion neurons in the auditory portion of the inner ear. The pivotal role of ROS/RNS in ototoxicity makes them potentially valuable candidates for effective otoprotective strategies. In this review, we describe the major characteristics of ROS/RNS and the different oxidative processes observed during ototoxic cascades. At each step, we discuss their potential as therapeutic targets because an increasing number of compounds that modulate ROS/RNS processing or targets are being identified. PMID- 20738244 TI - Common genetic variants of the mitochondrial trafficking system and mitochondrial uncoupling proteins affect the development of two slowly developing demyelinating disorders, leukoaraiosis and multiple sclerosis. AB - As the central energy source, the mitochondria are of great importance in the maintenance of the glia cells of the brain. It is presumed that mitochondrial energy production is affected not only by well-characterized genetic mutations of the mitochondria, which are associated with severe malfunctions and resultant acute glia and neuronal cell death, but also by a number of other unfavorable genetic variants. The genetic variants of the kinesin motor proteins and mitochondrial uncoupling proteins (UCPs) are believed to influence the mitochondrial energy production in different distress states of the glia cells. The kinesin motor proteins carry the mitochondria from the central parts to the peripheral parts of the glia cells, where myelin protein synthesis takes place. The UCPs are essential for regulation of the mitochondrial membrane potential under different physiological conditions, thereby finally attuning mitochondrial energy production in environmental states such as cold exposure, fasting or chronic mild hypoxia. While the capacity of the kinesin motor proteins can affect the number of mitochondria in the peripheral parts of the glia cells, the functional features of the UCPs can affect the degree of energy production of the mitochondria by influencing the mitochondrial membrane potential. The different genetic variants may display different activities, and some may result in a slowly developing energy shortage in the glia cells. In this context, this article discusses the roles of genetic variants of the kinesin motor proteins and UCPs in slowly developing diseases of the white matter of the brain as multiple sclerosis and leukoaraiosis. PMID- 20738245 TI - Ring-fused thiadiazines as core structures for the development of potent AMPA receptor potentiators. AB - Amongst ionotropic glutamatergic receptors, the AMPA receptor subtype has been recognized as a major contributor to the fast excitatory neurotransmission in the central nervous system and the expression and maintenance of longterm potentiation. This receptor subtype also represents an interesting target to develop innovative therapeutic drugs such as positive allosteric modulators (AMPA receptor potentiators) since the enhancement of AMPA signals is expected to be beneficial in the management of several neurological disorders such as depression, schizophrenia, Parkinson's disease and learning-memory deficits linked to Alzheimer's disease. This article is dedicated to the use of (hetero) aromatic ring-fused thiadiazines (i.e. benzo- pyrido- and thienothiadiazines) as core structures for the discovery of new positive allosteric modulators of AMPA receptors. Recent advances exploring other chemotypes in the field of AMPA potentiators is the object of a separate review of the present issue. PMID- 20738246 TI - Hormonal action of plant derived and anthropogenic non-steroidal estrogenic compounds: phytoestrogens and xenoestrogens. AB - Herbivorous and omnivorous vertebrates have evolved in the presence of a variety of phytoestrogens, i.e., plant-derived compounds that can mimic, modulate or disrupt the actions of endogenous estrogens. Since the discovery of the estrus inducing effects of some plant products in 1926, considerable effort has been devoted to the isolation and structural and pharmacological characterization of phytoestrogens. Recently, agricultural and industrial pollution has added anthropogenic estrogenic compounds to the list of environmental estrogens. Unlike phytoestrogens, these xenoestrogens tend to accumulate and persist in adipose tissue for decades and may cause long-lasting, adverse endocrine effects. Here we review the endocrine effects of known phytoestrogens and xenoestrogens with special emphasis on molecular structure-activity relationships. Phytoestrogens include flavonoids, isoflavonoids, chalcons, coumestans, stilbenes, lignans, ginsenosides and other saponins, as well as the recently discovered tetrahydrofurandiols. Fungal estrogenic compounds may enter the food chain via infested crops. Since some phytoestrogens have been shown to display organ specific actions, pharmaceutical estrogen analogues with similar properties (selective estrogen receptor modulators, SERMs) are also discussed. Xenoestrogens include dichlorodiphenyltrichloroethane (DDT) and its metabolites, bisphenols, alkylphenols, dichlorophenols, methoxychlor, chlordecone, polychlorinated benzol derivatives (PCBs), and dioxins. While most of these compounds act through estrogen receptors alpha and beta, some of their effects may be mediated by other nuclear or membrane-bound receptors or receptor-independent mechanisms. Some might also interfere with the production and metabolism of ovarian estrogens. Better understanding of the molecular pharmacology of phyto- and xenoestrogens may result in the development of novel compounds with therapeutic utility and improved environmental protection. PMID- 20738247 TI - Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease. AB - Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease. PMID- 20738248 TI - Insights into the molecular mechanism of hERG1 channel activation and blockade by drugs. AB - Blockade of the human ether-a-go-go related gene 1 (hERG1) channel has been associated with an increased duration of ventricular repolarization, causing prolongation of the time interval between Q and T waves (long QT syndrome, or LQTS). LQTS may result in serious cardiovascular disorders such as tachyarrhythmia and sudden cardiac death. Diverse types of organic compounds bind to the wide intracellular cavity in the pore domain of hERG channels, leading to a full or partial blockade of ion current through the pore. The drug-induced blockade of the hERG-related component of the potassium current is thought to be a major reason for drug-induced arrhythmias in humans. Identification of specific interactions governing the high-affinity blockade of cardiac potassium (K-) channels is crucial both for the prevention of unintended ion channel block and for the design of ion channel modulators. A plethora of ligand- and receptor based models of K-channels have been created to address these challenges. In this paper, we review the current state of knowledge regarding the structure-function relationship of hERG and discuss progress in the use of molecular modeling for developing both blockers and activators of hERG. PMID- 20738249 TI - Recent advances in the discovery of selective AMPA receptor positive allosteric modulators. AB - This article highlights recent advances in the discovery of new positive allosteric modulators of the AMPA receptor, excluding compounds of thiadiazine chemotype, most of which were developed by Servier and the University of Liege. The field of AMPA receptor modulators continues to be a fertile area for the discovery of new potential therapeutic agents, and recent years have seen a marked diversification in the range of chemotypes prepared. An overview is also given of the recent key new biological data. PMID- 20738250 TI - Allosteric enhancers of A1 adenosine receptors: state of the art and new horizons for drug development. AB - Adenosine is an important autocoid, exerting its physiological effects on the human body by activation of four different G-protein-coupled-receptors (GPCRs) classified as A(1), A(2A), A(2B), and A(3). These receptors are coupled to secondary messenger systems including adenylate cyclase, inositol phosphate metabolism, and K(+), K(ATP) and Ca(2+) channels. Pharmacological agents that increase the activation of A(1) adenosine receptors in response to adenosine would be useful for treatment of cardiovascular, central nervous system, and inflammatory pathologies. Compounds that are able to enhance the activity of the A(1)-adenosine receptors by the endogenous ligand within specific tissues may have potential therapeutic advantages over non-endogenous agonists. Such an opportunity for intervention is provided by the concept of allosteric modulation of GPCRs. Therefore the use of allosteric enhancers to increase the responsiveness of the A(1) receptors to endogenous adenosine at sites of its production is an appealing alternative to activation by exogenous agonists. This approach minimizes side effects because allosteric enhancers amplify the action of the agonist by stabilizing the agonist-A(1)-receptor-G protein ternary complex. The allosteric enhancement of the GABA(A) receptor by benzodiazepines is the most famous and successful example of this strategy. The aim of this article is to give an overview of the results obtained in this field and discuss the opportunities and challenges that this class of ligands might offer for medicinal chemistry and pharmacology. PMID- 20738251 TI - Recent advancement in nonsteroidal aromatase inhibitors for treatment of estrogen dependent breast cancer. AB - Estrogen-dependent breast cancer (EDBC) is a kind of common malignant tumor in postmenopausal women with growing tendency in recent years. Aromatase (AR) is the key enzyme responsible for estrogen biosynthesis and has been considered as an important target for designing inhibitors as potent therapeutic agents for EDBC. AR inhibitors (AIs) are divided into steroidal and nonsteroidal compounds, and the latter shows high inhibitory potency against AR. This review summarizes recent advancement in nonsteroidal AIs. PMID- 20738252 TI - Semaphorins and their receptors in stem and cancer cells. AB - There is a growing body of evidence that links cancer with genes and pathways that are required for normal embryonic development, increasing the possibility that cancer cells with stem cell properties, particularly self-renewal and multipotentiality, are primarily involved in tumor formation and progression. One novel pathway that is important in regulating the morphogenesis, proliferation, survival and growth in a variety of adult and embryonic tissues is the semaphoring signaling pathway. Semaphorins are a large family of secreted, transmembrane and GPI-linked proteins with a broad spectrum of functions. Semaphorin signaling is transduced by plexins which, in the case of most class 3 semaphorins, require high affinity neuropilin receptors. The neuropilins also function as receptors for VEGF and other growth factors, and their expression is abnormal in tumors. Various semaphorins can either promote or inhibit tumor progression through the promotion or inhibition of processes such as tumor angiogenesis, metastasis and tumor cell survival. In normal tissues, semaphoring signaling is mainly active in precursor cells. This increases the possibility of tumors being derived from such cells, possibly even stem cells, which are unable to differentiate and/or to stop proliferating. In this review, we summarize the molecular mechanisms of semaphorin signal transduction involved in the stem cell compartment, and describe the evidence that links semaphorins to the control of tumor progression. PMID- 20738253 TI - The thyroid gland: a crossroad in inflammation-induced carcinoma? An ongoing debate with new therapeutic potential. AB - Chronic infection and inflammation contribute to around 25% of cancer cases worldwide. While a direct link between several types of human malignancies and inflammation has now been established, in particular at the gastrointestinal level, the relationship between inflammation and thyroid cancer and the pathophysiology of chronic inflammation that induces papillary thyroid carcinoma (PTC) are still subjects of debate. However, several epidemiological and morphological studies have strongly suggested an increased risk of PTC in patients with Hashimoto's thyroiditis (HT). As in HT, an intense immune infiltrate is associated with certain PTC and might play a critical role in the regulation of carcinogenesis and in carcinoma progression. Proinflammatory molecules, such as cytokines and chemokines, which are produced by immune infiltrate in the tumor microenvironment, contribute to the regulation of key cellular processes for cancer onset and progression, in particular for tumor cell proliferation, apoptosis, autophagy, angiogenesis and metastasis. Molecular studies have identified activation of the RET/PTC rearrangement-induced MAPK signaling pathway as the driving force in the development of PTC in the context of HT. These genetic alterations may be favored by chronic inflammation. In this regard, the RET oncoprotein and its downstream effectors, such as those implicated in the activation of the MAPK pathway, as well as inflammatory molecules of the tumor microenvironment could be promising molecular targets for new therapeutic strategies for thyroid cancer. This review focuses on the complex link between thyroid cancer and chronic inflammation and highlights the different current hypotheses regarding the role of the immune cell microenvironment in the initiation and progression of PTC. PMID- 20738254 TI - Subunit composition of an energy-coupling-factor-type biotin transporter analysed in living bacteria. AB - BioMNY, a bacterial high-affinity biotin transporter, is a member of the recently defined class of ECF (energy-coupling factor) transporters. These systems are composed of ABC (ATP-binding-cassette) ATPases (represented by BioM in the case of the biotin transporter), a universally conserved transmembrane protein (BioN) and a core transporter component (BioY), in unknown stoichiometry. The quaternary structure of BioY, which functions as a low-affinity biotin transporter in the absence of BioMN, and of BioMNY was investigated by a FRET (Forster resonance energy transfer) approach using living recombinant Escherichia coli cells. To this end, the donor-acceptor pair, of Cerulean and yellow fluorescent protein respectively, were fused to BioM, BioN and BioY. The fusion proteins were stable and the protein tags did not interfere with transport and ATPase activities. Specific donor-acceptor interactions were characterized by lifetime-based FRET spectroscopy. The results suggest an oligomeric structure for the solitary BioY core transporter and oligomeric forms of BioM and BioY in BioMNY complexes. We surmise that oligomers of BioY are the functional units of the low- and high affinity biotin transporter in the living cell. Beyond its relevance for clarifying the supramolecular organization of ECF transporters, the results demonstrate the general applicability of lifetime-based FRET studies in living bacteria. PMID- 20738256 TI - Guanylate cyclase-G, expressed in the Grueneberg ganglion olfactory subsystem, is activated by bicarbonate. AB - GC (guanylate cyclase)-G is the most recently identified member of the receptor GC family. However, the regulation of its activity and protein expression in the mammalian olfactory system remains unclear. In the present study, we used a GC-G specific antibody to validate that the GC-G protein is expressed in Grueneberg ganglion neurons, a newly recognized olfactory subsystem co-expressing other cGMP signalling components such as the cGMP-regulated PDE2A (phosphodiesterase 2A) and the cGMP-gated ion channel CNGA3 (cyclic nucleotide-gated cation channel alpha 3). Further molecular and biochemical analyses showed that heterologously expressed GC-G protein, specifically the C-terminal cyclase domain, was directly stimulated by bicarbonate in both in vivo cellular cGMP accumulation assays in human embryonic kidney-293T cells and in vitro GC assays with a purified recombinant protein containing the GC domain. In addition, overexpression of GC-G in NG108 neuronal cells resulted in a CO2-dependent increase in cellular cGMP level that could be blocked by treatment with acetazolamide, an inhibitor of carbonic anhydrases, which implies that the stimulatory effect of CO2 requires its conversion to bicarbonate. Together, our data demonstrate a novel CO2/bicarbonate-dependent activation mechanism for GC-G and suggest that GC-G may be involved in a wide variety of CO2/bicarbonate-regulated biological processes such as the chemosensory function in Grueneberg ganglion neurons. PMID- 20738255 TI - Inhibition of the mitochondrial permeability transition by protein kinase A in rat liver mitochondria and hepatocytes. AB - NO and cGMP administered at reperfusion after ischaemia prevent injury to hepatocytes mediated by the MPT (mitochondrial permeability transition). To characterize further the mechanism of protection, the ability of hepatic cytosol in combination with cyclic nucleotides to delay onset of the calcium-induced MPT was evaluated in isolated rat liver mitochondria. Liver cytosol plus cGMP or cAMP dose-dependently inhibited the MPT, required ATP hydrolysis for inhibition and did not inhibit mitochondrial calcium uptake. Specific peptide inhibitors for PKA (protein kinase A), but not PKG (protein kinase G), abolished cytosol-induced inhibition of MPT onset. Activity assays showed a cGMP- and cAMP-stimulated protein kinase activity in liver cytosol that was completely inhibited by PKI, a PKA peptide inhibitor. Size-exclusion chromatography of liver cytosol produced a single peak of cGMP/cAMP-stimulated kinase activity with an estimated protein size of 180-220 kDa. This fraction was PKI-sensitive and delayed onset of the MPT. Incubation of active catalytic PKA subunit directly with mitochondria in the absence of cytosol and cyclic nucleotide also delayed MPT onset, and incubation with purified outer membranes led to phosphorylation of a major 31 kDa band. After ischaemia, administration at reperfusion of membrane-permeant cAMPs and cAMP-mobilizing glucagon prevented reperfusion injury to hepatocytes. In conclusion, PKA in liver cytosol activated by cGMP or cAMP acts directly on mitochondria to delay onset of the MPT and protect hepatocytes from cell death after ischaemia/reperfusion. PMID- 20738257 TI - Transcriptional activation requires protection of the TATA-binding protein Tbp1 by the ubiquitin-specific protease Ubp3. AB - Tbp1, the TATA-binding protein, is essential for transcriptional activation, and Gal4 and Gcn4 are unable to fully activate transcription in a Saccharomyces cerevisiae TBP1E86D mutant strain. In the present study we have shown that the Tbp1E186D mutant protein is proteolytically instable, and we have isolated intragenic and extragenic suppressors of the transcription defects of the TBP1E186D mutant strain. The TBP1R6S mutation stabilizes the Tbp1E186D mutant protein and suppresses the defects of the TBP1E186D mutant strain. Furthermore, we found that the overexpression of the de-ubiquitinating enzyme Ubp3 (ubiquitin specific protease 3) also stabilizes the Tbp1E186D mutant protein and suppresses of the defects of the TBP1E186D mutant strain. Importantly, the deletion of UBP3 and its cofactor BRE5 lead to increased degradation of wild-type Tbp1 protein and to defects in transcriptional activation by Gal4 and Gcn4. Purified GST (glutathione transferase)-Ubp3 reversed Tbp1 ubiquitination, and the deletion of UBP3 lead to the accumulation of poly-ubiquitinated species of Tbp1 in a proteaseome-deficient genetic background, demonstrating that Ubp3 reverses ubiquitination of Tbp1 in vitro and in vivo. Chromatin immunoprecipitation showed that Ubp3 was recruited to the GAL1 and HIS3 promoters upon the induction of the respective gene, indicating that protection of promoter-bound Tbp1 by Ubp3 is required for transcriptional activation. PMID- 20738258 TI - Antagonistic roles of the ERK and p38 MAPK signalling pathways in globin expression, haem biosynthesis and iron uptake. AB - Late-stage erythroid cells synthesize large quantities of haemoglobin, a process requiring the co-ordinated regulation of globin and haem synthesis as well as iron uptake. In the present study, we investigated the role of the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) signalling pathways in MEL (mouse erythroleukaemia) cell differentiation. We found that treatment of HMBA (hexamethylene bisacetamide)-induced MEL cells with the ERK pathway inhibitor UO126 results in an increase in intracellular haem and haemoglobin levels. The transcript levels of the genes coding for beta(major) globin, the haem biosynthesis enzyme 5-aminolevulinate synthase 2 and the mitochondrial iron transporter mitoferrin 1 are up-regulated. We also showed enhanced expression of globin and transferrin receptor 1 proteins upon UO126 treatment. With respect to iron uptake, we found that ERK inhibitor treatment led to an increase in both haem-bound and total iron. In contrast, treatment of MEL cells with the p38 MAPK pathway inhibitor SB202190 had the opposite effect, resulting in decreased globin expression, haem synthesis and iron uptake. Reporter assays showed that globin promoter and HS2 enhancer-mediated transcription was under the control of MAPKs, as inhibition of the ERK and p38 MAPK pathways led to increased and decreased gene activity respectively. Our present results suggest that the ERK1/2 and p38alpha/beta MAPKs play antagonistic roles in HMBA-induced globin gene expression and erythroid differentiation. These results provide a novel link between MAPK signalling and the regulation of haem biosynthesis and iron uptake in erythroid cells. PMID- 20738259 TI - Genetic variants within chromosome 4q28.3 are not reproducibly associated with age-related macular degeneration (AMD). PMID- 20738260 TI - Redefining tissue engineering for nanomedicine in ophthalmology. AB - Working at the nanoscale means to completely rethink how to approach engineering in the body in general and in the eye in particular. In nanomedicine, tissue engineering is the ability to influence an environment either by adding, subtracting or manipulating that environment to allow it to be more conducive for its purpose. The goal is to function at the optimum state, or to return to that optimum state. Additive tissue engineering replaces cells or tissue, or tries to get something to grow that is no longer there. Arrestive tissue engineering tries to stop aberrant growth which, if left uncontrolled, would result in a decrease in function. Nano delivery of therapeutics can perform both additive and arrestive functions influencing the environment either way, depending on the targeting. By manipulating the environment at the nanoscale, the rate and distribution of healing can be controlled. It infers that potential applications of nanomedicine in ophthalmology include procedures, such as corneal endothelial cell transplantation, single retinal ganglion cell repair, check of retinal ganglion cell viability, building of nanofibre scaffolds, such as self-assembling peptides, to create a scaffold-like tissue-bridging structure to provide a framework for axonal regeneration in the case of optic nerve reconnection or eye transplantation, and ocular drug delivery. Examples of potential arrestive therapies include gene-related treatment modalities to inhibit intraocular neovascularization and to block retinal cell apoptosis. Looking towards the future, this review focuses on how nanoscale tissue engineering can be and is being used to influence that local environment. PMID- 20738261 TI - Cytokine and chemokine levels in tears from healthy subjects. AB - PURPOSE: There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. SUBJECTS AND METHODS: Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. RESULTS: Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-gamma, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-alpha, epidermal growth factor, and CCL4/MIP-1beta were present at 5-100 pg/ml. IL-1beta, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. CONCLUSION: Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. PMID- 20738262 TI - Reproducibility of viscoelastic property and intraocular pressure measurements obtained with the Ocular Response Analyzer. AB - PURPOSE: To analyse the reproducibility of corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) obtained with the ocular response analyzer (ORA). METHODS: This is a prospective study, nonmasked, of eight successive examinations with the ORA device in 60 normal eyes. Using 30 eyes (one eye per subject), the reproducibility was assessed by comparing the first series of four examinations to the second four and by calculating the within-subject coefficient of variation. The correlation and difference with the fellow eye were analysed, respectively. RESULTS: The mean values were 10.7 +/- 1.8 mmHg, CRF; 10.6 +/- 1.6 mmHg, CH; 15.9 +/- 3.9 mmHg, IOPg and 16.2 +/- 3.7 mmHg, IOPcc. The reproducibility was significantly different for CRF (5.2 +/- 5.9%), CH (7.3 +/- 8.6%), IOPg (7.7 +/- 6.7%) and IOPcc (10.1 +/- 8.0%); p < 0.001. Considering the reproducibility, CRF correlated with CH (rs = 0.55; p < 0.001) and showed to be independent of IOPg and IOPcc. The score spread was best for CRF (2.6 +/- 1.5 mmHg; 24.0%) compared to IOPg (4.3 +/- 1.5 mmHg; 28.1%) and CH (3.1 +/- 1.7 mmHg; 29.9%) and worst for IOPcc (5.5 +/- 2.5 mmHg; 34.4%). The lowest difference with the fellow eye was observed for CRF (5.0%; p = 0.09). The correlation with the fellow eye was high, especially for IOPcc and CRF (rs > 0.9; p < 0.001) followed by IOPg and CH (rs > 0.8; p < 0.001). CONCLUSION: The ORA device provides reproducible information on viscoelastic properties of the cornea in normal eyes notably CRF and CH. IOPcc was less reproducible. Four measurements per eye were necessary to reach a 10% precision and six for 5%. PMID- 20738263 TI - Proton pump inhibitors and long-term risk of recurrent upper gastrointestinal bleeding. PMID- 20738264 TI - Effects of early conceptus signals on circulating immune cells: lessons from domestic ruminants. AB - While there are few similarities between mechanisms for extending corpus luteum (CL) function during early pregnancy in ruminants and primates, there is increasing evidence that conceptus-immune crosstalk in ruminants and primates affects the function of circulating immune cells at the very earliest stages of pregnancy. Most notable are changes in immune cell phenotypes with increased numbers of cells exhibiting the T regulatory phenotype and suppression of Th1 cytokines that promote tolerance to paternal alloantigens. Until recently, interferon tau produced by the ruminant trophectoderm was thought to act exclusively on the uterine endometrium; however, it is now clear that this unique embryonic interferon escapes the uterus and alters gene expression in the CL and in peripheral blood leukocytes (PBL). In fact, a large number of interferon stimulated genes are now known to be increased during early pregnancy in PBL. What is not known is how this conceptus-immune system cross-talk affects maternal immune status outside the reproductive tract. It is attractive to hypothesize that some of these effects are designed to counter-balance progesterone-induced immunosuppression so as not to place the dam at a greater risk of infection on top of the tremendous stresses already induced by pregnancy. Furthermore, recent evidence suggests that pregnancy induced changes in peripheral immune cells may aid in orchestrating establishment of pregnancy. Existing evidence points toward a greater convergence of systemic immune responses to early pregnancy signaling between ruminants and primates. PMID- 20738265 TI - Negative pressure wound therapy used to heal complex urinary fistula wounds following renal transplantation into an ileal conduit. AB - Transplantation into an ileal conduit is an established option for patients with end-stage renal failure and a nonfunctioning urinary tract. Urinary fistulae are more common following these complex transplants. Urinary fistula in this scenario can cause substantial morbidity and even result in graft loss. The management options depend on the viability of the transplant ureter, the level of local sepsis and the overall condition of the patient. Urinary diversion with a nephrostomy and ureteric stents has been described in aiding the healing of urinary leaks in renal transplants into a functioning urinary tract. We describe the successful use of negative wound pressure therapy to eradicate the local sepsis and help the healing of a recurrent urinary fistula following kidney transplantation into an ileal conduit. To our knowledge these are the first such cases reported in the literature. PMID- 20738267 TI - Successful isolated liver transplantation in a child with atypical hemolytic uremic syndrome and a mutation in complement factor H. AB - A male infant was diagnosed with atypical hemolytic uremic syndrome (aHUS) at the age of 5.5 months. Sequencing of the gene (CFH) encoding complement factor H revealed a heterozygous mutation (c.3644G>A, p.Arg1215Gln). Despite maintenance plasmapheresis he developed recurrent episodes of aHUS and vascular access complications while maintaining stable renal function. At the age of 5 years he received an isolated split liver graft following a previously established protocol using pretransplant plasma exchange (PE) and intratransplant plasma infusion. Graft function, renal function and disease remission are preserved 2 years after transplantation. Preemptive liver transplantation prior to the development of end stage renal disease is a valuable option in the management of aHUS associated with CFH mutations. PMID- 20738270 TI - Reproductive aging: theoretical perspectives, mechanisms, nonhuman models, and health correlates. AB - Every 365.2421999 days--more or less--the earth rotates, revolves, wobbles, and precesses along an elliptical path around the sun. Those of us who survive the journey are a year older: we have aged one solar year. Some years we seem to age faster than other years; some people seem to age faster than other people; some systems seem to age faster than other systems. As we begin to mature, reach our middle years, and become elderly, reproductive changes are among the markers of aging that are most notable, particularly among women. What--if anything--can we learn about more general processes of aging from reproductive aging? Does our postreproductive survival contribute to our fitness, or is it just a chance event, a result of selection on other characteristics? Can our insights and research be translated into improved clinical practice? We explore reproductive aging with a wide-angle multidisciplinary lens that we use to focus on four articulating areas: theoretical perspectives, mechanisms, nonhuman models, and health correlates. We propose directions for future work. PMID- 20738271 TI - Life historical perspectives on human reproductive aging. AB - A commentary is offered on the chapters that comprise the section on Theoretical Foundations, emphasizing novel contributions of each. Three additional points are then made. First, while the biology of reproductive aging may be common to all human populations, its actual course can be expected to vary between individuals and between populations depending on ecological conditions and developmental histories. Second, increasing fertility (such as that typical of humans compared with hominoid relatives and imputed ancestral species) decreases the opportunity and impact of contributions from ascendant relatives and increases the opportunity and impact of contributions from collateral and descendent relatives in promoting the fitness of a focal individual. Finally, an argument is made that the major change in human life history physiology in the Pleistocene has been the extension of adult lifespan, not any change in ovarian physiology or rate of reproductive senescence, and that extended lifespan created a selection pressure for the emergence of indirect reproductive effort among postreproductive individuals, not the reverse. PMID- 20738272 TI - The connections between general and reproductive senescence and the evolutionary basis of menopause. AB - We consider the relationship between the factors responsible for the general biology of aging and those that specifically influence the aging of the reproductive system. To understand this relationship it is necessary to be clear about the evolutionary forces acting on both sets of factors. Only in this way can the correct causal connections be established. Of particular significance is the existence in some species of a distinct period of postreproductive life. This is most striking in the case of the human menopause, for which a particular combination of biological and sociobiological factors appear to be responsible. PMID- 20738273 TI - Learning, menopause, and the human adaptive complex. AB - This paper presents a new two-sex learning- and skills-based theory for the evolution of human menopause. The theory proposes that the role of knowledge, skill acquisition, and transfers in determining economic productivity and resource distribution is the distinctive feature of the traditional human ecology that is responsible for the evolution of menopause. The theory also proposes that male reproductive cessation and post-reproductive investment in descendants is a fundamental characteristic of humans living in traditional foraging and simple horticultural economies. We present evidence relevant to the theory. The data show that whereas reproductive decline is linked to increasing risks of mortality in chimpanzees, human reproductive senescence precedes somatic senescence. Moreover under traditional conditions, most human males undergo reproductive cessation at the same time as their wives. We then present evidence that after ceasing to reproduce, both men and women provide net economic transfers to children and grandchildren. Given this pattern of economic productivity, delays in menopause would produce net economic deficits within families. PMID- 20738274 TI - Do women stop early? Similarities in fertility decline in humans and chimpanzees. AB - Two kinds of evidence suggest that female fertility may end at an earlier age in modern people than in ancestral populations or in our closest living relatives, chimpanzees. We investigate both to see whether fertility schedules or ovarian follicle counts falsify the alternative hypothesis that the age of terminal fertility changed little in the human lineage while greater longevity evolved due to grandmother effects. We use 19th century Utah women to represent non contracepting humans, and compare their fertility by age with published records for wild chimpanzees. Then we revisit published counts of ovarian follicular stocks in both species. Results show wide individual variation in age at last birth and oocyte stocks in both humans and chimpanzees. This heterogeneity, combined with interspecific differences in adult mortality, has large and opposing effects on fertility schedules. Neither realized fertility nor rates of follicular atresia stand as evidence against the hypothesis that ages at last birth changed little while greater longevity evolved in our lineage. PMID- 20738275 TI - An evolutionary and life history perspective on human male reproductive senescence. AB - Unlike menopause, male reproductive senescence does not involve an acute drop in fertility. Men do, however, manifest distinct changes in somatic and gonadal function with age. Moreover, population variation in male reproductive senescence reveals phenotypic plasticity resulting from environmental, lifestyle, and genetic factors. An evolutionary and life history perspective is vital for understanding male reproductive senescence because aging involves biological constraint as well as adjustments to reproductive strategies and the allocation of somatic resources. An awareness of life history-related tradeoffs between energetic and time constraints is especially useful because biological aspects of male senescence are products of environmental challenges and natural selection. This article reviews the adaptive significance of the evolutionary biology of human male senescence with particular attention to population variation. An evolutionary perspective cannot only shed light on the origins and biology of human male senescence but also provide insights into contemporary issues of male aging and health. PMID- 20738276 TI - Dynamic heterogeneity and life histories. AB - Biodemography is increasingly focused on the large and persistent differences between individuals within populations in fitness components (age at death, reproductive success) and fitness-related components (health, biomarkers) in humans and other species. To study such variation we propose the use of dynamic models of observable phenotypes of individuals. Phenotypic change in turn determines variation among individuals in their fitness components over the life course. We refer to this dynamic accumulation of fitness differences as dynamic heterogeneity and illustrate it for an animal population in which longitudinal data are studied using multistate capture-mark-recapture models. Although our approach can be applied to any characteristic, for our empirical example we use reproduction as the phenotypic character to define stages. We indicate how our stage-structured model describes the nature of the variation among individual characteristics that is generated by dynamic heterogeneity. We conclude by discussing our ongoing and planned work on animals and humans. We also discuss the connections between our work and recent work on human mortality, disability and health, and life course theory. PMID- 20738277 TI - Mechanisms of reproductive aging: conserved mechanisms and environmental factors. AB - The interplay of neuroendocrine processes and gonadal function is exquisitely expressed during aging. In females, loss of ovarian function results in decreased circulating estradiol. As a result, estrogen-dependent endocrine and behavioral responses decline, including impaired cognitive function reflecting the impact of declining estrogen on the hippocampus circuits, and decreased metabolic endocrine function. Concurrently, age-related changes in neuroendocrine response also contribute to the declining reproductive function. Our session considered key mechanisms in reproductive aging including the roles of ovarian function (Finch and Holmes) and the hypothalamic median eminence (Yin and Gore) with an associated age-related cognitive decline that accompanies estrogen loss (Morrison and colleagues). Effects of smoking, obesity, and insulin resistance (Sowers and colleagues) impact the timing of the perimenopause transition in women. Animal models provide excellent insights into conserved mechanisms and key overarching events that bring about endocrine and behavioral aging. Environmental factors are key triggers in timing endocrine aging with implications for eventual disease. Session presentations will be considered in the context of the broader topic of indices and predictors of aging-related change. PMID- 20738278 TI - Ovarian aging in developmental and evolutionary contexts. AB - Evolutionary theory predicts that aging-related fertility declines result from tradeoffs between reproduction and somatic maintenance. Developmental programs for oogenesis also contribute to variation in aging-related reproductive declines among female vertebrates. Documented reproductive aging patterns in female vertebrates, including humans, are consistent with canonical aging patterns determined developmentally and require no special adaptive explanation. Here we discuss patterns of aging-related ovarian decline in diverse female vertebrates, and place human ovarian aging in comparative context. Depletion of finite oocyte stores accompanied by fertility loss occurs in a variety of nonhuman mammals and vertebrates, including short-lived rodents, birds, and some fishes; moreover, postreproductive lifespans of considerable length clearly are not limited to long lived, social species with well-developed kin networks. We argue for a more rigorous comparative approach for understanding the evolutionary and developmental bases of ovarian aging in vertebrates with a wider range of aging patterns and social structures. PMID- 20738279 TI - Relating smoking, obesity, insulin resistance, and ovarian biomarker changes to the final menstrual period. AB - To determine if smoking, obesity, and insulin resistance mediated age at final menstrual period (FMP), we examined anti-Mullerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH) as biomarkers of changing follicle status and ovarian aging. We performed a longitudinal data analysis from a cohort of premenopausal women followed to their FMP. Our results found that smokers had an earlier age at FMP (P < 0.003) and a more rapid decline in their AMH slope relative to age at FMP (P < 0.002). Smokers had a lower baseline inhibin B level relative to age at the FMP than nonsmokers (P = 0.002). Increasing insulin resistance was associated with a shorter time to FMP (P < 0.003) and associations of obesity and time to FMP were observed (P = 0.004, in model with FSH). Change in ovarian biomarkers did not mediate the time to FMP. We found that smoking was associated with age at FMP and modified associations of AMH and inhibin B with age at FMP. Insulin resistance was associated with shorter time to FMP independent of the biomarkers. Interventions targeting smoking and insulin resistance could curtail the undue advancement of reproductive aging. PMID- 20738280 TI - Estrogen and the aging brain: an elixir for the weary cortical network. AB - The surprising discovery in 1990 that estrogen modulates hippocampal structural plasticity launched a whole new field of scientific inquiry. Over the past two decades, estrogen-induced spinogenesis has been described in several brain areas involved in cognition in a number of species, in both sexes and on multiple time scales. Exploration into the interaction between estrogen and aging has illuminated some of the hormone's neuroprotective effects, most notably on age related cognitive decline in nonhuman primates. Although there is still much to be learned about the mechanisms by which estrogen exerts its actions, key components of the signal transduction pathways are beginning to be elucidated and nongenomic actions via membrane bound estrogen receptors are of particular interest. Future studies are focused on identifying the most clinically relevant hormone treatment, as well as the potential identification of new therapeutics that can prevent or reverse age-related cognitive impairment by intercepting specific signal transduction pathways initiated by estrogen. PMID- 20738282 TI - Animal models of reproductive aging: what can they tell us? AB - This commentary explores the relationship between what can be learned about reproductive senescence from studies in the laboratory compared with what can be learned from studies in the field. Laboratory studies allow researchers to isolate and analyze detailed cellular and molecular mechanisms of reproductive senescence, however drawing evolutionary inferences from captive studies can be misleading. The ideal study would combine field and laboratory observations and experiments. As with most other biological phenomena, understanding the nature of genetic and environmental interactions is central to understanding of reproductive aging. PMID- 20738281 TI - The hypothalamic median eminence and its role in reproductive aging. AB - The median eminence at the base of the hypothalamus serves as an interface between the neural and peripheral endocrine systems. It releases hypothalamic releasing hormones into the portal capillary bed for transport to the anterior pituitary, which provides further signals to target endocrine systems. Of specific relevance to reproduction, a group of about 1000 neurons in mammals release the gonadotropin-releasing hormone (GnRH) peptide from neuroterminals in the median eminence. During the life cycle, there are dramatic changes in reproductive demands, and we focus this review on how GnRH terminals in the median eminence change during reproductive senescence. We discuss morphological and functional properties of the median eminence, and how relationships among GnRH terminals and their microenvironment of nerve terminals, glial cells, and the portal capillary vasculature determine the ability of GnRH peptide to be secreted and to reach its target in the anterior pituitary gland. PMID- 20738283 TI - Life history context of reproductive aging in a wild primate model. AB - The pace of reproductive aging has been of considerable interest, especially in regard to the long postreproductive period in modern women. Here we use data for both sexes from a 37-year longitudinal study of a wild baboon population to place reproductive aging within a life history context for this species, a primate relative of humans that evolved in the same savannah habitat as humans did. We examine the patterns and pace of reproductive aging, including birth rates and reproductive hormones for both sexes, and compare reproductive aging to age related changes in several other traits. Reproductive senescence occurs later in baboon females than males. Delayed senescence in females relative to males is also found in several other traits, such as dominance status and body condition, but not in molar wear or glucocorticoid profiles. Survival, health, and well being are the product of risk factors in morphological, physiological, and behavioral traits that differ in rate of senescence and in dependence on social or ecological conditions; some will be very sensitive to differences in circumstances and others less so. PMID- 20738284 TI - Reproductive aging in tephritid fruit flies. AB - The broad objective of this paper is to present an overview and synthesis of selected studies on reproduction and aging in two model tephritid fruit fly species including the Mediterranean fruit fly, Ceratitis capitata, and the Mexican fruit fly, Anastrepha ludens. We summarize the research findings from empirical studies and modeling investigations involving reproduction in the two tephritid species. At the end we identify and discuss four general principles regarding reproductive aging in tephritids including reciprocity of reproductive and aging costs, qualitative tradeoffs, plasticity of lifespan and reproduction, and life history constraints and determinacy. PMID- 20738286 TI - A pathway that links reproductive status to lifespan in Caenorhabditis elegans. AB - In the nematode Caenorhabditis elegans and the fruit fly Drosophila, loss of the germline stem cells activates lifespan-extending FOXO-family transcription factors in somatic tissues and extends lifespan, suggesting the existence of an evolutionarily conserved pathway that links reproductive state and aging. Consistent with this idea, reproductive tissues have been shown to influence the lifespans of mice and humans as well. In C. elegans, loss of the germ cells activates a pathway that triggers nuclear localization of the FOXO transcription factor DAF-16 in endodermal tissue. DAF-16 then acts in the endoderm to activate downstream lifespan-extending genes. DAF-16 is also required for inhibition of insulin/insulin-like growth factor 1 (IGF-1) signaling to extend lifespan. However, the mechanisms by which inhibition of insulin/IGF-1 signaling and germline loss activate DAF-16/FOXO are distinct. As loss of the germ cells further doubles the already-long lifespan of insulin/IGF-1 pathway mutants, a better understanding of this reproductive longevity pathway could potentially suggest powerful ways to increase healthy lifespan in humans. PMID- 20738285 TI - Reproductive aging in invertebrate genetic models. AB - The invertebrate genetic systems of Caenorhabditis elegans and Drosophila melanogaster are emerging models to understand the underlying mechanisms of reproductive aging and the relationship between reproduction and lifespan. Both animals show progressive decline in egg production beginning at early middle age, caused in part by reduction in germline stem cell proliferation as well as in survival of developing eggs. Molecular genetic analysis reveals that insulin and TGF-beta signaling are regulators of germline stem cell maintenance and proliferation during aging. Furthermore, the lifespan of both C. elegans and D. melanogaster appears to be regulated by signaling that depends on the presence of germline stem cells in the adult gonad. These invertebrate models provide powerful tools to dissect conserved causes of reproductive aging. PMID- 20738287 TI - Health consequences of reproductive aging: a commentary. AB - This commentary discusses the intersection of human ovarian and somatic aging. It argues for re-contextualizing estrogen's role in and impact on ovarian aging and, more broadly, on women's health, considering in particular the importance of timing, dose, and the broader endocrine milieu. Distinguishing between current clinical needs and optimizing women's future options, the paper outlines an approach to broadening the research agenda to better understand the role of ovarian aging in supporting the metabolic demands of longevity. Three overarching issues important to consider explicitly as we pursue research on the health correlates of reproductive aging are discussed, including implications of a lifespan approach, population diversity, and selection bias. PMID- 20738288 TI - Reproductive aging, menopause, and health outcomes. AB - Changes in ovarian hormone production may affect numerous health outcomes including vasomotor symptoms, cardiovascular disease (CVD), osteoporosis, cognition, depression, mood disorders, sexual function, and vaginal atrophy. We will compare age-related changes to those associated with reproductive aging and menopause and the effects of estrogen therapy on selected health outcomes. Hormone therapy (HT) reduces frequency and severity of hot flashes, prevents bone loss and osteoporotic fractures, and relieves vaginal atrophy. Nonhormone therapy trials with antidepressants or gabapentin for hot flash relief are promising. To date, clinical trial data are insufficient to recommend the use of HT for prevention or treatment of CVD, mood disorders, cognition, or sleep disorders. For some disease states, such as CVD and cognition, a "critical time window" has been proposed but not proven, such that estrogen use early in the menopause transition may be beneficial while estrogen use later in life would lead to increased health risks. PMID- 20738289 TI - Reproductive aging and its consequences for general health. AB - Reproductive aging coincides with endocrine changes that are not solely reproductive in nature and culminates in hypergonadotropic hypogonadism and amenorrhea. These changes are identifiable biochemically regardless of clinical manifestations. Changes in the hypothalamic-pituitary-ovarian axis are associated with changes in other hormonal axes, specifically the adrenal androgen and the somatotropic axis. A large body of literature indicates that reproductive aging is associated with a decline in the somatotropic axis. The interactions between reproductive aging and changes in the adrenal androgen axis are more complex and complicated by age-related declines in the adrenal axis early in the reproductive years. These changes may play an important role in overall health maintenance. Attempts to ameliorate hormonal declines with exogenous hormonal therapy have produced mixed results. Finally, the age-specific timing as well as the rapidity of the changes that occur with reproductive aging seems to have important consequences on metabolism, cardiovascular risk, cognition, bone density, and even mortality. PMID- 20738290 TI - Longitudinal, epidemiologic studies of female reproductive aging. AB - Human female reproductive aging consists of multiple processes and interacts with other physiological systems in unique ways. Here we discuss eight recent longitudinal, epidemiologic studies of female reproductive aging that include endocrine data to highlight their contributions to our understanding of these various aging processes and their interactions. Specifically, we review data on ovarian and nonovarian reproductive aging processes and reproductive staging. We consider these data in the context of longitudinal research design and research goals, identify limitations of the studies but also ways in which existing longitudinal data can further our understanding of aging processes, and make recommendations for future studies of female reproductive aging. PMID- 20738292 TI - Abstracts of the Royal Australasian College of Surgeons, Victorian Region, Annual General Scientific and Fellowship Meeting. Victoria, Western Australia, Australia. September 10-12, 2010. PMID- 20738293 TI - Update on the management of T1 renal cortical tumours. AB - There are a range of treatment strategies for the management of patients with small incidental renal cortical tumours including active surveillance, radiofrequency ablation, cryotherapy, radical nephrectomy and partial nephrectomy. A large number of such tumours are benign and might therefore be over-treated with radical nephrectomy. There are emergent short-term oncological and clinical outcomes for cryotherapy and radiofrequency ablation, and recent studies have illustrated the benefits of partial nephrectomy for minimizing the risk of progression to chronic kidney disease. The outcomes of these different treatment methods are discussed. PMID- 20738294 TI - Artificial urinary sphincter (AMS 800) implantation for women with intrinsic sphincter deficiency: a technique for insiders? AB - Artificial urinary sphincter (AUS) implantation is one of several surgical options for the treatment of female stress urinary incontinence. It is indicated for women with both clinically and urodynamically defined intrinsic sphincter deficiency that significantly affects quality of life. The erosion/revision risk increases after several previous surgical interventions. Therefore, women believed to be candidates for AUS implantation should be rapidly (after the failure of a maximum of two previous surgical procedures) referred to specialized centres, where the knowledge and experience concerning the diagnosis, surgery and management of female stress urinary incontinence is concentrated. To refer correctly, non-academic urologists/gynaecologists should also be well informed about AUS implantation. Only in this way can the patient weigh the high long-term success rate and high quality of life improvement of AUS implantation against the greater complication/revision risk and take a well-considered decision. PMID- 20738295 TI - Improving patient safety in urology. PMID- 20738296 TI - Left-right determination factor is down-regulated in fibrotic renal tissue of human hydronephrosis. AB - OBJECTIVE: * To compare the expressions of common fibrosis-relevant genes in hydronephrosis-induced fibrotic renal tissues and normal human renal tissues, thereby providing insights into the cellular and molecular mechanisms of renal fibrosis resulting from hydronephrosis. PATIENTS AND METHODS: * A total of 12 extensively fibrotic renal tissue samples from patients with hydronephrosis (H group) and six normal renal tissue samples from patients who underwent nephrectomy for renal cell carcinoma (N-group), along with their clinical data, were collected at Renmin Hospital of Wuhan University in China between October 2005 and August 2007. * These tissue samples were compared for their transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP) pathway-related gene profiles using a real-time polymerase chain reaction (PCR) microarray. * Subsequently, reverse transcriptase-PCR assays were used to validate the expression changes of left-right determination factor (LEFTY), a gene of interest, at the mRNA level. * The different expression of LEFTY at the protein level was confirmed by western blotting and immunohistochemistry assays. RESULTS: * The results showed that 49 genes were differently expressed in fibrotic renal tissues relative to normal control tissues. Among these genes, 25 were up regulated and 24 were down-regulated. * LEFTY-B, one of the most markedly altered genes, was down-regulated 13.55-fold compared with N-group tissues. * RT-PCR showed that the LEFTY-A (6.05-fold down-regulated, P < 0.001) and LEFTY-B (12.5 fold down-regulated, P < 0.001) genes, two members of the LEFTY family in human tissues, were both significantly down-regulated in H-group tissues. * Similarly, down-regulations of LEFTY-A (0.25-fold vs N-group, P < 0.001) and LEFTY-B (0.20 fold vs N-group, P < 0.001) proteins were detected by western blotting (P < 0.001). * Immunohistochemical staining showed different distributions of LEFTY in the two tissue samples, and quantitative image analyses confirmed that LEFTY protein expression was lower in H-group tissues than in N-group tissues (P < 0.001). CONCLUSIONS: * The gene and protein expressions of LEFTY were found to be down-regulated in extensively fibrotic renal tissues induced by hydronephrosis. * LEFTY may represent an ideal candidate for a therapeutic target for renal fibrosis. PMID- 20738297 TI - Impaired skin wound healing in lumican-null mice. AB - BACKGROUND: Previous studies have demonstrated that the lack of lumican delayed corneal wound healing in lumican-null (Lum(-/-) ) mice. This defect is rescued by the addition of glycosylated lumican core protein to the injured corneas. OBJECTIVES: We examined the hypothesis that lumican is also required for the healing of cutaneous wounds using Lum(-/-) mice. METHODS: We demonstrated the basic thinner skin phenotypes in Lum(-/-) mice at different time points and the changes in arrangement of collagen fibres by transmission electron microscopy (TEM). A full skin thickness wound was generated by punch biopsy (6 mm diameter) in experimental Lum(-/-) and wild-type mice. The closure of injured skin was measured after various periods of time (3, 6, 12, 18 days). Specimens of injured and uninjured skin (serving as control) were then subjected to morphological examination with haematoxylin and eosin and Masson trichrome stains, and by TEM. Immunohistochemical staining with anti-CD68 antibody was used to assess the presence of macrophages in injured skin healing for various periods of time. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to elucidate the transforming growth factor (TGF)-beta1-induced myofibroblast phenotypic genes. RESULTS: Skin of adult Lum(-/-) mice (3 months and older) was much thinner (40% less) than that of age-matched wild-type mice. This phenomenon was aggravated in older mice. TEM revealed disoriented and irregular collagen fibrils in the dermis of Lum(-/-) mice. Delayed wound healing with an increase in inflammatory macrophages was compatible with the delayed response of the expression of TGF-beta1, type I collagen alpha1 and fibronectin at the mRNA level by semiquantitative RT-PCR in the Lum(-/-) mice. CONCLUSIONS: Our data demonstrate that lumican plays pivotal roles in skin collagen fibrillogenesis and wound healing. PMID- 20738298 TI - Jumping translocations of the long arms of chromosome 1 in myeloid malignancies is associated with a high risk of transformation to acute myeloid leukaemia. PMID- 20738299 TI - Genome gains at chromosome 21q21/22 segment leads to co-amplification of Down Syndrome Critical Regions and known oncogenes in a case of donor cell-derived acute myeloid leukaemia following allogeneic sex mismatched umbilical cord blood transplantation for chronic myeloid leukaemia. PMID- 20738300 TI - Images in haematology. Pneumatosis intestinalis and pneumoperitoneum after allogeneic haematopoietic stem cell transplantation. PMID- 20738301 TI - Genetic variability of TMPRSS6 and its association with iron deficiency anaemia. AB - Transmembrane Protease, Serine 6 (TMPRSS6) has an important role in iron homeostasis and its mutations, performed in TMPRSS6-deficient mice, have been recently associated with iron-refractory iron deficiency anaemia (IRIDA). Several variants of TMPRSS6 have been already identified; however the role of polymorphisms and TMPRSS6 haplotypes, causing iron deficiency anaemia, have not yet been investigated. This study sequenced the TMPRSS6 gene in 16 subjects with IRIDA phenotype and identified 27 DNA polymorphisms. Eight single nucleotide polymorphisms and four haplotypes were significantly associated with iron refractory anaemia (P < 0.001). Our preliminary results suggest a possible association between specific haplotypes of TMPRSS6 and IRIDA. PMID- 20738302 TI - Images in haematology. Noonan syndrome associated with bleeding disorders. PMID- 20738303 TI - Pandemic influenza A (2009-H1N1) infection in paediatric oncology patients in Hong Kong. PMID- 20738304 TI - The impact of bleeding history, von Willebrand factor and PFA-100((r)) on the diagnosis of type 1 von Willebrand disease: results from the European study MCMDM 1VWD. AB - The relationships between the Platelet Function Analyzer (PFA)-100 and von Willebrand factor (VWF) levels and bleeding score (BS) were evaluated within a multicentre project on Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand disease (MCMDM-1VWD). PFA-100 closure time, either with epinephrine (EPI) or adenosine diphosphate (ADP)-cartridges, was measured in 107 index cases, 105 affected and 71 unaffected family members, and 79 healthy controls. By regression analysis VWF levels were strongly related to both closure times, with a non-linear progression. In a multiple stepwise regression model, age- and sex-adjusted PFA-100 ADP and VWF ristocetin cofactor activity (VWF:RCo) were independently associated with BS. Most of the variation of BS was predicted by PFA-100 ADP and VWF:RCo alone. In the subgroup of patients with subtle abnormalities of the multimeric pattern, VWF was invariably reduced and closure time prolonged in almost all of them. Neither PFA-100 ADP nor EPI closure times appeared to significantly improve the diagnostic capability of VWF antigen (VWF:Ag) measurement. Thus, in an unselected population a normal PFA-100 would be useful to exclude VWD, but whether it could replace the more specific VWF assay in patients with significant mucocutaneous bleeding symptoms remains to be investigated prospectively. PMID- 20738305 TI - Primary central nervous system lymphoma in the elderly: a multicentre retrospective analysis. AB - Elderly patients with primary central nervous ystem lymphoma (PCNSL) do not tolerate treatment with combined radio-chemotherapy well because of leuco encephalopathy; they are usually treated initially with chemotherapy or radiotherapy alone. Little is known about the efficacy and toxicity of these treatments outside clinical studies. This study was a retrospective analysis of all patients aged 60 years or over who were admitted with PCNSL to one of five Dutch centers between 1998 and 2007. A total of 74 patients were identified. Twenty-nine were treated with radiotherapy only (Group A), in 36 the intended treatment was chemotherapy alone (Group B), and nine were planned to receive chemotherapy followed by radiotherapy (Group C). Median overall survival was 20 months; 4 months in patients with a Karnofsky performance status (KPS) <70, 25 months in patients with a KPS >= 70 (P < 0.001). Treatment modality was not an independent prognostic factor. Forty patients were treated with methotrexate 3 g/m(2) : there were two toxic deaths. Ten patients discontinued chemotherapy because of toxicity. Delayed encephalopathy was reported in 10 patients. In conclusion, community hospitals still frequently utilize whole brain radiotherapy in elderly PCNSL patients, though a majority tolerates chemotherapy well. Performance status was the most important variable determining prognosis. Short and long term toxicities must be weighed against possible clinical benefits of each treatment, making treatment decisions a highly individualized process. PMID- 20738306 TI - The microenvironment differentially impairs passive and active immunotherapy in chronic lymphocytic leukaemia - CXCR4 antagonists as potential adjuvants for monoclonal antibodies. AB - Direct contact with stromal cells protects chronic lymphocytic leukaemia (CLL) B cells from chemotherapy-induced apoptosis in vitro. Blockade of CXCR4 signalling antagonizes stroma-mediated interactions and restores CLL chemosensitivity. In vivo, administration of CXCR4 antagonists effectively mobilizes haematopoietic progenitor cells. Therefore, combinations of CXCR4 blockade and cytoreductive treatment with selective activity on CLL cells may avoid potential haematotoxicity. Hence, we tested CXCR4 antagonists in the context of passive and active immunotherapeutic approaches. We evaluated how efficiently rituximab, alemtuzumab and cytotoxic T cells killed CLL cells cocultured with stromal cells in the presence and absence of a CXCR4 antagonist. Stromal cell contact attenuated rituximab- and alemtuzumab-induced complement-dependent cytotoxicity of CLL cells. Addition of CXCR4 antagonists abrogated the protective effect of stroma. In contrast, stromal cells did not impair antibody-dependent cell mediated cytotoxicity and cytotoxicity induced by activated T cells. Destruction of microtubules in CLL target cells restored the protective effect of stroma coculture for CLL cells during Natural Killer cell attack by preventing mitochondrial relocalization towards the immunological synapse. Our data identify the combination of CXCR4 antagonists with passive - but not active - immunotherapy as a promising potential treatment concept in CLL. PMID- 20738308 TI - Outpatient reduced intensity conditioning allogeneic stem cell transplantation for acute myeloid leukaemia in children. PMID- 20738307 TI - Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95. AB - Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucemies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas. PMID- 20738309 TI - Common occurrence of monoclonal B-cell lymphocytosis among members of high-risk CLL families. AB - Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic haematological condition characterized by low absolute levels of B-cell clones with a surface immunophenotype similar to that of chronic lymphocytic leukaemia (CLL). In the general population, MBL increases with age with a prevalence of 5-9% in individuals over age 60 years. It has been reported to be higher among first degree relatives from CLL families. We report results of multi-parameter flow cytometry among 505 first-degree relatives with no personal history of lymphoproliferative disease from 140 families having at least two cases of CLL. Seventeen percent of relatives had MBL. Age was the most important determinant where the probability for developing MBL by age 90 years was 61%. MBL clustered in certain families but clustering was independent of the number of known CLL cases in a family. As is the case with CLL, males had a significantly higher risk for MBL than did females (P = 0.04). MBL patients had significantly higher mean absolute lymphocyte counts (2.4 * 10(9) /l) and B-cell counts (0.53 * 10(9) /l) than those with a normal B-cell immuno-phenotype. Our findings show that MBL occurs at a very high rate in high risk CLL families. Both the age and gender distribution of MBL are parallel to CLL, implying a shared inherited risk. PMID- 20738310 TI - The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway. AB - Inhibitors of heat-shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP 70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL. PMID- 20738311 TI - Hairy cell leukaemia, negative for conventional cell markers, diagnosed using antibodies to annexin A1 and T-bet. PMID- 20738312 TI - Binding of cordycepin monophosphate to AMP-activated protein kinase and its effect on AMP-activated protein kinase activation. AB - It had been reported that cordycepin could activate AMP-activated protein kinase. One possible mechanism is that cordycepin mediated AMP-activated protein kinase activation by conversion into cordycepin monophosphate, which acts as an AMP analog to activate AMP-activated protein kinase. To confirm the aforementioned hypothesis, we investigate the binding of cordycepin monophosphate to AMP activated protein kinase using molecular docking. The modeling results indicate that cordycepin monophosphate binds to AMP-activated protein kinase with high affinity. The hydrogen bonds provide attractive forces between molecules. Our results further identify the key residues contributing to the interaction. Also, the modeling results predict that cordycepin monophosphate and AMP would have similar binding modes with AMP-activated protein kinase. Further investigation of AMP-activated protein kinase activation in vitro provides the evidence that cordycepin monophosphate functioned as an AMP mimic to activate AMP-activated protein kinase. PMID- 20738313 TI - The complexity of laboratory testing and diagnosis of steroid excess syndromes associated with herbal remedy use. PMID- 20738314 TI - Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover. AB - BACKGROUND: The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF). PATIENTS AND METHODS: In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4 week cycles of pSSR (transdermal oestradiol, 100 MUg daily for week 1, 150 MUg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 MUg and 1.5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12 month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment. RESULTS: Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z-score was -0.89 (95% CI -1.27 to -0.51) and increased by +0.17 (CI +0.07 to +0.27) in response to pSSR (P = 0.003), compared with +0.07 (CI -0.03 to +0.18) during standard HRT (P = 0.2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0.49, P = 0.04) and inversely to FSH (r = -0.65, P = 0.004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0.001) but decreased in the sHRT arm (P < 0.01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0.001). CONCLUSION: We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption. PMID- 20738315 TI - What is the best approach to an apparently nonmetastatic adrenocortical carcinoma? AB - In suspected nonmetastatic adrenocortical carcinoma (ACC) a careful preoperative diagnostic work up is needed including comprehensive endocrine analysis as recommended by the European Network for the Study of Adrenal Tumors (http://www.ENSAT.org/ACC.htm). Staging prior surgery, in particular chest CT, is indispensable to exclude distant metastases. Open surgery is still the recommended approach in ACC. However, in localized non-invasive ACC with a diameter <10 cm laparoscopic adrenalectomy by an expert surgeon is probably similarly effective and safe. As many patients will suffer from tumor recurrence after seemingly complete removal of ACC, adjuvant treatment based on the individual risk status is recommended. Key factors for risk assessment are tumor stage, resection status and the proliferation marker Ki67. All patients considered at high risk for recurrence should receive adjuvant mitotane for a minimum of 2 years aiming at a drug level of 14-20 mg/l. In selected patients (e.g. R1 resection) we recommend additional radiotherapy of the tumor bed. Patients with a low/intermediate risk for recurrence should be included in the Adiuvo trial comparing adjuvant mitotane with observation only (http://www.adiuvo trial.org). In low/intermediate risk patients who cannot be included in this trial observation only can be justified in cases with a tumor diameter of <8 cm and no microscopic evidence for invasion of blood vessels or tumor capsule. In all patients a structured follow-up for 10 years is strongly recommended. PMID- 20738316 TI - Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects. AB - OBJECTIVE: Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects. DESIGN: Randomized, double-blinded, placebo-controlled crossover. SUBJECTS: Seven lean [mean body mass index (BMI) 23.6 +/- 0.9 kg/m(2) ], seven morbidly obese (mean BMI 50.9 +/- 4.4 kg/m(2) ) and seven post-gastrectomy subjects (mean BMI 22.0 +/- 1.1 kg/m(2) ). MEASUREMENTS: Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 min. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Total power (TP) represents overall autonomic function, low-frequency (LF) power represents sympathetic and parasympathetic activity, and high-frequency (HF) power represents parasympathetic activity. Very low (VLO) frequency represents the frequency band associated with thermogenesis. RESULTS: Preliminary anova analysis, looking at all three subject groups together, showed that ghrelin had an overall highly significant inhibitory effect on TP (P = 0.001), HF power (P = 0.04), VLO power (P = 0.03) and no effect on LF (P = 0.07). Further subset analysis revealed that ghrelin had a significant effect on TP (P = 0.03), borderline effect on LF power (P = 0.06) and no effect on HF power (P = 0.1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (P = 0.3), LF (P = 0.5) and HF (P = 0.06) and also no effect in the vagotomized subjects on TP (P = 0.7), LF (P = 0.7) and HF (P = 0.9). Ghrelin had no effect on the LF/HF ratio. CONCLUSIONS: Ghrelin inhibits SNS activity in healthy controls with a moderate effect on parasympathetic nervous system activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin, suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS. PMID- 20738317 TI - Cbl-b regulates airway mucosal tolerance to aeroallergen. AB - BACKGROUND: As an E3 ubiquitin ligase and a molecular adaptor, Cbl-b controls the activation threshold of the antigen receptor and negatively regulates CD28 costimulation, functioning as an intrinsic mediator of T cell anergy that maintains tolerance. However, the role of Cbl-b in the airway immune response to aeroallergens is unclear. OBJECTIVE: To determine the contribution of Cbl-b in tolerance to aeroallergens, we examined ovalbumin (OVA)-induced lung inflammation in Cbl-b-deficient mice. METHODS: Cbl-b(-/-) mice and wild-type (WT) C57BL/6 mice were sensitized and challenged with OVA intranasally, a procedure normally tolerated by WT mice. We analysed lung histology, bronchoalveolar lavage fluid total cell counts and differential, cytokines and chemokines in the airway, and cytokine response by lymphocytes after re-stimulation by OVA antigen. RESULTS: Compared with WT mice, OVA-challenged Cbl-b(-/-) mice showed significantly increased neutrophilic and eosinophilic infiltration in the lung and mucus hyperplasia. The serum levels of IgG2a and IgG1, but not IgE, were increased. The levels of inflammatory mediators IFN-gamma, IL-10, IL-12, IL-13, IP-10, MCP-1, MIP-1alpha, eotaxin, and RANTES, but not IL-17A or IL-6, were elevated in the airway of Cbl-b(-/-) mice. Lymphocytes from Cbl-b(-/-) mice released increased amount of IFN-gamma, IL-10, IL-13, and IP-10 in response to OVA re-stimulation. However, no significant changes were noted in the CD4(+) CD25(+) T regulatory cell populations in the lung tissues after OVA stimulation and there was no difference between WT and Cbl-b(-/-) mice. CONCLUSION: These results demonstrate that Cbl-b deficiency leads to a breakdown of tolerance to OVA allergen in the murine airways, probably through increased activation of T effector cells, indicating that Cbl-b is a critical factor in maintaining lung homeostasis upon environmental exposure to aeroallergens. PMID- 20738318 TI - Hyperviscosity syndrome associated with systemic plasmacytosis. AB - Systemic plasmacytosis is characterized by plasma cell proliferation in multiple organs including skin, and by polyclonal hypergammaglobulinaemia. Hyperviscosity related retinopathy has never been described with this condition, to our knowledge. We report a case of systemic plasmacytosis in a 49-year-old Japanese woman, who presented with fever, multiple erythematous plaques, hypergammaglobulinaemia, renal failure and bilateral retinal haemorrhage. Reduction of immunoglobulin with oral steroid reversed the retinopathy related to hyperviscosity syndrome. When marked hypergammaglobulinaemia is found in a patient with systemic plasmacytosis, funduscopic examination should be performed to reveal early asymptomatic retinal changes, because the retinopathy is treatable by control of the underlying disease. PMID- 20738319 TI - Photodynamic therapy for the treatment of keratolytic winter erythema. PMID- 20738320 TI - Drug-induced subacute cutaneous lupus erythematosus associated with omeprazole. AB - Subacute cutaneous lupus erythematosus (SCLE) is characterized by annular scaly erythematous plaques in a photosensitive distribution, and the presence of anti Ro (SSA) and/or anti-La (SSB) antibodies. Most cases of SCLE are idiopathic, but occasional cases may be drug-induced or associated with a hereditary deficiency of complement components. We report two cases of drug-induced SCLE precipitated by the proton pump inhibitor, omeprazole. Drug-induced disease should be considered in all atypical or extensive cases of SCLE, especially in elderly patients. PMID- 20738321 TI - Dermatology referrals in an East Asian tertiary hospital: a need for inpatient medical dermatology. AB - BACKGROUND: Within hospitals, there is a need for dermatological expertise, as hospitalized patients have a wider spectrum of severe and serious dermatological conditions, associated with significant morbidity. AIM: To characterize the patient profile and referral pattern of inpatient dermatology consultations, and to evaluate the diagnostic accuracy of non-dermatologists. METHODS: This was a retrospective study reviewing all inpatient referrals for dermatology consultations during a 1-year period from July 2005 to June 2006 (inclusive), at the largest multi-disciplinary tertiary hospital in Singapore. RESULTS: Of the 731 referrals made for dermatology consultations, 26.9% of patients had >= 3 important underlying comorbidities. Eczema/dermatitis (33.1%; n = 242) and cutaneous infections (23.4%; n = 171) accounted for over half of the dermatological consultations, followed by cutaneous adverse drug reactions (12.3%; n = 90). The provisional diagnoses of the referring doctors agreed with the final diagnoses confirmed by dermatologists in only 30.2% of all referrals; incorrect diagnoses were made in 35.2% of cases, and no provisional diagnoses were made in the remaining 34.6% of cases. Most misdiagnosed skin diseases were in fact common dermatoses (such as eczemas, cutaneous infections, drug rash) that required only standard treatment. CONCLUSION: Our study reiterates the importance of inpatient medical dermatology in terms of both service and education. There should be continual efforts to ensure that dermatologists have the highest level of training and experience in medical dermatology, to provide collaborative optimum care for hospitalized patients with dermatological diseases. PMID- 20738322 TI - Cutaneous adverse drug reactions in a hospital-based Chinese population. AB - BACKGROUND: Cutaneous adverse drug reactions (CADRs) are common skin adverse reactions associated with drugs. AIM: To assess recent trends in CADRs and the drugs associated with them, using data from the past 5 years in the largest single database available on a hospital-based population in China. METHODS: All clinical records of inpatients admitted with a diagnosis of CADR to the Dermatology Ward, Huashan Hospital from January 2004 to December 2008 were retrospectively studied. RESULTS: In the 734 patients, the three most common types of CADRs were nonsevere reactions, erythema multiforme (EM)-like eruptions (n = 255), urticaria (n = 192) and exanthematous reactions (n = 159), followed by three severe reactions: Stevens-Johnson syndrome (n = 58), toxic epidermal necrolysis (n = 29) and exfoliative dermatitis (n = 22). The most common single drug associated with the development of all drug eruptions was allopurinol, followed by amoxicillin, cephalosporins, antiepileptic agents and antipyretic/analgesic agents. However, the most common single drugs associated with severe reactions were antiepileptic agents, followed by allopurinol, antipyretic/analgesic agents and cephalosporins. In contrast to patients with nonsevere reactions, patients with severe reactions were more likely to be male (P < 0.001) and to have a greater mean age of onset (P < 0.001), a longer latency period (P < 0.001) and a longer duration of hospitalization (P < 0.001). CONCLUSION: In contrast to previous studies, we found allopurinol to be the most common single drug associated with CADRs followed by antibiotics (amoxicillin and cephalosporins), and antiepileptic, especially carbamazepine. A higher incidence of EM-like eruptions and urticaria was also seen. PMID- 20738323 TI - What's new in acne? An analysis of systematic reviews published in 2009-2010. AB - This review highlights clinically important findings about acne treatment identified in nine systematic reviews published or indexed in the period March 2009 to February 2010. A systematic review of dietary influences on acne suggested that a possible role of dietary factors in acne cannot be dismissed, as the studies to date have not been sufficiently large or robust. Another review looked at benzoyl peroxide, which may be enjoying a comeback because of increasing bacterial resistance to antibiotics, and suggested that there was a lack of evidence that stronger preparations were more effective than weaker ones. The same team also carried out a systematic review addressing the question of whether topical retinoids cause an initial worsening of acne. They found no evidence to suggest initial worsening of acne severity, although there was evidence of skin irritation that typically settled by 8-12 weeks. A review of oral isotretinoin and psychiatric side-effects reinforced a possible link between the two, although it pointed out that the better-quality primary studies were still inconclusive. An updated Cochrane Review confirmed the efficacy of combined oral contraceptives (COCs) in reducing acne lesion counts. It also found that the evidence to support COCs containing cyproterone acetate over others was very limited. Another Cochrane Review failed to show any benefit of spironolactone for acne, based on limited studies. Three reviews examined laser and light therapies, and found some evidence of superiority only for blue or blue/red light treatment over placebo light, but a general absence of comparisons against other acne treatments. Photodynamic therapy had consistent benefits over placebo but was associated with significant side-effects and was not shown to be better than topical adapalene. PMID- 20738324 TI - Intraocular lens alignment from purkinje and Scheimpflug imaging. AB - The improved designs of intraocular lenses (IOLs) implanted during cataract surgery demand understanding of the possible effects of lens misalignment on optical performance. In this review, we describe the implementation, set-up and validation of two methods to measure in vivo tilt and decentration of IOLs, one based on Purkinje imaging and the other on Scheimpflug imaging. The Purkinje system images the reflections of an oblique collimated light source on the anterior cornea and anterior and posterior IOL surfaces and relies on the well supported assumption of the linearity of the Purkinje images with respect to IOL tilt and decentration. Scheimpflug imaging requires geometrical distortion correction and image processing techniques to retrieve the pupillary axis, IOL axis and pupil centre from the three-dimensional anterior segment image of the eye. Validation of the techniques using a physical eye model indicates that IOL tilt is estimated within an accuracy of 0.261 degree and decentration within 0.161 mm. Measurements on patients implanted with aspheric IOLs indicate that IOL tilt and decentration tend to be mirror symmetric between left and right eyes. The average tilt was 1.54 degrees and the average decentration was 0.21 mm. Simulated aberration patterns using custom models of the patients eyes, built using anatomical data of the anterior cornea and foveal position, the IOL geometry and the measured IOL tilt and decentration predict the experimental wave aberrations measured using laser ray tracing aberrometry on the same eyes. This reveals a relatively minor contribution of IOL tilt and decentration on the higher-order aberrations of the normal pseudophakic eye. PMID- 20738325 TI - Leptin induces hypertrophy through activating the peroxisome proliferator activated receptor alpha pathway in cultured neonatal rat cardiomyocytes. AB - 1. Our previous study has shown that leptin induces cardiomyocyte hypertrophy; however, the mechanisms are poorly understood. Recent studies have shown that peroxisome proliferator-activated receptor alpha (PPARalpha) activation might be responsible for pathological remodeling and severe cardiomyopathy. Leptin, as an endogenous activator of PPARalpha, regulates energy metabolism through activating PPARalpha in many cells. Therefore, we hypothesized that leptin induces cardiomyocyte hypertrophy through activating the cardiac PPARalpha pathway. 2. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of PPARalpha on hypertrophy. The selective PPARalpha antagonist GW6471 concentration dependently decreased atrial natriuretic factor mRNA expression by 23%, 36%, 44% and 59%, and significantly decreased total RNA levels, protein synthesis and cell surface areas, all of which were elevated by 72h of leptin treatment. The augmentation of reactive oxygen species levels in leptin treated cardiomyocytes was reversed by 0.1-10MUmol/L GW6471 (40%, 52% and 58%). After 24h of treatment, leptin concentration-dependently enhanced mRNA expression by 7%, 93%, 100% and 256%, and protein expression by 31.2%, 64.2%, 143% and 199%, and the activity of PPARalpha. Meanwhile, cardiomycytes receiving 72h of treatment with the PPARalpha agonist, fenofibrate, concentration-dependently increased total RNA levels, atrial natriuretic factor mRNA expression, protein synthesis and cell surface area. Treatment of fenofibrate for 4 h also elevated oxygen species levels in a concentration-dependent manner. 3. In conclusion, these findings show that leptin induces hypertrophy through the activation of the PPARalpha pathway in cultured neonatal rat cardiomyocytes. PMID- 20738326 TI - Matrix metalloproteinase-2 regulates the expression of tissue inhibitor of matrix metalloproteinase-2. AB - 1. Matrix metalloproteinases (MMP) are associated with the vascular remodelling seen in atherosclerosis and aneurysm. The activation and activity of MMP-2 are regulated by the intrinsic tissue inhibitor of MMP-2 (TIMP-2). The aim of the present study was to examine whether, conversely, MMP-2 can affect the gene and protein expression of TIMP-2. 2. In the present study, we examined the mRNA and protein expression of MMP-2 and TIMP-2 in cultured smooth muscle cells (SMC) from the aortas of MMP-2(+/+) and MMP-2(-/-) mice. We also examined the roles of MMP-2 in SMC cellular events. 3. Western blotting showed that less TIMP-2 protein was present in the conditioned medium of MMP-2(-/-) SMC than in that of MMP-2(+/+) SMC. Real-time reverse transcription polymerase chain reaction analysis showed that MMP-2 deficiency reduced TIMP-2 mRNA expression in SMC. Recombinant MMP-2 enhanced the expression of TIMP-2 protein in cultured SMC from MMP-2(-/-) mice. Furthermore, a siRNA targeting MMP-2 impaired the gene and protein expression of MMP-2 in cultured SMC from MMP-2(+/+) mice. MMP-2 deficiency impaired SMC invasion, but not their proliferation, adhesion or migration. 4. Our findings suggest that MMP-2 is likely to be responsible, at least in part, for regulating TIMP-2 expression and is thus a potential target, in addition to TIMP-2, for therapeutics aimed at preventing cardiovascular remodelling in response to injury. PMID- 20738327 TI - Wolfram syndrome and WFS1 gene. AB - Wolfram syndrome (WS) (MIM 222300) is a rare multisystem neurodegenerative disorder of autosomal recessive inheritance, also known as DIDMOAD (diabetes insipidus, insulin-deficient diabetes mellitus, optic atrophy and deafness). A Wolfram gene (WFS1) has been mapped to chromosome 4p16.1 which encodes an endoplasmic reticulum (ER) membrane-embedded protein. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium omeostasis. Disturbances or overloading of these functions induce ER stress responses, including apoptosis. Most WS patients carry mutations in this gene, but some studies provided evidence for genetic heterogeneity, and the genotype-phenotype relationships are not clear. Here we review the data regarding the mechanisms and the mutations of WFS1 gene that relate to WS. PMID- 20738328 TI - Novel homozygous mutation in DSP causing skin fragility-woolly hair syndrome: report of a large family and review of the desmoplakin-related phenotypes. AB - Desmoplakin is an important cytoskeletal linker for the function of the desmosomes. Linking desmoplakin to certain types of cardiocutaneous syndromes has been a hot topic recently. Skin fragility-woolly hair syndrome is a rare autosomal recessive disorder involving the desmosomes and is caused by mutation in the desmoplakin gene (DSP). We report five members from a large family with skin fragility-woolly hair syndrome. The index is a 14-year-old girl with palmoplantar keratoderma, woolly hair, variable alopecia, dystrophic nails, and excessive blistering to trivial mechanical trauma. No cardiac symptoms were reported. Although formal cardiac examination was not feasible, the echocardiographic evaluation of the other two affected younger siblings was normal. Homozygosity mapping and linkage analysis revealed a high LOD score region in the short arm of chromosome 6 that harbors the DSP. Full sequencing of the DSP showed a novel homozygous c.7097 G>A (p.R2366H) mutation in all affected members, and the parents were heterozygous. This is the report of the third case/family of the skin fragility-woolly hair syndrome in the literature. We also present a clinical and molecular review of various desmoplakin-related phenotypes, with emphasis on onset of cardiomyopathy. The complexity of the desmoplakin and its variable presentations warrant introducing the term 'desmoplakinopathies' to describe all the phenotypes related to defects in the desmoplakin. PMID- 20738329 TI - Contribution of VANGL2 mutations to isolated neural tube defects. AB - Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non-canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi-ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations. PMID- 20738330 TI - Silver-Russell patients showing a broad range of ICR1 and ICR2 hypomethylation in different tissues. AB - In all known congenital imprinting disorders an association with aberrant methylation or mutations at specific loci was well established. However, several patients with transient neonatal diabetes mellitus (TNDM), Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) exhibiting multilocus hypomethylation (MLH) have meanwhile been described. Whereas TNDM patients with MLH show clinical symptoms different from carriers with isolated 6q24 aberrations, MLH carriers diagnosed as BWS or SRS present only the syndrome specific features. Interestingly, SRS and BWS patients with nearly identical MLH patterns in leukocytes have been identified. We now report on the molecular findings in DNA in three SRS patients with hypomethylation of both 11p15 imprinted control regions (ICRs) in leukocytes. One patient was a monozygotic (MZ) twin, another was a triplet. While the hypomethylation affected both oppositely imprinted 11p15 ICRs in leukocytes, in buccal swab DNA only the ICR1 hypomethylation was visible in two of our patients. In the non-affected MZ twin of one of these patients, aberrant methylation was also present in leukocytes but neither in buccal swab DNA nor in skin fibroblasts. Despite mutation screening of several factors involved in establishment and maintenance of methylation marks including ZFP57, MBD3, DNMT1 and DNMT3L the molecular clue for the ICR1/ICR2 hypomethylation in our patients remained unclear. Furthermore, the reason for the development of the specific SRS phenotype is not obvious. In conclusion, our data reflect the broad range of epimutations in SRS and illustrate that an extensive molecular and clinical characterization of patients is necessary. PMID- 20738331 TI - Nature vs nurture: genetic susceptibility and weight loss in hepatic steatosis. PMID- 20738332 TI - Yet another gene mutation: dysfunction in mitochondrial protein quality control causing hereditary ataxia. PMID- 20738333 TI - DNA repair deficiency in a newly identified neurological disease. PMID- 20738334 TI - TNM classification of malignant tumours 7th edition: what's new for head and neck? PMID- 20738335 TI - Evidence-based management of oropharyngeal cancer. PMID- 20738336 TI - The role of anthropometric measurements in nasal surgery and research: a systematic review. AB - BACKGROUND: Anthropometric measurements of the nose provide objective data about the size and shape of the nose. Data of average nasal anthropometric values for various ethnic groups is promoted to be of great importance in planning aesthetic nasal surgery, but there may be fundamental problems with this approach. OBJECTIVE OF REVIEW: To collate existing knowledge on nasal anthropometry and, determine its value to the nasal surgeon, in planning aesthetic nasal surgery and in research. SEARCH STRATEGY: A structured search of PubMed was performed from 1 January 1973 to 31 December 2009 focussing on nasal anthropometry. The MeSH keywords used were nasal/nose, anthropometry/history/methods/measurements, aesthetic, surgery, nose, otorhinolaryngologic surgical procedures. RESULTS: There is published literature on the average values of the nasal dimensions for various ethnic groups, to aid surgeons in planning improvements of the face. However the large overlap of anthropometric data between racial groups and the lack of any scientific basis for the concept of race means that the published data for racial groups is of little use in planning nasal surgery. Nasal anthropometry, however, helps to answer important clinical questions in research. It has established the role of primary rhinoplasty in patients with cleft lip nasal deformity. It serves as an objective tool to investigate whether reconstructive nasal septoplasty in the paediatric population has any deleterious effect on nasal growth. Anthropometry also helps in the characterisation of dysmorphic syndromes. CONCLUSIONS: The published anthropometric data for racial groups is of little use in planning nasal surgery. Anthropometric measurements of the nose may help to answer important clinical questions in research on the effects of surgery on nasal and facial development. PMID- 20738338 TI - The relationship between patients' perception of the effects of neurofibromatosis type 2 and the domains of the Short Form-36. AB - OBJECTIVES: To investigate the relationship between those issues concerning quality of life in patients with neurofibromatosis type 2 (NF2) as identified by the closed set NF2 questionnaire and the eight norm-based measures and the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form-36 (SF-36) Questionnaire. DESIGN: Postal questionnaire study. SETTING: Questionnaires sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult subjects under the care of the Manchester Multidisciplinary NF2 Clinic were invited to participate. MAIN OUTCOME MEASURES: Sixty-two (71%) completed sets of closed set NF2 questionnaires and SF-36 questionnaires were returned. RESULTS: Subjects with NF2 scored less than the norm of 50 on both the physical component summary and mental component summary scores and the eight individual norm-based measures of the Short Form-36 questionnaire. Correlations (using Kendall's tau) were examined between patients' perceptions of their severity of difficulty with the following activities and the eight norm-based measures and the physical component summary and mental component summary scores of the Short Form-36 questionnaire: Communicating with spouse/significant other (N = 61). The correlation coefficients were significant at the 0.01 level for the mental component summary score, together with three of the norm-based scores [vitality (VT), social functioning and role emotional]. Social communication (N = 62). All 10 correlations were significant at the 0.01 or 0.001 level. Balance (N = 59). All 10 correlations were highly significant at the P < 0.001 level. Hearing difficulties (N = 61). All correlations were significant at either the 0.01 level or less apart from the mental component summary score and three of the norm-based scores (role physical, VT and mental health). Mood change (N = 61). All correlations were significant at the 0.01 level or less, apart from one norm based score (role physical). CONCLUSIONS: The Short Form-36 questionnaire has allowed us to relate patients' perceptions of their difficulties, as identified by the closed set NF2 questionnaire, to the physical and mental domains measured by this validated and widely used scale, and has provided further insight into areas of functioning affected by NF2. PMID- 20738337 TI - The bone-anchored hearing aid in the rehabilitation of single-sided deafness: experience with 58 patients. AB - OBJECTIVES: To assess the efficacy of the bone-anchored hearing aid (BAHA) in the rehabilitation of single-sided deafness (SSD). STUDY DESIGN: Retrospective case control series review. SETTING: Tertiary referral unit. PATIENTS: Fifty-eight consecutive patients that had a bone-anchored hearing aid for single-sided deafness completed outcome questionnaires, building upon earlier audiological assessment of 19 patients. Single-sided deafness controls (n = 49) were mainly acoustic neuroma patients. MAIN OUTCOME MEASUREMENTS: speech discrimination testing in directional noise, speech and spatial qualities of hearing questionnaire and the Glasgow Benefit Inventory (GBI). RESULTS: The mean follow up time was 28.4 months. Five (13%) of the bone-anchored hearing aid patients were non-users because of lack of benefit. The audiometric testing confirmed that when noise was on the bone-anchored hearing aid side speech perception was reduced but benefited when noise was on the side of the hearing ear. There was no difference between the Speech and Spatial Qualities of Hearing Scores in bone anchored hearing aid users and controls. In particular there was no difference in the spatial subscores. In the bone-anchored hearing aid users the median Glasgow Benefit Inventory score was 11. If the non-users are included then 13 (22%) patients had no or detrimental (negative) Benefit scores. No or negative benefit scores were more frequent in those deaf for <10 years. In open-field questions, patients felt the bone-anchored hearing aid was most useful in small groups or in 'one-to-one' conversation. CONCLUSIONS: Bone-anchored hearing aid rehabilitation for single-sided deafness is less successful than for other indications, reflected here by relatively low median Glasgow Benefit Inventory scores. There was also no significant difference between controls and bone-anchored hearing aid users in the Speech and Spatial Qualities of Hearing Questionnaire. Patients with a longer duration of deafness report greater subjective benefit than those more recently deafened, perhaps due to differing expectations. PMID- 20738339 TI - Outcomes of endoscopic sinus surgery in an elderly population: comparison with those in an adult population. AB - OBJECTIVE: The aim of this study was to compare the surgical outcomes of endoscopic sinus surgery in two patient groups: adults younger than 65 years of age and adults aged 65 years or older. DESIGN: A retrospective study. SETTING: This study was conducted at an academic tertiary referral centre. PARTICIPANTS: One hundred and eighty consecutive older patients (> or =65 years), and 180 adult patients (>15, <65 years) with chronic rhinosinusitis who underwent endoscopic sinus surgery under local anaesthesia between 1997 and 2007 were enrolled in this study. MAIN OUTCOME MEASURES: Recurrence and complication rates were analyzed. Data were analyzed using the Mann-Whitney test, Fisher's Exact test, the Pearson Chi-Square test, and univariate and multivariate logistic regression. P < 0.05 was considered statistically significant. RESULTS: When looked at without control for other factors the surgical complication rates were higher in the older group patients (31%) compared with the younger patients (11%). However, multivariate logistic regression analysis showed that preoperative duration of symptoms, length of follow-up, and diabetes mellitus were positively correlated with complications. In this analysis, the older patients, once controlled for these factors, were less likely to have complications. Regarding recurrence, in multivariate analysis there was no difference between the older and the younger group with preoperative duration and length of postoperative follow-up having a small effect. CONCLUSIONS: Comorbidity especially diabetes mellitus and duration of the condition should be the factors considered preoperatively to predict the likely hood of complications rather than whether the patient is younger or older that 65 years of age. PMID- 20738340 TI - Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome. AB - OBJECTIVE: To assess the possible effect of young age on clinical behaviour and survival outcome of squamous cell carcinoma of the oral tongue. DESIGN: Retrospective, case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Eighty-five patients with oral tongue squamous cell carcinoma with at least 2 years of follow-up. MAIN OUTCOME MEASUREMENTS: Clinical and histopathological staging, disease-free survival, disease-specific survival and overall survival. RESULTS: Eleven patients (13%) were younger than 30 years. Compared to the older patients, they had a significantly worse N stage (P = 0.041), more perineural invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with distant metastases, versus 35%, nearly all locoregional) and mortality (100% of treatment failures versus 73%). There were no significant between-group differences in 5-year disease-free, disease-specific, and overall survival. CONCLUSION: In this study, patients younger than 30 years of age presented with advanced tumour stages and with a different failure pattern compared to the older age group. This may be attributable to age-related biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could not be established. PMID- 20738341 TI - 12 minute consultation: a patient with nasal crusting. AB - BACKGROUND: Nasal crusting is frequently encountered by the otorhinolaryngologist and often requires no specific treatment. It is, however, important to carry out a full history and examination, followed by appropriate investigations, in order to detect the small number of cases in which crusting is caused by systemic or malignant disease. METHODS: This review was based on a literature search last performed on 30th July 2009. The MEDLINE, EMBASE and Cochrane databases were searched using the subject headings (nasal crusting OR crusts) and in combination with diagnosis, therapy and surgery. Similar searches were performed for relevant diseases, e.g. Wegener's granulomatosis, sarcoidosis. Results were limited to English language articles including clinical trials, meta-analyses, systematic reviews and review articles. Relevant references from selected articles were reviewed. RESULTS: Knowledge of the causes of nasal crusting will help to target the history, examination and investigation of patients with this condition. Screening tests for systemic conditions can be useful but most have limited sensitivity and must be interpreted cautiously. Nasal septal biopsy is indicated when there is a suspicion of malignancy, or to support a suspected diagnosis of vasculitis. The treatment offered depends upon the cause of crusting and the severity of symptoms. CONCLUSION: A careful and thorough history and examination, and targeted investigation, of the patient with nasal crusting will ensure correct diagnosis and treatment of patients with this common condition. PMID- 20738344 TI - A SIGN guideline that has considerable interpretation bias. PMID- 20738345 TI - Fibre-optic laryngoscope and endotracheal tube assembly: a robust method of monitoring recurrent laryngeal nerve function during thyroid surgery: how we do it. PMID- 20738346 TI - The rhinotopic protocol for chronic refractory rhinosinusitis: how we do it. PMID- 20738348 TI - Re: Correlation between subjective and objective evaluation of the nasal airway. A systematic review of the highest level of evidence. PMID- 20738347 TI - The internal mammary artery perforator pedicled island flap for reconstruction of the lower head and neck and supraclavicular region: how we do it. PMID- 20738349 TI - 'Raised leucocyte levels as a marker for post-tonsillectomy haemorrhage - a useful tool?' More questions than answers. PMID- 20738351 TI - Permacol in augmentation rhinoplasty. PMID- 20738352 TI - A simple method for dilating tracheostomal stenosis. PMID- 20738353 TI - Fingertip support technique and instrument support for reducing unintentional instrument movements in otology. PMID- 20738354 TI - Comparative trends in ENT junior doctor pay. PMID- 20738355 TI - Tilley's dressing forceps: a life-saving instrument. PMID- 20738356 TI - Revalidation. PMID- 20738357 TI - i-Phone applications for the modern day otolaryngologist. PMID- 20738358 TI - Apoptosis and cell proliferation correlated with tumour grade in peritoneal fluids of patients with serous ovarian cancer. AB - OBJECTIVE: Apoptosis and cell proliferation in peritoneal fluids of patients with ovarian serous adenocarcinoma have not been well described in cytology. To investigate the contribution of cell death to the growth of this tumour we analysed both apoptosis and cell proliferation in peritoneal fluids of patients with ovarian serous adenocarcinoma. METHODS: We studied 40 tumours from 40 patients with ovarian serous adenocarcinoma. Twelve tumours were high grade, 13 were moderately differentiated and 15 were poorly differentiated. The detection of DNA fragments in situ using the terminal deoxyribonucleotidy transferase (TDT) mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay was applied to investigate active cell death (apoptosis), and the MIB-1 antigen was used to investigate cell proliferation. RESULTS: The TUNEL indices were 0.29 +/- 0.05, 0.79 +/- 0.10 and 2.1 +/- 0.90 in Grade I, Grade II and Grade III ovary carcinomas, respectively. The MIB-1 antigen labelling indices were 6.5 +/- 0.09, 12.9 +/- 3 and 25.8 +/- 6.2, respectively, in the same order of tumour differentiation. The differences in both TUNEL and MIB-1 labelling indices were statistically significant between Grade I, Grade II and Grade III carcinomas and there was a positive correlation between the two indices (P < 0.001). CONCLUSIONS: Apoptosis and cell proliferation increased as the grade of tumour increased in ovarian serous adenocarcinoma, suggesting a rapid turnover of the tumour cells in tumours of higher grade, and may play an important role in the growth and the extension of such cancer cells in the peritoneal cavity. PMID- 20738359 TI - Role and accuracy of rapid on-site evaluation of CT-guided fine needle aspiration cytology of lung nodules. AB - OBJECTIVE: To prospectively investigate the role of trans-thoracic fine needle aspiration cytology (FNA) and the value of rapid on-site evaluation (ROSE) in the clinical management of patients with pulmonary nodules/masses. Computed tomography (CT)-guided FNA is commonly employed for the diagnosis of lung lesions although its position in the diagnostic work-up is still a matter of debate. METHODS: We reviewed 311 patients (211 males and 100 females, mean age 69.5 years) admitted to the University of Padova from 2004 to 2008, correlating the results of cytology with the available histological findings obtained from biopsies, surgery or autopsy. RESULTS: Smears were adequate in 305 cases (98%) and inadequate in six (2%); a diagnosis of malignancy was achieved in 263 cases (86.2%); 39 cases (12.8%) were classified as non-malignant; and three cases (1%) were classified as suspect for malignancy. When correlated with histology, FNA with ROSE discriminated malignant versus non-malignant lesions (Cohen's kappa 0.78), with three false negatives (sensitivity 96.3%, specificity 100%). Moreover, a satisfactory overall agreement of 71.4% was achieved in differentiating the cancer histological types. Pneumothorax occurred in 13 cases, haemoptysis in four, and chest pain in three. A single aspiration was sufficient in 79.6% of patients; two aspirations were needed in 17.4% and three in 3%. The low complication rate was related to the limited number of aspirations needed due to ROSE. CONCLUSIONS: FNA with ROSE is a safe and useful tool in the diagnostic work-up of lung cancer patients, with no contraindications to its use as the first diagnostic procedure for all patients with peripheral lung lesions. FNA with ROSE should be reconsidered in the guidelines for diagnosing and managing lung cancer. PMID- 20738360 TI - Immediate self-replantation of an avulsed permanent mandibular incisor - a case report. AB - BACKGROUND: Approximately 50% of children under the age of 15 years are subjected to various kinds of injuries in the orofacial region. In the permanent dentition, the most severe dental injury affects the surrounding alveolar bone structure and leads to loss of the tooth. The current literature emphasizes that the awareness of appropriate triage procedures following dental trauma is unsatisfactory and that delay in treatment is the single most influential factor affecting prognosis. RESULTS: This case report presents the immediate self-replantation of a right lateral mandibular incisor of a 12-year-old male patient following a traumatic avulsion. The same patient had earlier, aged 10 years, experienced a trauma leading to the loss of all four maxillary incisors. The missing incisors were replaced by a removable acrylic denture. Having the requisite experience from the earlier accident, the child performed on himself an immediate replantation of the tooth at the site of the accident. After avulsion, the tooth was not splinted timely nor was an endodontic procedure carried out and no antibiotics were prescribed. The first dental examination after the trauma was performed 6 months later and since then, radiographic follow-up has been introduced. One year after the trauma, following the late endodontic treatment performed 6 months after reimplantation, the tooth is asymptomatic and stable. CONCLUSIONS: Immediate self-replantation of an avulsed tooth is the best treatment choice, even without any other proceeding treatment. However, the healing process should be followed up to allow for the treatment of the early signs of pulpal necrosis and/or root resorption. PMID- 20738361 TI - Prevalence and etiological factors related to dental injuries amongst 18-22-year olds in United Arab Emirates. AB - BACKGROUND: Dental injuries in children and adolescents living across the globe are a serious public health problem. There are no data on dental injuries in United Arab Emirates (UAE). For the development of effective preventive measures, the present study was conducted to investigate the etiology and environment where dental injuries occurred, and to assess the relationship between traumatic dental injuries and socioeconomic status. MATERIAL AND METHODS: This study was undertaken in different colleges of University of Sharjah, UAE. 412 participants aged 18-22 years were screened using Dental Trauma Index (DTI), following the questionnaire phase of the study. RESULTS: Prevalence of dental injury was 25.9%, mostly (46.9%) with restored teeth; followed by 42.3% of minor injury (untreated enamel fracture), affecting one upper central incisor (53%). The mean age at the time of dental injury was 10.5 years (SD = 1.52; range 8-13 years) in females vs 14 years (SD = 1.71; range 12-16 years) in males. Dental injuries among males mostly occurred at public places such as on streets (27%) with (19%) of injuries were related to motor bike/micro scooters followed by bicycles (17%) and traffic accidents (9%). Socioeconomic indicators chosen were not statistically significant with the exception of family income (P = 0.01). CONCLUSION: The findings of this study show that dental traumas are prevalent among middle and high socioeconomic groups. There is a need for potential interventions like educating parents, caretakers, and older siblings on how to reduce the risk factors related to dental injuries. PMID- 20738362 TI - Viability of fibroblasts in a novel probiotic storage media. AB - A number of storage media have been investigated as to their ability to maintain the viability of the periodontal ligament (PDL) cells and thus to permit longer extra-alveolar periods prior to replantation of avulsed teeth. The aim of the present in vitro study was to evaluate the number of viable PDL cells of avulsed teeth treated by Hank's Balanced Salt Solutions (HBSS), saline, a novel probiotic solution and milk. Thirty-six freshly extracted single-rooted human teeth with closed apices were divided into one of the four experimental groups and two control groups (N = 6 each). The positive and negative controls corresponded to 0 min and an 8-h dry time respectively. Following extraction, the coronal 3 mm of PDL tissue was scraped with a #15 scalpel to remove cells that might have been damaged. The experimental teeth were dried for 30 min followed by a 45 min immersion in one of the four experimental media. Each experimental tooth, after drying and soaking, was incubated for 30 min with a 2.5 ml solution of 0.2 mg ml( 1) of collagenase CLS II and a 2.4 mg ml(-1) solution of dispase grade II in phosphate buffer saline (PBS). The cells were then labelled with 0.4% Trypan blue for determination of viability. The teeth stored in positive control demonstrated the highest number of viable PDL cells followed in rank order by HBSS, saline, Lactobacillus reuteri solution and milk. There was no significant difference in the number of viable PDL cells between HBSS, milk, L. reuteri solution and saline. Within the parameters of this study, it appears that probiotic may be able to maintain PDL cell viability as HBSS, milk, or saline. PMID- 20738363 TI - Bonding of fractured permanent central incisor crown following radiographic localization of the tooth fragment in the lower lip: a case report. AB - This study describes the case of an 8-year-old boy who fractured his left maxillary central incisor, exposing the pulp. The trauma also resulted in a cut on his mentum. Radiographic examination revealed the fractured tooth fragment embedded in the lower lip. The fractured tooth, with incomplete root formation, was treated endodontically and received a temporary restoration. After 15 days, the temporary restoration was removed and the fractured tooth fragment was etched with 37% phosphoric acid. A bonding system was then applied to the etched fractured tooth surface without polymerization. The same bonding procedure was carried out on the tooth fragment. A layer of flowable resin composite was applied to the fragment, which was positioned on the remaining tooth. The resin composite was then polymerized, finished, and polished. PMID- 20738364 TI - Tamponade physiology from a hepatic external mass. PMID- 20738365 TI - Acute myocardial infarction caused by sinus of valsalva aneurysm. PMID- 20738366 TI - Long-term exposure to biomass fuel and its relation to systolic and diastolic biventricular performance in addition to obstructive and restrictive lung diseases. AB - BACKGROUND: Previous studies have demonstrated an increased risk for cardiovascular events and pulmonary disease in patients with biomass fuel exposure (BFE). However, biventricular heart function has yet to be investigated in these patients. Left ventricular (LV) myocardial performance index (LVMPI), which is an index of global ventricular function, incorporates ejection, isovolumic relaxation, and contraction times. In this study, pulmonary function and biventricular heart function were investigated in nonsmoking female patients with BFE. METHODS: Our study population consisted of 46 female patients with BFE (group 1) and 31 control subjects (group 2). Pulmonary function tests and transthoracic echocardiographic examination were performed. Right ventricular myocardial performance index (RVMPI) and LVMPI were obtained by tissue Doppler imaging echocardiography (TDI). RESULTS: BFE caused obstructive and restrictive spirometric impairments. RVMPI was higher in group 1 (0.55 +/- 0.07) than group 2 (0.46 +/- 0.06) (P = 0.042) and LVMPI was higher in group 1 (0.54 +/- 0.08) than group 2 (0.47 +/- 0.05) (P = 0.032). Also, pulmonary artery systolic pressure was higher in group 1 than group 2 (P = 0.02). CONCLUSIONS: BFE causes both obstructive and/or restrictive lung disease and systolic and diastolic biventricular dysfunction. Nonetheless, long-term studies are needed to understand on BFE-related ventricular dysfunctions and to document subsequent cardiovascular events. PMID- 20738367 TI - The role of intraoperative transesophageal echocardiography in robotic mitral valve repair. AB - BACKGROUND: Robotic mitral valve (MV) repair is a new surgical technique that uses small incisions. Previous studies have demonstrated the importance of intraoperative transesophageal echocardiography (TEE) for conventional MV surgery with the use of a median sternotomy incision. The aim of the present study was to delineate the utility of intraoperative TEE in robotic MV repair. METHODS: Intraoperative TEE was performed in 22 consecutive patients undergoing robotic MV repair for severe degenerative mitral regurgitation (MR) over a period of 2 years. Before cardiopulmonary bypass (CPB), TEE was used to define the lesions of degenerative MR and the localization of the prolapsed leaflets, and to evaluate the severity of MR. During establishment of peripheral CPB, TEE was used to guide placement of the cannulae in the inferior vena cava (IVC), superior vena cava (SVC), and ascending aorta (AAO). After weaning from CPB, TEE was used to assess immediately the competency of the surgical repair. RESULTS: Agreement between TEE and surgical findings was excellent: 92.3% (kappa, 0.873) for the lesions of degenerative MR, and 98.5% (kappa, 0.943) for the localization of the prolapsed leaflets. Under TEE guidance, all the cannulae (100%) in the SVC, IVC, and AAO were placed correctly. TEE demonstrated all the patients (100%) had successful robotic MV repairs. CONCLUSIONS: Intraoperative TEE is a valuable adjunct in the assessment of robotic MV repair. (Echocardiography 2011;28:85-91). PMID- 20738368 TI - Serum N-terminal brain natriuretic peptide indicates exercise induced augmentation of pulmonary artery pressure in patients with mitral stenosis. AB - INTRODUCTION: To determine whether elevated N-terminal pro-BNP (NT pro-BNP) predicts pulmonary artery systolic pressure increase on exercise stress echocardiography in asymptomatic or mildly symptomatic patients with moderate to severe mitral stenosis. METHODS AND RESULTS: Forty-one asymptomatic or mildly symptomatic patients with moderate to severe mitral stenosis and 21 age- and sex matched healthy subjects. Transthoracic echocardiography was performed in all patients to assess the severity of the valve disease and to measure pulmonary artery pressure before and immediately after treadmill exercise. Blood samples for NT pro-BNP were also collected before and immediately after treadmill exercise at the time of echocardiographic examination. The plasma concentrations of NT pro-BNP levels were significantly higher in patients with mitral stenosis than in control subjects before and after exercise (P < 0.001). Patients with atrial fibrillation had significantly higher NT pro-BNP levels compared to those with sinus rhythm (P < 0.001). Pre- and postexercise NT pro-BNP levels correlated statistically significantly with the left atrial (LA) dimension, right ventricle enddiastolic diameter, exercise duration, heart rate, rest, and exercise pulmonary artery systolic pressure, after exercise mitral valve mean gradient. Area under the receiver-operating characteristic curve for NT pro-BNP as an exercise induced augmentation of pulmonary artery pressure was 0.78. Using an optimized cutoff value of 251 pg/mL for NT pro-BNP, sensitivity was 89.47%. The independent determinants of higher pulmonary artery pressure were LA diameter and pretest NT pro-BNP levels in multivariante analysis. CONCLUSION: NT pro-BNP levels correlate with functional class and echocardiographic findings in patients with mitral stenosis and indicate exercise induced augmentation of peak PAP > 60 mmHg. (Echocardiography 2011;28:8-14). PMID- 20738369 TI - Detection of early cardiac dysfunction in patients with Beta thalassemia by tissue Doppler echocardiography. AB - BACKGROUNDS: In this study we tried to evaluate the prognostic significance of several echocardiographic parameters on the occurrence of heart failure or arrhythmias in patients with beta thalassemia. METHODS: We investigated possible differences in myocardial function between a population of 37 asymptomatic patients with beta thalassemia and 25 age-matched healthy controls, all of whom underwent an echocardiographic study, including tissue Doppler imaging (TDI), moreover plasmatic levels of N-terminal pro-BNP (NT-pro BNP) were measured in all patients. We followed the patients for 22 +/- 8 months to evaluate adverse cardiac events. RESULTS: Conventional echocardiographic parameters of left ventricle were comparable in both groups. Whereas TDI peak systolic velocity (Sm) and diastolic parameter (E/Em ratio) were significantly abnormal in patients with thalassemia. Moreover eleven adverse cardiac events were observed during follow up. Baseline systolic velocity (Sm) <7.9 cm/s was significantly associated with cardiac complications (P < 0.05). We also demonstrated that systolic velocity is inversely related to NT-proBNP plasmatic levels (P < 0.001). CONCLUSIONS: Our study suggests that mitral annular systolic velocity <7.9 cm/s is associated to the onset of adverse cardiac events. PMID- 20738371 TI - Large Mass in Left Atrium by Transesophageal Echocardiography: An Unusual Case of Cardiac Angiosarcoma Mimicking a Cystic Mass. AB - Primary cardiac tumors are extremely rare. Among them, malignant tumors constitute approximately 15% of primary cardiac tumors. Angiosarcomas are the most frequent. They often appear as mural masses in the right atrium and completely replace the atrial wall and fill the entire cardiac chamber. We report an unusual case of angiosarcoma in a 75-year-old woman with a cystic appearance, located in the left atrium and causing critical mitral stenosis. (Echocardiography, ****;**:E1-E2). PMID- 20738372 TI - Multimodality Imaging of a Saphenous Vein Graft Aneurysm. AB - The use of multimodality cardiac imaging including echocardiography, cardiac computed tomography and cardiac catheterization for the diagnosis of a saphenous vein graft aneurysm is described. (Echocardiography, ****;**:E1-E2). PMID- 20738373 TI - Diversity of virus-host systems in hypersaline Lake Retba, Senegal. AB - Remarkable morphological diversity of virus-like particles was observed by transmission electron microscopy in a hypersaline water sample from Lake Retba, Senegal. The majority of particles morphologically resembled hyperthermophilic archaeal DNA viruses isolated from extreme geothermal environments. Some hypersaline viral morphotypes have not been previously observed in nature, and less than 1% of observed particles had a head-and-tail morphology, which is typical for bacterial DNA viruses. Culture-independent analysis of the microbial diversity in the sample suggested the dominance of extremely halophilic archaea. Few of the 16S sequences corresponded to known archeal genera (Haloquadratum, Halorubrum and Natronomonas), whereas the majority represented novel archaeal clades. Three sequences corresponded to a new basal lineage of the haloarchaea. Bacteria belonged to four major phyla, consistent with the known diversity in saline environments. Metagenomic sequencing of DNA from the purified virus-like particles revealed very few similarities to the NCBI non-redundant database at either the nucleotide or amino acid level. Some of the identifiable virus sequences were most similar to previously described haloarchaeal viruses, but no sequence similarities were found to archaeal viruses from extreme geothermal environments. A large proportion of the sequences had similarity to previously sequenced viral metagenomes from solar salterns. PMID- 20738375 TI - Evolutionary and functional diversity of the Pseudomonas type IVa pilin island. AB - In Pseudomonas aeruginosa, most proteins involved in type IVa pilus (T4aP) biogenesis are highly conserved except for the major pilin PilA and the minor pilins involved in pilus assembly. Here we show that each of the five major pilin alleles is associated with a specific set of minor pilins, and unrelated strains with the same major pilin type have identical minor pilin genes. The sequences of the minor pilin genes of strains with group III and V pilins are identical, suggesting that these groups diverged recently through further evolution of the major pilin cluster. Both gene clusters are localized on a single 'pilin island' containing putative tRNA recombinational hotspots, and a similar organization of pilin genes was identified in other Pseudomonas species. To address the biological significance of group-specific differences, cross-complementation studies using group II (PAO1) and group III (PA14) minor pilins were performed. Heterologous minor pilins complemented twitching motility to various extents except in the case of PilX, which was non-functional in non-native backgrounds. A recombinant PA14 strain expressing the PAO1 minor pilins regained motility only upon co-introduction of the PA14 pilX gene. Comparison of PilX and PilQ secretin sequences from group II, III and V genomes revealed discrete regions of sequence that co-varied between groups. Our data suggest that changes in PilX sequence have led to compensatory changes in the PilQ secretin monomer such that heterologous PilX proteins are no longer able to promote opening of the secretin to allow pili to appear on the cell surface. PMID- 20738376 TI - Sensing of environmental signals: classification of chemoreceptors according to the size of their ligand binding regions. AB - Central to the different forms of taxis are methyl-accepting chemotaxis proteins (MCPs). The increasing number of genome sequences reveals that MCPs differ enormously in sequence, topology and genomic abundance. This work is a one-by-one bioinformatic analysis of the almost-totality of MCP genes available and a classification of motile bacteria according to their lifestyle. On average, motile archaea have 6.7 MCP genes per genome whereas motile bacteria have more than twice as much. We show that the number of MCPs per genome depends on bacterial lifestyle and metabolic diversity, but weakly on genome size. Signal perception at an MCP occurs at the N-terminal ligand binding region (LBR). Here we show that around 88% of MCPs possess an LBR that remains un-annotated in SMART. MCPs can be classified into two clusters according to the size of the LBR. Cluster I receptors have an LBR between 120 and 210 amino acids whereas cluster II receptors have larger LBRs of 220-299 amino acids. There is evidence that suggests that some cluster II LBRs are composed of two cluster I LBRs. Further evidence indicates that other cluster II LBRs might harbour novel sensor domains. Cluster II receptors are dominant in archaea whereas cluster I receptors are prevalent in bacteria. MCPs can be classified into six different receptor topologies and this work contains a first estimation of the relative abundance of different receptor topologies in bacteria and archaea. Topologies involving extracytoplasmic sensing are prevalent in bacteria whereas topologies with cytosolic signal recognition are abundant in archaea. PMID- 20738378 TI - A case of SUDEP in a patient with Dravet syndrome with SCN1A mutation. AB - A boy with a clinical history of pharmacologically resistant Dravet syndrome died suddenly after falling asleep. The autopsy concluded that the cause of death was sudden unexpected death in epilepsy (SUDEP). Postmortem molecular analysis of the SCN1A gene by multiplex ligation-dependent probe amplification (MLPA), high resolution melting curve analysis (HRMCA), and sequencing revealed a frameshift duplication of adenosine at position 504. The incidence of this mutation is discussed as a potential cause of SUDEP. PMID- 20738377 TI - Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease. AB - PURPOSE: Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD. METHODS: Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation. RESULTS: Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene. DISCUSSION: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy. PMID- 20738379 TI - From mesial temporal lobe to temporoperisylvian seizures: a quantified study of temporal lobe seizure networks. AB - PURPOSE: The determination of epileptogenic structures in partial epilepsy is crucial in the context of epilepsy surgery. In this study we have quantified the "epileptogenicity" of mesial temporal lobe structures (M), lateral neocortical regions (L), and extratemporal perisylvian structures (ET) in patients with temporal lobe epilepsy (TLE), in order to classify the brain networks involved in seizure generation. METHODS: Thirty-four patients having TLE investigated by intracerebral recordings using stereotactic electroencephalography (EEG) (SEEG) were selected. Epileptogenicity of M, L, and ET structures was quantified according to the "epileptogenicity index" (EI), a new way to quantify rapid discharges at seizure onset, ranging from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). RESULTS: Automatic clustering using EI values from M, L, and ET separated patients into four classes: mesial group (max EI in M), lateral group (max EI in L), mesiolateral group (high EI in both M and L) and temporoperisylvian group (TPS) (high values in ET). The median number of highly epileptogenic structures (defined by EI >0.3) was four, a result confirming that most TLE is organized as "epileptogenic networks." We found that the duration of epilepsy was correlated with the number of epileptogenic structures and that surgical prognosis was also related to the extent of the epileptogenicity in the brain. CONCLUSIONS: Several distinct epileptogenic networks are involved in seizure generation in TLE. Findings advocate for a progressive recruitment of epileptogenic structures in human brain with time. PMID- 20738380 TI - Generalized convulsive status epilepticus management in adults: a cohort study with evaluation of professional practice. AB - PURPOSE: Generalized convulsive status epilepticus (GCSE) needs immediate management. Despite guidelines, adherence to management protocols is often poor, this contributing to poor outcome. We aimed to evaluate the usefulness of a management protocol in GCSE. METHODS: This is a prospective population-based study of consecutive adults with GCSE in Haute-Garonne district, France. Demographics and treatment procedures were documented. Factors associated with seizure termination and refractoriness were analyzed using logistic regression. RESULTS: One hundred eighteen episodes in 111 adults (mean age 55 years) between October 2006 and February 2008 were included. SE was convulsive in 101 episodes. Incidence was 6.6 per 100,000 and case fatality was 9%. Adequate initial treatment according to protocol was observed in 38%; 64% were treated out-of hospital, and SE was refractory in 27% [no response after two antiepileptic drugs (AED)]. Patients who received adequate first-line treatment were 6.8 times [95% confidence interval (CI) 2.8-16.9] more likely to have seizure termination, with 74% versus 29% efficacy rate (p < 0.0001). Inadequate initial management was 4.7 times (1.9-11.1) more likely to need several benzodiazepine doses (p = 0.0004) and 9.1 times (3.7-20) more likely to require a long-acting AED as next treatment (p < 0.0001). Seizure termination after initial treatment was associated with decreased intensive care unit stay [1 (1-2) versus 2 (1-5.5) days, p < 0.0001] and hospital stay [3 (2-11) versus 7 (3-18) days, p = 0.009]. DISCUSSION: GCSE termination and outcome seem clearly associated with adherence to treatment protocol. Results add to the debate on appropriate allocation of resources for out-of-hospital treatment, licensed drugs, and achievement of guideline implementation to improve SE outcome. PMID- 20738374 TI - A comparative molecular analysis of water-filled limestone sinkholes in north eastern Mexico. AB - Sistema Zacaton in north-eastern Mexico is host to several deep, water-filled, anoxic, karstic sinkholes (cenotes). These cenotes were explored, mapped, and geochemically and microbiologically sampled by the autonomous underwater vehicle deep phreatic thermal explorer (DEPTHX). The community structure of the filterable fraction of the water column and extensive microbial mats that coat the cenote walls was investigated by comparative analysis of small-subunit (SSU) 16S rRNA gene sequences. Full-length Sanger gene sequence analysis revealed novel microbial diversity that included three putative bacterial candidate phyla and three additional groups that showed high intra-clade distance with poorly characterized bacterial candidate phyla. Limited functional gene sequence analysis in these anoxic environments identified genes associated with methanogenesis, sulfate reduction and anaerobic ammonium oxidation. A directed, barcoded amplicon, multiplex pyrosequencing approach was employed to compare ~100,000 bacterial SSU gene sequences from water column and wall microbial mat samples from five cenotes in Sistema Zacaton. A new, high-resolution sequence distribution profile (SDP) method identified changes in specific phylogenetic types (phylotypes) in microbial mats at varied depths; Mantel tests showed a correlation of the genetic distances between mat communities in two cenotes and the geographic location of each cenote. Community structure profiles from the water column of three neighbouring cenotes showed distinct variation; statistically significant differences in the concentration of geochemical constituents suggest that the variation observed in microbial communities between neighbouring cenotes are due to geochemical variation. PMID- 20738381 TI - Semiologic aspects of epileptic seizures in 31 patients with hypothalamic hamartoma. AB - PURPOSE: Characterization of seizure semiology in patients with hypothalamic hamartoma (HH) based on video-electroencephalography (EEG) monitoring (VEM). METHODS: We retrospectively analyzed seizure semiology of 31 patients (20 male, mean age 23.5 years) who underwent VEM at the University Hospitals Freiburg or Heidelberg, Germany. Inclusion criteria were magnetic resonance evidence of an HH, no prior surgical or radiosurgical treatment, and at least two video documented seizures. A total of 263 seizures were included (mean number of seizures/patient 8.5, range 2-10). To analyze age-dependent changes in seizure semiology, patients were grouped into "children" (3-11 years, n = 5), "adolescents" (12-17 years, n = 4), and "adults" (>=18 years, n = 22). RESULTS: According to patient history, gelastic seizures had occurred in all patients, in 74% as the initial seizure type at epilepsy onset. In VEM, epileptic laughter varied from facial grinning to intense contractions of the diaphragm and body shaking. Unilateral motor signs were seen ipsi- and contralaterally to the HH. Tonic seizures were frequent and did not depend on the state of vigilance. Children, in contrast to adults and adolescents, did not show secondarily generalized tonic-clonic seizures, the gelastic component was the dominating and initial semiologic element, and seizures were significantly shorter. CONCLUSION: Seizure semiology is highly variable and age dependent. This may reflect network modulations with different propagation of ictal activity and/or secondary epileptogenesis. Detailed knowledge about such changes may contribute to both earlier recognition of seizures during childhood and better assignment of seizure types to a hypothalamic origin. PMID- 20738382 TI - Utility of 3-T FLAIR and 3D short tau inversion recovery MR imaging in the preoperative diagnosis of hippocampal sclerosis: direct comparison with 1.5-T FLAIR MR imaging. AB - PURPOSE: To examine the utility of fluid-attenuated inversion recovery (FLAIR) imaging and three-dimensional short tau inversion recovery (3DSTIR) imaging using a 3-Tesla (3-T) magnetic resonance (MR) imager in the preoperative evaluation of hippocampal sclerosis (HS). METHODS: Thirteen patients with intractable medial temporal lobe epilepsy who underwent anterior temporal lobectomy with amygdalohippocampectomy were studied. MR images were obtained twice, once with a 1.5-T imager and once with a 3-T imager. The extent of hippocampal resection was determined according to the findings on intraoperative hippocampal electroencephalography. We compared the diagnostic utility of FLAIR for HS between 1.5-T and 3-T MR imaging. In addition, the relationship between the existence of hypointense areas in the hippocampus (HIAs) on 3DSTIR and the severity of HS pathology (as evaluated using Watson's grading) was examined. The relationship between postoperative seizure outcome and postoperatively remaining HIAs was also evaluated. RESULTS: There was no difference between FLAIR images from 1.5-T and 3-T imaging in the detection of HS. With 3DSTIR, an HIA in unilateral hippocampus was observed in all of the nine cases exhibiting severe pathologic HS (Watson's grade III-V). In seven cases with HIA, the extent of hippocampal resection was smaller than the HIAs. Every case showed good seizure outcome (Engel's class I and II). DISCUSSION: In the diagnosis of HS, no substantial difference was noted between 1.5-T and 3-T MR imaging. However, 3DSTIR using 3-T MR imaging is useful for evaluating the extent of HS, although postoperative HS remnants are not correlated with surgical outcomes. PMID- 20738383 TI - Comparative pharmacodynamic and pharmacokinetic analysis of two anticonvulsant halo derivatives of 2,2,3,3-tetramethylcyclopropanecarboxamide, an amide of a cyclic analog of valproic acid. AB - PURPOSE: alpha-Fluoro-2,2,3,3-tetramethylcyclopropanecarboxamide (alpha-F-TMCD) and alpha-Cl-TMCD, are alpha-halo derivatives of TMCD, the corresponding amide of a cyclopropane analog of valproic acid (VPA). This study aimed to comparatively evaluate the pharmacodynamics and pharmacokinetics of alpha-F-TMCD and alpha-Cl TMCD in rodent models of epilepsy and for antiepileptic drug (AED)-induced teratogenicity. The potential of alpha-F-TMCD as an antiallodynic and antinociceptive compound was also evaluated. METHODS: alpha-F-TMCD and alpha-Cl TMCD were synthesized. alpha-Cl-TMCD anticonvulsant activity was evaluated in comparison to VPA in the mouse maximal-electroshock-seizure (MES), Metrazol (scMet), and 6-Hz psychomotor-seizure tests. Neurotoxicity was assessed by the Rotorod-ataxia test. Induction of neural tube defects (NTDs) by alpha-Cl-TMCD and alpha-F-TMCD was evaluated after intraperitoneal administration to a mouse strain highly susceptible to VPA-induced teratogenicity. The ability of alpha-F-TMCD to reduce pain was evaluated in the rat spinal nerve ligation (SNL) model for neuropathic pain and in the formalin test. alpha-F-TMCD and alpha-Cl-TMCD pharmacokinetics was evaluated following intraperitoneal (40 mg/kg) and oral (60 mg/kg) administration to rats. RESULTS: alpha-F-TMCD and alpha-Cl-TMCD had similar potencies in the 6-Hz test and were more potent than VPA in this model and in the scMet test. Neither induced NTDs, and both exhibited wide safety margins. alpha-F-TMCD was active in the two pain models, and was found to be equipotent to gabapentin in the SNL model (ED(50) = 37 and 32 mg/kg, respectively). Comparative pharmacokinetic analysis showed that alpha-Cl-TMCD is less susceptible to liver first-pass effect than alpha-F-TMCD because of lower total (metabolic) clearance and liver extraction ratio. CONCLUSIONS: Based on their potent anticonvulsant activity and lack of teratogenicity, alpha-F-TMCD and alpha-Cl-TMCD have the potential for development as new antiepileptics and central nervous system (CNS) drugs. PMID- 20738384 TI - What's shaking in the ICU? The differential diagnosis of seizures in the intensive care setting. AB - To analyze what conditions mimic seizures in the intensive care unit (ICU) setting, we reviewed all bedside electroencephalography (EEG)-videos obtained in the adult ICU setting over an 18-month period. Only those studies performed for "possible seizures" due to motor phenomena and whose clinical events were captured on video were analyzed. A total of 52 studies were performed. Fourteen patients (27%) had epileptic seizures. Thirty-eight (73%) had nonepileptic events. These consisted of 12 (23%) with tremor-like movements, 7 (13.5%) with multifocal myoclonic jerks without electrographic changes, 7 (13.5%) with slow semipurposeful movements, and 10 with other movements. Therefore, seizure mimics in the ICU setting were diverse and distinct from the usual differential diagnosis of seizures seen in ambulatory patients. PMID- 20738385 TI - Reliability of patterns of hippocampal sclerosis as predictors of postsurgical outcome. AB - PURPOSE: Around one-third of patients undergoing temporal lobe surgery for the treatment of intractable temporal lobe epilepsy with hippocampal sclerosis (HS) fail to become seizure-free. Identifying reliable predictors of poor surgical outcome would be helpful in management. Atypical patterns of HS may be associated with poorer outcomes. Our aim was to identify atypical HS cases from a large surgical series and to correlate pathology with clinical and outcome data. METHODS: Quantitative neuropathologic evaluation on 165 hippocampal surgical specimens and 21 control hippocampi was carried out on NeuN-stained sections. Neuronal densities (NDs) were measured in CA4, CA3, CA2, and CA1 subfields. The severity of granule cell dispersion (GCD) was assessed. RESULTS: Comparison with control ND values identified the following patterns based on the severity and distribution of neuronal loss: classical HS (CHS; n = 60) and total HS (THS; n = 39). Atypical patterns were present in 30% of cases, including end-folium sclerosis (EFS; n = 5), CA1 predominant pattern (CA1p; n = 9), and indeterminate HS (IHS, n = 35). No HS was noted in 17 cases. Poorest outcomes were noted for no HS, and CA1p groups with 33-44% International League Against Epilepsy (ILAE) class I at up to 2 years follow-up compared to 69% for CHS (p < 0.05). GCD associated with HS type (p < 0.01), but not with outcome. CONCLUSIONS: These findings support the identification and delineation of atypical patterns of HS using quantitative methods. Atypical patterns may represent distinct clinicopathologic subtypes and may have predictive value following epilepsy surgery. PMID- 20738386 TI - Induction of sodium channel Na(x) (SCN7A) expression in rat and human hippocampus in temporal lobe epilepsy. AB - PURPOSE: In a recent large-scale gene-expression study in a rat model of temporal lobe epilepsy (TLE) a persistent up-regulation in the expression of the SCN7A gene was revealed. The SCN7A gene encodes an atypical sodium channel (Na(x) ), which is involved in osmoregulation via a sensing mechanism for the extracellular sodium concentration. Herein we investigated the expression and cellular distribution of SCN7A mRNA and protein in normal and epileptic rat and human hippocampus. METHODS: SCN7A/Na(x) expression analysis was performed by polymerase chain reaction (PCR), immunocytochemistry, and western blot analysis. RESULTS: Increased expression of SCN7A/Na(x) mRNA/protein was observed during epileptogenesis and in the chronic epileptic phase in the post-status epilepticus (SE) model of TLE. The up-regulation was confirmed in human hippocampal tissue resected from pharmacoresistant patients with hippocampal sclerosis (HS). In both epileptic rat and human hippocampus, increased Na(x) expression was observed in neurons and reactive astrocytes compared to control tissue. CONCLUSIONS: The increased and persistent expression of SCN7A/Na(x) in the epileptic rat and human hippocampus supports the possible involvement of this channel in the complex reorganization occurring within the hippocampus during the epileptogenic process in TLE. Further studies are needed for a complete understanding of the functional role of SCN7A in epilepsy. PMID- 20738387 TI - Role of cortical dysplasia in epileptogenesis following prolonged febrile seizure. AB - PURPOSE: Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. METHODS: Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography). RESULTS: The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. DISCUSSION: Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE. PMID- 20738388 TI - Identity and psychological ownership in chronic illness and disease state. AB - Psychological ownership is rarely considered in health discourse related to chronic illness or disease state. Construction of identity is an important consideration within this framework. This autoethnographic study explores psychological ownership and identity related to prostate cancer and chronic illness. Conclusions about the nature of psychological ownership and identity were gathered from the relevant literature and personal experience. Themes include the patient-healthcare professional relationship and that psychological ownership is personal and grounded in an individual's sense of identity, control and perceived capacity to control illness or disease. Personal reflection through autoethnography guides discussion of psychological ownership and identity. PMID- 20738389 TI - Participation of haemato-oncological patients in medical decision making and their confidence in decisions. AB - Increasingly more clinical care and research acknowledge the patients' interest in participating in medical decision making. However, for haematological patients, there are as yet only modest findings. The current study explores patients' perceptions of their role in the medical decision-making process in a sample of 117 haematological patients. The majority of patients surveyed (63.9%) took a passive role in the medical decision-making process, which is a significantly greater proportion compared with individuals suffering from solid cancers. Despite passive majority, most of the participants reported a positive evaluation of the decision-making process. Importantly, patients' evaluations were significantly more negative either if patients were treated as inpatients (vs. outpatients), or if they experienced no control over the decision (vs. collaboration with the doctor, or deciding autonomously). The results and limitations of the study are discussed. PMID- 20738390 TI - What models of peer support do people with colorectal cancer prefer? AB - While colorectal cancer is the most common cancer affecting both men and women in Australia, disease-specific peer support services are lacking. This study examined the acceptability and preferred models of peer support among people with colorectal cancer. First, a mixed-method study examined enablers and barriers to peer support participation and model preferences. Participants were recruited from metropolitan and regional areas of Victoria. Fifty-three participants completed a questionnaire and four focus groups and 10 telephone interviews were conducted (n = 34). Participants demonstrated enthusiasm for peer support. Feeling unwell and worry about accessing toilet facilities were main barriers, while accessing information about treatment side effects and making treatment decisions were main positive features. Second, a pilot study determined the response to a face-to-face group and one-on-one telephone programme, the preferred models from study 1. In total, 34 support recipients recruited through clinicians, participated. Half elected to participate in the telephone programme and half in the group programme. Support recipients completed surveys before and after the programmes. Both models were acceptable to participants with high satisfaction rates reported (94-100%) and findings suggested that the two models catered to different peer support needs. Timing of referral and clinician promotion contributed to participation. PMID- 20738391 TI - Fast screening of depression in cancer patients: the effectiveness of the HADS. AB - In oncology clinics, there is an increasing need for fast and accurate screening scales and procedures in order to evaluate cancer patients for depression. The present study investigated the comparative effectiveness in recognising depressed patients of the Hospital Anxiety and Depression Scale (HADS), a self-report screening scale, and the Montgomery-Asberg Depression Rating Scale (MADRS), a semi-structured clinician-rated scale, in 151 patients affected by mixed cancer pathologies. With the MADRS, 73.5% of the patients were identified as depressed, whereas the HADS identified 36.4% and 58.3% as depressed, using the cut-offs of 11 and 8 respectively. The results suggest moderate agreement between the MADRS and the HADS when a cut-off of 8 is used (K-test: 0.44), while using a HADS cut off of 11 gave a significantly higher underestimation of depressed patients (K test: 0.29). In conclusion, the results suggest that the HADS can be useful as a sufficiently accurate first-step screening tool for depression in mixed oncology settings. PMID- 20738392 TI - Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates. AB - Clinical trials are crucial to improve cancer treatment but recruitment is difficult. Optimised patient information has been recognised as a key issue. In line with the increasing focus on patients' perspectives in health care, we aimed to study patients' opinions about the written information used in three clinical trials for breast cancer. Primary data collection was done in focus group interviews with breast cancer patient advocates. Content analysis identified three major themes: comprehensibility, emotions and associations, and decision making. Based on the advocates' suggestions for improvements, 21 key issues were defined and validated through a questionnaire in an independent group of breast cancer patient advocates. Clear messages, emotionally neutral expressions, careful descriptions of side effects, clear comparisons between different treatment alternatives and information about the possibility to discontinue treatment were perceived as the most important issues. Patients' views of the information in clinical trials provide new insights and identify key issues to consider in optimising future written information and may improve recruitment to clinical cancer trials. PMID- 20738393 TI - Mobilization strategies in hard-to-mobilize patients with lymphoid malignancies. AB - Depending on definitions and patient characteristics, 5-40% of patients with lymphoid malignancies are hard-to-mobilize. Several premobilization factors such as previous chemotherapy (CT), disease, marrow infiltration and platelet count at the time of mobilization influence the efficacy of CD34(+) cell mobilization. In general, however, prediction of hard-to-mobilize patient is difficult. Postmobilization factors especially low blood CD34(+) counts are important in clinical practice as we have now ways to enhance mobilization at this point. Plerixafor combined with granulocyte-colony stimulating factor (G-CSF) has significantly increased efficacy of remobilization in patients who have failed a previous mobilization attempt with a success rate of about 70%. Addition of plerixafor to G-CSF or more recently to a mobilization regimen consisting of CT + G-CSF is promising as blood CD34(+) counts can be increased three to fivefold to facilitate effective collection with less aphaeresis sessions. As plerixafor is expensive, development of practical algorithms for its use is important to make blood stem cell mobilization and collection more efficient in a cost-effective way. This review attempts to summarize current treatment strategies in hard-to mobilize patients with lymphoid malignancies. PMID- 20738395 TI - Enzyme kinetics informatics: from instrument to browser. AB - A limited number of publicly available resources provide access to enzyme kinetic parameters. These have been compiled through manual data mining of published papers, not from the original, raw experimental data from which the parameters were calculated. This is largely due to the lack of software or standards to support the capture, analysis, storage and dissemination of such experimental data. Introduced here is an integrative system to manage experimental enzyme kinetics data from instrument to browser. The approach is based on two interrelated databases: the existing SABIO-RK database, containing kinetic data and corresponding metadata, and the newly introduced experimental raw data repository, MeMo-RK. Both systems are publicly available by web browser and web service interfaces and are configurable to ensure privacy of unpublished data. Users of this system are provided with the ability to view both kinetic parameters and the experimental raw data from which they are calculated, providing increased confidence in the data. A data analysis and submission tool, the kineticswizard, has been developed to allow the experimentalist to perform data collection, analysis and submission to both data resources. The system is designed to be extensible, allowing integration with other manufacturer instruments covering a range of analytical techniques. PMID- 20738397 TI - Association of marine viral and bacterial communities with reference black carbon particles under experimental conditions: an analysis with scanning electron, epifluorescence and confocal laser scanning microscopy. AB - Black carbon (BC), the product of incomplete combustion of fossil fuels and biomass, constitutes a significant fraction of the marine organic carbon pool. However, little is known about the possible interactions of BC and marine microorganisms. Here, we report the results of experiments using a standard reference BC material in high concentrations to investigate basic principles of the dynamics of natural bacterial and viral communities with BC particles. We assessed the attachment of viral and bacterial communities using scanning electron, epifluorescence and confocal laser scanning microscopy and shifts in bacterial community composition using 16S rRNA gene denaturing gradient gel electrophoresis (DGGE). In 24-h time-course experiments, BC particles showed a strong potential for absorbing viruses and bacteria. Total viral abundance was reduced, whereas total bacterial abundance was stimulated in the BC treatments. Viral and bacterial abundance on BC particles increased with particle size, whereas the abundances of BC-associated viruses and bacteria per square micrometer surface area decreased significantly with BC particle size. DGGE results suggested that BC has the potential to change bacterial community structure and favour phylotypes related to Glaciecola sp. Our study indicates that BC could influence processes mediated by bacteria and viruses in marine ecosystems. PMID- 20738396 TI - Structural features of proinsulin C-peptide oligomeric and amyloid states. AB - The formation and structure of proinsulin C-peptide oligomers has been investigated by PAGE, NMR spectroscopy and dynamic light scattering. The results obtained show that C-peptide forms oligomers of different sizes, and that their formation and size distribution is altered by salt and divalent metal ions, which indicates that the aggregation process is mediated by electrostatic interactions. It is further demonstrated that the size distribution of the C-peptide oligomers, in agreement with previous studies, is altered by insulin, which supports a physiologically relevant interaction between these two peptides. A small fraction of oligomers has previously been suggested to be in equilibrium with a dominant fraction of soluble monomers, and this pattern also is observed in the present study. The addition of modest amounts of sodium dodecyl sulphate at low pH increases the relative amount of oligomers, and this effect was used to investigate the details of both oligomer formation and structure by a combination of biophysical techniques. The structural properties of the SDS-induced oligomers, as obtained by thioflavin T fluorescence, CD spectroscopy and IR spectroscopy, demonstrate that soluble aggregates are predominantly in beta-sheet conformation, and that the oligomerization process shows characteristic features of amyloid formation. The formation of large, insoluble, beta-sheet amyloid-like structures will alter the equilibrium between monomeric C-peptide and oligomers. This leads to the conclusion that the oligomerization of C-peptide may be relevant also at low concentrations. PMID- 20738398 TI - Inter- and intraspecific comparison of the bacterial assemblages in the hindgut of humivorous scarab beetle larvae (Pachnoda spp.). AB - The larvae of scarab beetles are model organisms for studying the role of physicochemical gut conditions and intestinal microbiota in symbiotic digestion, particularly of humus. Here, we address the question of whether the enlarged hindgut paunch of Pachnoda ephippiata and Pachnoda marginata, two closely related, but allopatric species, harbors a specific bacterial microbiota. Terminal restriction length fragment polymorphism (T-RFLP) analysis revealed that in both species, the bacterial hindgut community differs strongly from that in the midgut, food soil, and fecal pellets. High intra- and interspecific similarities between the T-RFLP profiles of different larvae indicate the presence of a hindgut-specific microbiota. Nevertheless, we found a clear separation of the two species. A 16S rRNA gene clone library from the hindgut of P. ephippiata identified the major phylogenetic groups as members of the Clostridia, Betaproteobacteria, and Bacteroidetes, followed by Bacillales and Deltaproteobacteria. A comparison with a previously obtained clone library of the same species corroborates both the similarities and the intraspecific variance of the hindgut microbiota. PMID- 20738399 TI - Physiological significance of the peptidoglycan hydrolase, LytM, in Staphylococcus aureus. AB - Autolysins in bacteria are peptidoglycan hydrolases with roles in growth, turnover and cell lysis. LytM was identified as the only autolysin in a previously reported autolysis-deficient (lyt(-) ) strain of Staphylococcus aureus. Purified LytM has been studied in great detail for its lytic properties and its production is elevated in vancomycin-resistant S. aureus. However, the postulated roles of LytM in S. aureus are largely speculative. Studies utilizing a reporter strain where the lytM promoter was cloned in front of a promoterless lacZ gene and fused in S. aureus strain SH1000 suggest that the expression of lytM is the highest during the early exponential phase. Additionally, lytM expression was downregulated in agr(-) mutants. The expression of lytM was not affected by the presence of cell wall inhibitors in the growth medium. To further determine the significance of LytM in staphylococcal autolysis, the gene encoding LytM was deleted by site-directed mutagenesis. The deletion of lytM, however, did not alter the rate of staphylococcal cell autolysis. Surprisingly, when the lytM mutation was combined with the lyt(-) mutant, the lytic activity band of the lyt( ) strain was still apparent in the lytM:lyt(-) double mutant. Purified full length His-tagged LytM did not demonstrate any lytic activity against S. aureus cells. Surprisingly, cultures of S. aureus lytM deletion mutant lysed at a significantly faster rate compared with the wild-type S. aureus in the presence of oxacillin. The findings of this study raise questions about LytM as an autolysin and the significance of this protein should thus be investigated beyond its role as an autolysin. PMID- 20738400 TI - Cell surface characteristics of nontypeable isolates of Streptococcus suis. AB - Streptococcus suis is a worldwide cause of various swine infections and is also an important agent of zoonosis. Strains of S. suis are classified according to their serotype, and currently, 35 serotypes are recognized. The aim of this study was to characterize nontypeable isolates of S. suis with regard to their cell surface properties and compare them with serotype 2 strains, the most frequently associated with infections. The seven nontypeable strains of S. suis isolated from infected animals demonstrated a stronger capacity to adhere to a fibronectin coated polystyrene surface than the serotype 2 isolates. Three nontypeable strains were also tested for their ability to adhere to endothelial cells and were found to attach in higher amounts compared with the serotype 2 isolates. Electron microscopy analysis revealed the absence of a capsule in the seven nontypeable isolates, which correlated with a much higher cell surface hydrophobicity than that of serotype 2 isolates. All nontypeable isolates of S. suis also showed the capacity to form a biofilm while serotype 2 isolates were unable to do so. In conclusion, the nontypeable isolates of S. suis examined in this study possess surface properties different from those of serotype 2 isolates. PMID- 20738401 TI - Screening, identification and evaluation of potential biocontrol fungal endophytes against Rhizoctonia solani AG3 on potato plants. AB - Rhizoctonia solani is an important soilborne pathogen of potato plants whose control typically depends on chemicals. Here, we screened six fungal endophytes for the suppression of R. solani growth both in vitro and in a greenhouse. These isolates were identified using morphology and internal transcribed spacer regions of rDNA as Alternaria longipes, Epicoccum nigrum, Phomopsis sp., and Trichoderma atroviride. Both T. atroviride and E. nigrum showed significant in vitro inhibition of mycelial growth of R. solani, with the greatest inhibition zone observed for E. nigrum species in dual cultures. The highest inhibition was observed for T. atroviride. The inhibition rate was also significantly correlated with the culture filtrates of these isolates. Confocal microscopy showed that T. atroviride acts as a mycoparasite and competitor. However, E. nigrum and A. longipes produce secondary metabolites, while Phomospsis sp. competes for nutrients and space. Greenhouse experiments confirmed that T. atroviride and E. nigrum improved potato yield significantly and decreased the stem disease severity index of sensitive potato. PMID- 20738402 TI - Production of sophorolipid biosurfactants by multiple species of the Starmerella (Candida) bombicola yeast clade. AB - Sophorolipids are carbohydrate-based, amphiphilic biosurfactants that are of increasing interest for use in environmentally benign cleaning agents. Sophorolipid production was tested for 26 strains representing 19 species of the Starmerella yeast clade, including Starmerella bombicola and Candida apicola, which were previously reported to produce sophorolipids. Five of the 19 species tested showed significant production of sophorolipids: S. bombicola, C. apicola, Candida riodocensis, Candida stellata and a new species, Candida sp. NRRL Y 27208. A high-throughput matrix-assisted laser desorption/ionization-time of flight MS assay was developed that showed S. bombicola and C. apicola to produce a lactone form of sophorolipid, whereas C. riodocensis, C. stellata and Candida sp. NRRL Y-27208 produced predominantly free acid sophorolipids. Phylogenetic analysis of sequences for the D1/D2 domains of the nuclear large subunit rRNA gene placed all sophorolipid-producing species in the S. bombicola subclade of the Starmerella clade. PMID- 20738403 TI - Anthropogenic perturbations in marine microbial communities. AB - Human activities impact marine ecosystems at a global scale and all levels of complexity of life. Despite their importance as key players in ecosystem processes, the stress caused to microorganisms has been greatly neglected. This fact is aggravated by difficulties in the analysis of microbial communities and their high diversity, making the definition of patterns difficult. In this review, we discuss the effects of nutrient increase, pollution by organic chemicals and heavy metals and the introduction of antibiotics and pathogens into the environment. Microbial communities respond positively to nutrients and chemical pollution by increasing cell numbers. There are also significant changes in community composition, increases in diversity and high temporal variability. These changes, which evidence the modification of the environmental conditions due to anthropogenic stress, usually alter community functionality, although this aspect has not been explored in depth. Altered microbial communities in human impacted marine environments can in turn have detrimental effects on human health (i.e. spread of pathogens and antibiotic resistance). New threats to marine ecosystems, i.e. related to climate change, could also have an impact on microbial communities. Therefore, an effort dedicated to analyse the microbial compartment in detail should be made when studying the impact of anthropogenic activities on marine ecosystems. PMID- 20738405 TI - Lipid-induced ER stress in yeast and beta cells: parallel trails to a common fate. AB - Exposure to long-chain saturated fatty acids (SFAs; e.g. palmitate) induces apoptosis in pancreatic beta cells, a process that may contribute to the development of type 2 diabetes. Under palmitate treatment, beta cells undergo a so-called endoplasmic reticulum (ER) stress that can be counteracted by the unfolded protein response (UPR). The UPR is a coordinated response, which is primarily devoted to helping the ER to cope with the accumulation of misfolded proteins. Sustained SFA exposure may ultimately overwhelm the UPR, resulting in cell death. By contrast, unsaturated fatty acids (e.g. oleate) are much less harmful to the cells and can even alleviate palmitate toxicity. Surprisingly, recent evidences indicate that a simple unicellular eukaryote, the budding yeast Saccharomyces cerevisiae, which is not routinely exposed to high-fat diets, also undergoes ER stress under lipotoxic conditions. This suggests that the mechanisms of SFA toxicity are largely conserved throughout eukaryotes and are not specific of a given cell type. The present review discusses the mechanisms of SFA toxicity in yeast and beta cells, with a main emphasis on their potential impacts on ER membrane organization/function and ER-based processes. PMID- 20738406 TI - The Saccharomyces cerevisiae zinc factor protein Stb5p is required as a basal regulator of the pentose phosphate pathway. AB - In Saccharomyces cerevisiae, the oxidative stress-activated zinc cluster protein Stb5p activates genes involved in NADPH production and most genes of the pentose phosphate (PP) pathway. To gain insight into the role of Stb5p, we studied the behaviour of stb5 deletion mutants during aerobic and anaerobic growth on glucose. stb5 mutants were auxotrophic for methionine and pyrimidine nucleotides. The methionine auxotrophy phenotype was air dependent, suggesting an impaired aerobic NADPH status. Consistent with this, the acetate level was reduced and the alpha-ketoglutarate level was increased in the stb5 mutant. stb5 cells also required pyrimidine nucleotides for aerobic and anaerobic growth, consistent with a reduction in 5-phosphoribosyl-1-pyrophosphate production caused by a reduced flux through the PP pathway. Strains overexpressing STB5 could not grow on glucose. This growth defect was restored by overproduction of an NADPH-butanediol dehydrogenase, which reoxidizes the excess NADPH in the oxidative PP pathway. These findings suggest a major role for the transcription factor Stb5p in maintaining a basal flux through the PP pathway to meet the NADPH requirements for aerobic growth, and to provide the nucleotide precursors. Our data also demonstrate the potential use of a system based on overproduction of this transcription factor to increase flux through the PP pathway. PMID- 20738407 TI - Transcriptomic and proteomic insights of the wine yeast biomass propagation process. AB - Transcriptome and proteome profiles have been established for the commercial wine yeast strain T73 during an important industrial process: yeast biomass propagation. The data from both analyses reveal that the metabolic transition from fermentation to respiration is the most critical step in biomass propagation. We identified 177 ORFs and 56 proteins among those most expressed during the process, thus highlighting cell stress response, mitochondrial and carbohydrate metabolism as the most represented functional categories. A direct correlation between mRNA changes and protein abundance was observed for several functional categories such as tricarboxylic acid cycle proteins, heat shock proteins, chaperons and oxidative stress response-related proteins. However, we found no concordance in the transcript and proteomic levels for glycolytic proteins, which is probably due to post-translational modifications increasing the number of protein isoforms, especially at the end of biomass propagation. The correlation between protein abundance and the enzyme activities of alcohol dehydrogenase, pyruvate decarboxylase and glyceraldehyde-3-phosphate dehydrogenase was not affected by these modifications. We suggest post translational mechanisms during biomass propagation that affect the stability of those proteins that play an important role in the produced biomass' fermentative capacity. PMID- 20738408 TI - Evidence for plasticity genotypes in a gene-gene-environment interaction: the TRAILS study. AB - The purpose was to study how functional polymorphisms in the brain derived neurotrophic factor gene (BDNF val66met) and the serotonin transporter gene linked promotor region (5-HTTLPR) interact with childhood adversities in predicting Effortful Control. Effortful Control refers to the ability to regulate behavior in a goal-directed manner and is an interesting endophenotype for psychopathology because of its heritability and the association of low Effortful Control with both internalizing and externalizing problems. In a longitudinal population-based study Effortful Control was assessed with the parent version of the Early Adolescent Temperament Questionnaire at age 11. Pregnancy and delivery adversities and childhood events were assessed in a parent interview at age 11. Long-term difficulties until age 11 were assessed with a parent questionnaire at age 13.5. Blood or buccal cells were collected at age 16 for genotyping the rs6265 and rs25531 SNPs and the 5-HTTLPR length polymorphism. The study included 1032 complete data sets. Effortful Control was significantly predicted by the interaction between BDNF val66met, 5-HTTLPR and childhood events. The BDNF val66met val/val-5-HTTLPR l'/l' genotype was unaffected by childhood events, while having either at least one BDNF val66met met or 5-HTTLPR s' allele (l'/l' met-carrier; l'/s'-val/val; s'/s'-val/val) made children sensitive to childhood events. Predictions of Effortful Control by pregnancy and delivery adversities and long-term difficulties were largely independent of genotype. We concluded that the l'/l'-met-carrier, l'/s'-val/val and the s'/s'-val/val genotypes showed greatest plasticity while the l'/l'-val/val genotype was unaffected by childhood events. PMID- 20738404 TI - Quinolones: from antibiotics to autoinducers. AB - Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2 alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4 hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc(1) complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression. PMID- 20738410 TI - Effects of cognitive function and depressive mood on the quality of life in Chinese Alzheimer's disease patients in Hong Kong. AB - AIM: In view of the paucity of data on the quality of life (QOL) in Chinese Alzheimer's disease (AD) patients, we investigated the effects of cognitive function and depressive mood on QOL among our Chinese AD patients in Hong Kong, using the Cantonese Chinese version of Quality of Life in Alzheimer's disease (QOL-AD). METHODS: This was a cross-sectional study. The Cantonese Chinese version of QOL-AD was adapted from the Mandarin Chinese and English versions of QOL-AD, and was administered to 111 AD patients and their caregivers. RESULTS: The Cantonese Chinese version of QOL-AD showed good internal consistency, test retest and inter-rater reliability. The patients' and caregivers' reports of QOL AD were moderately correlated (r=0.516, P<0.001). Both QOL-AD scores from patient and caregiver reports varied significantly in relation to the severity of cognitive impairment, being lowest in the subgroup with Mini-Mental State Examination scores of 10 or less. The mean QOL-AD scores from both patient and caregiver reports were also significantly lower in the depressed (Geriatric Depression Scale [GDS] scores>=15) than non-depressed groups (GDS scores<=15) (QOL-AD patient report 23.8 and 34.2, respectively, P<0.001, Student's t-test; QOL-AD caregiver report 28.9 and 31.0, respectively, P<0.05, Student's t-test). General linear model analyses showed that only the MMSE and GDS scores were independent significant factors associated with the patient but not the caregiver reports of the QOL-AD. CONCLUSION: Among Chinese AD patients in Hong Kong, depressive mood and low MMSE score adversely affect the QOL-AD from the patient but not the caregiver perspectives. PMID- 20738409 TI - Anxiety-related behavioral inhibition in rats: a model to examine mechanisms underlying the risk to develop stress-related psychopathology. AB - Behavioral inhibition (BI) is an adaptive defensive response to threat; however, children who display extreme BI as a stable trait are at risk for development of anxiety disorders and depression. The present study validates a rodent model of BI based on an ethologically relevant predator exposure paradigm. We show that individual differences in rat BI are stable and trait-like from adolescence into adulthood. Using in situ hybridization to quantify expression of the immediate early genes homer1a and fos as measures of neuronal activation, we show that individual differences in BI are correlated with the activation of various stress responsive brain regions that include the paraventricular nucleus of the hypothalamus and CA3 region of the hippocampus. Further supporting the concept that threat-induced BI in rodents reflects levels of anxiety, we also show that BI is decreased by administration of the anxiolytic, diazepam. Finally, we developed criteria for identifying extreme BI animals that are stable in their expression of high levels of BI and also show that high BI (HBI) individuals exhibit maladaptive appetitive responses following stress exposure. These findings support the use of predator threat as a stimulus and HBI rats as a model to study mechanisms underlying extreme and stable BI in humans. PMID- 20738411 TI - Immune response to influenza vaccine in the elderly: association with nutritional and physical status. AB - AIM: To investigate the distribution of hemagglutination inhibition (HI) titers before and after influenza vaccination and to examine the relationship between physical and nutritional factors and the change in HI titer after influenza vaccination in the elderly. METHODS: Pre-post-vaccination HI titers were determined from 203 individuals aged 65 years or older residing in a nursing home. For the assessment of physical and nutritional status, information was retrieved from care records. RESULTS: The immune response to vaccination was assessed as good in 122 subjects based on a fourfold rise or more in HI titer after vaccination for at least one of three vaccine strains. In univariate logistic regression analysis with poor versus good immune response as the dependent variable, factors found to be significantly associated with a poor immune response were disability, a combination of body mass index less than 18.5 and bodyweight loss in 6 months or 5% or more, mid-upper-arm circumference of less than 80%, arm muscle circumference of less than 80% and total protein of less than 6.5 g/dL. Physical and nutritional indicators might be useful in identifying individuals who are unlikely to have a good immune response to influenza vaccination. In a multivariate analysis, the association remained significant for a low level of activities of daily living and a combination of body mass index of less than 18.5 and bodyweight loss in 6 months of 5% or more. CONCLUSION: Elderly individuals with poor physical and nutritional status tended to respond poorly to influenza vaccination. A low level of activities of daily living and a combination of being underweight and having had recent bodyweight loss are good indicators of a poor immune response. PMID- 20738412 TI - Outcomes in total elbow arthroplasty in patients with haemophilia at the University of California, San Francisco: a retrospective review. AB - Severe haemophilic arthropathy of the elbow is a significant cause of morbidity among adults with haemophilia. However, previous reports of total elbow arthroplasty (TEA) in the haemophilic population have been based on small numbers of patients with relatively short-term follow-up. The records of seven total elbow arthroplasties in six adult men with haemophilia at the University of California, San Francisco who underwent TEA over a period of 25 years were retrospectively reviewed. Type of haemophilia, age at time of TEA, HIV infection status, pre- and postoperative range-of-motion (ROM) scores, complications (including infections), need for subsequent surgical revision and functional outcomes were recorded. Four patients had severe factor VIII deficiency and two patients had severe factor IX deficiency. None of the patients had an inhibitor. The mean age at the time of surgery was 34 years (range, 22-46 years) and the mean follow-up period was 118 months (range, 37-176 months). One of the six patients had TEA in both elbows. Five of the six patients were infected with HIV. There were no immediate perioperative complications. At a mean of 19.2 months postoperatively, ROM had improved in five of seven TEAs: mean flexion had increased from 110.7 degrees (SD = 15.0) to 120.1 degrees (SD = 14.5), whereas mean preoperative extension increased from -44.3 degrees (SD = 21.5) to -36.9 degrees (SD = 27.0). One patient required a revision at 30 months because of ulnar component loosening. This same patient sustained a staph epidermidis infection and ultimate removal of the prosthesis 15 years postoperatively. At a mean of 118 months postoperatively, five of six patients continued to report reduced pain and preserved functionality, with ability to perform normal daily activities. TEA resulted in favourable results in six of seven procedures. Our findings support the viability of TEA for individuals with severe haemophilic arthropathy of the elbow, especially to reduce pain and preserve or restore functionality. PMID- 20738413 TI - Whiplash and minor head injury: the problem is finding the problem. PMID- 20738414 TI - Massive pneumocephalus with delayed meningitis. PMID- 20738415 TI - Head tilt in a young girl with headache. PMID- 20738416 TI - Migraine and vertigo: a marriage of convenience? AB - "Migraine associated vertigo" is emerging as a popular diagnosis for patients with recurrent vertigo. However, in view of our current understanding of both migraine and vertigo, "migraine associated vertigo," in contrast to basilar artery migraine, is neither clinically nor biologically plausible as a migraine variant. PMID- 20738417 TI - Vertebral artery dissection presenting with isolated occipital headache. PMID- 20738418 TI - Primary mucin-producing tumours of the salivary glands: a clinicopathological and morphometric study. AB - AIMS: To determine clinicopathological and morphometric features that discriminate between mucin-producing primary salivary gland carcinomas. MATERIALS AND RESULTS: Fifteen mucin-producing tumours were stratified into five colloid carcinomas (CCs), four mucinous cystadenocarcinomas (MCAs), three mucin-rich salivary duct carcinomas (SDCs) and three mucin-rich mucoepidermoid carcinomas (MECs). The mean patient age was 70, 58, 43 and 63 years for CC, MCA, SDC and MEC, respectively. Eleven of 15 patients were female. The majority of CC cases originated from major salivary glands; MCA showed a predilection for the minor salivary glands. No disease-related mortality was observed in the CC group; one patient died in the MCA group, and one in the SDC group. Receiver-operating characteristic curve analysis revealed an optimal cut-off point of 17% of the tumour cells in contact with stroma that best distinguished between the CC and MCA. Histomorphometric measurements revealed that CC was best differentiated from MCA by smaller nuclear size and more regular chromatin. CONCLUSIONS: Strict morphological criteria of CC coupled with assessment of the tumour cell/stroma relationship and the nuclear features facilitate discrimination between mucinous tumours of salivary gland. PMID- 20738419 TI - Interplay of T-cell receptor and interleukin-2 signalling in Vgamma2Vdelta2 T cell cytotoxicity. AB - Human peripheral blood Vgamma2Vdelta2 T cells are important for host defence and tumour immunity. Their unusual T-cell receptor (TCR) recognizes small molecule phosphoantigens; stimulated cells produce inflammatory cytokines and are potently cytotoxic for a variety of tumours. However, molecular mechanisms linking phosphoantigen stimulation and cytotoxicity are incompletely understood. We know that isopentenyl pyrophosphate (IPP) activates mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/Erk) and phosphoinositide 3 kinase (PI-3K)/Akt pathways; specific inhibition of Erk or Akt significantly impairs the functional response to IPP. We now show that interleukin-2 also activates MEK/Erk and PI-3K/Akt pathways but on its own, fails to induce cytokine expression or cytotoxicity. Hence, MEK/Erk and PI-3K/Akt activation are necessary but not sufficient to induce effector responses in Vgamma2Vdelta2 T cells and a TCR-dependent signal is still required for tumour cell killing. Cyclosporin A, an inhibitor of calcineurin, blocked calcium-dependent nuclear translocation of nuclear factor of activated T cell (NFAT) and significantly reduced IPP-induced cytokine production, degranulation and cytotoxicity. The IPP-induced calcium mobilization and NFAT translocation were necessary to activate Vgamma2Vdelta2 effector functions; interleukin-2, acting on the MEK/Erk pathway, regulated the strength of these responses. The TCR has a specific role in Vgamma2Vdelta2 T-cell killing of tumour cells, which is distinct from its role in triggering cellular proliferation in response to phosphoantigens. PMID- 20738420 TI - A role for the B-cell CD74/macrophage migration inhibitory factor pathway in the immunomodulation of systemic lupus erythematosus by a therapeutic tolerogenic peptide. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease that involves dysregulation of B and T cells. A tolerogenic peptide, designated hCDR1, ameliorates disease manifestations in SLE-afflicted mice. In the present study, the effect of treatment with hCDR1 on the CD74/macrophage migration inhibitory factor (MIF) pathway was studied. We report here that B lymphocytes from SLE afflicted mice express relatively elevated levels of CD74, compared with B cells from healthy mice. CD74 is a receptor found in complex with CD44, and it binds the pro-inflammatory cytokine MIF. The latter components were also up-regulated in B cells from the diseased mice, and treatment with hCDR1 resulted in their down-regulation and in reduced B-cell survival. Furthermore, up-regulation of CD74 and CD44 expression was detected in brain hippocampi and kidneys, two target organs in SLE. Treatment with hCDR1 diminished the expression of those molecules to the levels determined for young healthy mice. These results suggest that the CD74/MIF pathway plays an important role in lupus pathology. PMID- 20738421 TI - Varying expression of four genes sharing a common regulatory sequence may differentiate rheumatoid arthritis from ageing effects on the CD4(+) lymphocytes. AB - The CD28 gene is similarly down-regulated in CD4(+) lymphocytes from both healthy elderly people and patients with rheumatoid arthritis (RA) because of impaired protein-binding activity of the 'alpha' sequence in its promoter region. Other genes important for the CD4(+) cell function may share that sequence and may be similarly regulated and affected. We searched GenBank for possible 'alpha' homologues and then compared transcriptional activities of the respective genes in the CD4(+) cells of young and older healthy individuals and those with RA by real-time PCR. We show here that genes encoding one of the zinc finger proteins (ZNF334), the 'aging hormone' Klotho, the retinoid acid receptor beta2 (RARbeta2) and the T-cell adapter protein GRAP-2, contain sequences with various (exceeding 70%) degrees of homology to the 'alpha' sequence near their promoters. These genes are transcribed in human CD4(+) lymphocytes; the expressions of RARbeta2, KLOTHO and ZNF334 are significantly decreased in a correlated manner in the cells of patients with RA compared with those of healthy individuals. In RA patients, the extremely reduced expression of ZNF334 does not depend on the individual's age, apparently constituting a disease-related phenomenon; whereas that of RARbeta2 and KLOTHO occurs mostly in the cells of relatively younger patients, making them similar to the lymphocytes of healthy elderly in this aspect. PMID- 20738422 TI - Nature and nurture: T-cell receptor-dependent and T-cell receptor-independent differentiation cues in the selection of the memory T-cell pool. AB - The initiation of a T-cell response begins with the interaction of an individual T-cell clone with its cognate antigen presented by MHC. Although the strength of the T-cell receptor (TCR) -antigen-MHC (TCR-pMHC) interaction plays an important and obvious role in the recruitment of T cells into the immune response, evidence in recent years has suggested that the strength of this initial interaction can influence various other aspects of the fate of an individual T-cell clone and its daughter cells. In this review, we will describe differences in the way CD4(+) and CD8(+) T cells incorporate antigen-driven differentiation and survival signals during the response to acute infection. Furthermore, we will discuss increasing evidence that the quality and/or quantity of the initial TCR-pMHC interaction can drive the differentiation and long-term survival of T helper type 1 memory populations. PMID- 20738424 TI - Functional analysis and molecular characterization of two acetylcholinesterases from the German cockroach, Blattella germanica. AB - Two acetylcholinesterases (AChEs; BgAChE1 and BgAChE2) from Blattella germanica were functionally expressed using the baculovirus system. Kinetic analysis demonstrated that BgAChE2 had higher catalytic efficiency but lower substrate specificity than BgAChE1. With the exceptions of paraoxon and propoxur, BgAChE1 was generally less sensitive to inhibitors than BgAChE2. Western blot analysis using anti-BgAChE antibodies revealed that BgAChE1 was far more abundant in all examined tissues compared to BgAChE2, which is only present in the central nervous system. Both BgAChEs existed in dimeric form, covalently connected via a disulphide bridge under native conditions. Most fractions of BgAChE1 had a glycophosphatidylinositol (GPI) anchor, but a small fraction comprised a collagen like tail. BgAChE2 appeared to have a collagen-GPI-fused tail. Based on the kinetic and molecular properties, tissue distribution and abundance, BgAChE1 was confirmed to play a major role in postsynaptic transmission. PMID- 20738423 TI - Human cytomegalovirus-specific CD8(+) T-cell expansions contain long-lived cells that retain functional capacity in both young and elderly subjects. AB - The immune response to human cytomegalovirus (HCMV) infection is characterized by the accumulation of HCMV-specific CD8(+) T cells, particularly in the elderly; such expansions may impair immune responses to other pathogens. We investigated mechanisms underlying HCMV-specific expansions in 12 young and 21 old healthy subjects (although not all analyses were performed on all subjects). Phenotypically, HCMV-pentamer(+) CD8(+) T cells were characterized by marked Vbeta restriction, advanced differentiation (being predominantly CD27(-) CD28(-) ), and variable CD45RO/RA expression. Although more common and larger in older subjects, expansions had similar phenotypic characteristics in the young. In one old subject, repeated studies demonstrated stability in size and Vbeta distribution of pentamer(+) populations over 6 years. We tested whether HCMV specific CD8(+) T-cell expansions arose from accelerated proliferation or extended lifespan by in vivo labelling with deuterated glucose and ex vivo Ki-67 expression. Uptake of deuterated glucose was lower in pentamer(+) cells than in pentamer(-) CD8(+) CD45RO(+) or CD8(+) CD45RA(+) cells in three old subjects, consistent with reduced proliferation and extended lifespan. Similarly Ki-67 labelling showed no evidence for increased proliferation in HCMV-specific CD8(+) expansions in older subjects, although pentamer(-) CD45RA(+) cells from young donors expressed very little Ki-67. We investigated Bcl-2 and CD95 as possible anti-apoptotic mediators, but neither was associated with pentamer-positivity. To investigate whether expansion represents a compensatory response to impaired functionality, we performed two tests of functionality, peptide-stimulated proliferation and CD107 expression; both were intact in pentamer(+) cells. Our data suggest that HCMV-specific CD8(+) expansions in older subjects accumulate by extended lifespan, rather than accelerated proliferation. PMID- 20738425 TI - Transgene-mediated suppression of dengue viruses in the salivary glands of the yellow fever mosquito, Aedes aegypti. AB - Controlled sex-, stage- and tissue-specific expression of antipathogen effector molecules is important for genetic engineering strategies to control mosquito borne diseases. Adult female salivary glands are involved in pathogen transmission to human hosts and are target sites for expression of antipathogen effector molecules. The Aedes aegypti 30K a and 30K b genes are expressed exclusively in adult female salivary glands and are transcribed divergently from start sites separated by 263 nucleotides. The intergenic, 5'- and 3'-end untranslated regions of both genes are sufficient to express simultaneously two different transgene products in the distal-lateral lobes of the female salivary glands. An antidengue effector gene, membranes no protein (Mnp), driven by the 30K b promoter, expresses an inverted-repeat RNA with sequences derived from the premembrane protein-encoding region of the dengue virus serotype 2 genome and reduces significantly the prevalence and mean intensities of viral infection in mosquito salivary glands and saliva. PMID- 20738426 TI - Genome-wide analysis of transcriptomic divergence between laboratory colony and field Anopheles gambiae mosquitoes of the M and S molecular forms. AB - Our knowledge of Anopheles gambiae molecular biology has mainly been based on studies using inbred laboratory strains. Differences in the environmental exposure of these and natural field mosquitoes have inevitably led to physiological divergences. We have used global transcript abundance analyses to probe into this divergence, and identified transcript abundance patterns of genes that provide insight on specific adaptations of caged and field mosquitoes. We also compared the gene transcript abundance profiles of field mosquitoes belonging to the two morphologically indistinguishable but reproductively isolated sympatric molecular forms, M and S, from two different locations in the Yaounde area of Cameroon. This analysis suggested that environmental exposure has a greater influence on the transcriptome than does the mosquito's molecular form specific genetic background. PMID- 20738427 TI - Bioactivity of novel carboxymethyl chitosan scaffold incorporating MTA in a tooth model. AB - AIM: To characterise the bioactivity of a novel carboxymethyl chitosan (CMCS) scaffold with and without incorporating mineral trioxide aggregate (MTA) in a tooth model. METHODOLOGY: Cross-linked CMCS scaffold (CaC) and MTA-coated CaC (CaMT) scaffold were prepared by freeze-drying. The bioactivity of the scaffolds was tested in vitro in four different mineralisation solutions (bulk system) and ex vivo in simulated body fluid (SBF) in the tooth model. After mineralisation, the mineral deposits on the scaffolds were analysed using scanning electron microscopy, energy dispersive X-ray, and inductively coupled plasma mass spectroscopy. All data were statistically analysed using the two-sample t-test (P < 0.05). RESULTS: Hydroxyapatite (HAP) deposition was observed on CaC and CaMT scaffolds after 1 week of mineralisation in the tooth model and in the bulk system. The deposition was significantly higher (P < 0.05) on CaMT scaffold than that on CaC scaffold. The amount of HAP formed in the tooth model was significantly lower (P < 0.05) than that in the bulk solution. CONCLUSIONS: The CMCS scaffolds are bioactive and capable of biomineralisation by forming HAP within a tooth model ex vivo. The bioactivity of the CMCS scaffold can be enhanced by incorporating MTA. PMID- 20738428 TI - Radiolucent inflammatory jaw lesions: a twenty-year analysis. AB - AIM: To determine the range and demographic and clinical features of radiolucent inflammatory jaw lesions. METHODOLOGY: Histopathology reports were reviewed to identify radiolucent jaw lesions. There were no clinical exclusive criteria, and the samples represented a wide range of clinical presentation and treatment history from multiple providers. Data were analysed using SPSS. To evaluate concordance of clinical and histological diagnoses, the clinician's provisional diagnosis was compared with the final histopathological diagnosis. RESULTS: A total of 17 038 specimens were reviewed; of these, 4983 (29.2%) were radiolucent jaw lesions, of which inflammatory lesions accounted for 72.8% (n = 3626). Periapical granulomas (59.7%) were the largest group followed by radicular cysts (29.2%). The mean age was 44 years (range 2-100 years), men and women were equally represented and the anterior maxilla was the most common site for the biopsied lesions. A provisional diagnosis was correct for only 48.3% of periapical granulomas and 36% of radicular cysts. CONCLUSIONS: This study included all presentations of periapical radiolucent lesions and showed that the incidence of cystic change in periapical lesions of endodontic origin is high at approximately 30% of all inflammatory lesions. Notwithstanding the relative frequencies, demographics and location of radiolucent inflammatory lesions presenting in the New Zealand population are comparable to that of other populations. No inflammatory radiolucent lesion can be reliably accurately diagnosed from clinical presentation and/or radiographic appearance alone. PMID- 20738429 TI - Endogenous reactive oxygen species content and modulation of tyrosine phosphorylation during sperm capacitation. AB - Generation of controlled amounts of reactive oxygen species (ROS) and phosphorylation of protein tyrosine (Tyr) residues are two main cellular changes involved in sperm capacitation. This study examined the relationship between tyrosine-phosphorylation (Tyr-P) and endogenous ROS production during sperm capacitation, and correlated them with both sperm motility and functionality expressed as acrosome-reacted cells. Immediate ROS generation was observed to peak after a 45-min incubation, followed by a rapid decrease in ROS content and successive regeneration of the ROS peak in 3 h and later. These two peaks were directly correlated with both the Tyr-P process involving sperm heads and tails, and the acrosome reaction (69 +/- 8% and 65 +/- 4%, respectively). The period of low-ROS content resulted in low Tyr-P patterns, located exclusively in the cell midpiece, and drastic reduction in acrosome-reacted cells. Ascorbic acid addition inhibited both Tyr-P patterns and acrosome reactions, whereas NADPH induced high ROS generation, with Tyr-P patterns located only on sperm tails, and prevented the acrosome reaction. Sperm hyperactivation was insensitive to ROS content. This is an important parameter for evaluation of sperm capacitation, which is achieved only when both ROS generation reaches a peak and Tyr-P involves the sperm head. PMID- 20738430 TI - Role of serum- and glucocorticoid-inducible kinase-1 in regulating torsion induced apoptosis in rats. AB - Serum- and glucocorticoid-inducible kinase-1 (SGK1) is a serine/threonine protein kinase that responds to various stimuli and mediates cell survival. Although it is known that testicular torsion leads to testicular damage and male infertility, the role of SGK1 in torsion remains unclear. This study investigated whether torsion-induced apoptosis is associated with changes in phosphoinositide dependent protein kinase-1 (PDK1), SGK1 and forkhead transcription factor FOXO3a expression and/or phosphorylation in rats. Sprague-Dawley rats were divided into four groups: sham (control), 1, 2 and 4 h of unilateral torsion. Bilateral testes, testicular interstitial fluid (TIF) and blood samples were collected immediately after torsion. Our results revealed that SGK1 protein and mRNA were abundantly present in testes and were induced by 2 h of torsion, but that phosphorylation of SGK1, PDK1 and FOXO3a decreased simultaneously. After 2 h of torsion, the testosterone secretion capacity of the primary Leydig cells and testicular interstitial cells (TICs) was impaired and apoptotic spermatogonia and TICs were observed; in addition, the mean seminiferous tubular diameter was decreased. Torsion increased plasma corticosterone levels, but decreased plasma luteinizing hormone and testosterone levels. However, the testosterone levels of the TIF in the ipsilateral testes were significantly enhanced after 2 h of torsion, but suppressed in the contralateral testes. This animal study suggests that PDK1, SGK1 and FOXO3a are involved in torsion-induced apoptosis and that medical therapy should be performed as early as 2 h after the occurrence of torsion to prevent further damage. PMID- 20738431 TI - Repeat general anaesthesia, a 6-year follow up. AB - OBJECTIVE: To investigate the number of children who subsequently required further dental general anaesthesia (DGA) following the baseline DGA for exodontia in 1997 over the next 6 year period, and identify any common factors related to these repeat DGAs. DESIGN: A retrospective longitudinal analysis. MATERIALS AND METHODS: Records from a UK teaching hospital for patients who had extractions under DGA within the calendar year of 1997 were identified and analysed. The individual's demographic details, reasons for the baseline DGA, teeth extracted, number of subsequent DGAs, the reasons for repeat DGA and finally any episodes of pain and/or infection after 1997 were recorded. RESULTS: During 1997, a total of 484 children with mean age of 6.35 (ranged between 1 and 16 years) received a DGA for exodontias. The most common reason for the exodontias carried out at this baseline DGA was dental caries and mean number of exodontias was 4.24. Of the total study population 8.9% subsequently had at least one unplanned repeat DGA, with dental caries being a factor in 84% of the cases. Of the subsequently extracted teeth 71.9% were caries free or unerupted at the time of the initial DGA. Of the children who had a repeat DGA, 61% had experienced at least one episode of pain and/or infection subsequent to the first episode of DGA. The pattern of the child's attendance and the recorded experience of oral pain and infection after the baseline DGA in 1997 were variables proved to be strongly associated with the risk of having an unplanned repeat DGA, with the children who were irregular attenders having a four times increased risk. CONCLUSIONS: Two common factors were identified which might predict the potential for a child requiring a repeat DGA; irregular attendance and oral pain and infection. PMID- 20738432 TI - Seeking children's perspectives in the management of visible enamel defects. AB - AIM: To undertake a child-centred evaluation of treatment provision for visible enamel defects. DESIGN: Postal questionnaires, developed with children, were sent to 88 patients, aged 7-16 years, with visible enamel defects of permanent incisors and who had received microabrasion, with/without additional composite restoration at Sheffield Dental Hospital, UK. The questionnaires sought children's perceptions about their teeth before and after the intervention, as well as their evaluation of how they had been treated. Anonymised responses were graded using a 10 cm visual analogue scale (VAS) where a score of 10 indicated the most negative response, and zero the most positive response. RESULTS: Sixty three questionnaires were returned (72% response). Prior to treatment, children reported high levels of worry (VAS=6.8), embarrassment (VAS=6.9) and a perception that their teeth looked yellow and discoloured (VAS=7.3). Following treatment, children thought their teeth looked much better (VAS=1.6), felt happier (VAS=2.2) and more confident (VAS=1.6). They also felt very positive about their clinical experiences, rating the staff as extremely friendly and kind (VAS=0.4) and reporting that procedures were clearly explained (VAS=0.6). CONCLUSIONS: Simple non-invasive dental treatment can have a positive effect on appearance-related satisfaction. The use of child-centred approaches offers an invaluable insight into patient perspectives. PMID- 20738433 TI - Risk factors for dental erosion in a group of 12- and 16-year-old Brazilian schoolchildren. AB - BACKGROUND: Dental erosion is a multifactorial disease and is associated with dietary habits in infancy and adolescence. AIM: To investigate possible associations among dental erosion and diet, medical history and lifestyle habits in Brazilian schoolchildren. DESIGN: The sample consisted of a random single centre cluster of 414 adolescents (12- and 16-years old) of both genders from private and public schools in Bauru (Brazil). The O'Brien [Children's Dental Health in the United Kingdom, 1993 (1994) HMSO, London] index was used for dental erosion assessment. Data on medical history, rate and frequency of food and drinks consumption, and lifestyle habits were collected by a self-reported questionnaire. Odds ratios with 95% confidence intervals were used to assess the univariate relationships between variables. Analysis of questionnaire items was performed by multiple logistic regression analysis. The statistical significance level was set at 5%. RESULTS: The erosion present group comprised 83 subjects and the erosion absent group 331. There were no statistically significant correlations among dental erosion and the consumption of food and drinks, medical history, or lifestyle habits. CONCLUSION: The results indicate that there was no correlation between dental erosion and the risk factors analysed among adolescents in Bauru/Brazil and further investigations are necessary to clarify the multifactorial etiology of this condition. PMID- 20738434 TI - Molar incisor hypomineralization: prevalence, severity and clinical consequences in Brazilian children. AB - BACKGROUND: The prevalence of molar incisor hypomineralization (MIH) varies considerably around the world; however, few studies have examined MIH in South American countries. OBJECTIVE: To evaluate the prevalence, severity, and clinical consequences of MIH in Brazilian children residing in rural and urban areas of the municipality of Botelhos, Minas Gerais, Brazil. METHODS: Children aged 6 to 12 years (n = 918) with all four-first permanent molars erupted had these teeth evaluated according to the European Academy of Paediatric Dentistry (EAPD) criteria. The examinations were conducted by two previously trained examiners, and the dental impact caused by MIH was evaluated with the Decayed, Missing and Filled Teeth (DMFT) index (WHO). RESULTS: Molar incisor hypomineralization was present in 19.8% of the 918 children, with a higher prevalence in rural areas. The majority of the defects presented were demarcated opacities without post eruptive structural loss, which has been considered as mild defects. Children with MIH had higher DMFT values. CONCLUSION: Despite the high prevalence of MIH, the severity of the defects was mild. The results indicate a positive association between MIH and the presence of dental caries. PMID- 20738435 TI - The practice of continuous palliative sedation in elderly patients: a nationwide explorative study among Dutch nursing home physicians. AB - OBJECTIVES: To study the practice of continuous palliative sedation (CPS) by Dutch nursing home physicians in 2007. DESIGN: A structured retrospective questionnaire. SETTING: Nationwide nursing home physician study in the Netherlands. PARTICIPANTS: One thousand two hundred fifty-four nursing home physicians received a questionnaire concerning their last case of CPS in 2007; 54% (n=675) responded. MEASUREMENTS: Characteristics of CPS and requests for euthanasia were measured. RESULTS: Three hundred sixteen patients were described. The majority had cancer or dementia. The most-reported refractory symptoms were pain (52%), anxiety (44%), exhaustion (44%), dyspnea (40%), delirium (24%), loss of dignity (18%), and existential distress (16%). In 98% of cases, CPS was aimed at symptom relief. Of patients with cancer, 17% had previously requested euthanasia. The mean starting dose of midazolam was 31 mg every 24 hours (range 0 240 mg/24 h), and the mean end dose was 48 mg every 24 hours (range 0-480 mg/24 h). CONCLUSION: In addition to physical symptoms, anxiety, exhaustion, loss of dignity, and existential distress are often mentioned as refractory symptoms in the decision to start CPS by nursing home physicians. Furthermore, close to one in five patients with cancer had made a previous request for euthanasia. The dosage range of midazolam in this study fits the recommendations of the Dutch national guideline on palliative sedation, although international studies show smaller dosage ranges. Finally, prospective research about the acceptability and assessment of nonphysical symptoms as indications for CPS is recommended. PMID- 20738436 TI - Habitual physical activity levels are associated with performance in measures of physical function and mobility in older men. AB - OBJECTIVES: To determine whether objectively measured physical activity levels are associated with physical function and mobility in older men. DESIGN: Cross sectional. SETTING: Academic research center. PARTICIPANTS: Eighty-two community dwelling men aged 65 and older with self-reported mobility limitations were divided into a low-activity and a high-activity group based on the median average daily physical activity counts of the whole sample. MEASUREMENTS: Physical activity according to triaxial accelerometers; physical function and mobility according to the Short Physical Performance Battery (SPPB), gait speed, stair climb time, and a lift-and-lower task; aerobic capacity according to maximum oxygen consumption (VO(2) max); and leg press and chest press maximal strength and peak power. RESULTS: Older men with higher physical activity levels had a 1.4 point higher mean SPPB score and a 0.35-m/s faster walking speed than those with lower physical activity levels. They also climbed a standard flight of stairs 1.85 seconds faster and completed 60% more shelves in a lift-and-lower task (all P<.01); muscle strength and power measures were not significantly different between the low- and high-activity groups. Correlation analyses and multiple linear regression models showed that physical activity is positively associated with all physical function and mobility measures, leg press strength, and VO(2) max. CONCLUSION: Older men with higher physical activity levels demonstrate better physical function and mobility than their less-active peers. Moreover, physical activity levels are predictive of performance in measures of physical function and mobility in older men. Future work is needed to determine whether modifications in physical activity levels can improve or preserve physical performance in later life. PMID- 20738437 TI - Relationship between physical functioning and physical activity in the lifestyle interventions and independence for elders pilot. AB - OBJECTIVES: To determine whether participation in usual moderate-intensity or more-vigorous physical activity (MVPA) is associated with physical function performance and to identify sociodemographic, psychosocial, and disease-related covariates that may also compromise physical function performance. DESIGN: Cross sectional analysis of baseline variables of a randomized controlled intervention trial. SETTING: Four academic research centers. PARTICIPANTS: Four hundred twenty four older adults aged 70 to 89 at risk for mobility disability (scoring <10 on the Short Physical Performance Battery (SPPB)) and able to complete the 400-m walk test within 15 minutes. MEASUREMENTS: Minutes of MVPA (dichotomized according to above or below 150 min/wk of MVPA) assessed according to the Community Healthy Activities Model Program for Seniors questionnaire, SPPB score, 400-m walk test, sex, body mass index (BMI), depressive symptoms, age, and number of medications. RESULTS: The SPPB summary score was associated with minutes of MVPA (rho=0.16, P=.001). In multiple regression analyses, age, minutes of MVPA, number of medications, and depressive symptoms were associated with performance on the composite SPPB (P<.05). There was an association between 400-m walk time and minutes of MVPA (rho=-0.18; P<.001). In multiple regression analyses, age, sex, minutes of MVPA, BMI, and number of medications were associated with performance on the 400-m walk test (P<.05). CONCLUSION: Minutes of MVPA, sex, BMI, depressive symptoms, age, and number of medications are associated with physical function performance and should all be taken into consideration in the prevention of mobility disability. PMID- 20738438 TI - Length of stay for older adults residing in nursing homes at the end of life. AB - OBJECTIVES: To describe lengths of stay of nursing home decedents. DESIGN: Retrospective cohort study. SETTING: The Health and Retirement Study (HRS), a nationally representative survey of U.S. adults aged 50 and older. PARTICIPANTS: One thousand eight hundred seventeen nursing home residents who died between 1992 and 2006. MEASUREMENTS: The primary outcome was length of stay, defined as the number of months between nursing home admission and date of death. Covariates were demographic, social, and clinical factors drawn from the HRS interview conducted closest to the date of nursing home admission. RESULTS: The mean age of decedents was 83.3 +/- 9.0; 59.1% were female, and 81.5% were white. Median and mean length of stay before death were 5 months (interquartile range 1-20) and 13.7 +/- 18.4 months, respectively. Fifty-three percent died within 6 months of placement. Large differences in median length of stay were observed according to sex (men, 3 months vs women, 8 months) and net worth (highest quartile, 3 months vs lowest quartile, 9 months) (all P <.001). These differences persisted after adjustment for age, sex, marital status, net worth, geographic region, and diagnosed chronic conditions (cancer, hypertension, diabetes mellitus, lung disease, heart disease, and stroke). CONCLUSION: Nursing home lengths of stay are brief for the majority of decedents. Lengths of stay varied markedly according to factors related to social support. PMID- 20738439 TI - Cry genes profiling and the toxicity of isolates of Bacillus thuringiensis from soil samples against American bollworm, Helicoverpa armigera. AB - AIMS: The aim of this study was to search for Bacillus thuringiensis (Bt) harbouring cry1A gene which could effectively control cotton pest, American bollworm, Helicoverpa armigera. METHODS AND RESULTS: cry gene profiling of 50 Bt isolates showed the presence of cry1, cry2, cry3, cry4, cry7, cry8 and cry9 genes. None of the isolates harboured cry1 gene alone. It was always found in combination with cry3. There was no isolate positive for cry10 gene. Considering isolates with single cry genes, the frequency of cry4 was predominant (22%) followed cry2 (6%), cry3 (4%) and cry8 (2%). Isolates having two cry genes in combination had 14% incidence for cry2 + cry4, 12% for cry3 + cry4 and 10% for cry1 + cry3. The most dominant three gene linkage was cry1 + cry3 + cry4. Further profiling of cry1 gene showed that cry1K gene was abundantly present in all combinations such as cry1A, cry1D, cry1F and cry1I. However, cry1C existed independent of other subtypes. Finally, the Bt isolates with cry1A were analyzed for 16S rRNA gene, which showed two distinct groups of isolates on the basis of sequence homology. Bioassays of spore-crystal mixtures of SBS-Bt4, 8, 17, 21 and 26 harbouring cry1 against neonate larvae of H. armigera showed LC(50) 1288, 1202, 467.7, 524.8 and 108.5 MUg ml(-1) . The SBS-Bt26 showed fourfold higher toxicity than the cry 1Ac harbouring positive control, HD-73. CONCLUSIONS: None of the isolates harboured single cry 1 gene. They were always in combination of two or three genes. A Bt isolate (Bt26) had fourfold higher toxicity against H. armigera larvae compared with the positive control HD 73 and hence can be commercially exploited to control insect pest. SIGNIFICANCE AND IMPACT OF THE STUDY: The inter relationship between the cry genes content and the toxicity may allow better understanding of Bt ecology. PMID- 20738440 TI - The effect of bovine diet on Salmonella survival in synthetic abomasal fluid. AB - AIMS: To investigate the effect of diet on the survival of Salmonella in the bovine abomasum. METHODS AND RESULTS: Five fistulated cows were randomly assigned to one of five diets denoted as: (i) 100% grass, (ii) grass + 5.3 kg DM concentrate, (iii) 100% grass silage, (iv) 100% hay and (v) maize/grass silage plus concentrates. Rumen fluid was harvested from each dietary treatment and inoculated with nonacid (NA) and acid-adapted (AA) 5-strain Salmonella cocktails. After 24-h incubation period, Salmonella were acid challenged to synthetic abomasum fluid (SAF, pH 2.5) for 5 h to determine their resistance to low pH. The study found that the volatile fatty acids composition and the pH profile of bovine rumen fluid were significantly altered (P <0.05) by some of the dietary treatments but not others. Regression analysis found that significantly higher numbers of acid-adapted Salmonella survived in SAF after incubation in rumen fluid from diets 1, 2 and 4, but fewer significant differences were found between diets for nonacid-adapted Salmonella. The results suggest that the acid-adapted cells were subjected to a higher level of cell injury than the nonadapted cells. CONCLUSIONS: Pre-incubation in rumen fluid did influence the resistance of nonacid and acid-adapted Salmonella to SAF but it was dependant on the dietary treatment fed to the cows. SIGNIFICANCE AND IMPACT OF THE STUDY: This study examined the use of diet, as a modulating factor to limit the bovine excretion of Salmonella with a view to providing a scientific basis for the design of dietary management controls in the future. PMID- 20738441 TI - Use of multiple-locus variable-number tandem-repeats analysis (MLVA) typing to characterize Salmonella Typhimurium DT41 broiler breeder infections. AB - AIMS: To characterize isolates of Salmonella Typhimurium DT41 obtained from infected flocks of broiler breeders by multiple-locus variable-number tandem repeats analysis (MLVA) and compare results with a diverse strain collection from Germany and United Kingdom and isolates from Danish patients. METHODS AND RESULTS: A total of 102 isolates of Salm. Typhimurium phage type DT41 were MLVA typed. MLVA typing showed 4, 12, 25, 9 and 8 different alleles at the five MLVA loci 9, 5, 6, 10 and 3, respectively. A dendrogram based on MLVA types was constructed, and one large group, nine minor groups and 29 more unrelated MLVA types were obtained. The major group included 20 of the 30 human isolates. Isolates obtained from broiler breeders demonstrated major diversity, indicating the existence of several independent introductions of DT41 at farm level. When comparison was made to isolates included from Germany and England, DT41 seems to be ubiquitous in the wild fauna which might represent a risk factor for poultry. CONCLUSIONS: Transmission from Danish broilers to humans was not demonstrated, neither was the transmission from rearing farms to broiler breeder farms. Sources of infection at broiler breeder farm level remained unidentified. SIGNIFICANCE AND IMPACT OF THE STUDY: Major diversity was demonstrated for DT41 MLVA types. A persisting problem with infection of broiler breeder flocks with DT41 was not reflected in broiler flocks originating from these flocks. PMID- 20738442 TI - Detection and differentiation of live and heat-treated Salmonella enterica serovars inoculated onto chicken breast using Fourier transform infrared (FT-IR) spectroscopy. AB - AIMS: To evaluate Fourier transform infrared (FT-IR) techniques for detecting, quantifying, and differentiating viable and heat-treated cells of Salmonella enterica serovars from chicken breast. METHODS AND RESULTS: Salmonella enterica serovars were captured from inoculated chicken breast by filtration and immunomagnetic separation (IMS) prior to spectral collection using an FT-IR spectrometer and IR microscopy. The detection limits, based on amide II peak area (1589 to 1493 cm(-1) ), for the Filtration-FT-IR and IMS-FT-IR methods were 10(6) and 10(4) CFU g(-1) , respectively. The bacteria were detectable after 6 h of culture enrichment during a sensitivity experiment with lower initial inoculum of 10(1) CFU g(-1) . Canonical variate analysis differentiated experimental from control spectra at a level of 10(3) CFU g(-1) . Partial least squares models were established for the quantification of Salm. enterica from chicken breast using Filtration-FT-IR (R(2) >= 0.95, RMSEC <= 0.62) and IMS-FT-IR (R(2) >= 0.80, RMSEC <= 1.61) methods. Filtration-FT-IR was also used to detect and quantify live Salm. enterica in the presence of heat-treated cells with R(2) = 0.996, and this approach was comparable to the results of a commercial stain (BacLightTM; R(2) = 0.998). Discriminant and canonical variate analyses of the spectra differentiated live and dead cells of different serovars of Salm. enterica. CONCLUSIONS: FT-IR analysis coupled with separation methods is useful for the rapid detection and differentiation of Salm. enterica separated from chicken. SIGNIFICANCE AND IMPACT OF THE STUDY: FT-IR-based methods are faster than traditional microbiological methods and can be used for the detection of live and dead bacteria from complex foods. PMID- 20738443 TI - Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury. AB - Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS <= 8). The GCS reflects the risk of dying from TBI, which is low after mild (~1%), intermediate after moderate (up to 15%) and high (up to 40%) after severe TBI. Intracranial damage can be focal, such as epidural and subdural haematomas and parenchymal contusions, or diffuse, for example traumatic axonal injury and diffuse cerebral oedema, although this distinction is somewhat arbitrary. Study of the cellular and molecular post-traumatic processes is essential for the understanding of TBI pathophysiology but even more to find therapeutic targets for the development of neuroprotective drugs to be eventually used in human beings. To date, studies in vitro and in vivo, mainly in animals but also in human beings, are unravelling the pathological TBI mechanisms at high pace. Nevertheless, TBI pathophysiology is all but completely elucidated. Neuroprotective treatment studies in human beings have been disappointing thus far and have not resulted in commonly accepted drugs. This review presents an overview on the clinical aspects and the pathophysiology of focal and diffuse TBI, and it highlights several acknowledged important events that occur on molecular and cellular level after TBI. PMID- 20738444 TI - Antiplatelet therapy in secondary stroke prevention--state of the art. AB - Our objective is to provide the reader with an overview as well as an update on current antiplatelet therapy for secondary stroke prevention. Relevant journals were hand-searched by the authors to compile a broad but by far not comprehensive summary of innovative and clinically relevant studies. Aspirin, clopidogrel and the combination of dipyridamole plus aspirin are the cornerstone therapy in secondary prevention after non-cardio-embolic stroke or transient ischaemic attack. A head-to-head comparison showed no difference in the prevention of recurrent stroke between dipyridamole plus aspirin and clopidogrel. More potent antiplatelet drugs or the combination of aspirin and clopidogrel prevent more ischaemic events, but also lead to more bleeding complications. For secondary stroke prevention in patients with atrial fibrillation, oral anticoagulation is more effective than aspirin or the combination of aspirin and clopidogrel. PMID- 20738446 TI - Adolescent inpatient psychiatric admission rates and subsequent one-year mortality in England: 1998-2004. AB - BACKGROUND: Adolescence is a time of very rapid change not only in physical but also psychological development. During the teenage years there is a reported rise in the prevalence of psychiatric disorders. The aim of this study was to investigate age- and sex-specific National Health Service (NHS) hospital inpatient admission rates for psychiatric conditions in adolescents in England, and to examine their mortality within one year of discharge. METHOD: Using a record-linked NHS Hospital Episode Statistics (HES) dataset for England, and linked death certificates, age- and sex-specific admission rates and subsequent mortality rates were analysed by single year of age for people aged 10-19 years. RESULTS: There were similar numbers of admissions for males and females: 29,595 and 28,188 respectively. Admission rates increased substantially with increasing age, from .2 per 1000 population per year aged 10 years to 2.2 per 1000 aged 19 years. There was no appreciable difference in death rates for males and females in the year following discharge--males .23% (based on 68 deaths), females .18% (52 deaths). However, these death rates were significantly higher than those found in the general population of equivalent age: expressed as standardised mortality ratios (SMRs), setting the SMRs for males and females in the general population each as 100, the SMR in the psychiatric population were 518 (95% CI 402-657) for males and 937 (692-1225) for females. The diagnostic groups with the highest mortality were development disorders (SMR 3017, 95% CI 1757-4831), eating disorders (SMR 1103, 443-2272), and affective disorders (SMR 940, 589-1423). CONCLUSION: Adolescent psychiatric disorders represent a serious public health issue, with a steep rise in hospital admissions during the teenage years, and a six-fold increased death rate within one year of discharge compared to the general population of the same age. PMID- 20738445 TI - Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention. AB - Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: adenosine 5'-diphosphonate receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischaemic stroke is a heterogeneous disease caused by multiple aetiologies and the blood-brain barrier is disturbed after stroke which may result in a higher intracerebral bleeding risk. Several small randomized trials indicated that the combination of aspirin and clopidogrel might be superior to antiplatelet monotherapy in the acute and early post-ischaemic phase. There is an ongoing debate about antiplatelet resistance. Decreasing response to aspirin is correlated independently with an increased risk of cardiovascular events. However, there is still no evidence from randomized trials linking aspirin resistance and recurrent ischaemic events. Similarly, randomized trials have not demonstrated a clinical significantly decreased antiplatelet effect by the concomitant use of clopidogrel and proton pump inhibitors. Nevertheless, a routine use of this drug combination is not recommended. PMID- 20738447 TI - Co-occurring problems of early onset persistent, childhood limited, and adolescent onset conduct problem youth. AB - BACKGROUND: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems differentially co-develop with the EOP, CL and AO trajectories across the childhood and adolescent years. METHOD: Using data from the Avon Longitudinal Study of Parents and Children, an epidemiological, longitudinal cohort of boys and girls, we estimated growth curves for parent reported hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors conditional on trajectories of conduct problems (i.e., EOP, CL and AO) from ages 4 to 13 years. At ages 7-8 years, DSM-IV-based diagnoses of conduct disorder, oppositional-defiant disorder, attention deficit/hyperactivity disorder (ADHD), anxiety, depression were examined by conduct problems trajectory. RESULTS: Overall, the development of hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors mirrored the development of conduct problems, showing similar trajectories. CONCLUSIONS: Results indicated that the problems of EOP youth were persistent across domains, CL youth showed decreased behavior problems while increasing in prosocial behaviors, and AO youth increased in adjustment problems after 10 years of age. PMID- 20738448 TI - Predictive validity of DSM-IV oppositional defiant and conduct disorders in clinically referred preschoolers. AB - BACKGROUND: Diagnostic validity of oppositional defiant and conduct disorders (ODD and CD) for preschoolers has been questioned based on concerns regarding the ability to differentiate normative, transient disruptive behavior from clinical symptoms. Data on concurrent validity have accumulated, but predictive validity is limited. Predictive validity is critical to refuting the hypothesis that diagnosing ODD and CD in young children leads to pathologizing normal behavior. ODD and CD have emerged as gateway disorders to many forms of adult psychopathology. Establishing how early we can identify symptoms and disorders that herald poor prognosis is one of the most important goals for research on etiology and prevention. METHODS: Subjects were 3-5-year-old consecutive referrals to a child psychiatry clinic (n=123) and demographically matched children from a pediatric clinic (n=100). A diagnostic interview was used to assess DSM-IV ODD and CD in a prospective follow-up design from preschool to school age. Stability of ODD and CD diagnoses and level of impairment were tested as a function of preschool diagnosis. RESULTS: Over 80% of preschoolers diagnosed with ODD and approximately 60% of preschoolers diagnosed with CD met criteria for the same disorder during follow-up. Impairment over time varied significantly as a function of stability of diagnosis across three years. CONCLUSIONS: These results provide the first evidence of the predictive validity of DSM-IV ODD and CD in clinically referred preschool children. The findings challenge the assumption that symptoms of disruptive behavior disorders that occur during the preschool period tend to be transient. PMID- 20738450 TI - The long-term benefits of cardiac rehabilitation on depression, anxiety, physical activity and quality of life. AB - AIMS: To investigate the long-term benefits of a six-week comprehensive cardiac rehabilitation programme on physical activity, psychological well-being and quality of life in patients with coronary heart disease. BACKGROUND: Cardiac rehabilitation (CR) in short term improves exercise capacity and quality of life in patients with cardiac disease. However, the long-term benefits of CR are inconclusive. DESIGN: A prospective CR programme with repeated measures follow-up over 12 months. METHODS: A six-week outpatient cardiac rehabilitation programme was conducted including 147 patients with coronary heart disease. Patients completed the physical activity energy expenditure (seven-day recall activity), MacNew Heart Disease Health-Related Quality of Life (MacNew) and Hospital Anxiety and Depression scale (HADs) at baseline, six weeks, six and 12 months. RESULTS: One hundred and five (71%) patients (76 male) mean age of 61.8 (SD 9.7) completed the four-measurement points. Analysis of variance revealed that total energy expenditure (F (2, 231) = 131, p < 0.001), HADs (F (2, 237) = 19.3, p < 0.001), depression score (F (2, 235) = 21.06, p < 0.001), anxiety score (F (2,237) = 17.02, p < 0.001) and MacNew (F (2, 197) = 77.02, p < 0.001) were all statistically significant over time. Bonferroni pairwise follow-up confirmed significant positive differences (p < 0.05) between baseline values and all subsequent measures over time. Depression was independently explained in 22% of the variance in quality of life at 6 or 12 months. The energy expenditure was significantly higher for men compared to women (F (1, 103) = 31, p < 0.001). CONCLUSION: A six-week cardiac rehabilitation programme is beneficial in improving quality of life, physical activity status, anxiety and depression. These benefits were maintained at 12 months. Elevated levels of depression were associated with impaired quality of life. RELEVANCE TO CLINICAL PRACTICE: All relevant health care staff should be aware of the benefits of CR and routinely refer and encourage patients with cardiac disease to attend a cardiac rehabilitation programme. Depression and anxiety intervention strategies should be incorporated in cardiac rehabilitation programmes. PMID- 20738449 TI - Sensory processing in internationally adopted, post-institutionalized children. AB - BACKGROUND/METHODS: Sensory processing capacities of 8-12-year-old internationally adopted (IA) children who experienced prolonged institutional care (> 12 months with 75% of pre-adoption lives in institutional care) prior to adoption into family environments (PI) were compared to a group of IA children who were adopted early (< 8 months) predominantly from foster care with little or no institutional experience (EA/FC) and another group of non-adopted (NA) children raised by their birth parents in the United States. All children had estimated IQs within the normal range and did not evidence major neurodevelopmental disorders (e.g., cerebral palsy, fetal alcohol syndrome, Down's syndrome). Sensory processing was evaluated with a commonly used parent report measure and a laboratory assessment. RESULTS: Children who had experienced prolonged institutionalization showed higher levels of reactivity to sensation and displayed both more aversion and approach to sensory stimuli than the other groups. The comparison groups (EA/FC & NA) did not differ on any of the sensory processing measures. CONCLUSIONS: These results suggest that early institutional rearing which typically involves both sensory and social deprivation is associated with problems in sensory modulation capacities. PMID- 20738451 TI - Experiences of day care and collaboration among people with mild dementia. AB - AIMS: The study was designed to assess how a day care programme once a week, for seven weeks, with group collaboration and social and cultural activities was experienced by clients. The aim was to provide some insight into how older adults with mild cognitive impairment perceive and experience day care. BACKGROUND: As a consequence of social withdrawal, older adults with mild dementia may suffer a loss of meaningful social life and mental stimulus. Person-centred and collaborative day care may provide support to remaining abilities and facilitate for social activities. Little is known about client experiences and whether and how day care gives meaning to everyday life of persons with mild dementia. DESIGN: A qualitative interview study in a narrative content analysis design. METHODS: This study involved narrative interviews with nine Norwegian clients, aged 77-88 years of age, living at home, all being old people with mild dementia. RESULTS: Three main themes emerged: 'Ambivalence Shifts to Interest', 'Meaningful Engagement Engenders Wellbeing' and 'Social Fellowship Promotes Life Contentment'. The findings gave insights into how people with mild dementia had positive experiences from a once-a-week day programme. CONCLUSIONS: This study demonstrates feelings of more meaningful lives, well-being and contentment as effects of collaborative day care participation. Safe transfer was a prerequisite to participate. There is a need of more research on how to facilitate person centred and collaborative day care provided for groups in different contexts, culturally pluralistic groups and groups of younger seniors with mild dementia. RELEVANCE TO CLINICAL PRACTICE: Persons with mild dementia may practice remaining social and collaborative skills when care facilitate and moderate participant involvement. Therefore, facilitating for clients' feelings of control in secure environments, narrative conversations, group activities and collaborative group interaction are suggested. PMID- 20738452 TI - h-Indices and the performance of professors of nursing in the UK. PMID- 20738453 TI - A meta-synthesis of qualitative research into needs and experiences of significant others to critically ill or injured patients. AB - AIMS AND OBJECTIVES: This study aimed to describe the significant others' experiences and needs when a person is critically ill or injured in an acute care setting. BACKGROUND: Being a significant other to a hospitalised critically ill or injured patient is a heavily distressing life event. Addressing significant others' needs adequately has been shown to be essential to mitigate the psychological consequences of such distressing events. DESIGN: A systematic review of qualitative research. METHODS: Meta-ethnographic synthesis was used for analysis. RESULTS: The key findings are described in five major themes: uncertainty and emotional 'roller coaster'; information--balancing hope and reality; to guard and to protect the loved one; alliance with caregivers--crucial support; and social network--support and disequilibrium. CONCLUSIONS: The study can provide a broader understanding of the significant others' situation. They are facing an overwhelming and emotionally challenging situation and need to be seen and heard. RELEVANCE TO CLINICAL PRACTICE: The results point towards the nurses' key position in handling the needs of the significant others. This kind of description might be helpful in taking on this delicate task and might also serve as a body of knowledge to influence clinical practice guidelines and nursing interventions in this field. PMID- 20738454 TI - An integrative review of the literature on registered nurses' medication competence. AB - AIMS AND OBJECTIVES: The aim of this integrative literature review was to describe registered nurses' medication competence. The objectives of the literature review were to chart the need for future studies and use the results for instrument development. BACKGROUND: Nurses play a vital role in different phases of a patient's medication process and thus need adequate competence to fulfil their role. Research on nurses' level of medication competence in different competency areas has been published. However, previous studies have lacked a comprehensive or integrated definition or description of medication competence in nursing. DESIGN: Integrative literature review. METHODS: The integrative literature review followed five stages: (1) problem identification, (2) literature search, (3) data evaluation, (4) data analysis and (5) presentation. Eligible articles were identified via systematic literature search of research and evidence-based--databases. Twenty-one studies met the selection criteria. RESULTS: Eleven competency areas that constitute nurses' medication competence were identified: (1) anatomy and physiology, (2) pharmacology, (3) communication, (4) interdisciplinary collaboration, (5) information seeking, (6) mathematical and medication calculation, (7) medication administration, (8) medication education, (9) assessment and evaluation, (10) documentation and (11) promoting medication safety as part of patient safety. The analysis revealed three major categories which integrate these competency areas: (1) decision making competence, (2) theoretical competence and (3) practical competence. CONCLUSIONS: Medication competence requires a solid knowledge base and the ability to apply that knowledge in real-life situations during often complex and dynamic patient medication processes. Decision making competence was found to be an important and integral part of a nurses' theoretical and practical competence. These main competence categories integrated all of the 11 competency areas identified in this review. RELEVANCE TO CLINICAL PRACTICE: It is important to determine registered nurses' medication competence in the context of developing nursing education and migration of the nursing workforce. This literature review contributes an integrated perspective on nurses' medication competence and in doing so has clinical relevance for curriculum development and to future research in this area. PMID- 20738455 TI - 'It's not worth stopping now': why do smokers with chronic obstructive pulmonary disease continue to smoke? A qualitative study. AB - AIM: This study aims to explore the experience of cigarette smokers with Chronic obstructive pulmonary disease (COPD) who have received smoking cessation support and describe their personal decision-making processes regarding their smoking behaviour. BACKGROUND: Previous studies have demonstrated poor smoking cessation rates in people with COPD, despite this being the primary intervention for disease management. There is limited research exploring the reasons why this population continues to smoke. DESIGN: Retrospective qualitative interviews were conducted and analysed using Giorgi's (1985) process of analysis. METHOD: Following a randomised controlled trial to evaluate national smoking cessation guidelines, semi-structured interviews were conducted with a purposive sample (n = 6) of those patients who were unable to stop smoking. RESULTS: Six themes that typified patients' decision-making were identified during six interviews; too late to stop now, finding motivation, guilt about continued smoking, bargaining/contemplation, need to stop and reduced quality of life. CONCLUSION: The reasons why smokers with COPD continue to smoke despite poor health and following support are complex. Cigarettes are regarded as friends, despite the knowledge that they are contributing to severe disability and poor quality of life. Owing to their inability to stop smoking, many patients avoid healthcare opportunities, further contributing to their poor health. RELEVANCE TO CLINICAL PRACTICE: Smoking cessation is associated with ambivalence in this population. Health professionals need to understand the volatility of patients' decision making and tailor advice and support to achieve more realistic goals such as reduced consumption. PMID- 20738457 TI - Cocaine-related retiform purpura: evidence to incriminate the adulterant, levamisole. AB - The term 'cocaine-induced pseudovasculitis' was coined to encompass a constellation of clinical and laboratory findings which mimics a systemic vasculitis but lacks confirmatory evidence of vasculitis on biopsy. Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase (HNE) have been reported to distinguish the cocaine-related syndrome from a true autoimmune vasculitis. Published cases of retiform purpura related to cocaine use are rare and an etiologic role for levamisole, a common adulterant of cocaine, has been postulated. We describe two female patients aged 39 and 49 years with cocaine-related retiform purpura, mainly affecting the legs. The initial clinical and serological profile in case 1 led to a suspicion of anti-phospholipid syndrome and in case 2 to Wegener's granulomatosis with an unexplained associated neutropenia. Skin biopsies revealed a mixed pattern of leukocytoclastic vasculitis and microvascular thrombosis in case 1 and pure microvascular thrombosis in case 2. Identification of anti-HNE antibodies in both patients linked their disease to cocaine. The mixed vasculopathic pattern in case 1 and the associated neutropenia in case 2, both known adverse effects of levamisole, point to this as the true etiologic agent. Urine toxicology shortly after a binge of cocaine use in each case was positive for levamisole. PMID- 20738456 TI - A randomized, controlled clinical trial on the clinical, microbiological, and staining effects of a novel 0.05% chlorhexidine/herbal extract and a 0.1% chlorhexidine mouthrinse adjunct to periodontal surgery. AB - BACKGROUND: Chlorhexidine (CHX) rinsing after periodontal surgery is common. We assessed the clinical and microbiological effects of two CHX concentrations following periodontal surgery. MATERIALS AND METHODS: In a randomized, controlled clinical trial, 45 subjects were assigned to 4 weeks rinsing with a 0.05 CHX/herbal extract combination (test) or a 0.1% CHX solution. Clinical and staining effects were studied. Subgingival bacteria were assessed using the DNA DNA checkerboard. Statistics included parametric and non-parametric tests (p<0001 to declare significance at 80% power). RESULTS: At weeks 4 and 12, more staining was found in the control group (p<0.05 and p<0.001, respectively). A higher risk for staining was found in the control group (crude OR: 2.3:1, 95% CI: 1.3 to 4.4, p<0.01). The absolute staining reduction in the test group was 21.1% (9 5% CI: 9.4-32.8%). Probing pocket depth (PPD) decreases were significant (p<0.001) in both groups and similar (p=0.92). No rinse group differences in changes of bacterial counts for any species were found between baseline and week 12. CONCLUSIONS: The test CHX rinse resulted in less tooth staining. At the study endpoint, similar and high counts of periodontal pathogens were found. PMID- 20738458 TI - The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. AB - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) represents a severe, acute, pustular skin reaction that is most often induced by drugs. AGEP can be difficult to differentiate from generalized pustular psoriasis (GPP) both clinically and histopathologically. We present a systematic description of the histopathological spectrum of AGEP and GPP with a focus on discriminating features. MATERIALS AND METHODS: A retrospective, descriptive, comparative histopathological study was completed utilizing step sections of 43 biopsies of 29 cases with a validated diagnosis of probable or definite AGEP and 24 biopsies of 19 cases with an established diagnosis of GPP. RESULTS: In AGEP, biopsies from erythema and pustules showed minor differences, whereas histopathology of the acute stage of GPP showed major differences compared to the chronic stage. Comparing AGEP and GPP, the presence of eosinophils, necrotic keratinocytes, a mixed interstitial and mid-dermal perivascular infiltrate and absence of tortuous or dilated blood vessels were in favor of AGEP. Moreover, chronic GPP was characterized by prominent epidermal psoriatic changes. The frequency of a psoriatic background of AGEP patients in our study was higher than that of psoriasis in the general population. However, histopathology of a subgroup of AGEP patients with a personal history of psoriasis revealed no significant differences from the other AGEP patients. CONCLUSIONS: The spectrum of histopathological features of both AGEP and GPP is presented. Despite considerable overlap, subtle consistent histopathological differences and the grade of severity of specific features can help in differentiation. We could neither substantiate earlier reports that follicular pustules exclude AGEP nor did we see vasculitis as a specific feature in AGEP. Our study also supports the concept that AGEP is a separate entity that is distinct from GPP. PMID- 20738459 TI - Juvenile psoriasis and its clinical management: a European expert group consensus. AB - BACKGROUND: Psoriasis, an inflammatory disorder of the skin, can significantly impact on a patient's quality of life, affecting their daily activities and families. The onset of psoriasis in childhood is quite common; however, the treatment of moderate-to-severe disease in this population is challenging, with a paucity of data reported and few licensed agents available. METHODS: A Delphi survey was conducted among a panel of European expert dermatologists and physicians with a particular interest in pediatric inflammatory disorders. The survey covered the aspects of psoriasis types, psoriatic arthritis, diagnosis and treatment options in childhood. RESULTS: A series of consensus opinions were reached, detailing the current practice in Europe for the diagnosis and treatment of psoriasis in childhood. These opinions are presented in the context of evidence from the literature and the current licensure status and indications of therapies for psoriasis in childhood. CONCLUSIONS: These data provide detailed information on the current practices in Europe for treating psoriasis in childhood. PMID- 20738460 TI - Today's treatments options for onychomycosis. AB - Onychomycosis can be cured even if fungi are sometimes difficult to eradicate; the treatment is often lengthy and requires patience. The choice of agents should be based on numerous factors including patient's age and health, causative organism, clinical type of onychomycosis, number of affected nails and severity of nail involvement. We review current and future treatments for onychomycosis. We will also consider treatment options in patients with poor prognostic factors suggesting possible treatment failure. PMID- 20738462 TI - Penile enhancement surgery. PMID- 20738463 TI - Marked amplification and diversification of products of ras genes from rat brain, Rab GTPases, in the ciliates Tetrahymena thermophila and Paramecium tetraurelia. AB - Small GTPase Rab (products of ras genes from rat brain) is a widely conserved molecular switch among eukaryotes and regulates membrane trafficking pathways. It is generally considered that the number of Rab encoded in the genome correlates with multicellularity; however, we found that unicellular ciliates Tetrahymena thermophila (Tt) and Paramecium tetraurelia (Pt) possess many more Rab genes in their genome than the 64 HsRab genes in the human genome. We succeeded in isolating 86 cDNA clones of 88 TtRab genes in the Tetrahymena genome. By comparing the amino acid sequence of Rab in humans and the budding yeast Saccharomyces cerevisiae, 42 TtRab belonged to subfamilies functionally characterized and designated as conventional Rab, while the remaining 44 TtRab were considered to be species-specific. To examine the diversity of Rab in ciliates, we searched for Rab genes in the genome database of P. tetraurelia. Overall, 229 PtRab genes were found and categorized as 157 conventional and 72 species-specific PtRab, respectively. Among them, nine PtRab genes showed high homology to seven TtRab, suggesting the conservation of ciliate-specific Rab. These data suggested that the range of Rab is markedly amplified and diversified in ciliates, which may support the elaborate cellular structures and vigorous phagocytosis of those organisms. PMID- 20738464 TI - Evidence for DNA synthesis in Pneumocystis carinii trophozoites treated with the beta-1,3-glucan synthesis inhibitor pneumocandin L-693,989. AB - Pneumocandins inhibit beta-1,3-glucan synthesis preventing the development of Pneumocystis cysts that are absent from the lungs of treated rats. To determine whether treated trophozoites are capable of DNA replication, cytochemical analyses were performed on 4',6-diamidino-2-phenylindole (DAPI)- and DB181 stained Pneumocystis carinii isolated from pneumocandin L-693-989-treated rats. Fluorescence intensities of trophozoite nuclei from drug-treated rats were greater than those of untreated controls, suggesting that DNA replication was not inhibited but that cytokinesis and perhaps karyokinesis were blocked. PMID- 20738465 TI - Prevalence of benign cutaneous disease among Oxford renal transplant recipients. AB - BACKGROUND: The burden of malignant and benign cutaneous disease among renal transplant recipients (RTR) is substantial. Little attention is given to non malignant skin problems in the literature despite their potential impact on quality of life or on aesthetics - which may contribute to poor compliance with immunosuppressive medications post-transplantation. OBJECTIVES: The aim of this study was to examine prevalence of benign cutaneous disease in a group of RTRs and identify risk factors for individual cutaneous conditions. METHODS: All cutaneous findings were recorded in a single full body skin examination of 308 RTRs. Data on medical, transplant and medication history were obtained from questionnaire and medical records. Odds ratios were calculated to look at associations between benign cutaneous diseases and various potential risk factors after controlling for gender, age, time since transplantation and skin type. RESULTS: Cutaneous infections such as viral warts (38%), fungal infection (18%) and folliculitis (27%) were common and usually chronic. A range of pilosebaceous unit disorders were observed with hypertrichosis being strongly associated with ciclosporin (P<0.0001). Other iatrogenic cutaneous effects included gingival hyperplasia (27%) and purpura (41%). We identified seborrhoeic warts and skin tags in 55% and 33% respectively. Inflammatory dermatoses were rare (<2%) apart from seborrhoeic dermatitis (9.5%). DISCUSSION: In this first comprehensive study on prevalence of benign cutaneous diseases in a UK transplant population, a wide range of skin disorders was identified. It is therefore important that RTRs have access to dermatology services post-transplantation for appropriate management of benign cutaneous conditions as well as early detection of cutaneous malignancy and education regarding risks of sun exposure. PMID- 20738466 TI - Reasons for non-use of proven pharmacotherapeutic interventions: systematic review and framework development. AB - RATIONALE, AIMS AND OBJECTIVES: The quality of patient care and safety is dependent on addressing both errors of commission (e.g. overuse of medications) and errors of omission (e.g. patients receiving too little care). Despite guidelines recommending the use of certain proven pharmacotherapeutic interventions, a large gap exists between the patients that have an indication for, and those that actually receive such interventions. To address how the rate of implementation of proven interventions can be improved is dependent on a comprehensive knowledge of the factors contributing to their underuse. The aim of the review is to create an evidence-based framework of reasons why eligible patients do not receive proven pharmacotherapeutic interventions. METHODS: A systemic review of the published reasons for non-use based on the Cochrane methodology. RESULTS: The systematic review identified 67 articles meeting the inclusion criteria. The reasons for non-use were extracted from the studies and a framework was created from the results. CONCLUSIONS: The factors associated with lack of implementation of proven pharmacotherapeutic interventions are complex and heterogeneous but can be understood from the perspectives of clinicians, patients and health care delivery systems. Efforts to increase the utilization of proven interventions should focus on disease/intervention-specific programmes that take into account the identified modifiable clinician, patient and system factors. PMID- 20738467 TI - Roles of managers, frontline staff and local champions, in implementing quality improvement: stakeholders' perspectives. AB - BACKGROUND: Translating promising research findings into routine clinical care has proven difficult to achieve; even highly efficacious programmes remain unadopted. Critical to changing care is an understanding of the context within which the improvement effort occurs, including the climate or culture. Health care systems are multicultural due to the wide variety of professionals, subgroups, divisions and teams within them. Yet, little work describes and compares different stakeholders' views on their and others' roles in promoting successful quality improvement implementation. OBJECTIVE: To identify manager and frontline staff perspectives about which organizational stakeholders should play a role in implementation efforts as well as what implementation roles these stakeholders should perform. METHODS: We conducted qualitative semi-structured interviews of a purposive sample of stakeholders at the clinic, medical centre and regional network levels. Participants included stakeholders across five clinics (n = 49), their four affiliated medical centres (n = 12) and three regional networks (n = 7). Working in coding teams, we conducted a content analysis utilizing Atlas.ti Version 5. RESULTS: According to informants, individuals at each organizational level have unique and critical roles to play in implementing and sustaining quality improvement efforts. Informants advocated for participation of a wide range of organizational members, described distinct roles for each group, and articulated the need for and defined the characteristics of frontline programme champions. CONCLUSIONS: Involvement of multiple types of stakeholders is likely to be costly for health care organizations. Yet, if such organizations are to achieve the highest quality care, it is also likely that such involvement is essential. PMID- 20738468 TI - The disparity of frontline clinical staff and managers' perceptions of a quality and patient safety initiative. AB - RATIONALE, AIMS AND OBJECTIVES: Arguably, a shared perspective between managers and their clinical staff on an improvement initiative would allow for most effective implementation and increase programme success. However, it has been reported that research has failed to differentiate between managers and line employees on quality management implementation and examine their differences in perceptions of quality and safety initiatives. The aim of this study was to compare clinical frontline staff and senior managers' perceptions on the importance of an organization-wide quality and safety collaborative: the Safer Patients Initiative (SPI). METHOD: A quantitative study obtained 635 surveys at 20 trusts participating in SPI. Participants included the teams and frontline staff involved within the programme at each organization. Independent T-tests were carried out between frontline staff and senior managers' perceptions of SPI programme elements, success factors and impact & sustainability. RESULTS: Statistically significant differences were found between the perceptions of frontline staff and senior managers on a wide number of issues, including the frontline perceiving a significantly larger improvement on the timeliness of care delivery (t = 2.943, P = 0.004), while managers perceived larger improvement on the culture within the organization for safe, effective and reliable care (t = 2.454, P = 0.014). CONCLUSION: This study has identified statistically significant disparities in perceptions of an organization-wide improvement initiative between frontline staff and senior managers. This holds valuable implications for the importance of getting both frontline and management perspectives when designing such interventions, in monitoring their performance, and in evaluating their impact. PMID- 20738469 TI - Non-adherence to antibiotic prescription guidelines in treating urinary tract infection of children: a population-based study in Taiwan. AB - OBJECTIVES: Inappropriate use of antibiotics may increase antibiotic resistance and health care service load. Few studies have been conducted to investigate physician non-adherence to antibiotic prescription guidelines for treating urinary tract infections (UTIs) in child patients. This study aimed to examine the rates of and factors associated with non-adherence to antibiotic prescription guidelines for treating uncomplicated UTIs in child patients. METHODS: This is a cross-sectional study in which a random sample of 8921 children who received antibiotics prescription for UTIs (ICD-9-CM: 590.1, 595.0, 595.9 or 599.0) at age 17 years or less, between 2000 and 2007, were analysed. Data analysed were retrieved from Taiwan's National Health Insurance database. Non-adherence was determined by antibiotic prescription not recommended by the Infectious Disease Society of Taiwan. Multivariate logistic regression model was employed to assess the potential predictors for non-adherence, including various characteristics of patients, physicians and medical institutions. RESULTS: The overall non-adherence rate was estimated at 20.05%. Older patients, older physicians and physicians from community clinics were associated with higher rates of non-adherence. Compared with pediatricians who had the lowest rate (13.15%) of non-adherence, certain specialties were found to have significantly elevated adjusted odds ratio (AOR) of non-adherence, with the highest one noted for gynecologists (35.11%, AOR = 2.29, 95% confidence interval: 1.89-2.77). We also observed that the most frequently prescribed antibiotics not recommended on guidelines varied with physician specialty. CONCLUSIONS: Special attention should be concentrated on older physicians, gynecologists and physicians who practiced at community clinics to reduce non-adherence of antibiotic prescription for treating UTIs in child patients. PMID- 20738470 TI - Effect of feedback in promoting adherence to an exercise programme: a randomized controlled trial. AB - OBJECTIVE: We investigated whether providing participants in an exercise programme with regular feedback on their exercise progress affected their adherence to the programme regimen. METHOD: We conducted a randomized controlled trial. Adult men and women with borderline hypertension and a body mass index >= 25.0 were randomized to two intervention groups (groups A and B) and one control group (group C) and were prescribed regular aerobic exercise. During the 12-week study period, group A was provided with both feedback information on their exercise progress and a health letter, while group B was provided with the health letter only. The main outcome measure was exercise performance, per cent achievement of target exercise level (%) defined as the number of weeks during which the exercise target was reached divided by the number of weeks in the programme. Results were compared using the Kruskal-Wallis test. RESULTS: A total of 105 study subjects were randomized into three groups (A, n = 37; B, n = 37 and C, n = 31). Per cent achievement of target exercise level during the 12-week period was highest in group A (26.5%), followed by groups B (22.9%) and C (17.4%) (P = 0.36). Subjects who received regular feedback during the exercise programme tended to have higher exercise performance. CONCLUSIONS: In improving adherence to exercise intervention, the provision of regular feedback to participants in an exercise programme may be an effective intervention. PMID- 20738471 TI - Optimal two-stage breast cancer screening for countries with intermediate or low incidence of breast cancer. AB - OBJECTIVES: This study is to identify an optimal cut-off for two-stage breast cancer screening making allowance for variation of the baseline incidence rate and utility values between sensitivity and specificity. METHODS: We used data from a two-stage breast cancer screening of Taiwanese women aged 50-69 years for whom risk stratification was based on a composite risk score (conventional risk factors); subjects with a risk score greater than the cut-off score were screened using mammography. The Bayesian posterior risk for breast cancer was computed by incorporation of the baseline incidence rate and the risk score. Bayes' maximum utility decision rule was then developed to determine the optimal screening cut off. RESULTS: With a risk score of -9 applied to the current two-stage breast cancer screening programme, we could detect one breast cancer case for every 1406 women. Given different predetermined risks, the selected cut-offs were -9 for 1:1200, -8 for 1:800, -4 for 1:600, -1 for 1:400 and 3 for 1:200 for women aged 50-59 years. When the regret utility ratio of positive predictive value to negative predictive value was set at 1:10, the specificity and sensitivity were 58.5% and 70.4%, respectively, and the optimal cut-off was -5.5. When the ratio was set at 10:1, the sensitivity and specificity were 75.5% and 57.1%, respectively, and the optimal cut-off value was -7.5. CONCLUSIONS: This study demonstrates that Bayes' maximum utility decision rule can be used to determine optimal cut-off values for two-stage breast cancer screening in countries or areas with lower or intermediate incidence of breast cancer. PMID- 20738472 TI - Analysis of dyadic data: a guideline applied to erectile dysfunction. AB - RATIONALE: Research on relationships often does not refer to a single person but rather to two persons. Nonetheless, such data has been often analysed by examining individuals in isolation, which falls short of capturing their truly interpersonal and non-independent nature. AIMS AND OBJECTIVES: This paper highlights and illustrates some analytic tools for such dyadic data that are essential for theories about dyadic relationships to be tested adequately. METHODS: The methodology is applied to clinical trial data from male patients treated for their erectile dysfunction and data from their partners with respect to treatment satisfaction. Multi-level modelling was used to analyse the data. RESULTS: The approaches outlined allow researchers to assess both individual effects and companion effects (e.g. of baseline intercourse satisfaction on subsequent treatment satisfaction), role of participant (e.g. patient or partner) or treatment condition (e.g. test or placebo) on outcome (e.g. treatment satisfaction), and differences on individual and companion effects when couples differ on important variables (e.g. differences on the individual and companion effects of baseline intercourse satisfaction on treatment satisfaction when couples differ with respect to treatment condition). CONCLUSION: Researchers are encouraged to consider implementing dyadic data analysis in their own work. PMID- 20738473 TI - Relationship between pre-discharge occupational therapy home assessment and prevalence of post-discharge falls. AB - RATIONALE, AIMS AND OBJECTIVE: Pre-discharge occupational therapy home assessments are common practice, and considered important for falls prevention in older people. This prospective, observational cohort study describes the association between pre-discharge home assessment and falls in the first month post-discharge from a rehabilitation hospital. METHODS: 342 inpatients were recruited and followed up 1 month post-discharge. Patients were classified into diagnostic groups (cardiac, orthopaedic trauma, spinal, peripheral joint surgery, neurological and deconditioned). Age, gender, falls risk [Falls Risk Assessment Scoring System (FRASS)], functional independence scores (FIMTM) and receipt (or not) of a home assessment were recorded. Patients completed a diary to document post-discharge falls. Logistic regression analysis tested the effect on falling of receiving a home assessment, age, gender, diagnostic group, FRASS and FIMTM. RESULTS: Considering all subjects, not receiving a home assessment increased the risk of falling 1 month post-discharge [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-4.7, P=0.003]. Neurological and orthopaedic trauma patients had significantly elevated risks of falling [OR (95% CI), respectively, 12.5 (4.7 33.2), 3.4 (1.4-8.4)] relative to the orthopaedic joint group. For all diagnostic groups except neurological, falls risk was mitigated by a home assessment. In non neurological patients, adjusting for the effect of diagnostic group, FRASS and FIMTM scores indicated a significant association between not receiving a home assessment and falling (OR 4.2, 95% CI 2.1-8.2, P<0.001). CONCLUSIONS: Pre discharge occupational therapy home assessments are sound post-discharge falls prevention strategies in non-neurological patients. The decision to conduct a home assessment should consider diagnosis, falls risk and functional independence. PMID- 20738474 TI - Effects of inpatient rehabilitation for children with atopic dermatitis: a prospective controlled evaluation study. PMID- 20738475 TI - The importance of organizational climate and implementation strategy at the introduction of a new working tool in primary health care. AB - RATIONALE, AIMS AND OBJECTIVES: The transmission of research findings into routine care is a slow and unpredictable process. Important factors predicting receptivity for innovations within organizations have been identified, but there is a need for further research in this area. The aim of this study was to describe contextual factors and evaluate if organizational climate and implementation strategy influenced outcome, when a computer-based concept for lifestyle intervention was introduced in primary health care (PHC). METHOD: The study was conducted using a prospective intervention design. The computer-based concept was implemented at six PHC units. Contextual factors in terms of size, leadership, organizational climate and political environment at the units included in the study were assessed before implementation. Organizational climate was measured using the Creative Climate Questionnaire (CCQ). Two different implementation strategies were used: one explicit strategy, based on Rogers' theories about the innovation-decision process, and one implicit strategy. After 6 months, implementation outcome in terms of the proportion of patients who had been referred to the test, was measured. RESULTS: The CCQ questionnaire response rates among staff ranged from 67% to 91% at the six units. Organizational climate differed substantially between the units. Managers scored higher on CCQ than staff at the same unit. A combination of high CCQ scores and explicit implementation strategy was associated with a positive implementation outcome. CONCLUSIONS: Organizational climate varies substantially between different PHC units. High CCQ scores in combination with an explicit implementation strategy predict a positive implementation outcome when a new working tool is introduced in PHC. PMID- 20738476 TI - A comparison of the scientific quality of publicly and privately funded randomized controlled drug trials. AB - BACKGROUND: There is disagreement but few objective data on the relative quality of publicly or privately funded research. Cochrane reviews of randomized trials provide a good comparison opportunity because there is widespread agreement on how trial quality should be assessed and the Cochrane reviewers routinely do this. AIMS: To compare the quality of publicly or privately funded randomized controlled trials. METHODS: A total of 105 trials included in two Cochrane reviews were studied. Their quality assessments were abstracted from the relevant review and information about their funding source was collected from the original trial publications. MAIN RESULTS: Funding information was obtained for 87 trials. Of these, trials funded by pharmaceutical companies were larger (median sample size 126 vs. 45, P<0.001), more likely to have avoided ascertainment bias 11/14 vs. 15/41 (P=0.05). Non-significant trends in avoiding entry bias 19/19 vs. 35/37 and performance bias 13/22 vs. 14/48 also favoured the commercial trials. Commercial trials also had higher recorded attrition rates (median 6% vs. 1%, P=0.007), but this difference was entirely caused by more non-commercial trials reporting a zero attrition rate. DISCUSSION: The apparently lower attrition rate in the non-commercial trials should be interpreted with caution. Zero attrition in clinical trials with follow-up of many months is somewhat implausible. MAIN CONCLUSION: Commercially funded randomized trials tend to be of higher methodological quality than government-funded ones. PMID- 20738477 TI - Cancer patients' perception of information exchange between hospital-based doctors and their general practitioners. AB - RATIONALE, AIMS AND OBJECTIVES: The quality of communication between health care professionals is a key issue determining health outcomes in cancer care. This study aims to find out what importance cancer patients in Austria attach to information exchange between hospital-based doctors and their general practitioners (GPs) and how patients perceive this flow of information. METHODS: In this cross-sectional study, cancer patients seeking help at a community-based organization in the voluntary sector (Viennese Cancer League) were polled with a 16-item questionnaire. Contingency tables were evaluated by means of the chi squared and Mantel-Haenszel test. RESULTS: The mean age of the 252 respondents - 92.6% of those polled (272) - was 51.9 years (SD +/- 13.6). 87.5% [female (f): 92.1%, male (m): 80.2%] considered the exchange of information between the hospital-based specialists and their GP 'very important' or 'important'; 12.5% (f: 8.0%, m: 19.8%) 'not so important' or 'not at all important'; 28.1% (f: 26.0%, m: 31.2%) of patients considered the flow of information as 'very good' or 'fairly good', but 50.9% (f: 58.7, m: 40.0%) as 'rather poor' or 'poor'. Some 34.8% of patients thought that their cancer disease was first suspected by a hospital-based specialist; 42.1% thought that it was first suspected by a doctor outside the hospital. Even when patients were counselled elsewhere they gave high importance to the provision of appropriate information to their GP. CONCLUSIONS: Cancer patients in Austria attach high importance to the provision of appropriate information to their GP by hospitals and perceive this exchange of information as insufficient, a finding that could well be prevalent in other European health systems. PMID- 20738478 TI - Consensus on 'core/essential' and 'ideal world' criteria of a pre-discharge occupational therapy home assessment. AB - RATIONALE, AIMS AND OBJECTIVES: There are no standard criteria for an occupational therapy (OT) home assessment for patients about to be discharged from an acute rehabilitation facility. This has implications for benchmarking, quality improvement and research. The aim of this paper is to establish 'core/essential' and 'ideal world' elements of OT home assessments for patients about to be discharged from acute rehabilitation settings. METHODS: A piloted open-ended questionnaire initiated a Delphi study involving knowledgeable OTs working in Australian public and private acute rehabilitation settings. 'Core/essential' and 'ideal world' elements of OT home assessments were confirmed when 70% agreement was reached. RESULTS: Of 242 facilities in two Australian states, 110 were invited to participate, and 81 OTs from 84 facilities did so. Four Delphi rounds were required to reach consensus on 30 'core/essential' and 25 'ideal world' elements. CONCLUSION: Standard use of 'core/essential' pre discharge home assessment elements should improve standards of care and the quality of discharge planning. OTs should consider including 'ideal world' criteria in pre-discharge assessments to optimize recently ill patients' community independence. PMID- 20738479 TI - Liver size reveals social status in the African cichlid Neolamprologus pulcher. AB - Wild groups (n = 167) of the cooperatively breeding Lake Tanganyika cichlid, Neolamprologus pulcher, were used to investigate how social status and sex influence liver investment. In contrast to expectations, males and females (controlling for body size) had similar liver investment and subordinates (both sexes) had relatively larger livers compared with dominants. Three hypotheses were considered for why social status results in liver size disparity: liver mass might reflect status-dependent differences in (1) energy expenditure, (2) energy storage and (3) energy acquisition. First, dominants performed more energetically costly behaviours (e.g. social policing and care) compared with subordinates, supporting the notion that energy expenditure drives liver investment. Moreover, dominants in large groups (with many subordinates to monitor) and those holding multiple territories (with large areas to patrol), tended to have smaller livers. Second, subordinates did not appear to use the liver as a strategic energy storage organ. In laboratory and field experiments, subordinates ascending in rank had similar or larger livers during periods of rapid growth compared with non-ascending controls. Third, although subordinates fed more frequently than dominants, a negative relationship was found between feeding rates and liver size. Hence, these results contrast with previous liver studies and suggest that liver investment patterns were linked to status-driven differences in energy expenditure but not to energy intake or storage in N. pulcher. PMID- 20738480 TI - Embryonic staging series for the beach spawning, terrestrially incubating California grunion Leuresthes tenuiswith comparisons to other Atherinomorpha. AB - California grunion Leuresthes tenuis synchronize spawning with tidal cycles, so the embryos incubate in a terrestrial environment, delay hatching until cued by a specific environmental trigger, and may extend incubation for up to an additional four weeks. These adaptations, however, do not appear to alter the morphology or sequence of early developmental stages as compared to other Atherinomorph fishes in the Orders Beloniformes and Cyprinodontiformes. Embryonic development is described in a series of 30 stages based on morphology observed by light microscopy. Stages are placed in five periods: zygote and cleavage, blastula, gastrula, segmentation and organogenesis, and hatching competence. Embryos from a southern population of L. tenuis in Los Angeles are compared with embryos found > 560 km north in San Francisco Bay. Northern L. tenuis embryos developed more slowly at several stages than southern embryos and reached hatching competence later, but both locations maintained synchrony with the tidal cycle for both spawning and hatching. The variation in rates of development and stage at hatching readiness are forms of developmental heterochrony that may be associated with evolutionary adaptation or morphological plasticity within this highly successful clade. PMID- 20738481 TI - The effects of temperature and water concentration on the otolith incorporation of barium and manganese in black rockfish Sebastes melanops. AB - Observations of multiple years of geographic variation in [Ba:Ca](otolith) and [Mn:Ca](otolith) in black rockfish Sebastes melanops prompted this study to examine the effects of temperature and water concentration on the otolith incorporation of Ba and Mn in this wholly marine species. The replicated experiment design consisted of two water temperatures (7.4 and 13.0 degrees C) and four water concentrations of Ba:Ca and Mn:Ca. A positive, linear relationship between [Ba:Ca](water) and [Ba:Ca](otolith) was observed at both temperatures. A positive temperature effect was also observed with mean partition coefficients for Ba (D(Ba)) greater in the 13 degrees C than in the 7.4 degrees C treatments (mean = 0.061 and 0.048, respectively). There was no relationship between [Mn:Ca](water) and [Mn:Ca](otolith) although a negative temperature effect was observed. Mean partition coefficients for Mn (D(Mn)) were lower in the 13 degrees C than in the 7.4 degrees C treatments (mean = 0.027 and 0.036, respectively). The data presented support the assumption of a positive, linear relationship between water and otolith Metal:Ca concentrations for Ba:Ca but not for Mn:Ca. Thus, although indicative of residence in distinct water masses, observed variation in [Metal:Ca](otolith) may not reflect variation in water concentration and can be affected by temperature. Caution should be applied in the interpretation of geographic variation of [Mn:Ca](otolith) until the mechanisms regulating its incorporation are more fully understood. PMID- 20738482 TI - Lunar and daily spawning rhythms of Senegal sole Solea senegalensis. AB - A periodicity of 29 days was observed in spawning rhythms in Senegal sole Solea senegalensis, with an acrophase around the last quarter and the new moon. In both spring and autumn, a very marked nocturnal spawning rhythm was registered, with spawning beginning after dusk and the acrophase occurring around 2300 hours. When the photoperiod was artificially extended (from 10L:14D to 14L:10D), S. senegalensis synchronized to the new photoperiod: spawning took place after the new 'dusk', the beginning gradually shifting from 2100 to 2300 hours and the acrophase from 2325 to 0032 hours. Under continuous light conditions, fish sustained rhythmicity for 2 days, with an acrophase at 2249 hours, which suggested the existence of an endogenous pacemaker controlling the daily spawning rhythm. These findings provided new insights for better understanding the reproductive physiology of this species and for optimizing the timing protocols of egg collection and larvae production in S. senegalensis aquaculture. PMID- 20738483 TI - Variation in prey selection of a piscivorous fish after the impoundment of a neotropical reservoir: prey size and type. AB - The relative abundance and size of prey fish in the stomachs of the predator Acestrorhynchus pantaneiro were compared with those recorded in the field to estimate prey selection. Fish samples were taken monthly in the Manso Reservoir (State of Mato Grosso, Brazil) immediately after the impoundment, from March 2000 to February 2001 (period I) and from March 2003 to February 2004 (period II). In period I, the small relative dominance of the prey in the environment seemed to have lead to random foraging. In period II, however, when the forage fish Moenkhausia dichroura was dominant in the environment, the predator shifted its diet, foraging mainly on this prey. Species with short relative body depth were positively selected. The prey size classes between 30 and 49 mm, and 50 and 69 mm standard length (L(S)) were the most abundant in the environment. Small prey were predominantly selected by A. pantaneiro. Even when a given prey or prey size was predominant in the environment, A. pantaneiro was a selective predator and maintained its preferences associated to prey type and L(S), although it consumed the most abundant resource. PMID- 20738485 TI - Modelling the growth of Japanese eel Anguilla japonica in the lower reach of the Kao-Ping River, southern Taiwan: an information theory approach. AB - Information theory was applied to select the best model fitting total length (L(T))-at-age data and calculate the averaged model for Japanese eel Anguilla japonica compiled from published literature and the differences in growth between sexes were examined. Five candidate growth models were the von Bertalanffy, generalized von Bertalanffy, Gompertz, logistic and power models. The von Bertalanffy growth model with sex-specific coefficients was best supported by the data and nearly overlapped the averaged growth model based on Akaike weights, indicating a similar fit to the data. The Gompertz, generalized von Bertalanffy and power growth models were also substantially supported by the data. The L(T) at age of A. japonica were larger in females than in males according to the averaged growth mode, suggesting a sexual dimorphism in growth. Model inferences based on information theory, which deal with uncertainty in model selection and robust parameter estimates, are recommended for modelling the growth of A. japonica. PMID- 20738484 TI - The structure and possible functions of the milkfish Chanos chanos adipose eyelid. AB - Basic histological sections (with different staining methods) and scanning electron microscopy (SEM) examinations showed that there were three distinctive layers in the adipose eyelid of milkfish Chanos chanos, which is found in the cephalie region and covers the entire eye. The outer and inner layers were epithelial tissues and the middle layer was composed of connective tissue formed by type I collagen fibrils. No adipose tissue was found in any of the three layers of the so-called adipose eyelid. Examination by transmission spectrophotometer showed that the adipose tissue could filter out ambient light with a wavelength shorter than 305 nm. A photoretinoscope was used to investigate whether the adipose eyelid influenced the mechanism of eye focusing. Eye diopter values did not differ before or after eyelid removal, which indicated that the adipose eyelid did not play a role in eye focusing. In light of these findings, it is suggested that the adipose eyelid serves to block exposure of harmful ultraviolet light into eyes and may also to offer some protection against impact to the eye in the aquatic environment. PMID- 20738486 TI - Multi-scale habitat selection by Murray cod Maccullochella peelii peelii in two lowland rivers. AB - This study provides information on habitat selection by the threatened Murray cod Maccullochella peelii peelii at two spatial scales in the Ovens and Murray Rivers in south-eastern Australia. Both adult (> 450 mm total length, L(T)) and age 0 year (< 150 mm L(T)) M. p. peelii selected macro and microhabitats based on structural variables. At the macrohabitat scale, adults selected channel habitats in the river, floodplain channels at high floods and within Lake Mulwala, whereas the floodplain proper was avoided. Adult and age 0 year fish selected similar microhabitats regardless of site or hydrologic conditions, and selection was primarily influenced by the presence of higher loadings of structural woody habitat, higher c.v. in depth, more overhanging vegetation, shallower comparative depths and lower water velocities, closer to the bank. Age 0 year M. p. peelii appeared to select shallower habitats with greater amounts of structural woody habitat, closer to the river bank than adult fish. PMID- 20738487 TI - Influence of the photoperiod on growth rate and insulin-like growth factor-I gene expression in Nile tilapia Oreochromis niloticus. AB - The effects of the duration of the light phase photoperiod (8 h light or 16 h light) on the growth and hepatic insulin-like growth factor-I (IGF-I) gene expression in Nile tilapia Oreochromis niloticus were evaluated. There was a slight but not significant tendency for fish in the long light phase group (L(P)) to display elevated specific growth rate (G) both in mass (M) and standard length (L(S)) compared with that in the short light phase group (S(P);P = 0.057 for G(M);P = 0.055 for G(L)). Significantly, higher food conversion efficiency was observed in the L(P) than in the S(P). There were significant positive correlations between IGF-I concentrations and G, both in M and L(S). A significantly negative correlation was observed between IGF-I mRNA level and eye colour pattern. The lack of significant differences in G and hepatic IGF-I gene expression, despite the significant difference in feed conversion efficiency, may be related partly to the development of different levels of social interactions in the different groups within a photoperiod regime leading to increased variation of results within each group. These findings suggest that hepatic IGF-I gene expression has potential utility as a growth rate indicator for this species of fish and social status, as quantified by eye colour pattern, appears to be a much stronger determinant of growth rate and IGF-I transcript level than does light phase photoperiod length. PMID- 20738488 TI - Melatonin concentrations during larval and postlarval development of gilthead sea bream Sparus auratus: more than a time-keeping molecule? AB - In this study, melatonin (MEL) and thyroxine (T(4)) concentrations were measured during larval and postlarval development of gilthead sea bream Sparus auratus Hormones were measured in whole bodies of larvae or the head and trunk of postlarvae after 67 days of exposure to constant light, 24L:0D, constant darkness, 0L:24D or 12L:12D and in the plasma of 6 month juveniles kept under the 12L:12D, 0L:24D and 24L:0D regimes. High MEL concentrations in larvae suggested a distinct role of MEL in early organogenesis and development of S. auratus. In larvae, the gastro-intestinal tract seemed to be an important extrapineal and extraretinal source of MEL. No endogenous rhythm of MEL synthesis was demonstrated in 67 day larvae; however, in 6 month juveniles, it was evident. At early ontogenesis of S. auratus, the role of MEL is probably related mostly to the control of development and protection against free radicals, whereas its action as a time-keeping molecule develops later. The increase in T(4) concentration during the S. auratus larva-juvenile transition, i.e. between 50 and 70 days post-hatch, which was observed concurrently with the decrease of MEL concentration, may suggest an inverse relationship between T(4) and MEL. PMID- 20738489 TI - Stock structure of blue threadfin Eleutheronema tetradactylum on the Queensland east coast, as determined by parasites and conventional tagging. AB - Blue threadfin Eleutheronema tetradactylum (Polynemidae) were examined from four areas (Princess Charlotte Bay, Trinity Inlet, Halifax Bay and Upstart Bay) in eastern Queensland covering a distance of c. 950 km of coastline. Parasites were used as biological markers to infer stock structure of E. tetradactylum. Parasites designated as 'temporary' biological markers were the copepod Thysanote eleutheronemi, the acanthocephalan Neoechinorhynchus topseyi, the nematode Philometra rajani and hemiurid trematodes. The larval nematodes Anisakis sp. Type 1 and Terranova sp. Type 2; and the larval cestodes Pterobothrium pearsoni and Callitetrarhynchus gracilis were considered 'permanent' biological markers. Both univariate and multivariate analyses demonstrated that there was little difference in temporary parasite abundance between the four areas. In contrast, the same analyses revealed that most areas had two or more significant differences in permanent parasite abundance, with the exception of Halifax Bay and Upstart Bay, which were significantly different only in the multivariate analysis. Biological markers predicted that Princess Charlotte Bay and Trinity Inlet consisted of distinct populations, whereas Halifax Bay and Upstart Bay were not clearly differentiated. Tag recapture data supported this hypothesis; the majority of recaptures were within 100 km of the initial tagging location. Geographical movement of E. tetradactylum may be limited due to their biology and ecology, as well as the distances and oceanographic boundaries that separate habitats. Contrary to current management definitions, the stock structure of E. tetradactylum on the east coast of Queensland appears to be geographically differentiated at a small spatial scale. PMID- 20738490 TI - Rapid fluctuation in infection levels of Neoheterobothrium hirame (Monogenea) in Japanese flounder Paralichthys olivaceus in the Joban area, Japan. AB - Neoheterobothrium hirame a haematophagous monogenean parasite on Japanese flounder Paralichthys olivaceus occurred at high prevalences (> 70%) from 1999 to 2002 but thereafter declined and remained low (< 20%) from 2003 to 2005 in the Joban area, Japan. In 2006, N. hirame became abundant again reaching a prevalence of 63%. Generalized linear models explained these rapid fluctuations in infection in relation to inshore water temperature, which affected the reproductive success of the parasite, and also the encounter rate between host and parasite through changes in their respective population densities. Severely anaemic fish were few, 2.4% even in 1999-2002 and 2006, suggesting that the effect of N. hirame infection on the P. olivaceus population was small in this area. PMID- 20738492 TI - Patterns of migration and residency in coastal cutthroat trout Oncorhynchus clarkii clarkii from two tributaries of the lower Columbia River. AB - Coastal cutthroat trout Onchorhynchus clarkii clarkii life-history variants, migration and freshwater residency were monitored using stationary passive integrated transponder (PIT) tag arrays in two tributaries of the Columbia River from 2001 to 2005 (Abernathy Creek, river kilometre, rkm 76) and from 2002 to 2005 (Chinook River, rkm 6). In 2001-2003 and 2002-2003 (Abernathy and Chinook, respectively), 300-500 coastal O. c. clarkii were captured in each tributary by electrofishing and implanted with 23 mm PIT tags. PIT arrays monitored movements from the initiation of tagging through the spring of 2005. Rotary screw traps were also operated on both tributaries. In Abernathy Creek, 28% of tagged individuals were observed through either active capture or passive interrogation. Of these, 32% were identified as migrants and 68% were identified as residents. In the Chinook River, 48% of tagged fish were observed subsequent to tagging; 92% of these fish were migrants and only 8% were resident. In both tributaries, a greater proportion of resident fish were in the upper reaches. The majority of migrants (78-93%) moved the spring following tagging. Migrants leaving at age 2+ years tended to grow faster than those that migrated at age 3+ years or residents. Patterns of growth or growth opportunities may influence both patterns of life-history expression and the timing of migration. PMID- 20738491 TI - Winter lipid depletion of juvenile walleye pollock Theragra chalcogramma in the Doto area, northern Japan. AB - Seasonal variation in body size and nutritional condition of juvenile walleye pollock Theragra chalcogramma was examined to elucidate the mechanism underlying their first-winter survival on the continental shelf of the Doto area, northern Japan, based on monthly samples collected over 2 years. Stored lipid mass was highest during autumn, but 93% (2004) and 80% (2005) of lipids were exhausted by the onset of winter. Lipid levels in the winter of 2004 remained low (7-14% of the autumnal maximum), and there was reduced growth rate until the spring, whereas in 2005 lipid levels were higher and more variable (10-46% of the maximum) and some growth occurred. An analysis of the allometric relationships between body size and stored energy showed that larger individuals accumulated disproportionately more energy in the autumn, but the advantage disappeared prior to the winter. In January 2004, stored lipid energy was low throughout the Doto continental shelf relative to the continental slope area. These results suggest that winter feeding opportunities on the shelf are severely limited but not completely absent. Previous studies have shown that winter temperatures on the shelf are lower than those in the slope area. It is possible that juvenile T. chalcogramma survive winter on the shelf without a high level of pre-winter lipid storage because the occasional feeding in the cold shelf water benefits energy conservation. PMID- 20738493 TI - Reproductive characteristics and population decline of four species of skate (Rajidae) off the eastern coast of Canada. AB - Four of the most common species of skate (Rajidae) were studied off eastern Canada to determine if their reproductive characteristics were linked to their population trajectories. The fecundity of the winter skate Leucoraja ocellata, the little skate Leucoraja erinacea, the thorny skate Amblyraja radiata and the smooth skate Malacoraja senta averaged between 41 and 56 egg cases per year for each species. For all species but L. ocellata, males matured at larger sizes and at later ages than females. Theoretical rates of population increase for non equilibrium populations of L. ocellata (c. 0.07), M. senta (c. 0.14) and L. erinacea and A. radiata (c. 0.20) were low compared to most fishes, indicating that north-west Atlantic skates are intrinsically unproductive, yet are theoretically capable of supporting low-level fisheries. Nevertheless, the results of 36 years of research surveys indicate that the abundance of mature L. ocellata, A. radiata and M. senta all decreased by >90% since 1970, indicating that past fishing mortality (both directed and undirected) has outstripped the net productivity of the skate populations on the eastern Scotian Shelf. The relationship between maximum age (t(max)) and age of maturity (t(mat)) was a better predictor of population growth rate than was body size, with the species exhibiting the highest ratios of t(mat) :t(max) (L. ocellata = 0.68, M. senta = 0.66) having the lowest predicted population growth rates. L. ocellata appears to have the lowest productivity and has experienced the greatest population decline, thus raising concerns over its future status. PMID- 20738494 TI - Feeding guilds and food resource partitioning in a lake fish assemblage: an ontogenetic approach. AB - Ontogenetic diet patterns and trophic guild structure of a 15 species temperate lake fish assemblage were analysed over wide size intervals (up to seven orders of magnitude in body mass), representing practically the whole life span in most species. A two-step objective clustering technique supplemented with other multivariate statistical tools proved that size-related diet changes clearly played an important role in structuring trophic organization of fishes inhabiting Lake Balaton. As many as 13 out of the 15 fish species showed marked size-related dietary changes with two to four ontogenetic feeding stages. At the assemblage level, 11 trophic guilds were separated. Guild membership was size-dependent in 11 fish species that participated in two to four trophic guilds during their life span. The most complex trophic ontogeny was observed in roach Rutilus rutilus and asp Aspius aspius with four guild memberships. This study showed that trophic status of fishes may be very size-sensitive and thus a universal classification of fish species to general trophic guilds, such as 'planktivore', 'benthivore', 'piscivore' or 'herbivore', should be applied very carefully even in environmental monitoring and fisheries management applications, unless it is supported by relevant results of life span diet analyses. PMID- 20738495 TI - A validation of intracellular pH measurements in fish exposed to hypercarbia: the effect of duration of tissue storage and efficacy of the metabolic inhibitor tissue homogenate method. AB - This study assessed the effect of tissue storage duration and accuracy of the metabolic inhibitor tissue homogenate (MITH) method on intracellular pH (pHi) values of tissues of white sturgeon Acipenser transmontanus during hypercarbia. No effect of storage in liquid nitrogen of up to 30 days was observed and MITH appears appropriate for measurement of pH in fish exposed to up to 10% CO2 (10000 Pa pCO2). PMID- 20738496 TI - Prey selection and functional response of juvenile lemon sharks Negaprion brevirostris. AB - Prey preference of juvenile lemon sharks Negaprion brevirostris was examined in experiments conducted in field-based pens where the fish were offered meals of live teleosts: grey snapper Lutjanus griseus and yellow fin majorra Gerres cinereus in ratios of L. griseus:G. cinereus varying from 10:0 to 2:8. Relative electivity indices for each treatment showed that N. brevirostris preyed on G. cinereus rather than L. griseus. They showed a prey preference relating to density of G. cinereus (type II functional response) but not to L. griseus. PMID- 20738497 TI - Contrasting trends in two condition indices: bathymetric and spatial variation in autumn condition of Icelandic cod Gadus morhua. AB - Bathymetric and regional variation in condition of Icelandic cod Gadus morhua in autumn is compared to that previously observed in spring. Once again, contradicting patterns in the hepato-somatic index and a morphometric index of fish condition were observed. The relevance of this persistent spatial variation in condition in relation to emerging evidence of behavioural types is discussed. PMID- 20738498 TI - Some Atlantic cod Gadus morhua in the Baltic Sea visit hypoxic water briefly but often. AB - Individual behaviour of Atlantic cod Gadus morhua in the presence of hypoxic water was measured in situ in the vertically stratified Bornholm Basin of the Baltic Sea. Considering all recaptured individuals, the use of hypoxic habitat was comparable to data derived by traditional survey data, but some G. morhua had migrated towards the centre of the c.100 m deep basin and spent about a third of their time at oxygen saturation <50%, possibly to forage on zoobenthos. Maximal residence time per visit in such hypoxic water was limited to a few hours, allowing for the digestion of consumed prey items in waters with sufficient dissolved oxygen. PMID- 20738500 TI - A review of the likely effects of climate change on anadromous Atlantic salmon Salmo salar and brown trout Salmo trutta, with particular reference to water temperature and flow. AB - The present paper reviews the effects of water temperature and flow on migrations, embryonic development, hatching, emergence, growth and life-history traits in light of the ongoing climate change with emphasis on anadromous Atlantic salmon Salmo salar and brown trout Salmo trutta. The expected climate change in the Atlantic is for milder and wetter winters, with more precipitation falling as rain and less as snow, decrease in ice-covered periods and frequent periods with extreme weather. Overall, thermal limits for salmonids are species specific. Scope for activity and growth and optimal temperature for growth increase with temperature to an optimal point before constrain by the oxygen content of the water. The optimal temperature for growth decreases with increasing fish size and varies little among populations within species, whereas the growth efficiency may be locally adapted to the temperature conditions of the home stream during the growth season. Indirectly, temperature influences age and size at smolting through its effect on growth. Time of spawning, egg hatching and emergence of the larvae vary with temperature and selective effects on time of first feeding. Traits such as age at first maturity, longevity and fecundity decrease with increasing temperature whilst egg size increases with temperature. Water flow influences the accessibility of rivers for returning adults and speed of both upstream and downstream migration. Extremes in water flow and temperature can decrease recruitment and survival. There is reason to expect a northward movement of the thermal niche of anadromous salmonids with decreased production and population extinction in the southern part of the distribution areas, migrations earlier in the season, later spawning, younger age at smolting and sexual maturity and increased disease susceptibility and mortality. Future research challenges are summarized at the end of the paper. PMID- 20738501 TI - Contrasting pragmatic and suffering-centred approaches to fish welfare in recreational angling. AB - Two views dealing with fish welfare in recreational fishing are discussed in an effort to stimulate the current discourse on the topic. The pragmatic approach asks whether and how strongly recreational fishing compromises the health and fitness of individual fishes and what can be done to avoid or mitigate such effects. Its implementation rests on accepting recreational fishing as a principally legitimate activity. The second approach to fish welfare focuses on suffering and pain in fishes and is usually morally prescriptive. Its central tenet is that some or all recreational fishing practices may be unacceptable unless sufficient benefits to humans are created, which justify the supposedly cruel treatment of the fishes. The pragmatic approach to fish welfare is preferred because it relies on objectively measurable variables of impaired fish welfare (e.g. physiological, behavioural or fitness indicators) and does not question recreational fishing on moral grounds. Contrary to a suffering-centred approach to fish welfare, a pragmatic perspective emphasizes positive messages and facilitates constructive dialogue among stakeholders. In contrast, a suffering-centred approach to fish welfare tends to promote tension and enduring conflict that cannot be reconciled objectively and thus should be avoided. PMID- 20738502 TI - Stable-isotope comparisons between embryos and mothers of a placentatrophic shark species. AB - Stable nitrogen (delta(15)N) and carbon (delta(13)C) isotopes of Atlantic sharpnose shark Rhizoprionodon terraenovae embryos and mothers were analysed. Embryos were generally enriched in (15)N in all studied tissue relative to their mothers' tissue, with mean differences between mother and embryo delta(15)N (i.e. Deltadelta(15)N) being 1.4 per thousand for muscle, 1.7 per thousand for liver and 1.1 per thousand for cartilage. Embryo muscle and liver were enriched in (13)C (both Deltadelta(13)C means = 1.5 per thousand) and embryo cartilage was depleted (Deltadelta(13)C mean = -1.01 per thousand) relative to corresponding maternal tissues. While differences in delta(15)N and delta(13)C between mothers and their embryos were significant, muscle delta(15)N values indicated embryos to be within the range of values expected if they occupied a similar trophic position as their respective mothers. Positive linear relationships existed between embryo total length (L(T)) and Deltadelta(15)N for muscle and liver and embryo L(T) and Deltadelta(13)C for muscle, with those associations possibly resulting from physiological differences between smaller and larger embryos or differences associated with the known embryonic nutrition shift (yolk feeding to placental feeding) that occurs during the gestation of this placentatrophic species. Together these results suggest that at birth, the delta(15)N and delta(13)C values of R. terraenovae are likely higher than somewhat older neonates whose postpartum feeding habits have restructured their isotope profiles to reflect their postembryonic diet. PMID- 20738503 TI - Diet and reproduction in the Australian butterfly ray Gymnura australis from northern and north-eastern Australia. AB - The diet of Gymnura australis was dominated by teleosts (99.8% index of relative importance). A wide-ranging species, females matured at 446 mm disc width (W(D)), had a single functional ovary and two functional uteri. Males matured at 377 mm W(D) and had a single functional testis. PMID- 20738504 TI - Validated annual band-pair periodicity and growth parameters of blue-spotted maskray Neotrygon kuhlii from south-east Queensland, Australia. AB - Age and growth parameters were derived for blue-spotted maskray Neotrygon kuhlii from Moreton Bay in subtropical eastern Australia. Maximum age estimates of 13 and 10 years were obtained from female (n = 76) and male (n = 44) N. kuhlii, respectively. Estimated ages at maturity for 50% of females and males were 6.32 and 3.95 years, respectively. A three-parameter power function provided the best statistical fit to size at age data in both sexes, providing parameter estimates of y(0) = 163.13, a = 58.52 and b = 0.58 for females and y(0) = 165.13, a = 59.02 and b = 0.54 in males. The two-parameter von Bertalanffy growth function was used to estimate biological parameters based on disc width (W(D)) for both female (W(Dinfinity) = 465.81 mm, K = 0.13 year(-1), b = 0.63) and male N. kuhlii (W(Dinfinity) = 385.19 mm, K = 0.20 year(-1), b = 0.54). Annual band-pair deposition was observed in three calcein-injected N. kuhlii after periods of liberty ranging from 631 to 1081 days. Centrum edge analysis indicated that annual band-pair formation was generally consistent within this population, with translucent bands formed over spring and summer and opaque bands formed in autumn and winter. Individual growth rates obtained from tagged specimens were similar to power function growth predictions. These results support previous characterizations of this common trawl by-catch species as comparatively resilient to non-targeted catches, although higher catch rates outside Australia infer a need for cautious management. PMID- 20738505 TI - Small-scale demographic variation in the stoplight parrotfish Sparisoma viride. AB - Age-based analysis of the stoplight parrotfish Sparisoma viride was used to examine whether observed differences in their abundance and size structure among reefs in a cross-shelf portion of the upper Florida Keys could be explained by variation in demographic rates. Annual and daily sagittal otolith increments were enumerated for 176 individuals collected from replicates of reefs in two strata, inshore and offshore reefs (2-6 m depth). von Bertalanffy growth functions fitted to size-at-age plots for each site were similar between reefs within each stratum (inshore and offshore), but differed between strata. Sparisoma viride on offshore reefs attained greater average standard length (L(S)) at age, greater mean asymptotic size and were longer lived than fish from inshore reefs. Fish on inshore reefs attained only half the maximum age observed on offshore reefs (4 v. 8 years, respectively). No terminal phase fish >4 years of age were found on either reef type. Estimates of mortality rates from age-frequency data of collected fish revealed higher mortality on inshore reefs. Demographic variables obtained in this study were similar to published values for S. viride from Caribbean reefs but differed significantly from published values from reefs at a similar latitude (Bahamas), reflecting high demographic plasticity on both local and regional scales. PMID- 20738506 TI - Life-history characteristics of the large Amazonian migratory catfish Brachyplatystoma rousseauxii in the Iquitos region, Peru. AB - The main life-history traits of the dorado Brachyplatystoma rousseauxii, a large Amazonian catfish undertaking the largest migration known for a freshwater fish species (from the nursery area in the estuary of the Amazon to the breeding zones in the head waters of the western Amazon basin close to the Andes), were determined from a 5 year sampling of >15,000 specimens in the Peruvian Amazon. The breeding season occurred during the falling and low-water periods, which is hypothesized to be an adaptation to maximize the chances of young stages to reach the estuary. The size at first sexual maturity was slightly larger for females than males, c. 91 and 83 cm standard length (L(S)), respectively. Both males and females reproduce for the first time at >3 years old. The fecundity per spawning event ranged from 481,734 to 1,045,284 oocytes for females weighing 25 and 34 kg, respectively. Seasonal variations of body condition were similar among sexes, but differed between immature specimens that had a higher condition during the low water period and lower condition during rising waters, and mature individuals that showed the opposite pattern. The growth characteristics were estimated by L(S) frequency analysis. For females, the best fitting models gave a mean birth date in August, during the height of the breeding cycle, with the following von Bertalanffy growth function parameters: L(Sinfinity) = 153.3, K = 0.29 and t(0) = 0.37 years. For males, the best fitting model gave a mean birth date in July, also during the height of the breeding period, with L(Sinfinity) = 142, K = 0.30 and t(0) =- 0.36 years. At a given age, females were systematically larger than males and the size difference increased with age. The largest females sampled (148 cm L(S)) was 11 years old and the largest male (134 cm L(S)) was 9 years old. The mortality estimates were higher for males total (Z) = 1.34, natural (M) = 0.52 and fishing (F) = 0.82 than for females (Z = 0.98, M = 0.50, F = 0.48). The life-history patterns of B. rousseauxii are discussed in light of the available knowledge about this species and the understanding of its complex life cycle. PMID- 20738507 TI - Characterization of an Atlantic salmon Salmo salar stream at the southern limit of its eastern Atlantic distribution. AB - Ten reaches of an Atlantic stream located in north-west Spain were sampled intensively during one summer to characterize the conditions where Atlantic salmon Salmo salar have been re-introduced along the stream. Fish species richness and diversity showed a downstream increase, which was mainly attributed to the higher number of cyprinid species found in the lower reaches. Moreover, except for brown trout Salmo trutta that appeared to be the most ubiquitous species, the densities of the other species was higher in the lower than in the upper stream reaches. Redundancy analysis showed that the pattern of fish assemblages observed along the studied stream was mainly related to the expected gradient observed in the levels of dissolved oxygen, discharge and mean current speed. There was a significant differentiation between midstream and downstream reaches, both in terms of the composition of their fish assemblages and the freshwater habitat. This study emphasizes the importance of describing the variations in fish assemblages and habitat characteristics along a river to explore its relation to potential changes in the survival of fish populations. In particular, the development of habitat-fish relationships may be a useful tool for water managers to assess the effects of development and restoration projects on the habitat of S. salar. PMID- 20738508 TI - Captive hybridization of two geographically isolated pygmy angelfish species, Centropyge fisheri and Centropyge resplendens. AB - This study documents the rearing of two pygmy angelfish species, Centropyge fisheri and Centropyge resplendens, and the early life history and reproduction of their hybrid offspring. A C. fisheri female, collected from Hawaii, and a C. resplendens male, captive-bred from parental stock collected from Ascension Island, were maintained at the hatchery facility for 7 months. Continuous spawning was achieved at a photoperiod cycle of 14L:10D and a water temperature of 26.5 degrees C, range +/-1 degrees C. Over the 110 day period, the C. fisheri female spawned 102 times, 57% of which resulted in embryos (fertilized eggs). The mean +/-s.d. fecundity per spawn was 730 +/- 459 eggs (range 52-1967). Fertility (% eggs that developed into embryos) of all eggs that were preserved was 22.4 +/- 25.6%. A total of 235 hybrid juveniles were raised through metamorphosis with an average larval survival of 16.4%. Eight F(1) hybrid juveniles isolated for further study began to display signs of reproductive behaviour c. 300 days post hatch (dph). Spawn resulting in non-fertile eggs were first obtained 319 dph, and fertilized eggs developing into embryos were obtained after 411 dph from at least two female individuals. While no attempt was made at rearing the F(2) larvae, embryo and larval development were normal up to 8 dph. Reproduction and development observed for all hybrid generations in this study were normal, similar to other Centropyge species and indicates a very close phylogenetic relationship between what are currently considered distinct species, e.g. C. fisheri and C. resplendens. PMID- 20738509 TI - Food partitioning and spatial subsidy in shelter-limited fishes inhabiting patchy reefs of Patagonia. AB - The diets of the most conspicuous reef-fish species from northern Patagonia, the carnivorous species Pseudopercis semifasciata, Acanthistius patachonicus, Pinguipes brasilianus and Sebastes oculatus were studied. Pinguipes brasilianus had the narrowest diet and most specialized feeding strategy, preying mostly on reef-dwelling organisms such as sea urchins, limpets, bivalves, crabs and polychaetes. The diet of A. patachonicus was characterized by the presence of reef and soft-bottom benthic organisms, mainly polychaetes, crabs and fishes. Pseudopercis semifasciata showed the broadest spectrum of prey items, preying upon reef, soft-bottom and transient organism (mainly fishes, cephalopods and crabs). All S. oculatus guts were empty, but stable-isotope analyses suggested that this species consumed small fishes and crabs. In general, P. brasilianus depended on local prey populations and ate different reef-dwelling prey than the other species. Pseudopercis semifasciata, A. patachonicus and probably S. oculatus, however, had overlapping trophic niches and consumed resources from adjacent environments. The latter probably reduces the importance of food as a limiting resource for these reef-fish populations, facilitating their coexistence in spite of their high trophic overlap. PMID- 20738510 TI - Otolith chemistry of prey fish consumed by a fish predator: does digestion hinder Russian doll techniques? AB - The effect of digestion by a predatory fish (largemouth bass Micropterus salmoides) on stable isotopic (delta(13)C and delta(18)O) and trace elemental (Sr:Ca and Ba:Ca) compositions of prey fish (bluegill Lepomis macrochirus) otoliths was investigated in a laboratory experiment. Trace element and stable isotopic signatures of L. macrochirus otoliths were not significantly altered for up to 16 h after L. macrochirus were consumed by M. salmoides. Prey fish otoliths recovered from predator digesta can retain environmental stable isotopic and trace elemental signatures, suggesting that determination of environmental history for prey fishes by stable-isotope and trace-element analysis of otoliths recovered from stomachs of piscivorous fishes will be feasible. PMID- 20738511 TI - New species of Moenkhausia Eigenmann (Characiformes: Characidae) from Rio Xingu and Rio Tapajos basins, Brazil, with comments on a putative case of polymorphic Batesian mimicry. AB - A new species of Moenkhausia is described from Rio Xingu and Rio Tapajos basins, Brazil. The new species is distinguished from its congeners, except from Moenkhausia moisae, by having more scales in the lateral series, 43-47 (v. 23-41 in the remaining congeners). The new species is distinguished from M. moisae by its colour pattern, which consists of a dark midlateral stripe, and an asymmetrical caudal blotch (inconspicuous or faded in specimens from the Rio Arinos) continuous with the midlateral stripe (v. narrow dark midlateral line and conspicuous, regularly rounded and symmetrical blotch not continuous with the midlateral line). The new species is putatively assumed to be mimetic to Jupiaba apenima, in the Rio Xingu and Rio Teles Pires drainages, and to Jupiaba yarina in the Rio Arinos. The two species of Jupiaba are sympatric and remarkably similar in size, general external morphology and colouration to the new species. A small difference occurs in the colouration between the two species of Jupiaba and is also observed in the two respectively sympatric morphotypes of the new species of Moenkhausia. The occurrence of polymorphic Batesian mimicry is therefore discussed for neotropical freshwater fishes. PMID- 20738512 TI - Post-release predation on hatchery-reared Japanese flounder Paralichthys olivaceus in the coast of Fukushima, Japan. AB - To determine the predators of 100 mm total length hatchery-reared juvenile Japanese flounder Paralichthys olivaceus, fishes and crabs were collected using gillnets and a small trawl net off the coast of Fukushima Prefecture, Japan. Predation on juvenile P. olivaceus by older conspecifics, the snailfish Liparis tanakai, ocellate spot skate Okamejei kenojei and the swimming crab Ovalipes punctatus, was detected based on analogical observation and molecular techniques. These predators are nocturnal feeders except for P. olivaceus. Liparis tanakai with body sizes large enough to consume juveniles only appeared in winter, whereas the large O. punctatus was abundant in early summer and in late autumn. Such seasonal variation in predator abundance indicates that the release season can be optimized for reducing predation mortality. PMID- 20738513 TI - Temporal dynamics of epidermal responses of guppies Poecilia reticulata to a sublethal range of waterborne zinc concentrations. AB - This study assessed the histological changes in the epidermis of guppies Poecilia reticulata induced by waterborne zinc (Zn). Laboratory-reared P. reticulata fry were maintained individually in separate vessels containing artificial water (8 microg l(-1) Zn) to which 0, 15, 30, 60 or 120 microg l(-1) Zn was added. Their epidermal response to Zn was monitored regularly over 4 weeks. Compared with controls, mucus was rapidly released and mucous cell numbers decreased at all concentrations. Thereafter mucous release, epidermal thickness, numbers and size of mucous cells fluctuated at a rate that varied with Zn concentration, but fluctuations declined after day 18. Results clearly highlight the dynamic nature of the epidermal response to sublethal concentrations of waterborne Zn. In general, low concentrations of Zn induced a rapid response with reduced numbers and size of mucous cells and shift in mucin composition, and a subsequent thickening of the epidermis. Epidermal thickness and mucous cell area fluctuated over time but were normal after a month of exposure to low Zn concentrations. The number of mucous cells, however, remained low. Virtually all mucous cells from fish maintained in 15 and 60 microg l(-1) Zn contained acidic mucins throughout the month, whereas fish maintained at 30 microg l(-1) Zn responded by production of neutral mucins during the first 12 days followed by a mixture of neutral and acidic mucins. At 120 microg l(-1) Zn, the most dramatic effects were the gradual but sustained decrease in numbers and area of mucous cells, and the shift to acidic mucins in these cells. Thus, as concentration of Zn increased, the epidermal responses indicated a disturbed host response (dramatic decline in mucous cell numbers, with mixed composition of mucins), which may have been less effective in preventing Zn uptake across the epithelium. PMID- 20738514 TI - Older triploid fish retain impaired reproductive endocrinology in the European sea bass Dicentrarchus labrax. AB - This paper reports on an evaluation of growth, gonadal development and reproductive endocrinology of older triploid (3n) European sea bass Dicentrarchus labrax in comparison with their diploid (2n) counterparts throughout their fifth and seventh annual cycle of life. While older triploids retained impaired reproductive endocrinology, a sexually related dimorphic growth was observed with 3n females attaining the largest sizes. Comparisons of some body indexes showed that 3n females had a significantly lower hepato-somatic index (I(H)) than 2n females but a significantly higher viscero-somatic index (I(F)). In contrast, both male and female triploids showed significantly lower gonado-somatic index (I(G)) than diploids. Accordingly, diploids produced mature gametes but triploids did not, demonstrating that despite the longer time given to triploids for gonadal development, they could not reproduce. Furthermore, older triploids had lower levels of plasma sex steroids (testosterone, T; 11-ketotestosterone, 11-KT and oestradiol-17beta, E(2)) and luteinizing hormone (LH) than their 2n counterparts with 3n females showing drastic effects of triploidization on their reproductive endocrinology. Vitellogenin (VTG) was undetectable in 3n females. Gonadal content of steroid hormones and Sparus aurata-type gonadotropin-releasing hormone (sbGnRH) in the brain and pituitary were also lower in triploids compared with diploids. These results suggest that older 3n D. labrax retain functional sterility in both sexes, and 3n females might reach larger sizes than 3n males and their 2n counterparts in this species. PMID- 20738515 TI - Courtship and spawning sounds in bird wrasse Gomphosus varius and saddle wrasse Thalassoma duperrey. AB - Acoustic signals from the bird wrasse Gomphosus varius and saddle wrasse Thalassoma duperrey were recorded on coral reefs in Hawaii. Terminal phase males in both species emit two types of pulse trains (type I and type II). Type I pulses were produced during spawning and courtship, while type II pulses were associated only with courtship behaviours. Gomphosus varius type I pulses were of lower frequency than T. duperrey type I pulses (271 v. 840 Hz) and were of narrower band. Discriminant function analyses revealed interspecific differences between type I pulse trains and individual pulses of both types. This study is the first documentation of courtship and spawning sounds in sympatric labrids and shows divergence in acoustic signals. PMID- 20738516 TI - Cytotaxonomy in distinct populations of Hoplias aff. malabaricus (Characiformes, Erythrinidae) from lower Paranapanema River basin. AB - Cytogenetic and morphometric analyses were carried out in Hoplias aff. malabaricus specimens from six distinct populations from the lower Paranapanema River basin, located between the states of Parana and Sao Paulo, Brazil. Measurements were also taken from a specimen collected in Surinam. In a population from a fish farm station at Universidade do Norte do Parana (EPUNOPAR), two sympatric cytotypes (2n = 40 and 2n = 42 chromosomes) are found. A population from a fish farm station at Universidade Estadual de Londrina (EPUEL) shows 2n = 42 meta-submetacentric chromosomes for males and females with a simple sex chromosome system of XX/XY type. Populations from the Vermelho and Rancho Alegre Rivers, Tres Bocas Stream and Paranapanema River have 2n = 39 chromosomes in males and 2n = 40 chromosomes in females, showing a multiple sex chromosome system of X(1)X(1)X(2)X(2)/X(1)X(2)Y type. Twenty morphological variables were studied. These measurements were used for an analysis of the canonical variables and standard analysis of proportional measurements. The most variable measurements among the specimens are the maxilla length (MXL) and the pre-dorsal distance (PDD). Analysis of canonical variables indicates three distinct groups in the first canonical axis formed by: (1) Tres Bocas Stream, (2) Rancho Alegre + Vermelho River + EPUNOPAR and (3) EPUEL + Paranapanema River. This axis retained 79.4% of information from the original matrix. Analysis of morphometrics reveals differences among populations from the Paranapanema River basin and between these and the specimen from Surinam. The morphometric and cytogenetic differences among the studied populations suggest a species complex. PMID- 20738517 TI - Digestive capacities, inbreeding and growth capacities in juvenile Arctic charr Salvelinus alpinus. AB - Genetic variation in growth performance was estimated in 26 families from two commercial strains of Arctic charr Salvelinus alpinus. Physiological determinants of growth and metabolic capacities were also assessed through enzymatic assays. A relatedness coefficient was attributed to each family using parental genotypes at seven microsatellite loci. After 15 months of growth, faster growing families had significantly lower relatedness coefficients than slower growing families, suggesting their value as indicators of growth potential. Individual fish that exhibited higher trypsin activity also displayed higher growth rate, suggesting that superior protein digestion capacities can be highly advantageous at early stages. Capacities to use amino acids as expressed by glutamate dehydrogenase (GDH) activities were lower in the liver of fast-growing fish (13-20%), whereas white muscle of fast-growing fish showed higher activities than that of slow growing fish for amino acid metabolism and aerobic capacity [22-32% increase for citrate synthase (CS), aspartate aminotransferase (AAT) and GDH]. The generally higher glycolytic capacities (PK and LDH) in white muscle of fast-growing fish indicated higher burst swimming capacities and hence better access to food. PMID- 20738518 TI - Do otolith annular structures correspond to the first freshwater entry for yellow European eels Anguilla anguilla in the Baltic countries? AB - To examine the relationship between freshwater entry and otolith annular structures, a total of 113 naturally recruited European eels Anguilla anguilla from Lithuania and Latvia that entered fresh water at least once were collected. In some individuals (8.3-11.3%), the first freshwater entry coincided with a dark check that was distinctly different from neighbouring annuli. In most individuals (81.7-84.9%), the first freshwater entry occurred on rings and increments indistinguishable from other annuli. For the remaining individuals (3.8-10%), the first freshwater entry did not correspond to any otolith ring, band or annulus. According to recent evidence, the observed high correspondence between the first freshwater entry and otolith annuli was more likely due to the movement into fresh water during winter when the annulus was deposited, rather than stress resulting from habitat change. Consequently, the age estimation based on otoliths might be less influenced by this habitat change during the yellow eel stage. PMID- 20738519 TI - Fluctuating asymmetry and fitness correlations in two Engraulis encrasicolus populations. AB - Correlations among several measures of fluctuating asymmetry (FA) and fitness related variables were assessed in two populations of the European anchovy Engraulis encrasicolus with fast growth (Aegean Sea) and slow growth (Ionian Sea), respectively. FA levels were borderline significantly higher in the Ionian than in the Aegean for some variables. Variation in otolith shape (deviation from population norm) was lower in the Ionian than the Aegean, contrary to expectation. Within the Aegean, there was no relation between any of the FA indexes and fitness estimators, while in the Ionian a composite otolith FA index was significantly negatively correlated to standard length at age only in 2 year old individuals. This difference between the Aegean and Ionian may have been related to the lower growth rate in the Ionian, as FA-fitness relations may be more apparent in less-beneficial environments. The absence of significant correlations in the Aegean and the low correlation in one age group in the Ionian suggests that FA is not a sensitive indicator of individual fitness in adult E. encrasicolus. PMID- 20738520 TI - Effects of angling on post-release mortality, gonadal development and somatic condition of Australian bass Macquaria novemaculeata. AB - This study assessed the protracted effects of two angling treatments (mild and harsh) on the post-release mortality, gonadal development and somatic condition of Australian bass Macquaria novemaculeata in a pond-based experiment. Angled fish were destructively sampled (along with controls) three times: immediately before, and 1 or 4 weeks after release into cages. Compared with the other groups, harshly angled fish had similar, low immediate and short-term mortalities (< or =5%), but significant delayed mortality (25%) and fed only minimally. None of these fish ejected ingested hooks. Forty-six per cent of captive fish (across all groups) and 20% of wild fish had non-ripening gonads (stage I) prior to, or during, the experiment. In females with ripening ovaries (stages II or III), neither angling treatment significantly reduced standardized gonadal mass. The mean per cent of atretic oocytes increased among females in all groups, but was significantly greater in those that were harshly angled. The results demonstrated that the gonadal development of M. novemaculeata could be suppressed or impaired (by angling, handling and confinement), and that further research is warranted. In particular, the timing and severity of angling in relation to the stage of gonadal development could have important implications for the introduction of temporal restrictions to angling. PMID- 20738521 TI - Morphological differences between two ecologically similar sympatric fishes. AB - Morphological differentiation and microhabitat segregation of two ecologically similar populations of pelagic planktivorous fishes, Coregonus albula and the smaller Coregonus fontanae, were studied in Lake Stechlin (northern Germany). Both populations performed diel vertical migrations, although C. fontanae was always situated in deeper pelagic water than C. albula both during day and night. Landmark-based geometric morphometrics revealed that sympatric C. albula and C. fontanae differ in external morphology, with main differences found in head length and eye position, as well as in length and width of the caudal peduncle. Moreover, while C. albula has a similar morphology over all sizes, the shape of C. fontanae changes with size. Accordingly, the morphology of the two is most different at smaller size. Although the morphological differences may reflect adaptations to the slightly differing microhabitats of the two populations, there is no conclusive evidence that this correspondence between ecology and morphology is the main mechanism behind the coexistence of the closely related coregonids in Lake Stechlin. PMID- 20738522 TI - Field hearing measurements of the Atlantic sharpnose shark Rhizoprionodon terraenovae. AB - Field measurements of hearing thresholds were obtained from the Atlantic sharpnose shark Rhizoprionodon terraenovae using the auditory evoked potential method (AEP). The fish had most sensitive hearing at 20 Hz, the lowest frequency tested, with decreasing sensitivity at higher frequencies. Hearing thresholds were lower than AEP thresholds previously measured for the nurse shark Ginglymostoma cirratum and yellow stingray Urobatis jamaicensis at frequencies <200 Hz, and similar at 200 Hz and above. Rhizoprionodon terraenovae represents the closest comparison in terms of pelagic lifestyle to the sharks which have been observed in acoustic field attraction experiments. The sound pressure levels that would be equivalent to the particle acceleration thresholds of R. terraenovae were much higher than the sound levels which attracted closely related sharks suggesting a discrepancy between the hearing threshold experiments and the field attraction experiments. PMID- 20738523 TI - Female ornamentation and egg carotenoids of six sympatric gobies. AB - Belly colouration, gonad carotenoid concentration and skin transparency were quantified in gravid Gobiusculus flavescens, as well as in females of five sympatric gobies where belly ornamentation has not been described. Although G. flavescens females did, indeed, have far more colourful bellies than the other species, this could only in part be explained by a high concentration of total gonad carotenoids. Comparable, or occasionally higher, carotenoid levels were found in the gonads of other species. Instead, the unusual ornamentation of G. flavescens arises from a unique combination of carotenoid-rich gonads and a highly transparent abdominal skin. PMID- 20738524 TI - Age validation and variation in growth, mortality and population structure of Liza argentea and Myxus elongatus (Mugilidae) in two temperate Australian estuaries. AB - This study investigated variation in the rates of growth and mortality, and age and fork-length (L(F)) compositions of two exploited species of Mugilidae, Liza argentea and Myxus elongatus, in two south-east Australian estuaries (Lake Macquarie and St Georges Basin). An ageing protocol was developed by counting opaque growth zones on sectioned otoliths which was validated by periodically examining the otoliths of captive-reared young-of-the-year fishes, and marginal increment analysis of wild fishes. The maximum recorded age was 17 years for L. argentea and 12 years for M. elongatus, which is greater than generally observed in other species of mugilids. Growth models of each species significantly differed between sexes and, except for male L. argentea, between estuaries. Fishes from Lake Macquarie generally had a greater mean L(F) at age than those from St Georges Basin and females of both species generally attained a greater maximum L(F) and age than males. Gillnet catches of L. argentea were of similar L(F) and age compositions in both estuaries, whereas the age composition of catches of M. elongatus in Lake Macquarie contained a greater proportion of younger fish. Estimates of total, natural and fishing mortality were greater for M. elongatus than L. argentea across both estuaries, and estimates of total mortality were greatest for both species in Lake Macquarie. The data indicate that neither species has been overfished in these estuaries. PMID- 20738525 TI - Morphological characters and occurrence patterns of juveniles of two estuarine gobies, Acentrogobius kranjiensis and Acentrogobius malayanus, verified by molecular identification. AB - Juveniles of two Acentrogobius species collected in a mangrove estuary in Sikao Creek, southern Thailand, were identified by morphological and molecular methods. A total of 1315 Acentrogobius specimens were collected and grouped into types A (n = 1107, 4.4-12.0 mm standard length, L(S)) (melanophore absent or indistinct on posterodorsal contour of caudal peduncle; two rows of melanophore blotches on lateral midline) and B (n = 208, 4.8-12.6 mm L(S)) (distinct melanophore on posterodorsal contour of caudal peduncle; a single row of melanophore blotches on lateral midline). Based on the reverse series method, the melanophore patterns of larger juveniles were linked with the smallest specimens possessing adult characters. The homogeneities of mitochondrial cytochrome b region sequences between the two juvenile types and adult Acentrogobius species collected in the study area indicated type A to be A. kranjiensis (homogeneity between type A and A. kranjiensis: 99.3-100%), and type B to be A. malayanus (homogeneity between latter 98.1 and 99.7%). No Acentrogobius juveniles were collected from the surf zone outside the creek mouth, both species apparently spending most of their life histories within the estuarine habitat. During their pelagic phase, A. kranjiensis and A. malayanus dispersed in the upper, middle and lower reaches of the creek. On the other hand, occurrence patterns during the benthic phase of A. kranjiensis and A. malayanus differed, the former showing upstream movement and the latter downstream movement with growth. These results emphasize the necessity of analysing early fish life histories at the species level, and the collaboration between morphological and molecular methods should prove valuable in accurately identifying of larvae and juveniles. PMID- 20738526 TI - Size-dependent growth of individual Atlantic salmon Salmo salar alevins from hatch to first feeding. AB - Variation in egg size, hatch timing and size at hatch, and their influence on individual growth rates of Atlantic salmon Salmo salar alevins up to first feeding were examined in pure strain and hybrid crosses of fish from Scotland and Canada. At the intra-female, intra-cross type and inter-cross type levels, specific growth rates prior to first feed were strongly size dependent, with smaller and later hatching alevins growing significantly faster. The magnitude of this size-dependent growth was greatest in the hybrid crosses. This resulted in a 40% reduction in the coefficient of variation (c.v.) in alevin size from post hatch to first feeding at the intra-female level, and a reduction of both intra- and inter-cross differences in alevin sizes in the same period. PMID- 20738527 TI - Age and size at sexual maturity of the smooth skate Malacoraja senta from the western Gulf of Maine. AB - Age and size at sexual maturity was determined for 185 male and 96 female smooth skates Malacoraja senta (ranging in size from 370 to 680 mm total length L(T)), collected from the western Gulf of Maine. Maturity ogives for males, based on clasper length, testis mass and the proportion of mature spermatocysts in the testes, suggest that 50% maturity occurs between 9 and 10 years and 560 mm L(T). Maturity ogives for females, based on ovary mass, shell-gland mass and maximum follicle size, suggest that 50% maturity occurs at age 9 years and 540 mm L(T). PMID- 20738528 TI - Gill-filament ossifications: a possible morphological synapomorphy uniting the families Balitoridae and Cobitidae (Ostariophysi: Cypriniformes). AB - Ossifications associated with the gill filaments of members of the Balitoridae and Cobitidae are described for the first time. Although gill-filament ossifications are common in teleosts, similar ossifications were not observed in other members of the order Cypriniformes. Their presence is interpreted as a shared and derived character uniting the families Balitoridae and Cobitidae as a monophyletic group. PMID- 20738529 TI - Sea-run migratory behaviour in the Japan Sea form of three-spined stickleback Gasterosteus aculeatus in the tidal pool of eastern Hokkaido Island, Japan. AB - Juveniles in the Japan Sea form of three-spined stickleback Gasterosteus aculeatus collected from a tidal pool in eastern Hokkaido Island, Japan, had a unimodal standard length (L(S)) frequency distribution in each period, ranging from 11.9 to 31.6 mm, and those of sea-run migrating individuals collected from the outlet of this tidal pool ranged from 17.0 to 36.0 mm, suggesting juveniles of this form would migrate towards the sea when they reached >17.0 mm. In general linear models (GLM) for testing the best model, there was a relationship between the number of sea-run migratory individual and precipitation, which suggests that precipitation may trigger migration. PMID- 20738530 TI - Introduction to papers on fish welfare in commercial fisheries. PMID- 20738531 TI - Welfare in wild-capture marine fisheries. AB - In contrast to terrestrial farming or aquaculture, little, if any, welfare regulation exists that constrains how fishes are handled or killed in wild capture marine fisheries. Given that welfare in wild-capture fisheries is moving further up the public agenda, an unbiased, dispassionate account of what happens to fishes caught in wild-capture marine fisheries is needed so as to identify where the main animal welfare issues exist. PMID- 20738532 TI - Taking account of fish welfare: lessons from aquaculture. AB - This paper explores the possibility that lessons learned from aquaculture might contribute to current debate on welfare and fisheries. After looking briefly at the history of research interest in the welfare of farmed fishes, some implications of using different definitions of and approaches to the concept of welfare are discussed. Consideration is given to the way in which the aquaculture industry has responded to public concern about fish welfare and, for cases where these responses have been effective, why this might be the case. Finally, possible cross-over points between aquaculture and fisheries in the context of fish welfare, as well as experience and expertise that might be shared between these two areas, are identified. PMID- 20738533 TI - Balancing the needs and preferences of humans against concerns for fishes: how to handle the emerging ethical discussions regarding capture fisheries? AB - How can stakeholders within the fisheries community engage in constructive ethical discussions? Drawing on experiences from previous debates surrounding the human use of animals, this paper presents a proactive approach whereby stakeholders can create a framework for ethical discussion of capture fisheries. PMID- 20738534 TI - The ethics of fish welfare. AB - The topic of fish welfare in the context of commercial fisheries is a difficult one. From traditionally anthropocentric or human-centred perspectives, fishes are simply objects for humans to use as they see fit. When it is argued that anthropocentrism is arbitrary, it may appear that a strong animal rights position is the only recourse, with the result that humans ought not to use animals in the first place, if it is at all possible. It can be argued that both positions fail to view human beings as part of the natural world. If human beings are viewed as part of the world from which they live, then it has to be asked what it means to be respectful of the animals which humans use and from which they live. From this perspective, concern for the welfare of the fishes humans eat is simply what should be expected from humans as good citizens in the community of living creatures. PMID- 20738540 TI - Population genetics and management units of invasive common carp Cyprinus carpio in the Murray-Darling Basin, Australia. AB - Common carp Cyprinus carpio were introduced into Australia on several occasions and are now the dominant fish in the Murray-Darling Basin (MDB), the continent's largest river system. In this study, variability at 14 microsatellite loci was examined in C. carpio (n = 1037) from 34 sites throughout the major rivers in the MDB, from 3 cultured populations, from Prospect Reservoir in the Sydney Basin and from Lake Sorrell in Tasmania. Consistent with previous studies, assignment testing indicated that the Boolara, Yanco and koi strains of C. carpio are present in the MDB. Unique to this study, however, the Prospect strain was widely distributed throughout the MDB. Significant genetic structuring of populations (Fisher's exact test, AMOVA and distribution of the different strains) amongst the MDB sub-drainages was detected, and was strongly associated with contemporary barriers to dispersal and population history. The distributions of the strains were used to infer the history of introduction and spread of C. carpio in the MDB. Fifteen management units are proposed for control programmes that have high levels of genetic diversity, contain multiple interbreeding strains and show no evidence of founder effects or recent population bottlenecks. PMID- 20738541 TI - Genetic evidence of two stocks of the whitemouth croaker Micropogonias furnieri in the Rio de la Plata and oceanic front in Uruguay. AB - Analysis of the mitochondrial DNA control region resolved two stocks of whitemouth croaker Micropogonias furnieri in Uruguayan waters, one in the Rio de la Plata and the other on the Uruguayan shelf. The whitemouth croaker is the most important coastal fishery resource along the coast and has the greatest commercial importance in the Rio de la Plata and its oceanic front. The number of pair-wise differences (pi) and haplotype diversity (h) showed significant differences between the two regions. Frequencies of mtDNA haplotypes did not differ between Rio de la Plata from Bahia Blanca M. furnieri. Samples from the oceanic front showed greater genetic variability and a larger effective number of females that were an order of magnitude larger than that in Rio de la Plata. Mismatch distributions showed evidence of a recent population expansion in the oceanic region, beginning c. 40,000 b.p. The presence of two stocks of the M. furnieri in the study area should be considered in the management of this species' fishery. PMID- 20738542 TI - Matrilinear phylogeography and demographical patterns of Rutilus rutilus: implications for taxonomy and conservation. AB - A phylogeographic analysis of mitochondrial DNA sequence variation was carried out to infer the geographical distribution of the genealogical lineages and the historical demography of roach Rutilus rutilus (L.). A total of 265 individuals from 52 sites covering most of the Eurasian distribution range were sequenced for a 475 bp fragment of the mitochondrial cytochrome b gene. The monophyletic roach contained two deep clades that dated back to the Pliocene. The Ponto-Caspian clade comprised populations from Greece to Siberia with a likely palaeorefugium at the west coast of the Caspian Sea. This clade largely corresponds to individuals with morphological features described as Rutilus heckelii. The west European clade included individuals from central and western Europe with the Danube and Dniester basins as possible palaeorefugia. This clade largely corresponds to individuals with morphological features described as R. rutilus. A suture-zone of the two main lineages was observed along the coastal region of the Black Sea. The neutrality tests and the mismatch distributions indicated a demographic expansion during the Middle-Pleistocene for both clades. PMID- 20738543 TI - Phylogeographical analysis of an estuarine fish, Salanx ariakensis (Osmeridae: Salanginae) in the north-western Pacific. AB - This study extended the geographic coverage of a previous study to explore population genetic structure and demographic history in the Ariake icefish Salanx ariakensis from three populations of continental coastlines and one island population in the north-western Pacific based on a partial sequence of the mitochondrial cytochrome b gene. The S. ariakensis showed high genetic diversity and strong genetic structure. Phylogenetic analysis showed a shallow gene tree with no clear phylogeographical structure. Contiguous range expansion and restricted gene flow were inferred to be main population events by nested-clade analysis. Significant genetic differentiations between populations could be attributable to negligible gene flow by coalescent analysis. High nucleotide diversity of each population was due to geographic mixing of heterogenous haplotypes during lowering sea levels of the Pleistocene. These findings indicate that cycles of geographic isolation and secondary contact happened in the Pleistocene glacial-interglacial cycles shaping genetic structure and population demography of S. ariakensis. PMID- 20738544 TI - Phylogeography and sympatric differentiation of the Arctic charr Salvelinus alpinus (L.) complex in Siberia as revealed by mtDNA sequence analysis. AB - Sequence variation in the mtDNA control region of Arctic charr Salvelinus alpinus and Dolly Varden Salvelinus malma from 56 Siberian and North American populations was analysed to assess their phylogeographic relationships and the origins of sympatric forms. Phylogenetic trees confirm the integrity of phylogroups reported in previous mtDNA studies except that the Siberian group does not separate as a single cluster. Haplotype network analysis indicates the proximity of Siberian and Atlantic haplotypes. These are considered as one Eurasian group represented by the Atlantic, east Siberian (interior Siberia including Transbaikalia, Taimyr) and Eurosiberian (Finland, Spitsbergen, Taimyr) sub-groups. Salvelinus alpinus with presumably introgressed Bering group (malma) haplotypes were found along eastern Siberian coasts up to the Olenek Bay and the Lena Delta region, where they overlap with the Eurasian group and in the easternmost interior region. It is proposed that Siberia was colonized by S. alpinus in two stages: from the west by the Eurasian group and later from the east by the Bering group. The high diversity of Eurasian group haplotypes in Siberia indicates its earlier colonization by S. alpinus as compared with the European Alps. This colonization was rapid, proceeded from a diverse gene pool, and was followed by differential survival of ancestral mtDNA lineages in different basins and regions, and local mutational events in isolated populations. The results presented here support a northern origin of Transbaikalian S. alpinus, the dispersion of S. alpinus to the Lake Baikal Basin from the Lena Basin, segregation of S. alpinus between Lena tributaries and their restricted migration over the divides between sub-basins. These results also support sympatric origin of intralacustrine forms of S. alpinus. PMID- 20738545 TI - Phylogeography of the flathead mullet Mugil cephalus in the north-west Pacific as inferred from the mtDNA control region. AB - The population genetic structure and historical demography of the flathead mullet Mugil cephalus were investigated using the mtDNA control region (CR) sequences (909-1015 bp) of 126 individuals collected from seven locations in the north-west Pacific between 2005 and 2007. Haplotype diversity (h = 0.9333-1.000) and nucleotide diversity (pi = 0.0046-0.1467) varied greatly among the sampling locations. Phylogenetic analysis of the CR sequences indicated that M. cephalus in the north-west Pacific belongs to two highly divergent lineages (lineages 1 and 2), with the inferred population structure being closely associated with the distribution of both lineages. Two populations were identified, one from the East China Sea and the other from the South China Sea. The former samples were obtained from Taiwan and Qingdao of north China and associated with lineage 1 haplotypes. The latter samples were collected from the Philippines, Pearl River of South China and two samples from Japan, all of which were associated with lineage 2. Japanese samples from Okinawa and Yokosuka had different degrees of mixing between lineages 1 and 2. Historical demographic variables in both populations indicated that Pleistocene glaciations had a strong impact on M. cephalus in the north-west Pacific, resulting in a recent demographic decline of the East China Sea population but in demographic equilibrium for the South China Sea population. Japan appears to be a contact zone between lineages 1 and 2, but it may also be indicative of coexistence between resident and migratory populations. Further global studies are required to clarify the taxonomic status of this cosmopolitan species. PMID- 20738546 TI - Chromosomal location and distribution of As51 satellite DNA in five species of the genus Astyanax (Teleostei, Characidae, Incertae sedis). AB - Constitutive heterochromatin makes up a substantial portion of the genome of eukaryotes and is composed mainly of satellite DNA repeating sequences in tandem. Some satellite DNAs may have been derived from transposable elements. These repetitive sequences represent a highly dynamic component of rapid evolution in genomes. Among the genus Astyanax, the As51 satellite DNA is found in species that have large distal heterochromatic blocks, which may be considered as derived from a transposable DNA element. In the present study, As51 satellite DNA was mapped through in situ fluorescent hybridization in the chromosomes of five species of the genus. The possible roles of this type of saltatory DNA type in the genome of the species are discussed, along with its use for the phylogenetic grouping of the genus Astyanax, together with other shared chromosomal characters. However, the number of As51 clusters is presented as a homoplastic characteristic, thereby indicating evident genomic diversification of species with this type of DNA. PMID- 20738547 TI - Microsatellite-centromere mapping in Cynoglossus semilaevis using gynogenetic diploid families produced by the use of homologous and non-homologous sperm. AB - Twenty-one microsatellite markers were studied in three meiogynogenetic families of Cynoglossus semilaevis gunther for centromere mapping using half-tetrad analysis. Among the 13 mapped loci, 10 were estimated to be located in the telomeric region, one in the centromeric region, and two in the intermediate region of the chromosome. This study provides a basis for constructing a linkage map of C. semilaevis. PMID- 20738548 TI - First record of the natural occurrence of hexaploid loach Misgurnus anguillicaudatus in Hubei Province, China. AB - Natural occurrence of hexaploid loach Misgurnus anguillicaudatus detected in central China is reported here for the first time. The evidences from karyotyping, DNA content analysis and nuclear volume measurements were described to confirm the hexaploid nature of the identified individual. PMID- 20738549 TI - Complex evolution of a highly conserved microsatellite locus in several fish species. AB - The evolutionary dynamics of a highly conserved microsatellite locus (Dla 11) were studied in several fish species. The data indicated that multiple types of compound microsatellites arose through point mutations that were sometimes followed by expansion of the derived motif. Furthermore, extensive length variation was detected among species in the regions immediately flanking the repeat region. PMID- 20738550 TI - An unusual ZZ/ZW sex chromosome system in Characidium fishes (Crenuchidae, Characiformes) with the presence of rDNA sites. AB - Characidium fishes with a sex chromosome system form a monophyletic group. This work presents data of Characidium lanei from the South Atlantic basin (Brazil), including an unknown type of ZW sex chromosome system for the groups including the presence of rDNA sites on sex chromosomes. PMID- 20738551 TI - The effects of anthropogenic sources of sound on fishes. AB - There is increasing concern about the effects of pile driving and other anthropogenic (human-generated) sound on fishes. Although there is a growing body of reports examining this issue, little of the work is found in the peer-reviewed literature. This review critically examines both the peer-reviewed and 'grey' literature, with the goal of determining what is known and not known about effects on fish. A companion piece provides an analysis of the available data and applies it to estimate noise exposure criteria for pile driving and other impulsive sounds. The critical literature review concludes that very little is known about effects of pile driving and other anthropogenic sounds on fishes, and that it is not yet possible to extrapolate from one experiment to other signal parameters of the same sound, to other types of sounds, to other effects, or to other species. PMID- 20738552 TI - Group cohesion in juvenile weakly electric fish Mormyrus rume proboscirostris. AB - The current study demonstrated that juvenile Mormyrus rume proboscirostris, an African freshwater weakly electric fish, used their active electrosense in group cohesion. Data also indicated that sight and mechano-reception could play a synergistic role in controlling this behaviour. The developmental change from a larval monophasic electric organ discharge to the adult biphasic waveform was accompanied by a reversal of the fish's social spacing. Light was aversive to social spacing in the younger fish (aged 49 and 65 days), but facilitated aggregation in the older fish (245 days). PMID- 20738553 TI - Post-settlement migratory behaviour and growth-related costs in two diadromous fish species, Galaxias maculatus and Galaxias brevipinnis. AB - The physiological challenges incurred during the transition from sea to fresh water and the constraints they place on the rate at which the common galaxiid Galaxias maculatus and the climbing galaxiid Galaxias brevipinnis can migrate from marine to freshwater habitats were examined. The duration of the marine to freshwater transition, the relationship between post-settlement age (PSA) and standard length (L(S)) as a proxy for energetic costs incurred during settlement and the potential effects of estuary geomorphology on migratory behaviour was investigated. Rate of upstream migration after settlement was not uniform. Upstream migration rate was slowest directly after settlement and increased with increasing PSA and distance from the river mouth, indicating a delay in upstream migration by newly recruited galaxiids. L(s) did not increase with age, at least within the first 21 days post settlement. These patterns were consistent for both species, in spite of differences in their life histories, across the recruitment season, despite seasonal variation in recruit size, and among estuaries with different properties. The results suggest that the timing and speed of migratory behaviour primarily reflect physiological constraints. Given the duration of residency of these species in estuaries, this study indicates that estuaries are critical transitional habitats for diadromous fishes during their migration from marine to freshwater habitats. PMID- 20738554 TI - Effects of egg size, parental origin and feeding conditions on growth of larval and juvenile cod Gadus morhua. AB - An experimental study was performed to disentangle parental and environmental effects on the growth of Atlantic cod Gadus morhua larvae and juveniles. Eggs were collected during the spawning season from spawning pairs (families) kept separately in specially designed spawning compartments. Newly hatched larvae were released simultaneously into two mesocosms of 2,500 and 4,400 m(3). Larval growth was monitored by sampling over a 10 week period, after which juveniles were transferred to on-growing tanks, where they were tagged and kept for up to 2 years. Maternal origin was determined by individual microsatellite genotyping of the larvae (n = 3949, 24 families) and juveniles (n = 600). The results showed significant positive correlations between egg size and larval size during the whole mesocosm period. Correlations, however, weakened with time and were no longer significant at the first tank-rearing sampling at an age of 9 months. Significant family-specific differences in growth were observed. The coefficient of variation (c.v.) was calculated in order to examine variation in standard length of larvae during the mesocosm period. Inter-family c.v. was on average 69% of intra-family c.v. Differences in zooplankton densities between the two mesocosms were reflected in larval growth, condition factor and c.v. Low food abundance appeared to reduce c.v. and favour growth of larvae that showed relatively slow growth at high food abundance. It is suggested that genetically determined variation in growth potential is maintained by environmental variability. PMID- 20738555 TI - Persistent parental effects on the survival and size, but not burst swimming performance of juvenile sockeye salmon Oncorhynchus nerka. AB - Sockeye salmon Oncorhynchus nerka were used as a model in an artificial fertilization experiment to investigate the relationships between individual adult O. nerka and their offspring. Survival, size and burst swimming ability were assessed in fry of known parentage (adult spawners from the Weaver Creek population, British Columbia, Canada). Maternal identity significantly affected the survival rate of eggs at hatch time, though this effect did not extend to fry life stages. The results were also suggestive of a paternal effect on both egg and fry survival, though this could not be separated from the experimental block design. After 4 months of exogenous feeding, fry mass remained under significant maternal influence, though fork length did not, despite having a high correlation with mass. Burst swimming performance was highly variable among individuals, and was not significantly influenced by maternal identity or individual fry size. Collectively, the findings presented here suggest that maternal, and possibly paternal, effects can be integral components of population dynamics in the early life stages of O. nerka. A good understanding of these factors will be essential for scientists and fisheries managers in developing a more holistic view of population-level spawning success and fry survival. PMID- 20738556 TI - Social context, competitive interactions and the dynamic nature of antipredator responses of juvenile rainbow trout Oncorhynchus mykiss. AB - The effects of food ration and social context, as well as possible interactions, on the antipredator behaviour of juvenile rainbow trout Onchorhynchus mykiss were investigated in a pair of laboratory studies. In experiment 1, pairs of dominant and subordinate O. mykiss were exposed to conspecific alarm cues when maintained under high or low food rations. Under high food rations, dominant individuals responded to predation risk, whereas subordinates used the opportunity to feed. Under low food ration, however, the opposite pattern was observed, where subordinates responded to predation cues and dominants did not. Experiment 2 consisted of performing the same experiment, however separating the dominant and subordinate O. mykiss 3 h before testing. When tested separately, dominant and subordinate individuals did not differ in their responses to alarm cues, regardless of food ration. These results demonstrate that there is a complex interaction between current energy status and social context on decision making by prey animals. PMID- 20738557 TI - Flexibility of reproductive tactics and their consequences in the brood parasitic fish Pungtungia herzi (Teleostei: Cyprinidae). AB - Although previous studies have claimed that Pungtungia herzi (Cyprinidae) is an obligate brood parasite, in this study a significant proportion of P. herzi egg masses was found in crevices formed by stones and rocks, which was not guarded by hosts. Egg masses were also found in almost all nests of a goby Odontobutis obscura, suggesting that P. herzi has two alternative reproductive tactics: brood parasitic spawning and non-parasitic crevice spawning, the latter of which may occur when a shortage of reproductive resources (i.e. host nests) exists. The hatching rates of parasitic egg masses were significantly higher than those of non-parasitic egg masses, and the hatching rate of P. herzi eggs exhibited a strong positive correlation with continuous egg guarding by a reproductive O. obscura male. These results indicate that brood parasitism effectively improves reproductive success in P. herzi. The alternative reproductive tactic of this species suggests that brood parasitism has evolved directly from crevice spawning via the sharing of spawning habitat with host species. PMID- 20738558 TI - Prey selection and functional morphology through ontogeny of Amphiprion clarkii with a congeneric comparison. AB - The relationship between the complexity of the feeding apparatus and prey selection through ontogeny was examined in Amphiprion clarkii larvae. Larvae were reared from 1 to 10 days post-hatch (dph) on a diet of rotifers, wild-caught plankton and newly hatched Artemia sp. nauplii. Results were compared with available data on the relationship between functional morphology and prey selection of Amphiprion frenatus to establish patterns of functional morphology and prey selection between the larvae of two species of coral-reef fishes. Larvae of both species exhibited an increase in selection of larger prey through ontogeny coincident with an increase in the complexity of the feeding apparatus. The first elements to ossify in larvae of both species were the pharyngeal teeth (A. clarkii: 5 dph, near +/-s.d. Standard length, L(S),4. 3 +/- 0. 2 mm; A. frenatus: 5 dph, L(S)5. 0 +/- 0. 4 mm) which, in combination with the development of a more functional feeding apparatus, may have permitted larvae to better process new types and sizes of prey. Prey items, however, were selected differentially between the two fish species, which could not be fully explained by the functional state of the feeding apparatus. While prey selection is influenced by the functional state of the feeding apparatus, all aspects of larval fish biology (morphology, behaviour and physiology) should be considered. PMID- 20738559 TI - Swimming in four goldfish Carassius auratus morphotypes: understanding functional design and performance employing artificially selected forms. AB - Four goldfish Carassius auratus morphotypes of similar length (50 mm): common (streamlined, full complement of paired and median fins, bifurcated caudal fin), comet ('common like' but with a long, deeply forked caudal fin), fantail (short, deep body with twinned caudal and anal fins) and eggfish (similar to the fantail but lacking a dorsal fin) were compared. Drag, steady swimming kinematics, energetics, fast-start performance, stability in yaw and roll and propulsive muscle ultrastructural characteristics were measured. A performance 'pairing' (common and comet; fantail and eggfish) was a recurrent theme for most performance variables. Fantail and eggfish drag were higher (requiring more thrust at any given velocity) than those for the more streamlined common and comet. This was reflected in kinematics; tailbeat frequency and stride length at any given velocity for the common and comet were lower and higher, respectively, than that of the fantail and eggfish. Common and comet fatigue times were not significantly different from those of their ancestor, crucian carp Carassius carassius, and higher than the fantail and eggfish. The cost of transport of the common and comet (c. 0. 6 mg O(2) kg(-1) m(-1)) was accurately predicted by the mass scaling relationship for fish, but values for the fantail and eggfish (c. 1. 3 mg O(2) kg(-1) m(-1)) were not. Rolling and yawing motions in eggfish (dorsal fin absent) during steady swimming were associated with significant energy losses. Eggfish maximum fast-start acceleration (c. 5 m s(-2)) was poor due to the absence of inertial and lifting contributions to thrust from the dorsal fin and energy wasting rolling motions. Common and comet fast-start performance (average velocity c. 0. 45 m s(-1), maximum velocity c. 1. 2 m s(-1), average acceleration c. 7. 5 m s(-2), maximum acceleration c. 35 m s(-2)) was similar to that of other locomotor generalists (e.g. rainbow trout Oncorhynchus mykiss). Artificially selected fishes can contribute to the understanding of form and movement in fishes and complement studies of the role of locomotor adaptations in natural systems. PMID- 20738560 TI - Effect of spawning number and ration on reproductive performance of the batch spawning three-spined stickleback Gasterosteus aculeatus. AB - An experiment quantified the effect of food ration and spawning number on the breeding season reproductive performance of batch-spawning, female three-spined sticklebacks Gasterosteus aculeatus. Individually housed females were maintained on fixed rations of 2, 4, 8 or 16% of their initial postspawning mass of live enchytraeid worms from immediately after their first spawning until they ceased spawning. Number of spawnings correlated positively with ration. Total breeding season reproductive investment (total wet mass of eggs produced as a percentage of initial postspawning female mass) ranged from 38% at the 2% ration to 147% at the 16% ration. At the lower rations, postspawning mass, batch fecundity and wet and dry masses of the batch declined over successive spawnings, with the rate of decline inversely related to ration. At the highest ration, there was no decline in batch fecundity and postspawning mass increased over successive spawnings. Mean reproductive investment per inter-spawning interval was higher at the highest ration, but at all rations declined over successive spawnings. Mean reproductive effort per inter-spawning interval (wet mass of eggs spawned as a percentage of the wet mass of food consumed over the inter-spawning interval) was inversely related to ration. At the higher rations, reproductive effort showed no trend over successive spawnings. Neither spawning number nor ration had a systematic effect on egg diameter, wet mass per egg, dry mass per egg or total lipid content of the eggs. If the rate of food intake was insufficient, although batch fecundity declined, the main adjustment was a reduction in the number of spawnings in the breeding season. PMID- 20738561 TI - Interannual distribution of Pacific hake Merluccius productus larvae in the southern part of the California Current. AB - The interannual distribution of early life stages of Pacific hake Merluccius productus, within the southern part of the California Current (32-23 degrees N) from 1951 to 2001, was examined to describe the relationship between spawning habitat and environmental conditions. Mean annual abundance was affected by different factors along the west coast of the Baja California Peninsula. In the northern areas (Ensenada and Punta Baja), reduced abundance of larvae coincided with the El Nino and a North Pacific Ocean climatic regime shift, but in the southern areas (San Ignacio to Bahia Magdalena), the drastic reductions suggested a fishery effect for large adults of the coastal migratory population, starting in 1966. Two spawning stocks, coastal and dwarf, were evident in comparisons of latitudinal differences in occurrence of early stages and differences in temperature preferences that seemed to break at Punta Eugenia. PMID- 20738562 TI - Distribution, size frequency, and sex ratios of blacktip reef sharks Carcharhinus melanopterus at Palmyra Atoll: a predator-dominated ecosystem. AB - Blacktip reef sharks Carcharhinus melanopterus were the most abundant predator in the lagoons at Palmyra Atoll. They were evenly distributed throughout the lagoons, although there was some evidence of sexual segregation. Males reach sexual maturity between 940-1,020 mm L(T). Bird remains were found in some C. melanopterus stomachs. C. melanopterus at Palmyra appear to be smaller than those at other locations. PMID- 20738563 TI - The reproductive ecology of the southern red tabira bitterling Acheilognathus tabira jordani in Japan. AB - The life history, population and reproductive variables of the southern red tabira bitterling Acheilognathus tabira jordani were investigated in a lowland reach of the River Ohara in Shimane Prefecture, western Honshu, Japan. Acheilognathus t. jordani, like all other species of bitterling, lays its eggs on the gills of freshwater mussels. It was the only species of bitterling present in the study reach, and three species of bivalve mussel were available to it for spawning: Anemina arcaeformis, Anodonta lauta and Corbicula leana. Spawning by A.t. jordani was recorded between early April and early July in 2003 and began at a size of 38. 0 mm standard length (L(S)) in the 1+ age class. Ovipositor length (L(OP)) during oviposition was positively correlated with female L(S), and showed significant seasonal variation, with a mean +/-s.d.L(OP) of 27. 5 +/- 5. 3 mm ranging from 16. 8 to 42. 0 mm during the spawning period, which was shorter than that of a previously studied A. t. tabira population. Eggs of this subspecies are relatively long and elliptic in shape, with a volume of c. 2. 4 mm(3). Egg number correlated positively with female L(S) and both egg shape and volume changed significantly with season. The population size of adults was estimated to be 850 individuals, and comprised age 0+ to 3+ individuals with L(S) ranging from 12. 0 to 72. 2 mm. The population sex ratio was significantly female biased, with seven females: three males. Egg shape and size and L(OP) during oviposition in the present A. tabira population may be the result of local adaptations to the mussel species utilized and no competition with other bitterling species for spawning sites. PMID- 20738564 TI - Transgenerational marking of freshwater fishes with enriched stable isotopes: a tool for fisheries management and research. AB - A promising new method of marking larval freshwater fishes with enriched stable isotopes by means of injecting the maternal parent with the marking agent was investigated. The (138)Ba:(137)Ba ratios in the otoliths of larval golden perch Macquaria ambigua were compared to determine the effect of injecting female broodstock with different dosages of enriched (137)Ba at various times before spawning. There was 100% mark success in the progeny of fish injected with 20 microg g(-1) of enriched (137)Ba 24 h before inducing spawning with hormones and 40 microg g(-1) administered at the same time as inducement of spawning. Injection of 40 microg g(-1) enriched (137)Ba 21 days before spawning resulted in only 81% mark success and suggests rapid elimination of barium in M. ambigua. Injection with enriched (137)Ba did not significantly affect the fertilization rate, number of fertilized eggs or hatching rate compared with long-term hatchery records. These results suggest that transgenerational marking is an effective and affordable means of mass-marking larval fishes. Thousands of larval fishes can be permanently marked with a unique artificial isotopic mark via a single injection into the maternal parent, thus avoiding the handling of individual fishes or having to deal with chemical baths. Because no single mark or tagging method is suitable for all situations, transgenerational marking with enriched stable isotopes provides another method for researchers and managers to discriminate both hatchery-reared and wild fishes. PMID- 20738565 TI - Equivalent whole-body concentrations of 11-ketotestosterone in female and male coral goby Gobiodon erythrospilus, a bidirectional sex-changing fish. AB - The relationship between whole-body concentrations of 11-ketotestosterone (11-KT) and sexual function was examined in the coral goby Gobiodon erythrospilus, a bi directional sex-changing fish. 11-KT occurred in both female and male G. erythrospilus, but levels were not always higher in males than in females within heterosexual pairs, and were not related to the stage of gonadal development of individual fish. These results suggest that comparable 11-KT levels in both sexes may allow serial adult sex change to take place in bi-directional sex-changing species, such as Gobiodon spp. PMID- 20738566 TI - Is global climate change influencing the overwintering distribution of weakfish Cynoscion regalis? AB - The pattern of stable isotope signatures in a sub-sample of 67 juvenile weakfish Cynoscion regalis, captured at the mouth of the Christina River, 113 km upstream of the mouth of Delaware Bay (U.S.A) in the autumn of 2000, suggested that they resided at the location since recruitment. The possibility that young C. regalis departed from the generally characteristic life-history pattern of marine migrants at this latitude, i.e. emigrating offshore with the adults in autumn was bolstered by the collection of 69 individuals during the winters of 2000-2006 from the travelling screens of a power plant located at river kilometre 88 including an 118 mm total length juvenile captured in mid-February 2006. PMID- 20738567 TI - Effect of biological fouling on passive collectors used to estimate fish recruitment. AB - Evidence is provided that biofouling of artificial substrata for estimating recruitment of nearshore reef fishes influences recruitment, and it is recommended that investigators consider the effects of fouling when estimating recruitment over space and time. PMID- 20738568 TI - Diet of pre-settlement larvae of coral-reef fishes: selection of prey types and sizes. AB - This study examines the diet of nine taxa from seven families of pre-settlement coral-reef fish larvae collected in the lagoon of New Caledonia, south-west Pacific. Chesson's index of electivity indicated that the major prey groups in the diets, i.e. small copepods, small unidentified crustaceans and eggs, were positively selected by all larvae, provided they were at least 150 microm wide. This result emphasizes the role of larvae's behaviour on their feeding. PMID- 20738569 TI - Increased accuracy of batch fecundity estimates using oocyte stage ratios in Plectropomus leopardus. AB - Using the ratio of the number of migratory nuclei to hydrated oocytes to estimate batch fecundity of common coral trout Plectropomus leopardus increases the time over which samples can be collected and, therefore, increases the sample size available and reduces biases in batch fecundity estimates. PMID- 20738570 TI - Twenty-four hours in the life of Zingel asper. AB - For the first time, radio-tracking observations were made over 24 h cycles during the growing season to quantify the habitat use and home range of Zingel asper, a critically endangered fish species, endemic to the Rhone River with a high risk of extinction (IUCN). New advances in radio telemetry with regard to the size of tags provided an opportunity to collect behavioural and habitat use information while remaining non-lethal. Zingel asper was characterized by small ranges of habitat use and, contrary to previous assumptions, the species was diurnal as illustrated by a smaller home range during the night than during daytime. PMID- 20738571 TI - Kinship affects innate responses to a predator in bluegill Lepomis macrochirus larvae. AB - Naive kin groups and mixed-family groups of bluegill Lepomis macrochirus larvae were exposed to a novel predator cue. The larvae responded by increasing shoal cohesiveness in kin groups but not in mixed-family groups; moreover, larvae sired by males of the 'cuckolder' life history tended to have an enhanced ability to respond to direct cues of kinship v. larvae sired by males of the 'parental' life history, which instead appeared to respond to cues of life history rather than relatedness per se. The increased shoal cohesion among related individuals probably confers a survival benefit and indicates that the antipredatory shoaling response is innate in L. macrochirus. PMID- 20738572 TI - Computer animation as a tool to study preferences in the cichlid Pelvicachromis taeniatus. AB - Four choice experiments were conducted with both sexes of the cichlid Pelvicachromis taeniatus using computer-manipulated stimuli of digital images differing in movement, body shape or colouration. The results show that computer animations can be useful and flexible tools in studying preferences of a cichlid with complex and variable preferences for different visual cues. PMID- 20738573 TI - 31P nuclear magnetic resonance measurements of phosphate metabolites and intracellular pH in turbot Psetta maxima red blood cells using a novel flow method. AB - A method for oxygenating and mixing suspensions of turbot Psetta maxima red blood cells (RBC) was tested in (31)P nuclear magnetic resonance (NMR) spectroscopy. In normoxia, the levels of inorganic phosphate (Pi) and nucleoside triphosphates (NTP) were stable up to 140 min and intracellular pH (pHi) was maintained and decreased oxygen partial pressure (P(O ( 2) )) from 30 to 15 and 600 Pa produced a significant fall in the intensity of NTP resonance, balanced by an increase in the Pi signal. Treatment of RBC with 0. 5 M isoproterenol during hypoxia exposure did not affect the pattern of changes in NTP or pHi induced by hypoxia and the effect was manifest only on Pi levels. PMID- 20738578 TI - Morphometric convergence and molecular divergence: the taxonomic status and evolutionary history of Gymnura crebripunctata and Gymnura marmorata in the eastern Pacific Ocean. AB - To clarify the taxonomic status of Gymnura crebripunctata and Gymnura marmorata, the extent of morphological and nucleotide variation between these nominal species was examined using multivariate morphological and mitochondrial DNA comparisons of the same characters with congeneric species. Discriminant analysis of 21 morphometric variables from four species (G. crebripunctata, G. marmorata, Gymnura micrura and Gymnura poecilura) successfully distinguished species groupings. Classification success of eastern Pacific species improved further when specimens were grouped by species and sex. Discriminant analysis of size corrected data generated species assignments that were consistently accurate in separating the two species (100% jackknifed assignment success). Nasal curtain length was identified as the character which contributed the most to discrimination of the two species. Sexual dimorphism was evident in several characters that have previously been relied upon to distinguish G. crebripunctata from G. marmorata. A previously unreported feature, the absence of a tail spine in G. crebripunctata, provides an improved method of field identification between these species. Phylogenetic and genetic distance analyses based on 698 base pairs of the mitochondrial cytochrome b gene indicate that G. crebripunctata and G. marmorata form highly divergent lineages, supporting their validity as distinct species. The closely related batoid Aetoplatea zonura clustered within the Gymnura clade, indicating that it may not represent a valid genus. Strong population structuring (overall Phi(ST) = 0.81, P < 0.01) was evident between G. marmorata from the Pacific coast of the Baja California peninsula and the Gulf of California, supporting the designation of distinct management units in these regions. PMID- 20738579 TI - Responses to handling and confinement stressors in juvenile great sturgeon Huso huso. AB - The effects of acute stressors on physiological responses of juvenile great sturgeon or beluga Huso huso L. were investigated in two experiments. In the first experiment, fish were handled by placing them in containers at either low density (LD, one fish l(-1)) or high density (HD, four fish l(-1)) for 60 s. Concentrations of plasma cortisol, glucose and lactate were determined from blood collected at 0, 1, 3, 6 and 12 h after application of the stressor. Plasma cortisol concentrations increased after the disturbance in H. huso from both handling treatments, but changes were not significant. Plasma glucose rose significantly by 22.9 and 31.6% in LD and HD handling treatments, respectively, after 3 h. Significant increases in plasma lactate occurred within 1 h in both treatment groups, but that of the HD group was much higher. In the second experiment, fish were held at two different densities, LD (2 kg m(-2) tank bottom surface area) and HD (7 kg m(-2)), for 8 weeks and then subjected to an aerial emersion handling stressor in a net for 60 s; blood samples were taken before handling (resting, 0 h) and at 1, 3, 6 and 9 h after handling. Plasma cortisol increased significantly in fish from the HD treatment from 8.8 +/- 0.3 to 19.2 +/ 2.4 ng ml(-1) (mean +/-s.e.) by 1 h after stress, but post-handling changes in the LD group were not significant. Significant increases in both plasma glucose and lactate were observed by 1 h in both treatment groups, with peak levels of plasma glucose evident at 3 h [69.4 +/- 2.9 and 60.9 +/- 1.7 mg dl(-1) (mean +/ s.e.) in LD and HD groups, respectively]. Plasma glucose levels were significantly higher in the LD group than in the HD group at 3 and 6 h. Post handling haemoglobin content increased by 1 h and white blood cell numbers were reduced by 3 and 6 h in the HD treatment group compared with resting values, but changes in these blood features in the LD group were not significant. Acute handling did not affect haematocrit in either treatment. The results suggest that H. huso is relatively resistant to handling and confinement, and could tolerate normal hatchery practices associated with aquaculture. Because changes in cortisol concentrations were relatively low compared with those in most teleosts, glucose and lactate concentrations may be more useful as stress indicators in juvenile H. huso. This study also demonstrated that prior exposure to a chronic stressor, specifically high stocking density, could alter the physiological response to subsequent acute handling in H. huso. PMID- 20738580 TI - Fishes of the family Ipnopidae (Teleostei: Aulopiformes) collected on the Brazilian continental slope between 11 degrees and 23 degrees S. AB - A collection of fishes from the Brazilian continental slope between 11 degrees and 23 degrees S obtained through trawling revealed nine species of Ipnopidae. Bathypterois bigelowi and Bathytyphlops marionae represent first records from the south-western Atlantic Ocean and Bathypterois grallator is reported off Brazil for the first time. Four species have their distribution extended in Brazilian waters: Bathypterois phenax, Bathypterois quadrifilis, Bathypterois viridensis and Ipnops murrayi. An identification key of Ipnopidae species from the south western Atlantic Ocean is included. PMID- 20738581 TI - The role of free amino acids in semen of rainbow trout Oncorhynchus mykiss and carp Cyprinus carpio. AB - The present study investigated (1) the free amino acid (FAA) composition in semen of rainbow trout Oncorhynchus mykiss and carp Cyprinus carpio, (2) enzyme systems involved in amino acid metabolism and (3) the effect of amino acids on sperm viability under in vitro storage conditions. In the seminal plasma of O. mykiss, the main FAAs were arginine, glutamic acid, isoleucine, leucine, methionine and proline, in spermatozoa cysteine, arginine and methionine. In the seminal plasma of C. carpio, the main FAAs were alanine, arginine, cysteine, glutamic acid, histidine, leucine, lysine, methionine and proline, in spermatozoa arginine, glutamic acid, histidine, leucine and lysine. When spermatozoa were incubated for 48 h together with the seminal plasma, the quantitative amino acid pattern changed in both species indicating their metabolism. In spermatozoa and seminal plasma of O. mykiss and C. carpio, the following enzymes were found to be related to amino acid metabolism: transaminases (specific for alanine, aspartate, isoleucine and leucine), decarboxylases (specific for valine and lysine), glutamate dehydrogenase and alpha-keto acid dehydrogenases (substrates: 3-methyl 2-oxovaleric acid and 4-methyl-2-oxovalerate). These data demonstrate that amino acid catabolism by transamination, decarboxylation and oxidative deamination can occur in semen of the two species. Also activity of methionine sulphoxide reductase was detected, an enzyme which reduces methionine sulphoxide to methionine. This reaction plays an important role in antioxidant defence. To determine the effect of FAAs on the sperm viability, C. carpio and O. mykiss spermatozoa were incubated in sperm motility inhibiting saline solution containing different amino acids. Methionine had a positive effect on the sperm viability in both species. Taken together this result with the in vivo occurrence of methionine and of methionine reductase in semen, it can be assumed that this amino acid plays an important role in antioxidant defence. Also isoleucine in O. mykiss and leucine in C. carpio had a positive effect on sperm viability. As seminal plasma and spermatozoa of the two species exhibit enzyme activities to catabolize leucine and isoleucine, they might serve as additional energy resources especially during prolonged incubation and storage periods. PMID- 20738582 TI - Distribution of cholecystokinin-immunoreactive cells in the gut of developing Atlantic cod Gadus morhua L. larvae fed zooplankton or rotifers. AB - One of the main gastrointestinal hormones, cholecystokinin (CCK), was studied in order to advance understanding of the control of the digestive process in Atlantic cod Gadus morhua larvae after onset of first feeding. Larvae were fed either natural zooplankton or enriched rotifers in similar rearing systems and sampled from hatching to 22 days post-hatch (dph). CCK was visualized by immunohistochemistry and the first CCK-immunoreactive (IR) cells were detected at 8 dph corresponding to 6 days after first feeding. The CCK-IR cells were mostly found in the anterior midgut, and the number of CCK-IR cells was lower in the posterior midgut. They were also present in the hindgut of some of the larvae, but not in the foregut. No clear differences were found in the ontogenetic appearance and the distribution pattern of CCK-IR cells between the two dietary treatments. This indicates that the onset of CCK production in the gut as well as the spatial distribution of the CCK-IR cells is not differentially affected by these diets. To what extent the hormone production itself is influenced by dietary factors needs to be studied by more sensitive methods. PMID- 20738583 TI - A histochemical study on the snout tentacles and snout skin of bristlenose catfish Ancistrus triradiatus. AB - Histological sections of the tentacles of Ancistrus triradiatus revealed that they contain many goblet cells with granule-like sections distributed along the edge of the tentacles (mean 302 cells mm(-1)). Various histochemical methods were used to characterize the contents of the goblet cells. The results indicated that the contents were periodic acid-Schiff (PAS) positive, glycogen negative and no sulphated mucins could be found. The contents of the goblet cells were acid mucins and O-acetylated sialomucins which had high energy content. The snout skin of the male also contained goblet cells with higher density (mean 755 cells mm( 1)) than that of the tentacles. Snout skin of female A. triradiatus, on the contrary, did not contain any goblet cells. Instead, many minute spines could be found. Based on the acid mucins and O-acetylated sialomucins secretions of goblet cells which are of high nutritional values, it is hypothesized that snout tentacle secretions are used to provide nutrients to fish larvae when they are under paternal care. PMID- 20738584 TI - Ionoregulatory physiology of two species of African lungfishes Protopterus dolloi and Protopterus annectens. AB - Basic ionoregulatory physiology was characterized in two species of African lungfish, slender African lungfish Protopterus dolloi and West African lungfish Protopterus annectens, largely under aquatic conditions. There were no substantive differences between the two species. Plasma [Na], [Cl] and [Ca] were only 60-80% of those typical of freshwater teleosts, and plasma Ca activity was particularly low. Unidirectional Na and Cl influx rates from water were also very low, only c. 10% of teleost values, whereas unidirectional Ca influx rates were comparable with teleost rates. Protopterus spp. were fed a 3% ration of bloodworms every 48 h. The bloodworm diet provided similar amounts of Na and Ca as uptake from water, but almost no Cl. Efflux rates of Na and Cl through the urine were greater than via the faeces, whereas the opposite was true for Ca. Net ion flux measurements and ionic balance sheet calculations indicated that (1) both water and dietary uptake routes are important for Na and Ca acquisition; (2) the waterborne route predominates for Cl uptake; (3) unidirectional ion effluxes across the body surface (gills and skin) rather than urine and faeces are the major routes of loss for Na, Cl and Ca. Tissues (muscle, liver, lung, kidney, intestine and heart) and plasma ions were also examined in P. dolloi'terrestrialized' in air for up to 5 months, during which plasma ion concentrations (Na, Cl, Ca and Mg) did not change and there were only a few alterations in tissue ions, that is, increased [Na] in intestine, decreased [Cl] in kidney and increased [Ca] in liver and kidney. PMID- 20738585 TI - Latitudinal variability in lunar spawning rhythms: absence of a lunar pattern in the northern mummichog Fundulus heteroclitus macrolepidotus. AB - In this study, the natural spawning season of the northern mummichog Fundulus heteroclitus macrolepidotus was examined from May to July in the lower St John River, New Brunswick, Canada (45 degrees N), through measurements of gonado somatic index (I(G)), liver-somatic index (I(L)) and condition factor (K). I(G) increased during the prespawning phase (mean +/-s.e. 5.49 +/- 0.20%), peaked during the spawning phase (14.68 +/- 0.51%) and dropped during the regression phase (3.23 +/- 0.29%). A single peak of spawning was observed in F. h. macrolepidotus, contrasting with multiple peaks observed in studies south of 41 degrees N in North America. Within the prespawning phase, there were significant differences between sampling dates in female body mass, gonad mass, liver mass and K. On the basis of results from this study, water temperature is believed to be the predominant factor controlling initiation of spawning in F. h. macrolepidotus. PMID- 20738586 TI - The volitional travel speed varies with reproductive state in mature female brown trout Salmo trutta. AB - This study tested the effect of reproduction on the volitional travel speed of mature female brown trout Salmo trutta L. The downstream travel speed in the pre spawning state was 0.25 m s(-1) (95% CI : 0.19, 0.34) while it increased significantly to 0.65 m s(-1) (95% CI: 0.49, 0.87) in the post-spawning state. The results suggest state-dependent travel speed in S. trutta. PMID- 20738587 TI - Agonistic sounds in the skunk clownfish Amphiprion akallopisos: size-related variation in acoustic features. AB - Fourteen individuals of the skunk clownfish Amphiprion akallopisos of different sizes and of different sexual status (non-breeder, male or female) were analysed for four acoustic features. Dominant frequency and pulse duration were highly correlated with standard length (r = 0.97), and were not related to sex. Both the dominant frequency and pulse duration were signals conveying information related to the size of the emitter, which implies that these sound characteristics could be useful in assessing size of conspecifics. PMID- 20738588 TI - Rare occurrence of a bigeye tuna Thunnus obesus in British waters, with notes on other occurrences of sub-tropical tunas. AB - A freshly dead bigeye tuna Thunnus obesus was washed ashore near Burry Port, Wales (51 degrees 40' N; 4 degrees 15' W) in August, 2006. This is only the third occasion that the species has been observed in British waters, and is the largest and most northerly recorded specimen. PMID- 20738589 TI - Sperm design and function in the redside dace Clinostomus elongatus. AB - A study was undertaken to examine sperm morphometry in relation to sperm velocity and sperm longevity in the redside dace Clinostomus elongatus. There was significant between-male variance in sperm size and shape metrics (total sperm length, sperm head length, flagellum length and sperm head length to width ratio) and positive relationships were found between these morphometrics and sperm velocity. There were no significant relationships found between sperm morphometry and sperm longevity, nor was there a trade-off between sperm velocity and sperm longevity. PMID- 20738590 TI - Assessment of digestive enzymes activity during the fry development of the endangered Caspian brown trout Salmo caspius. AB - The study of digestive enzymes activity at Salmo caspius fry showed that enzymes were available at the moment of mouth opening on the first day post hatching (dph) and the activity of enzymes showed no significant difference from the hatching day 28 dph. An increased activity was seen between 32 and 43 dph and this activity was significantly higher than the activity during the first 28 days. In the primary stages after yolk sac resorption (43-58 dph), enzymes activity showed an increased profile, however none of them showed a significant difference between 43 and 58 dph. PMID- 20738591 TI - The effects of acute temperature change on cost of transport at maximal labriform speed in bluegill Lepomis macrochirus. AB - The effects of acute temperature change on the cost of bluegill Lepomis macrochirus swimming were quantified. At 14 degrees C, maximum labriform swimming speed (U(lab,max)) was reduced relative to that at the acclimation temperature of 22 degrees C, but total cost of transport (T(TC)) remained unchanged. At 30 degrees C, U(lab,max) was the same as at 22 degrees C, but T(TC) was 66% greater. PMID- 20738593 TI - Molecular biological research on olfactory chemoreception in fishes. AB - This review describes recent molecular biological research on olfactory chemoreception in fishes. The recent rapid development of molecular biological techniques has provided new valuable information on the main and vomeronasal olfactory receptor (OR) genes, the axonal projection from ciliated, microvillous and crypt-olfactory receptor cells to the olfactory bulb, properties of odorant substances and olfactory imprinting and homing in salmon. Many important questions, however, remain unanswered on functional differences among OR genes, on ligand binding to each OR and on the molecular biological mechanisms underlying olfactory imprinting and homing in salmon. Olfactory chemoreception is believed to be the oldest sensory cue for both animal survival and adaptation to various different environments. Further intensive molecular biological research on olfactory memory formation and remembrance should be carried out to clarify the fundamental process of olfactory chemoreception in fishes. PMID- 20738594 TI - Ecological speciation in marine v. freshwater fishes. AB - Absolute barriers to dispersal are not common in marine systems, and the prevalence of planktonic larvae in marine taxa provides potential for gene flow across large geographic distances. These observations raise the fundamental question in marine evolutionary biology as to whether geographic and oceanographic barriers alone can account for the high levels of species diversity observed in marine environments such as coral reefs, or whether marine speciation also operates in the presence of gene flow between diverging populations. In this respect, the ecological hypothesis of speciation, in which reproductive isolation results from divergent or disruptive natural selection, is of particular interest because it may operate in the presence of gene flow. Although important insights into the process of ecological speciation in aquatic environments have been provided by the study of freshwater fishes, comparatively little is known about the possibility of ecological speciation in marine teleosts. In this study, the evidence consistent with different aspects of the ecological hypothesis of speciation is evaluated in marine fishes. Molecular approaches have played a critical role in the development of speciation hypotheses in marine fishes, with a role of ecology suggested by the occurrence of sister clades separated by ecological factors, rapid cladogenesis or the persistence of genetically and ecologically differentiated species in the presence of gene flow. Yet, ecological speciation research in marine fishes is still largely at an exploratory stage. Cases where the major ingredients of ecological speciation, namely a source of natural divergent or disruptive selection, a mechanism of reproductive isolation and a link between the two have been explicitly documented are few. Even in these cases, specific predictions of the ecological hypothesis of speciation remain largely untested. Recent developments in the study of freshwater fishes illustrate the potential for molecular approaches to address specific questions related to the ecological hypothesis of speciation such as the nature of the genes underlying key ecological traits, the magnitude of their effect on phenotype and the mechanisms underlying their differential expression in different ecological contexts. The potential provided by molecular studies is fully realized when they are complemented with alternative (e.g. ecological, theoretical) approaches. PMID- 20738595 TI - Phylogeography of bleaks Alburnus spp. (Cyprinidae) in Italy, based on cytochrome b data. AB - Sequence variation of a fragment of the mitochondrial DNA encoding for the cytochrome b gene was used to reconstruct the phylogeography of the two species of bleaks occurring in Italy: the alborella Alburnus arborella in northern Italy and the vulturino Alburnus albidus in southern Italy. The study includes four populations of the alborella and 14 populations of the vulturino. A total of 57 haplotypes were identified; these could not be sorted into two reciprocally monophyletic clusters. Multiple phylogenetic methods and nested clade phylogeographical analysis consistently retrieved three well-supported clades, two of which contained both Northern and Southern Italian haplotypes. A third clade is limited to southern Italy. This clade is tentatively assigned to the vulturino. The placement in the same clade of northern and southern Italian haplotypes is explained in light of the introductions of fishes operated from northern to central and southern Italy. The origin of the vulturino dates back to the last two million years. This divergence time estimate identifies the Pleistocene confluences between adjacent river basins along the Adriatic slope of the Italian peninsula and their subsequent isolation as the cause that triggered the diversification of the genus in the area. The existence of a clade endemic to southern Italy supports the recognition of the area as a new peri-Mediterranean ichthyogeographic district, the borders of which correspond to the northern and southern edges of the vulturino range. PMID- 20738596 TI - A new mastacembelid species from Lake Tanganyika: a case of complex evolutionary history. AB - A detailed morphometric study of 123 specimens identified as Mastacembelus albomaculatus and the six syntypes of M. tanganicae was undertaken. On each specimen, 27 morphometric measurements and 12 meristics were taken. The type series of M. tanganicae contains more than one species, with four specimens attributed to a new species M. reygeli sp. nov. A redescription of M. albomaculatus and a description of the new species are provided. Both species are endemic to the northern and central part of Lake Tanganyika. They can be distinguished based on the number of caudal vertebrae [47-52 (median 49) in M. albomaculatus v. 42-46 (44) in M. reygeli sp. nov.], the total number of vertebrae [85-90 (88) v. 78-83 (81)] and the distance from the snout to the last externally visible dorsal spine (S-LDS) [61.8-67.0 (mean 64.0) v. 66.6-71.5 (68.6)% L(S)]. In addition, intermediate specimens and populations between M. albomaculatus and M. reygeli were discovered from several parts of the lake, but mainly from the southern part. The latter intermediate populations were provisionally identified as introgressed populations. PMID- 20738597 TI - Characterization and expression of a myosin heavy-chain isoform in juvenile walleye Sander vitreus. AB - In this study, myosin, the major component of myofibrillar protein in the skeletal muscle, was characterized and its expression was monitored during growth in juvenile walleye Sander vitreus. First, the coding region of myosin heavy chain (MyHC) from the fast skeletal muscle of walleye was amplified by long distance PCR using a full-length cDNA. Phylogenetic analysis was used to determine the evolutionary relationship of this S. vitreus myosin sequence to other vertebrate myosin sequences. Next, it was established that the myosin isoform was most prevalent in the white muscle, compared with the red and cardiac muscle. Myosin expression was monitored over a series of experiments designed to influence growth. Specifically, change in MyHC mRNA was monitored after acute changes in feeding. Fish exposed to a one-week fasting period showed significant decreases in MyHC mRNA levels by the end of the fast. The effect of feeding was also examined more closely over a 24 h period after feeding, but results showed no significant change in myosin expression levels through this time period. Finally, fish with higher growth rates had higher MyHC mRNA and protein expression levels. This study indicates that MyHC mRNA expression is sensitive to the factors that may influence growth in juvenile S. vitreus. PMID- 20738598 TI - The importance of genetic cluster recognition for the conservation of migratory fish species: the example of the endangered European huchen Hucho hucho (L.). AB - European huchen Hucho hucho (L.) is an endangered flagship species, which is endemic to the Danube drainage in central Europe. To date, no genetic information has been available as a basis for ongoing conservation and breeding programmes for the species. It is suspected that most populations in the wild share one common gene pool and that they exclusively depend on stocking with hatchery fish. In this study, highly variable microsatellite markers were established and the genetic diversity and differentiation from four important hatchery-reared stocks were compared with that of eight H. hucho populations sampled in the wild. Overall, eight genetic clusters with a moderate to very great degree of genetic differentiation and high assignment rates were identified. Each cluster contained individuals from two to 10 different populations and 9-100% of specimens from hatchery stocks. It is proposed that genetic cluster-based management in the conservation of European huchen is advantageous compared with the consideration of single local populations. A combined approach of maintaining the evolutionary potential of wild populations and genetically variable hatchery stocks can maximize the conservation of the species' evolutionary potential. PMID- 20738600 TI - A one-year investigation of the relationship between serum GH levels and the growth of F(4) transgenic and non-transgenic common carp Cyprinus carpio. AB - It has been demonstrated that growth hormone (GH) transgenic fish often posses a trait for fast growth. Here, we investigated the growth of F(4)'all-fish' GH transgenic carp Cyprinus carpio and their serum GH levels for a year. The results showed that F(4) all-fish GH transgenic carp were significantly larger in body mass (c. two-fold, P < 0.001) and body length (c. 1.3 fold, P < 0.001), compared with the non-transgenic group. The discrepancy of serum GH levels between the transgenic carp group and control group is 54 fold, when the water temperature was 12-34 degrees C. When the water temperature decreased to 3.5 degrees C in January, the discrepancy was 256 fold. The serum GH level of the transgenic group was relatively constant, while that of control varied greatly based on month and water temperature. The changes of growth rates between the transgenic group and the control group were similar for a year. Taken together, the results indicated that F(4) all-fish GH transgenic carp had not only higher and constant serum GH levels but also a significant fast-growing effect, compared with the control. To our knowledge, this is the first report on a one-year investigation of growth trait and serum growth hormone level in F(4) all-fish GH transgenic carp. PMID- 20738599 TI - Karyotypic diversity and evolution of seven mahseer species (Cyprinidae) from India. AB - Mahseer is a group of fish species that are well known as food and game fishes. The taxonomy of the mahseer species is confusing owing to the morphological variations and habitat adaptation. Detailed karyomorphological investigations have been carried out in seven species of mahseer, using karyotyping, Ag-NOR and fluorescent staining techniques. The basic diploid chromosome number (2n), in all mahseer species, was observed to be 100; however, the karyotype formula varied among the species, which were recorded as: 20m + 14sm + 22st + 44t (fundamental arm number, FN = 134) in Tor khudree; 22m + 24sm + 24st + 30t (FN = 146) in Tor mussullah; 12m + 22sm + 14st + 52t (FN = 134) in Tor putitora; 20m + 24sm + 24st + 32t (FN = 144) in Tor tor; 20m + 30sm + 24st + 26t (FN = 150) in Tor chelynoides; 20m + 20sm + 20st + 40t (FN = 140) in Tor progeneius; and 20m + 18sm + 14st + 48t (FN = 138) in Neolissochilus hexagonolepis. Silver staining of the chromosomes revealed the presence of multiple nucleolar organizer regions (NOR) in these mahseer species. The highest number of NORs was observed in T. tor (four pairs of chromosomes), whereas the other six species possessed Ag-NOR signals on only two pairs of chromosomes. Although chromomycin A(3) (CMA(3)) staining induced bright fluorescence signals on same Ag-NORs sites, with CMA(3), one additional signal was observed on the p arm of subtelocentric chromosomes in T. tor, T. chelynoides, T. progeneius and N. hexagonolepis, which may indicate the presence of inactive NOR in these species. The information on cytogenetic profile of these mahseer species is discussed in the light of cytotaxonomic implications and understanding the karyoevolution of these fish species. PMID- 20738601 TI - Identification of weakfish Cynoscion (Gill) in the Bay of Panama with RFLP markers. AB - A molecular approach, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), was developed to identify the planktonic larvae of Cynoscion species. Species-specific mitochondrial DNA markers were developed using three restriction endonucleases (DdeI, HaeIII and HinfI). These markers permitted the accurate discrimination of the five Cynoscion species in the Bay of Panama. PMID- 20738602 TI - A cryptic lineage within the pupfish Cyprinodon dearborni suggests multiple colonizations of South America. AB - The coastal South American species Cyprinodon dearborni contains two lineages distinct at both mitochondrial and nuclear loci. One appears to be a long-term South American endemic, whereas the other is a more recent colonizer related to the widespread Cyprinodon variegatus. PMID- 20738603 TI - Diversity and distribution of gynogenetic hybrids between Fundulus diaphanus and Fundulus heteroclitus in Porter's Lake (Nova Scotia) in relation to salinity. AB - Unisexual hybrids between Fundulus diaphanus and Fundulus heteroclitus were found in low proportions at intermediate salinity in Porter's Lake, Nova Scotia. One clone accounted for 72% of the hybrids, with most other hybrids being different at a single microsatellite allele. This clone thrives over a wide range of salinities, suggesting a general-purpose genotype. PMID- 20738604 TI - Cryptic dietary components reduce dietary overlap among sympatric butterflyfishes (Chaetodontidae). AB - This study used three different methods to ascertain dietary composition for 21 Chaetodontidae species co-occurring on a single fringing reef in Derawan Island, East Kalimantan, Indonesia. The combination of in situ feeding observations, examination of gut contents and stable-isotope analyses was expected to identify previously unresolved prey items that contribute to dietary separation. In situ feeding observations identified five species that feed predominantly on anthozoans (Chaetodon baronessa, Chaetodon bennetti, Chaetodon lunulatus, Chaetodon punctatofasciatus and Chaetodon speculum). Stable-isotope ratios for these species, as well as for Chaetodon ornatissimus (for which no feeding observations were completed), were very similar and consistent with diets comprising mostly anthozoans. Feeding observations, however, showed that they mostly fed on different coral species, while the identifiable portion of their gut contents showed clear separation based on cryptic dietary components. For example, C. baronessa and C. bennetti appeared to ingest annelid worms during the course of coral feeding, whereas gut contents of C. punctatofasciatus and C. speculum were dominated by crustaceans. In situ feeding observations further identified the following groups: coral-bottom feeders, bottom feeders, sponge feeders and pelagic feeders, feeding on a wide variety of prey items such as Annelida, Crustacea, Cnidaria, Mollusca and macroalgae. Overall, many chaetodontid species had similar reliance on major prey items (e.g. anthozoans or polychaetes) but differed greatly in the minor prey items that they utilized. Partitioning of minor prey items may be important in reducing interspecific competition and facilitating coexistence of chaetodontids on coral reefs. PMID- 20738605 TI - The role of predation in variation in body shape in guppies Poecilia reticulata: a comparison of field and common garden phenotypes. AB - The body shapes of both wild-caught and laboratory-reared male and female Trinidadian guppies Poecilia reticulata from two low-predation and two high predation populations were studied, but predation regime did not seem to be the most important factor affecting body shape. Instead, complicated patterns of plasticity in body shape among populations and the sexes were found. In particular, populations differed in the depth of the caudal peduncle, which is the muscular region just anterior to the tail fin rays and from which most swimming power is generated. Strikingly, the direction of population differences in caudal peduncle depth observed in wild-caught individuals was reversed when P. reticulata were raised in a common laboratory environment. PMID- 20738606 TI - Effects of the timing of initial feeding on growth and survival of spotted mandarin fish Siniperca scherzeri larvae. AB - The effects of delayed first feeding on growth and survival of spotted mandarin fish Siniperca scherzeri larvae were examined under controlled conditions. Morphometric characters [yolk-sac volume, oil globule volume, head depth (H(D)), body depth (B(D)), eye diameter (E(D)), musculature height (M(H)), mouth diameter (M(D)) and total length (L(T))], body mass (M), specific growth rate (S(GR)) and survival were evaluated under different first-feeding time (2, 3, 4 and 5 days after hatching). Larvae began to feed exogenously at 2 days after hatching (DAH) and the point of no return (P(NR)) occurred between 5 and 6 DAH at 23 degrees C, range +/-1.0 degrees C. The yolk volume of larvae first-fed at 2 days had a significant difference compared with that of larvae first-fed at 3, 4 and 5 days on 3 and 4 DAH. The larvae first-fed at 2 days achieved comparatively better growth performance than that of 3, 4 and 5 days. On 5 DAH, all morphometric characters had significant differences between 2 and 5 days and 2 and 4 days initial feeding, respectively. Total mortality was recorded on 9 DAH for the larvae first-fed at 5 days. On 12 DAH, significant differences were observed between 2 and 4 days and 3 and 4 days initial feeding for all morphometric characters. From 16 DAH to the end of experiment, all growth variables of the larvae first-fed at 2 days were significantly higher than those in other treatments. The S(GR) (2-9 DAH) first-fed at 2 and 3 days were significantly higher than 4 and 5 day treatments, and the S(GR) (9-16 DAH) first-fed at 2 days was significantly higher than 3 and 4 day treatments. There was no significant difference, however, of S(GR) (16-28 DAH) among treatments. Survival rate was significantly higher at 2 days initial feeding (27.42%) when compared with 3 (15.96%) and 4 days (7.92%) initial feeding at the end of experiment. The present study suggests that the first feeding of S. scherzeri larvae should be initiated at 2 days after hatching for achieving good growth and survival. PMID- 20738607 TI - Spatio-temporal variation in the elemental compositions of otoliths of southern bluefin tuna Thunnus maccoyii in the Indian Ocean and its ecological implication. AB - The elements Na, Mg, Mn, Ca, Sr and Ba in otoliths of southern bluefin tuna Thunnus maccoyii, collected from their feeding ground in the central Indian Ocean and spawning ground between southern Java and north-western Australia were measured by laser-ablation inductively coupled plasma mass spectrometry (LA ICPMS) and compared among sampling locations and developmental stages. The Na, Mg and Mn to Ca concentration ratios were significantly higher at the larval stage than at the adult stage, and the ratio reached a peak at the first inflection point of the otolith, mean +/-s.d. 43.3 +/- 4.9 days after hatching and decreased sharply to a low level thereafter. The temporal change of the elements:Ca ratios in the first inflection point corresponded to the life stage transition from larva to juvenile, indicating that the uptake rate of elements from ambient waters was significantly influenced by the ontogenetic change in the fish. The elemental composition at the otolith edge differed significantly in sub-adults on the feeding grounds and adults on the spawning grounds. Thus, the otolith elemental composition can be used as a biological tracer to study the time of the ontogenetic shift and to reconstruct the past migratory environmental history of T. maccoyii. In addition, the elemental composition of the otolith core of the adult was similar between feeding and spawning grounds, indicating that the fish in the Indian Ocean had the same larval origin, which is consistent with the single spawning population hypothesis. PMID- 20738608 TI - Localization of tyrosine hydroxylase immunoreactive neurons in the forebrain of the guppy Poecilia reticulata. AB - The current study reports for the first time the distribution of tyrosine hydroxylase immunoreactive (TH-ir) neurons in the forebrain of the guppy Poecilia reticulata. Numerous small TH-ir neurons were observed in the olfactory bulbs, located mainly in the periphery of the bulbs. The TH-ir telencephalic neurons are localized in the ventral telencephalic area where they are grouped in three distinct nuclei (Vv,Vd and Vp) composed of a small number of cells forming a continuous strip. The largest number of forebrain TH-ir neurons was observed in the diencephalon where both small and larger neurons are present. Diencephalic TH ir neurons are subdivided in large nuclei located in the preoptic region (nSC, nPOp and nPOm), the thalamus (nDM), the pretectal region (nPPv and nAP), the hypothalamus (nPP and nRP) and the posterior tuberculum (nPT). Many diencephalic nuclei are distributed in periventricular regions and no TH-ir cells were observed in the paraventricular organ. A comparative analysis indicates that the present observations are consistent with the general pattern of TH-ir neurons distribution reported for the forebrain of other teleosts, but with some interspecies variability present, mainly in the diencephalon. This paper also provides valuable neuroanatomical information for P. reticulata, a teleost frequently used in toxicological tests, for future studies investigating the effects of environmental pollutants on the catecholaminergic system. PMID- 20738609 TI - Behavioural and morphological differences between feral and domesticated strains of common carp Cyprinus carpio. AB - Morphological and behavioural traits of a feral strain of the common carp Cyprinus carpio from Lake Biwa in Japan were compared with those of two domesticated strains reared in Japan (one commercial strain and one ornamental koi). To compare genetically inherited traits, all fish were reared from eggs under similar environmental conditions. Using these fish, the following five traits were compared among the three strains: body shape, consumption rate of two types of free-swimming shrimp, medaka Oryzias latipes and bottom-dwelling chironomid larvae prey items, preference for a bottom habitat, feeding skills in detecting prey and escape response to predator attack. The feral strain of fish had more streamlined bodies, higher consumption rates for free-swimming prey, a greater preference for a bottom habitat, possessed greater skill in detecting prey and were more cautious of predator attacks, compared with the fish of the two domesticated strains. These characteristics shown by the feral fish are probably adaptive to the natural environment. A genetic analysis based on five nuclear single nucleotide polymorphism markers, however, suggested that the feral strain was relatively recently derived from domesticated stocks. Considering this, the present results appear to indicate the possibility that domesticated C. carpio could re-adapt to the wild environment during a short evolutionary period, although further research using more feral strains is required. PMID- 20738610 TI - A histological investigation of the occurrence of non-reproductive female bluefin tuna Thunnus thynnus in the Mediterranean Sea. AB - The presence of non-reproductive Atlantic bluefin tuna Thunnus thynnus females in the Mediterranean Sea was investigated through histological analysis of the gonads. Three hundred and twenty-six ovary samples were collected from adults captured at different locations in the Mediterranean Sea during the reproductive seasons between 1998 and 2008. Only three specimens were considered to be in a non-reproductive state: two of them were in a reabsorbing state showing ovaries with early vitellogenic oocytes and extensive alpha and beta atresia of vitellogenic follicles; the third showed gonads with perinucleolar oocytes and was considered to be in a resting state. The low occurrence of non-reproductive individuals found in this study makes it unlikely that non-reproductive individuals aggregate with reproductive ones during their migration towards spawning grounds. Further research is suggested in order to investigate the potential presence of non-reproductive individuals on non-spawning grounds during the reproductive season. PMID- 20738611 TI - Food niche segregation between two herbivorous cyprinid species in a turbid lake. AB - The diet and growth of two cyprinids, roach Rutilus rutilus and rudd Scardinius erythrophthalmus, in the clay-turbid Kirkkojarvi basin in Lake Hiidenvesi (Finland) were studied. Young R. rutilus fed mainly on detritus, molluscs, chironomids and zooplankton, while older individuals consumed mostly detritus, molluscs and filamentous algae. In the food of S. erythrophthalmus, detritus was less prevalent and animal food and plants contributed to most of the diets. The animal food of S. erythrophthalmus consisted mostly of surface insects. Of the plant food, the macrophytes Potamogeton obtusifolius and Ranunculus circinatus had the highest representation, while the proportion of filamentous algae was low. The growth rate of S. erythrophthalmus was significantly higher than that of R. rutilus. The results suggested that the species composition of vascular macrophytes was not favourable for R. rutilus. Small submerged species suitable for R. rutilus were absent and they fed on filamentous algae and detritus, which resulted in a slow growth rate. The results suggested that in a clay-turbid lake the food spectrum is more suitable for S. erythrophthalmus than for R. rutilus. In such conditions, R. rutilus may have no benefit from its generalistic feeding abilities. PMID- 20738612 TI - The influence of maternal condition on offspring performance in sockeye salmon Oncorhynchus nerka. AB - Eggs were taken from adult sockeye salmon Oncorhynchus nerka that had reached their journey's end in spawn-ready and moribund condition, and fertilized by healthy males. Egg number, size, hatching success and offspring growth did not differ with maternal condition, which suggests the absence of any persisting physiological maternal effects. Differences were noted in the swimming behaviour and physiology of the offspring at parr stage. In a 30 min schooling test conducted using groups of five in a flume, parr from moribund females were more likely to fatigue, were not as tightly schooled, and had a diminished startle response, both in the per cent responding and the burst distance. In individual, confined swimming tests conducted within a tube, post-exercise plasma lactate concentration, which is an indicator of white muscle use, was greater for parr from moribund adult females. The moribund females also had elevated lactate following exercise (their migration), which suggests heritable differences may exist in muscle use. This study shows that juvenile O. nerka artificially propagated from females exhausted by their return migration can exhibit swimming performance differences, indicating that maternal condition may need to be considered in breeding programmes. PMID- 20738613 TI - Assessment of the dorsal fin spine for chimaeroid (Holocephali: Chimaeriformes) age estimation. AB - Previous attempts to age chimaeroids have not rigorously tested assumptions of dorsal fin spine growth dynamics. Here, novel imaging and data-analysis techniques revealed that the dorsal fin spine of the spotted ratfish Hydrolagus colliei is an unreliable structure for age estimation. Variation among individuals in the relationship between spine width and distance from the spine tip indicated that the technique of transverse sectioning may impart imprecision and bias to age estimates. The number of growth-band pairs observed by light microscopy in the inner dentine layer was not a good predictor of body size. Mineral density gradients, indicative of growth zones, were absent in the dorsal fin spine of H. colliei, decreasing the likelihood that the bands observed by light microscopy represent a record of growth with consistent periodicity. These results indicate that the hypothesis of aseasonal growth remains plausible and it should not be assumed that chimaeroid age is quantifiable by standard techniques. PMID- 20738614 TI - Multi-scale recruitment patterns and effects on local population size of a temperate reef fish. AB - Recruitment of the temperate reef fish Coris julis was studied across the Azores Archipelago (central North Atlantic), over four consecutive recruitment seasons and at three spatial scales: between islands (separated by 100s of km), sites within islands (separated by 10s of km) and transects within sites (separated by 10s of m). At the largest scale (i.e. between islands) spatial recruitment patterns were highly variable, suggesting the influence of stochastic processes. Recruitment was spatially consistent within islands, even though magnitude was unpredictable between years, indicating that processes at meso-scales are probably more deterministic. Recruits settled randomly at the transect scale, probably reflecting habitat homogeneity. It was proposed that large and island scale patterns reflect larval availability, driven by physical and biological processes occurring in the plankton. No evidence was found for a density dependent relationship between newly settled and 2 week settled C. julis nor between cumulative recruitment and young-of-the-year. It appears that adult density is limited by larval supply (pre-settlement regulation) at low recruitment sites, and determined by post-settlement, density-dependent processes at high recruitment sites. This work is one of few to investigate multiple spatial and temporal scales of recruitment for a coastal fish species inhabiting isolated, temperate oceanic islands and hence, provides a novel comparison to the many studies of recruitment on coral reefs and other, more connected systems. PMID- 20738615 TI - Linking marine and freshwater growth in western Alaska Chinook salmon Oncorhynchus tshawytscha. AB - The hypothesis that growth in Pacific salmon Oncorhynchus spp. is dependent on previous growth was tested using annual scale growth measurements of wild Chinook salmon Oncorhynchus tshawytscha returning to the Yukon and Kuskokwim Rivers, Alaska, from 1964 to 2004. First-year marine growth in individual O. tshawytscha was significantly correlated with growth in fresh water. Furthermore, growth during each of 3 or 4 years at sea was related to growth during the previous year. The magnitude of the growth response to the previous year's growth was greater when mean year-class growth during the previous year was relatively low. Length (eye to tail fork, L(ETF)) of adult O. tshawytscha was correlated with cumulative scale growth after the first year at sea. Adult L(ETF) was also weakly correlated with scale growth that occurred during freshwater residence 4 to 5 years earlier, indicating the importance of growth in fresh water. Positive growth response to previous growth in O. tshawytscha was probably related to piscivorous diet and foraging benefits of large body size. Faster growth among O. tshawytscha year classes that initially grew slowly may reflect high mortality in slow growing fish and subsequent compensatory growth in survivors. Oncorhynchus tshawytscha in this study exhibited complex growth patterns showing a positive relationship with previous growth and a possible compensatory response to environmental factors affecting growth of the age class. PMID- 20738616 TI - Early development of the digestive tract (pharynx and gut) in the embryos and pre larvae of the European sea bass Dicentrarchus labrax. AB - The European sea bass Dicentrarchus labrax is a marine teleost important in Mediterranean aquaculture. The development of the entire digestive tract of D. labrax, including the pharynx, was investigated from early embryonic development to day 5 post hatching (dph), when the mouth opens. The digestive tract is initialized at stage 12 somites independently from two distinct infoldings of the endodermal sheet. In the pharyngeal region, the anterior infolding forms the pharynx and the first gill slits at stage 25 somites. The other three gill arches and slits are formed between 1 and 5 dph. Posteriorly, in the gut tube region, a posterior infolding forms the foregut, midgut and hindgut. The anus opens before hatching, at stage 28 somites. Associated organs (liver, pancreas and gall bladder) are all discernable from 3 dph. Some aspects of the development of the two independent initial infoldings seem original compared with data in the literature. These results are discussed and compared with embryonic and post embryonic development patterns in other teleosts. PMID- 20738617 TI - Female guppies Poecilia reticulata prefer males that can learn fast. AB - The role of learning ability as a potentially desirable male trait in sexual selection was investigated in the guppy Poecilia reticulata. Mate preference tests and the rate at which a male learnt two mazes were used to determine whether female preference was related to male learning ability. In addition, male body size and saturation of the orange patches were measured. Female preference was found to be related to rate of learning, such that males that learnt the mazes faster were found to be more attractive to females, but was not found to be related to body size or saturation. PMID- 20738618 TI - Resource utilization by deep-sea sharks at the Le Danois Bank, Cantabrian Sea, north-east Atlantic Ocean. AB - The feeding habits of birdbeak dogfish Deania calcea, velvet belly lantern shark Etmopterus spinax and blackmouth catshark Galeus melastomus at Le Danois Bank, Cantabrian Sea, south Bay of Biscay were studied in relation to their bathymetric distribution. Deep-sea sharks were collected during two multidisciplinary surveys carried out in October 2003 and April 2004 at the Le Danois Bank. Two different habitats were defined: (1) the top of the bank, ranging from 454 to 642 m depth and covered by fine-sand sediments with a low percentage of organic matter, and (2) the inner basin located between the bank and the Cantabrian Sea's continental shelf, at depths of 810-1048 m, which was characterized by a high proportion of silt and organic matter. Deania calcea was not present at the top of the bank but was abundant below 642 m, while E. spinax was abundant in the shallower top of the bank but was not found in the deeper inner basin. There was almost no bathymetric overlap between these two deep-sea shark species. Galeus melastomus was found over the whole depth range. There seemed to be an ontogenetic segregation with depth for this species, however, since 80% of the specimens collected at the top of the bank were < 600 mm total length (L(T)) (mean 510 mm L(T)), whereas larger individuals (mean 620 mm L(T)) inhabited deeper zones. Galeus melastomus exhibited a significantly higher feeding intensity than both E. spinax at the top of the bank and D. calcea in the inner basin. Little dietary overlap between D. calcea and G. melastomus in the inner basin was found, with D. calcea being an ichthyophagous predator while the diet of G. melastomus at these depths was composed of a variety of meso-bathypelagic shrimps (e.g. Acantephyra pelagica, Pasiphaea spp. and Sergia robusta), cephalopods and fishes. The diets of E. spinax and G. melastomus at the top of the bank showed a high dietary overlap of euphausiids, which represented the main prey taxa for both species. Euphausiids declined in abundance with depth which was reflected in the diet of G. melastomus. The cluster analysis of prey affinities among hauls depicted two major groups, corresponding to the two different habitats (top of the bank and inner basin). Redundancy analysis also indicated top-basin segregation, with euphausiids representing the main prey taxa at the top of the bank and bathypelagic shrimps in the inner basin. Euphausiids and Micromesistius poutassou were key prey within the Le Danois Bank ecosystem since they were positively selected by the three deep-sea shark species. These results show that the feeding ecology of these predators in Le Danois Bank ecosystem is highly influenced by depth-related variables, as a result of changes in prey availability. Overall results were analysed in relation to the deep-sea Le Danois ecosystem structure and functioning. PMID- 20738619 TI - Intercalibration of hydroacoustic and mark-recapture methods for assessing the spawning population size of a threatened fish species. AB - Hydroacoustic counting and a three-year mark-recapture study with passive integrated transponders (PIT tags) were used to estimate the size of a spawning population of nase Chondrostoma nasus, a threatened potamodromous cyprinid that undertakes annual spawning migrations into a tributary of the Danube River. In 2005, the estimates of the size of the spawning population from the hydroacoustic counts (N = 2234, 95% CL 1929-2538) and from the Jolly-Seber model (N = 1198, 95% CL 461-5842) corresponded well. Estimates from the jackknife-estimator based on the hydroacoustic counts yielded slightly higher values (N = 2783, 95% CL 2529 3037), but were still in the same order of magnitude as those from the hydroacoustic and mark-recapture approach. At low run-size, hydroacoustic counting was more time consuming and technically demanding than mark-recapture studies. At the same time, it was non-invasive, provided real-time data on a fine temporal scale, and estimates showed less variability than the Jolly-Seber model. Mark-recapture of fish in spawning streams involved substantial disturbance at a sensitive stage of the life cycle. Hence, hydroacoustics is highly suited for population estimates of threatened potamodromous fishes, where interference needs to be minimized. PMID- 20738620 TI - Population subdivision in Siamese mud carp Henicorhynchus siamensis in the Mekong River basin: implications for management. AB - A molecular approach was employed to investigate stock structure in Siamese mud carp Henicorhynchus siamensis populations collected from 14 sites across mainland south-east Asia, with the major focus being the lower Mekong River basin. Spatial analysis of a mitochondrial DNA fragment (ATPase 6 and 8) identified four stocks in the Mekong River basin that were all significantly differentiated from a population in the nearby Khlong River, Thailand. In the Mekong River basin, populations in northern Lao People's Democratic Republic and northern Thailand represent two independent stocks, and samples from Thai tributaries group with those from adjacent Mekong sites above the Khone Falls to form a third stock. All sites below the Khone Falls constituted a single vast stock that includes Cambodia and the Mekong Delta in Vietnam. While H. siamensis is considered currently to undertake extensive annual migrations across the Mekong River basin, the data presented here suggest that natural gene flow may occur over much more restricted geographical scales within the basin, and hence populations may need to be managed at finer spatial scales than at the whole-of-drainage-basin level. PMID- 20738621 TI - Structural and functional connectivity of marine fishes within a semi-enclosed Newfoundland fjord. AB - The interplay between structural connectivity (i.e. habitat continuity) and functional connectivity (i.e. dispersal probability) in marine fishes was examined in a coastal fjord (Holyrood Pond, Newfoundland, Canada) that is completely isolated from the North Atlantic Ocean for most of the year. Genetic differentiation was described in three species (rainbow smelt Osmerus mordax, white hake Urophycis tenuis and Atlantic cod Gadus morhua) with contrasting life histories using seven to 10 microsatellite loci and a protein-coding locus, PanI (G. morhua). Analysis of microsatellite differentiation indicated clear genetic differences between the fjord and coastal regions; however, the magnitude of difference was no more elevated than adjacent bays and was not enhanced by the fjord's isolation. Osmerus mordax was characterized by the highest structure overall with moderate differentiation between the fjord and St Mary's Bay (F(ST)c.0.047). In contrast, U. tenuis and G. morhua displayed weak differentiation (F(ST) < 0.01). Nonetheless, these populations did demonstrate high rates (< 75%) of Bayesian self-assignment. Furthermore, elevated differentiation was observed at the PanI locus in G. morhua between the fjord and other coastal locations. Interestingly, locus-specific genetic differentiation and expected heterozygosity were negatively associated in O. mordax, in contrast to the positive associations observed in U. tenuis and G. morhua. Gene flow in these species is apparently unencumbered by limited structural connectivity, yet the observed differentiation suggests that population structuring exists over small scales despite high dispersal potential. PMID- 20738622 TI - Behavioural type in newly emerged steelhead Oncorhynchus mykiss does not predict growth rate in a conventional hatchery rearing environment. AB - Behavioural assays were conducted on newly emerged steelhead Oncorhynchus mykiss to investigate the presence of behavioural syndromes and to determine whether behavioural type in young fish predicts growth rate in a conventional hatchery rearing environment. Individual fry were consistent in their position choice and activity behaviours across safe and unsafe contexts, as well as among assays conducted on different days. Position choice and activity behaviours, however, were not necessarily correlated to each other. Both behaviours predicted feeding rates during behavioural assays, but there was no relationship between fry behaviour and subsequent growth rate or survival during the first 3 months of hatchery rearing. These results support the hypothesis that selection in captivity may be relaxed with respect to behavioural type rather than directional, allowing for increased behavioural variance in domesticated populations. Modest magnitudes of correlations among fry behaviours, however, suggest that behavioural type may be unstable at the onset of the juvenile feeding stage. PMID- 20738623 TI - Effects of temperature on biological and biochemical indicators of the life history strategy of bullhead Cottus gobio. AB - The biological and biochemical effects of temperature on life-history strategy of female bullhead Cottus gobio were investigated. Fish from two populations (Bez Basin, south-east France) experiencing contrasted thermal environments (i.e. more or less stable) were reared during 4 months at three distinct temperatures (7, 9 or 12 degrees C). Both somatic (soma fresh mass and muscle triglyceride content) and reproductive (gonad fresh mass, fecundity, mean diameter of eggs and gonad triglyceride content) indicators were examined. Mixed models indicated that an increasing temperature had significant negative effects on all life-history indicators except for soma fresh mass. Differences in life-history strategy with regard to muscle and gonad triglyceride contents, however, suggest that populations experiencing more variable thermal environments may be better adapted than others to cope with an increasing temperature. These findings may have important implications for C. gobio populations, within the context of climate warming. PMID- 20738624 TI - Effects of crude rapeseed oil on lipid composition in Arctic charr Salvelinus alpinus. AB - This study investigated the effects of crude rapeseed oil (RO) on lipid content and composition in muscle and liver of Arctic charr Salvelinus alpinus. Triplicate groups were fed diets containing fish oil (FO):RO ratio of 100:0, 75:25, 50:50 and 25:75 until two-fold mass increase. Total lipid content increased significantly in the liver with higher proportion of RO in the diet. Profound effects were seen in the fatty acid composition in the analysed tissues with a reduction in 20:5n-3 and 22:6n-3 and an increase in 18:2n-6 with higher RO content in the diets. A drop in cholesterol content was seen at 25% inclusion of RO in both tissues. Wild-caught fish contained a considerably higher amount of 20:4n-6 in both storage and membrane lipids of white muscle compared with the experimental fish. PMID- 20738625 TI - Elevated ability to compete for limited food resources by 'all-fish' growth hormone transgenic common carp Cyprinus carpio. AB - Food consumption, number of movements and feeding hierarchy of juvenile transgenic common carp Cyprinus carpio and their size-matched non-transgenic conspecifics were measured under conditions of limited food supply. Transgenic fish exhibited 73.3% more movements as well as a higher feeding order, and consumed 1.86 times as many food pellets as their non-transgenic counterparts. After the 10 day experiment, transgenic C. carpio had still not realized their higher growth potential, which may be partly explained by the higher frequency of movements of transgenics and the 'sneaky' feeding strategy used by the non transgenics. The results indicate that these transgenic fish possess an elevated ability to compete for limited food resources, which could be advantageous after an escape into the wild. It may be that other factors in the natural environment (i.e. predation risk and food distribution), however, would offset this advantage. Thus, these results need to be assessed with caution. PMID- 20738626 TI - Ecological niche specialization inferred from morphological variation and otolith strontium of Arctic charr Salvelinus alpinus L. found within open lake systems of southern Baffin Island, Nunavut, Canada. AB - The presence of two morphotypes of Arctic charr Salvelinus alpinus was confirmed via morphological variation and otolith strontium (Sr) within three open-lake systems of southern Baffin Island, Nunavut, Canada: Qinngu (LH001), Iqalugaarjuit Lake (PG082) and Qasigiat (PG015). Analysis of otolith Sr indicates that a component of each S. alpinus population within lakes LH001 and PG082 is migratory (large-maturing S. alpinus), whereas another component is lake-resident (small maturing S. alpinus). Alternatively, small and large maturing S. alpinus may both inhabit tidal habitats during their lifetime in lake PG015. Three morphological characters were identified by principal factor analysis (PFA) as characters that were different between maturity groups for all lakes studied: eye diameter, pectoral fin length and pelvic fin length. As well, upper jaw length (LH001 and PG082) and fork depth (PG015) were identified in PFA as traits that differed between morphs. Univariate tests of morphological characters identified by PFA demonstrated maturity group differences with the exception of eye diameter in Lake PG015 and upper jaw length and pelvic fin length in lake LH001. No difference was found in the MANOVA test of upper and lower gill raker number between small-maturing and undeveloped fish within all lakes studied. Clear morphological variation observed between small-maturing and undeveloped fish in all three lakes of the study suggests ecological niche separation between morphotypes. This is the first documented case of lake-resident S. alpinus use of the tidal habitat in the presence of a migratory large-maturing morphotype. PMID- 20738627 TI - Food selection of a corallivorous butterflyfish Chaetodon austriacus in the Red Sea, with particular emphasis on size and fish symbionts of corals. AB - The exquisite butterflyfish Chaetodon austriacus feeds mainly on Acropora, Pocillopora, Montipora and Stylophora in the northern Red Sea. Large colonies of Acropora are preferred over smaller colonies and other coral genera, whereas avoidance is indicated for corals that are occupied by certain coral-associated gobiid fishes of the genus Gobiodon. It is suggested that, apart from coral identity, colony size and potential repellent effects of particular coral symbionts are both important sources of variation in the food selectivity of corallivorous chaetodotids. PMID- 20738628 TI - First occurrence of the lined seahorse Hippocampus erectus in the eastern Atlantic Ocean. AB - A seahorse specimen from Banco Acores (Azores Archipelago) was identified using morphological and molecular genetic data as Hippocampus erectus. This specimen represents the first record of H. erectus in the eastern Atlantic Ocean, well outside its reported range, and may provide evidence of long-distance translocation in what are assumed to be relatively sedentary fish. PMID- 20738629 TI - First record of Randall's snapper Randallichthys filamentosus (Perciformes: Lujanidae) from the eastern Indian Ocean (north-western Australia). AB - The rare Randall's snapper Randallichthys filamentosus is recorded here for the first time in the eastern Indian Ocean from Scott Reef, north-western Australia. A single specimen of R. filamentosus, measuring 495 mm fork length, was captured on 9 July 2006 at a depth of 211 m on the outer reef slopes of Scott Reef. The capture of this specimen indicates that this deepwater fish is more widely distributed than was previously acknowledged and further implies that this species has a dispersal capacity that extends across ocean boundaries. PMID- 20738630 TI - Factors affecting mark quality of alizarin complexone-stained otoliths in juvenile black bream Acanthopagrus butcheri and a prescription for dosage. AB - The relationships between otolith score, a function of increasing stain visibility, and the ratio of alizarin complexone (mg) to fish biomass (g) for 0.1, 0.6 and 7 g black bream Acanthopagrus butcheri show that acceptable marks are produced in all size classes using a stain-to-biomass ratio of 3.3 mg g(-1) following an immersion period of 24 h. PMID- 20738631 TI - Effect of temperature on the gastric evacuation in sprat Sprattus sprattus. AB - Gastric evacuation of groups of juvenile (mean 63 mm total length, LT, 0.283 g dry mass, MD) sprat Sprattus sprattus feeding on brine shrimp Artemia sp. nauplii was studied at six temperatures (7.5, 10, 13, 16, 19.5 and 21.5 degrees C) in the laboratory. Gastric evacuation was best described with a general model: St=S0(1 B)-R(1-B)t)1-B(-1), with St=stomach content at time t, S0=stomach content at time 0, t=time , R, B=constants. The shape parameter was estimated as B=0.668. For comparison with other studies, an exponential model was fitted also to the data. The evacuation constant (R) of the general gastric evacuation model increased exponentially with temperature between 7.5 and 16 degrees C. The slope of the increase was reduced between 16 and 19.5 degrees C and a slight decrease was observed between 19 and 21.5 degrees C. Additionally, the effect of mean MD (range 0.286-1.025 g) was examined. A simple power function (R=R'MDC) described the influence of predator mass on exponential evacuation constant with C=0.503. The results of this investigation were integrated into a consumption model for the calculation of daily rations of S. sprattus: C24=0.0177e0.0775T/S0.668 MD0.503 (1-{1[1+e(-0.659)(T-23.989)](-1)})24/S0.668, with T=ambient temperature (degrees C) and /S0.668= mean of field stomach contents (g dry) individually raised to the power of 0.668. PMID- 20738632 TI - The effect of different kinds of electrolyte and non-electrolyte solutions on the survival rate and morphology of zebrafish Danio rerio embryos. AB - The effect of electrolyte and non-electrolyte solutions on the survival and on the morphology of zebrafish Danio rerio embryos was investigated. Embryos in different ontogenetic stages were incubated in electrolyte (NaCl, KCl, MgCl2 and CaCl2) and non-electrolyte solutions [sucrose and polyvinylalcohol (PVA)] of different concentrations for 5-15 min. The embryos were hatched to the long-pec stage and the effective concentrations which caused a 50% decrease in embryo development (EC50) were determined. The morphometric changes, which were caused by the test solutions, were measured. Ion channel blockers were used to see if active ion transport played a role for embryo survival. Finally, dechorionated embryos were exposed to the test solutions to get indications about the importance of chorion and perivitelline space. For 12 hours post fertilization (hpf) embryos and a 15 min exposure period, EC50 was highest for MgCl2 (1.60 mol l(-1)), followed by sucrose (0.73 mol l(-1)), NaCl (0.49 mol l(-1)), KCl (0.44 mol l(-1)), CaCl2 (0.43 mol l(-1)) and PVA [0.0005 mol l(-1) (2.2%)]. EC50 were lower for early embryonic stages than for advanced stages for all solutions with exception of MgCl2 and sucrose. At the EC50, MgCl2 and CaCl2 solutions did not induce morphometric changes. NaCl and sucrose solutions induced reversible morphometric changes, which were compensated within 10 min. Only the EC50 of KCl and PVA solutions induced permanent morphometric changes, which could not be compensated. Incubation of embryos in electrolyte and non-electrolyte solutions together with ouabain (blocker of Na+- K+ ATPase), HgCl3 (dose-dependent inhibition of aquaporine channels), verapamil (inhibition of calcium and magnesium uptake) and amiloride (inhibition of sodium uptake) significantly decreased the per cent of embryos developing to the long-pec stage in comparison to the same solutions without blockers. Ouabain and HgCl(3) also induced morphometric changes. For dechorionated embryos the survival rates in water and in the different test solutions were similar to untreated embryos. PMID- 20738633 TI - Spawning dynamics and biomass estimates of an anchovy Engraulis australis population in contrasting gulf and shelf environments. AB - The spawning biomass of Australian anchovy Engraulis australis in gulf and shelf waters of South Australia was compared using the daily egg production method (DEPM). The total survey area was 128 700 km2 with recorded spawning areas in gulf and shelf waters of 4898 and 44 618 km2, respectively. High egg densities in the warm, shallow gulf waters were produced by small, young (<1 year old) E. australis that spawned relatively small batches of eggs (c. 855) approximately every 3 days. In cooler, deeper shelf waters, where larger, older E. australis are found, lower egg densities occurred despite individuals producing much larger batches of eggs (c. 15,572) approximately every 7 days. In shelf waters, the highest densities were recorded at inshore sampling stations. Spawning appeared to peak between 0000 and 0100 hours. Females were more abundant than males in samples from both gulf and shelf waters with sex ratios of 0.61 and 0.56, respectively. The spawning biomass of E. australis in shelf waters was 101 522 t, whereas the estimate for gulf waters was 25 374 t. Due to the differences in mean size of the spawning females, however, c. 6x10(9)E. australis were present in each region. The results support the hypothesis that variability in habitat conditions may directly influence E. australis reproduction. A large reserve of young fish in the relatively stable gulf environment may increase the resilience of the E. australis population in South Australia to unfavourable interannual changes in offshore environmental conditions. PMID- 20738634 TI - Functional constraints on nest characteristics of pebble mounds of breeding male hornyhead chub Nocomis biguttatus. AB - Breeding male hornyhead chub Nocomis biguttatus constructed nests in areas with relatively high but less than maximum flow rate and greater than average water depth. Nests comprised c. 3000 pebbles for a total mass of 11 kg. Males selected pebbles of smaller diameter but higher density than pebbles in the immediate vicinity. Thus, nests balanced the risk of mound erosion and energetic cost of nest construction with the benefits of protection from egg predators and a stable internal flow rate for oxygenation. These data help establish environmental management goals for the conservation of N. biguttatus and the lotic ecosystems dependent upon them. PMID- 20738635 TI - Postprandial metabolic increment of southern bluefin tuna Thunnus maccoyii ingesting high or low-lipid sardines Sardinops sagax. AB - This study examined the postprandial metabolism and swimming speed of southern bluefin tuna Thunnus maccoyii when fed sardines Sardinops sagax of either high lipid and high-energy content or low-lipid and low-energy content. Five groups of two or three T. maccoyii (mean+/-s.e. mass=19.8+/-0.5 kg, n=14) were fed either low [2.2% lipid, 5.5 MJ kg(-1) gross energy (GE)] or high-lipid (12.9%, 9.2 MJ kg(-1) GE) S. sagax. Before feeding, T. maccoyii swam at 0.74+/-0.03 body lengths s(-1) (n=5) and their routine metabolic rate was 305+/-15 mg kg(-1) h(-1). Swimming speed and metabolic rate of T. maccoyii increased following feeding. Thunnus maccoyii swam 1.3 and 1.8 times faster during digestion of low and high lipid S. sagax, respectively. Postprandial peak metabolic rate, duration of elevated metabolism and total postprandial metabolic increment were all greater for T. maccoyii that ingested high-lipid S. sagax. When total postprandial increment is represented as a proportion of ingested energy, there was no difference between high and low-lipid meals, equating to between 30 and 35% of ingested energy. It was estimated that increased postprandial swimming costs account for 25 and 46% of the total postprandial metabolic response for low and high-lipid S. sagax meals, respectively. Specific dynamic action (SDA) accounts for c. 20% of ingested energy regardless of S. sagax lipid level. These results confirm that the postprandial metabolic increment of T. maccoyii is greater than most other fish species. Much of the high cost of postprandial metabolic increment can be attributed to increased postprandial swimming costs. For T. maccoyii, it appears that activity and SDA are not independent, which complicates bioenergetic evaluation. High postprandial metabolic costs accentuate the great energetic requirements of T. maccoyii. PMID- 20738636 TI - Ontogeny of the cranial musculature in Corydoras aeneus Callichthyidae, Siluriformes. AB - A complete study of the early ontogeny of the cranial muscles of Corydoras aeneus (Callichthyidae) was undertaken and results were compared with those for the loricariid Ancistrus cf. triradiatus. This comparison reveals a high degree of similarity in the ontogeny of both species' cranial muscles. Both species lack a musculus protractor hyoidei, and the musculus intermandibularis posterior is divided into two different parts that have partly obtained a novel function (serving the lower lip) in A. cf. triradiatus. A similar increase in muscular complexity in this species is found in the dorsal constrictor of the hyoid muscle plate. This constrictor gives rise to the same muscles in both C. aeneus and A. cf. triradiatus, but in A. cf. triradiatus the musculus levator operculi later hypertrophies. In C. aeneus the musculus extensor tentaculi forms a single muscle diverging posteriorly, whereas in A. cf. triradiatus the musculus extensor tentaculi differentiates into two separate bundles. Also, a loricariid neoformation is present called the musculus levator tentaculi. PMID- 20738637 TI - The effect of progressive hypoxia on spontaneous activity in single and shoaling golden grey mullet Liza aurata. AB - The hypothesis of a differential effect of hypoxia on activity in shoaling v. solitary fish was tested in golden grey mullet Liza aurata. In both solitary and shoaling fish, (1) swimming activity increased significantly at 0.05) among swim tests and ranged from 4.54 to 5.20 body lengths s(-1). This result supports the hypothesis that at an early life stage, O. gorbuscha display the same fatigue speeds independent of the swimming test utilized. Whole body and plasma [Na+] and [Cl-] measured at the conclusion of these tests were significantly elevated when compared with control values (P<0.05) and appear to be predominantly associated with dehydration rather than net ion gain. Given this finding for a small salmonid, estimates of swim performance can be accurately measured with acceleration tests lasting<10 min, allowing a more rapid processing than is possible with a longer critical swim speed test. PMID- 20738639 TI - Effect of turbulence on feeding intensity and survival of Japanese flounder Paralichthys olivaceus pelagic larvae. AB - Three-day rearing experiments were conducted to study the effect of turbulence on the feeding intensity and survival of pelagic larvae of Japanese flounder Paralichthys olivaceus. Four levels of turbulence as control (10(-7.2) m2 s(-3)), low (10(-6.2) m2 s(-3)), mid (10(-5.6) m2 s(-3)) and high (10(-5.0) m2 s(-3)) were set by changing the flow rate of water pumped through pipes set on the bottom of the tanks. In B-stage larvae, defined as having buds of elongated dorsal fin rays, the feeding intensity and growth were higher in the low and mid turbulence levels, while survival was highest in the control level. Most of the larvae surviving in the control level, however, were judged to be in a seriously starved condition leading to subsequent high mortality. Because the three-day span of the rearing experiments was thought to be a little shorter than the periods before starvation-induced, high mortality occurs. In contrast, for D stage larvae, their feeding and growth were optimal in the control and low levels. Feeding was more adversely affected in the high level for D-stage larvae compared with B-stage larvae. This is probably due to the compressed body shape and elongated dorsal fin rays of D-stage larvae, which may be more strongly affected by turbulence and, as a consequence, the larval feeding behaviour such as pursuit and capture of prey organisms becomes less efficient than in lower turbulence. Considering the vertical distribution of B and D-stage larvae in the oceanic water column, the optimum turbulence level range found in the present study corresponded to a wind speed of 7-10 m s(-1). Therefore, moderate weather conditions of this wind speed range are considered to potentially enhance survival of early larval stages of P. olivaceus. PMID- 20738640 TI - Size and age estimates at sexual maturity for the little skate Leucoraja erinacea from the western Gulf of Maine, U.S.A. AB - Size and age estimates at sexual maturity were determined for 162 male and 273 female little skates Leucoraja erinacea collected from the western Gulf of Maine. Maturity ogives suggest that 50% maturity in females occurs at age 9.5 years and 480 mm total length (LT), whereas 50% maturity in males occurs at a slightly younger age of 7.7 years and smaller size of 460 mm LT. Age estimates were made from 389 L. erinacea ranging in size from 93 to 570 mm LT. The index of average per cent error and age-bias plots indicated that the ageing methods were precise and non-biased. Additionally, annual periodicity of band formation was validated with oxytetracycline in eight individuals (three males and five females) ranging in age from 3 to 12 years. In conclusion, results from this study indicate that L. erinacea exhibits characteristics that make other elasmobranch populations highly susceptible to overexploitation. PMID- 20738641 TI - Interactions between immunocompetence, somatic condition and parasitism in the chub Leuciscus cephalus in early spring. AB - Relationships between immunocompetence, somatic condition, parasitism and water temperature in a wild population of chub Leuciscus cephalus were investigated. The effects of a rapid temperature increase in early spring were studied for both sexes as water temperature affects immunocompetence. Investment in gonads and activity of mucus lysozyme were negatively correlated; lysozyme activity decreased as temperature increased. No correlations were found between lysozyme activity and parasitism or intensity of infection by monogeneans, the most abundant metazoan parasite group in L. cephalus. There was a positive correlation, however, between respiratory burst intensity and parasitism. Indices of investment in gonads and spleen were correlated, showing that energetic reserves allowed either investment in gonads and spleen, or that spleen investment, even if often used in other studies in immunoecology, was not always a significant indicator of immunocompetence during this period. This last proposition is supported by the lack of correlation between spleen investment and other factors linked to immunocompetence. PMID- 20738642 TI - Specialized morphology for a generalist diet: evidence for Liem's Paradox in a cichlid fish. AB - The stable isotope ratio and seasonal changes in diet of Alluaud's haplo Astatoreochromis alluaudi, a cichlid fish with massive pharyngeal jaws well known for its ability to process hard-bodied prey, are described. The diet of A. alluaudi was quantified in Lake Saka, Uganda, over a period of 30 months. Variation in physico-chemical variables (mean monthly rainfall, water temperature, turbidity and dissolved oxygen), as well as potential competitor density and food abundance, was measured throughout the second half of the study (14 months). Stomach contents and isotope analysis revealed a diet comprised mainly of fishes and insects, with a low contribution of molluscs (0-33%) in any given month. No correlation was detected between diet and either macroinvertebrate abundance or competitor abundance. The running average rainfall was positively related to the percentage of fish consumed per month. Although A. alluaudi exhibits an apparent molluscivorous trophic morphology in Lake Saka, molluscs did not appear to compose a major portion of its diet. Gradients of rainfall seemed to be the most important environmental predictor of diet choice in Lake Saka. These results are discussed with reference to Liem's Paradox that apparently morphologically specialized fishes often function as generalist feeders in the wild. PMID- 20738643 TI - Migratory behaviour and survival rates of wild northern Atlantic salmon Salmo salar post-smolts: effects of environmental factors. AB - To study smolt behaviour and survival of a northern Atlantic salmon Salmo salar population during river descent, sea entry and fjord migration, 120 wild S. salar were tagged with acoustic tags and registered at four automatic listening station arrays in the mouth of the north Norwegian River Alta and throughout the Alta Fjord. An estimated 75% of the post-smolts survived from the river mouth, through the estuary and the first 17 km of the fjord. Survival rates in the fjord varied with fork length (LF), and ranged from 97.0 to 99.5% km(-1). On average, the post smolts spent 1.5 days (36 h, range 11-365 h) travelling from the river mouth to the last fjord array, 31 km from the river mouth. The migratory speed was slower (1.8 LF s(-1)) in the first 4 km after sea entry compared with the next 27 km (3.0 LF s(-1)). Post-smolts entered the fjord more often during the high or ebbing tide (70%). There was no clear diurnal migration pattern within the river and fjord, but most of the post-smolts entered the fjord at night (66%, 2000-0800 hours), despite the 24 h daylight at this latitude. The tidal cycle, wind-induced currents and the smolts' own movements seemed to influence migratory speeds and routes in different parts of the fjord. A large variation in migration patterns, both in the river and fjord, might indicate that individuals in stochastic estuarine and marine environments are exposed to highly variable selection regimes, resulting in different responses to environmental factors on both temporal and spatial scales. Post-smolts in the northern Alta Fjord had similar early marine survival rates to those observed previously in southern fjords; however, fjord residency in the north was shorter. PMID- 20738644 TI - Feeding ecology of pelagic fish larvae and juveniles in slope waters of the Gulf of Mexico. AB - Stable isotope ratios of carbon (delta13C) and nitrogen (delta15N) were used to investigate feeding patterns of larval and early juvenile pelagic fishes in slope waters of the Gulf of Mexico. Contribution of organic matter supplied to fishes and trophic position within this pelagic food web was estimated in 2007 and 2008 by comparing dietary signatures of the two main producers in this ecosystem: phytoplankton [based on particulate organic matter (POM)] and Sargassum spp. Stable isotope ratios of POM and pelagic Sargassum spp. were significantly different from one another with delta13C values of POM depleted by 3-6 per thousand and delta15N values enriched by 2 relative to Sargassum spp. Stable isotope ratios were significantly different among the five pelagic fishes examined: blue marlin Makaira nigricans, dolphinfish Coryphaena hippurus, pompano dolphinfish Coryphaena equiselis, sailfish Istiophorus platypterus and swordfish Xiphias gladius. Mean delta13C values ranged almost 2 among fishes and were most depleted in I. platypterus. In addition, mean delta15N values ranged 4-5 with highest mean values found for both C. hippurus and C. equiselis and the lowest mean value for M. nigricans during both years. Increasing delta13C or delta15N with standard length suggested that shifts in trophic position and diet occurred during early life for several species examined. Results of a two-source mixing model suggest approximately an equal contribution of organic matter by both sources (POM=55%; pelagic Sargassum spp.=45%) to the early life stages of pelagic fishes examined. Contribution of organic matter, however, varied among species, and sensitivity analyses indicated that organic source estimates changed from 2 to 13% for a delta(13)C fractionation change of +/-0.25 per thousand or a delta15N fractionation change of +/-1.0 per thousand relative to original fractionation values. PMID- 20738645 TI - Risk-taking behaviour variation over time in sea bass Dicentrarchus labrax: effects of day-night alternation, fish phenotypic characteristics and selection for growth. AB - Differences in bold and shy personality on sea bass Dicentrarchus labrax were investigated between a population (wild) produced from wild-brood fish and a population (selected) produced from selected-brood fish. During the experiment (112 days), fish were reared under self-feeding condition to characterize the feeding behaviour of each individual fish. Three risk-taking tests (T1, T2 and T3 of 24 h with day-night alternation) were carried out at >1 month intervals on 180 fish of each strain in order to monitor D. labrax behaviour over time and in relation to the light:dark period. A risk-taking score was evaluated via a preference choice between a safe zone (without food) and a risky zone (potentially with food) by recording the number and the duration of individual passages through an opening in an opaque divider. Results showed that fish performed passages preferentially during the night period and that wild fish were generally bolder than selected fish during T1 and T2 but showed a decrease in risk taking during T3, contrary to selected fish which showed a constant increase in their risk-taking behaviour. The phenotypic characteristics of the bold fish were different in the two strains: wild bold fish were the smallest within the wild strain and selected bold fish presented the higher growth rate within the selected strain. For both strains, these bold fish were also generally characterized by a high feed-demand activity. Fish hunger state thus seemed to be the highest motivation for risk-taking behaviour under the present conditions. Furthermore, behavioural variations over tests such as higher risk taking (number of passages) and faster exploratory responses (higher score emergence) could be interpreted as relevant indicators of the learning process and habituation. According to the results, however, no real difference in coping strategy between strains could be observed at this first stage of domestication and selection. PMID- 20738646 TI - Age and growth of the gulf toadfish Opsanus beta based on otolith increment analysis. AB - In the present study, sagittal otoliths of confirmed male and female specimens of the gulf toadfish Opsanus beta that were collected monthly over the course of a year from Biscayne Bay, Florida, U.S.A. were analysed. The timing and frequency of O. beta spawning seasons are reported by examination of the gonado-somatic index. The estimated ages of males and females ranged from <1 year to 6 and 5 years, respectively. Strong sexual dimorphism in growth was apparent with von Bertalanffy parameter estimates for males of Linfinity=393.8 mm, K=0.30, t0=0.36 and females of Linfinity=201.1 mm, K=0.79, t0=0.47. Comparison with previously published growth trajectories of the more northerly distributed conspecific Opsanus tau showed that O. beta males had a higher growth rate. Female O. beta and O. tau growth trajectories appear similar, with an indication that the former becomes asymptotic at least a year before the latter. Results are discussed in the context of temperature regimes, reproductive energy allocation and waste urea excretion in the two species. PMID- 20738647 TI - Coronary vascular volume remodelling in rainbow trout Oncorhynchus mykiss. AB - The 34% increase in relative ventricular mass (Mrv) resulting from chronic anaemia (induced by an intraperitoneal injection of phenylhydrazine hydrochloride) was accompanied by a 117% increase in coronary vascular volume of diploid rainbow trout Oncorhynchus mykiss. Coronary vascular volume of normocythemic triploid fish was similar to that of normocythemic diploid fish despite a larger Mrv. These observations, in combination with previous studies, suggest that the vascularity of compact myocardium in O. mykiss can vary independently of Mrv. PMID- 20738648 TI - Methods for estimating detection efficiency and tracking acoustic tags with mobile transect surveys. AB - Mobile transect surveys were conducted for 5 years in a deep fjord looking for weak acoustic tags, most of which were in dead fishes lying on the seabed. Detection efficiencies were quantified because inferences about fish presence were made from tag detection data but a considerable proportion of tags were not detected. Methods for assessing transect widths using cumulative probabilities of measured perpendicular distances from blind transect lines to triangulated tag locations are described. Three methods for estimating detection efficiencies are presented: fitting attenuation functions to perpendicular distance data, simultaneous use of two receiver systems and test tag surveys. Several factors that influenced these detection efficiencies and ranges are shown, including boat speed, depth of tag, tag type, different hydrophone-receiver systems and variation among individual hydrophones and receivers of the same model. The trade off between detection efficiency per unit area and area swept is discussed, which is largely based on boat speed during transects. Finally, several methods are suggested for increasing decoding efficiencies in mobile tracking studies when tags are heard but are difficult to decode. PMID- 20738649 TI - Hypoxia and life-history traits in a eurytopic African cichlid. AB - This study quantified variation in key life-history traits of the widespread African mouth-brooding cichlid Pseudocrenilabrus multicolor victoriae. Egg size, number, batch reproductive effort, size at maturity and brooding efficiency were compared among field populations across a wide range of dissolved oxygen (DO) concentrations from extreme hypoxia to normoxia. In the laboratory, a similar suite of characters was quantified in F1 of low- and high-DO origin reared under low or high DO. In general, females from low-DO habitats and females reared under low DO were characterized by a smaller size at maturity and no difference in batch reproductive effort when compared with females from high-DO habitats or females reared under normoxia. A trade-off between egg size and number was evident in the field and in the laboratory-rearing experiment, but the direction of the trade-off differed. Egg size was negatively correlated with egg number across field populations; females collected from low-DO sites generally had more, smaller eggs relative to females from high-DO sites. In the laboratory-rearing experiment, F1 females of high-DO origin produced larger, fewer eggs than F1 females of low-DO origin, lending support to the field results and suggesting a heritable component to these traits. There was also an element of developmental plasticity, F1 females raised under low DO produced larger, fewer eggs compared with F1 females raised under high DO (regardless of population) suggesting that DO may interact with other variables to determine egg size in the field. PMID- 20738650 TI - Diet and trophic plasticity of an herbivorous blenny Scartella cristata of subtropical rocky shores. AB - The goals of the present study were to investigate the feeding rates of Scartella cristata, accounting for different water temperature regimes, and to analyse spatial and seasonal variations in its diet. The feeding rate of S. cristata was higher in warmer waters and was not correlated with season. A typical herbivorous diel feeding pattern was observed, with a steady increase in bite rate throughout the morning until a plateau in the early afternoon, followed by an abrupt decrease until the end of the daylight period. The gut contents of S. cristata included at least 41 different items. Detritus and algae (mainly filamentous) comprised most of the bulk of S. cristata's diet. Scartella cristata also exhibited significant seasonal and spatial variability in its diet. This study highlights the importance of detritus within the epilithic algal matrix in the diet of S. cristata and pinpoints that, as in coral reefs, the detrital pathway exerts an important role in the trophodynamics of subtropical rocky shores where these fish are abundant. PMID- 20738651 TI - Are the dynamics of gastric evacuation of natural prey in a piscivorous flatfish different from what is going on in a gadoid? AB - Despite the fact that the stomach of turbot Psetta maxima is a curved tube that forms a half circle, it was demonstrated that gastric evacuation in this predatory flatfish fed natural prey closely followed the surface-dependent cylinder model developed from studies on gadoids with a straight stomach. Evacuation experiments were performed on two size groups of P. maxima fed sandeel Ammodytes tobianus as well as on P. maxima fed brown shrimp Crangon crangon at three different temperatures. This enabled the provision of a gastric evacuation model for studies on P. maxima, which takes into account the effects of the explanatory variables predator size, temperature, prey energy density and resistance of prey to the digestive processes in the stomach. Basically, the cylinder model predicts that a square-root function accurately describes gastric evacuation, which is inconsistent with the conclusion of a previous study on P. maxima that evacuation of A. tobianus is essentially linear with time. Use of the cylinder model to the values of the explanatory variables presented in the latter study, however, gave accurate predictions of the actually acquired evacuation data, which points to the generic value of the model. PMID- 20738652 TI - Reproductive parasitism: male and female responses to conspecific and heterospecific intrusions at spawning in a mouth-brooding cichlid Ophthalmotilapia ventralis. AB - A rare form of alternative reproductive behaviour without simultaneous parasitic spawning was observed in Ophthalmotilapia ventralis, a lekking mouth-brooding cichlid from Lake Tanganyika. Floater males attempted to sneak opportunistically into the territory to actively court the female, while the owner (bourgeois male) defended the territory against other potential intruders. Floater males had more body fat than territory owners and generally higher condition factors. In field experiments, the response of bourgeois males and courted females was tested towards floaters and egg predators (a catfish Synodontis multipunctatus) present in the territories. Territory owners responded aggressively particularly to floaters, and female responsiveness to bourgeois male courtship tended to decline when floaters were present. The potential influence of reproductive parasitism on sexual selection in mouth-brooding cichlids is discussed. PMID- 20738653 TI - Restoring depleted coral-reef fish populations through recruitment enhancement: a proof of concept. AB - To determine whether enhancing the survival of new recruits is a sensible target for the restorative management of depleted coral-reef fish populations, settlement-stage ambon damsel fish Pomacentrus amboinensis were captured, tagged and then either released immediately onto small artificial reefs or held in aquaria for 1 week prior to release. Holding conditions were varied to determine whether they affected survival of fish: half the fish were held in bare tanks (non-enriched) and the other half in tanks containing coral and sand (enriched). Holding fish for this short period had a significantly positive effect on survivorship relative to the settlement-stage treatment group that were released immediately. The enrichment of holding conditions made no appreciable difference on the survival of fish once released onto the reef. It did, however, have a positive effect on the survival of fish while in captivity, thus supporting the case for the provision of simple environmental enrichment in fish husbandry. Collecting and holding settlement-stage fish for at least a week before release appear to increase the short-term survival of released fish; whether it is an effective method for longer-term enhancement of locally depleted coral-reef fish populations will require further study. PMID- 20738654 TI - Evaluation of a non-invasive tagging system for laboratory studies using three spined sticklebacks Gasterosteus aculeatus. AB - A non-invasive tagging system for individual identification of three-spined sticklebacks Gasterosteus aculeatus was evaluated. The tags were easily detected via video, and tagged and non-tagged fish did not differ in terms of growth, activity levels or shoaling behaviour. PMID- 20738656 TI - Courtship sounds and associated behaviours in the Canestrini's goby Pomatoschistus canestrinii. AB - Courtships sounds and associated behaviours were recorded in the Canestrini's goby Pomatoschistus canestrinii using a simultaneous video-acoustic system: the male exhibited a display composed of both a visual (rapid head movements) and an acoustic component (thump sound), and its intensity was positively associated with that of a female visual display. PMID- 20738655 TI - Observations on the seasonal breeding biology and fine structure of the egg surface in the white piranha Serrasalmus brandtii from the Sao Francisco River basin, Brazil. AB - In the Juramento Reservoir, south-eastern Brazil, the white piranha Serrasalmus brandtii showed a prolonged reproductive season, with evidence for multiple spawning and a reproductive peak associated with seasonal rains. The egg surface exhibited a honeycomb-like pore canal arrangement and an adhesive apparatus surrounding the micropyle. Electron microscopic analysis suggests a role for the micropylar cell and neighbouring follicular cells in secretion of substances for egg attachment. PMID- 20738657 TI - The efficacy of the aquatic anaesthetic AQUI-S for anaesthesia of a small freshwater fish, Melanotaenia australis. AB - For stage four anaesthesia of the western rainbowfish Melanotaenia australis the most efficacious concentration of AQUI-S was found to be 80 mg l(-1) when five different doses were tested at 27 degrees C (range 26.5-27.5 degrees C). This gave a mean+/-s.e. (n=10) induction time of 140.4+/-8.9 s and recovery time of 180.2+/-8.9 s and resulted in 10% mortality when fish were continuously exposed for 15 min. All fish given this dose during induction and recovery time trials ate within 1 h of recovery, and there was zero mortality during a subsequent 1 month monitoring period. PMID- 20738658 TI - Preliminary examination of oxidative stress in juvenile spring Chinook salmon Oncorhynchus tshawytscha of wild origin sampled from transport barges. AB - Migrating juvenile wild Chinook salmon Oncorhynchus tshawytscha, collected and loaded onto transport barges at Lower Granite Dam on the Snake River, were sampled from barges at John Day Dam, 348 km downstream, at 5 day intervals beginning in late April and ending in late May. An increase in lipid peroxidation and decrease in vitamin E in liver were observed from early to late in the barge transportation season. These changes seemed unrelated to changes in plasma cortisol or corresponding glucose levels, which declined from early to late in the season, or the concentration of n-3 highly unsaturated fatty acid (HUFA) concentrations in tissue but may be related to water temperature, which increased during the transport season, or other changes associated with the parr-smolt transformation. PMID- 20738666 TI - The Darwinian stickleback Gasterosteus aculeatus: a history of evolutionary studies. AB - The history of studies on the taxonomy and evolutionary biology of the three spined stickleback Gasterosteus aculeatus from the 18th century to the present is reviewed. After the publication of Darwin's Origin of the Species, four important dates, 1925, 1947, 1967 and 2001, are identified as marking major gains in the understanding of the evolution of the diversity in morphological, life-history, physiological and behavioural traits that characterizes G. aculeatus. The period 1925-1970 led to the identification of the main themes of research: status and adaptive significance of lateral-plate morphs; inter and intrapopulation trait variation in freshwater resident G. aculeatus and the adaptive significance of the variation. Between 1970 and 2001, these themes were investigated using variation observed particularly along the Pacific coast of the U.S.A. and Canada, notably in the Cook Inlet region of Alaska and the Haida Gwaii Archipelago. Studies on adaptive radiation and reproductive isolation in lacustrine, ecomorph pairs (limnetics and benthics) discovered in the Strait of Georgia region have been particularly productive. From 2001, the application of genomic studies to these problems began to open up the study of the relationships between genotype, phenotype and selective advantage to causal analysis. PMID- 20738667 TI - Three-spined sticklebacks Gasterosteus aculeatus as a model for exploring behavioural biology. AB - Niko Tinbergen chose the three-spined stickleback Gasterosteus aculeatus for his classic behavioural studies because they are small, robust, common and easy to house in the laboratory under reasonably natural conditions and also because their behaviour, while sufficiently simple to be tractable, is still sufficiently complex to be interesting. An analysis of citation records shows that this was an inspired choice. Research on these small fish has addressed all four of Tinbergen's famous questions (causation, development, functions and evolution) and has contributed to the understanding of many different behavioural systems. The G. aculeatus literature is used here to explore several themes in fundamental behavioural biology (diet choice, shoaling, behavioural syndromes and sexual signalling) and the extent to which research using G. aculeatus has informed both fundamental and applied behavioural biology, the latter in the context of aquaculture research. PMID- 20738668 TI - Implications of a fossil stickleback assemblage for Darwinian gradualism. AB - Darwin postulated that a complete fossil record would contain numerous gradual transitions between ancestral and descendant species, but 150 years after publication of The Origin of Species, few such transitions have materialized. The fossil stickleback Gasterosteus doryssus and the deposit in which it occurs provide excellent conditions to detect such transitions. Abundant, well-preserved fossils occur in a stratigraphic setting with fine temporal resolution. The paleoecology of G. doryssus resembles the ecology of modern lakes that harbour the phenotypically similar three-spined stickleback Gasterosteus aculeatus. Gasterosteus aculeatus are primitively highly armoured, but G. doryssus comprised two contemporaneous biological species with relatively weak armour, including a near-shore, benthic feeder (benthic) and an offshore planktivore (limnetic). The benthic species expanded its range into the limnetic zone of the lake, where it apparently switched to planktivory and evolved reduced armour within c. 5000 years in response to directional selection. Although gradual evolution of mean phenotypes occurred, a single major gene caused much of evolutionary change of the pelvic skeleton. Thus, Darwin's expectation that transitions between species in the fossil record would be gradual was met at a fine time scale, but for pelvic structure, a well-studied trait, his expectation that gradual change would depend entirely on numerous, small, heritable differences among individuals was incorrect. PMID- 20738669 TI - Along the speciation continuum in sticklebacks. AB - Speciation can be viewed as a continuum, potentially divisible into several states: (1) continuous variation within panmictic populations, (2) partially discontinuous variation with minor reproductive isolation, (3) strongly discontinuous variation with strong but reversible reproductive isolation and (4) complete and irreversible reproductive isolation. Research on sticklebacks (Gasterosteidae) reveals factors that influence progress back and forth along this continuum, as well as transitions between the states. Most populations exist in state 1, even though some of these show evidence of disruptive selection and positive assortative mating. Transitions to state 2 seem to usually involve strong divergent selection coupled with at least a bit of geographic separation, such as parapatry (e.g. lake and stream pairs and mud and lava pairs) or allopatry (e.g. different lakes). Transitions to state 3 can occur when allopatric or parapatric populations that evolved under strong divergent selection come into secondary contact (most obviously the sympatric benthic and limnetic pairs), but might also occur between populations that remained in parapatry or allopatry. Transitions to state 4 might be decoupled from these selective processes, because the known situations of complete, or nearly complete, reproductive isolation (Japan Sea and Pacific Ocean pair and the recognized gasterosteid species) are always associated with chromosomal rearrangements and environment-independent genetic incompatibilities. Research on sticklebacks has thus revealed complex and shifting interactions between selection, adaptation, mutation and geography during the course of speciation. PMID- 20738670 TI - Rapid ecological speciation in three-spined stickleback Gasterosteus aculeatus from Middleton Island, Alaska: the roles of selection and geographic isolation. AB - Morphological analysis of three-spined stickleback Gasterosteus aculeatus collected in Middleton Island, Alaska, was conducted in order to study how gene flow and selection interact during divergence. Middleton Island was uplifted by 3.4 m during the Great Alaska Earthquake in 1964; this event formed a series of new freshwater sites, triggering rapid evolution, and probably rapid speciation, in G. aculeatus populations that colonized them. The level of hybridization between the anadromous and the resident freshwater populations is reflected by the level of morphological variance of the resident freshwater G. aculeatus. Therefore, geographic isolation of the sites from the sea (approximating gene flow) and ionic concentration of the water (reflecting selection pressures) were correlated with morphological variance of the resident freshwater populations. Geographic isolation was negatively correlated with morphological variance in a majority of the analysed traits. Both selection and gene flow surrogates were found to be important influences on variance in morphology, though selection had a larger effect, especially on armour traits. It was concluded that gene flow appeared to constrain ecological speciation, but even in the presence of gene flow the strong selection in the freshwater environment was apparently leading to rapid divergence. PMID- 20738671 TI - Occurrence of four-spined Gasterosteus aculeatus in an isolated Croatian river population. AB - An isolated population of the three-spined stickleback Gasterosteus aculeatus in Croatia was found to have a high incidence of specimens either having a fourth dorsal spine or showing remnants of a fourth spine. Juvenile individuals showed a 9.4% incidence of a fourth spine. The population was examined for asymmetry of the skeletal defensive complex in order to determine whether the additional spine could be the result of developmental instability, a response to predation or environmental conditions. PMID- 20738672 TI - Body armour and lateral-plate reduction in freshwater three-spined stickleback Gasterosteus aculeatus: adaptations to a different buoyancy regime? AB - Several factors related to buoyancy were compared between one marine and two freshwater populations of three-spined stickleback Gasterosteus aculeatus. Fish from all three populations had buoyancy near to neutral to the ambient water. This showed that neither marine nor freshwater G. aculeatus used swimming and hydrodynamic lift to prevent sinking. Comparing the swimbladder volumes showed that freshwater completely plated G. aculeatus had a significantly larger swimbladder volume than both completely plated marine and low-plated freshwater G. aculeatus. Furthermore, body tissue density was lower in low-plated G. aculeatus than in the completely plated marine and freshwater fish. The results show that G. aculeatus either reduce tissue density or increase swimbladder volume to adapt to lower water density. Mass measurements of lateral plates and pelvis showed that loss of body armour in low-plated G. aculeatus could explain the tissue density difference between low-plated and completely plated G. aculeatus. This suggests that the common occurrence of plate and armour reduction in freshwater G. aculeatus populations can be an adaptation to a lower water density. PMID- 20738673 TI - Latitudinal variation in photoperiodic response of the three-spined stickleback Gasterosteus aculeatus in western North America. AB - Reproductive maturation in both male and female three-spined stickleback Gasterosteus aculeatus was strongly photoperiodic in a northern population (Alaska, 61 degrees N) but not in a southern population (Oregon, 43 degrees N) from western North America. Increasing reliance on photoperiod with increasing latitude is a general phenomenon among vertebrates, and is probably due to the anticipation of a narrower window of opportunity for reproduction and development at higher latitudes. PMID- 20738674 TI - Further refinement of the non-invasive procedure for measuring steroid production in the male three-spined stickleback Gasterosteus aculeatus. AB - Measurement of steroids that are released into the water via the gills has previously been shown to be an effective way of studying the reproductive endocrinology of the male three-spined stickleback Gasterosteus aculeatus without having to kill the fish. In the present paper, a previous observation on the existence of a compound other than 11-ketotestosterone (11-KT) in water, which cross-reacted in the 11-KT radioimmunoassay was repeated. The amounts of this compound, however, were not sufficient to warrant a separation step prior to carrying out assay. The lack of association between androstenedione levels in water and those in plasma was also confirmed. For the first time, the amounts of testosterone released into the water were shown to be positively correlated with the amounts in plasma, the sampling procedure (placing the fish for 30 min in 50 ml water) had no effect on the rate of release of cortisol but caused a rapid drop in the rate of release of 11-KT (which means that the fish should not be sampled twice in short succession), physical interaction between two nesting males (which was accompanied by aggression) significantly increased the rate of release of 11-KT, androstenedione and testosterone (but not of cortisol) and the rate of release of 11-KT was at its maximum between 2 and 4 h after exposure. PMID- 20738675 TI - Reproductive potential of Schistocephalus solidus-infected male three-spined stickleback Gasterosteus aculeatus from two U.K. populations. AB - Male three-spined stickleback Gasterosteus aculeatus from two U.K. populations with endemic infections of the cestode Schistocephalus solidus were brought into the laboratory prior to the breeding season and transferred to nesting tanks under conditions designed to stimulate sexual maturation. Nesting and courtship behaviours were scored over a 35 day period, after which fish were euthanized and the liver, spleen, kidney and gonads were weighed. Among G. aculeatus from a park pond in Leicester, U.K., infected males rarely engaged in reproductive behaviours and exhibited reduced indices of sexual development, body condition and general health, with effects being largely independent of relative parasite mass (parasite index, I(P)). In contrast, the reproductive behaviour of infected fish from Kendoon Loch in Dumfriesshire, U.K. appeared to be less severely affected, with infected fish regularly building nests and courting females under laboratory conditions. This was paralleled by a more limited effect of infection on physiological indicators of development, condition and general health. Furthermore, behavioural and physiological variables typically correlated with I(P) among infected fish from this population. Although comparing the performance of infected fish from the two populations directly was difficult due to potentially confounding factors, the results support the findings of recent studies showing that the effects of S. solidus on host reproduction are unlikely to be uniform across G. aculeatus populations. One possibility is that variation in the effects of infection arises from differences in the co-evolutionary association times of G. aculeatus with the parasite. PMID- 20738676 TI - Population responses to anthropogenic disturbance: lessons from three-spined sticklebacks Gasterosteus aculeatus in eutrophic habitats. AB - Human-induced environmental changes differ from most natural changes in which they happen at a faster rate and require quicker responses from populations. The first response of populations is usually phenotypically plastic alterations of morphology, physiology and behaviour. This plasticity can be favourable and move the population closer to an adaptive peak in the altered environment and, hence, maintain a viable population, or be maladaptive and move the population further from the peak and increase the risk of extinction. The radiation of the three spined stickleback Gasterosteus aculeatus from the ocean to different freshwater habitats has provided much information on adaptation to new environmental conditions. Currently, human-induced eutrophication is changing the breeding areas of these fish, which creates a model system for investigation of responses to rapid environmental disturbance. Results show that a primary reaction is plastic alterations of behaviour, with some adjustments being adaptive while others are not. At the same time, the strength of sexual selection on several traits is relaxed, which could increase the relative importance of survival selection. Whether this will restore population viability depends on the amount of standing genetic variation in the right direction. Human disturbances can be dramatic and resolution of the limit of flexibility and the possibility of genetic adaptation should be important targets of future research. PMID- 20738677 TI - Disentangling the role of MHC-dependent 'good genes' and 'compatible genes' in mate-choice decisions of three-spined sticklebacks Gasterosteus aculeatus under semi-natural conditions. AB - To investigate and disentangle the role of major histocompatibility complex (MHC) based 'good genes' and 'compatible genes' in mate choice, three-spined sticklebacks Gasterosteus aculeatus with specific MHC IIB genotypes were allowed to reproduce in an outdoor enclosure system. Here, fish were protected from predators but encountered their natural parasites. Mate choice for an intermediate genetic distance between parental MHC genotypes was observed, which would result in intermediate diversity in the offspring, but no mate choice based on good genes was found under the current semi-natural conditions. Investigation of immunological variables revealed that the less-specific innate immune system was more active in individuals with a genetically more divergent MHC allele repertoire. This suggests the need to compensate for an MHC-diminished T-cell repertoire and potentially explains the observed mate choice for intermediate MHC genetic distance. The present findings support a general pattern of mate choice for intermediate MHC diversity (i.e. compatible genes). In addition, the potentially dynamic role of MHC good genes in mate choice under different parasite pressures is discussed in the light of present and previous results. PMID- 20738678 TI - Predator-inspection behaviour in female three-spined sticklebacks Gasterosteus aculeatus is associated with status of gravidity. AB - Differences in predator-inspection behaviour between gravid and non-gravid female as well as between male and female three-spined sticklebacks Gasterosteus aculeatus were investigated. Gravid females confronted with a live rainbow trout Oncorhynchus mykiss showed bolder inspection behaviour than non-gravid ones. The behaviour of gravid females was comparable with that of males, maybe because both face a high risk of predation. The results indicate that antipredator behaviour in female G. aculeatus is not fixed but adjusted to their reproductive state. PMID- 20738679 TI - Cain and Abel reloaded? Kin recognition and male-male aggression in three-spined sticklebacks Gasterosteus aculeatus L. AB - The influence of relatedness on male-male aggression was tested in three-spined sticklebacks Gasterosteus aculeatus. The intensity of aggression against brothers and non-kin males did not differ significantly, indicating that kin recognition plays at most a minor role in aggressive interactions between male G. aculeatus. PMID- 20738680 TI - How not to be seen: does eutrophication influence three-spined stickleback Gasterosteus aculeatus sneaking behaviour? AB - Experiments done in aquaria under control and either turbid or densely vegetated conditions indicated that three-spined stickleback Gasterosteus aculeatus sneaking behaviour is affected by decreased underwater visibility. Success of sneaking behaviour decreased significantly under increased turbidity but not increased vegetation density. The total number of sneaking attempts, including unsuccessful ones, was not affected by either form of decreasing visibility. PMID- 20738681 TI - Molecular pathways during marine fish egg hydration: the role of aquaporins. AB - The pre-ovulatory hydration of the oocyte of marine teleosts, a unique process among vertebrates that occurs concomitantly with meiosis resumption (oocyte maturation), is a critical process for the correct development and survival of the embryo. Increasing information is available on the molecular mechanisms that control oocyte maturation in fish, but the identification of the cellular processes involved in oocyte hydration has remained long ignored. During the past few years, a number of studies have identified the major inorganic and organic osmolytes that create a transient intra-oocytic osmotic potential for hydrating the oocytes, whereas water influx was believed to occur passively. Recent work, however, has uncovered the role of a novel molecular water channel (aquaporin), designated aquaporin-1b (Aqp1b), which facilitates water permeation and resultant swelling of the oocyte. The Aqp1b belongs to a teleost-specific subfamily of water-selective aquaporins, similar to mammalian aquaporin-1 (AQP1) that has possibly evolved by duplication of a common ancestor and further neofunctionalization in oocytes of marine teleosts for water uptake. Strikingly, Aqp1b shows specific regulatory domains at the cytoplasmic tail, which are key to the vesicular trafficking and temporal insertion of Aqp1b in the oocyte plasma membrane during the phase of maximal hydration. These findings are revealing that the mechanism of oocyte hydration in marine teleosts is a highly regulated process based on the interplay between the generation of inorganic and organic osmolytes and the controlled insertion of Aqp1b in the oocyte surface. The discovery of Aqp1b in teleosts provides an important insight into the molecular basis of the production of viable eggs in marine fish. PMID- 20738682 TI - Molecular phylogeny of the Cobitoidea (Teleostei: Cypriniformes) revisited: position of enigmatic loach Ellopostoma resolved with six nuclear genes. AB - Molecular variation in six nuclear genes provides substantive phylogenetic evidence for the recognition of a new cypriniform family, the Ellopostomatidae, to include the enigmatic Southern Asia loach genus Ellopostoma. The current six loach families form a monophyletic group, with the Nemacheilidae as the sister group to Ellopostomatidae; Vaillantellidae forms the sister group to all families exclusive of Botiidae. While the superfamily Cobitoidea includes eight families, the monophyly of this large clade within the Cypriniformes remains a vexing problem despite extensive molecular analyses and is in need of further investigation. PMID- 20738683 TI - Mechanisms of chromosomal evolution and its possible relation to natural history characteristics in Ancistrus catfishes (Siluriformes: Loricariidae). AB - Ancistrus is the most speciose genus of the tribe Ancistrini, with 58 valid species and many yet to be described. Cytogenetic studies were conducted on five apparently undescribed species from the Amazon basin, which showed different diploid numbers: Ancistrus sp. Purus (2n = 34); Ancistrus sp. Macoari (2n = 46); Ancistrus sp. Dimona (2n = 52); Ancistrus sp. Vermelho (2n = 42) and Ancistrus sp. Trombetas (2n = 38). All species possessed only one pair of NOR-carrying chromosomes, but with extensive variation in both the location on the chromosome as well as in the position of the ribosomal sites on the karyotype. The karyotypic evolution of Ancistrus species seems to be based on chromosomal rearrangements, with a tendency to a reduction of the diploid number. Two new instances of XX/XY sex chromosomes for Ancistrus species, based on the heteromorphism in the male karyotype, were also recorded. The large karyotypic diversity among Ancistrus species may be related to biological and behavioural characteristics of these fish that include microhabitat preferences, territoriality and specialized reproductive tactics. These characteristics may lead to a fast rate of fixation of chromosomal mutations and eventually speciation across the basin. PMID- 20738684 TI - Spermatic cell characteristics in Gymnotiformes (Teleostei: Ostariophysi) and their phylogenetic meaning. AB - Spermatic characteristics were studied in representatives of the families Rhamphichthyidae, Sternopygidae and Apteronotidae, and compared with pre-existent data from Gymnotidae and Hypopomidae. The spermatic characteristics found in Gymnotiformes were also compared with data from other Ostariophysi spermatic cells. The spermatic characteristics as the type of spermiogenesis and the structural pattern of the sperm, considering nuclear form, pattern of chromatin condensation, nuclear fossa and its relation with the centriolar complex, form and localization of mitochondria, form of midpiece, presence or absence of cytoplasmic canal and cytoplasmic sleeve, and flagellar fins were utilized. The comparative analysis of the spermatic cell of Gymnotiformes better support the previous proposals for the order considering Gymnotidae as a derived group, than the more recent ones that located Gymnotidae in a basal position as the sister group of the remaining Gymnotiformes. Regarding the Ostariophysi, the comparative analyses based on the spermatic cell characteristics is consistent with a recent systematic proposal that consider Gymnotiformes as a sister group of Characiformes. PMID- 20738686 TI - Shallow phylogeographic structuring of Vimba vimba across Europe suggests two distinct refugia during the last glaciation. AB - Genetic variation and geographical structuring of vimba Vimba vimba were analysed across 26 sites (80 individuals) by means of mtDNA sequences (cyt b gene, mitochondrial control region) to localize hypothesized glacial refugia and to reconstruct postglacial recoloniation routes. Although genetic diversity among sequenced individuals was low, a combined analysis of the two sequenced fragments revealed a western (central and northern Europe: Danube, Elbe and lakes of Sweden) and an eastern clade (eastern Europe: Dnieper-South Bug, Don, Neman). Furthermore, a number of divergent ancestral haplotypes distributed around the Black and Caspian Seas became apparent. Mismatch analyses supported a sudden expansion model for the populations of the western clade between 50 and 10 000 bp. Overall, the study provides strong evidence for a northward and westward expansion of V. vimba from two refugial regions located in the Danubian drainage and the northern Pontic regions respectively. PMID- 20738685 TI - Landscape genetic patterns of the rainbow darter Etheostoma caeruleum: a catchment analysis of mitochondrial DNA sequences and nuclear microsatellites. AB - Catchment population structure and divergence patterns of the rainbow darter Etheostoma caeruleum (Percidae: Teleostei), an eastern North American benthic fish, are tested using a landscape genetics approach. Allelic variation at eight nuclear DNA microsatellite loci and two mitochondrial DNA regions [cytochrome (cyt) b gene and control region; 2056 aligned base pairs (bp)] is analysed from 89 individuals and six sites in the Lake Erie catchment (Blanchard, Chagrin, Cuyahoga and Grand Rivers) v. the Ohio River catchment (Big Darby Creek and Little Miami River). Genetic and geographic patterning is assessed using phylogenetic trees, pair-wise F(ST) analogues, AMOVA partitioning, Mantel regression, Bayesian assignment, 3D factorial correspondence and barrier analyses. Results identify 34 cyt b haplotypes, 22 control region haplotypes and 137 microsatellite alleles whose distributions demonstrate marked genetic divergence between populations from the Lake Erie and Ohio River catchments. Etheostoma caeruleum populations in the Lake Erie and Ohio River catchments diverged c. 1.6 mya during the Pleistocene glaciations. Greater genetic separations characterize the Ohio River populations, reflecting their older habitat age and less recent connectivity. Divergence levels within the Lake Erie catchment denote more recent post-glacial origins. Notably, the western Lake Erie Blanchard River population markedly differs from the three central basin tributary samples, which are each genetically distinguishable using microsatellites. Overall relationships among the Lake Erie sites refute a genetic isolation by geographic distance hypothesis. Etheostoma caeruleum populations thus exchange few genes and have low migration among tributaries and catchments. PMID- 20738687 TI - Normal development of the tomato clownfish Amphiprion frenatus: live imaging and in situ hybridization analyses of mesodermal and neurectodermal development. AB - The normal embryonic development of the tomato clownfish Amphiprion frenatus was analysed using live imaging and by in situ hybridization for detection of mesodermal and neurectodermal development. Both morphology of live embryos and tissue-specific staining revealed significant differences in the gross developmental programme of A. frenatus compared with better-known teleost fish models, in particular, initiation of somitogenesis before complete epiboly, initiation of narrowing of the neurectoderm (neurulation) before somitogenesis, relatively early pigmentation of melanophores at the 10-15 somite stage and a distinctive pattern of melanophore distribution. These results suggest evolutionary adaptability of the teleost developmental programme. The ease of obtaining eggs, in vitro culture of the embryo, in situ staining analyses and these reported characteristics make A. frenatus a potentially important model marine fish species for studying embryonic development, physiology, ecology and evolution. PMID- 20738688 TI - MHC class IIB additive and non-additive effects on fitness measures in the guppy Poecilia reticulata. AB - The genetic architecture of fitness at the class IIB gene of the major histocompatibility complex (MHC) in the guppy Poecilia reticulata was analysed. Diversity at the MHC is thought to be maintained by some form of balancing selection; heterozygote advantage, frequency-dependent selection or spatially and temporally fluctuating selection. Here these hypotheses are evaluated by using an algorithm that partitions the effect of specific MHC allele and genotypes on fitness measures. The effect of MHC genotype on surrogate measures of fitness was tested, including growth rate (at high and low bulk food diets), parasite load following a parasite challenge and survival. The number of copies of the Pore_a132 MHC allele was inversely related to infection by Gyrodactylus flukes and it appeared to be positively related to faster growth. Also, genotypes combining the Pore_a132 or other relatively common alleles paired with rare MHC alleles produced both advantageous and detrimental non-additive effects. Thus, the genetic architecture underlying fitness at the MHC is complex in the P. reticulata. PMID- 20738689 TI - Differentiated ZZ/ZW sex chromosomes in Apareiodon ibitiensis (Teleostei, Parodontidae): cytotaxonomy and biogeography. AB - Conventional and molecular chromosomal analyses were carried out on three populations of Apareiodon ibitiensis sampled from the hydrographic basins of the Sao Francisco River and Upper Parana River (Brazil). The results reveal a conserved diploid number (2n = 54 chromosomes), a karyotype formula consisting of 50 m-sm + 4st and a ZZ/ZW sex chromosome system that has not been previously identified for the species. C-banding analysis with propidium iodide staining revealed centromeric and terminal bands located in the chromosomes of the specimens from the three populations and allowed the identification of heteromorphism of heterochromatin regions in the Z and W chromosomes. The number of 18S sites located through fluorescent in situ hybridization (FISH) varied between the populations of the Sao Francisco and Upper Parana Rivers. The location of 5S rDNA sites proved comparable in one pair of metacentric chromosomes. Thus, the present study proposes a ZZ/ZW sex chromosome system for A. ibitiensis among the Parodontidae, and a hypothesis is presented regarding possible W chromosome differentiation stages in this species through DNA accumulation, showing geographical variations for this characteristic, possibly as a consequence of geographical reproductive isolation. PMID- 20738690 TI - Molecular and karyotypic phylogeography in the Neotropical Hoplias malabaricus (Erythrinidae) fish in eastern Brazil. AB - The sedentary, predatory characin Hoplias malabaricus has one of the widest distributions of freshwater fishes in South America and is characterized by seven karyomorphs (A-G) that occur in sympatric and allopatric populations. Karyotypical patterns of variation in wild populations have been interpreted as evidence of multiple lineages within this nominal species, a possibility that may limit the validity of experimental data for particular karyomorphs. This study used the phylogeographic and genealogical concordance between cytogenetic (N = 49) and molecular (mitochondrial DNA) (N = 73) data on 17 samples, collected in 12 basins from south-eastern and north-eastern Brazil, to assess the systematic value of cytogenetic data. Cytogenetic patterns show a sex chromosome system in the 2n = 40F karyomorph. Molecular and cytogenetic data indicate a long, independent evolutionary history of karyomorphs and a coastal origin of continental populations in south-eastern Brazil. The lack of fit with molecular clock expectations of divergence between groups is likely to be due to strong demographic fluctuations during the evolution of this species complex. The results indicate that karyotypical identification provides a reliable baseline for placing experimental studies on Hoplias spp. in a phylogenetic context. PMID- 20738691 TI - Mitochondrial DNA variation of an isolated population of the Adriatic brook lamprey Lampetra zanandreai (Agnatha: Petromyzontidae): phylogeographic and phylogenetic inferences. AB - Two mitochondrial genes were examined to compare an isolated population of the Adriatic brook lamprey Lampetra zanandreai in central Italy with other populations in the species range (Po plain) and with parasitic and freshwater lampreys. A single haplotype, identical to one in a Venetian sample, was found in 10 individuals from the isolated population. The reduced variability is consistent with a history of dispersal after the Pleistocene expansion of the Po basin. The results support the hypothesis of an origin of L. zanandreai and L. fluviatilis-L. planeri from a common anadromous ancestor. PMID- 20738692 TI - Development and characterization of microsatellite markers to study population genetic diversity of Przewalski's naked carp Gymnocypris przewalskii in China. AB - Two populations of Przewalski's naked carp Gymnocypris przewalskii, 30 individuals per population, were screened for 10 microsatellite loci. Moderate allele variation was found in these loci with two to eight alleles per locus. The expected and observed heterozygosity ranged from 0.019 to 0.805 and from 0.160 to 0.575, respectively. PMID- 20738693 TI - Molecular data reveal a diverse Astyanax species complex in the upper Iguacu River. AB - Astyanax is among the most speciose genera in the Characidae. In this study, molecular markers were used to assess the extent to which some of the commonly recognized Astyanax species of the upper Iguacu River correspond to natural groups. These results indicate that the diversity of Astyanax has been severely underestimated with several potential cryptic species. PMID- 20738694 TI - Mitochondrial DNA divergence in the critically imperilled pygmy madtom, Noturus stanauli (Siluriformes: Ictaluridae). AB - The mitochondrial cytochrome b gene was sequenced for six individuals of the pygmy madtom, Noturus stanauli, a globally imperilled catfish, from both known localities in Tennessee (U.S.A.) separated by over 1055 river km. Phylogenetic and population genetic analyses revealed little divergence between these populations for this locus. PMID- 20738695 TI - Formation of chromosome aberrations in androgenetic rainbow trout Oncorhynchus mykiss. AB - Residues of maternal nuclear DNA in the form of chromosome fragments were observed in the healthy and morphologically normal androgenetic rainbow trout Oncorhynchus mykiss. A hypothetical model for formation of chromosome re arrangements caused by the incomplete maternal nuclear DNA inactivation in the androgenetic rainbow trout was proposed in the present paper. PMID- 20738697 TI - Reproductive physiology of fishes. PMID- 20738698 TI - External and internal controls of lunar-related reproductive rhythms in fishes. AB - Reproductive activities of many fish species are, to some extent, entrained to cues from the moon. During the spawning season, synchronous spawning is repeated at intervals of c. 1 month (lunar spawning cycle) and 2 weeks (semi-lunar spawning cycle) or daily according to tidal changes (tidal spawning cycle). In species showing lunar-related spawning cycles, oocytes in the ovary develop towards and mature around a specific moon phase for lunar spawners, around spring tides for semi-lunar spawners and at daytime high tides for tidal spawners. The production of sex steroid hormones also changes in accordance with synchronous oocyte development. Since the production of the steroid hormones with lunar related reproductive periodicity is regulated by gonadotropins, it is considered that the higher parts of the hypothalamus-pituitary-gonad axis play important roles in the perception and regulation of lunar-related periodicity. It is likely that fishes perceive cues from the moon by sensory organs; however, it is still unknown how lunar cues are transduced as an endogenous rhythm exerting lunar related spawning rhythmicity. Recent research has revealed that melatonin fluctuated according to the brightness at night, magnetic fields and the tidal cycle. In addition, cyclic changes in hydrostatic pressure had an effect on monoamine contents in the brain. These factors may be indirectly related to the exertion of lunar-related periodicity. Molecular approaches have revealed that mRNA expressions of light-sensitive clock genes change with moonlight, suggesting that brightness at night plays a role in phase-shifting or resetting of biological clocks. Some species may have evolved biological clocks in relation to lunar cycles, although it is still not known how lunar periodicities are endogenously regulated in fishes. This review demonstrates that lunar-related periodicity is utilized and incorporated by ecological and physiological mechanisms governing the reproductive success of fishes. PMID- 20738699 TI - Current knowledge on the photoneuroendocrine regulation of reproduction in temperate fish species. AB - Seasonality is an important adaptive trait in temperate fish species as it entrains or regulates most physiological events such as reproductive cycle, growth profile, locomotor activity and key life-stage transitions. Photoperiod is undoubtedly one of the most predictable environmental signals that can be used by most living organisms including fishes in temperate areas. This said, however, understanding of how such a simple signal can dictate the time of gonadal recruitment and spawning, for example, is a complex task. Over the past few decades, many scientists attempted to unravel the roots of photoperiodic signalling in teleosts by investigating the role of melatonin in reproduction, but without great success. In fact, the hormone melatonin is recognized as the biological time-keeping hormone in fishes mainly due to the fact that it reflects the seasonal variation in daylength across the whole animal kingdom rather than the existence of direct evidences of its role in the entrainment of reproduction in fishes. Recently, however, some new studies clearly suggested that melatonin interacts with the reproductive cascade at a number of key steps such as through the dopaminergic system in the brain or the synchronization of the final oocyte maturation in the gonad. Interestingly, in the past few years, additional pathways have become apparent in the search for a fish photoneuroendocrine system including the clock-gene network and kisspeptin signalling and although research on these topics are still in their infancy, it is moving at great pace. This review thus aims to bring together the current knowledge on the photic control of reproduction mainly focusing on seasonal temperate fish species and shape the current working hypotheses supported by recent findings obtained in teleosts or based on knowledge gathered in mammalian and avian species. Four of the main potential regulatory systems (light perception, melatonin, clock genes and kisspeptin) in fish reproduction are reviewed. PMID- 20738700 TI - Temperature and salmonid reproduction: implications for aquaculture. AB - Fish reproduction is likely to be affected by increasing water temperatures arising from climate change. Normal changes in environmental temperature have the capacity to affect endocrine function and either advance or retard gametogenesis and maturation, but above-normal temperatures have deleterious effects on reproductive processes. In Atlantic salmon Salmo salar, exposure to elevated temperature during gametogenesis impairs both gonadal steroid synthesis and hepatic vitellogenin production, alters hepatic oestrogen receptor dynamics and ultimately results in reduced maternal investment and gamete viability. Exposure to high temperature during the maturational phase impairs gonadal steroidogenesis, delaying or inhibiting the preovulatory shift from androgen to maturation-inducing steroid production. There are also deleterious effects on reproductive development of female broodstock of rainbow trout Oncorhynchus mykiss and Arctic charr Salvelinus alpinus when they are exposed to elevated temperature. Less is known about temperature effects on male fishes but inhibition of spermiation has been observed in S. salar and O. mykiss. Among wild stocks, the response to elevated temperature will involve behavioural thermoregulation with consequent change in geographical ranges and the possibility of local extinctions in some regions. For domesticated stocks, containment in the culture environment precludes behavioural thermoregulation and aquaculturists will be required to develop adaptive strategies in order to maintain productivity. The most direct strategy is to manage the thermal environment using one or more of a range of developing aquaculture technologies. Alternatively, there is potential to mitigate the effects of elevated temperature on reproductive processes through endocrine therapies designed to augment or restore natural endocrine function. Studies largely on S. salar have demonstrated the capacity for synthetic luteinizing hormone-releasing hormone to offset the inhibitory effects of elevated temperature on maturational events in both sexes, but the potential for hormone therapy to provide protection during gametogenesis is still largely unexplored. PMID- 20738701 TI - Stressors, glucocorticoids and ovarian function in teleosts. AB - The purpose of this overview is to re-examine the postulated direct and indirect actions of glucocorticoids on ovarian function in teleosts. The re-examination is undertaken in light of recent advances in the understanding of the stress response itself, the mode of action of the hypothalamus-pituitary gland-ovarian (HPO) axis, the mechanisms of control of oestrogen-dependent hepatic vitellogenin (VtG) secretion and the apparent roles of corticotrophin-releasing hormone (CRH) and CRH-related factors in the regulation of feeding activity. Many of the results of different studies, particularly whole-animal studies, are conflicting, and little is known as to whether the hormone acts directly on various components of the HPO axis or indirectly by virtue of redirection of energy resources away from ovarian growth to provide a source of metabolic resources for other organ systems involved in the physiological stress response. In vitro studies provide some new insights into the direct actions of glucocorticoid on hepatic VtG synthesis and ovarian follicle steroidogenesis, but even here, in some studies the cellular sites of action of these hormones is not altogether clear. The overview emphasizes the complexity of the stress response, the complexity of the regulation of glucocorticoid-dependent gene expression and the extensive interactive nature of the HPO with other hypothalamus-pituitary gland-peripheral endocrine gland axes, such as the thyroid (HPT), 'somatic' (GH-IGF) and interrenal tissue (HPI) axes. PMID- 20738702 TI - Testing the synergistic effects of GnRH and testosterone on the reproductive physiology of pre-adult pink salmon Oncorhynchus gorbuscha. AB - To test the hypothesis that the hypothalmic gonadotropin-releasing hormone (GnRH) and testosterone (T) co-treatment stimulates both the hypothalmo-pituitary gonadal (HPG) and hypothalmo-pituitary-interrenal axes, the reproductive and osmoregulatory responses of pre-adult pink salmon Oncorhynchus gorbuscha were compared after GnRH and T administration either alone or in combination. Relative to controls, neither GnRH nor T treatment resulted in significantly greater ovarian or testicular growth, but co-treatment significantly increased ovarian growth after 5 months. Interestingly, the stimulation was undetectable after 3 months. However, once daily photoperiod began shortening after the summer solstice, c. 2 months before the natural spawning date, GnRH+T-treated females were stimulated to produce larger ovaries. Final fish body length and the size of individual eggs did not differ among treatment groups. GnRH+T eggs, however, showed signs of advanced vitellogenesis relative to GnRH-treated and control eggs, whereas T-treated eggs became atretic. Testis size increased significantly from initial values and most males were spermiating, but this growth and development were independent of hormone treatments. Final plasma ion, metabolite and cortisol concentrations did not differ among treatment groups. It is concluded that GnRH+T co-treatment was effective in stimulating female but not male maturation. GnRH and T treatment, however, presumably had little effect on the hypothalmo-pituitary-interrenal axis as observed by ionoregulatory status. PMID- 20738703 TI - Neuroendocrine control by dopamine of teleost reproduction. AB - While gonadotropin-releasing hormone (GnRH) is considered as the major hypothalamic factor controlling pituitary gonadotrophins in mammals and most other vertebrates, its stimulatory actions may be opposed by the potent inhibitory actions of dopamine (DA) in teleosts. This dual neuroendocrine control of reproduction by GnRH and DA has been demonstrated in various, but not all, adult teleosts, where DA participates in an inhibitory role in the neuroendocrine regulation of the last steps of gametogenesis (final oocyte maturation and ovulation in females and spermiation in males). This has major implications for inducing spawning in aquaculture. In addition, DA may also play an inhibitory role during the early steps of gametogenesis in some teleost species, and thus interact with GnRH in the control of puberty. Various neuroanatomical investigations have shown that DA neurones responsible for the inhibitory control of reproduction originate in a specific nucleus of the preoptic area (NPOav) and project directly to the region of the pituitary where gonadotrophic cells are located. Pharmacological studies showed that the inhibitory effects of DA on pituitary gonadotrophin production are mediated by DA-D2 type receptors. DA-D2 receptors have now been sequenced in several teleosts, and the coexistence of several DA-D2 subtypes has been demonstrated in a few species. Hypophysiotropic DA activity varies with development and reproductive cycle and probably is controlled by environmental cues as well as endogenous signals. Sex steroids have been shown to regulate dopaminergic systems in several teleost species, affecting both DA synthesis and DA-D2 receptor expression. This demonstrates that sex steroid feedbacks target DA hypophysiotropic system, as well as the other components of the brain-pituitary gonadotrophic axis, GnRH and gonadotrophins. Recent studies have revealed that melatonin modulates the activity of DA systems in some teleosts, making the melatonin-DA pathway a prominent relay between environmental cues and control of reproduction. The recruitment of DA neurons for the neuroendocrine control of reproduction provides an additional brain pathway for the integration of various internal and environmental cues. The plasticity of the DA neuroendocrine role observed in teleosts may have contributed to their large diversity of reproductive cycles. PMID- 20738704 TI - Functional and evolutionary insights into vertebrate kisspeptin systems from studies of fish brain. AB - The kiss1 gene product kisspeptin is now considered to be an essential regulator of the hypothalamic-pituitary-gonadal (HPG) axis in most vertebrate species. Recent findings in fishes are beginning to set a new stage for the kisspeptin study; the existence of paralogous kisspeptin genes as well as kisspeptin receptor (formerly called GPR54) genes has quite recently been reported in several fish and amphibian species. The fishes may provide excellent animal models for the study of general principles underlying the kisspeptin and kisspeptin receptor systems of vertebrates from the evolutionary viewpoint. Unlike placental and marsupial mammalian species mainly studied so far, many teleost species have two paralogous genes of kisspeptin, kiss1 and kiss2. Medaka, Oryzias latipes, in which kiss1 and kiss2 are expressed in distinctive hypothalamic neuron populations, is a good model system for the study of central regulation of reproduction. Here, the kiss1 system but not the kiss2 system shows expression dynamics strongly indicative of its direct involvement in the HPG axis regulation via its actions on GnRH1 neurons. On the other hand, the kiss1 gene is missing, and only kiss2 is expressed in some fish species. Also, there are some recent reports that Kiss2 peptide may be a potent regulator of reproduction in some fish species. The ancestral vertebrate probably already had two paralogous kiss genes, and their main function was the HPG axis regulation. In the species that retained both paralogues during evolution, either Kiss1 or Kiss2 predominantly retains its ability for the HPG axis regulation, while the other may assume new non-reproductive functions (neofunctionalization). Alternatively, both the paralogues may assume complementary functions in the HPG axis regulation (subfunctionalization). After the divergence of teleost and tetrapod lineages, either one of the two paralogues, or even both in birds, have been lost (degradation) or became a pseudogene (non-functionalization), but the remaining paralogue retained its original function of HPG axis regulation. The identification of multiple forms of kisspeptin receptors and the rather promiscuous ligand-receptor relationships has led to the further proposal that such promiscuousness may be the basis for the functional robustness of kisspeptin and kisspeptin receptor systems in the HPG axis regulation, when one or both paralogous genes are lost or functionally partitioned during evolution. PMID- 20738705 TI - The role of the maturation-inducing steroid, 17,20beta-dihydroxypregn-4-en-3-one, in male fishes: a review. AB - The major progestin in teleosts is not progesterone, as in tetrapods, but 17,20beta-dihydroxypregn-4-en-3-one (17,20beta-P) or, in certain species, 17,20beta,21-trihydroxy-pregn-4-en-3-one (17,20beta,21-P). Several functions for 17,20beta-P and 17,20beta,21-P have been proposed (and in some cases proved). These include induction of oocyte final maturation and spermiation (milt production), enhancement of sperm motility (by alteration of the pH and fluidity of the seminal fluid) and acting as a pheromone in male cyprinids. Another important function, initiation of meiosis (the first step in both spermatogenesis and oogenesis), has only very recently been proposed. This is a process that takes place at puberty in all fishes and once a year in repeat spawners. The present review critically examines the evidence to support the proposed functions of 17,20beta-P in males, including listing of the evidence for the presence of 17,20beta-P in the blood plasma of male fishes and discussion of why, in many species, it appears to be absent (or present at low and, in some cases, unvarying concentrations); consideration of the evidence, obtained mainly from in vitro studies, for this steroid being predominantly produced by the testis, for its production being under the control of luteinizing hormone (gonadotrophin II) and, at least in salmonids, for two cell types (Leydig cells and sperm cells) being involved in its synthesis; discussion of the factors involved in the regulation of the switch from androgen to 17,20beta-P production that seems to occur in many species just at the time of spermiation; discussion of the effects of in vivo injection and application of 17,20beta-P (and closely related compounds) in males; a listing of previously published evidence that supports the proposed new function of 17,20beta-P as an initiator of meiosis; finally, discussion of the evidence for environmental endocrine disruption by progestins in fishes. PMID- 20738706 TI - Roles of hepatocyte nuclear factors (HNF) in the regulation of reproduction in teleosts. AB - Hepatocyte nuclear factor (HNF) families are composed of liver-enriched transcription factors and upstream regulators of many liver-specific genes. HNF are involved in liver-specific gene expression, metabolism, development, cell growth and many cellular functions in the body. HNF genes can be activated or influenced by several hormones and insulin-like growth factors (IGF), and different combinations of the four HNF factors form a network in controlling the expression of liver-specific or liver-enriched genes. The functions of these factors and their interactions within the gonads of bony fishes, however, are not well understood, and the related literature is scant. Recently, several members of the HNF families have been detected in teleost gonads together with their downstream genes (IGF-I and IGF-II), suggesting that these HNF could be upregulated in vitro by steroid hormones. Thus, the hormone-HNF-IGF-gonad interaction may be an alternative axis in the reproductive mechanism that acts in concert with the conventional hypothalamus-pituitary-gonad pathway. This may help the early development and maturation of the gonad or gamete, sexual maturity or reversion and spawning-regulating mechanisms among fishes to be understood. PMID- 20738707 TI - Frenetic activation of fish spermatozoa flagella entails short-term motility, portending their precocious decadence. AB - In most species, fish spermatozoa activate their motility on contact with the external medium (sea or fresh water depending of their reproductive habitat). Their flagella immediately develop waves propagated at high beat frequency (up to 70 beats s(-1)), which propel these sperm cells at high velocity (6-10 mm min( 1)), but for a quite short period of time, usually limited to minutes. Their specific inability to restore their energy content (mostly adenosine triphosphate) fast enough relatively to their high rate of energy consumption by flagellar contributes mainly to the activity arrest of motility, as the spermatozoa need to rely on early accumulated energy prior to activation. This review of the published data explains the present understanding of physico chemical mechanisms by which flagellar motility is activated (mostly through osmotic and ionic regulation) and then propels sperm cells at speed. It aims also to describe the gradual arrest of their motility much of which occurs within a few minutes. PMID- 20738708 TI - Comparative energetics and physiology of parental care in smallmouth bass Micropterus dolomieu across a latitudinal gradient. AB - The energetic and physiological status of parental smallmouth bass Micropterus dolomieu was investigated across the majority of their latitudinal range at the onset and near the end of care. Variables such as tissue lipid stores, plasma indicators of nutritional status and chronic stress and white muscle were used to define energetic and physiological status. Results showed that northern males (48 degrees N) were larger and heavier than mid-northern (44 degrees N) and southern (36 degrees N) latitude males. For a given body size, northern males had greater whole-body lipid across the parental care period and tended to feed more (based on gut contents) than mid-northern and southern latitude conspecifics. Indicators of nutritional status were also highest in northern males. Conversely, the southern males exhibited the greatest capacity for biosynthesis across the entire parental care period as indicated by the highest level of nucleoside diphosphate kinase activities. Collectively, these finding suggest that the energetic costs and physiological consequences of care vary across latitudes, providing some of the first mechanistic evidence of how environmental conditions can influence both the ecological and physiological costs of reproduction for wild animals during parental care. The data also suggest that lake-specific processes that can vary independently of latitude may be important, necessitating additional research on fish reproductive physiology across landscapes. PMID- 20738709 TI - Molecular adaptations in haemoglobins of notothenioid fishes. AB - Since haemoglobins of all animal species have the same haem group, differences in their properties, including oxygen affinity, electrophoretic mobility and pH sensitivity, must result from the interaction of the prosthetic group with specific amino-acid residues in the primary structure. For this reason, fish globins have been the subject of extensive studies in recent years, not only for their structural characteristics, but also because they offer the possibility to investigate the evolutionary history of these ancient molecules in marine and freshwater species living in a great variety of environmental conditions. This review summarizes the current knowledge on the structure, function and phylogeny of haemoglobins of notothenioid fishes. On the basis of crystallographic analysis, the evolution of the Root effect is analysed. Adaptation of the oxygen transport system in notothenioids seems to be based on evolutionary changes, involving levels of biological organization higher than the structure of haemoglobin. These include changes in the rate of haemoglobin synthesis or in regulation by allosteric effectors, which affect the amount of oxygen transported in blood. These factors are thought to be more important for short-term response to environmental challenges than previously believed. PMID- 20738710 TI - Phylogeographic structure of brown trout Salmo trutta in Britain and Ireland: glacial refugia, postglacial colonization and origins of sympatric populations. AB - The phylogeographical structure of brown trout Salmo trutta in Britain and Ireland was studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of four mitochondrial DNA segments (16S/ND1, ND5/6, COXIII/ND5 and ND5/12S). Analysis of 3636 individuals from 83 sites morphotypes revealed a total of 25 haplotypes. These haplotypes were nested in seven two-step clades. Although there was a clear geographical patterning to the occurrence of derived clades, admixture among ancestral clades was extensive throughout the studied area. A relevant feature of the data was that some populations contained mixtures of highly divergent clades. This type II phylogeographic pattern is uncommon in nature. Clade intermixing is likely to have taken place during earlier interglacials as well as since the Last Glacial Maximum. The anadromous life history of many S. trutta populations has probably also contributed to clade mixing. Based on the data presented here and published data, postglacial colonization of Britain and Ireland most likely involved S. trutta from at least five potential glacial refuges. Probable locations for such refugia were: south of England-western France, east of the Baltic Sea, western Ireland, Celtic Sea and North Sea. Ferox S. trutta, as defined by their longevity, late maturation and piscivory, exhibited a strong association with a particular clade indicating that they share a common ancestor. Current evidence indicates that the Lough Melvin gillaroo S. trutta and sonaghen S. trutta sympatric types diverged prior to colonization of Lough Melvin and, although limited gene flow has occurred since secondary contact, they have remained largely reproductively isolated due to inlet and outlet river spawning segregation. Gillaroo S. trutta may reflect descendents of a previously more widespread lineage that has declined due to habitat alterations particularly affecting outlet rivers. The mosaic-like distribution of mtDNA lineages means that conservation prioritization in Britain and Ireland should be based on the biological characteristics of local populations rather than solely on evolutionary lineages. PMID- 20738711 TI - Phylogeny of Glaucosomatidae inferred from molecular evidence. AB - Most species of glaucosomatids (Teleostei: Glaucosomatidae) are endemic to Australia, except Glaucosoma buergeri that is widely distributed from Australia to Japan. This study elucidated phylogenetic relationships among glaucosomatids based on the morphological characters of the saccular-otolith sagitta, in addition to molecular evidence of mitochondrial 16S rDNA, cytochrome oxidase I (COI) and cytochrome b (cyt b) sequences, and nuclear rhodopsin sequences. The topologies of individuals' phylogenetic trees, based on 16S rDNA, COI and cyt b sequences, were statistically indistinguishable from one another, and were only slightly different from a tree based on rhodopsin sequences. These molecular tree topologies, however, differed from species relationships in morphology-based phylogenetic hypothesis proposed in previous studies. Specimens of G. buergeri from Australia and Taiwan showed differences in the sagitta and molecular differentiation at the four genes, suggesting a possible speciation event. Both molecular and morphological evidences indicate that Glaucosoma magnificum is the plesiomorphic sister species of other glaucosomatid species. Glaucosoma hebraicum is the sister species of a clade composed of G. buergeri and Glaucosoma scapulare. Molecular and morphological evidences also support the species status of G. hebraicum. PMID- 20738712 TI - Molecular phylogeographic analyses of the loach Oxynoemacheilus bureschi reveal post-glacial range extensions across the Balkans. AB - Rivers on the Balkan Peninsula can be separated into ichthyofaunistic areas with different endemic fish species. The Vardar River contains a particularly large number of endemics, indicating its complete and long-term isolation from neighbouring river systems. One of the few species shared with other rivers is the loach species Oxynoemacheilus bureschi. In this study, the genetic analyses of 175 individuals of O. bureschi from 17 sites, covering the entire distribution of the species, including the Rivers Vardar (= Axios), Struma (= Strymon), Mesta (= Nestos) and Danube, were performed using one mitochondrial and one nuclear marker. Genetic differentiation among populations was in general low. Shared haplotypes were common and occurred even between distant localities and different river systems. This points to a high degree of gene flow among populations and rejects the hypothesis that the population in the Vardar River represents a relict from an early colonization of the Balkan Peninsula. In contrast, the results suggest that populations in the Vardar River, as well as those in the Danube River, are of recent origin, and a human-mediated introduction cannot be excluded. On the other hand, the populations in the Aggitis River, a left tributary of the lower Struma River, were clearly separated from the rest of the species and represent a long-term isolated lineage. Demographic analyses suggest a recent population expansion for O. bureschi, in which the population in the Aggitis River was not involved. PMID- 20738713 TI - Distribution and species composition of juvenile and adult scombropids (Teleostei, Scombropidae) in Japanese coastal waters. AB - Two scombropid fishes, Scombrops boops and Scombrops gilberti, are closely related and commercially important species in Japan. These species are often confused in commercial markets because of their morphological similarity. In this study, scombropid specimens collected from various Japanese coastal waters were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and phylogenetic analysis of the 16S rRNA gene in mitochondrial DNA. These analyses showed that all the scombropid specimens collected from localities in the Sea of Japan were identified as S. boops, whereas those from the Pacific Ocean included two species, S. boops and S. gilberti. Almost all juvenile (<200 mm standard body length, S(L)) S. gilberti originated from the Pacific coastal waters of the northern Japan, whereas adults (>400 mm S(L)) were found only in deep water off the Izu Peninsula to the Izu Islands. This suggests that S. gilberti might migrate extensively during its life cycle. In addition, differences in the number of specimens and the distribution between the two species suggest that S. gilberti is less abundant than S. boops in Japanese waters. PMID- 20738714 TI - Molecular cloning and brain distribution of three types of gonadotropin-releasing hormone from mummichog Fundulus heteroclitus. AB - Complementary DNAs encoding gonadotropin-releasing hormone (GnRH) precursors were cloned from the mummichog Fundulus heteroclitus brain, showing that this species has three GnRH forms, i.e. medaka Oryzias latipes GnRH (mdGnRH), chicken GnRH-II (cGnRH-II) and Atlantic salmon Salmo salar GnRH (sGnRH). The F. heteroclitus prepro GnRHs have common structural architectures of vertebrate GnRHs, consisting of the signal peptide, 10 amino acids of mature peptide, GKR sequence and GnRH associated peptide (GAP). Phylogenetic analysis of fish prepro GnRHs showed that F. heteroclitus mdGnRH is a homologue of sbGnRHs and mdGnRHs of other acanthopterygian. Quantitative real-time PCR revealed that mdGnRH was abundantly expressed in the olfactory bulb and in olfactory lobe areas and is expressed in the pituitary. The cGnRH-II was mainly expressed in the midbrain and interbrain areas, and the sGnRH was expressed not only in the olfactory bulb but also in other regions of the brain. These results suggest that the mdGnRH is involved in the stimulation of gonadotrophs in the pituitary, whereas cGnRH-II and sGnRH are involved in neurotransmission and neuromodulation. PMID- 20738715 TI - Grayling (Thymallinae) phylogeny within salmonids: complete mitochondrial DNA sequences of Thymallus arcticus and Thymallus thymallus. AB - The phylogenetic relationships among the three subfamilies (Salmoninae, Coregoninae and Thymallinae) in the Salmonidae have not been addressed extensively at the molecular level. In this study, the whole mitochondrial genomes of two Thymallinae species, Thymallus arcticus and Thymallus thymallus were sequenced, and the published mitochondrial genome sequences of other salmonids were used for Bayesian and maximum-likelihood phylogenetic analyses. These results support an ancestral Coregoninae, branching within the Salmonidae, with Thymallinae as the sister group to Salmoninae. PMID- 20738716 TI - PCR-RFLP analysis of mitochondrial DNA in tench Tinca tinca. AB - Polymorphism was detected at ND1, ND6, D-loop and cyt b segments of mtDNA in 105 tench (Tinca tinca L.), using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and five composite haplotypes were identified. The diversity indices and the results of the population comparisons revealed that the identified markers provide a powerful tool for further studies on this species. PMID- 20738717 TI - No sex-specific markers detected in bluegill sunfish Lepomis macrochirus by AFLP. AB - The amplified fragment-length polymorphism (AFLP) technique was used to identify sex-specific markers in bluegill sunfish. A total of 12 835 loci were produced by 256 primer combinations, of which nine (0.73 per thousand) exhibited presumed sex associated amplifications in the pooled samples; however, none of which revealed sex specificity upon individual evaluation. PMID- 20738718 TI - Molecular identification of Na(+)-H(+) exchanger isoforms (NHE2) in the gills of the euryhaline teleost Fundulus heteroclitus. AB - In the current study, reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) PCR were used to clone full-length putative Na(+)-H(+) exchanger isoforms (NHE2a) cDNA from the gills of Fundulus heteroclitus. The 2480 bp cDNA includes a coding region for a protein that shows a 57% amino acid homology to rabbit NHE2. These sequences allowed data mining of available fish genome data, which revealed at least three NHE2 subtypes in some teleost species. PMID- 20738719 TI - In vitro expansion of autonomously contracting, cardiomyogenic structures from rainbow trout Oncorhynchus mykiss. AB - In primary cell preparations from larvae of rainbow trout Oncorhynchus mykiss, the formation of autonomously contracting cell aggregates was observed after 7 days. These contracting elements could be propagated and some aggregates were maintained over a period of 35 days. Electron microscopical and immunocytochemical examination revealed the presence of cardiomyocytes. PMID- 20738720 TI - Pliocene isolation of a north-west Saharan cichlid fish. AB - The evolutionary origin of the only north-west Saharan haplochromine cichlid, Astatotilapia desfontainii, was explored using mitochondrial DNA sequences. Phylogenetic analyses revealed that this species belonged to the main East African-Nilotic haplochromine clade, but was a distinct lineage that diverged from modern haplochromines in the Pliocene. The results suggest that A. desfontainii is a relict haplochromine lineage that has endured major climate fluctuations in North Africa. PMID- 20738721 TI - The cysteine pairs in CLV2 are not necessary for sensing the CLV3 peptide in shoot and root meristems. AB - Receptor-like proteins (RLPs) are involved in both plant defense and developmental processes. Previous genetic and biochemical studies show that the leucine-rich repeat (LRR) receptor-like protein CLAVATA2 (CLV2) functions together with CLAVATA1 (CLV1) and CORYNE (CRN) in Arabidopsis to limit the stem cell number in shoot apical meristem, while in root it acts with CRN to trigger a premature differentiation of the stem cells after sensing the exogenously applied peptides of CLV3p, CLE19p or CLE40p. It has been proposed that disulfide bonds might be formed through two cysteine pairs in the extracellular LRR domains of CLV1 and CLV2 to stabilize the receptor complex. Here we tested the hypothesis by replacing these cysteines with alanines and showed that depletions of one or both of the cysteine pairs do not hamper the function of CLV2 in SAM maintenance. In vitro peptide assay also showed that removal of the cysteine pairs did not affect the perception of CLV3 peptides in roots. These observations allow us to conclude that the formation of disulfide bonds is not needed for the function of CLV2. PMID- 20738722 TI - Fingerprinting analysis of Saposhnikovia divaricata using 1H nuclear magnetic resonance spectroscopy and high performance liquid chromatography. AB - The (1)H nuclear magnetic resonance ((1)H NMR) fingerprints of fractionated non polar and polar extracts (control substance for plant drug [CSPD] A and B) from the roots of 12 specimens of Saposhnikovia divaricata (Turcz.) Schischk were achieved with Fourier Transform (FT)-NMR spectrometer and assigned by comparison to each other and to the (1)H NMR spectra of the isolated individual compounds. These fingerprints were found to be uniform in terms of the specificity for the implication of all 12 specimens being systematically of the same origin. The uniformity was further affirmed by high performance liquid chromatography (HPLC), which also revealed exactly identical specificity for the identified S. divaricata species with the (1)H NMR appearances of corresponding CSPD on the part of the composition of characteristic constituents when comparing to corresponding individual compounds. This investigation unambiguously shows that the specific signals from the chemotaxonomically significant compounds of chromones and coumarins in S. divaricata are exhibited distinctively in the composite features of both (1)H NMR fingerprints and HPLC profiles. The (1)H NMR and HPLC profiles established can successfully be used as reference for the authentication of the origin of S. divaricata species as well as for chemotaxonomic studies. PMID- 20738723 TI - Fast isolation of highly active photosystem II core complexes from spinach. AB - Purification of photosystem II (PSII) core complexes is a time-consuming and low efficiency process. In order to isolate pure and active PSII core complexes in large amounts, we have developed a fast method to isolate highly active monomeric and dimeric PSII core complexes from spinach leaves by using sucrose gradient ultracentrifugation. By using a vertical rotor the process was completed significantly faster compared with a swing-out rotor. In order to keep the core complexes in high activity, the whole isolation procedure was performed in the presence of glycine betain and pH at 6.3. The isolated pigment-protein complexes were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, absorption spectroscopy, 77 K fluorescence spectroscopy and high performance liquid chromatography. Our results show that this method is a better choice for quick and efficient isolation of functionally active PSII core complexes. PMID- 20738724 TI - Overexpression of AHL20 negatively regulates defenses in Arabidopsis. AB - Plants are equipped to recognize invading pathogenic microbes and activate innate immune responses by sensing pathogen-associated molecular patterns (PAMPs). PAMP triggered immunity (PTI) is critical for plant resistance to potential pathogens. Although the mechanism by which PTI is activated has been intensively studied, exactly how plants prevent unregulated immune responses is less well understood. Here we provide evidence that AHL20, an AT-hook containing DNA-binding protein, negatively regulates PTI. Overexpression of AHL20 as a stable transgene suppressed PAMP-induced NHO1 and FRK1 expression in Arabidopsis plants. Similarly, transient expression of the closely related family members AHL19, AHL15, and AHL27 in protoplasts also blocked PAMP-induced gene expression. The AHL20 overexpression plants displayed greater susceptibility to virulent Pseudomonas syringae bacteria. These results indicate that AHL proteins play an important role in plant immunity. PMID- 20738725 TI - Light regulation to chlorophyll synthesis and plastid development of the chlorophyll-less golden-leaf privet. AB - Ligustrum vicaryi L. is a hybrid of Ligustrum ovalifolium Hassk. var. aureo marginatum and Ligustrum vulgale L., and displays a chlorophyll-less phenotype. Therefore it is widely used as a horticultural shrub because of its golden-color leaves. Its putative mechanism, light responses, chlorophyll synthesis and plastid development were studied. L. vicaryi has a higher level of 5 aminolevulinic acid (ALA), but lower levels of chlorophylls compared with L. quihoui. The yellowish phenotype of L. vicaryi upper leaves could be attributed to their hampered conversion from chlorophyllide into chlorophyll a. Despite the enhanced ALA level and the decreased thylakoid stacking in plastids, L. vicaryi golden leaves contain normal levels of Lhcb transcripts and photosystem apoproteins. Furthermore, reactive oxygen species (ROS) accumulation is almost the same in L. vicaryi and L. quihoui. The golden leaves often turn green and the contents of chlorophylls increase with decreasing light intensity. Dynamic changes of chlorophyll-synthesis-system under the light transition were also analyzed. PMID- 20738726 TI - SLOW WALKER3, encoding a putative DEAD-box RNA helicase, is essential for female gametogenesis in Arabidopsis. AB - RNA helicases are adenosine tri-phosphatases that unwind the secondary structures of RNAs and are required in almost any aspect of RNA metabolism. They are highly conserved from prokaryotic to eukaryotic organisms. However, their precise roles in plant physiology and development remain to be clarified. Here we report that the mutation in the gene SLOW WALKER3 (SWA3) results in the slow and retarded progression of mitosis during megagametogenesis in Arabidopsis. SWA3 is a putative RNA helicase of the DEAD-box subfamily. Mutant megagametophyte development is arrested at four- or eight-nucleate stages, furthermore, one of the synergids in about half of the mutant embryo sacs displays abnormal polarity, with its nucleus locating at the chalazal end, instead of the micropylar end in the wild-type. Transmission of the mutation through female gametophytes is severely reduced in swa3. However, a small portion of mutant embryo sacs are able to develop into mature and functional female gametophytes when pollination was postponed. The SWA3 in Arabidopsis is a homolog of Dbp8 in yeast. Dbp8 interacts with Efs2 and is essential for biogenesis of 18S rRNA in yeast. Our data suggest that SWA3 may form a complex with AtEfs2 and take roles in ribosomal biogenesis as RNA helicase during megagametogenesis in Arabidopsis. PMID- 20738727 TI - MALE GAMETOPHYTE DEFECTIVE 2, encoding a sialyltransferase-like protein, is required for normal pollen germination and pollen tube growth in Arabidopsis. AB - Sialyltransferases (SiaTs) exist widely in vertebrates and play important roles in a variety of biological processes. In plants, several genes have also been identified to encode the proteins that share homology with the vertebrate SiaTs. However, very little is known about their functions in plants. Here we report the identification and characterization of a novel Arabidopsis gene, MALE GAMETOPHYTE DEFECTIVE 2 (MGP2) that encodes a sialyltransferase-like protein. MGP2 was expressed in all tissues including pollen grains and pollen tubes. The MGP2 protein was targeted to Golgi apparatus. Knockout of MGP2 significantly inhibited the pollen germination and retarded pollen tube growth in vitro and in vivo, but did not affect female gametophytic functions. These results suggest that the sialyltransferase-like protein MGP2 is important for normal pollen germination and pollen tube growth, giving a novel insight into the biological roles of the sialyltransferase-like proteins in plants. PMID- 20738728 TI - Natural hybridization between Rhododendron delavayi and R. cyanocarpum (Ericaceae), from morphological, molecular and reproductive evidence. AB - The natural hybridization that occurs between two sympatric species of Rhododendron subgenus Hymenanthes in Yunnan, China, was investigated. In field observations, it was noted that the putative hybrids between R. delavayi Franch. and R. cyanocarpum (Franch.) Franch. ex W.W. Sm. had intermediate morphologies. On the basis of morphology, chloroplast DNA (trnL-rpl32) and nuclear DNA (waxy), hybrids and parental species were identified. Hybridization occurred in both directions, but was asymmetrical, with R. delavayi as the major maternal parent. Reciprocal hand pollination treatments showed that either species, as pollen donor or pollen receiver, could produce fruits. It was noted that fruit set varied among treatments. The same pollinators (bumblebees) were shared in both parental species. From these results, we conclude that individuals with intermediate morphologies are indeed of hybrid origin from natural hybridization between R. cyanocarpum and R. delavayi. Furthermore, we presume the hybridization at the study site could have been initiated by habitat disturbance in the 1950s, and we may hence witness the early stages of hybrid swarm formation. PMID- 20738729 TI - Balloon aortic valvuloplasty for aortic stenosis using a novel percutaneous dilation catheter and power injector. AB - Calcific aortic stenosis is the most common valvular heart disease in the Western world. Although definitive treatment is valve replacement, many patients are not replacement candidates due to high surgical risk from older age and comorbid illness or lack of desire for a surgical or replacement procedure. Percutaneous balloon aortic valvuloplasty (BAV) is an option for palliative treatment in nonsurgical patients, although this procedure is complicated during the immediate postprocedure period by bleeding requiring transfusion for about 1 in 5 patients and subsequent restenosis. This report describes BAV using a smaller profile balloon designed to withstand higher pressures, rapidly inflated with a power injector. Twenty consecutive high-risk patients with severe aortic stenosis were treated. In all cases, New York Heart Association (NYHA) class improved from IV before BAV to I or II at 30 days follow-up. Six-month posttreatment follow-up data were available for 19 of 20 patients: 15 patients were either NYHA class I or II, 1 patient was class III, and 3 deaths occurred unrelated to aortic stenosis. One patient was lost to follow-up. Average systolic gradient peak-to peak pressure decreased by 40.0% (range 18.0-70.0%) and mean gradient decreased by 30.0% (range 13.7-70.8%). Aortic valve area increased from 0.59 +/- 0.16 cm(2) to 0.92 +/- 0.23 cm(2), representing a mean increase of 30.0% (range 7.8%-58.2%). There were no significant bleeding complications. The only procedural complication was a single case of pericardial tamponade. There were no other complications during the first 24 hours post-BAV. These data support that the reported BAV technique may offer an effective alternative for patients with severe aortic stenosis who are not surgical candidates or prefer to avoid aortic valve replacement. PMID- 20738730 TI - Circadian alteration in neurobiology during protracted opiate withdrawal in rats. AB - Protracted opiate withdrawal can extend for months of disrupted hormonal circadian rhythms. We examined rodent behaviors and these circadian disturbances in hormone and peptide levels as well as brain clock gene expression during 60 days of protracted withdrawal. Our behavioral tests included open field, elevated plus maze, and sucrose preference tests at 36 h, 10, 30, and 60 days after stopping chronic morphine. At these four assessment points, we collected samples every 4 h for 24 h to examine circadian rhythms in blood hormone and peptide levels and brain expression of rPER1, rPER2, and rPER3 clock genes. Decreased locomotor activity and elevated adrenocorticotropic hormone and melatonin levels persisted for 2 months after morphine withdrawal, but corticosterone was elevated only at 36 h and 10 days after withdrawal. Orexin levels were high at 36 h after withdrawal, but then reversed during protracted withdrawal to abnormally low levels. Beta-endorphin (beta-EP) levels showed no differences from normal. However, circadian rhythms were blunted for all of these hormones. Corticosterone, adrenocorticotropic hormone, and orexin blunting persisted at least for 60 days. The blunted circadian rhythm of beta-EP and melatonin recovered by day 60, but the peak phase of beta-EP was delayed about 8 h. Blunted circadian rhythms and reduced expression of rPER1, rPER2, and rPER3 persisted at least for 60 days in the suprachiasmatic nucleus, prefrontal cortex, nucleus accumbens core, central nucleus of the amygdala, Hippocampus, and ventral tegmental area. Circadian rhythms of rPER1 in the nucleus accumbens shell and basolateral nucleus of the amygdala and of rPER2 in the central nucleus of the amygdala were reversed. Disrupted circadian rhythms of rPER1, rPER 2, and rPER3 expression in reward-related brain circuits and blunted circadian rhythms in peripheral hormones and peptides may play a role in protracted opiate withdrawal and contribute to relapse. PMID- 20738731 TI - Investigating heterogeneity of intracellular calcium dynamics in anterior pituitary lactotrophs using a combined modelling/experimental approach. AB - Cell responses are commonly heterogeneous, even within a subpopulation. In the present study, we investigate the source of heterogeneity in the Ca(2+) response of anterior pituitary lactotrophs to a Ca(2+) mobilisation agonist, thyrotrophin releasing hormone. This response is characterised by a sharp increase of cytosolic Ca(2+) concentration as a result of mobilisation of Ca(2+) from intracellular stores, followed by a decrease to an elevated plateau level that results from Ca(2+) influx. We focus on heterogeneity of the evoked Ca(2+) spike under extracellular Ca(2+) free conditions. We introduce a method that uses the information provided by a mathematical model to characterise the source of heterogeneity. This method compares scatter plots of features of the Ca(2+) response obtained experimentally with those made from the mathematical model. The model scatter plots reflect random variation of parameters over different ranges, and matching the experimental and model scatter plots allows us to predict which parameters are most variable. We find that a large degree of variation in Ca(2+) efflux is a likely key contributor to the heterogeneity of Ca(2+) responses to thyrotrophin-releasing hormone in lactotrophs. This technique is applicable to any situation in which the heterogeneous biological response is described by a mathematical model. PMID- 20738732 TI - Impact and scholarship. PMID- 20738733 TI - Systematic review of educational interventions for improving advance directive completion. AB - PURPOSE: To systematically analyze evidence about the outcome and percent of newly completed ADs, focusing on the effectiveness of (a) types of educational interventions versus controls and (b) one educational intervention over another. DESIGN: Systematic review of literature based on Cochrane review criteria. METHODS: Twelve randomized and four nonrandomized studies were selected from the nursing, medical, and social work literature that met the following criteria: described educational interventions, provided information to calculate the percent of newly completed ADs as an outcome, and published between 1991 and 2009. The review focused primarily on randomized studies. Reviewers calculated the percent of newly completed ADs by determining the number of subjects per group without an AD at baseline and the percentage of those who then completed one by the end of the studies. FINDINGS: Findings were inconsistent regarding all types of educational interventions studied versus controls. Sufficient evidence exists to conclude that combined written and verbal educational interventions were more effective than single written interventions in increasing the percent of newly completed ADs in adult clinic outpatients and hospitalized elderly. CONCLUSIONS: Calculating the percent of newly completed ADs was successful in allowing for study result comparisons. Overall, the evidence base regarding the effectiveness of single or combined educational interventions in increasing AD completion is weak. Randomized studies with diverse samples should be conducted against controls before more studies comparing interventions are undertaken. CLINICAL RELEVANCE: This article provides nurses with a summary of research related to educational interventions and AD completion and identifies where future study is needed. PMID- 20738734 TI - Perceived social support and quality of life in Iranian hemodialysis patients. AB - PURPOSE: To describe the relationship between perceived social support and the quality of life in hemodialysis patients from an Islamic cultural background in Iran. DESIGN: A cross-sectional, correlational design was used. Data were collected in hemodialysis units affiliated to Iran University of Medical Sciences. Two hundred and two Muslim hemodialysis patients were selected by census during 2007. METHODS: The Persian versions of the Personal Resources Questionnaire 85 (PRQ-85) Part II and the Ferrans and Powers Quality of Life Index-dialysis version were used. The data were analyzed using chi-square test and Spearman's rho correlation coefficients. FINDINGS: There were a statistically significant relationship between perceived social support and health-functioning (r = .65, p < or = .05), socioeconomic (r = .67, p < or = .05), psychological spiritual (r = .63, p < or = .05), and family subscales of quality of life (r = .51, p < or = .05). Total quality of life was also significantly correlated with perceived social support (r = 0.72, p= .00). CONCLUSIONS: Perceived social support is associated with quality of life in Iranian hemodialysis patients. CLINICAL RELEVANCE: It is important to reflect on the impact of culture and religion of Iran on quality of life of hemodialysis patients and their perceived social support. PMID- 20738735 TI - Impact of childhood cancer on parents' relationships: an integrative review. AB - PURPOSE: The diagnosis of cancer and the treatment decisions associated with it may cause uncertainty, stress, and anxiety among parents. Emotional tensions can affect parents' relationships during the trajectory of the child's cancer illness. We conducted an integrative review to examine the evidence related to the effects of childhood cancer on parents' relationships. METHODS: An integrative literature search of studies published between 1997 and 2009 was conducted in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychology Information (PsycINFO), PubMed, Scopus, CUIDEN, and Latin American and Caribbean Health Science Literature (LILACS). The key words used were neoplasms, child, marriage, spouses, family relations, and nursing. Articles were reviewed if the (a) topic addressed parents' relationships during childhood cancer; (b) participants were mothers, fathers, or both; (c) design was either qualitative or quantitative; (d) language was English, Portuguese, or Spanish; (e) date of publication was between January 1997 and October 2009; and (f) abstract was available. RESULTS: Fourteen articles met the search criteria and were reviewed using Cooper's framework for integrative reviews. Four themes emerged: (a) changes in the parents' relationship during the trajectory of the child's illness; (b) difficulty in communication between couples; (c) gender differences in parental stress and coping; and (d) role changes. CONCLUSIONS AND IMPLICATIONS: Findings revealed positive and negative changes in parents' relationships, communication, stress, and roles. Nurses need to assess the impact of cancer diagnosis and treatments on parent relationships, offer support and encouragement, and allow expression of feelings. Future research is needed to develop and test interventions that increase parents' potentials and strengthen relationships during the challenging trajectory of their children's cancer and treatment. CLINICAL RELEVANCE: The multiple sources of stress and uncertainty associated with a child's cancer diagnosis and treatment affect parents' relationships. Difficulties in communication appear frequently in parents' relationship. Our findings may guide healthcare professionals in identifying parents at risk for developing conflicts, communication problems, and lack of alignment between parents that could interfere with providing optimal care for their child with cancer. Healthcare professionals may promote dialogue and encourage parents to express their feelings, seek mutual support, and establish a partnership in dealing with the child's illness. PMID- 20738736 TI - Nurses' perceptions and experiences at daycare for elderly with stroke. AB - PURPOSE: While adult daycare (ADC) is considered a culturally acceptable model of long-term care in countries with a tradition of family-oriented caregiving, Korea is struggling as soaring needs for ADC outpace qualified staff and regulatory systems. This study aimed to describe Korean daycare nurses' perceptions of key daycare services and their working experiences with stroke patients and their families. DESIGN: A mixed-method design was used. First, we conducted a cross sectional descriptive survey to assess Korean nurses' perceptions about the importance of daycare services. Then focus group interviews were performed to explore the nurses' experiences at ADC. METHODS: Seventy of a total of 96 nurses at ADC that specialized in the care of stroke patients responded to the survey (response rate 72.9%) and rated the importance of 11 key daycare service items on a visual analogue scale (0-10). Using a purposive sampling design, 16 eligible nurses were interviewed as a group. The qualitative data from focus group interviews were analyzed using thematic analysis to classify common themes into larger categories. FINDINGS: Survey data revealed that the nurses perceived "skilled nursing services,""functional recovery," and "general health counseling" as the most important daycare service areas. Focus group data resulted in five themes: "Providing the same, standard care,""Lack of partnership with family caregivers,""Conflict with other staff: ambiguity of the roles and tasks,""Lack of proper education and training," and "Need for quality control and monitoring." CONCLUSIONS: Daycare nurses fully recognized the importance of direct nursing care services that are keys to adequate recovery and rehabilitation of older patients with stroke. However, they experienced substantial barriers to carrying out these services due to role confusion, insufficient number of qualified nursing staff, and lack of partnership with family caregivers. CLINICAL RELEVANCE: The results provide insight into changing healthcare policy to support daycare nurses in a country with limited resources and regulations. Strategies such as better quality control and monitoring of daycare services, provision of continuing education, and prioritizing key services should be considered as a way to address challenges experienced by daycare nurses. PMID- 20738737 TI - Exploring women's participation in a U.S. Microcredit Program. AB - PURPOSE: The purpose of this ethnographic study was to explore and describe women's participation in a U.S. microcredit program in the Pacific Northwest and to examine the relationship between the participants' businesses and their health. DESIGN AND METHODOLOGY: In 2006, an ethnographic study was conducted with a microcredit organization in the Pacific Northwest using the following methods: (a) 10 audiotaped, semistructured interviews with clientele; (b) observation of microcredit groups four times a month for 6 months; (c) conversations with organization executive directors; and (d) review of organizational documents. The participants were women 32 to 64 years of age who had received one or more loans from the microcredit organization. FINDINGS: Four broad themes emerged from the data: (a) Microcredit: The introduction; (b) Microcredit: The place; (c) Stereotypes; and (d) Health. Despite the challenges associated with participation, all of the study participants were enthusiastic about the advantages of microcredit and would recommend it to others. CONCLUSIONS: Many international microcredit organizations have incorporated health care and health education into their programs and have reported successful economic and social outcomes for women. In the United States (US), reports are varied, and there is a lack of literature that explores the economic and health link that is addressed in some international microcredit literature. The findings from this study might be used to initiate discussions around conjoint health education programs and microcredit as a health intervention. CLINICAL RELEVANCE: Nurses, as a trusted presence in the community, are in a position to partner with microcredit organizations to improve the health of clientele. PMID- 20738738 TI - Implications of food insecurity on global health policy and nursing practice. AB - PURPOSE: The purpose is to discuss the concept of food insecurity (FI) and its impact on current global health policy and nursing practice. ORGANIZING CONSTRUCT: Food insecurity. METHODS: Literature review. FINDINGS: FI means a nonsustainable food system that interferes with optimal self-reliance and social justice. Individuals experiencing FI lack nutritionally adequate and safe foods in their diet. Resources play a significant role in FI by affecting whether or not people obtain culturally, socially acceptable food through regular marketplace sources as opposed to severe coping strategies, such as emergency food sources, scavenging, and stealing. Persons who are living in poverty, female heads of household, single parents, people living with many siblings, landless people, migrants, immigrants, and those living in certain geographical regions constitute populations at risk and most vulnerable to FI. CONCLUSIONS: FI influences economics through annual losses of gross domestic product due to reduced human productivity. FI affects individuals and households and is largely an unobservable condition, making data collection and analysis challenging. Policy and research have focused on macronutrient sufficiency and deprivation, making it difficult to draw attention and research dollars to FI. CLINICAL RELEVANCE: Persons experiencing FI exhibit clinical signs such as less healthy diets, poor health status, poor diabetes and chronic disease management, and impaired cognitive function. Nurses can recognize the physical, psychosocial, and personal consequences that those with FI face and manage daily. PMID- 20738739 TI - The STTI Practice-Academe Innovative Collaboration Award: honoring innovation, partnership, and excellence. AB - PURPOSE: To describe the benefits and barriers associated with practice-academe partnerships and introduce Sigma Theta Tau International's (STTI's) Practice Academe Innovative Collaboration Award and the 2009 award recipients. DESIGN AND METHODS: In 2008, STTI created the CNO-Dean Advisory Council and charged it with reviewing the state of practice-academe collaborations and developing strategies for optimizing how chief nursing officers (CNOs) and deans work together to advance the profession and discipline of nursing. The Council, in turn, developed the Practice-Academe Innovative Collaboration Award to encourage collaboration across sectors, recognize innovative collaborative efforts, and spotlight best practices. A call for award submissions resulted in 24 applications from around the globe. FINDINGS: An award winner and seven initiatives receiving honorable mentions were selected. The winning initiatives reflect innovative academe service partnerships that advance evidence-based practice, nursing education, nursing research, and patient care. The proposals were distinguished by their collaborators' shared vision and unity of purpose, ability to leverage strengths and resources, and willingness to recognize opportunities and take risks. CONCLUSIONS: By partnering with one another, nurses in academe and in service settings can directly impact nursing education and practice, often effecting changes and achieving outcomes that are more extensive and powerful than could be achieved by working alone. CLINICAL RELEVANCE: The award-winning initiatives represent best practices for bridging the practice-academe divide and can serve as guides for nurse leaders in both settings. PMID- 20738740 TI - Developing a financial framework for academic service partnerships: models of the United States and Europe. AB - PURPOSE: Academic service partnerships (ASPs) are structured linkages between academe and service which have demonstrated higher levels of innovation. In the absence of descriptions in the literature on financial frameworks to support ASPs, the purpose of this paper is to present the supporting financial frameworks of a Swiss and a U.S. ASP. METHODS: This paper used a case study approach. RESULTS: Two frameworks are presented. The U.S. model presented consists of a variety of ASPs, all linked to the School of Nursing of the University of Pennsylvania. The structural integration and governance system is elucidated. Each ASP has its own source of revenue or grant support with the goal to be fiscally in the black. Joint appointments are used as an instrument to realize these ASPs. The Swiss ASP entails a detailed description of the financial framework of one ASP between the Institute of Nursing Science at the University of Basel and the Inselspital Bern University Hospital. Balance in the partnership, in terms of both benefit and cost between both partners, was a main principle that guided the development of the financial framework and the translation of the ASP in budgetary terms. The model builds on a number of assumptions and provides the partnership management within a simple framework for monitoring and evaluation of the progress of the partnership. CONCLUSIONS: In operationalizing an ASP, careful budgetary planning should be an integral part of the preparation and evaluation of the collaboration. The proposed Swiss and U.S. financial frameworks allow doing so. CLINICAL RELEVANCE: Outcomes of care can be improved with strong nursing service and academic partnerships. Sustaining such partnerships requires attention to financial and contractual arrangements. PMID- 20738741 TI - Critical thinking of nurse managers related to staff RNs' perceptions of the practice environment. AB - BACKGROUND INFORMATION AND SIGNIFICANCE: Critical thinking (CT) skills and the inclination to engage in critical thinking are essential for nurse managers to function as transformational leaders capable of influencing staff to align with organizational goals. In an extensive literature review, numerous studies were found examining the concept of CT in students and no studies were found exploring CT in nurse managers. Identifying the attributes, such as CT, that lead to success in the nurse manager role is useful when preparing nurse managers to lead effectively in the current healthcare climate. RESEARCH QUESTION: Is there a difference between nurse managers' CT dispositions and their respective staff nurses' perceptions of the practice environment? DESIGN: A convenience sample of 12 nurse managers and a random sample of 132 of their respective staff registered nurses (RNs) participated in this descriptive study. CT in nurse managers was measured by the California Critical Thinking Disposition Inventory (CCTDI). Staff RNs' perceptions of the practice environment were measured by the Practice Environment Scale (PES). The research question was answered using a t test. FINDINGS: Significant (p < .001) differences were found between specific nurse managers' CCTDI scores for open-mindedness, analyticity, and critical thinking confidence, and significant differences (p < .01) were found for systematicity when compared with their respective staff RNs' mean subscale and overall PES scores. CONCLUSIONS: Results of the study support the positive relationship between strength in critical thinking dispositions of nurse managers and their respective staff RNs' perceptions of the practice environment. Nurse managers with stronger CT dispositions may be better able to create positive practice environments that are conducive to job satisfaction and thus the retention of staff RNs. Inclusion of strategies to support the development and use of CT in nurse managers is recommended. CT and other leadership attributes and skills including emotional and social intelligence and management of change through an appreciative inquiry process may provide opportunities to improve leadership effectiveness in nurse managers. CLINICAL RELEVANCE: Enhancing critical thinking skills and dispositions of nurse managers may help to create positive work environments for staff RNs. Staff RNs who work in an environment perceived to be positive may be in a better position to deliver high quality, safe patient care. PMID- 20738742 TI - Recovered Medical Error Inventory. AB - PURPOSE: To describe the development and psychometric testing of the Recovered Medical Error Inventory (RMEI). DESIGN AND METHODS: Content analysis of structured interviews with expert critical care registered nurses (CCRNs) was used to empirically derive a 25-item RMEI. The RMEI was pilot tested with 345 CCRNs. The data set was randomly divided to use the first half for reliability testing and the second half for validation. A principal components analysis with Varimax rotation was conducted. Cronbach's alpha values were examined. A t test and Pearson correlation were used to compare scores of the two samples. FINDINGS: The RMEI consists of 25 items and two subscales. Evidence for initial reliability includes a total scale alpha of .9 and subscale alpha coefficients of .88 (mistake) and .75 (poor judgment). CONCLUSIONS: The RMEI subscales have satisfactory internal consistency reliability and evidence for construct validity. Additional testing is warranted. CLINICAL RELEVANCE: A tool to measure CCRNs' experiences with recovering medical errors allows quantification of nurse surveillance in promoting safe care and preventing unreimbursed hospital costs for treating nosocomial events. PMID- 20738743 TI - Measurement of students' perceptions of nursing as a career. AB - PURPOSE: Middle school has been identified as the prime age group to begin nursing recruitment efforts because students have malleable perceptions about nursing as a future career choice. The purpose of this integrative review is to present a brief overview of research processes related to middle school students' perceptions of nursing as a future career choice and to critically evaluate the current instruments used to measure middle and high school students' perceptions of nursing as a career choice. DESIGN: An integrative review of the years 1989 to 2009 was conducted searching Cumulative Index to Nursing and Allied Health Literature (CINAHL), National Library of Medicine PubMed service (PubMed), and Ovid MEDLINE databases using the key words career, choice, future, ideal, nursing, and perception. Reference lists of retrieved studies were hand searched, yielding a total of 22 studies. METHODS: Inclusion criteria were (a) sample of middle school students, (b) sample of high school students, (c) mixed sample including middle or high school students, and (4) samples other than middle or high school students if the instrument was tested with middle or high school students in a separate study. Ten studies met these criteria. FINDINGS: Of the 10 studies, samples were 30% middle school students; 40% high school students; 10% mixed, including school-aged students; and 20% college students with an instrument tested in middle school students. Eighty percent of participants were White females. Overall, participants' socioeconomic status was not identified. A single study included a theoretical framework. Five instruments were identified and each could be completed in 15 to 30 min. The most commonly used instrument is available free of charge. Seventy percent of the studies used Cronbach's alpha to report instrument reliability (0.63 to 0.93), whereas 30% failed to report reliability. Fifty percent of the studies established validity via a "panel of experts," with three of those studies further describing the panel of experts. CONCLUSIONS: Samples of white females may hinder generalization. Socioeconomic status was not consistently reported and may be an important factor with regard to perceptions of nursing as a career choice. An overall absence of theoretical framework hinders empirical data from being applied to nursing theories that in turn may support nursing concepts. The reporting of reliability and validity may be improved by further defining panel of experts and expanding the number of experts (more than seven). More in-depth evaluation of the psychometric properties of the instruments with more diverse populations is needed. CLINICAL RELEVANCE: Rigorously tested instruments may be useful in determining middle school students' perceptions about nursing. Therefore, future researchers should consider testing existing instruments in the middle school population, adhering to theoretical frameworks, diversifying the sample population, and clearly reporting reliability and validity to gain knowledge about middle school students' perceptions about a nursing career. PMID- 20738744 TI - "Give me some sugar!" the diabetes self-management activities of African-American primary caregiving grandmothers. AB - PURPOSE: To compare the diabetes self-management activities of African American primary caregiving grandmothers before and after the initiation of caregiving and to compare the diabetes self-management activities of African American primary caregiving grandmothers to diabetic women who were not caring for their grandchildren. DESIGN: Using a cross-sectional, descriptive design, 68 African American women 55 to 75 years of age were recruited as part of a larger study examining the impact of caregiving responsibilities on the diabetic health of African American primary caregiving grandmothers. Each participant was asked the frequency of their performance of six self-management activities. Caregiving grandmothers were asked about these activities before and after the initiation of caregiving. RESULTS: Dependent and independent t-tests with Bonferroni correction were used to analyze the data. Statistically significant differences were noted in diet (t=4.400, p=.000) and self-monitoring of blood glucose (SMBG; t=3.484, p=.001) before and after the initiation of caregiving. For the caregiver versus non-caregiver comparison, statistically significant differences were noted in SMBG (t=-3.855, p=.000) and eye examinations (t=-3.211, p=.001). CONCLUSIONS: The findings provide preliminary data to support further research examining the self management activities of diabetic African American primary caregiving grandmothers. Diabetic African American primary caregiving grandmothers may have a decreased ability to integrate self-management activities into their daily patterns of living. Additional research is needed to determine what factors prevent this population from performing these tasks routinely. CLINICAL RELEVANCE: African American primary caregiving grandmothers were found to have more difficulty performing some of their self-management activities, which may severely impact their overall diabetic health. PMID- 20738745 TI - Sleep in dementia caregivers and the effect of a nighttime monitoring system. AB - PURPOSE: The purpose of this study was to determine if a nighttime home monitoring system, designed to track the movements of a care recipient with dementia, would relieve worry and improve sleep in caregivers of persons with dementia. DESIGN AND METHODS: In this controlled clinical trial, 49 dementia caregivers were followed for up to 1 year. Sleep was measured for 7-day intervals at nine points in time using actigraphy and a sleep diary. FINDINGS: Although the experimental caregivers generally reported that the system was "of great help" in relieving worry about nighttime activity, no significant group differences were found using multilevel modeling analyses. With regard to total sleep time, time awake after sleep onset, and sleep quality, multilevel models did not demonstrate any changes in sleep between groups, either averaged over time or for the interaction of group and time. CONCLUSIONS: Since previous analysis of our qualitative data suggested improvements in caregiver worry and sleep, problems other than night awakenings may be perpetuating the sleep problem. Future studies should include testing of multimodal sleep interventions. CLINICAL RELEVANCE: Caregivers have high amounts of unwanted wake time during the night and additional research is needed to identify effective interventions to improve their sleep. PMID- 20738746 TI - Mammography decision making in older women with a breast cancer family history. AB - PURPOSE: This study's purpose is to describe and explain how women 55 years of age and older with a family history of breast cancer make screening mammography decisions. DESIGN: A qualitative design based on grounded theory. This purposeful sample consisted of 23 women 55 years of age or older with one more first-degree relatives diagnosed with breast cancer. METHOD: Open-ended interviews were conducted with 23 women 55 years of age and older with a family history of breast cancer using a semistructured interview guide. Transcribed interview data were analyzed using constant comparative analysis to identify the conditions, actions, and consequences associated with participant's screening mammography decision making. FINDINGS: Women reported becoming aware of their breast cancer risk usually due to a triggering event such as having a family member diagnosed with breast cancer, resulting in women "guarding against cancer." Women's actions included having mammograms, getting health check-ups, having healthy behaviors, and being optimistic. Most women reported extraordinary faith in mammography, often ignoring negative mammogram information. A negative mammogram gave women peace of mind and assurance that breast cancer was not present. Being called back for additional mammograms caused worry, especially with delayed results. CONCLUSIONS: The "guarding against cancer" theory needs to be tested in other at risk populations and ultimately used to test strategies that promote cancer screening decision making and the adoption of screening behaviors in those at increased risk for developing cancer. CLINICAL RELEVANCE: Women 55 years of age and older with a breast cancer family history need timely mammogram results, mammography reminders, and psychosocial support when undergoing a mammography recall or other follow-up tests. PMID- 20738747 TI - Erythema multiforme: diagnosis, clinical manifestations and treatment in a retrospective study of 22 patients. AB - BACKGROUND: Erythema multiforme (EM) is an acute disorder of the skin and mucosal membranes manifesting in the oral cavity (60-70% of all patients) as polymorphic erosive, ampullar, and bloodstained crusts. The etiology is unclear, although an autoimmune mechanism is involved. Infections and drugs have been implicated in the etiopathogenesis. With the exception of corticosteroids, no specific treatment for EM is available. METHODS: Data were collected on the clinical manifestations, antecedents of viral infection, and the use of drugs substances as possible etiological factors, treatment, and response to topical and systemic corticotherapy. RESULTS: A total of 22 patients were studied (14 males and 8 females), with a mean age of 47+/-20.4 years. A relationship was clearly suspected between drug use and lesion outbreak in 6 patients (27.2%). On the contrary, in 7 patients (31.8%) the triggering factor could have been herpes virus infection (herpes labialis). One half of the patients (11 cases) were classified as presenting minor EM, 36.4% (8 cases) presented major forms of the disease, and 13.6% (3 cases) were classified as corresponding to Stevens-Johnson syndrome. Systemic and/or topical corticosteroids proved effective in controlling the outbreaks in all of our patients. CONCLUSION: The oral mucosa is the most affected mucosal region in EM, with a predilection for the lip mucosa, erosive forms and bloodstained crusts. Systemic corticosteroids are effective in controlling the outbreaks, although their use as maintenance therapy is not clearly indicated. PMID- 20738749 TI - Apoptosis in displaced temporomandibular joint disc with and without reduction: an immunohistochemical study. AB - Internal derangement (ID) of the temporomandibular joint (TMJ) is due to an abnormal relationship of the articular disc to the mandibular condyle, glenoid fossa and articular eminence. The two most common types of internal derangement are anterior disc displacement with (ADDwR) and without reduction (ADDwoR). Disc displacement is associated with degenerative tissue changes. The histological features of discs from patients with TMJ ID reflect a general remodelling caused by abnormal loading. A correlation has been demonstrated between TMJ ID and apoptosis. Few investigations have addressed the role of apoptosis or caspase activity in TMJ ID. The apoptosis activation process was studied in different areas of discs from 18 patients with ID (both ADDwR and ADDwoR) and four cadavers (controls), with emphasis on the expression of caspase 3, whose activation makes the death process irreversible. The results showed a greater proportion of caspase 3-positive cells in ADDwR and ADDwoR than in control discs. Immunopositivity also varied between disc areas; in particular, in ADDwoR sections labelled cells were significantly more numerous (P < 0.01) in the posterior disc attachment than in the anterior and intermediate bands. In addition, a significantly greater proportion of labelled cells was seen in the anterior (+) and intermediate (++) band of ADDwR compared with ADDwoR discs both bands (P < 0.05). These data suggest the importance of programmed cell death in the progression of TMJ ID. PMID- 20738748 TI - Antifungal activity of lawsone methyl ether in comparison with chlorhexidine. AB - OBJECTIVE: The aim of this study was to determine the antifungal activity of lawsone methyl ether mouthwash (LME) in comparison with chlorhexidine mouthwash (CHX) in vitro and in vivo. MATERIALS AND METHODS: For in vitro study, each mouthwash preparation was added into the inoculum of Candida. The turbidity was recorded after incubation at 37 degrees C for 48 h. Candidal culture was performed and the number of colony of Candida albicans was recorded. For in vivo study, a crossover clinical trial was conducted in 22 HIV-infected subjects and 32 denture wearers. Clinical examination was performed and oral rinse technique was carried out immediately before and 0, 1, 2 h after using each mouthwash. Allergy and subjective assessment of the mouthwashes were recorded. Statistical analysis was performed using one-way ANOVA and linear mixed effect modeling. RESULTS: In vitro, antifungal activity of 0.25% LME was significantly greater than that of 0.12% CHX (P < 0.05) and comparable with that of 0.2% CHX. In vivo, antifungal activity up to 2 hours of 0.025% LME mouthwash was evidenced in both groups of subjects, although significantly lower than that of 0.12% CHX. No allergic reaction was reported. LME mouthwash was graded to have less bitter taste than that of CHX. Subjects' satisfaction on taste and smell of LME mouthwash was significantly greater than that of CHX (P < 0.05). CONCLUSIONS: Lawsone methyl ether mouthwash possesses potent antifungal activity both in vitro and in vivo. However, concentration of the mouthwash needs to be adjusted in addition to further clinical trials on long-term use. PMID- 20738750 TI - Does the neuromotor abnormality type affect the salivary parameters in individuals with cerebral palsy? AB - BACKGROUND: Previous studies reported alterations in salivary flow rate and biochemical parameters of saliva in cerebral palsy (CP) individuals; however, none of these considered the type of neuromotor abnormality among CP individuals, thus it remains unclear whether the different anatomical and extended regions of the brain lesions responsible for the neurological damage in CP might include disruption of the regulatory mechanism of saliva secretion as part of the encephalopathy. The aim of this study was to evaluate salivary flow rate, pH and buffer capacity in saliva of individuals with CP, aged 3-16 years, with spastic neuromotor abnormality type and clinical patterns of involvement. METHODS: Sixty seven individuals with CP spasticity movement disorder, were divided in two groups according to age (3-8- and 9-16-years-old) and compared with 35 sibling volunteers with no neurological damage, divided in two groups according to age (3 8- and 9-16-years-old). Whole saliva was collected under slight suction and pH and buffer capacity were determined using a digital pH meter. Buffer capacity was measured by titration using 0.01N HCL, and flow rate was calculated in ml/min. RESULTS: In both age groups studied, whole saliva flow rate, pH and buffer capacity were significantly lower in the spastic CP group (P<0.05). The clinical patterns of involvement did not influence the studied parameters. CONCLUSION: These findings show that individuals with spastic cerebral palsy present lower salivary flow rate, pH and buffer capacity that can increase the risk of oral disease in this population. PMID- 20738751 TI - In vitro effect of sodium fluoride on antioxidative enzymes and apoptosis during murine odontogenesis. AB - Excessive fluoride ingestion has been identified as a risk factor for fluorosis and oxidative stress. The oxidative stress results from the loss of equilibrium between oxidative and antioxidative mechanisms that can produce kinase activation, mitochondrial disturbance and DNA fragmentation, resulting in apoptosis. Actually many people are exposed to no-adverted fluoride consumption in acute or chronic way. The aim of this study was to determine the effect of sodium fluoride on first molar germ in relation to its effect on antioxidative enzymes immunoexpression and apoptosis. Thirty first molar germs from 1-day-old Balb/c mice were cultured for 24 h with sodium fluoride (0 mM, 1 mM and 5 mM). Immunoexpression determination of CuZnSod, MnSod, catalase, Bax, Bid, caspase 8, caspase 9, caspase 3 and TUNEL assay were performed. Cellular disorganization in ameloblast and odontoblast-papilla zones was observed. CuZnSod and MnSod immunoexpression decrease in experimental groups. Caspase 8, caspase 3, Bax, Bid increase expression and more TUNEL positive cells in both experimental groups than control, suggest that apoptosis induced by fluoride is related to oxidative stress due to reduction of the enzymatic antioxidant. PMID- 20738752 TI - TP53 mutations in clinically normal mucosa adjacent to oral carcinomas. AB - BACKGROUND: The tumour-suppressor protein p53 often accumulates in histologically normal epithelium adjacent to oral squamous cell carcinomas (OSCC). We investigated whether this was associated with mutations in TP53, the gene for p53, and might implicate impending malignancy. METHODS: Specimens from 18 human squamous cell carcinomas were stained with monoclonal p53 antibodies. Positive cells were microdissected with laser-captured microscopy from the tumour and adjacent normal and dysplastic epithelium. DNA was extracted, and exons 5-9 of the TP53 gene were amplified by PCR. Amplified products were separated by denatured gradient gel electrophoresis. Fragments with a deviant DGEE pattern were sequenced. RESULTS: TP53 mutations were found in six of 18 tumours. Fourteen specimens contained histologically normal mucosa adjacent to the tumour; 13 of these showed small clusters of p53 positive cells. Seven specimens contained both histological normal and dysplastic epithelial tissues adjacent to the tumour. A TP53 mutation was found in only one specimen; this mutation appeared in the normal mucosa, the adjacent tumour, and the epithelial dysplasia. CONCLUSION: We found that upregulation of p53 was a frequent event in histological normal mucosa adjacent to OSCC; however, it was rarely associated with a mutation in the TP53 gene. PMID- 20738753 TI - Is workplace screening for potentially malignant oral disorders feasible in India? AB - BACKGROUND: Because of delays in diagnosis, oral cancer usually presents for therapy at a late stage. Patients are unaware of having lesions as they are mostly asymptomatic and physicians generally do not examine the mouth sufficiently. People in rural areas or are underserved may not frequently visit the dentist who can easily pick up these lesions early. Screening programs are useful in that regard. Such programs in general are conducted by either inviting people to come to a screening center or by health care workers visiting the individual households. However, those who work during the day may not visit screening centers or be at home during the day of the screening by a visiting health care worker. Workplace screening overcomes these challenges. METHODS: To assess the feasibility of a screening program to detect potentially pre-malignant oral disorders in a workplace in India, clinically visible mucosal lesions were compared with the clinical photographs of the same lesions assessed by an expert. Role of smoking, alcohol, and chewing betel quid and tobacco in the etiology of those lesions were assessed. RESULTS: Sixty-nine percent of the eligible subjects participated in the screening (n=1613). Prevalence of leukoplakia was 5%. Bidi (OR=35.6), and cigarette smoking (OR=22.8), alcohol (OR=17.6), and tobacco and areca nut chewing (OR=7.5), were significantly associated with leukoplakia and erythroplakia (all P< 0.05). CONCLUSIONS: Conduction of a screening program by valid visual inspection to detect potentially malignant oral disorders within a workplace is not only feasible but also effective. PMID- 20738754 TI - Expression and importance of zinc-finger transcription factor Slug in adenoid cystic carcinoma of salivary gland. AB - BACKGROUND: It has been reported that zinc-finger transcription factor Slug plays a critical role in tumor proliferation and differentiation, relapse, invasion, metastasis, and decreased survival. However, there is little information on the expression and role of Slug in salivary adenoid cystic carcinoma (ACC). METHOD: Demographic variables and primary tumor site, dates of diagnoses, perineural invasion, local regional recurrence, and distant metastasis of 121 cases of salivary ACC treated at the Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University between 1996 and 2005 were retrieved. The Slug expression of all these cases was examined by immunohistochemical methods. The association between Slug expression and clinicopathological variables was analyzed using Chi-squared test, and the prognostic factors were examined by univariate and multivariate analyses. RESULTS: Our data demonstrated that the positive expression of Slug was observed in 71.90% (87/121) of cases. Slug expression was significantly associated with tumor site, TNM stage, histological pattern, perineural invasion, local regional recurrence and distant metastasis of patients with ACC (P<0.05). And Slug expression, local regional recurrence and distant metastasis were independent and significant prognostic factors in all patients. CONCLUSIONS: It is proposed that Slug may play an important role in the invasion and metastasis of ACC, and that Slug had the potential for one of the strong invasion and metastasis indicators at presentation of ACC patients. PMID- 20738755 TI - The mechanism for the neuroprotective effect of melatonin against methamphetamine induced autophagy. AB - Methamphetamine (METH) is a common drug of abuse that induces toxicity in the central nervous system and is connected to neurological disorders such as Parkinson's disease. METH neurotoxicity is induced by reactive oxygen species (ROS) production and apoptosis. Moreover, autophagy is an alternative to cell death and a means for eliminating dysfunctional organelles. In other cases, autophagy can end up in cell death. Nonetheless, it is not clear whether autophagy is also correlated with apoptotic signaling in drug-induced neurotoxicity. Therefore, we hypothesized that METH-generated toxicity associated with initiating the apoptotic signaling cascade can also increase the autophagic phenotype in neuronal cells. Using the SK-N-SH dopaminergic cell line as our model system, we found that METH-induced autophagy by inhibiting dissociation of Bcl-2/Beclin 1 complex and its upstream pathway that thereby led to cell death. We uncovered a novel function for the anti-apoptotic protein Bcl-2, as it played a role in negatively regulating autophagy by blocking an essential protein in the signaling pathway, Beclin 1. Furthermore, Bcl-2 was activated by c-Jun N-terminal kinase 1 (JNK 1), which is upstream of Bcl-2 phosphorylation, to induce Bcl 2/Beclin 1 dissociation. Furthermore, we demonstrated a novel role for melatonin in protecting cells from autophagic cell death triggered by the Bcl-2/Beclin 1 pathway by inhibiting the activation of the JNK 1, Bcl-2 upstream pathway. This study provides information regarding the link between apoptosis and autophagy signaling, which could lead to the development of therapeutic strategies that exploit the neurotoxicity of drugs of abuse. PMID- 20738756 TI - Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARgamma expression and enhancing Runx2 expression. AB - Adipogenesis and osteogenesis, a reciprocal relationship in bone marrow, are complex processes including proliferation of precursor cells, commitment to the specific lineage, and terminal differentiation. Accumulating evidence from in vitro and in vivo studies suggests that melatonin affects terminal differentiation of osteoblasts and adipocytes, but little is known about the effect of melatonin on the process of adipogenesis and osteogenesis, especially adipogenesis. This study was performed to determine the effect of melatonin on adipogenesis and osteogenesis in human mesenchymal stem cells (hMSCs). Cell proliferation assays demonstrated that melatonin had no apparent effect on the proliferation of hMSCs. When melatonin was added to the adipogenic/osteogenic medium, it directly inhibited adipogenesis and simultaneously promoted osteogenesis of hMSCs in a dose-dependent manner. Furthermore, quantitative RT PCR demonstrated that melatonin significantly suppressed peroxisome proliferator activated receptor gamma (PPARgamma) expression (day 3, 25% decrease; day 6, 47% decrease), but promoted Runx2 expression (day 3, 87% increase; day 6, 56% increase) in the early stages of adipogenesis and osteogenesis of hMSCs. Moreover, melatonin down-regulated several markers of terminal adipocyte differentiation, including leptin (30%), lipoprotein lipase (LPL, 41%), adiponectin (51%), and adipocyte protein 2 (alphaP2, 45%). Meanwhile, melatonin up-regulated several markers of osteoblast differentiation, including alkaline phosphatase (110%), osteopontin (218%), and osteocalcin (310%). These results suggest that melatonin directly inhibits hMSCs adipogenic differentiation and significantly enhances hMSCs osteogenic differentiation by suppressing PPARgamma expression and enhancing Runx2 expression; this provides further evidence for melatonin as an anti-osteoporosis drug. PMID- 20738758 TI - Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event. AB - BACKGROUND: The risk of recurrent venous thrombosis is higher in men than in women, and this is so far unexplained. We set out to determine the influence of age, time between first and second event, type of first event, oral contraception, pregnancy and surgery. METHODS: We performed a prospective follow up study of 474 patients with a first objective diagnosis of deep vein thrombosis, aged 18-70 years (Leiden Thrombophilia Study cohort). RESULTS: During 3477 person-years of follow-up, 90 recurrences occurred. The overall incidence rates of recurrence (IRs) were 40.9 per 1000 person-years in men and 15.8 per 1000 person-years in women. Men with an unprovoked first event had the highest risk of recurrence, with almost one-third experiencing a second unprovoked event within 8 years (IR 41.2 per 1000 person-years). This risk was three-fold lower in women [IR 14.2 per 1000 person-years; hazard ratio 2.8 (95% confidence interval 1.4-5.7)]. Age at diagnosis had little effect on recurrence rate, and nor had time elapsed since the first event. In women, almost half of the recurrences were provoked and were mainly related to oral contraceptive use or pregnancy. CONCLUSIONS: The higher recurrence rate in men than in women is not the result of differences in the environmental or transient risk factors that we studied. The risk profile for a second thrombotic event is clearly different from that of a first. PMID- 20738757 TI - Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging. AB - This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals. PMID- 20738759 TI - Increased risk of pulmonary embolism among patients with hyperthyroidism: a 5 year follow-up study. AB - BACKGROUND: Although studies have indicated that hyperthyroidism is associated with hypercoagulability, most such studies have focused only on examining the incidence of venous thrombosis. As far as we know, no study has attempted to explore the risk of pulmonary embolism (PE) among patients with hyperthyroidism. OBJECTIVE: Using a nationwide population-based dataset, this study was aimed at estimating the risk of PE among hyperthyroidism patients during a 5-year period, as compared with non-hyperthyroidism patients during the same period. METHODS: Data sourced from the Taiwan Longitudinal Health Insurance Database were analyzed. The study included 8903 patients with hyperthyroidism as a study cohort and 44,515 randomly selected patients without hyperthyroidism as a comparison cohort. Stratified Cox proportional hazard regressions were used to compute the 5 year PE-free survival rate between these two cohorts. RESULTS: Of the total of 53,418 patients, 41 patients (0.08%) were identified as having PE during the follow-up period, 14 from the study cohort (0.16% of the hyperthyroidism patients) and 27 comparison patients (0.06% of patients from the comparison cohort). After adjustment for geographic region, monthly income, hypertension, diabetes, hyperlipidemia, peripheral vascular disease, coronary heart disease, cancer, recent surgery, recent fracture, pregnancy and the use of anticoagulants, the risk of having PE during the 5-year follow-up period was 2.31 times greater (95% confidence interval 1.20-4.45, P=0.012) for patients with hyperthyroidism than for patients in the comparison cohort. CONCLUSION: We found an increased risk of PE in patients with hyperthyroidism. Clinicians should be aware of this increased risk. PMID- 20738761 TI - Risk of recurrent venous thromboembolism after stopping treatment in cohort studies: recommendation for acceptable rates and standardized reporting. PMID- 20738760 TI - Src family kinases are essential for primary aggregation by G(i) -coupled receptors. AB - INTRODUCTION AND BACKGROUND: Adrenaline stimulates biphasic aggregation in plasma through the G(i) -coupled alpha(2A) -adrenoreceptor. In the present study, we demonstrate that both primary and secondary wave aggregation induced by adrenaline in plasma is blocked by two structurally distinct inhibitors of Src family kinases, dasatinib and PD0173952. METHODS AND RESULTS: In contrast, primary aggregation is partially inhibited or unaffected in the presence of inhibitors of cyclo-oxygenase, phosphoinositide (PI) 3-kinases, and P2Y(1) and P2Y(12) ADP receptors, although secondary aggregation is abolished. The ability of adrenaline to inhibit adenylyl cyclase and to synergize with platelet agonists in mediating platelet activation in plasma is retained in the presence of Src family kinase inhibition. Moreover, adrenaline does not activate Src family kinases, as determined by western blotting of their regulatory tyrosines, suggesting that constitutive signaling from Src family kinases may underlie their role in activation. Adrenaline is widely used in clinical laboratories for investigation of patients with suspected bleeding disorders. In a group of 90 unrelated patients with a clinically diagnosed platelet bleeding disorder, we identified four who did not exhibit primary wave aggregation in response to adrenaline, although the catecholamine potentiated the response to other agonists, and five who failed to undergo secondary wave aggregation. In contrast, adrenaline stimulated biphasic aggregation in 60 controls. All of the patients with a defective response to adrenaline had impaired ADP-induced platelet activation. CONCLUSIONS: The present results indicate a previously unappreciated role for Src family kinases in mediating G(i) signaling in plasma, and demonstrate heterogeneity in response to adrenaline in patients with a clinically diagnosed platelet disorder. PMID- 20738762 TI - Relation between serum osteoprotegerin and carotid intima media thickness in a general population - the Tromso Study. AB - BACKGROUND: Previous studies have reported conflicting results on the relation between serum osteoprotegerin (OPG) concentration and carotid intima media thickness (CIMT). PATIENTS/METHODS: The present study was conducted to investigate the relations between OPG, risk factors for cardiovascular diseases (CVD) and carotid intima media thickness (CIMT) in a large cross-sectional study including 6516 subjects aged 25-85years who participated in a population-based health survey. RESULTS: CIMT increased significantly across tertiles of OPG after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C reactive protein (CRP), body mass index (BMI), systolic blood pressure, CVD and diabetes mellitus (P<0.0001). There was a significant interaction between age and OPG (P=0.026). The risk of being in the uppermost quartile of CIMT was reduced (OR 0.52, 95% CI 0.30-0.88) with each standard deviation (SD) higher level of OPG in subjects <45years (n=444), whereas subjects >=55years of age (n=4884) had an increased risk of being in the uppermost quartile of CIMT (OR 1.19, 95% CI 1.10 1.29) after adjustment for traditional CVD risk factors. CONCLUSIONS: Age has a differential impact on the association between OPG and CIMT in a general population. The present findings may suggest that increased serum OPG does not promote early atherosclerosis in younger subjects. PMID- 20738763 TI - Abstracts of the 20th International Society for Fibrinolysis and Proteolysis (ISFP) Congress. Amsterdam, The Netherlands. August 24-28, 2010. PMID- 20738764 TI - A novel mechanism of cytokine release in phagocytes induced by aggretin, a snake venom C-type lectin protein, through CLEC-2 ligation. AB - BACKGROUND: Macrophages are major immune cells and play an important role in modulating homeostasis and the immune defense mechanism. In inflammatory responses to the infection of pathogens, macrophages are activated, producing various inflammatory mediators. Snake venom C-type lectin proteins (snaclecs) have diverse targets, including platelet GPVI, GPIb, integrin alpha2beta1 or CLEC 2 expressed in platelets, endothelial cells or myeloid cells. METHODS: In this study, murine macrophages (RAW 264.7 cells) and human monocytes (THP-1) were treated with different snaclecs, including aggretin, gramicetin, trowaglerix and convulxin, in the absence or presence of LPS for 24 h. RESULTS: The production of cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL 6), in supernatants was measured by ELISA. Aggretin increased the production of TNF-alpha and IL-6 in both RAW264.7 and THP-1 cells; however, the other snaclecs did not. Aggretin induced extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) tyrosine phosphorylation of RAW264.7 cells. Pretreatments with inhibitor of ERK, JNK, p38 or NF-kappaB abolished cytokine release caused by aggretin. Aggretin bound to THP-1 cells in a concentration dependent manner and it displaced the CLEC-2 mAb binding to THP-1 cells and the immobilized aggretin selectively bound to CLEC-2 of both platelets and THP-1 cell lysates. Furthermore, aggretin elevated the plasma level of IL-6 in ICR mice as it was administered intramuscularly. CONCLUSION: These results indicate that aggretin may induce cytokine TNF-alpha/IL-6 release via interacting with CLEC-2 receptor and the subsequent MAPK and NF-kappaB activation in monocytes/macrophages. PMID- 20738765 TI - A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. AB - BACKGROUND: Prophylaxis of venous thromboembolism (VTE) in hospitalized medical patients is largely underused. We sought to assess the value of a simple risk assessment model (RAM) for the identification of patients at risk of VTE. METHODS: In a prospective cohort study, 1180 consecutive patients admitted to a department of internal medicine in a 2-year period were classified as having a high or low risk of VTE according to a predefined RAM. They were followed-up for up to 90 days to assess the occurrence of symptomatic VTE complications. The primary study outcome was to assess the adjusted hazard ratio (HR) of VTE in high risk patients who had adequate in-hospital thromboprophylaxis in comparison with those who did not, and that of VTE in the latter group in comparison with low risk patients. RESULTS: Four hundred and sixty-nine patients (39.7%) were labelled as having a high risk of thrombosis. VTE developed in four of the 186 (2.2%) who received thromboprophylaxis, and in 31 of the 283 (11.0%) who did not (HR of VTE, 0.13; 95% CI, 0.04-0.40). VTE developed also in two of the 711 (0.3%) low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with low-risk patients, 32.0; 95% CI, 4.1-251.0). Bleeding occurred in three of the 186 (1.6%) high-risk patients who had thromboprophylaxis. CONCLUSIONS: Our RAM can help discriminate between medical patients at high and low risk of VTE. The adoption of adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding. PMID- 20738766 TI - Utility of transesophageal echocardiography for transcatheter occlusion of patent ductus arteriosus in dogs: influence on the decision-making process. AB - BACKGROUND: Appropriate device selection for transcatheter occlusion of patent ductus arteriosus (PDA) is essential to procedural success. OBJECTIVES: To determine if transesophageal echocardiography (TEE) influences device selection for PDA occlusion and to report benefits, limitations, and complications associated with TEE. ANIMALS: Twenty-two client-owned dogs with left-to-right shunting PDA. METHODS: PDA dimensions were obtained via transthoracic echocardiography (TTE) and then TEE followed by angiography. Based solely on information from TTE and angiography, an initial device type and size were selected. After initial device selection, TEE measurements were disclosed and changes in device selection were recorded. After device release, angiography, TEE, or both were performed to assess occlusion. RESULTS: An Amplatz canine duct occluder (ACDO) was securely positioned and released in 21 dogs and an embolization coil was deployed in 1 dog. Based on TEE evaluation, initial selected device type was unchanged but ACDO size was changed in 3 dogs. TEE was utilized throughout the procedure allowing real time visualization of device deployment, release and assessment of closure in 17 dogs. No complications occurred related to TEE. Complete PDA closure was achieved in all dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: TEE provided anatomic information regarding PDA morphology that closely approximated angiographic ductal dimensions while aiding in device deployment, release and confirmation of closure. We conclude that TEE provides complementary anatomical and intraprocedural information and is well tolerated in dogs. PMID- 20738767 TI - Assessment of left ventricular systolic function by strain imaging echocardiography in various stages of feline hypertrophic cardiomyopathy. AB - BACKGROUND: Diastolic dysfunction occurs in many cats with hypertrophic cardiomyopathy (HCM). Less is known about systolic function in various stages of HCM. Myocardial strain analysis by tissue Doppler imaging (TDI) is a noninvasive echocardiographic method to assess systolic function that has not been reported previously in cats. OBJECTIVES: To evaluate systolic function in various stages of feline HCM by measurement of myocardial strain. ANIMALS: Two hundred and sixty three cats. METHODS: Cats were classified by echocardiography into one of the following groups: clinically healthy (control) group (n=160), mild HCM (n=22), moderate HCM (n=39), and severe HCM (n=42). Peak myocardial strain, measured by TDI in the basal and midventricular segment of the interventricular septal wall (IVS) and the left ventricular posterior wall (LVPW), was compared among different HCM and control groups. RESULTS: Whereas conventional echocardiography demonstrated an apparently normal or supernormal contractile state based on percentage of fractional shortening, myocardial strain in all HCM groups was significantly decreased compared with the control group (P<.001). There was a significant correlation between strain values and wall thickness (P<.001). Reproducibility of strain analysis was 6.3% in the IVS and 9.7% in the LVPW. CONCLUSIONS AND CLINICAL IMPORTANCE: Myocardial strain analysis is a new, valuable, and reproducible method in cats. This method allows noninvasive detection of abnormal systolic deformation in cats with HCM despite apparently normal left ventricular systolic function as assessed by conventional echocardiography. The abnormal systolic deformation already was present in mild HCM and increased with progressive left ventricular concentric hypertrophy. PMID- 20738768 TI - Pulmonary abnormalities in dogs with leptospirosis. AB - BACKGROUND: Leptospirosis in dogs is a multiorgan disease affecting mostly kidneys and liver. OBJECTIVES: The objective was to characterize prevalence, clinical, and radiological features and outcome of dogs with leptospirosis and pulmonary abnormalities. ANIMALS: Fifty dogs with leptospirosis. METHODS: Medical records of dogs diagnosed with leptospirosis at the Small Animal Clinic, Berlin, were reviewed. Diagnosis was based on microscopic agglutination test, blood or urine polymerase chain reaction, and histopathology. Based on clinical and/or radiological signs, patients were grouped into dogs with lung abnormalities (group 1) or without (group 2). Severity of respiratory distress was scored as mild to moderate (grade 1) or severe (grade 2). Thoracic radiographs were scored based on pulmonary changes and location as grade 1 (caudal interstitial pattern), 2 (generalized mild to moderate reticulonodular interstitial pattern), or 3 (generalized severe reticulonodular interstitial pattern with patchy alveolar consolidations). Results of CBC and biochemistry were compared between groups. RESULTS: Thirty-five dogs had radiological pulmonary changes (grade 1: 5; grade 2: 14; grade 3: 16); 31 of them had pulmonary distress (grade 1: 13, grade 2: 18). Sixty-seven percent of the dogs with dyspnea grade 2 were mainly euthanized because of respiratory distress. Fifteen percent of the dogs with dyspnea grade 1 and 21% without clinical respiratory signs were euthanized because of acute renal failure or sepsis. CONCLUSIONS AND CLINICAL IMPORTANCE: In 70% of dogs with leptospirosis pulmonary changes were detected. Lung involvement represented a severe complication causing increased case fatality depending on the severity of respiratory distress. PMID- 20738769 TI - The relationship between body weight, body condition, and survival in cats with heart failure. AB - BACKGROUND: Obese people with heart failure have improved survival compared with their normal or underweight counterparts. The purpose of this study was to determine if there is a relationship between body weight or body condition and survival in cats with heart failure. HYPOTHESIS: Body weight and body condition score (BCS) are predictors of survival in cats with heart failure. ANIMALS: One hundred and one cats with heart failure (International Small Animal Cardiac Health Council Classes II, IIIa, or IIIb) evaluated between March 2007 and June 2009. METHODS: Data regarding initial body weight and BCS, subsequent changes in body weight, and treatment were collected from records and compared with survival times. RESULTS: Median initial body weight was 5.1 kg (range, 2.2-9.5 kg). Median BCS was 5 (range, 3-9). Of the 68 cats that were discharged from the hospital, median body weight change was 0.0 kg (range, -2.6 to +2.3 kg). Survival time for all 101 cats was 93 days (0-811 days). Survival could be predicted using a model combining initial body weight (P=.02), body weight squared (P=.02), and survival to discharge (P<.001) with a resulting global P value for this model of P<.0001. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with the lowest and highest body weights had reduced survival times compared with those with body weights in the intermediate ranges, suggesting a U-shaped relationship between body weight and survival. Additional research into the effects of body composition could help to determine optimal management of cats with heart failure. PMID- 20738770 TI - Perceptions of quality of life and priorities of owners of cats with heart disease. AB - BACKGROUND: Owners' perceptions and priorities regarding quality of life (QoL) are important considerations given the unknown efficacy of many commonly administered medications, stress of hospital visits, difficulties providing home care, and personal choices including euthanasia. OBJECTIVE: To describe the relative importance of quality versus quantity of life to owners of cats with heart disease. ANIMALS: Two hundred and thirty-nine cats with heart disease. METHODS: Prospective questionnaire-based clinical study. Cat owners completed a questionnaire to identify important parameters when assessing their cat's QoL, the relative importance of quality versus quantity of life, and willingness to trade survival time for QoL. Variables associated with these parameters were evaluated with multivariate analyses. RESULTS: Appetite, owner interaction, sleep patterns, and litterbox habits were deemed important to QoL. Concern over pet suffering was significantly greater than concern over life expectancy. Ninety three percent of owners were willing to trade survival time for good QoL; 57% of these were willing to trade up to 6 months. On multivariate analysis, the only factor significantly (P=.002) associated with willingness to trade 6 months was study site. Owner concern regarding stress of administering medications at home increased with number and frequency of medications. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicated that QoL is more important to owners of cats with heart disease than longevity. The various priorities and concerns of cat owners should be taken into account in order to provide optimal care. PMID- 20738771 TI - Comparison of hematologic and biochemical results on blood obtained by jugular venipuncture as compared with intravenous catheter in adult horses. AB - BACKGROUND: During hospitalization, horses typically undergo frequent blood sampling for diagnostic testing and monitoring. The need for numerous samples in hospitalized horses makes acquisition from an intravenous catheter (IVC) both convenient and less stressful to the patient. HYPOTHESIS: We hypothesized that there would be no significant difference in the plasma chemistry and CBC variables from blood samples obtained from a jugular catheter as compared with direct jugular venipuncture. ANIMALS: Fifty adult hospitalized horses; 25 receiving constant rate crystalloid therapy, and 25 receiving low volume IV medication. METHODS: This study was conducted using a prospective, blinded, cross over design. Samples were obtained sequentially by direct venipuncture of the jugular vein and aspiration from an IVC in the contralateral vein after an appropriate presample of blood was obtained and discarded. Samples were submitted for blinded analysis including CBC, plasma chemistry analysis, stall side plasma glucose concentration, PCV, and total protein concentration. Data obtained were analyzed using a Student's t-test with compensation for unequal variances between the 2 groups. Analyses were Bonferroni corrected for a 5% 2-tailed hypothesis test. RESULTS: There were no statistically significant or clinically relevant differences associated with sampling method (venipuncture versus catheter) regardless of fluid administration status in any of the 24 analytes measured. CONCLUSIONS AND CLINICAL IMPORTANCE: Blood samples obtained by IVC have clinically equivalent values to those taken by direct venipuncture in commonly performed analyses. Additional investigation is warranted to establish if this technique is associated with increased complications such as phlebitis or bacteremia. PMID- 20738772 TI - Clinical and magnetic resonance imaging features of central nervous system blastomycosis in 4 dogs. PMID- 20738773 TI - GB virus C infection among young, HIV-negative injection drug users with and without hepatitis C virus infection. AB - Our study examined the association between GB virus C (GBV-C) and (i) hepatitis C virus (HCV) infection status, (ii) biomedical indicators of liver disease (alanine and aspartate aminotransferases) and (iii) HCV RNA level among young injection drug users (IDUs) recruited using street outreach and respondent-driven methods. Cross-sectional and longitudinal analyses were completed. GBV-C (active or resolved) infection was significantly (P < 0.05) more prevalent among HCV antibody-positive (anti-HCV+) (65.1%) than antibody-negative (anti-HCV-) (32.3%) (OR = 3.9, 95% CI: 2.3-6.9) IDUs. The prevalence of resolved GBV-C infection was highest among those with chronic HCV infection (41.9%), followed by those with resolved HCV infection (34.4%) and significantly lower (P < 0.05) among anti-HCV participants (16.9%). Although not statistically significant (P = 0.13), a similar pattern was observed for active GBV-C infection. No association between GBV-C infection status and biomedical indicators of liver disease or HCV RNA level over time was observed. In conclusion, GBV-C infection prevalence was higher among anti-HCV+ compared to anti-HCV- young IDUs, similar to prior studies among older populations. In particular, chronically HCV-infected young IDUs had an increased rate of GBV-C clearance. PMID- 20738774 TI - Conformational anti-cytochrome P4502E1 (CYP2E1) auto-antibodies contribute to necro-inflammatory injury in chronic hepatitis C. AB - Circulating auto-antibodies against cytochrome P4502E1 (CYP2E1) have been observed in a significant fraction of patients with chronic hepatitis C (CHC). This study investigated the clinical significance of these auto-antibodies in relation to their antigen specificity. The presence of anti-CYP2E1 IgG was investigated in 137 consecutive patients with biopsy-proven CHC. Anti-CYP2E1 IgG above control threshold levels was detected in 52 (38%) subjects. By combined immunoprecipitation and western blotting, we observed that among anti-CYP2E1 IgG positive sera, 23 (44%) were unreactive towards denaturated CYP2E1, indicating a prevalent recognition of conformational CYP2E1 antigens. Conformational anti CYP2E1 auto-antibodies were unrelated to circulating gamma-globulins, alcohol intake or infection by specific HCV genotypes. The presence of anti-CYP2E1 auto antibodies was associated with an 11-fold (OR 10.9 95%CI 1.4-86.6 P = 0.008) increased prevalence of necro-inflammatory grading >= 4 (Ishack's criteria) and 4 fold (OR 4.0; 95%CI 1.3-11-7: P = 0.014) increased prevalence of fibrosis staging >= 2, respectively. Multivariate analysis confirmed conformational anti-CYP2E1 IgG (P = 0.005) and age (P = 0.033) as independent predictors of necro inflammatory grading >= 4. The development of anti-CYP2E1 auto-antibodies targeting conformational CYP2E1 epitopes is associated with more severe liver damage in CHC. PMID- 20738776 TI - Transferrin saturation as a predictor of hepatic iron overload. PMID- 20738777 TI - Refractory ascites: can it be defined only by the response to furosemide and spironolactone? PMID- 20738775 TI - Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients. AB - The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 MUg/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 +/- 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline <1.19 log for genotype-1 and <0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second phase viral decline slope (i.e., measured from day 2 to 29) <0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (<0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV. PMID- 20738778 TI - Increased PD-1 and decreased CD28 expression in chronic hepatitis B patients with advanced hepatocellular carcinoma. AB - BACKGROUND/AIMS: Hepatitis B infection is a well-known cause of hepatocellular carcinoma (HCC). This study aims to investigate the role that the co-stimulatory molecule CD28 and co-inhibitory molecule programmed death-1 (PD-1) play in compromising the function of tumour-infiltrating lymphocytes (TIL) in hepatitis B virus (HBV)-related HCC. METHODS: A total of 45 patients with HBV-related HCC were enrolled during the period February 2008 to March 2010. The immune phenotype and the expression of PD-1, CD28 and CD127 in TIL in biopsy specimens and in peripheral blood lymphocytes (PBL) from the same patients were analysed by flow cytometry. RESULTS: Among the 45 patients, there was a male predominance (80%) and the mean age was 50 +/- 13.68 years (range: 29-71). The majority of TIL were CD45RO(+) CD69(+). PD-1 expression was higher and CD28 and CD127 expression levels were lower in TIL than in PBL. The prevalence of portal vein thrombosis was 40%. Furthermore, tumour thrombosis invasion into the portal vein correlated with the expression level of the PD-1 co-inhibitory molecule. CONCLUSION: PD-1(+) tumour-infiltrating lymphocytes correlate with portal vein thrombosis and might serve as a potential prognostic marker of and a novel therapeutic target for HBV related HCC. PMID- 20738779 TI - Hepatitis B screening, prophylaxis and re-activation in the era of rituximab based chemotherapy. AB - BACKGROUND: Hepatitis B re-activation is a well-described complication in patients with inactive chronic hepatitis B receiving chemotherapy. Screening for HBV and pre-emptive therapy are recommended. However, the rates of HBV screening, prophylaxis and re-activation during rituximab-containing chemotherapy are unknown. PATIENTS AND METHODS: We performed a retrospective study of patients with non-Hodgkin lymphoma (NHL) who received rituximab between August 1997 and September 2009. We evaluated patients for hepatitis B serologies, antiviral prophylaxis and hepatitis B re-activation during or up to 6 months after chemotherapy. RESULTS: One thousand four hundred and twenty-nine patients underwent rituximab-containing chemotherapy for NHL. Hepatitis B serologies were documented in 524 (36.6%) patients. Of these, 20 (3.8%) were HBsAg positive and 10 (50%) experienced HBV re-activation. Only half (5/10) had HBV serology documented before re-activation. Only 3/8 (37.5%) of patients with newly documented HBsAg positivity received antiviral prophylaxis. Virological breakthrough occurred in two of the patients on chronic therapy, in one of three inactive carriers on prophylaxis and in two of five patients not receiving prophylaxis. Re-activation developed in another five patients not screened previously for hepatitis B. One patient developed ALF and died. Re-activation did not occur in 25 patients with isolated positive core antibody. CONCLUSIONS: At tertiary care institutions hepatitis B serologies are infrequently assessed before rituximab-based chemotherapy and prophylaxis is uncommon. Greater adherence to recommendations for screening and prophylaxis is necessary. This suboptimal screening rate could be even lower in community hospitals and could result in significant harm to unscreened and unprophylaxed patients. PMID- 20738781 TI - Pedunculated hepatic mass. PMID- 20738780 TI - Effects of terlipressin and somatostatin on liver and thorax blood volumes in patients with cirrhosis. AB - BACKGROUND: Variceal bleeding in cirrhosis can cause liver ischaemia and deteriorate the hyperdynamic state; thus, the effects of vasoconstrictor therapy on liver blood volume (LBV) and thorax blood volume (ThBV) are important. AIM: To evaluate and compare the effects of terlipressin and somatostatin on LBV and ThBV in stable patients with cirrhosis and portal hypertension. METHODS: Twenty patients were studied (Child-Pugh class A/B/C: 5/8/7). The radioactivities in the liver region (LRR) and the thorax region (ThRR) by single-head gamma camera technique, as indicators of LBV and ThBV, respectively, and systemic haemodynamics were measured at baseline and after intravenous infusion of 2 mg of terlipressin (n=10) or somatostatin 250 mg/h after an initial bolus of 250 mg (n=10). RESULTS: LRR and ThRR decreased significantly with increasing severity of cirrhosis. Thirty minutes after terlipressin infusion, LRR and ThRR increased by 7.8 +/- 4.4% (NS) and 14 +/- 5.3% (P=0.01) compared with baseline values; the increase in ThRR was significantly related to the increase in LRR (r=0.682, P=0.03). In contrast, somatostatin reduced LRR and ThRR by 13.3 +/- 6.5% (P=0.07) and 1 +/- 4% (NS) respectively. LRR and ThRR increased significantly in the terlipressin group compared with the somatostatin group (P=0.01 and P=0.02 respectively). Terlipressin reduced cardiac output and heart rate (both P=0.01) and increased the mean arterial pressure (MAP) and systemic vascular resistance (P=0.009 and P=0.002 respectively); MAP decreased after somatostatin infusion (P=0.03). CONCLUSIONS: Terlipressin, but not somatostatin, maintains LBV, increases ThBV and improves the hyperdynamic state in cirrhosis. These effects can be beneficial in variceal bleeding, particularly in patients with advanced liver disease. PMID- 20738782 TI - Impact of mothers' negative affectivity, parental locus of control and child feeding practices on dietary patterns of 3-year-old children: the MoBa Cohort Study. AB - The aims of the current study were to (1) identify dietary patterns in 3-year-old children; (2) investigate the extent to which negative affectivity, external parental locus of control and control-oriented child-feeding practices (pressure to eat and restriction) relate to these dietary patterns; and (3) to examine to what extent external parental locus of control and control-oriented child-feeding practices serve as mediators for these effects. This study was part of the Norwegian Mother and Child Cohort Study, comprising 14,122 mothers completing assessments at 6 months, 18 months and 3 years post-partum. Factor analysis of the children's diet identified two weakly correlated dietary patterns, labeled 'unhealthy' and 'wholesome'. Mothers high in negative affectivity perceived they had little control over their child's behaviour, which in turn was associated with both pressuring their child to eat and restricting the child's food intake and a less wholesome and a more unhealthy diet in the child. Pressuring the child to eat was independently associated with a less wholesome and a more unhealthy diet. Restricting the child's diet was associated with a more wholesome and a less unhealthy diet. These findings held after controlling for maternal smoking, education, age, body mass index, marital status, homemaker status and child gender. PMID- 20738783 TI - Postglacial history of a widespread conifer produces inverse clines in selective neutrality tests. AB - Deviations of the site frequency spectrum of mutations (SFS) from neutral expectations may be caused by natural selection or by demographic processes such as population subdivision or temporal changes in population size. As most widespread temperate and boreal tree species have expanded from glacial refugia in the past 13,000 years, colonization bottlenecks associated with this migration may have left variable demographic signatures among geographic populations corresponding to distance from the refugia. To determine whether the signature of postglacial re-colonization has skewed the SFS in the widely distributed conifer Sitka spruce (Picea sitchensis (Bong.) Carr.), we re-sequenced 153 nuclear genes in six populations from across the species range. We found that while the SFS for the pooled sample produced negative values for Tajima's D and Fay and Wu's H, these statistics exhibited strong clinal variation when populations were analysed separately (R(2) = 0.84, P = 0.007 for Tajima's D and R(2) = 0.65, P = 0.033 for Fay and Wu's H). When historical bottlenecks of varying age were simulated using approximate Bayesian computation, distance of populations from the southern range limit explained most of the variation in bottleneck timing among populations (R(2) = 0.89, P = 0.003). These data suggest that sequential population bottlenecks during postglacial re-colonization have resulted in diverse among population signatures within the contemporary SFS in Sitka spruce, with rare variants more common in the south, and medium-frequency variants more common in the north. Our results also emphasize the need to consider sampling strategy and to explore population-specific null demographic models in surveys of nucleotide variation in widely distributed species. PMID- 20738784 TI - Multiple gains and losses of Wolbachia symbionts across a tribe of fungus-growing ants. AB - Although the intracellular bacterium Wolbachia is ubiquitous in insects, it has a unique relationship with New World ants on which particular bacterial strains have specialized. However, data are from distantly related hosts and detailed phylogenetic information which could reveal transmission dynamics are lacking. Here, we investigate host-Wolbachia relationships in the monophyletic fungus growing ant tribe Attini, screening 23 species and using multilocus sequence typing to reliably identify Wolbachia strains. This technique reduces the significant problem of recombination seen using traditional single gene techniques. The relationship between Wolbachia and the fungus-growing ants appears complex and dynamic. There is evidence of co-cladogenesis, supporting vertical transmission; however, this is incomplete, demonstrating that horizontal transmission has also occurred. Importantly, the infection prevalence is frequently different between closely related taxa, with the Acromyrmex leaf cutting ants appearing particularly prone to infection and there being no consistent relationship with any of the major life history transitions. We suggest that infection loss and horizontal transmission have driven epidemics or selective sweeps of Wolbachia, resulting in multiple gains and losses of infection across the fungus-growing ants. PMID- 20738785 TI - Leaf hydraulic vulnerability is related to conduit dimensions and drought resistance across a diverse range of woody angiosperms. AB - Hydraulic dysfunction in leaves determines key aspects of whole-plant responses to water stress; however, our understanding of the physiology of hydraulic dysfunction and its relationships to leaf structure and ecological strategy remains incomplete. Here, we studied a morphologically and ecologically diverse sample of angiosperms to test whether the water potential inducing a 50% loss in leaf hydraulic conductance (P50(leaf)) is predicted by properties of leaf xylem relating to water tension-induced conduit collapse. We also assessed the relationships between P50(leaf) and other traits considered to reflect drought resistance and ecological strategy. Across species, P50(leaf) was strongly correlated with a theoretical predictor of vulnerability to cell collapse in minor veins (the cubed ratio of the conduit wall thickness to the conduit lumen breadth). P50(leaf) was also correlated with mesophyll traits known to be related to drought resistance, but unrelated to traits associated with carbon economy. Our data indicate a link between the structural mechanics of leaf xylem and hydraulic function under water stress. Although it is possible that collapse may contribute directly to dysfunction, this relationship may also be a secondary product of vascular economics, suggesting that leaf xylem is dimensioned to avoid wall collapse. PMID- 20738786 TI - Pollinator behaviour and plant speciation: can assortative mating and disruptive selection maintain distinct floral morphs in sympatry? AB - * Pollinators, as gene flow vectors and selection agents, play a central role in the origin and maintenance of floral variation in natural populations. However, it is debatable whether pollination alone can complete the speciation process in sympatry. * Mating patterns and phenotypic selection on floral traits were characterized over two flowering seasons for sympatric corolla tube length morphs of the hawkmoth-pollinated iris Gladiolus longicollis. A mating model with genetic and spatial-temporal predictors was developed to identify seed paternity. A multivariate analysis was used to estimate selection on correlated floral traits based on maternal and paternal fitness. * Mating patterns among floral morphs were density dependent, resulting in assortative mating at low plant densities, and random mating among morphs at high densities. Weak disruptive selection on tube length was detected in one season for maternal fitness. Plant height was under opposing directional selection for maternal (+) and paternal (-) fitness functions. * These results indicate that G. longicollis morphs will introgress rather than diverge towards speciation. The lack of strong assortative mating, particularly at high densities, is predicted to result in the loss of rare morphs within populations, and indicates that spatial and temporal co occurrences of floral morphs are evolutionarily unstable. PMID- 20738787 TI - Flavonoid-induced calcium signalling in Rhizobium leguminosarum bv. viciae. AB - * Legume-rhizobium symbiosis requires a complex dialogue based on the exchange of diffusible signals between the partners. Compatible rhizobia express key nodulation (nod) genes in response to plant signals - flavonoids - before infection. Host plants sense counterpart rhizobial signalling molecules - Nod factors - through transient changes in intracellular free-calcium. Here we investigate the potential involvement of Ca(2+) in the symbiotic signalling pathway activated by flavonoids in Rhizobium leguminosarum bv. viciae. * By using aequorin-expressing rhizobial strains, we monitored intracellular Ca(2+) dynamics and the Ca(2+) dependence of nod gene transcriptional activation. * Flavonoid inducers triggered, in R. leguminosarum, transient increases in the concentration of intracellular Ca(2+) that were essential for the induction of nod genes. Signalling molecules not specifically related to rhizobia, such as strigolactones, were not perceived by rhizobia through Ca(2+) variations. A Rhizobium strain cured of the symbiotic plasmid responded to inducers with an unchanged Ca(2+) signature, showing that the transcriptional regulator NodD is not directly involved in this stage of flavonoid perception and plays its role downstream of the Ca(2+) signalling event. * These findings demonstrate a key role played by Ca(2+) in sensing and transducing plant-specific flavonoid signals in rhizobia and open up a new perspective in the flavonoid-NodD paradigm of nod gene regulation. PMID- 20738788 TI - Do you know Mike? Green is good for EP. PMID- 20738789 TI - Exploration of anger constructs in acute and chronic pain patients vs. community patients. AB - OBJECTIVES: (1) Determine and compare prevalence of forms of anger (FOA; anger, hostility, aggression, anger-in, anger-out, chronic anger) in community nonpatients (n=478), community patients (n=158), acute pain patients (APPs; n=326), chronic pain patients (CPPs; n=341); and (2) develop FOA predictor models in APPs and CPPs. DESIGN: A large set of items containing the FOA items was administered to the above groups, who were compared statistically for FOA endorsement. APPs and CPPs affirming the anger and chronic anger items were compared with those not affirming on all available variables including the Battery for Health Improvement (BHI-2) with significant variables (P<=0.001) utilized in predictor models for anger and chronic anger in APPs and CPPs. Setting community plus rehabilitation facilities. RESULTS: FOA affirmation ranged from 8.28% for chronic anger in nonpatients to 37.54% for anger in CPPs. Only CPPs were more likely to affirm anger (P<=0.04) and chronic anger (P<=0.01) at a significantly higher rate than community patients. In both APPs and CPPs, all FOA items except anger management-in were significantly correlated with other FOA items. For anger and chronic anger for CPPs and APPs, hostility was the strongest predictor. All models predicted anger and chronic anger significantly better than the base rate prediction. CONCLUSION: According to the results of this study anger and chronic anger are more frequently found in CPPs vs. community patients supporting the clinical perception that many CPPs are angry. As such,clinicians should actively screen CPPs for the presence of anger in order to engage these CPPs in anger management treatment. PMID- 20738790 TI - Congenital lymphedema with tuberous sclerosis and clinical Hirschsprung disease. AB - Case of an 18-month-old child with congenital lymphedema subsequently diagnosed with tuberous sclerosis and Hirschsprung disease. PMID- 20738791 TI - Cold panniculitis following ice therapy for cardiac arrhythmia. AB - Ice therapy has long been used as first line treatment of supraventricular tachycardia in neonates. We report a case of cold panniculitis developing in a 12 day-old neonate after ice therapy for cardiac arrhythmia. This is the first biopsy-proved case of cold panniculitis following ice therapy for supraventricular tachycardia in a newborn. PMID- 20738792 TI - Multiple subepidermal calcified nodules on the thigh mimicking molluscum contagiosum. AB - Subepidermal calcified nodule (SCN) is a rare form of calcinosis cutis that presents as a solitary verrucous nodule on the face. Here, we report an unusual case of SCN. A healthy 2-year-old boy presented with multiple, round, hard, yellow-white to erythematous lesions on his right thigh. Histopathologic examination of a punch biopsy specimen revealed deposition of calcium in the dermis. PMID- 20738793 TI - Basal cell carcinoma arising in a nevus sebaceus in a child with facial trichoepitheliomas. AB - Nevus sebaceus (NS) is a congenital skin hamartoma that presents in childhood. Tumors may arise within these lesions over time. Mutations in the PTCH gene have been associated with both NS and some of the developing tumors. Only nine documented cases of basal cell carcinoma arising in nevus sebaceus in childhood are available. We present a case of an 8-year-old male with nevus sebaceus who developed a basal cell carcinoma. Evaluation for constitutional PTCH gene mutation and loss of heterozygosity (LOH) from the BCC within the NS did not reveal an underlying mutation. We further discuss the literature regarding prophylactic excision of NS. PMID- 20738795 TI - Hypoglycemia as a result of propranolol during treatment of infantile hemangioma: a case report. AB - Propranolol is a new and promising treatment for hemangiomas of infancy. We report of a patient in whom steroid maintenance therapy is successfully tapered after introduction of propranolol. This patient, however, developed symptomatic hypoglycemic events presumably because of a concurrent deficiency of epinephrine and cortisol as a direct result of both beta-blockage by propranolol and adrenal insufficiency as a result of prednisone use. Extreme care should be taken in patients treated with both propranolol and prednisone as they are at increased risk of hypoglycemia. PMID- 20738796 TI - Terra firma-forme dermatosis in a 4-month-old girl. AB - Terra firma-forme dermatosis (TFFD) is an idiopathic condition characterized by asymptomatic, dirtlike, thinly papillomatous, hyperpigmented plaques which cannot be removed with routine cleansing, but clear with firm wiping with 70% isopropyl or ethyl alcohol. Commonly involved sites include the neck, trunk, and umbilicus. Most reports have described adolescents or young adults with a history of normal hygiene and vigorous but unsuccessful attempts at cleansing the affected areas. We describe a 4-month-old girl with TFFD, who is the youngest patient thus far reported with this condition. PMID- 20738797 TI - "Car seat dermatitis": a newly described form of contact dermatitis. AB - Over the last several years, our clinic has documented an increasing trend of contact dermatitis presenting in areas that are in direct contact with certain types of car seats composed of a shiny, nylon-like material. Our practice has encountered these cases in both atopic and nonatopic infants, with a seasonal predilection for the warmer months. This brief report highlights some of the key features of this condition and alerts the clinician to this newly described form of contact dermatitis. PMID- 20738794 TI - Albright hereditary osteodystrophy. AB - Albright hereditary osteodystrophy with pseudohypoparathyroidism is due to maternal loss-of-function mutations in the GNAS gene. Its typical clinical features encompass obesity, a round face and a short neck, osteoma of the skin, endocrinological abnormalities, and psychomotoric retardation. Here we present a 10-month-old Tunisian boy with a classical course of this rare disease. PMID- 20738798 TI - Neonatal rhabdomyosarcoma misdiagnosed as a congenital hemangioma. AB - Highly vascularized malignant soft-tissue tumors can clinically and radiologically mimic deep hemangiomas. We present a case of congenital rhabdomyosarcoma of the neck, which was initially identified as congenital hemangioma. PMID- 20738799 TI - Ankyloblepharon-ectodermal dysplasia-clefting syndrome: a novel p63 mutation associated with generalized neonatal erosions. AB - Ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome is a rare disorder characterized by ankyloblepharon (congenital adhesions of the eyelids), ectodermal dysplasia, and orofacial clefts. Here, we report the case of an infant born with severe ectodermal dysplasia including generalized neonatal erosions with scalp involvement, facial clefting but notably without ankyloblepharon. Mutational analysis of the p63 gene showed a novel heterozygous T>C nucleotide substitution on exon 14 (I597T). To our knowledge, this is a novel mutation that has not previously been reported in the pathogenesis of AEC, or other p63-related syndromes. This case further highlights the clinical and genetic heterogeneity of p63 syndromes. PMID- 20738800 TI - A case of cutaneous mastocytosis in a child with prominent Langerhans cell infiltration. AB - We recently encountered a 2-year-old boy with slightly infiltrative brown papules on the face, trunk, and extremities. Stroking of one of the papules produced an urticarial wheal (positive Darier's sign). Histopathologic tests revealed a dense infiltration of mast cells containing numerous granules and showing metachromasia under Toluidine blue staining. Immunohistochemical tests revealed that these cells were positive for CD68 and for c-kit. In addition, dermal dendritic cells that were positive for S100 and CD1a immunostaining were intermingled with the mast cells. We confirmed through electron microscopy that the dermal dendritic cells that were observed adjacent to the infiltration of mast cells had Birbeck granules in their cytoplasm, namely Langerhans cells. However, because of the greater numbers of mast cells than Langerhans cells, and because of the absence of both monomorphic LC proliferation and systemic symptoms of Langerhans cell histiocytosis, the present case favors a diagnosis of cutaneous mastocytosis in a child with Langerhans cell infiltration. PMID- 20738801 TI - A breath of life for inhaled insulin: severe subcutaneous insulin resistance as an indication? PMID- 20738802 TI - Characteristic alteration in the second derivative of photoplethysmogram in children. AB - BACKGROUND: The second derivative of the photoplethysmogram (SDPTG) has been verified as a useful method for analyzing pulse wave form in adults; however, there have been few studies on the SDPTG in children. METHODS: We examined age related alteration of SDPTG (study 1) and the SDPTG response to a vasodilator (study 2). The subjects in study 1 were 36 healthy children aged 0.9-16.0 years. The subjects in study 2 were 13 children aged 5.4-18.9 years with a history of Kawasaki disease. Subjects received an i.v. infusion of 0.568 mg/kg dipyridamole. We assessed the SDPTG by d/a ratio, b/a ratio and aging index (AGI). RESULTS: The d/a ratio increased with advance of age (r= 0.636, P < 0.001), and the b/a ratio and AGI decreased with advance of age (r=-0.343, P < 0.05 and r=-0.678, P < 0.001, respectively). The d/a ratio and AGI were correlated with height (r= 0.523, P < 0.01 and r=-0.623, P < 0.001, respectively), but the b/a ratio was not significantly correlated with height. In study 2, the d/a ratio increased significantly (P<= 0.05), but the b/a ratio and AGI did not alter. CONCLUSIONS: The SDPTG indices in children show characteristic alterations with advance of age and react to a vasodilator. PMID- 20738803 TI - Sodium chloride stress induces nitric oxide accumulation in root tips and oil body surface accompanying slower oleosin degradation in sunflower seedlings. AB - Present work highlights the involvement of endogenous nitric oxide (NO) in sodium chloride (NaCl)-induced biochemical regulation of seedling growth in sunflower (Helianthus annuus L., cv. Morden). The growth response is dependent on NaCl concentration to which seedlings are exposed, they being tolerant to 40 mM NaCl and showing a reduction in extension growth at 120 mM NaCl. NaCl sensitivity of sunflower seedlings accompanies a fourfold increase in Na(+) /K(+) ratio in roots (as compared to that in cotyledons) and rapid transport of Na(+) to the cotyledons, thereby enhancing Na(+) /K(+) ratio in cotyledons as well. A transient increase in endogenous NO content, primarily contributed by putative NOS activity in roots of 4-day-old seedlings subjected to NaCl stress and the relative reduction in Na(+) /K(+) ratio after 4 days, indicates that NO regulates Na(+) accumulation, probably by affecting the associated transporter proteins. Root tips exhibit an early and transient enhanced expression of 4,5 diaminofluorescein diacetate (DAF-2DA) positive NO signal in the presence of 120 mM NaCl. Oil bodies from 2-day-old seedling cotyledons exhibit enhanced localization of NO signal in response to 120 mM NaCl treatment, coinciding with a greater retention of the principal oil body membrane proteins, i.e. oleosins. Abolition of DAF positive fluorescence by the application of specific NO scavenger [2-phenyl-4,4,5,5-tetramethyllimidazoline-1-oxyl-3-oxide (PTIO)] authenticates the presence of endogenous NO. These novel findings provide evidence for a possible protective role of NO during proteolytic degradation of oleosins prior to/accompanying lipolysis. PMID- 20738804 TI - EMB1211 is required for normal embryo development and influences chloroplast biogenesis in Arabidopsis. AB - Chloroplast biogenesis is tightly linked with embryogenesis and seedling development. A growing body of work has been done on the molecular mechanisms underlying chloroplast development; however, the molecular components involved in chloroplast biogenesis during embryogenesis remain largely uncharacterized. In this paper, we show that an Arabidopsis mutant carrying a T-DNA insertion in a gene encoding a multiple membrane occupation and recognition nexus (MORN) containing protein exhibits severe defects during embryogenesis, producing abnormal embryos and thereby leading to a lethality of young seedlings. Genetic and microscopic studies reveal that the mutation is allelic to a previously designated Arabidopsis embryo-defective 1211 mutant (emb1211). The emb1211 +/- mutant plants produce approximately 25% of white-colored ovules with abnormal embryos since late globular stage when primary chloroplast biogenesis takes place, while the wild-type plants produce all green ovules. Transmission electron microscopic analysis reveals the absence of normal chloroplast development, both in the mutant embryos and in the mutant seedlings, that contributes to the albinism. The EMB1211 gene is preferentially expressed in developing embryos as revealed in the EMB1211::GUS transgenic plants. Taken together, the data indicate that EMB1211 has an important role during embryogenesis and chloroplast biogenesis in Arabidopsis. PMID- 20738805 TI - Loci controlling nitrate reductase activity in maize: ultraviolet-B signaling in aerial tissues increases nitrate reductase activity in leaf and root when responsive alleles are present. AB - Environmental factors, such as ultraviolet-B (UV-B) irradiation, have the ability to affect pathways such as nitrogen metabolism. As fixed nitrogen is the keystone mineral nutrient that controls grain crop yield, any alteration in this cycle can be detrimental to plant productivity. Nitrate reductase enzyme activity is responsible for the reduction of nitrate to nitrite, and nitrate is the major form of nitrogen assimilated in plants. In maize (Zea mays L.) production, nitrate assimilation kinetics are important for both high- and low-input agricultural systems. Nitrate reductase protein activity is controlled by phosphatases and kinases. Nitrate reductase activity is responsive to environmental signals such as light-dark cycles and UV-B radiation, although the regulatory controls are not yet fully understood. We have determined the location of maize genetic factors that control nitrate reductase activity and the extent of contribution of each of these factors, both locally in the leaf tissue and via long-distance signaling loci that affect root nitrate reductase activity upon leaf UV irradiation. In the IBM94 recombinant inbred mapping population, the loci controlling regulation of nitrate reductase activity under UV-B map to different positions than the loci controlling nitrate reductase activity in unexposed plants. PMID- 20738807 TI - Diagnostic biomarker for early stage of Alzheimer's disease: current state and view in the future. PMID- 20738806 TI - Smad7 restricts melanoma invasion by restoring N-cadherin expression and establishing heterotypic cell-cell interactions in vivo. AB - The list of transforming growth factor-beta (TGF-beta)-related proteins in non canonical TGF-beta signaling is growing. Examples include receptor-Smads directing micro-RNA processing and inhibitory-Smads, e.g. Smad7, directing cell adhesion. Human skin grafts with fluorescently tagged melanoma cells revealed Smad7-expressing cells positioned themselves proximal to the dermal-epidermal junction and failed to form tumors, while control cells readily invaded and formed tumors within the dermis. Smad7 significantly inhibited beta-catenin T41/S45 phosphorylation associated with degradation and induced a 4.5-fold increase in full-length N-cadherin. Cell adhesion assays confirmed a strong interaction between Smad7-expressing cells and primary dermal fibroblasts mediated via N-cadherin, while control cells were incapable of such interaction. Immunofluorescent analysis of skin grafts indicated N-cadherin homotypic interaction at the surface of both Smad7 cells and primary dermal fibroblasts, in contrast to control melanoma cells. We propose that Smad7 suppresses beta-catenin degradation and promotes interaction with N-cadherin, stabilizing association with neighboring dermal fibroblasts, thus mitigating invasion. PMID- 20738808 TI - Investigation of responders and non-responders to long-term donepezil treatment. AB - BACKGROUND: Donepezil is effective in maintaining the cognitive function of patients with mild to moderate Alzheimer's disease (AD). However, not all patients respond to donepezil. In the present study, we examined the clinical features of responders and non-responders to long-term donepezil treatment. METHODS: The present retrospective study was performed on 95 AD outpatients who had been taking donepezil for >or=2 years. All subjects underwent periodic examinations of cognitive function, namely Mini-Mental State Examination (MMSE) and Rorschach Cognitive Index (RCI), as well as clinical evaluations using the Clinical Dementia Rating (CDR) scale. Patients were divided into three groups as follows: (i) the 'maintained' group (MG), in which the global CDR score was maintained over the >or=2 years of treatment; (ii) the 'declined' group (DeG), in which the global CDR score increased one rank over the treatment period; and (iii) the 'obvious and rapid decline' group (ORDeG), in which the global CDR score increased two ranks early during the treatment period. Clinical features, treatment outcome, the time lag between a caregiver's recognition of the onset of dementia and the start of treatment, behavioral and psychological symptoms of dementia (BPSD), and cognitive functions were compared between the three groups. RESULTS: Patients in the ORDeG (i.e. non-responders) were significantly younger and had a longer time lag between the onset of dementia and the start of treatment than patients in the MG (P < 0.05). Of note, patients in the ORDeG had a longer period of executive dysfunction before treatment started than patients in the MG (P < 0.001). Evaluation of cognitive function revealed that mean changes from baseline on the MMSE and RCI were significantly lower for patients in the ORDeG compared with the MG at 8 and 4 months, respectively (P < 0.001 and P < 0.05, respectively). CONCLUSION: Donepezil non-responders are likely to be younger and to have a longer time lag between the onset of dementia and the start of treatment, in particular a longer duration of executive dysfunction. Furthermore, the non-responders do not demonstrate maintenance of cognitive functions in the short term. Thus, the early diagnosis of dementia and prompt initiation of donepezil treatment is indicated for a good outcome. To this end, it is important to educate people to recognize a deterioration of executive function in daily living. PMID- 20738809 TI - Detection of early amnestic mild cognitive impairment without significantly objective memory impairment: a case-controlled study. AB - BACKGROUND: We encountered eight early amnestic mild cognitive impairment (aMCI) patients (early MCI group) who did not fulfill the diagnostic criteria for aMCI. We compared the scores of neuropsychological examinations as well as the cerebral metabolic rate for glucose consumption (CMRglc) decrease on (18)F-FDG PET examination between the early MCI group and 10 aMCI patients (MCI group) or six normal elderly subjects (normal group), to examine whether the current diagnostic criteria can detect early-stage aMCI. METHODS: The three groups underwent Mini Mental State Examination (MMSE), Wechsler Adult Intelligence Scale - Third Edition (WAIS-III), Wechsler Memory Scale Revised (WMS-R), magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) examinations. RESULTS: The early MCI group did not show significant memory impairment of 1.0 SD or other cognitive dysfunctions on neuropsychological examinations, and did not fulfill the diagnostic criteria of aMCI. With one-way anova and Tukey's HSD post-hoc test, the early MCI group showed the highest scores for WAIS-III, whereas the MCI group showed the lowest scores for WMS-R, although there were no significant differences between the early MCI and normal groups. In order to show a discrepancy in scores between WAIS-III and WMS-R, we subtracted the scores of WMS-R from WAIS-III. Consequently, the normal group showed significantly smaller differences in scores than the other groups, although there were no significant differences between the early MCI and MCI groups. (18)F-FDG PET recognized a CMRglc decrease in the posterior cingulate gyrus and/or part of the parietotemporal area in both the MCI and early MCI groups, of which the extent and magnitude were weaker in the early MCI group. The normal group did not show a significant CMRglc. CONCLUSIONS: The early MCI group should be included in aMCI not only based on the discrepancy between intelligence and memory scores, but also based on the (18)F-FDG PET findings. The combination of these examinations would make it possible to diagnose early-stage aMCI. PMID- 20738810 TI - Argyrophilic grain disease with delusions and hallucinations: a pathological study. AB - No clear clinical syndrome for argyrophilic grain disease (AGD) has yet been identified. Previous studies have documented its clinical features, namely, personality changes characterized by emotional disorder involving aggression or ill temper and relatively well-preserved cognitive function, but the clinical manifestations of delusions and hallucinations as they appear in AGD have not been thoroughly described. Here, we report on a 72-year-old Japanese AGD patient who showed psychiatric symptoms, memory impairment and emotional change. He perceived and described a person who was not present and tried to grasp things on the floor though nothing was there. He also insisted that somebody was watching him and consequently always kept his curtains closed. These psychiatric symptoms were observed at an early stage in the patient's disease course. Serial neuroradiological examination showed progressive atrophy of the bilateral temporal lobes. The patient died at 79 years-of-age. Microscopic neuropathological examination showed transactivation responsive region (TAR)-DNA binding protein of 43 kDa (TDP-43) positive structures in addition to widespread argyrophilic grains and coiled bodies. According to recent recommendations for pathological diagnosis, this case corresponds to AGD with limbic TDP-43 pathology. This case shows that patients with AGD that is eventually confirmed through autopsy can present with delusions and hallucinations early in the course of their disease. The clinical significance of TDP-43 pathology in the brains of patients with AGD remains uncertain. PMID- 20738811 TI - Computerized visuo-spatial memory test as a supplementary screening test for dementia. AB - BACKGROUND: To prepare for a super-aging society, effective dementia screening tests are required. The most salient deficit appearing from the early stages of dementia/Alzheimer's disease (AD) is a deterioration in memory. The Hasegawa Dementia Scale-revised (HDS-R) and the Mini-Mental State Examination (MMSE) are widely used in Japan to screen for dementia. Both place an emphasis on memory function, but neither examines visuo-spatial memory (VSM) function, even though VSM deficits are a sensitive marker for the detection of conversion to dementia. Furthermore, brief tests of VSM that are appropriate for screening have not been standardized. Thus, in the present study, we devised a brief, computer-aided short-term VSM test. METHODS: Sixty-six aged people were evaluated. Using the Clinical Dementia Rating (CDR), it was found that 29 could be considered normal controls (NC; CDR 0), 10 had mild cognitive impairment (MCI; CDR 0.5), 15 had mild dementia (CDR 1), and 12 had moderate to severe dementia (CDR 2-3). The VSM test estimated how many locations each subject could memorize. Several numbered circles were shown on a monitor and subjects were required to memorize the location of these circles sequentially. After the numbers on the circles on the screen had disappeared, the subjects were required to indicate the circles in ascending order. A touch panel screen was used for this test to make it easier. The HDS-R was applied to subjects with MCI and dementia. RESULTS: The mean (+/ SD) VSM score in subjects with MCI (5.70 +/- 0.96) was significantly lower than that in NC subjects (6.69 +/- 0.82), but significantly higher than that in subjects classified as CDR 1 (4.67 +/- 0.87). There was no significant difference in VSM scores between subjects classified as CDR 1 and CDR 2-3 (3.80 +/- 0.80). There was a moderate significant correlation between VSM and HDS-R scores. CONCLUSION: In the present study, the VSM test detected differences in VSM function among NC subjects and subjects with MCI and mild dementia. The software program for the VSM test is distributed for free so that it can be widely used. PMID- 20738812 TI - Late-onset schizophrenic syndromes in socially isolated situations: a comparison of Janzarik's 'Kontaktmangelparanoid' and late paraphrenia. AB - The two concepts of Kontaktmangelparanoid (contact-deficit hallucinosis) and late paraphrenia at the level of symptomatology and psychopathology from the perspective of contributing to an understanding of these special problems of psychogeriatrics are discussed in the present study. This sheds light on the important role of isolation, especially in elderly females, as a pathogenic factor in late-onset paranoic state. Clinical physicians might naively associate late-onset paranoid (hallucinatory) syndrome with organic factors such as age and cerebrovascular processes, and particularly with dementia, but they do not associate it with the patient's living environment. Admittedly, treatment prospects for chronic, entrenched syndromes are limited, but there are these types of exceptions. We have evaluated the two concepts, from the perspective of their modern-day significance, with a view to the possibility that a more sophisticated exploration of the linkage among the various symptoms (symptomatology) and of the meaning inherent in the linkage of symptoms (psychopathology) in both concepts will pave the way to a therapeutic methodology that sheds light on the situation of elderly females living in imposed isolation. PMID- 20738813 TI - Issues facing home-based medical support services. AB - The first part of the present review describes the current status of elderly people with behavioral and psychological symptoms of dementia (BPSD) in the community and basic viewpoints for differentiating between different forms of dementia. Specifically, it focuses on four points among the data and research related to determining the current status of elderly people with BPSD. We also propose basic concepts for differentiating between the core symptoms of dementia and BPSD, BPSD and delirium, and agitation and delirium. In the second part of the present review, various aspects of the symptom 'agitation' are discussed based on the experience of our home visit medical service for people with dementia by describing two cases. In cases such as Case 1, where the subject was given high doses of antipsychotics, we believe the problem was that the physicians immediately abstracted all of the abnormal behavior in the subject's life as 'agitation', and provided treatment to the subject accordingly. In Case 2, where the subject had dementia with Lewy bodies (DLB), we propose that it is crucial to differentiate clearly between agitation and delirium. Both of these cases show the risks of focusing treatment simply on agitation. When BPSD occurs in a person with dementia, the burden on caregivers increases. At such times, physicians tend to side with the family rather than with the patient. However, medical care is intended to be for the afflicted person, and physicians should base their plans for medical intervention on this principle. PMID- 20738814 TI - Prospects of future measures for persons with dementia in Japan. AB - In May 2008, the Japanese government launched the 'Emergency Project for Improvement of Medical Care and Quality of Life for People with Dementia' under the idea that it is necessary to build a society, without delay, where people can live life safely without anxiety even after being affected by dementia, where they can be supported by appropriate and integrated services of medical care, long-term care and community care. We would like to introduce our future dementia policy standing on the outcome of this project, which was published as a report on 10 July 2008. The measures for people with dementia in Japan have gradually achieved good results. For example, public understanding and awareness of dementia has increased through renaming the term for dementia in Japanese from 'Chiho' to 'Ninchi-sho' in 2004, and the comprehensive care system was founded focusing on the importance of providing community based long-term care while maintaining the person's familiar human relationships and residential circumstances. However, case reports show that there are yet some cases that fail to deliver appropriate treatment or long-term care service as a result of a lack of timely definite diagnosis in an early stage or a lack of coordination between medical care and long-term care. Therefore, the future dementia policy should be designed by envisaging the flow of the measures that would support the life of the person and his/her family, and improve their quality of life; starting with measures that link early notice of the patient, his/her family or neighbor to early diagnosis, and then measures to develop well-designed comprehensive care planning that provides appropriate medical and long-term care services through good coordination, while promoting research and development of diagnosis/treatment technology. In addition, in regard to early-onset dementia, comprehensive self-support measures including employment assistance should be promoted. PMID- 20738815 TI - New national health program against dementia in Japan: the medical center for dementia. AB - Herein, the Medical Center for Dementia, which was introduced in 2008 as a new national health program in Japan, is reviewed from the perspective of the recent history of the national provision against dementia and the findings of a series of studies on the current status of medical care for dementia. The Medical Center for Dementia was developed to provide special medical services for dementia and connect with other community resources in order to contribute to building a comprehensive support network for demented patients. Specifically, the Medical Center for Dementia provides the following: (i) special medical consultation; (ii) differential diagnosis and early intervention; (iii) medical treatment for the acute stage of behavioral and psychological symptoms of dementia and concurrent medical conditions; (iv) education for general practitioners and other community professionals; (v) network meetings for the establishment of medical medical and medical-care connection; and (vi) provision of information regarding dementia to the public. Special Medical Consultation Rooms would play an important role in the efficient functioning of the Medical Center for Dementia. In cooperation with municipal governments, the Medical Center for Dementia is also expected to play an important role in policy making and to improve the local status of medical care for people with dementia. PMID- 20738817 TI - Interpreting null results from measurements with uncertain correlations: an info gap approach. AB - Null events-not detecting a pernicious agent-are the basis for declaring the agent is absent. Repeated nulls strengthen confidence in the declaration. However, correlations between observations are difficult to assess in many situations and introduce uncertainty in interpreting repeated nulls. We quantify uncertain correlations using an info-gap model, which is an unbounded family of nested sets of possible probabilities. An info-gap model is nonprobabilistic and entails no assumption about a worst case. We then evaluate the robustness, to uncertain correlations, of estimates of the probability of a null event. This is then the basis for evaluating a nonprobabilistic robustness-based confidence interval for the probability of a null. PMID- 20738816 TI - Psychotic symptoms complicate the clinical differentiation of Parkinson's disease with major depressive disorder from dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is diagnosed clinically according to the diagnostic criteria in the Third Report of the DLB Consortium. However, psychotic symptoms, such as visual hallucinations, delusions, and stupor, may complicate the clinical diagnosis of DLB. The present study reports on a patient with Parkinson's disease that was difficult to distinguish from DLB because of the presence of various psychotic symptoms. In making a diagnosis of DLB, it is important to assess essential psychiatric features and to observe patients for any changes in these features. PMID- 20738818 TI - Development of a self-regulated dynamic model for the propagation of Salmonella Typhimurium in pig farms. AB - A self-regulated epidemic model was developed to describe the dynamics of Salmonella Typhimurium in pig farms and predict the prevalence of different risk groups at slaughter age. The model was focused at the compartment level of the pig farms and it included two syndromes, a high and a low propagation syndrome. These two syndromes generated two different classes of pigs, the High Infectious and the Low Infectious, respectively, which have different shedding patterns. Given the two different classes and syndromes, the Infectious Equivalent concept was used, which reflected the combination of High and Low Infectious pigs needed for the high propagation syndrome to be triggered. Using the above information a new algorithm was developed that decides, depending on the Infectious Equivalent, which of the two syndromes should be triggered. Results showed that the transmission rate of S. Typhimurium for the low propagation syndrome is around 0.115, pigs in Low Infectious class contribute to the transmission of the infection by 0.61-0.80 of pigs in High Infectious class and that the Infectious Equivalent should be above 10-14% of the population in order for the high propagation syndrome to be triggered. This self-regulated dynamic model can predict the prevalence of the classes and the risk groups of pigs at slaughter age for different starting conditions of infection. PMID- 20738819 TI - The impact of consumer phase models in microbial risk analysis. AB - In quantitative microbiological risk assessment (QMRA), the consumer phase model (CPM) describes the part of the food chain between purchase of the food product at retail and exposure. Construction of a CPM is complicated by the large variation in consumer food handling practices and a limited availability of data. Therefore, several subjective (simplifying) assumptions have to be made when a CPM is constructed, but with a single CPM their impact on the QMRA results is unclear. We therefore compared the performance of eight published CPMs for Campylobacter in broiler meat in an example of a QMRA, where all the CPMs were analyzed using one single input distribution of concentrations at retail, and the same dose-response relationship. It was found that, between CPMs, there may be a considerable difference in the estimated probability of illness per serving. However, the estimated relative risk reductions are less different for scenarios modeling the implementation of control measures. For control measures affecting the Campylobacter prevalence, the relative risk is proportional irrespective of the CPM used. However, for control measures affecting the concentration the CPMs show some difference in the estimated relative risk. This difference is largest for scenarios where the aim is to remove the highly contaminated portion from human exposure. Given these results, we conclude that for many purposes it is not necessary to develop a new detailed CPM for each new QMRA. However, more observational data on consumer food handling practices and their impact on microbial transfer and survival are needed to generalize this conclusion. PMID- 20738820 TI - The challenge of degraded environments: how common biases impair effective policy. AB - Economic activity can damage natural systems and reduce the flow of ecosystem services. The harms can be substantial, as our case studies vividly illustrate. Most degraded landscapes have at least some potential to be reclaimed. However, uncertainty plagues decision making regarding degradation and reclamation, in relation to the extent of the damage, the success of reclamation, and how exposure will change in the future. We examine how a range of observed decision biases can lead to far-from-optimal policies regarding how much degradation to allow and when, as well as how and how much, to reclaim degraded sites. Despite our focus on degraded landscapes, we believe these are generic biases present in a wide range of risk situations. Our three case studies show these biases at work. The first two studies are of mining operations in the United States and Canada, and the third is of climate change. PMID- 20738821 TI - The role of neural tension in hamstring flexibility. AB - Resistance to stretch, electromyographic (EMG) response to stretch, stretch discomfort and maximum range of motion (ROM) were measured during passive hamstring stretches performed in the slump test position (neural tension stretch) and in the upright position (neutral stretch) in eight healthy subjects. Stretches were performed on an isokinetic dynamometer at 5 degrees /s with the test thigh flexed 40 degrees above the horizontal, and the seat back at 90 degrees to the horizontal. Surface EMG signals were recorded from the medial and lateral hamstrings during stretches. Knees were passively extended to maximum stretch tolerance with test order (neural tension vs neutral) alternated between legs. For neural tension stretches, the cervical and thoracic spine were manually flexed. Maximum ROM was 8 degrees less for the neural tension stretch vs the neutral stretch (P<0.01). Resistance to stretch was 14-15% higher for the neural tension stretch vs the neutral stretch (P<0.001) at common joint angles in the final third of ROM. Stretch discomfort and EMG response were unaffected by neural tension. In conclusion, an increased passive resistance to stretch with the addition of neural tension during passive hamstring stretch despite no change in the EMG response indicates that passive extensibility of neural tissues can limit hamstring flexibility. PMID- 20738822 TI - Injury risk on artificial turf and grass in youth tournament football. AB - The aim of this prospective cohort study was to investigate the risk of acute injuries among youth male and female footballers playing on third-generation artificial turf compared with grass. Over 60,000 players 13-19 years of age were followed in four consecutive Norway Cup tournaments from 2005 to 2008. Injuries were recorded prospectively by the team coaches throughout each tournament. The overall incidence of injuries was 39.2 (SD: 0.8) per 1000 match hours; 34.2 (SD: 2.4) on artificial turf and 39.7 (SD: 0.8) on grass. After adjusting for the potential confounders age and gender, there was no difference in the overall risk of injury [odds ratio (OR): 0.93 (0.77-1.12), P=0.44] or in the risk of time loss injury [OR: 1.05 (0.68-1.61), P=0.82] between artificial turf and grass. However, there was a lower risk of ankle injuries [OR: 0.59 (0.40-0.88), P=0.008], and a higher risk of back and spine [OR: 1.92 (1.10-3.36), P=0.021] and shoulder and collarbone injuries [OR: 2.32 (1.01-5.31), P=0.049], on artificial turf compared with on grass. In conclusion, there was no difference in the overall risk of acute injury in youth footballers playing on third-generation artificial turf compared with grass. PMID- 20738823 TI - Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise. AB - Unaccustomed exercise leads to satellite cell proliferation and increased skeletal muscle protein turnover. Several growth factors and cytokines may be involved in the adaptive responses. Non-steroidal anti-inflammatory drugs (NSAIDs) negatively affect muscle regeneration and adaptation in animal models, and inhibit the exercise-induced satellite cell proliferation and protein synthesis in humans. However, the cellular mechanisms eliciting these responses remain unknown. Eight healthy male volunteers performed 200 maximal eccentric contractions with each leg. To block prostaglandin synthesis locally in the skeletal muscle, indomethacin (NSAID) was infused for 7.5 h via microdialysis catheters into m. vastus lateralis of one leg. Protein synthesis was determined by the incorporation of 1,2-(13) C(2) leucine into muscle protein from 24 to 28 h post-exercise. Furthermore, mRNA expression of selected genes was measured in muscle biopsies (5 h and 8 days post-exercise) by real-time reverse transcriptase PCR. Myofibrillar and collagen protein synthesis were unaffected by the local NSAID infusion. Five hours post-exercise, the mRNA expression of cyclooxygenase-2 (COX2) was sixfold higher in the NSAID leg (P=0.016) compared with the unblocked leg. The expression of growth factors and matrix-related genes were unaffected by NSAID. Although NSAIDs inhibit the exercise-induced satellite cell proliferation, we observed only limited effects on gene expression, and on post-exercise protein synthesis. PMID- 20738824 TI - Cardiac alterations induced by a fish-catching diving competition. AB - Cardiac changes induced by repeated breath-hold diving were investigated after a fish-catching diving competition. Eleven healthy subjects carried out repeated breath-hold dives at a mean maximal depth of 20 +/- 2.7 msw (66 +/- 9 fsw) during 5 h. One hour after the competition, the body mass loss was -1.7 +/- 0.5 kg. Most of the breath-hold divers suffered from cold and although the core temperature remained normal, a decrease in cutaneous temperature was recorded in the extremities. Systolic blood pressure was reduced in both upper and lower limbs. Heart rate was unchanged, but left ventricular (LV) stroke volume was reduced leading to a decrease in cardiac output (-20%). Left atrial and LV diameters were significantly decreased. LV filling was assessed on a trans-mitral profile. An increase in the contribution of the atrial contraction to LV filling was observed. Right cavity diameters were increased. The cardiac autonomic alterations were in favor of sympathetic hyperactivity. After a fish-catching diving competition in cold water, alterations suggesting dehydration, contraction in plasma volume and sympathetic hyperactivity were observed. Furthermore, enlargements of right cavities were in favor of right ventricular strains. Repeated apnea and swimming in cold water may account for these alterations. PMID- 20738826 TI - Quality management in the transfusion service: case studies in process improvement. AB - BACKGROUND: Laboratory-based quality improvement (QI) initiatives can improve clinical outcomes and patient safety. STUDY DESIGN AND METHODS: We present three cases of QI that impact processes from the transfusion service (TS) laboratory to the patient's bedside. RESULTS: Case 1 was event discovery reporting (EDR). We were able to reduce our biologic product deviation reports from 41 (17%) of 238 EDRs to only 19 (7%) of 272 (p < 0.01) EDRs after implementation of a QI workflow process. Case 2 was antibody evaluation before elective surgery. We implemented process improvement strategies: 1) surgical safety checklist with confirmation of type-and-screen completion and antibody evaluation before patients can proceed to surgery; 2) specimen retention policy of 30 days to allow advance testing; and 3) daily review to identify specimens needed on day of surgery. After intervention, only 7 (0.3%) of 2298 patients required antibody evaluation on day of surgery, compared to 65 (0.75%) of 8656 patients (p < 0.01) before intervention. Case 3 was wrong blood in tube (WBIT). We have a two-specimen requirement for blood type verification before transfusion. To determine whether trauma patients should be exempted, we reviewed WBIT errors. Six WBIT errors were from the emergency department (an error rate of 1:400) and nine WBIT specimens were institution wide. Three patients were transfused after correction of the WBIT error. Based on this analysis, our institution agreed that no clinical units shall be exempted from our policy. CONCLUSION: Successful QI in the TS improves processes that promote efficiency, effectiveness, and patient safety. PMID- 20738825 TI - Red blood cell microparticles show altered inflammatory chemokine binding and release ligand upon interaction with platelets. AB - BACKGROUND: Storage of red blood cells (RBCs) under standard blood bank conditions results in reduced structural integrity leading to membrane budding and release of microparticles. Microparticles express the blood group Duffy antigen known to bind multiple inflammatory chemokines, but the functional chemokine binding properties of microparticles are not known. STUDY DESIGN AND METHODS: We determined whether storage-induced microparticles show inflammatory chemokine binding through the expression of the Duffy antigen, comparing the binding properties to intact RBCs, and assessed microparticle interactions with platelets (PLTs) that release chemokines upon activation. RESULTS: Intact RBCs retained similar equilibrium dissociation constants for CCL2 (Kd = 7.4 +/- 0.9 nmol/L), CXCL8 (Kd = 7.9 +/- 1.0 nmol/L), and CXCL1 (Kd = 4.4 +/- 1.0 nmol/L) throughout storage. In contrast, microparticles increased in relative counts with storage, showed higher percentages of surface phosphatidylserine, and demonstrated impaired Duffy-dependent chemokine binding affinity with wider variability in dissociation constant for CXCL1(Kd = 362 +/- 328 nmol/L; range, 0.6-2000 nmol/L). The altered chemokine binding affinity of RBC microparticles was associated with a propensity to release ligand upon incubation with PLTs. Relative quantification of microparticles, based on criteria of glycophorin A expression and size, underestimated particle numbers with functional chemokine binding, suggesting that glycophorin A-negative particles and nanoparticles contribute to overall chemokine binding capacity. CONCLUSION: Microparticle burden in transfusates, as determined by functional chemokine binding, is considerable. Altered membrane properties of RBC microparticles enhance PLT interactions to increase inflammatory chemokine bioavailability in vitro. PMID- 20738827 TI - RhD variant caused by an in-frame triplet duplication in the RHD gene. AB - BACKGROUND: The RHD gene is highly polymorphic and a large number of D variants have already been detected. Several mechanisms are involved in the origin of D variants. In-frame deletions, resulting in a single-amino-acid deletion, have been described associated with RhD and RhCE variants. No in-frame duplications and/or insertions have been reported in the RH genes to date. STUDY DESIGN AND METHODS: Blood samples from a Brazilian blood donor and his sister were serologically tested with routine anti-D reagents and anti-D panels (ALBAclone advanced partial D typing kit, Alba Bioscience Limited; and D-Screen, Diagast), followed by molecular biology techniques, RHD polymerase chain reaction with sequence-specific priming and sequencing. RESULTS: Samples tested negative with routine immunoglobulin M (IgM) anti-D reagents and positive with IgG anti-D, which detect weak D cells. The pattern of results with anti-D panels did not correspond to any described before. A 3-bp in-frame duplication within Exon 1 (c.75_77dupTCT), resulting in the duplication of leucine 26 (p.Leu26dup), was identified in the two samples. CONCLUSION: We report the first RhD variant associated with a 3-bp in-frame duplication in the RHD gene, predicted to be located within the RhD protein transmembrane domain that might be expected to result in a weak-D-like phenotype, concordant with serologic findings. PMID- 20738828 TI - Transfusion-associated infections: 50 years of relentless challenges and remarkable progress. PMID- 20738829 TI - Platelet apoptosis and activation in platelet concentrates stored for up to 12 days in plasma or additive solution. AB - BACKGROUND: Several studies suggest that apoptosis of platelets occurs during storage of platelet concentrates (PC). We sought to determine whether storage of PC in additive solution alters levels of apoptosis during storage beyond the current shelf life (5-7 days). STUDY DESIGN AND METHODS: Pooled buffy coat PC (n = 7) were prepared in either 100% plasma or 70% Composol and stored at 22 degrees C for 12 days. A third arm of the study stored PC in 100% plasma at 37 degrees C, which is thought to induce apoptosis. PC were tested for mitochrondrial membrane potential, annexin V binding, microparticles, caspase-3/7 activity and decoy cell death receptor 2, as well as standard platelet quality tests. RESULTS: Composol units remained >=pH 6.88, with 36% lower lactate and higher pH vs plasma by day 12 (P < 0.001). Platelet function was better maintained, and activation and apoptotic markers tended to be lower in Composol units towards the end of storage. However, levels of all apoptosis markers assessed were not significantly different in units stored in Composol. Storage at 37 degrees C saw stronger correlation of apoptotic markers with standard quality tests compared to 22 degrees C, but loss of correlation of caspase-3/7 activity with other apoptosis markers. CONCLUSION: We conclude that storage of platelets in 70% Composol vs 100% plasma does not increase the rate of platelet apoptosis. Our data agree with other studies suggesting that platelet apoptosis is sequential to high levels of activation, but share a significant degree of overlap. PMID- 20738830 TI - Increased risk of bacterial infection after engraftment in patients treated with allogeneic bone marrow transplantation following reduced-intensity conditioning regimen. AB - Although bacterial infection is a major cause of death even after reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), little is known about the epidemiology and risk factors. The incidence of bacterial infection in 43 patients who received allogeneic bone marrow transplantation (BMT) using a RIC regimen was compared with that in 68 patients who received BMT using a myeloablative conditioning regimen, and risk factors for bacterial infection were identified. Before engraftment, incidences of febrile neutropenia (FN) and documented infections (DI) were significantly decreased in RIC patients (FN: 59.5% vs. 89.6%, P<0.01, DI: 4.8% vs. 17.9%, P<0.01). However, incidence of bacterial infection was significantly increased in RIC patients in the post-engraftment phase (53.8% vs. 11.1%, log-rank, P<0.01). Blood stream was the most frequent focus of infection in both groups. In multivariate analysis, RIC and acute graft-versus-host disease were revealed to be significant risk factors for bacterial infection in this phase. In summary, risk of bacterial infection after engraftment was significantly higher in RIC patients, although infection was decreased before engraftment, and we need to develop a RIC-specific strategy against bacterial infection after RIC SCT. PMID- 20738831 TI - Catheter-associated aspergillosis of the chest wall following allogeneic hematopoietic stem cell transplantation. AB - Invasive aspergillosis (IA) at the insertion site of central venous catheters is a rare event. Here we report the occurrence of chest wall aspergillosis at the insertion site of a Broviac catheter in a 5-year-old child undergoing allogeneic hematopoietic stem cell transplantation. The infection arose during profound granulocytopenia under conditions of reverse isolation with laminar air flow and high efficiency particulate air filtration and was successfully managed with repeat surgical debridement, voriconazole/caspofungin combination therapy guided by therapeutic drug monitoring, and adjunctive use of granulocyte colony stimulating factor. The case reflects the occurrence of IA despite reverse isolation and air decontamination, the principles of treatment of Aspergillus soft tissue infections in granulocytopenic patients, and the need for therapeutic drug monitoring of voriconazole particularly in young children. PMID- 20738832 TI - Microbiological findings of culture-positive preservation fluid in liver transplantation. AB - Bacterial and fungal infections are the leading cause of mortality in liver transplant (LT) recipients. Few studies have examined the incidence of culture positive preservation fluid (PF) and the outcome of related recipients. The aim of this study was to determine the incidence and the microbiologic findings of PF positive cultures, and to evaluate the impact on morbidity and mortality of LT recipients. A retrospective analysis of PF cultures performed after 477 LTs from cadaveric grafts between January 2001 and February 2008 was conducted. Forty-five (9.5%) PFs were found to be positive with 1 or 2 pathogens. The demographic profiles of recipients of PF with positive or negative cultures were similar. Enterobacteriaceae species were the most frequent organisms (n = 30), followed by Staphylococcus aureus (n = 5), coagulase-negative staphylococci (n = 5), enterococci (n = 4), and yeasts (n = 3). Mortality rate at 1 month was not significantly different in recipients with positive or sterile PF cultures (88.1% vs. 87.7%, respectively). The rate of bacteremia among LT recipients with positive or negative PF cultures was not statistically different. Systemic infections caused by the pathogen cultured from the PF occurred in 8 (18%) of the 45 recipients, including bacteremia (4/8) or intra-abdominal sepsis (5/8). Causative organisms were Enterobacteriaceae species (n = 5), Candida species (n = 2), and Enterococcus faecium (n = 1). Among the 8 patients who developed infection with the PF organism, 4 (50%) died in the intensive care unit (ICU) vs. an ICU mortality rate of 8% (3/37) in those who did not develop infection with the PF organism (P < 0.05). Infection occurred less frequently in recipients who received antimicrobial therapy with activity against the PF isolate than in those without appropriate treatment (41% vs. 3.8%, P < 0.005). Those who develop infection with organisms recovered from PF cultures appear to have high early mortality rates; therefore, appropriate antimicrobial therapy against organisms cultured from PF should be given. PMID- 20738833 TI - Exophiala jeanselmei infection in solid organ transplant recipients: report of two cases and review of the literature. AB - Dematiaceous fungi are an opportunistic pathogen seen in solid organ transplant recipients. We report 2 cases of Exophiala infection and review the medical literature to summarize the spectrum of disease this pathogen can cause in this patient population. PMID- 20738834 TI - Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis. AB - Fungal pathogens are increasingly encountered after renal transplantation. Aspergillus causes significant morbidity and mortality in transplant patients. Fungal thyroiditis is a rare occurrence owing to unique features of the thyroid gland. Most cases are caused by Aspergillus species and have been described in immunocompromised patients. Presentation may be identical with that of subacute thyroiditis, in which hyperthyroidism features and painful thyroid are the prominent findings. Diagnosis can be ascertained by fine-needle aspiration of thyroid showing branching hyphae of Aspergillus. We describe a renal transplant patient who developed Aspergillus thyroiditis as part of a disseminated infection successfully treated with voriconazole. PMID- 20738835 TI - Double-balloon enteroscopy for bilioenteric anastomotic stricture after pediatric living donor liver transplantation. AB - Bilioenteric anastomotic stricture after liver transplantation is still frequent and early detection and treatment is important. We established the management using double-balloon enteroscopy (DBE) and evaluated the intractability for bilioenteric anastomotic stricture after pediatric living donor liver transplantation (LDLT). We underwent DBE at Jichi Medical University from May 2003 to July 2009 for 25 patients who developed bilioenteric anastomotic stricture after pediatric LDLT. The patients were divided into two types according to the degree of dilatation of the anastomotic sites before and after interventional radiology (IVR) using DBE. Type I is an anastomotic site macroscopically dilated to five times or more, and Type II is an anastomotic site dilated to less than five times. The rate of DBE reaching the bilioenteric anastomotic sites was 68.0% (17/25), and the success rate of IVR was 88.2% (15/17). There were three cases of Type I and 12 cases of Type II. Type II had a significantly longer cold ischemic time and higher recurrence rate than Type I (P = 0.005 and P = 0.006). In conclusion, DBE is a less invasive and safe treatment method that is capable of reaching the bilioenteric anastomotic site after pediatric LDLT and enables IVR to be performed on strictures, and its treatment outcomes are improving. Type II and long cold ischemic time are risk factors for intractable bilioenteric anastomotic stricture. PMID- 20738837 TI - Lactadherin functions as a probe for phosphatidylserine exposure and as an anticoagulant in the study of stored platelets. AB - BACKGROUND AND OBJECTIVES: Annexin V, the long established standard method of measuring phosphatidylserine (PS) exposure, is not the most suitable probe for the study of stored platelets because of calcium dependence and low sensitivity under 8% PS exposure. The aim of this study was to show lactadherin as a sensitive probe for PS exposure and an effective anticoagulant for stored platelets. MATERIALS AND METHODS: PS exposure and the associated procoagulant activity of platelets in 20 platelet concentrate units were investigated by flow cytometry, confocal microscopy, coagulation time analysis and enzymatic assays. Annexin V and lactadherin were utilized separately in this study. RESULTS: Using lactadherin, we identified higher levels of PS exposure on the platelets and microparticles compared to detection using annexin V by flow cytometry. Lactadherin staining showed earlier PS exposure localized to platelets membrane in the earlier stage of storage. Subsequently, PS was distributed on the narrow rim of the plasma membrane and blebbing vesicles. Lactadherin or annexin V(32 nm) prolonged coagulation time 2.4 fold versus twofold. The production of thrombin and intrinsic/extrinsic factor Xase were inhibited approximately 85~90% and 65~70% by lactadherin and annexin V, respectively. CONCLUSION: Lactadherin can provide the quantification and location of PS exposure on banked platelets in the absence of agonists. Furthermore, lactadherin is a more effective anticoagulant for inhibiting the procoagulant activity of stored platelets compared with annexin V. PMID- 20738836 TI - Blood donors in Kenya: a comparison of voluntary and family replacement donors based on a population-based survey. AB - BACKGROUND AND OBJECTIVES: Blood safety and sufficiency are major challenges in Kenya and other sub-Saharan African countries forcing many countries to rely on family replacement donors (FRD). We analysed data from a national AIDS indicator survey to describe blood donors in Kenya and potential risks of transfusion transmissible infections (TTI) comparing voluntary donors and FRD. MATERIALS AND METHODS: A population-based, cross-sectional survey was conducted in 2007 among 15- to 64-year-olds. Consenting participants were interviewed about blood donation history and were tested for HIV, HSV-2 and syphilis. RESULTS: Of the 17,940 people surveyed, 445 (2.3%) reported donating blood in the prior 12 months. Sixty-four per cent were voluntary donors, and the rest were FRD. Compared to FRD, the majority of voluntary donors were <25 years old (59% versus 18%), from the highest wealth quintile (57% versus 42%) and single (64% versus 23%). In addition, voluntary donors were less likely to have been sexually active than replacement donors (43% versus 13%). HIV prevalence was lower among voluntary donors than among FRD (2.6% versus 7.4%, P-value=0.07). CONCLUSIONS: The majority of blood donors in Kenya are voluntary with lower potential risk of TTI. PMID- 20738838 TI - 'Wrong blood in tube': solutions for a persistent problem. AB - BACKGROUND AND OBJECTIVES: This study was performed to determine the incidence of 'wrong blood in tube' (WBIT)-type errors at our institution during the past 5 years, to analyse their root cause and to evaluate the efficacy of preventive measures that have been implemented since 2006. METHODS: All reports of mislabelled and miscollected specimens detected between January 2005 and December 2009 were reviewed. Of these, WBIT-type errors were further analysed as they represent a major risk for mistransfusion. RESULTS: Between 2005 and 2009, 59,373 type and screens were performed at our institution and a total of 26 major errors (WBIT) were identified. Of the errors, eight were detected by discrepant typing results (in comparison with historic blood type), six were discovered by the clinical service and 12 were identified in the blood bank by other means. Our estimated 'raw' WBIT rate (1 in 2283 samples) is comparable to that (1:2262) in the published literature. Since 2006, our nursing policy mandates that 'all type, screen and cross will have two witnesses to the correct ID of the patient and labeling is done at the bedside at the time of the draw.' This has reduced (from 11 in 2006 to 5 in 2007), but did not eliminate, our WBIT problem that persisted into 2008 and 2009 (three and seven incidents, respectively). Since 2009, we also require a second, independently drawn sample in previously un-typed patients who are likely to be transfused. CONCLUSION: We conclude that WBITs continue to represent a leading cause of potential mistransfusions at our institution. Changes in nursing (two witnesses to correct ID) and/or blood bank policy (check type with a second specimen) may reduce, but not eliminate, this persistent problem. Clearly, additional safety measures are required to prevent WBIT-type errors. PMID- 20738839 TI - Immunomapping of desmosomal and nondesmosomal adhesion molecules in healthy canine footpad, haired skin and buccal mucosal epithelia: comparison with canine pemphigus foliaceus serum immunoglobulin G staining patterns. AB - Pemphigus foliaceus (PF) is the most common canine autoimmune skin disease. In contrast to human PF (hPF), desmoglein-1 is a minor autoantigen in the canine disease. The major autoantigen(s) of canine PF (cPF) remain(s) unknown, which limits the ability to perform mechanistic studies of lesion formation and the development of novel diagnostic and therapeutic strategies for this disease. The immunofluorescence patterns of selected desmosomal (desmoglein-1, desmoglein-3, desmocollin-1, desmocollin-3, desmoplakin-1/2, plakoglobin and plakophilin-1) and nondesmosomal adhesion proteins (E-cadherin, claudin-1, zona occludens-1 and occludin) in healthy canine footpad, haired skin and buccal mucosal epithelia were determined using hPF and pemphigus vulgaris sera and specific antibodies. The immunostaining patterns were then compared with that of indirect immunofluorescence staining with 66 cPF sera. Most cPF sera (58 of 66; 88%) exhibited positive staining along keratinocyte margins in the stratum spinosum and stratum granulosum of canine footpad. One serum contained autoantibodies binding solely to stratum granulosum keratinocytes. Concurrent intercellular fluorescence in the stratum basale was limited to seven of 66 cPF sera (11%). Only 12 of 66 cPF sera (18%) also exhibited positive IF staining of the buccal mucosa. This study confirms the immunological heterogeneity of cPF immunoglobulin G autoantibodies. Moreover, the major indirect immunofluorescence staining pattern and the inability of most cPF sera to label the buccal mucosa closely matched that of desmocollin-1. These observations warrant further investigation of desmocollin-1 as a potential major cPF autoantigen. PMID- 20738840 TI - Prediction error and accuracy of intraocular lens power calculation in pediatric patient comparing SRK II and Pediatric IOL Calculator. AB - BACKGROUND: Despite growing number of intraocular lens power calculation formulas, there is no evidence that these formulas have good predictive accuracy in pediatric, whose eyes are still undergoing rapid growth and refractive changes. This study is intended to compare the prediction error and the accuracy of predictability of intraocular lens power calculation in pediatric patients at 3 month post cataract surgery with primary implantation of an intraocular lens using SRK II versus Pediatric IOL Calculator for pediatric intraocular lens calculation. Pediatric IOL Calculator is a modification of SRK II using Holladay algorithm. This program attempts to predict the refraction of a pseudophakic child as he grows, using a Holladay algorithm model. This model is based on refraction measurements of pediatric aphakic eyes. Pediatric IOL Calculator uses computer software for intraocular lens calculation. METHODS: This comparative study consists of 31 eyes (24 patients) that successfully underwent cataract surgery and intraocular lens implantations. All patients were 12 years old and below (range: 4 months to 12 years old). Patients were randomized into 2 groups; SRK II group and Pediatric IOL Calculator group using envelope technique sampling procedure. Intraocular lens power calculations were made using either SRK II or Pediatric IOL Calculator for pediatric intraocular lens calculation based on the printed technique selected for every patient. Thirteen patients were assigned for SRK II group and another 11 patients for Pediatric IOL Calculator group. For SRK II group, the predicted postoperative refraction is based on the patient's axial length and is aimed for emmetropic at the time of surgery. However for Pediatric IOL Calculator group, the predicted postoperative refraction is aimed for emmetropic spherical equivalent at age 2 years old. The postoperative refractive outcome was taken as the spherical equivalent of the refraction at 3 month postoperative follow-up. The data were analysed to compare the mean prediction error and the accuracy of predictability of intraocular lens power calculation between SRK II and Pediatric IOL Calculator. RESULTS: There were 16 eyes in SRK II group and 15 eyes in Pediatric IOL Calculator group. The mean prediction error in the SRK II group was 1.03 D (SD, 0.69 D) while in Pediatric IOL Calculator group was 1.14 D (SD, 1.19 D). The SRK II group showed lower prediction error of 0.11 D compared to Pediatric IOL Calculator group, but this was not statistically significant (p = 0.74). There were 3 eyes (18.75%) in SRK II group achieved accurate predictability where the refraction postoperatively was within +/- 0.5 D from predicted refraction compared to 7 eyes (46.67%) in the Pediatric IOL Calculator group. However the difference of the accuracy of predictability of postoperative refraction between the two formulas was also not statistically significant (p = 0.097). CONCLUSIONS: The prediction error and the accuracy of predictability of postoperative refraction in pediatric cataract surgery are comparable between SRK II and Pediatric IOL Calculator. The existence of the Pediatric IOL Calculator provides an alternative to the ophthalmologist for intraocular lens calculation in pediatric patients. Relatively small sample size and unequal distribution of patients especially the younger children (less than 3 years) with a short time follow-up (3 months), considering spherical equivalent only. PMID- 20738841 TI - Class IIa bacteriocin resistance in Enterococcus faecalis V583: the mannose PTS operon mediates global transcriptional responses. AB - BACKGROUND: The class IIa bacteriocin, pediocin PA-1, has clear potential as food preservative and in the medical field to be used against Gram negative pathogen species as Enterococcus faecalis and Listeria monocytogenes. Resistance towards class IIa bacteriocins appear in laboratory and characterization of these phenotypes is important for their application. To gain insight into bacteriocin resistance we studied mutants of E. faecalis V583 resistant to pediocin PA-1 by use of transcriptomic analyses. RESULTS: Mutants of E. faecalis V583 resistant to pediocin PA-1 were isolated, and their gene expression profiles were analyzed and compared to the wild type using whole-genome microarray. Significantly altered transcription was detected from about 200 genes; most of them encoding proteins involved in energy metabolism and transport. Glycolytic genes were down-regulated in the mutants, but most of the genes showing differential expression were up regulated. The data indicate that the mutants were relieved from glucose repression and putative catabolic responsive elements (cre) could be identified in the upstream regions of 70% of the differentially expressed genes. Bacteriocin resistance was caused by reduced expression of the mpt operon encoding the mannose-specific phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS), and the same transcriptional changes were seen in a mptD-inactivated mutant. This mutant also had decreased transcription of the whole mpt operon, showing that the PTS is involved in its own transcriptional regulation. CONCLUSION: Our data confirm the important role of mannose PTS in class IIa bacteriocin sensitivity and we demonstrate its importance involving global carbon catabolite control. PMID- 20738842 TI - EphrinA5 protein distribution in the developing mouse brain. AB - BACKGROUND: EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. RESULTS: Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. CONCLUSION: Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic mapping of connections and to further characterise the mechanisms involved in pathway restoration following cell transplantation in the damaged brain. PMID- 20738843 TI - Long-term increase of fat mass after a four week intervention with fast food based hyper-alimentation and limitation of physical activity. AB - BACKGROUND: A sedentary lifestyle and increased consumption of energy dense food have become more common in many parts of the world. The aim of this study was to study long term effects on body composition after a four week intervention with fast food based hyper-alimentation and limited physical activity in young normal weight subjects. METHODS: Eighteen subjects, mean age 26 (6.6) years, increased their energy intake with in average 70% and physical activity were not to exceed 5000 steps/day. Body composition was measured by Dual energy x-ray (DXA) at baseline, after the intervention and after 12 months. A matched control group was also included. ANOVA and Student's paired and unpaired t-test were used. RESULTS: During the intervention body weight increased with 6.4 (2.8) kg and DXA measurements showed increases of both fat free mass and fat mass. Six months after the intervention the subjects had lost most of the weight gain, - 4.7 (3.1) kg. Twelve months after the intervention body weight had increased with 1.5 (2.4) kg compared to baseline (p = 0.018). DXA measurements at 12 months showed unchanged fat free mass compared to baseline but higher fat mass, + 1.4 (1.9) kg (p = 0.01). After 2.5 years the increase of body weight was 3.1 (4.0) kg (p = 0.01) while there was no change in controls compared to baseline, + 0.1(2.5) kg (p = 0.88). CONCLUSION: One year after a short term intervention with increased fast food based hyper-alimentation there was an increase of fat mass but unchanged fat free mass. As the change of fat mass was larger than expected from prospective epidemiological studies and as there was no increase of body weight in controls it raises the issue whether there is a long-term effect to increase fat mass of a short period of hyper-alimentation. PMID- 20738844 TI - A simple index of lipid overaccumulation is a good marker of liver steatosis. AB - BACKGROUND: Liver steatosis is often found in association with common cardiometabolic disorders, conditions that may all occur in a shared context of abdominal obesity and dyslipidemia. An algorithm for identifying liver steatosis is the fatty liver index (FLI). The lipid accumulation product (LAP) is an index formulated in a representative sample of the US population to identify cardiometabolic disorders. Because FLI and LAP share two components, namely waist circumference and fasting triglycerides, we evaluated the ability of LAP to identify liver steatosis in the same study population from the Northern Italian town where FLI was initially developed. METHODS: We studied 588 individuals (59% males) aged 21 to 79 years. Liver steatosis was detected by ultrasonography and coded ordinally as none, intermediate and severe. 44% of the individuals had liver steatosis. Using proportional-odds ordinal logistic regression, we evaluated the ability of log-transformed LAP (lnLAP) to identify liver steatosis. We considered the benefits to our model of including terms for sex, age, suspected liver disease and ethanol intake. We calculated the 3-level probability of liver steatosis according to lnLAP and sex, providing tables and nomograms for risk assessment. RESULTS: An ordinal proportional-odds model consisting of lnLAP and sex offered a reasonably accurate identification of liver steatosis. The odds of more severe vs. less severe steatosis increased for increasing values of lnLAP (odds ratio [OR] = 4.28, 95%CI 3.28 to 5.58 for each log-unit increment) and was more likely among males (OR = 1.88, 95%CI 1.31 to 2.69). CONCLUSION: In a study sample of adults from Northern Italy, the simple calculation of LAP was a reasonably accurate approach to recognizing individuals with ultrasonographic liver steatosis. LAP may help primary care physicians to select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. A more thorough assessment of LAP's potential for identifying liver steatosis will require its cross-evaluation in external populations. PMID- 20738845 TI - The liposoluble proteome of Mycoplasma agalactiae: an insight into the minimal protein complement of a bacterial membrane. AB - BACKGROUND: Mycoplasmas are the simplest bacteria capable of autonomous replication. Their evolution proceeded from gram-positive bacteria, with the loss of many biosynthetic pathways and of the cell wall. In this work, the liposoluble protein complement of Mycoplasma agalactiae, a minimal bacterial pathogen causing mastitis, polyarthritis, keratoconjunctivitis, and abortion in small ruminants, was subjected to systematic characterization in order to gain insights into its membrane proteome composition. RESULTS: The selective enrichment for M. agalactiae PG2T liposoluble proteins was accomplished by means of Triton X-114 fractionation. Liposoluble proteins were subjected to 2-D PAGE-MS, leading to the identification of 40 unique proteins and to the generation of a reference 2D map of the M. agalactiae liposoluble proteome. Liposoluble proteins from the type strain PG2 and two field isolates were then compared by means of 2D DIGE, revealing reproducible differences in protein expression among isolates. An in depth analysis was then performed by GeLC-MS/MS in order to achieve a higher coverage of the liposoluble proteome. Using this approach, a total of 194 unique proteins were identified, corresponding to 26% of all M. agalactiae PG2T genes. A gene ontology analysis and classification for localization and function was also carried out on all protein identifications. Interestingly, the 11.5% of expressed membrane proteins derived from putative horizontal gene transfer events. CONCLUSIONS: This study led to the in-depth systematic characterization of the M. agalactiae liposoluble protein component, providing useful insights into its membrane organization. PMID- 20738846 TI - Research protocol: a synthesis of qualitative studies on the process of adaptation to dependency in elderly persons and their families. AB - BACKGROUND: Dealing with dependency in the elderly and their families leads us to explore the life experience of those involved together with the processes of adaptation to this condition. A number of original studies have been published which, following a qualitative methodology, have dealt with both dimensions. METHODS/DESIGN: OBJECTIVES: 1) To present a synthesis of the qualitative evidence available on the process of adaptation to dependency in elderly persons and their families; 2) to conduct an in-depth study into the experiences and strategies developed by both to optimise their living conditions; 3) to enable standards of action/intervention to be developed in the caregiving environment.A synthesis of qualitative studies is projected with an extensive and inclusive bibliography search strategy. The primary search will focus on the major databases (CINAHL, MEDLINE, EMBASE, PsycInfo, PSICODOC, Cochrane Library, JBI, EMBASE, LILACS, CUIDEN, CUIDEN qualitative, CUIDATGE, British Nursing Index, SSCI). The secondary search will be conducted in articles taken from the references to studies identified in the articles and reports and the manual search in congresses and foundation papers. Article quality will be assessed by the guide proposed by Sandelowski & Barroso and data extraction done using the QARI data extraction form proposed by the Joanna Briggs Institute for Evidence Based Practice.The synthesis of the findings will be based on the principles and procedures of grounded theory: coding, identification and relationship between categories, and synthesis using constant comparison as a strategy. DISCUSSION: This synthesis of qualitative evidence will enable us to detect health needs as perceived by the receivers in their own interaction contexts. PMID- 20738847 TI - A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPbeta/zeta. AB - BACKGROUND: Pleiotrophin, also known as HARP (Heparin Affin Regulatory Peptide) is a growth factor expressed in various tissues and cell lines. Pleiotrophin participates in multiple biological actions including the induction of cellular proliferation, migration and angiogenesis, and is involved in carcinogenesis. Recently, we identified and characterized several pleiotrophin proteolytic fragments with biological activities similar or opposite to that of pleiotrophin. Here, we investigated the biological actions of P(122-131), a synthetic peptide corresponding to the carboxy terminal region of this growth factor. RESULTS: Our results show that P(122-131) inhibits in vitro adhesion, anchorage-independent proliferation, and migration of DU145 and LNCaP cells, which express pleiotrophin and its receptor RPTPbeta/zeta. In addition, P(122-131) inhibits angiogenesis in vivo, as determined by the chicken embryo CAM assay. Investigation of the transduction mechanisms revealed that P(122-131) reduces the phosphorylation levels of Src, Pten, Fak, and Erk1/2. Finally, P(122-131) not only interacts with RPTPbeta/zeta, but also interferes with other pleiotrophin receptors, as demonstrated by selective knockdown of pleiotrophin or RPTPbeta/zeta expression with the RNAi technology. CONCLUSIONS: In conclusion, our results demonstrate that P(122-131) inhibits biological activities that are related to the induction of a transformed phenotype in PCa cells, by interacing with RPTPbeta/zeta and interfering with other pleiotrophin receptors. Cumulatively, these results indicate that P(122-131) may be a potential anticancer agent, and they warrant further study of this peptide. PMID- 20738848 TI - The haematopoietic GTPase RhoH modulates IL3 signalling through regulation of STAT activity and IL3 receptor expression. AB - BACKGROUND: RhoH is a constitutively active member of the family of Rho GTPases. Its expression is restricted to the haematopoietic lineage, where it serves as a positive regulator for T cell selection and mast cell function and as a negative regulator for growth-related functions in other lineages. Here, we examined the activation of signal transducer and activator of transcription (STAT) proteins in response to stimulation with interleukin 3 (IL3). RESULTS: Using the murine IL3 dependent cell line BaF3 we investigated the influence of RhoH protein expression levels on IL3-mediated cellular responses. RhoH overexpressing cells showed lower sensitivity to IL3 and decreased STAT5 activation. SiRNA-mediated repression of RhoH gene expression led to an increase in proliferation and STAT5 activity which correlated with an increased number of IL3 receptor alpha chain molecules, also known as CD123, expressed at the cell surface. Interestingly, these findings could be reproduced using human THP-1 cells as a model system for acute myeloid leukaemia, where low RhoH levels are known to be an unfavourable prognostic marker. Overexpression of RhoH on the other hand caused an induction of STAT1 activity and western blot analysis revealed that activated STAT1 is phosphorylated on Tyr701. STAT1 is known to induce apoptosis or cell cycle arrest and we detected an upregulation of cyclin-dependent kinase inhibitors (CDKI) p21Cip1 and p27Kip1 in RhoH overexpressing BaF3 cells. CONCLUSIONS: We propose that RhoH functions as a negative regulator for IL3-induced signals through modulation of the JAK-STAT pathway. High levels of RhoH allow the IL3-dependent activation of STAT1 causing decreased proliferation through upregulation of p21Cip1 and p27Kip1. Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML patients. PMID- 20738849 TI - Identification of transcriptome induced in roots of maize seedlings at the late stage of waterlogging. AB - BACKGROUND: Plants respond to low oxygen stress, particularly that caused by waterlogging, by altering transcription and translation. Previous studies have mostly focused on revealing the mechanism of the response at the early stage, and there is limited information about the transcriptional profile of genes in maize roots at the late stage of waterlogging. The genetic basis of waterlogging tolerance is largely unknown. In this study, the transcriptome at the late stage of waterlogging was assayed in root cells of the tolerant inbred line HZ32, using suppression subtractive hybridization (SSH). A forward SSH library using RNA populations from four time points (12 h, 16 h, 20 h and 24 h) after waterlogging treatment was constructed to reveal up-regulated genes, and transcriptional and linkage data was integrated to identify candidate genes for waterlogging tolerance. RESULTS: Reverse Northern analysis of a set of 768 cDNA clones from the SSH library revealed a large number of genes were up-regulated by waterlogging. A total of 465 ESTs were assembled into 296 unigenes. Bioinformatic analysis revealed that the genes were involved in complex pathways, such as signal transduction, protein degradation, ion transport, carbon and amino acid metabolism, and transcriptional and translational regulation, and might play important roles at the late stage of the response to waterlogging. A significant number of unigenes were of unknown function. Approximately 67% of the unigenes could be aligned on the maize genome and 63 of them were co-located within reported QTLs. CONCLUSION: The late response to waterlogging in maize roots involves a broad spectrum of genes, which are mainly associated with two response processes: defense at the early stage and adaption at the late stage. Signal transduction plays a key role in activating genes related to the tolerance mechanism for survival during prolonged waterlogging. The crosstalk between carbon and amino acid metabolism reveals that amino acid metabolism performs two main roles at the late stage: the regulation of cytoplasmic pH and energy supply through breakdown of the carbon skeleton. PMID- 20738850 TI - Measuring the impact of health policies using Internet search patterns: the case of abortion. AB - BACKGROUND: Internet search patterns have emerged as a novel data source for monitoring infectious disease trends. We propose that these data can also be used more broadly to study the impact of health policies across different regions in a more efficient and timely manner. METHODS: As a test use case, we studied the relationships between abortion-related search volume, local abortion rates, and local abortion policies available for study. RESULTS: Our initial integrative analysis found that, both in the US and internationally, the volume of Internet searches for abortion is inversely proportional to local abortion rates and directly proportional to local restrictions on abortion. CONCLUSION: These findings are consistent with published evidence that local restrictions on abortion lead individuals to seek abortion services outside of their area. Further validation of these methods has the potential to produce a timely, complementary data source for studying the effects of health policies. PMID- 20738851 TI - Reticulate evolution in stick insects: the case of Clonopsis (Insecta Phasmida). AB - BACKGROUND: Phasmids show noteworthy abilities to overcome species-specific reproductive isolation mechanisms, including hybridization, polyploidy, parthenogenesis, hybridogenesis and androgenesis. From an evolutionary standpoint, such tangled reproductive interactions lead to the complex phyletic relationships known as "reticulate evolution". Moroccan stick insects of the genus Clonopsis include one bisexual (C. felicitatis) and two closely related parthenogenetic forms (C. gallica, C. soumiae), which represent a polyploid series in chromosome number, but with apparent diploid karyotypes. Moreover, two Clonopsis strains of ameiotic males have been described, C. androgenes-35 and C. androgenes-53. As a consequence, Clonopsis stick insects may have experienced complex micro-evolutionary events, which we try to disentangle in this study. RESULTS: Mitochondrial cox2 analysis supports a recent divergence of Clonopsis, while AFLPs evidence genetic differentiation not linked to karyotypes, so that parthenogenetic C. gallica and C. soumiae appear to be a mix of strains of polyphyletic origin rather than single parthenogenetic species. Moreover, an admixed hybrid origin seems to be confirmed for C. androgenes. CONCLUSION: On the whole, Clonopsis is an intriguing case of reticulate evolution. Actually, complex cladogenetic events should be taken into account to explain the observed genetic structure, including diploidization of polyploid karyotypes, possibly coupled with hybridization and androgenesis. We also proposed a "working hypothesis" to account for the observed data, which deserves further studies, but fits the observed data very well. PMID- 20738852 TI - Physiotherapy-supervised mobilization and exercise following cardiac surgery: a national questionnaire survey in Sweden. AB - BACKGROUND: Limited published data are available on how patients are mobilized and exercised during the postoperative hospital stay following cardiac surgery. The aim of this survey was to determine current practice of physiotherapy supervised mobilization and exercise following cardiac surgery in Sweden. METHODS: A prospective survey was carried out among physiotherapists treating adult cardiac surgery patients. A total population sample was identified and postal questionnaires were sent to the 33 physiotherapists currently working at the departments of thoracic surgery in Sweden. In total, 29 physiotherapists (response rate 88%) from eight hospitals completed the survey. RESULTS: The majority (90%) of the physiotherapists offered preoperative information. The main rationale of physiotherapy treatment after cardiac surgery was to prevent and treat postoperative complications, improve pulmonary function and promote physical activity. In general, one to three treatment sessions were given by a physiotherapist on postoperative day 1 and one to two treatment sessions were given during postoperative days 2 and 3. During weekends, physiotherapy was given to a lesser degree (59% on Saturdays and 31% on Sundays to patients on postoperative day 1). No physiotherapy treatment was given in the evenings. The routine use of early mobilization and shoulder range of motion exercises was common during the first postoperative days, but the choice of exercises and duration of treatment varied. Patients were reminded to adhere to sternal precautions. There were great variations of instructions to the patients concerning weight bearing and exercises involving the sternotomy. All respondents considered physiotherapy necessary after cardiac surgery, but only half of them considered the physiotherapy treatment offered as optimal. CONCLUSIONS: The results of this survey show that there are small variations in physiotherapy supervised mobilization and exercise following cardiac surgery in Sweden. However, the frequency and duration of exercises and recommendations for sternal precautions reinforced for the healing period differ between physiotherapists. This survey provides an initial insight into physiotherapy management in Sweden. Comparison with surveys in other countries is warranted to improve the physiotherapy management and postoperative recovery of the cardiac surgery patient. PMID- 20738853 TI - Skin cancers in albinos in a teaching Hospital in eastern Nigeria - presentation and challenges of care. AB - BACKGROUND: Albinism is a genetic disorder characterized by lack of skin pigmentation. It has a worldwide distribution but is commoner in areas close to the equator like Nigeria. Skin cancers are a major risk associated with albinism and are thought to be a major cause of death in African albinos. Challenges faced in the care of these patients need to be highlighted in order to develop a holistic management approach with a significant public health impact. The aim of the study was to determine the pattern of skin cancers seen in Albinos, and to highlight problems encountered in their management. METHOD: Case records of albinos managed in Imo state University teaching Hospital from June 2007 to May 2009 were reviewed. The data obtained was analyzed using descriptive statistics. RESULTS AND DISCUSSION: In the period under review, albinos accounted for 67% of patients managed for primary skin cancers. There were twenty patients with thirty eight (38) lesions. Sixty one percent of the patients were below 40 years. Average duration of symptoms at presentation was 26 months. The commonest reason for late presentation was the lack of funds. Squamous cell carcinoma was the commonest histologic variant. Most patients were unable to complete treatment due to lack of funds. CONCLUSION: Albinism appears to be the most important risk factor in the development of skin cancers in our environment. Late presentation and poor rate of completion of treatment due to poverty are major challenges. PMID- 20738854 TI - Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation. AB - INTRODUCTION: Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers. METHODS: CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to chemokine ligand 25 (CCL25)/TECK were used to study CCR9 function. RESULTS: CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in RA. In RA and non-RA synovia, CCR9 co-localised with cluster of differentiation 14+ (CD14+) and cluster of differentiation 68+ (CD68+) macrophages, and was more abundant in RA synovium. CCR9 mRNA was detected in the synovia of all RA patients and in some non-RA controls, and monocytes/macrophages from PB and SF of RA and healthy controls. CCL25 was detected in RA and non-RA synovia where it co-localised with CD14+ and CD68+ cells. Tumour necrosis factor alpha (TNFalpha) increased CCR9 expression on human acute monocytic leukemia cell line THP-1 monocytic cells. CCL25 induced a stronger monocyte differentiation in RA compared to healthy donors. CCL25 induced significant chemotaxis of PB monocytes but not consistently among individuals. CONCLUSIONS: CCR9 expression by monocytes is increased in RA. CCL25 may be involved in the differentiation of monocytes to macrophages particularly in RA. PMID- 20738855 TI - Relationship between patient-reported disease severity in osteoarthritis and self reported pain, function and work productivity. AB - INTRODUCTION: Understanding the relationship between patient-reported osteoarthritis (OA) severity and other patient-reported outcomes in the real world clinical setting can provide a basis for appropriate patient management. The objective of this study was to determine how patient-reported OA severity correlates with patient-reported outcomes including pain, function and productivity. METHODS: We used the Adelphi Disease Specific Programme (DSP) for OA, a database aggregated from large, multinational, observational studies for specific chronic diseases. Data were obtained based on a 0 to 100 mm pain visual analogue scale (VAS) and a series of questions including functioning (that is, activities of daily living) and work productivity. OA severity was rated by the patients based on the question "How bad would you say your arthritis is now?" with potential responses of "mild," "moderate," and "severe." Regression models and chi-square analyses were used to evaluate the relationships between self reported OA severity and other outcomes. RESULTS: Of 998 subjects in the OA DSP U.S. database, 714 (72.5%) agreed to participate. This sample was predominantly female (61.7%) with a mean age of 63.8 +/- 12.9 years. Increased OA severity was associated with an older population (P < 0.05). With increasing OA severity (mild, moderate, severe), statistically significant differences (P < 0.05) were observed in increased pain VAS scores (23.5, 50.2, 70.8, respectively), lower functioning outcomes, and a higher percent of overall work impairment due to OA (17%, 37%, 48%, respectively). The increased work impairment at greater severity levels also resulted in higher costs related to lost work productivity, with annual costs due to lost productivity estimated at $6,096, $13,2510, and $17,214 per patient for self-reported mild, moderate, and severe OA, respectively (P < 0.05 for pairwise comparisons). CONCLUSIONS: In the clinical practice setting, patient-reported OA severity was associated with other key patient-reported outcomes and thus may provide an accurate and tangible assessment of patients' perceptions of their disease. Identifying OA patients by their perceived severity level may be of benefit to patients and health-care providers when choosing treatment options aimed at reducing pain, and improving function and productivity. PMID- 20738856 TI - Digital expression profiling of novel diatom transcripts provides insight into their biological functions. AB - BACKGROUND: Diatoms represent the predominant group of eukaryotic phytoplankton in the oceans and are responsible for around 20% of global photosynthesis. Two whole genome sequences are now available. Notwithstanding, our knowledge of diatom biology remains limited because only around half of their genes can be ascribed a function based onhomology-based methods. High throughput tools are needed, therefore, to associate functions with diatom-specific genes. RESULTS: We have performed a systematic analysis of 130,000 ESTs derived from Phaeodactylum tricornutum cells grown in 16 different conditions. These include different sources of nitrogen, different concentrations of carbon dioxide, silicate and iron, and abiotic stresses such as low temperature and low salinity. Based on unbiased statistical methods, we have catalogued transcripts with similar expression profiles and identified transcripts differentially expressed in response to specific treatments. Functional annotation of these transcripts provides insights into expression patterns of genes involved in various metabolic and regulatory pathways and into the roles of novel genes with unknown functions. Specific growth conditions could be associated with enhanced gene diversity, known gene product functions, and over-representation of novel transcripts. Comparative analysis of data from the other sequenced diatom, Thalassiosira pseudonana, helped identify several unique diatom genes that are specifically regulated under particular conditions, thus facilitating studies of gene function, genome annotation and the molecular basis of species diversity. CONCLUSIONS: The digital gene expression database represents a new resource for identifying candidate diatom-specific genes involved in processes of major ecological relevance. PMID- 20738857 TI - Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression. AB - BACKGROUND: Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD. METHODS: We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. RESULTS: There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients. CONCLUSIONS: The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts. PMID- 20738858 TI - Genetic susceptibility to advanced retinopathy of prematurity (ROP). AB - Retinopathy of prematurity (ROP) is a vascular vitreoretinopathy that affects infants with short gestational age and low birth-weight. The condition is a multifactorial disease and is clinically similar to familial exudative vitreoretinopathy (FEVR), which is a bilateral hereditary eye disorder affecting full-term infants. Both of them are characterized by the abnormal vessel growth in the vitreous that can lead to vitreoretinal traction, retinal detachment and other complications resulting in blindness. Despite the recent advances in diagnosis and treatment, ROP remains a major cause of childhood blindness in developed countries. The etiology of pathogenesis of advanced ROP is currently unknown. In the past, many causative factors such as length of time exposed to supplemental oxygen, excessive ambient light exposure and hypoxia have been suggested but evidence for these as independent risk factors in recent years is not compelling. It is not clear why ROP in a subset of infants with low birth weight progresses to a severe stage (retinal detachment) despite timely intervention whereas in other infants with similar clinical characteristics ROP regresses spontaneously. Recent research with candidate gene approach, higher concordance rate in monozygotic twins and other clinical and experimental animal studies, suggest a strong genetic predisposition to ROP besides environmental factors such as prematurity. Three genes, which are involved in the Wnt signaling pathway, are mutated in both FEVR and in a small percentage of ROP disorder. However, none of the genetic factors identified thus far in ROP, account for a substantial number of patient population. Future studies involving genomics, bioinformatics and proteomics may provide a better understanding of the pathophysiology and management of ROP. PMID- 20738859 TI - Persistent Chlamydia Pneumoniae serology is related to decline in lung function in women but not in men. Effect of persistent Chlamydia pneumoniae infection on lung function. AB - BACKGROUND: Chlamydia pneumoniae (C pn) infection causes an acute inflammation in the respiratory system that may become persistent, but little is known about the long-term respiratory effects of C pn infections. AIM: To estimate the long term respiratory effects of C pn with change in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) as a main outcome variable. METHODS: The study comprised of 1109 subjects (500 men and 609 women, mean age 28 +/- 6 years) that participated in the Reykjavik Heart Study of the Young. Spirometry and blood samples for measurements of IgG antibodies for C pn were done at inclusion and at the end of the follow-up period (mean follow-up time 27 +/- 4 years). RESULTS: Having IgG against C pn at both examinations was significantly associated to a larger decrease in FEV1 (6 mL/year) and FVC (7 mL/year) in women but not in men. In women the association between C pn and larger FEV1 decline was only found in women that smoked at baseline where having C pn IgG was associated with 10 mL/year decline compared to smokers without C pn IgG. These results were still significant after adjustment for age, smoking and change in body weight. CONCLUSION: Our results indicate that persistent C pn serology is related to increased decline in lung function in women but not in men. This effect was, however, primarily found in smoking women. This study is a further indication that the pathophysiological process leading to lung impairment may differ between men and women. PMID- 20738861 TI - Prevalence of human papillomavirus infection and genotype distribution among high risk Korean women for prospecting the strategy of vaccine development. AB - We investigated the prevalence of human papillomavirus (HPV) infection and the distribution of high-risk HPV genotypes among 2,308 high-risk Korean women to predict how much the current prophylactic HPV vaccines might affect the prevention of cervical cancer in Korea. HPV DNA was detected in 939 women (40.7%) but only one-third of women were positive for HPV-16 and/or HPV-18, the genotypes used for developing the HPV vaccines. Thus, the development of area-specific HPV vaccines based on dominant HPV genotypes in our country is needed for preventing HPV infection and the development of premalignant lesions in the cervix of Korean women. PMID- 20738860 TI - The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation. AB - INTRODUCTION: The purpose of this study was to evaluate the effects of risedronate (Ris) in the modulation of bone formation in rats with glucocorticoid (GC)-induced osteoporosis by histomorphometric, immunohistochemical and gene expression analyses. METHODS: We analyzed structure, turnover and microarchitecture, cyclooxygenase 2 (COX-2) levels and osteocyte apoptosis in 40 female rats divided as follows: 1) vehicle of methylprednisolone (vGC) + vehicle of risedronate (vRis); 2) Ris 5 MUg/Kg + vGC; 3) methylprednisolone (GC) 7 mg/Kg + vRis; 4) GC 7 mg/Kg +Ris 5 MUg/Kg. In addition, we evaluated cell proliferation and expression of COX-2 and bone alkaline phosphatase (b-ALP) genes in bone marrow cells and MLO-y4 osteocytes treated with Ris alone or in co-treatment with the selective COX-2 inhibitor NS-398 or with dexametasone. RESULTS: Ris reduced apoptosis induced by GC of osteocytes (41% vs 86%, P < 0.0001) and increased COX 2 expression with respect to controls (Immuno-Hystochemical Score (IHS): 8.75 vs 1.00, P < 0.0001). These positive effects of Ris in bone formation were confirmed by in vitro data as the viability and expression of b-ALP gene in bone marrow cells resulted increased in a dose dependent manner. CONCLUSIONS: These findings suggest a positive effect of Ris in bone formation and support the hypothesis that the up-regulation of COX-2 could be an additional mechanism of anabolic effect of Ris. PMID- 20738862 TI - Immune regulation of a chronic bacteria infection and consequences for pathogen transmission. AB - BACKGROUND: The role of host immunity has been recognized as not only playing a fundamental role in the interaction between the host and pathogen but also in influencing host infectiousness and the ability to shed pathogens. Despite the interest in this area of study, and the development of theoretical work on the immuno-epidemiology of infections, little is known about the immunological processes that influence pathogen shedding patterns. RESULTS: We used the respiratory bacterium Bordetella bronchiseptica and its common natural host, the rabbit, to examine the intensity and duration of oro-nasal bacteria shedding in relation to changes in the level of serum antibodies, blood cells, cytokine expression and number of bacteria colonies in the respiratory tract. Findings show that infected rabbits shed B. bronchiseptica by contact up to 4.5 months post infection. Shedding was positively affected by number of bacteria in the nasal cavity (CFU/g) but negatively influenced by serum IgG, which also contributed to the initial reduction of bacteria in the nasal cavity. Three main patterns of shedding were identified: i- bacteria were shed intermittently (46% of individuals), ii- bacteria shedding fell with the progression of the infection (31%) and iii- individuals never shed bacteria despite being infected (23%). Differences in the initial number of bacteria shed between the first two groups were associated with differences in the level of serum antibodies and white blood cells. These results suggest that the immunological conditions at the early stage of the infection may play a role in modulating the long term dynamics of B. bronchiseptica shedding. CONCLUSIONS: We propose that IgG influences the threshold of bacteria in the oro-nasal cavity which then affects the intensity and duration of individual shedding. In addition, we suggest that a threshold level of infection is required for shedding, below this value individuals never shed bacteria despite being infected. The mechanisms regulating these interactions are still obscure and more studies are needed to understand the persistence of bacteria in the upper respiratory tract and the processes controlling the intensity and duration of shedding. PMID- 20738863 TI - Genome sequences of human adenovirus 14 isolates from mild respiratory cases and a fatal pneumonia, isolated during 2006-2007 epidemics in North America. AB - BACKGROUND: Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI). Last reported in Eurasia in 1963, this virus has since been conspicuously absent in broad surveys, and was never isolated in North America despite inclusion of specific tests for this serotype in surveillance methods. In 2006 and 2007, this virus suddenly emerged in North America, causing high attack rate epidemics of FRI and, in some cases, severe pneumonias and occasional fatalities. Some outbreaks have been relatively mild, with low rates of progression beyond uncomplicated FRI, while other outbreaks have involved high rates of more serious outcomes. METHODOLOGY AND FINDINGS: In this paper we present the complete genomic sequence of this emerging pathogen, and compare genomic sequences of isolates from both mild and severe outbreaks. We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in Eurasia 30 years ago and the closely related sequence of HAdV-11a, which has been circulating in southeast Asia. CONCLUSIONS: The data suggest that the currently circulating strain of HAdV-14 is closely related to the historically recognized prototype throughout its genome, though it does display a couple of potentially functional mutations in the fiber knob and E1A genes. There are no polymorphisms that suggest an obvious explanation for the divergence in severity between outbreak events, suggesting that differences in outcome are more likely environmental or host determined rather than viral genetics. PMID- 20738865 TI - Occurrence and genetic variability of Phlebotomus papatasi in an urban area of southern Italy. AB - BACKGROUND: A phlebotomine sand fly was noticed in the second floor of an old building in a highly urbanized area of southern Italy. A short-term entomological survey was carried out in the subsequent weeks to this event, allowing the collection of additional phlebotomine sand flies that were later identified as Phlebotomus papatasi. We assessed the genetic variability among P. papatasi sequences obtained in this study and those available from Italy using a mitochondrial DNA (mtDNA) fragment (from cytochrome b gene to NADH1) and the internal transcribed spacer 2 (ITS2) as genetic markers. RESULTS: From 9 June to 19 July, eight males and seven females (two blood-fed) of P. papatasi were collected in the old town of Bari (southern Italy). The insects were found near the bed and in the bathroom and potential blood sources (e.g., pigeons and dogs) for them were common in the neighbourhood. Again, five females of P. papatasi collected in Valenzano, another urban area in the province of Bari, were also identified and included in the genetic study. The mtDNA sequences (945 bp) obtained from Bari and Valenzano were identical except for a single transition (T <-> C) at the 793 nucleotide residue. Pairwise comparison of the last 440 bp of the mtDNA fragment analyzed herein with other sequences of P. papatasi from Italy revealed a nucleotide variation ranging from 0.2 to 1.3%. Three ITS2 sequence types were detected within specimens collected in Valenzano, one of them identical to that from Bari. Pairwise comparison of ITS2 sequences of P. papatasi from Italy revealed a nucleotide variation up to 1.8%. CONCLUSIONS: This study reports the occurrence of P. papatasi in an urban area of southern Italy and shows a low nucleotide difference among ITS2 and mtDNA sequences of this species available from Italy. The presence of P. papatasi in urban areas might represent a risk for human health, particularly for the potential transmission of sandfly fever viruses. PMID- 20738864 TI - Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. AB - Increased reliance on computational approaches in the life sciences has revealed grave concerns about how accessible and reproducible computation-reliant results truly are. Galaxy http://usegalaxy.org, an open web-based platform for genomic research, addresses these problems. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Pages are interactive, web-based documents that provide users with a medium to communicate a complete computational analysis. PMID- 20738866 TI - Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. AB - BACKGROUND: Pericytes are integral members of the neurovascular unit. Using mouse models lacking endothelial-secreted platelet derived growth factor-B (PDGF-B) or platelet derived growth factor receptor beta (PDGFRbeta) on pericytes, it has been demonstrated that PDGF-B/PDGFRbeta interactions mediate pericyte recruitment to the vessel wall in the embryonic brain regulating the development of the cerebral microcirculation and the blood-brain barrier (BBB). Relatively little is known, however, about the roles of PDGF-B/PDGFRbeta interactions and pericytes in the adult brain in part due to a lack of adequate and/or properly characterized experimental models. To address whether genetic disruption of PDGFRbeta signaling would result in a pericyte-specific insult in adult mice, we studied the pattern and cellular distribution of PDGFRbeta expression in the brain in adult control mice and F7 mice that express two hypomorphic Pdgfrbeta alleles containing seven point mutations in the cytoplasmic domain of PDGFRbeta that impair downstream PDGFRbeta receptor signaling. RESULTS: Using dual fluorescent in situ hybridization, immunofluorescent staining for different cell types in the neurovascular unit, and a fluorescent in situ proximity ligation assay to visualize molecular PDGF-B/PDGFRbeta interactions on brain tissue sections, we show for the first time that PDGFRbeta is exclusively expressed in pericytes, and not in neurons, astrocytes or endothelial cells, in the adult brain of control 129S1/SvlmJ mice. PDGFRbeta co-localized only with well-established pericyte markers such as Chondroitin Sulfate Proteoglycan NG2 and the xLacZ4 transgenic reporter. We next confirm pericyte-specific PDGFRbeta expression in the brains of F7 mutants and show that these mice are viable in spite of substantial 40-60% reductions in regional pericyte coverage of brain capillaries. CONCLUSIONS: Our data show that PDGFRbeta is exclusively expressed in pericytes in the adult 129S1/Sv1mJ and F7 mouse brain. Moreover, our findings suggest that genetic disruption of PDGFRbeta signaling results in a pericyte-specific insult in adult F7 mutants and will not exert a primary effect on neurons because PDGFRbeta is not expressed in neurons of the adult 129S1/SvlmJ and F7 mouse brain. Therefore, mouse models with normal and deficient PDGFRbeta signaling on a 129S1/SvlmJ background may effectively be used to deduce the specific roles of pericytes in maintaining the cerebral microcirculation and BBB integrity in the adult and aging brain as well as during neurodegenerative and brain vascular disorders. PMID- 20738868 TI - When snacks become meals: How hunger and environmental cues bias food intake. AB - BACKGROUND: While environmental and situational cues influence food intake, it is not always clear how they do so. We examine whether participants consume more when an eating occasion is associated with meal cues than with snack cues. We expect their perception of the type of eating occasion to mediate the amount of food they eat. In addition, we expect the effect of those cues on food intake to be strongest among those who are hungry. METHODS: One-hundred and twenty-two undergraduates (75 men, 47 women; mean BMI = 22.8, SD = 3.38) were randomly assigned to two experimental conditions in which they were offered foods such as quesadillas and chicken wings in an environment that was associated with either meal cues (ceramic plates, glasses, silverware, and cloth napkins at a table), or snack cues (paper plates and napkins, plastic cups, and no utensils). After participants finished eating, they were asked to complete a questionnaire that assessed their hunger, satiety, perception of the foods, and included demographic and anthropometric questions. In addition, participants' total food intake was recorded. RESULTS: Participants who were in the presence of meal-related cues ate 27.9% more calories than those surrounded with snack cues (416 versus 532 calories). The amount participants ate was partially mediated by whether they perceived the eating occasion to be a meal or a snack. In addition, the effect of the environmental cues on intake was most pronounced among participants who were hungry. CONCLUSIONS: The present study demonstrated that environmental and situational cues associated with an eating occasion could influence overall food intake. People were more likely to eat foods when they were associated with meal cues. Importantly, the present study reveals that the effect of these cues is uniquely intertwined with cognition and motivation. First, people were more likely to eat ambiguous foods when they perceived them as a meal rather than a snack. Second, the effect of the environmental cues on intake was only observed among those who were hungry. PMID- 20738867 TI - Mesenchymal cell survival in airway and interstitial pulmonary fibrosis. AB - Fibrotic reactions in the airways of the lung or the pulmonary interstitium are a common pathologic outcome after exposure to a wide variety of toxic agents, including metals, particles or fibers. The survival of mesenchymal cells (fibroblasts and myofibroblasts) is a key factor in determining whether a fibroproliferative response that occurs after toxic injury to the lung will ultimately resolve or progress to a pathologic state. Several polypeptide growth factors, including members of the platelet-derived growth factor (PDGF) family and the epidermal growth factor (EGF) family, are prosurvival factors that stimulate a replicative and migratory mesenchymal cell phenotype during the early stages of lung fibrogenesis. This replicative phenotype can progress to a matrix synthetic phenotype in the presence of transforming growth factor-beta1 (TGF beta1). The resolution of a fibrotic response requires growth arrest and apoptosis of mesenchymal cells, whereas progressive chronic fibrosis has been associated with mesenchymal cell resistance to apoptosis. Mesenchymal cell survival or apoptosis is further influenced by cytokines secreted during Th1 inflammation (e.g., IFN-gamma) or Th2 inflammation (e.g., IL-13) that modulate the expression of growth factor activity through the STAT family of transcription factors. Understanding the mechanisms that regulate the survival or death of mesenchymal cells is central to ultimately developing therapeutic strategies for lung fibrosis. PMID- 20738869 TI - Retraction: Trapping mosquitoes using milk products as odour baits in western Kenya. PMID- 20738870 TI - Dietary olive oil effect on antioxidant status and fatty acid profile in the erythrocyte of 2,4-D- exposed rats. AB - BACKGROUND: Oxidative stress produced by reactive oxygen species (ROS) has been linked to the development of several diseases such as cardiovascular, cancer, and neurodegenerative diseases. This study investigates the possible protective effect of extra virgin olive oil (EVOO), lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) on oxidative stress and fatty acid profile of erythrocytes in 2,4-D treated rats. METHODS: Male Wistar rats were divided randomly into eight groups: control (C), (2,4-D) at a dose of 5 mg/kg b.w., (2,4 D/EVOO) was given 2,4-D plus EVOO, (2,4-D/OOHF) that received 2,4-D plus hydrophilic fraction, (2,4-D/OOLF) treated with 2,4-D plus lipophilic fraction, (EVOO) that received only EVOO, (OOHF) was given hydrophilic fraction and (OOLF) treated with lipophilic fraction. These components were daily administered by gavages for 4 weeks. RESULTS: 2,4-D treatment lead to decrease of antioxidant enzyme activities, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) associated with a higher amount of MDA level. Erythrocyte membranes' fatty acid composition was also significantly modified with 2,4-D exposure. EVOO and hydrophilic fraction supplemented to rats with or not 2,4-D treatment enhanced the antioxidant enzyme activities and reduced the MDA level. However, lipophilic fraction did not show any improvement in oxidative damage induced by 2,4-D in spite its richness in MUFA and vitamins. CONCLUSION: EVOO administered to 2,4-D-treated rats protected erythrocyte membranes against oxidative damage by means of preventing excessive lipid peroxidation to increase the MUFA composition and increase maintaining antioxidants enzymes at normal concentrations. PMID- 20738871 TI - A cost minimisation analysis in teledermatology: model-based approach. AB - BACKGROUND: Although store-and-forward teledermatology is increasingly becoming popular, evidence on its effects on efficiency and costs is lacking. The aim of this study, performed in addition to a clustered randomised trial, was to investigate to what extent and under which conditions store-and-forward teledermatology can reduce costs from a societal perspective. METHODS: A cost minimisation study design (a model based approach) was applied to compare teledermatology and conventional process costs per dermatology patient care episode. Regarding the societal perspective, total mean costs of investment, general practitioner, dermatologists, out-of-pocket expenses and employer costs were calculated. Uncertainty analysis was performed using Monte Carlo simulation with 31 distributions in the used cost model. Scenario analysis was performed using one-way and two-way sensitivity analyses with the following variables: the patient travel distance to physician and dermatologist, the duration of teleconsultation activities, and the proportion of preventable consultations. RESULTS: Total mean costs of teledermatology process were ?387 (95%CI, 281 to 502.5), while the total mean costs of conventional process costs were ?354.0 (95%CI, 228.0 to 484.0). The total mean difference between the processes was ?32.5 (95%CI, -29.0 to 74.7). Savings by teledermatology can be achieved if the distance to a dermatologist is larger (> = 75 km) or when more consultations (> = 37%) can be prevented due to teledermatology. CONCLUSIONS: Teledermatology, when applied to all dermatology referrals, has a probability of 0.11 of being cost saving to society.In order to achieve cost savings by teledermatology, teledermatology should be applied in only those cases with a reasonable probability that a live consultation can be prevented. TRIAL REGISTRATION: This study is performed partially based on PERFECT D Trial (Current Controlled Trials No. ISRCTN57478950). PMID- 20738872 TI - Antibiotic control of antibiotic resistance in hospitals: a simulation study. AB - BACKGROUND: Using mathematical deterministic models of the epidemiology of hospital-acquired infections and antibiotic resistance, it has been shown that the rates of hospital-acquired bacterial infection and frequency of antibiotic infections can be reduced by (i) restricting the admission of patients colonized with resistant bacteria, (ii) increasing the rate of turnover of patients, (iii) reducing transmission by infection control measures, and (iv) the use of second line drugs for which there is no resistance. In an effort to explore the generality and robustness of the predictions of these deterministic models to the real world of hospitals, where there is variation in all of the factors contributing to the incidence of infection, we developed and used a stochastic model of the epidemiology of hospital-acquired infections and resistance. In our analysis of the properties of this model we give particular consideration different regimes of using second-line drugs in this process. METHODS: We developed a simple model that describes the transmission of drug-sensitive and drug-resistant bacteria in a small hospital. Colonized patients may be treated with a standard drug, for which there is some resistance, and with a second-line drug, for which there is no resistance. We then ran deterministic and stochastic simulation programs, based on this model, to predict the effectiveness of various treatment strategies. RESULTS: The results of the analysis using our stochastic model support the predictions of the deterministic models; not only will the implementation of any of the above listed measures substantially reduce the incidences of hospital-acquired infections and the frequency of resistance, the effects of their implementation should be seen in months rather than the years or decades anticipated to control resistance in open communities. How effectively and how rapidly the application of second-line drugs will contribute to the decline in the frequency of resistance to the first-line drugs depends on how these drugs are administered. The earlier the switch to second-line drugs, the more effective this protocol will be. Switching to second-line drugs at random is more effective than switching after a defined period or only after there is direct evidence that the patient is colonized with bacteria resistant to the first antibiotic. CONCLUSIONS: The incidence of hospital-acquired bacterial infections and frequencies of antibiotic resistant bacteria can be markedly and rapidly reduced by different readily implemented procedures. The efficacy using second line drugs to achieve these ends depends on the protocol used for their administration. PMID- 20738873 TI - Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis. AB - BACKGROUND: In mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral homeostasis (HH) by controlling water excretion at the level of the kidneys. Our current understanding of the HH and AVP secretion is the result of a vast amount of data collected over the five past decades. This experimental data was collected using a number of systems under different conditions, giving a fragmented view of the components involved in HH. RESULTS: Here, we present a high-level model of the rat HH based on selected published results to predict short-term (hours) to long-term (days) variation of six major homeostatic parameters: (1) the extracellular sodium concentration, (2) the AVP concentration, (3) the intracellular volume, (4) the extracellular volume, (5) the urine volume and (6) the water intake. The simulation generates quantitative predictions like the daily mean of the extracellular sodium concentration (142.2 mmol/L), the AVP concentration, (1.7 pg/ml), the intracellular volume (45.3 ml/100 g body weight--bw), the extracellular volume (22.6 ml/100 g bw), the urine volume (11.8 ml/100 g bw) and the cumulative water intake (18 ml/100 g bw). The simulation also computes the dynamics of all these parameters with a high temporal resolution of one minute. This high resolution predicts the circadian fluctuation of the AVP secretion (5 +/- 2 pg/ml) and defines the limits of a restoration and a maintenance phase in the HH (2.1 pg/ml). Moreover, the simulation can predict the action of pharmacological compounds that disrupt the HH. As an example, we tested the action of a diuretic (furosemide) combined with a sodium deficient diet to generate quantitative prediction on the extracellular sodium concentration (134 mmol/L) and the need induced water intake (20.3 ml/100 g bw). These simulated data are compatible with experimental data (136 +/- 3 mmol/L and 17.5 +/- 3.5 ml/100 g bw, respectively). CONCLUSION: The quantitative agreement of the predictions with published experimental data indicates that our simplified model of the HH integrates most of the essential systems to predict realistic physiological values and dynamics under a set of normal and perturbed hydromineral conditions. PMID- 20738874 TI - Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome. AB - BACKGROUND: Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1). Little is known about the function of human RAI1. RESULTS: We generated the full length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity. CONCLUSION: Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains. PMID- 20738875 TI - Speech recognition software and electronic psychiatric progress notes: physicians' ratings and preferences. AB - BACKGROUND: The context of the current study was mandatory adoption of electronic clinical documentation within a large mental health care organization. Psychiatric electronic documentation has unique needs by the nature of dense narrative content. Our goal was to determine if speech recognition (SR) would ease the creation of electronic progress note (ePN) documents by physicians at our institution. METHODS: SUBJECTS: Twelve physicians had access to SR software on their computers for a period of four weeks to create ePN. MEASUREMENTS: We examined SR software in relation to its perceived usability, data entry time savings, impact on the quality of care and quality of documentation, and the impact on clinical and administrative workflow, as compared to existing methods for data entry. DATA ANALYSIS: A series of Wilcoxon signed rank tests were used to compare pre- and post-SR measures. A qualitative study design was used. RESULTS: Six of twelve participants completing the study favoured the use of SR (five with SR alone plus one with SR via hand-held digital recorder) for creating electronic progress notes over their existing mode of data entry. There was no clear perceived benefit from SR in terms of data entry time savings, quality of care, quality of documentation, or impact on clinical and administrative workflow. CONCLUSIONS: Although our findings are mixed, SR may be a technology with some promise for mental health documentation. Future investigations of this nature should use more participants, a broader range of document types, and compare front- and back-end SR methods. PMID- 20738877 TI - Correction: Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus. PMID- 20738876 TI - Withdrawing intra-aortic balloon pump support paradoxically improves microvascular flow. AB - INTRODUCTION: The Intra-Aortic Balloon Pump (IABP) is frequently used to mechanically support the heart. There is evidence that IABP improves microvascular flow during cardiogenic shock but its influence on the human microcirculation in patients deemed ready for discontinuing IABP support has not yet been studied. Therefore we used sidestream dark field imaging (SDF) to test our hypothesis that human microcirculation remains unaltered with or without IABP support in patients clinically ready for discontinuation of mechanical support. METHODS: We studied 15 ICU patients on IABP therapy. Measurements were performed after the clinical decision was made to remove the balloon catheter. We recorded global hemodynamic parameters and performed venous oximetry during maximal IABP support (1:1) and 10 minutes after temporarily stopping the IABP therapy. At both time points, we also recorded video clips of the sublingual microcirculation. From these we determined indices of microvascular perfusion including perfused vessel density (PVD) and microvascular flow index (MFI). RESULTS: Ceasing IABP support lowered mean arterial pressure (74 +/- 8 to 71 +/- 10 mmHg; P = 0.048) and increased diastolic pressure (43 +/- 10 to 53 +/- 9 mmHg; P = 0.0002). However, at the level of the microcirculation we found an increase of PVD of small vessels <20 MUm (5.47 +/- 1.76 to 6.63 +/- 1.90; P = 0.0039). PVD for vessels >20 MUm and MFI for both small and large vessels were unaltered. During the procedure global oxygenation parameters (ScvO2/SvO2) remained unchanged. CONCLUSIONS: In patients deemed ready for discontinuing IABP support according to current practice, SDF imaging showed an increase of microcirculatory flow of small vessels after ceasing IABP therapy. This observation may indicate that IABP impairs microvascular perfusion in recovered patients, although this warrants confirmation. PMID- 20738879 TI - Necessity of immediate cardiopulmonary resuscitation in trauma emergency. AB - The ability to respond quickly and effectively to a cardiac arrest situation rests on nurses being competent in the emergency life-saving procedure of cardiopulmonary resuscitation. The objective of the current study was to evaluate the types of trauma and survival of patients that require immediate cardiopulmonary resuscitation in trauma emergencies. A total of 13301 patients treated as accident victims between July 2004 and December 2006 were evaluated in a prospective study. Patients requiring immediate cardiopulmonary resuscitation at admission were identified. The type of injury and the survival of these patients were evaluated.Of the 65 patients included in the study, 30% had suffered from gunshot wounds, 19% had been run over, 18% had been involved in car crashes, 13% in motor cycle accidents, 9% stabbings, 1% by cycle accidents and 10% other types of accidents including burns, hangings and falls. In only 12 of these patients, immediate resuscitation was successful and procedure such as chest drainage, exploratory laparotomy and interventions in the surgical center were performed. However all patients evolved to death; eight within 24 hours, two between 24 and 48 hours and the other 2 after 48 hours.Immediate cardiopulmonary resuscitation after accidents is a sign of high mortality requiring further studies to review indication and the ethical aspects involved. PMID- 20738878 TI - Seroepidemiology of pandemic influenza A (H1N1) 2009 virus infections in Pune, India. AB - BACKGROUND: In India, Pune was one of the badly affected cities during the influenza A (H1N1) 2009 pandemic. We undertook serosurveys among the risk groups and general population to determine the extent of pandemic influenza A (H1N1) 2009 virus infections. METHODS: Pre-pandemic sera from the archives, collected during January 2005 to March 2009, were assayed for the determination of baseline seropositivity. Serosurveys were undertaken among the risk groups such as hospital staff, general practitioners, school children and staff and general population between 15th August and 11th December 2009. In addition, the PCR confirmed pandemic influenza A (H1N1) 2009 cases and their household contacts were also investigated. Haemagglutination-inhibition (HI) assays were performed using turkey red blood cells employing standard protocols. A titre of >or=1:40 was considered seropositive. RESULTS: Only 2 (0.9%) of the 222 pre-pandemic sera were positive. The test-retest reliability of HI assay in 101 sera was 98% for pandemic H1N1, 93.1% for seasonal H1N1 and 94% for seasonal H3N2. The sera from 48 (73.8%) of 65 PCR-confirmed pandemic H1N1 cases in 2009 were positive. Seropositivity among general practitioners increased from 4.9% in August to 9.4% in November and 15.1% in December. Among hospital staff, seropositivity increased from 2.8% in August to 12% in November. Seropositivity among the schools increased from 2% in August to 10.7% in September. The seropositivity among students (25%) was higher than the school staff in September. In a general population survey in October 2009, seropositivity was higher in children (9.1%) than adults (4.3%). The 15-19 years age group showed the highest seropositivity of 20.3%. Seropositivity of seasonal H3N2 (55.3%) and H1N1 (26.4%) was higher than pandemic H1N1 (5.7%) (n = 2328). In households of 74 PCR-confirmed pandemic H1N1 cases, 25.6% contacts were seropositive. Almost 90% pandemic H1N1 infections were asymptomatic or mild. Considering a titre cut off of 1:10, seropositivity was 1.5-3 times as compared to 1:40. CONCLUSIONS: Pandemic influenza A (H1N1) 2009 virus infection was widespread in all sections of community. However, infection was significantly higher in school children and general practitioners. Hospital staff had the lowest infections suggesting the efficacy of infection control measures. PMID- 20738880 TI - The Gln27Glu polymorphism in beta2-adrenergic receptor gene is linked to hypertriglyceridemia, hyperinsulinemia and hyperleptinemia in Saudis. AB - BACKGROUND: beta2-adrenoceptor (beta2AR) gene polymorphism glutamine 27 glutamic acid (Gln27Glu) and Arg16Gly were reported to have an association with obesity and obesity related disorders in some population. We evaluated Gln27Glu polymorphism in the beta2AR gene in obese Saudi populations to investigate the association of beta2AR gene with obesity and other related metabolic parameters. DESIGN: We studied possible association of Gln27Glu in beta2AR gene with body mass index (BMI), anthropometric measurements and other metabolic parameters. The beta2AR gene polymorphism (Gln27Glu) was identified by sequencing PCR products representing locus of interest. Based on BMI, the subjects were divided into three groups, normal weight, overweight and obese. The genotype and allele frequency were calculated separately for each group. RESULTS: The allelic frequency of Glu27 did not differ amongst the three groups, though the Glu27 homozygote (Glu/Glu) were more in obese subjects and had higher concentration of triglyceride, leptin and insulin compared to in the Gln27 heterozygotes and Gln/Gln homozygotes. CONCLUSIONS: In this study we were able to provide evidence on the influence of Gln27Glu genetic variant of beta2AR gene on lipid phenotypes, insulin and leptin levels in the Saudi populations. PMID- 20738881 TI - The evolutionary history of histone H3 suggests a deep eukaryotic root of chromatin modifying mechanisms. AB - BACKGROUND: The phenotype of an organism is an outcome of both its genotype, encoding the primary sequence of proteins, and the developmental orchestration of gene expression. The substrate of gene expression in eukaryotes is the chromatin, whose fundamental units are nucleosomes composed of DNA wrapped around each two of the core histone types H2A, H2B, H3 and H4. Key regulatory steps involved in the determination of chromatin conformations are posttranslational modifications (PTM) at histone tails as well as the assembly of histone variants into nucleosomal arrays. Although the mechanistic background is fragmentary understood, it appears that the chromatin signature of metazoan cell types is inheritable over generations. Even less understood is the conservation of epigenetic mechanisms among eukaryotes and their origins. RESULTS: In the light of recent progress in understanding the tree of eukaryotic life we discovered the origin of histone H3 by phylogenetic analyses of variants from all supergroups, which allowed the reconstruction of ancestral states. We found that H3 variants evolved frequently but independently within related species of almost all eukaryotic supergroups. Interestingly, we found all core histone types encoded in the genome of a basal dinoflagellate and H3 variants in two other species, although is was reported that dinoflagellate chromatin is not organized into nucleosomes.Most probably one or more animal/nuclearid H3.3-like variants gave rise to H3 variants of all opisthokonts (animals, choanozoa, fungi, nuclearids, Amoebozoa). H3.2 and H3.1 as well as H3.1t are derivatives of H3.3, whereas H3.2 evolved already in early branching animals, such as Trichoplax. H3.1 and H3.1t are probably restricted to mammals.We deduced a model for protoH3 of the last eukaryotic common ancestor (LECA) confirming a remarkable degree of sequence conservation in comparison to canonical human H3.1. We found evidence that multiple PTMs are conserved even in putatively early branching eukaryotic taxa (Euglenozoa/Excavata). CONCLUSIONS: At least a basal repertoire of chromatin modifying mechanisms appears to share old common ancestry and may thus be inherent to all eukaryotes. We speculate that epigenetic principles responsive to environmental triggers may have had influenced phenotypic variation and concomitantly may potentially have had impact on eukaryotic diversification. PMID- 20738882 TI - Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy. AB - A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population. PMID- 20738883 TI - Soft-tissue perineurioma of the retroperitoneum in a 63-year-old man, computed tomography and magnetic resonance imaging findings: a case report. AB - INTRODUCTION: Soft-tissue perineuriomas are rare benign peripheral nerve sheath tumors in the subcutis of the extremities and the trunks of young patients. To our knowledge, this the first presentation of the computed tomography and magnetic resonance imaging of a soft-tissue perineurioma in the retroperitoneum with pathologic correlation. CASE PRESENTATION: A 63-year-old Japanese man was referred for assessment of high blood pressure. Abdominal computed tomography and magnetic resonance imaging showed a well-defined, gradually enhancing tumor without focal degeneration or hemorrhage adjacent to the pancreatic body. Tumor excision with distal pancreatectomy and splenectomy was performed, as a malignant tumor of pancreatic origin could not be ruled out. No recurrence has been noted in the 16 months since the operation. Pathologic examination of the tumor revealed a soft-tissue perineurioma of the retroperitoneum. CONCLUSION: Although the definitive diagnosis of soft-tissue perineurioma requires biopsy and immunohistochemical reactivity evaluation, the computed tomography and magnetic resonance imaging findings described in this report suggest inclusion of this rare tumor in the differential diagnosis when such findings occur in the retroperitoneum. PMID- 20738884 TI - Sampling and coverage issues of telephone surveys used for collecting health information in Australia: results from a face-to-face survey from 1999 to 2008. AB - BACKGROUND: To examine the trend of "mobile only" households, and households that have a mobile phone or landline telephone listed in the telephone directory, and to describe these groups by various socio-demographic and health indicators. METHOD: Representative face-to-face population health surveys of South Australians, aged 15 years and over, were conducted in 1999, 2004, 2006, 2007 and 2008 (n = 14285, response rates = 51.9% to 70.6%). Self-reported information on mobile phone ownership and usage (1999 to 2008) and listings in White Pages telephone directory (2006 to 2008), and landline telephone connection and listings in the White Pages (1999 to 2008), was provided by participants. Additional information was collected on self-reported health conditions and health-related risk behaviours. RESULTS: Mobile only households have been steadily increasing from 1.4% in 1999 to 8.7% in 2008. In terms of sampling frame for telephone surveys, 68.7% of South Australian households in 2008 had at least a mobile phone or landline telephone listed in the White Pages (73.8% in 2006; 71.5% in 2007). The proportion of mobile only households was highest among young people, unemployed, people who were separated, divorced or never married, low income households, low SES areas, rural areas, current smokers, current asthma or people in the normal weight range. The proportion with landlines or mobiles telephone numbers listed in the White Pages telephone directory was highest among older people, married or in a defacto relationship or widowed, low SES areas, rural areas, people classified as overweight, or those diagnosed with arthritis or osteoporosis. CONCLUSION: The rate of mobile only households has been increasing in Australia and is following worldwide trends, but has not reached the high levels seen internationally (12% to 52%). In general, the impact of mobile telephones on current sampling frames (exclusion or non-listing of mobile only households or not listed in the White Pages directory) may have a low impact on health estimates obtained using telephone surveys. However, researchers need to be aware that mobile only households are distinctly different to households with a landline connection, and the increase in the number of mobile-only households is not uniform across all groups in the community. Listing in the White Pages directory continues to decrease and only a small proportion of mobile only households are listed. Researchers need to be aware of these telephone sampling issues when considering telephone surveys. PMID- 20738885 TI - Effect of pathology type and severity on the distribution of MRI signal intensities within the degenerated nucleus pulposus: application to idiopathic scoliosis and spondylolisthesis. AB - BACKGROUND: Disc degeneration is characterized by a loss of cellularity, degradation of the extracellular matrix, and, as a result, morphological changes and biomechanical alterations. We hypothesized that the distribution of the MR signal intensity within the nucleus zone of the intervertebral disc was modified according to the pathology and the severity of the pathology. The objective of this study was to propose new parameters characterizing the distribution of the signal intensity within the nucleus zone of lumbar intervertebral discs, and to quantify these changes in patients suffering from spondylolisthesis or idiopathic scoliosis. METHODS: A retrospective study had been performed on T2-weighted MR images of twenty nine patients suffering from spondylolisthesis and/or scoliosis. The high intensity zone of the nucleus pulposus was semi-automatically detected. The distance "DX" between the center weighted by the signal intensity and the geometrical center was quantified. The sum of the signal intensity on the axis perpendicular to the longitudinal axis of the disc was plotted for each position of the longitudinal axis allowing defining the maximum sum "SM" and its position "PSM". RESULTS: "SM" was clearly higher and "PSM" was more shifted for scoliosis than for spondylolisthesis. A two-way analysis of variance showed that the differences observed on "DX" were not attributed to the pathology nor its severity, the differences observed on "SM" were attributed to the pathology but not to its severity, and the differences observed on "PSM" were attributed to both the pathology and its severity. CONCLUSIONS: The technique proposed in this study showed significant differences in the distribution of the MR signal intensity within the nucleus zone of intervertebral discs due to the pathology and its severity. The dependence of the "PSM" parameter to the severity of the pathology suggests this parameter as a predictive factor of the pathology progression. This new technique should be useful for the early diagnosis of intervertebral disc pathologies as it highlights abnormal patterns in the MRI signal for low severity of the pathology. PMID- 20738886 TI - Increase of aqueous inflammatory factors in macular edema with branch retinal vein occlusion: a case control study. AB - BACKGROUND: This study investigated whether soluble intercellular adhesion molecule-1 (sICAM-1) has a role in the pathogenesis of macular edema associated with branch retinal vein occlusion (BRVO) together with vascular endothelial growth factor (VEGF). METHODS: A retrospective case control study was performed in 22 patients with BRVO and macular edema, as well as 10 patients with nonischemic ocular diseases as the control group. Retinal ischemia was evaluated by measuring the area of capillary non-perfusion with Scion Image software, while the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained during the performance of combined vitrectomy and cataract surgery. sICAM-1 and VEGF levels in aqueous humor and plasma specimens were determined by enzyme-linked immunosorbent assay. RESULTS: Aqueous humor levels of sICAM-1 (median: 6.90 ng/ml) and VEGF (median: 169 pg/ml) were significantly elevated in BRVO patients compared with the control group (median: 3.30 pg/ml and 15.6 pg/ml, respectively) (P = 0.005 and P < 0.001, respectively). The aqueous humor level of sICAM-1 was significantly correlated with that of VEGF (P = 0.025). In addition, aqueous levels of both sICAM-1 and VEGF were correlated with the size of the non-perfused area of the retina in BRVO patients (P = 0.021 and P < 0.001, respectively). Furthermore, aqueous levels of sICAM-1 and VEGF were both correlated with the severity of macular edema (P = 0.020 and P = 0.005, respectively). CONCLUSIONS: Both sICAM-1 and VEGF may be involved in the pathogenesis of macular edema associated with BRVO. Measurement of aqueous humor sICAM-1 levels may be useful for assessment of BRVO patients with macular edema, in addition to measurement of VEGF. PMID- 20738887 TI - Ethics, economics and the regulation and adoption of new medical devices: case studies in pelvic floor surgery. AB - BACKGROUND: Concern has been growing in the academic literature and popular media about the licensing, introduction and adoption of surgical devices before full effectiveness and safety evidence is available to inform clinical practice. Our research will seek empirical survey evidence about the roles, responsibilities, and information and policy needs of the key stakeholders in the introduction into clinical practice of new surgical devices for pelvic floor surgery, in terms of the underlying ethical principals involved in the economic decision-making process, using the example of pelvic floor procedures. METHODS/DESIGN: Our study involves three linked case studies using, as examples, selected pelvic floor surgery devices representing Health Canada device safety risk classes: low, medium and high risk. Data collection will focus on stakeholder roles and responsibilities, information and policy needs, and perceptions of those of other key stakeholders, in seeking and using evidence about new surgical devices when licensing and adopting them into practice. For each class of device, interviews will be used to seek the opinions of stakeholders. The following stakeholders and ethical and economic principles provide the theoretical framework for the study: Stakeholders--federal regulatory body, device manufacturers, clinicians, patients, health care institutions, provincial health departments, and professional societies. Clinical settings in two centres (in different provinces) will be included. Ethics--beneficence, non-maleficence, autonomy, justice. Economics--scarcity of resources, choices, opportunity costs.For each class of device, responses will be analysed to compare and contrast between stakeholders. Applied ethics and economic theory, analysis and critical interpretation will be used to further illuminate the case study material. DISCUSSION: The significance of our research in this new area of ethics will lie in providing recommendations for regulatory bodies, device manufacturers, clinicians, health care institutions, policy makers and professional societies, to ensure surgical patients receive sufficient information before providing consent for pelvic floor surgery. In addition, we shall provide a wealth of information for future study in other areas of surgery and clinical management, and provide suggestions for changes to health policy. PMID- 20738888 TI - Watching TV news as a memory task--brain activation and age effects. AB - BACKGROUND: Neuroimaging studies which investigate brain activity underlying declarative memory processes typically use artificial, unimodal laboratory stimuli. In contrast, we developed a paradigm which much more closely approximates real-life situations of information encoding. METHODS: In this study, we tested whether ecologically valid stimuli--clips of a TV news show--are apt to assess memory-related fMRI activation in healthy participants across a wide age range (22-70 years). We contrasted brain responses during natural stimulation (TV news video clips) with a control condition (scrambled versions of the same clips with reversed audio tracks). After scanning, free recall performance was assessed. RESULTS: The memory task evoked robust activation of a left-lateralized network, including primarily lateral temporal cortex, frontal cortex, as well as the left hippocampus. Further analyses revealed that--when controlling for performance effects--older age was associated with greater activation of left temporal and right frontal cortex. CONCLUSION: We demonstrate the feasibility of assessing brain activity underlying declarative memory using a natural stimulation paradigm with high ecological validity. The preliminary result of greater brain activation with increasing age might reflect an attempt to compensate for decreasing episodic memory capacity associated with aging. PMID- 20738889 TI - Synchrotron UV fluorescence microscopy uncovers new probes in cells and tissues. AB - Use of deep ultraviolet (DUV, below 350 nm) fluorescence opens up new possibilities in biology because it does not need external specific probes or labeling but instead allows use of the intrinsic fluorescence that exists for many biomolecules when excited in this wavelength range. Indeed, observation of label free biomolecules or active drugs ensures that the label will not modify the biolocalization or any of its properties. In the past, it has not been easy to accomplish DUV fluorescence imaging due to limited sources and to microscope optics. Two worlds were coexisting: the spectrofluorometric measurements with full spectrum information with DUV excitation, which lacked high-resolution localization, and the microscopic world with very good spatial resolution but poor spectral resolution for which the wavelength range was limited to 350 nm. To combine the advantages of both worlds, we have developed a DUV fluorescence microscope for cell biology coupled to a synchrotron beamline, providing fine tunable excitation from 180 to 600 nm and full spectrum acquired on each point of the image, to study DUV excited fluorescence emitted from nanovolumes directly inside live cells or tissue biopsies. PMID- 20738890 TI - Cascading activation across levels of representation in children's lexical processing. AB - Recent work in adult psycholinguistics has demonstrated that activation of semantic representations begins long before phonological processing is complete. This incremental propagation of information across multiple levels of analysis is a hallmark of adult language processing but how does this ability develop? In two experiments, we elicit measures of incremental activation of semantic representations during word recognition in children. Five-year-olds were instructed to select a target (logs) while their eye-movements were measured to a competitor (key) that was semantically related to an absent phonological associate (lock). We found that, like adults, children made increased looks to competitors relative to unrelated control items. However, unlike adults, children continued to look at the competitor even after the target word was uniquely identified and were more likely to incorrectly select this item. Altogether, these results suggest that early lexical processing involves cascading activation but less efficient resolution of competing entries. PMID- 20738891 TI - Bilingual children's acquisition of the past tense: a usage-based approach. AB - Bilingual and monolingual children's (mean age=4;10) elicited production of the past tense in both English and French was examined in order to test predictions from Usage-Based theory regarding the sensitivity of children's acquisition rates to input factors such as variation in exposure time and the type/token frequency of morphosyntactic structures. Both bilingual and monolingual children were less accurate with irregular than regular past tense forms in both languages. Bilingual children, as a group, were less accurate than monolinguals with the English regular and irregular past tense, and with the French irregular past tense, but not with the French regular past tense. However, bilingual children were as accurate as monolinguals with the past tense in their language of greater exposure, except for English irregular verbs. It is argued that these results support the view that children's acquisition rates are sensitive to input factors, but with some qualifications. PMID- 20738892 TI - Mastering inflectional suffixes: a longitudinal study of beginning writers' spellings*. AB - This study tracked the order in which ten beginning spellers (M age=5 ; 05; SD=0.21 years) mastered the correct spellings of common inflectional suffixes in English. Spellings from children's journals from kindergarten and grade 1 were coded. An inflectional suffix was judged to be mastered when children spelled it accurately in 90 percent of the contexts in which it was grammatically required, a criterion used to study the order of acquisition of grammatical morphemes in oral language. The results indicated that the order in which children learned to spell inflectional suffixes correctly is similar to the order in which they learn to use them in oral language, before school age. Discrepancies between the order of mastery for inflectional suffixes in written and oral language are discussed in terms of English spelling conventions, which introduce variables into the spelling of inflected words that are not present in oral language. PMID- 20738897 TI - [Pay more efforts on lung cancer research, to improve the therapeutic effects of N2 lung cancer.]. PMID- 20738896 TI - Evolution in the management of Hirschsprung's disease in the UK and Ireland: a national survey of practice revisited. AB - INTRODUCTION: The management of Hirschsprung's disease continues to evolve. This questionnaire survey aimed to determine current surgical management strategies for Hirschsprung's disease in Britain. SUBJECTS AND METHODS: The survey was sent electronically to all British paediatric surgeons. Initial questions explored individual experience and regional service provision. Additional questions, reserved for surgeons who perform definitive Hirschsprung's disease surgery, addressed specific clinical scenarios. RESULTS: Surveys were sent to 142 surgeons yielding 85 responses. After exclusions, 64 surveys from 21 centres were analysed. Forty-seven respondents worked in centres with designated 'Hirschsprung's disease surgeons'. Forty respondents perform definitive Hirschsprung's disease surgery. In a well neonate with left-sided Hirschsprung's disease, 34 of 40 surgeons favour primary pull-through following bowel decompression with rectal washouts; 35 of 40 surgeons aim to perform definitive surgery at less than 3 months of age, with 17 favouring laparoscopic-assisted Soave-Boley and 15 favouring an open Duhamel pull-through. Of the 40 surgeons, 36 use a staged approach to right-sided/total colonic Hirschsprung's disease with 23 favouring a Duhamel or Long Duhamel pull-through. CONCLUSIONS: The primary pull through, using an open Duhamel or laparoscopic-assisted Soave-Boley technique, during the first 3 months of life, has become the operative strategy of choice in rectosigmoid Hirschsprung's disease in Britain. Marked variation in practice remains for right-sided Hirschsprung's disease. PMID- 20738898 TI - [Progress of surgical therapy for N2 non-small cell lung cancer.]. PMID- 20738899 TI - Is there a role for surgery in stage IIIA-N2 non-small cell lung cancer? AB - The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) remains controversial. Most important prognostic factors are mediastinal downstaging and complete surgical resection. Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive, invasive and alternative or minimally invasive techniques. In contrast to imaging or functional studies, remediastinoscopy provides pathological evidence of response after induction therapy. Although technically more challenging than a first procedure, remediastinoscopy can select patients for subsequent thoracotomy and provides prognostic information. An alternative approach consists of the use of minimally invasive staging procedures as endobronchial or endoscopic esophageal ultrasound to obtain an initial proof of mediastinal nodal involvement. Mediastinoscopy is subsequently performed after induction therapy to evaluate response. In this way, a technically more difficult remediastinoscopy can be avoided. Stage IIIA-N2 NSCLC represents a heterogenous spectrum of locally advanced disease and different subsets exist. When N2 disease is discovered during thoracotomy after negative, careful preoperative staging a resection should be performed if this can be complete. Postoperative radiotherapy will decrease local recurrence rate but not overall survival. Adjuvant chemotherapy increases survival and is presently recommended in these cases. Most patients with pathologically proven N2 disease detected during preoperative work-up will be treated by induction therapy followed by surgery or radiotherapy. In two large, recently completed, phase III trials there was no difference in overall survival between the surgical and radiotherapy arm, but in one trial there was a difference in progression-free survival in favor of the surgical arm. In the surgery arm the rate of local recurrences was also lower in both trials. Surgical resection may be recommended in those patients with proven mediastinal downstaging after induction therapy who can preferentially be treated by lobectomy. Pneumonectomy has a significantly higher mortality and morbidity rate, especially after induction chemoradiotherapy. Patients with bulky N2 disease are mostly treated with combined chemoradiotherapy although the precise treatment scheme has not been determined yet. PMID- 20738901 TI - Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes. PMID- 20738900 TI - N2 disease in non-small cell lung cancer patients, diagnosis and evaluation: a Turkish chest surgeon's perspective. AB - Mediastinal or N2 disease is the most important factor in selecting the optimal treatment strategy in patients without distant metastasis. A direct surgical resection has not generally been accepted as a treatment modality in whom mediastinal nodal involvement is demonstrated. Patients with lung cancer can be diagnosed as clinical N2 disease based on CT and PET-CT characteristics of the mediastinum and the clinical presentation. Invasive diagnostic modalities used in the detection of N2 disease are: mediastinoscopy, endoesophageal ultrasound guided biopsy (EUS), transbronchial needle aspiration (TBNA), endobronchial ultrasound guided biopsy (EBUS), video-assisted thoracoscopic surgery (VATS), and mediastinotomy/extended mediastinoscopy. In this article, the author discusses about invasive and noninvasive techniques on the evaluation of mediastinal disease and presents his experience on this topic. PMID- 20738902 TI - [Current status of radiotherapy for stage N2 non-small cell lung cancer.]. PMID- 20738903 TI - [Preoperative invasive staging for N2 Non-small cell lung cancer.]. PMID- 20738904 TI - [PET/CT for N2 staging in non-small cell lung cancer.]. PMID- 20738905 TI - [Nonivasive staging of N2 lung cancer: CT staging.]. PMID- 20738906 TI - [Perioperative chemotherapy of stage III N2 non-small cell lung cancer.]. PMID- 20738907 TI - [Chemotherapy on nonresectable stage III N2 non-small cell lung cancer.]. PMID- 20738908 TI - Mediastinal lymphadenectomy influences postoperative immune response after lung cancer surgery. PMID- 20738909 TI - Morbidity and mortality after neoadjuvant therapy and sleeve lobectomyin N2 disease. AB - BACKGROUND: Sleeve resections were introduced to preserve lung function in patients with limited pulmonary reserve. Increasing experience with sleeve resection has reduced the rate of pneumonectomy below 10%. The aim of the study was to assess the outcome after neoadjuvant chemo- or chemoradiotherapy and sleeve resection in patients with N2 non-small cell lung cancer. METHODS: Retrospective analysis of 41 patient records between 01.01.2005 and 31.12.2007 underwent induction therapy in N2-disease followed by tracheobronchial sleeve resection. These patients were compared to the overall results after sleeve resection in our institution. Data analysed were; length of chest tube drainage in days, length of hospital stay, complications, morbidity and hospital mortality. RESULTS: In 178 patients, an anatomical bronchoplastic resection was performed. Preoperative chemotherapy in N2-disease (n =42) was given in 30 patients and radiochemotherapy in 11 patients. The length of the operation was between 94 min-493 min (average 143 min). Chest tubes were removed on average after 5 days. Patients were discharged after 10 days. R0-resection was possible in 90%. The overall complication rate was 27% (11/41). The rate of bronchial anastomotic leakage was 9.7% (4/41). Two patients with postoperative respiratory insufficiency and mechanical ventilation, 1 patient with technical failure required early correction of the suture and one patient with a necrosis of the anastomosis. 30-day hospital mortality rate was 2.4% (1/41). CONCLUSIONS: Sleeve resection after neoadjuvant therapy has a higher local morbidity (anastomotic insufficiency 9.7% vs 2.8%). This may be explained by the quality of the surrounding tissue after neoadjuvant therapy, which compromises healing of the anastomosis. However, the results are comparable to those without induction therapy in terms of radicality, and 30-d mortality rate (P >0.05). We therefore believe that sleeve resection after neoadjuvant therapy should be performed whenever possible to preserve functioning lung tissue. PMID- 20738910 TI - [The value of mediastinoscopy in the staging of lung cancer with clinical N2 disease.]. AB - BACKGROUND: To determine the value of mediastinoscopy in the mediastinal staging of lung cancer with clinical N2 disease. METHODS: We retrospectively reviewed 87 patients received mediastinoscopy for known or suspected lung cancer, including 83 cervical mediastinoscopies and 4 parasternal mediastinoscopies. All patients were staged clinical N2 for enlarged ipsilateral mediastinal and/or subcarinal lymph nodes (short axis > 1.0 cm) on computed tomography scan. RESULTS: Of the 87 patients, 61 cases proved N2 disease on mediastinoscopy. The other 26 mediastinoscopy-negative patients underwent thoracotomy for lung resection and mediastinal lymph node dissection in the same operative session. Final pathologic N staging were consistent for mediastinoscopic sampling and surgical dissection in 24 patients. N2 disease was found in 2 patients (false-negative of mediastinoscopy). The sensitivity, specificity, and accuracy of mediastinoscopy were 96.8%, 100%, and 97.7%, respectively. There was no mortality and only 1 complication (1.1%) for all 87 mediastinoscopic procedures. CONCLUSIONS: Mediastinoscopy is a highly effective and safe procedure for the mediastinal staging of lung cancer with clinical N2 disease. PMID- 20738911 TI - [An experiment study of lung ischemia-reperfusion injury of pulmonary surgery in rabbit model.]. AB - BACKGROUND: The blocking of pulmonary vessels, including the blocking of pulmonary artery and pulmonary circulation, is always applied in the surgical treatment of locally advanced no-small cell lung cancer. However, the blocking of pulmonary vessels will induce lung ischemia-reperfusion injury (LIRI). The aim of this study is to establish pulmonary vessels blocking model in rabbit and to investigate the LIRI in pulmonary surgery. METHODS: 114 New Zealand rabbits were randomly divided into 3 groups: group I, control group; group II, block left pulmonary artery; group III, block left pulmonary artery and vein. After the time of opening chest (group I), 1 h ischemia and 1 h, 2 h, 4 h, 6 h, 24 h reperfusion, the changes of arterial oxygen partial pressure in left pulmonary vein (PaO2) and the content of MDA in left lung tissue were observed. Then the water content of left lung and pathological study was recorded. RESULTS: Homodynamic parameters were stable in all 3 groups. There were significant differences in PaO2, MDA and wet/dry ratio of the lung tissue between I and other two groups at the time of 1 h ischemia and 1 h, 2 h, 4 h, 6 h reperfusion (P <0.05 and P < 0.01), but there was no significant difference between group II and group III (P >0.05), and there was no significant difference among the three groups after 24 h reperfusion (P >0.05). Pathological study revealed that similar injury changes happened between group II and group III, and the obvious injury happened at the time of 4 h reperfusion. At the time of 6 h reperfusion pathological changes in both group II and group III began to recover, and completely recover after 24 h reperfusion. CONCLUSIONS: The lung ischemic reperfusion injury caused by blocking pulmonary artery is similar to that caused by blocking pulmonary artery and veins. It is safe to previously block pulmonary vessels within 1 h during pulmonary surgery. PMID- 20738912 TI - [Identification and characterization of SP cells in human lung adenocarcinoma SPC A1 cells.]. AB - BACKGROUND: Recently, eloquent studies from some solid tumors have provided proofs that cancers originate from cancer stem cells (CSC). The discovery of CSC has changed our view of carcinogenesis and chemotherapy. The aim of this study is to identify and characterize the CSC population that drives and maintains lung adenocarcinoma growth and metastasis. METHODS: Side population (SP) cell analysis combined with serum-free media (SFM) were applied to established human lung adenocarcinoma cell lines. Properties of SP cells were evaluated by their proliferative index, colony-forming efficiency and tumorigenic potential. RESULTS: Characteristic SP cells could be detected by FACS in lung adenocarcinoma cell lines. And the proportion of SP cells is greatly increased after serum-free culture. SP cells have a greater proliferative index, a higher colony-forming efficiency and a greater ability to form tumor in vivo . CONCLUSIONS: SP cells exist in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting. PMID- 20738913 TI - [Construction of a t7 human lung cancer cDNA library.]. AB - BACKGROUND: Currently, only a limited numbers of tumor markers for non small lung cancer (NSCLC) diagnosis, new biomarker, such as serum autoantibody may improve the early detection of lung cancer. Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients. METHODS: mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas, and then mRNA was reverse transcribed into double stranded cDNA. After digestion, the cDNA was inserted into T7Select 10-3 vector. The phage display cDNA library was constructed by package reaction in vitro and plate proliferation. Plaque assay and PCR were used to evaluate the library. RESULTS: Two T7 phage display cDNA library were established. Plaque assay show the titer of lung squamas carcinoma library was 1.8*10(6) pfu, and the adenocarcinoma library was 5*10(6) pfu. The phage titer of the amplified library were 3.2*10(10) pfu/mL and 2.5*10(10) pfu/mL. PCR amplification of random plaque show insert ratio were 100% (24/24) in adenocarcinoma library and 95.8% in human lung squamas carcinoma library (23/24). Insert range from 300 bp to 1 500 bp. CONCLUSIONS: Two phage display cDNA library from NSCLC were constructed. PMID- 20738915 TI - [Expression and significance of clusterin in Anip973/NVB cell lines.]. AB - BACKGROUND: To detect clusterin expression in Anip973/Navelbine (Anip973/NVB) and wild type Anip973, the last one as a control, so as to conform that clusterin be association with the resistance to NVB of NSCLC. We detect the expression of clusterin, p53 and Bax in normal lung tissues and cancer tissues so that to investigate its relationship with lung cancer formation and development. METHODS: Western blot was used to compare the differences in protein levels of clusterin in Anip973/NVB and wild type Anip973 cell lines; Flow cytometry was used to detect the clusterin positive rate, to analyze the relationship between clusterin and cell cycle, p53 or Bax RESULTS: The expression levels of clusterin and p53 in non-small cell lung cancer were significantly higher in Anip973/NVB, than wild type Anip973. It indicated that clusterin might be associated with resistance to NVB in NSCLC. As to drug resistant lung cancer cell lines, Anip973/NVB was more cells in G0-G1 stage while less cells in S stage or G2-M stage than non-resistant cell line. CONCLUSIONS: The expression levels of clusterin were higher in drug resistant NSCLC cell lines indicating that clusterin be associated with resistance to NVB in NSCLC. PMID- 20738914 TI - [The expression of ABCG4, V-ATPase and clinic significance of their correlation with NSCLC.]. AB - BACKGROUND: It has been proven that the multiple drug resistance is main reason for failure of chemotherapy in lung cancers and ABC transporter play a main role for chemoresistance in mediating drug efflux. So searching for new drug resistant protein of the ABC family and elucidating its resistant mechanism is very important. ABCG4 is one of ABC family and is expected to be candidate drug resistant protein; and the drug resistance probably correlated with pH value around cancer cell, while, V-ATPase play key role in modulating the pH. So our aim is to investigate the expressions of ABCG4, V-ATPase proteins in non small cell lung cancer (NSCLC), and analyze relationship of ABCG4, V-ATPase protein expressional rate in these cancers with the cancers' pathological grade and TNM stages. METHODS: To detect the expression rates of ABCG4, V-ATPase protein in NSCLC with immunohistochemical method and immuno- fluorescent method, and to observe the location, the collocation of the proteins under light microscope and confocal laser scanning microscope; the differences of the protein expression and their correlations were analyzed by statistics. RESULTS: ABCG4 protein was high expressed in squamous cell lung cancer, lung adenocarcinoma respectively, and between the two kinds of the cancers there was a significant difference (P =0.001) for their comparison; there were significant differences between pathological grade II and II-III of squamous cell lung cancer, between different differentiated lung adenocarcinoma. V-ATPase protein were also high expressed in these two kinds of cancers, and there was significant difference for their comparison; there were significant differences between pathological grade II and II-III of squamous cell lung cancer, between different differentiated lung adenocarcinoma; there were no significant differences among the squamous cell lung cancer and lung adenocarcinoma for TNM stages respectively. The P values of correlationship test of positive intensity between ABCG4 and V-ATPase expression in the total squamous cell lung cancer and lung adenocarcinoma, in the pathological grade II and II-III of the squamous cell lung cancer, in the moderately differentiated lung adenocarcinoma were all 0.000, while the correlation coefficients were 0.771, 0.765, 0.714, 0.777, 0.865 respectively; however, the P values of correlationship test of between ABCG4 and V-ATPase expression in the low differentiated lung adenocarcinoma was 0.048, and the correlation coefficient was 0.35. The ABCG4 and V-ATPase positive expression was mainly located in the plasma membrane and cytoplasm, and there was collocation among the ABCG4 and V-ATPase proteins. CONCLUSIONS: The ABCG4 and V-ATPase proteins are highly expressed in the NSCLC, and the expression rates of ABCG4, V ATPase proteins are correlated with the cancers' pathological grades and TNM stage; and there are all having correlationship between ABCG4 and V-ATPase proteins in the squamous cell lung cancer, in the lung adenocarcinoma, in all their pathological grades. PMID- 20738916 TI - [The mechanism of metastasis suppressor gene nm23-H1 involving in the Ras signaling of lung cancer.]. AB - BACKGROUND: It has been confirmed that nm23-H1 gene is one of the tumor metastasis suppressor genes. Up to now, the exact mechanism of nm23-H1 gebe is uncertain. The aim of this study the mechanism of metastasis suppressor gene nm23 H1 involving in the Ras signaling of lung cancer. METHODS: The wild and mutant type of pEGFP-nm23-H1 plasmids [WT (wild type), H118F, S120G, P96S, S44A] were transfected into the L9981 lung cancer cell lines through liposome method, and the complex of KSR and nm23-H1 was detected through co-immunoprecipitation and Western blot assay. RESULTS: The human KSR could be detected in the nm23-H1 immunoprecipitations in all the trasfected L9981 lung cancer cell lines. But no significant difference of KSR expression was found in the wild and mutant nm23-H1 trasfected cell lines (F =0.190, P =0.938). CONCLUSIONS: There was a close interaction between nm23-H1 and KSR, which was independent of the nm23-H1 mutation. Nm23-H1 involving in the Ras signaling of lung cancer may be through the KSR gene. PMID- 20738917 TI - [Effects of hypoxia on the expression of CCR7 and proliferation, invasiveness of A549 cells.]. AB - BACKGROUND: It has been proven that hypoxia could promote tumor cells invasion and metastasis by different mechanisms, but the relationship between hypoxia and CCR7 have not been reported. The aim of this investigate is to evaluate the effects of hypoxia on the expression of CCR7 and the invasiveness of lung adenocarcinoma A549 cells. METHODS: A549 cells were incubated at either normoxia (37 (o)C, 5%CO2, 21%O2) or hypoxia (37 (o)C, 5%CO2, 1%O2) condition for 4 h,12 h, 24 h. The expressions of CCR7 mRNA and protein levels were observed by RT-PCR and Western blotting; Cells invasiveness was measured by matrigel invasion assay. RESULTS: RT-PCR and Western blotting showed that the expression of CCR7 was detected in lung adenocarcinoma A549 cells, CCR7 mRNA and protein expression level were increased with culture time along either in normoxia or hypoxia condition; Furthermore, compared with normoxia group, the CCR7 mRNA and protein expression level in hypoxia group was increased (P <0.01). The results of Transwell invasion showed that The number of invasive cells was significantly increased in hypoxia group (t =0.006, P <0.01) and A549 cells invasive ability was inhibited after add anti-CCR7 Ab to culture medium (t =0.09, P <0.01). CONCLUSIONS: The results suggest that hypoxia plays an important role in the augmentation of the CCR7 expression and invasiveness of A549 cells. Invasion of A549 cells in hypoxia condition correlated with CCR7 expression level. PMID- 20738918 TI - [Effects of pulmonary veins ligation style for the patients' stress and cardiac on lung cancer.]. AB - BACKGROUND: It is needed to explore the effects of operation on stress statue, myocardial damage and arrhythmia to lung cancer. This study would compare the effects of two ligation styles of pulmonary vein on lung cancer patients' stress and cardiac postoperative. METHODS: 54 cases were divided into two groups randomly: the pulmonary vein trunk-ligation group (trunk group, 27 cases) and the pulmonary vein branch-ligation group (branch group, 27 cases). The blood concentrations of hydrocortisone (HC), blood glucose (BG) and cardial troponin-I (cTnI) were determined at different time point. The surgical data, the quantum of pain and ECG also recorded. RESULTS: (1) There were no significance difference of the operation time, blood loss during operation and drainage volume in first day after operation between two groups. (2) There're no differences of the quantum of pain between two groups. (3) The HC of the two groups' ascend obviously on the end of operation and descend during postoperative. (4) The BG of the two groups' rise on the 1st day obviously, maintain high level on the 2nd day, descend on the 3rd day but still higher than that of preoperation. (5) The BG and HC show a direct positive correlation postoperative. (6) The cTnIs of the trunk group ascend immediately after operation, but there's no statistically significance between two groups. (7) The arrhythmia incidence is higher in the trunk group, but the arrhythmia incidences classified by the date after operation of the two groups' show no distinction. CONCLUSIONS: (1) The effects of two pulmonary vein ligation styles on postoperative stress show no significance differences. (2) The style of pulmonary vein trunk-ligation has a more obvious tendency to do harm to heart than that of branch-ligation. (3) The style of pulmonary vein branch ligation may reduce the arrhythmia incidence after operation. PMID- 20738919 TI - [Effect of informing the diagnosis on depressive state in patients with non-small cell lung cancer of stage III.]. AB - BACKGROUND: As other tumors, unresectabe lung cancer can cause many psychological problems to the patients, such as depression and anxiety. The present paper aims to evaluate the status of depression before and after knowing the state of illness in patients with non-small cell lung cancer of stage III. METHODS: 43 cases of newly diagnosed non-small cell lung cancer (NSCLC) with stage III were enrolled in the study. All the patients were distributed into three groups and given different intervention, that was completely unknowing the state of illness (group A), partly knowing the state of illness (group B) and completely knowing the state of illness (group C). Before and after knowing the state of illness, the depression status was assessed with the Hamilton depression rating scale for depression (HAMD). RESULTS: The mean total score of HAMD was unchanged both in group A and C, while significantly reduced in group B. The scores of anxiety somatization, cognitive disorder, retardation and feeling of despair were all significant lower in the group B after the patients partly knowing the state of illness, while the scores of sleep disorder was obviously higher in group C after the patients completely knowing the state of illness. The hypochondriasis was much severer in the group A, and in the group C, the score of suicidal idea became significantly higher after the patient knowing the diagnosis. CONCLUSIONS: Depression is very common in the NSCLC patients with stage III. Partly knowing the state of illness can obviously ameliorate the symptoms of depression, while completely knowing or completely unknowing the state of illness have no effect on relieving the patients' depression. PMID- 20738920 TI - [Detection of CEA mRNA on non-small lung cancer and it's significance.]. AB - BACKGROUND: In recent years, many studies on micrometastasis in non-small cell lung cancer (NSCLC) have been reported, this study is to investigate the effect of operation on micrometastasis from NSCLC and evaluate the relation between micrometastasis and clincopathological parameters. METHODS: The blood samples were taken from 70 cases of NSCLC and 18 patients with benign diseases at 3 intervals during the operation from peripheral vein. The transcription of carcinoembryonic antigen messenger ribonucleic acid (CEA mRNA) was assayed by means of nested reverse transcriptase polymerase chain reaction (RT-PCR) and micro-fluid chip. RESULTS: The CEA mRNA positive rates of all 3 time spots were as follows: 50% at beginning of the operation (Time 1), 62.8% at ligating the pulmonary vein (Time 2) and 57.1% at 1 h after ligating pulmonary vein (Time 3). There is significant difference between Time 1 and Time 2 (Chi-Square=7.114, P <0.05). The positive rates of well-differentiation and middle-differentiation, stage I and state II, Tis, T1 and T2, N0 were significant less than non differentiation and low-differentiation, stage III and state IV, T3 and T4, N1, N2 and N3, respectively. No negative control samples was found to be positive, and no positive control samples was found to be negative. The sensitivity of our test was 10 cells/mL. CONCLUSIONS: The cancer cells dissemination during operation was demonstrated indirectly in our study, the time of pulmonary vein ligation (earlier or later) may affect the quantity of tumor cells released into circulation; The patients with lower differentiation, advanced TNM stage, larger tumor size and metastasis of lymph node have higher rates of metastasis in peripheral, so the detection of CEA mRNA can guide the therapy of NSCLC to a certain extent. PMID- 20738921 TI - [Upregulation of the Chemokine Receptor CCR7 expression by HIF-1alpha and HIF 2alpha in non-small cell lung cancer.]. AB - BACKGROUND: CCR7 is closely related with the lymph node metastasis of non-small cell lung cancer. The objective of this work is to investigate the expressions of chemokine receptor CCR7, hypoxia inducible factor 1alpha (HIF-1alpha) and hypoxia inducible factor 2alpha (HIF-2alpha) protein in non small cell lung cancer and the relationships of their expression, and to study the mechanism of CCR7 upregulation in NSCLC. METHODS: T he levels of expressions of CCR7, HIF-1alpha and HIF-2alpha protein were detected in 94 specimens of human primary non small cell lung cancer by immunohistochemical S-P method. Human lung adenocarcinoma cell line A549 cells were transfected by lipofection with HIF-1alpha siRNA, HIF 2alpha siRNA, the change of CCR7 was observed by RT-PCR and immunofluorescence staining. Correlations between the expression of CCR7 and HIF-1alpha, HIF-2alpha were respectively analyzed. RESULTS: Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells, HIF-1alpha, HIF-2alpha was distributed in nucleus and/or cytoplasm of tumor cells. The levels of expressions of CCR7, HIF-1alpha and HIF-2alpha protein were found to be 75.53% (71/94), 54.25% (51/ 94) and 70.21% (66/94) in non small cell lung cancer, respectively. the levels of expression of CCR7 protein were closely related to the clinical stages (P <0.001) and lymph node metastasis (P <0.001) of non small cell lung cancer, but there was no correlation with age, gender, histology (P >0.05). Furthermore, A significant correlation were found among CCR7, Hif-1alpha and HIF-2alpha (r =0.272, P <0.01) (r =0.225, P <0.05). In addition, the expression of CCR7 mRNA and protein levels were decreased in the transfected specific HIF-1alpha, HIF-2alpha siRNA group (P <0.05). CONCLUSIONS: CCR7 expression is significantly associated with non small cell lung cancer invasion and metastasis. The upregulation of CCR7 is regulated by HIF-1alpha and HIF 2alpha in non small cell lung cancer. PMID- 20738922 TI - [Expression of livin protein in lung cancer and its relation with the expression of pro-caspase3 protein.]. AB - BACKGROUND: Livin is a novel inhibitor of apoptosis protein (IAP), recent studies showed it overexpresses in a variety of carcinomas including lung cancer and contributes much to the cancerous development. The objective of this study is to explore the expression of livin in tissues of lung cancer and its relationship with histological types, chemotherapy, Lymph node metastasis and to study its correlation with the expression of pro-caspase3 as well. METHODS: Expressions of Livin and caspase3 were detected by Western blot assay in lung cancer tissues as well as in controls. RESULTS: Livin was expressed in 15 of 27 lung cancer, significantly more than those in lung para-cancerous (1/5) or benign disease lung tissues (2/12) (P <0.01). Moreover, it showed expression in 10 of 13 lung adenocarcinoma and in 5 of 13 squamocellular and large cell carcinoma respectively, but not detected in one small cell carcinoma. The levels of livin protein in lung cancer were significantly higher than those in controls by Gel Imaging System (P <0.05). Meanwhile, the levels of pro-caspase3 protein in lung cancer were significantly higher than those in controls (P <0.05), the levels of livin tended to be positively associated with that of pro-caspase3. Livin expression seemed to increase after chemotherapy but not related to lymph node metastasis (P >0.05). CONCLUSIONS: Livin are differently expressed in different histological types of lung cancer; High levels of livin expression do not relate to chemotherapy, lymph node metastasis (P >0.05). The levels of livin tends to be positively associated with those of accordingly pro-caspase3, it is presumed that livin could bind pro-caspase3 and suppress its activation. PMID- 20738923 TI - [Clinical research of perioperative serum VEGF and MMP-9 levels in patients with non-small cell lung cancer.]. AB - BACKGROUND: Angiogenesis is necessary in tumor progression and metastasis. Serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are important factors in angiogenesis. Elevated levels of VEGF and MMP-9 were reported in lung cancer. The aim of this research is to study the dynamic changes of serum VEGF and MMP-9 levels in non-small cell lung cancer (NSCLC) patients who underwent surgery. METHODS: Serum VEGF and MMP-9 levels were determined in 57 patients with NSCLC who were undergoing surgery by ELISA (enzyme linked immunosorbent assay) method before operation and on postoperative day 1, 7, 14. At the same time 18 patients with pulmonary benign diseases treated by surgery were studied as the control. Thirty healthy volunteers served to define normal VEGF and MMP-9. RESULTS: Preoperative serum VEGF levels (685.50 pg/mL) was significantly higher in the group of patients with NSCLC compared with the benign and healthy group (respectively: 160.90 pg/mL, 94.40 pg/mL) (P <0.01); Serum VEGF levels were elevated after surgery and the levels were 1055.60 pg/mL, 1533.90 pg/mL, 1882.10 pg/mL, respectively, on postoperative day 1, 7, 14 (P <0.01). 2 Preoperative serum MMP-9 level (84.48 ng/mL) was significantly higher in the group of patients with NSCLC compared with the benign and healthy group (respectively: 58.98 ng/mL and 42.94 ng/mL, P <0.01); Serum MMP-9 levels were elevated soon after surgery and the peak (282.99 ng/mL) was observed on postoperative day 1 in NSCLC. Then serum MMP-9 levels dropped (respectively: 221.14 ng/mL and 194.78 ng/mL on postoperative 7 and 14) (P <0.01). CONCLUSIONS: Preoperative serum VEGF and MMP-9 levels were both significantly higher in the group of patients with NSCLC compared with the benign and healthy group. Perioperative serum VEGF and MMP-9 levels were both significantly elevated in patients with NSCLC. PMID- 20738924 TI - [Surgical treatment for pulmonary focal ground-glass opacity.]. PMID- 20738925 TI - [The research advance in the effect of the Syk gene expression and invasion or metastasis of tumor by Syk DNA Methylation.]. PMID- 20738926 TI - [Research advance on molecular biology of lung cancer metastasis.]. PMID- 20738927 TI - [Perioperative nursing practice of total pneumonectomy on left central-type lung cancer patients.]. PMID- 20738928 TI - [Study of conducting low-dose chest computed tomography and P16 gene methylation in serum for early diagnosis of lung cancers.]. PMID- 20738929 TI - [A case report of benign metastasizing lung leiomyoma.]. PMID- 20738930 TI - Systematic review and economic modelling of the effectiveness and cost effectiveness of non-surgical treatments for women with stress urinary incontinence. AB - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of non surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling. DATA SOURCES: The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database. STUDY SELECTION: The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost effective for SUI. DATA EXTRACTION: Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person. RESULTS: Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when society's willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions. LIMITATIONS: Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies. CONCLUSIONS: More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies. PMID- 20738931 TI - Optical coherence tomography is now ready: sharpening the tool. PMID- 20738932 TI - Treatment strategies and risk stratification in acute coronary syndrome: how do we identify patients who would benefit from early invasive treatment? PMID- 20738933 TI - Genome-wide association studies --do not judge a book by its cover. PMID- 20738934 TI - Second-generation optical coherence tomography in clinical practice. High-speed data acquisition is highly reproducible in patients undergoing percutaneous coronary intervention. AB - INTRODUCTION AND OBJECTIVES: The development of second-generation optical coherence tomography (i.e. Fourier domain optical coherence tomography, FD-OCT) has made it possible to perform high speed pullbacks during image acquisition without the need for transient occlusion of the coronary artery. The objective of this study was to assess the reproducibility of FD-OCT systems for characterizing plaque and evaluating stent implantation in patients undergoing a percutaneous coronary intervention. METHODS: The study included 45 patients scheduled for percutaneous coronary intervention who were enrolled between May and December 2008. Image acquisition was performed by FD-OCT using a non-occlusive technique and employing pullback speeds ranging from 5 to 20 mm/s. Interstudy, interobserver and intraobserver reproducibility of plaque characterization and stent analysis were assessed. RESULTS: Fourier domain imaging was successfully performed in all patients (n=45). The average flush rate was 3+/-0.4 mL/s and the contrast volume per pullback was 16.1+/-3.5 mL. The mean pullback duration and length were 3.2+/-1.2 s and 53.3+/-12.4 mm, respectively. The interstudy reproducibility for visualizing edge dissection, tissue prolapse, intrastent dissection and malapposition was excellent (k=1). The kappa values for interstudy, interobserver and intraobserver agreement on plaque characterization were 0.92, 0.82 and 0.95, respectively. CONCLUSIONS: A second-generation OCT system (i.e. FD-OCT) involving high-speed data acquisition demonstrated good interstudy, interobserver and intraobserver reproducibility for characterizing plaque and evaluating stent implantation in patients undergoing a percutaneous coronary intervention. PMID- 20738935 TI - Simple versus complex approaches to treating coronary bifurcation lesions: direct assessment of stent strut apposition by optical coherence tomography. AB - INTRODUCTION AND OBJECTIVES: Stenting of coronary bifurcation lesions carries an increased risk of stent deformation and malapposition. Anatomical and pathological observations indicate that the high stent thrombosis rate in bifurcations is due to malapposition of stent struts. METHODS: Strut apposition was assessed with optical coherence tomography (OCT) in bifurcation lesions treated either using the simple technique of stent implantation in the main vessel only or a complex technique (i.e. Culotte's). A strut was regarded as malapposed if the gap between its endoluminal surface and the vessel wall was greater than its thickness plus an OCT resolution error margin of 15 microm. RESULTS: Simple and complex (i.e. Culotte's) approaches were used in 17 and 14 patients, respectively. Strut malapposition was significantly more frequent for the half of the bifurcation on same side as the vessel side branch (median, 46.1%; interquartile range [IQR], 35.3-62.5%) than for the half opposite the side branch (9.1%; IQR, 2.2-21.6%), the distal segment (7.5%; IQR, 2.3-20.2%) or the proximal segment (12.6%; IQR, 7.8-23.1%; P< .0001); the gap between strut and vessel wall in malapposed struts was significantly greater in the first segment than the others: 98 microm (IQR, 37-297 microm) vs. 31 microm (IQR, 13-74 microm), 49 microm (IQR, 20-100 microm) and 38 microm (IQR, 17-90 microm), respectively (P< .0001). Using the complex technique had no effect on the prevalence of strut malapposition in the four segments relative to the simple technique (P=.31) but was associated with a smaller gap in the proximal segment (47 microm vs. 60 microm; P=.0008). CONCLUSIONS: In coronary bifurcation lesions, strut malapposition occurred most frequently and was most significant close to the side branch ostium. The use of Culotte's technique did not significantly increase the prevalence of strut malapposition compared with a simple technique. PMID- 20738936 TI - Effect of invasive treatment on prognosis in non-ST-segment elevation acute coronary syndrome with or without systolic dysfunction. AB - INTRODUCTION AND OBJECTIVES: Few data are available on the use of invasive treatment in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) and systolic dysfunction. The aim of this study was to determine the effect of invasive treatment on the prognosis of patients with NSTEACS, with or without systolic dysfunction. METHODS: The study included 972 consecutive patients admitted for NSTEACS (i.e. ST-segment depression or an elevated troponin I level). Systolic dysfunction was defined as an ejection fraction <50% on transthoracic echocardiography. The primary long-term endpoint was death or myocardial infarction. The effect of invasive treatment on prognosis was evaluated by Cox regression analysis. RESULTS: Overall, 23.4% of patients had systolic dysfunction, and 303 (31.2%) reached the primary endpoint, which was more frequent in those with systolic dysfunction (49.8% vs. 25.5%; P< .001). Usage of coronary angiography and revascularization procedures were similar in patients with systolic dysfunction and those with an ejection fraction >/=50% (59% vs. 63.4%; P=.239; and 38.3% vs. 38.8%; P=.9; respectively). Detailed adjusted multivariate analysis, including the use of a propensity score, demonstrated that coronary angiography had a differential effect on prognosis depending on the presence or absence of systolic dysfunction (interaction, P=.01). Catheterization was clearly beneficial in patients with systolic dysfunction (hazard ratio [HR]=0.47; 95% confidence interval [CI], 0.3-0.75; P=.001) but not in those with an ejection fraction >/=50% (HR=0.9; 95% CI, 0.63 1.29; P=.567). CONCLUSIONS: The presence of systolic dysfunction identifies those patients with NSTEACS who will benefit most from invasive treatment. PMID- 20738937 TI - Additive effect of multiple genetic variants on the risk of coronary artery disease. AB - INTRODUCTION AND OBJECTIVES: Coronary artery disease (CAD) has a substantial genetic component and, in recent years, a number of genetic variants associated with the disease have been identified. The objective of this study was to evaluate the magnitude of the association between a genetic risk score, which is based on the accumulated number of risk alleles in all genetic variants of interest, and the presence of CAD. METHODS: The study involved in silico data from the Wellcome Trust Case-Control Consortium on 1988 patients with CAD and 5380 controls. The association between the genetic risk score and CAD was assessed using logistic regression analysis. RESULTS: Nine genetic variants independently associated with CAD irrespective of other cardiovascular risk factors were selected. There was a linear association between the number of risk alleles and the risk of presenting with CAD (odds ratio [OR] for an increase of one allele=1.18; 95% confidence interval [CI], 1.15-1.22; P=2 x 10-16). The OR for CAD for the last quintile of the accumulated number of risk alleles relative to the first was 2.21 (95%CI, 1.87-2.61; P=5 x 10-21). CONCLUSIONS: A genetic risk score based on nine genetic variants independently associated with CAD irrespective of other cardiovascular risk factors was associated with the presence of the disease. Cohort studies are needed to determine whether this genetic risk score can improve the predictive capacity or the risk classification of classical risk functions. PMID- 20738938 TI - Normal myocardial perfusion SPECT database for the Spanish population. AB - INTRODUCTION AND OBJECTIVES: The aims of this study were to create a Spanish database of normal myocardial perfusion SPECT (single-photon emission computed tomography) data, termed the normal Spanish database, and to compare it with a database of normal data from the North American population. METHODS: We selected 104 healthy volunteers (45 female, mean age 42+/-14 years) who underwent SPECT during stress and at rest. The findings were analyzed using the 4DM-SPECT commercial software package. The resulting normal Spanish database for males and females was compared with the North American population database (from 70 men and 60 women) provided with the 4DM-SPECT software. RESULTS: In the Spanish database, the highest percentage uptake during both stress and rest was observed in medial lateral region and the lowest, in the basal-septal region. The percentage uptake in the anterior-medial region was significantly lower in women than men, while uptake in the inferior, medial-septal and apical regions was lower in men than women. Data values in the Spanish database were significantly lower for the majority of heart regions than those in the database with the 4DM-SPECT software. CONCLUSIONS: A Spanish database of normal myocardial perfusion SPECT data was created and included separate data for men and women. Significant differences were observed between this database and a commercial North American database that is commonly used in semiquantitative studies. PMID- 20738940 TI - Optical coherence tomography: its value in intravascular diagnosis today. AB - Optical coherence tomography is a recently developed high-resolution intravascular diagnostic technique. Initially, it was mainly used for characterizing atherosclerotic plaque because it served a number of functions, from identifying plaque with high lipid content to detecting macrophage accumulation, both of which are associated with plaque instability. Currently, there is growing interest in the value of optical coherence tomography in the area of coronary intervention, where the technique offers significant advantages over more widespread intravascular diagnostic techniques such as intravascular ultrasound: its higher resolution means that the vessel lumen diameter can be measured more precisely, periprocedural complications such microdissection of the coronary artery can be detected, stent apposition relative to the vessel wall can be optimized, neointimal hyperplasia can be detected after stent implantation, and neointimal thickness can be measured. It would therefore appear to be a very useful technique for interventional cardiologists. This review article considers the technical details of the technique and its applications, and compares it with other intravascular diagnostic techniques. PMID- 20738941 TI - Arrhythmia and right heart disease: from genetic basis to clinical practice. AB - Historically, left ventricular cardiomyopathy and coronary heart disease have been regarded as the main causes of ventricular arrhythmia and sudden cardiac death. However, within last two decades, arrhythmias originating from the right ventricle have begun to attract the attention of the scientific world for a number of reasons. Ventricular arrhythmias originating from the right ventricle usually affect younger patients and can lead to sudden cardiac death. The pathophysiologic mechanism of these arrhythmias is not fully understood, which can leave room for a range of different interpretations. Moreover, the intriguing world of genetics is increasingly being drawn into the pathogenesis, diagnosis and prognosis of some of these arrhythmias. This review considers the pathogenesis, diagnosis and treatment of arrhythmogenic right ventricular cardiomyopathy or dysplasia (ARVD), Brugada syndrome, right ventricular outflow tract ventricular tachycardia, and arrhythmias in the right side of the heart due to congenital heart disease. In addition, because ventricular arrhythmias associated with right ventricular heart diseases such as Brugada syndrome and ARVD can explain up to 10-30% of sudden cardiac deaths in young adults in the general population and an even greater percentage in young athletes, this article contains a brief analysis of screening tests used before participation in sports, life-style modification, and treatment options for athletes affected by these conduction disorders. PMID- 20738939 TI - Prevalence of atrial fibrillation and use of antithrombotics in hypertensive patients aged >or=65 years. The FAPRES trial. AB - INTRODUCTION AND OBJECTIVES: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged >or=65 years in the Spanish region of Valencia. METHODS: Each study investigator enrolled the first three hypertensive patients aged >or=65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS2 score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records. RESULTS: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS2 score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm. CONCLUSIONS: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously. PMID- 20738942 TI - Isolated left ventricular apical hypoplasia. PMID- 20738943 TI - Severe cardiac conduction disturbances and pacemaker implantation in patients with hypertrophic cardiomyopathy. AB - The aims of this study were to determine the prevalence of severe cardiac conduction disturbances in a cohort of 451 patients with hypertrophic cardiomyopathy and to describe the characteristics of, and outcomes in, those who required a permanent pacemaker. A pacemaker was implanted in 48 patients (11%): 20 had sinus node dysfunction and 28 had an atrioventricular conduction disturbance. Primary bradyarrhythmia (which was not related to iatrogenic atrioventricular block or therapeutic ablation of the atrioventricular node) was the reason for permanent pacemaker implantation in 36 patients (8%). In 18% of cases, at least one other family member had a permanent pacemaker. In this patient series, a high prevalence of severe cardiac conduction disturbance leading to permanent pacemaker implantation was observed. Severe cardiac conduction disturbance in hypertrophic cardiomyopathy may also have a familial component. PMID- 20738944 TI - An analysis of cardiac remodeling in the elderly population. EPICARDIAN study. AB - The aims of this study were to investigate left ventricular morphology in a sample of elderly Spanish individuals and to assess differences between hypertensives and normotensives. Data were obtained from a subsample (N=242) of participants in the EPICARDIAN study who live to the Lista district of Madrid: they included 191 (78.8%) hypertensives and 51 (21.2%) normotensives. Left ventricular remodeling patterns were classified as: type I (normal), type II (concentric remodeling), type III (concentric hypertrophy) or type IV (eccentric hypertrophy). The overall prevalences were: 74 (30.5%) type I, 62 (25.9%) type II, 53 (21.8%) type III and 53 (21.8%) type IV. A comparison of hypertensives and normotensives showed that the prevalences were: 42 (22.3%) type I, 50 (26.1%) type II, 50 (26.1%) type III and 49 (25.5%) type IV in hypertensives and 31 (60%) type I, 13 (26%) type II, 3 (6%) type III and 4 (8%) type IV in normotensives (P< .0005). Ventricular remodeling without hypertrophy was common in the elderly, an observation that could have prognostic implications. PMID- 20738945 TI - Serum myostatin levels in chronic heart failure. AB - Muscle wasting is common in advanced heart failure. Myostatin is an important modulator of muscle catabolism. We measured serum levels of myostatin and its propeptide in patients with chronic heart failure and analyzed their relationships with clinical parameters and prognosis. The study included 70 patients: 30 in New York Heart Association (NYHA) functional class I-II and 40 in class III-IV. Their mean ejection fraction was 32%+/-12%. The mean follow-up time was 17.9+/-1.3 months. Thirteen patients (18.6%) died. No correlation was found between myostatin and myostatin propeptide levels. Nor was the myostatin or myostatin propeptide level correlated with age, sex, left ventricular ejection fraction, symptom duration, or the level of N-terminal probrain natriuretic peptide (NT-proBNP) or tumor necrosis factor-alpha receptor type-2 (TNFalpha R2). Moreover, no relationship was observed between the myostatin or myostatin propeptide level and NYHA functional class or mortality, in contrast to the relationships found with NT-proBNP (P< .001 and P< .001, respectively) and TNFalpha R2 (P=.001 and P=.005, respectively) levels. In conclusion, there was no relationship between the myostatin or myostatin propeptide level and any parameter of disease severity or prognosis in patients with chronic heart failure. PMID- 20738946 TI - Induction of coronary spasm after dipyridamole administration. PMID- 20738947 TI - Cor triatriatum dexter in adults. PMID- 20738948 TI - Importance of identifying renal disease early. PMID- 20738949 TI - Aldosterone antagonists: from cirrhosis to heart failure? PMID- 20738952 TI - [Editorial independence and scientific publications]. AB - INTRODUCTION: Various cases of editors of leading journals resigning has led to a debate on the question of editorial independence, understood as the unconditional freedom of editors to approve the contents of their journals. METHOD: An analysis is made of cases in which editorial independence has been questioned, as well as the position those who resolutely defend it against those who consider that it must be limited by the institutions of which they are their organs of expression. CONCLUSIONS: Editors of scientific publications not only have to be judges of the articles they receive, but they must also be judged by their decisions, and editorial independence cannot be a refuge for personal stances. By independence it must be understood as the meticulousness in accepting manuscripts and the application of transparent criteria. PMID- 20738953 TI - [Hypercoagulability and ischemic stroke in young patients]. AB - INTRODUCTION: Hypercoagulable states have been reported as an established risk factor for cerebral venous thrombosis, but they have also been proposed as a predisposing factor for cerebral ischemia of arterial origin, especially among young patients. This may have implications on therapeutic management and secondary prevention. We have studied the frequency of prothrombotic abnormalities in young patients with ischaemic stroke, as other classic risk factors are less common in this group. MATERIALS AND METHODS: Observational study with sequential inclusion of patients under 55 with stroke or transient ischaemic attack (TIA) admitted to the Stroke Unit from January 2005 through December 2007. We analysed demographic data, severity and subtype of stroke, risk factors, including the presence of hypercoagulable states, and outcome. RESULTS: We included 100 patients, of whom 65 were men. The mean age was 42.6 +/- 8.9 years, 46% with a hypercoagulable state, and no sex differences. Acquired hyperhomocysteinemia was the most common abnormality (18%), followed by protein C or S deficiency (8%), factor V Leiden mutation (5%) and methyl-tetrahydro-folate reductase (MTHFR) C677T mutation (5%). Other findings included anticardiolipin antibodies (3%), presence of lupus anticoagulant (2%), thrombocytosis (3%) and G20210A prothrombin gene mutation (3%). No association was found between these states and the presence of other vascular risk factors, or more severe stroke or worse outcomes. There was an increased presence of these abnormalities in patients who were classified as atherothrombotic stroke (p = 0.04). CONCLUSIONS: The hypercoagulable states are common in young patients with ischaemic stroke, being present in up to 46% of them. PMID- 20738954 TI - [Stendhal syndrome: origin, characteristics and presentation in a group of neurologists]. AB - INTRODUCTION: Travelling, when searching for knowledge and emotion, can cause psychic discomfort that occasionally leads the traveller to seek medical attention. The psychiatrist Graziella Magherini described, in tourists visiting Florence, acute attacks including disorders of thought and affects, and even including, anxiety attack. She named it the Stendhal syndrome (SS) remembering the experience of the writer when visiting the Basilica of Santa Croce in Florence. METHODS: We attempt to investigate the incidence of SS or isolated symptoms related to it, in a homogeneous group of travellers. We review other artists who experienced emotion sickness during their trips throughout history. RESULTS: At the end of the III Neurohistory Meeting (Spanish Neurology Society, Italy, February, 2008) a questionnaire was handed out to the participant neurologists, in order to evaluate if during the practical workshops included in the meeting they had experienced symptoms as those described in SS. A total of 48 questionnaires were completed. The mean age was 50+/-9 years and the male/female ratio 1.7/1. Twenty-five percent of the subjects considered they had experienced a partial SS. No panic attacks or thought disorders were identified, but they did suffer artistic effects, mainly in pleasure (83%) and emotion (62%). CONCLUSIONS: No SS case was identified among neurologists attending this Neurohistory meeting, but most of them experienced mild disorders of affects and one out of four recognized they have had a partial form of the syndrome. PMID- 20738955 TI - [Validation of supra-aortic trunks ultrasound in the diagnosis of atherosclerotic disease of the internal carotid artery. Comparison of the results with angiography]. AB - INTRODUCTION: Arteriosclerosis of the extra-cranial arteries is believed to be responsible for almost one-third of all ischaemic strokes. The sound diagnosis of the degree of stenosis is essential in deciding the best therapeutic strategy. Although cerebral angiography is considered the reference technique, ultrasound study (UST) is a more readily available, non-invasive and well-established procedure for quantifying carotid stenosis. However, on being a dependent exploratory technique, it is recommended that each laboratory validates its results against angiography. OBJECTIVES: To establish the validity of the neuro ultrasound study in our laboratory for use in the diagnosis of extracranial atheromatous disease, and determine its capacity to quantify the degree of stenosis in the internal carotid artery. MATERIAL AND METHODS: A retrospective study of patients with extracranial carotid atheromatous disease, in whom the diagnostic process was carried out with carotid ultrasound as well as supra aortic trunk digital-subtraction angiography. RESULTS: A total of 254 carotids were evaluated and the degree of stenosis being classified into > 50%, 70-99% and 100%. The UST for the first group had a sensitivity (Se) of 97%, a specificity (Sp) of 90%, a positive predictive value (PPV) of 94.6% and a negative predictive value (NPV) of 94.2%. The second group had an Se of 96.4%, Sp 93%; PPV 94.4% and NPV 95.4%. The respective values for carotid occlusion were, 85%, 96.8%, 80% and 97.8%. CONCLUSIONS: Our data validates the ability of UST performed in our Laboratory to diagnose the degree of carotid stenosis. PMID- 20738956 TI - [Cerebrospinal fluid cytotoxicity in lateral amyotrophic sclerosis]. AB - INTRODUCTION: The cytotoxicity of cerebrospinal fluid (CSF) in patients with lateral amyotrophic sclerosis in cell cultures that include neurons may be considered as a diffusion mechanism of the disease, due to the proximity of the CSF to the spinal column. DEVELOPMENT: Various literature studies suggest that the motor neurons are more susceptible to cytotoxicity compared to other neuron cells, including glial, in cell cultures. The review of the composition of CSF in lateral amyotrophic sclerosis gives few clues on how this mechanism causes pre apoptotic and apoptotic changes on the addition on CSF to the cultures, although it could be associated with the glutamate receptors, to a greater extent in those that respond to AMPA/kainate, and have a role in ion channels. CONCLUSIONS: The cytotoxicity of CSF is a peculiarity of lateral amyotrophic sclerosis, which could explain some aspects of how the disease progresses. More studies are required in order to understand more about this mechanism, including better identification of patients from whom samples are obtained, as well as their characteristics, differentiating them into familial or sporadic. PMID- 20738957 TI - [Descartes' influence on the development of the anatomoclinical method]. AB - The development of the anatomical-clinical method was a huge advance for modern medicine since it revealed a new approach to understanding diagnostic procedures. This change in medical thinking towards a more scientific basis has gradually evolved over several centuries, reaching its brilliant zenith with the contributions of the French school. There are certain similarities between the guidelines of the anatomical-clinical method and Rene Descartes' philosophical principles, so it is fair to consider him as one of the major precursors in this new line of thinking that definitely influenced the historical course of medicine. PMID- 20738958 TI - [Spanish Neurology Society consensus document on the use of drugs in multiple sclerosis: escalating therapy]. AB - INTRODUCTION: Treatment of multiple sclerosis has advanced considerably in the last few years, at the same time as its complexity has increased. The purpose of this consensus document is to provide specific recommendations and rules on the strategy to follow in the treatment of multiple sclerosis in order to modify its course. MATERIAL AND METHODS: Experts on the treatment and clinical research on multiple sclerosis proposed by the Demyelinating Diseases Group of the Spanish Neurology Society (SEN) prepared an initial document with recommendations for the treatment of this disease. The final version of this document was submitted to members of the Demyelinating Diseases Group of the SEN, who were able to make modifications and suggest changes to the final manuscript. RESULTS AND CONCLUSIONS: A review has been made of the evidence levels and indications for the treatment of the different clinical forms of multiple sclerosis, and recommendations made for the use of drugs. As well as authorised drugs, a review has also been made of other occasionally used products, as well as combined therapy, therapeutic response criteria, levels of treatment changes, and finally a proposal is made on therapeutic escalation. PMID- 20738959 TI - [Posterior leukoencephalopathy syndrome associated with amyloid angiopathy]. PMID- 20738960 TI - [Sleep disorders and restless legs syndrome in an adult with Asperger's disorder, a case report]. PMID- 20738964 TI - [Farewell from the editors]. PMID- 20738961 TI - [Papillary oedema: true or false?]. PMID- 20738965 TI - [Geoffrey Rose and how to foster clinical research in Spanish dermatology]. PMID- 20738966 TI - [Annular erythema of infancy]. AB - Many skin diseases appear as annular lesions. Some are more typical of adults or older children, whereas others usually appear in young children. Annular or figurate erythema of infancy comprises a group of dermatoses in which the primary lesion adopts an annular, oval circinate, or polycyclic pattern. Similarities in clinical presentation, age at onset, and duration of lesions mean that these conditions are difficult to diagnose; sometimes, they can only be identified by subtle differences in their clinicopathologic features. Clinical pictures enable us to distinguish one member of this group of diseases from another and also to differentiate them from other annular eruptions. For ease of description, we classify annular erythema of infancy into 2 types: conditions with a known etiology and conditions with characteristic reaction patterns but uncertain etiology. PMID- 20738967 TI - [Psychotropic treatment of psychodermatologic disorders]. AB - Psychotropic drugs act by correcting the chemical changes associated with mental disorders and their symptoms. The use of such drugs in medical specialties other than psychiatry is not new and has been growing since a relationship has been demonstrated between mental states and the skin. Besides the so-called psychodermatoses, there are many skin diseases directly related to stress. For this reason, and in view of the reluctance of many patients to consult a psychiatrist, all dermatologists should have a basic understanding of the pharmacology and use of psychotropic drugs. PMID- 20738968 TI - [Inherited epidermolysis bullosa: from diagnosis to reality]. AB - Inherited epidermolysis bullosa (EB) refers to a group of diseases that is well known to dermatologists. The diagnosis of an EB disease, which is usually straightforward, is devastating for affected families. The manifestations of forms of EB run well beyond the boundaries of dermatology, as patients frequently present a wide range of associated systemic conditions that can be considerably more severe than the skin disease itself. As dermatologists, we must be aware of the potential complications of EB because our intervention is essential for the correct referral of patients and coordination of all the specialists involved in their care. PMID- 20738969 TI - [Impact of melanoma diagnosis on sun protection]. AB - INTRODUCTION: Knowledge of the dangers of sun exposure does not always lead to changes in behavior. Failure to make behavioral adjustments is of particular concern in high-risk patients. OBJECTIVES: a) To assess the impact of melanoma diagnosis on knowledge, attitudes, and behaviors relating to sun protection, and b) to identify factors that could influence sun protection behaviors. METHODS: A coded, anonymous questionnaire was given to 195 patients with a recent diagnosis of melanoma. Data were collected on clinical and demographic variables and on knowledge, attitudes, and behaviors relating to sun protection before and after diagnosis. The questionnaire also addressed patients' sense of distress and guilt following diagnosis. RESULTS: Sun protection behaviors improved following diagnosis in 66% of patients. Although 98% of patients reported having received advice on sun protection following diagnosis, 15% continued to take inadequate sun protection measures. The probability of behavioral improvement following diagnosis was 4 times greater in women than in men. The subgroup of patients whose behavior improved had worse behaviors prior to diagnosis than did those who showed no improvement. Patients who expressed distress and feelings of guilt following diagnosis were more likely to improve their sun protection behavior. Age, tumor site, intensiveness of treatment, and belief that a suntan is healthy had no significant influence on behavioral change. CONCLUSIONS: Melanoma diagnosis is associated with increased knowledge of sun protection measures and improvement in behaviors. Nevertheless, patients continue to use inadequate sun protection measures. Identification of barriers to optimal sun protection behavior may be instrumental in designing targeted educational campaigns. PMID- 20738970 TI - [Solar elastosis in cutaneous squamous cell carcinoma]. AB - INTRODUCTION: Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. MATERIAL AND METHODS: We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. RESULTS: Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. CONCLUSIONS: Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both. PMID- 20738971 TI - [Epidemiologic study of 20 cases of pemphigus at Hospital Clinico Universitario Virgen de la Victoria de Malaga, Spain]. AB - INTRODUCTION: Pemphigus comprises a group of autoimmune blistering diseases that affect the skin and mucous membranes. Its clinical and epidemiologic features vary according to geographic location and ethnic background. OBJECTIVE: An exhaustive search of the literature reveals very few reports of the epidemiology of pemphigus in setting. Our aim, thus, was to conduct a retrospective study of the clinical and epidemiologic features of pemphigus at a secondary care hospital in Malaga, Spain. MATERIAL AND METHODS: We studied 20 patients diagnosed with pemphigus in our department over a period of 13 years (January 1995 to January 2008). RESULTS: We analyzed a large variety of clinical and epidemiologic parameters including sex; age; type of pemphigus; time since onset; associated symptoms; type, morphology, and location of lesions at the time of diagnosis; extent of skin and mucosal involvement; treatment received; treatment-related adverse effects and complications; number of hospital admissions; and patient outcome. CONCLUSIONS: Except for minor differences, our results are in agreement with published data on pemphigus regarding sex, age, and clinical presentation. According to our results, male sex is a predictor of poor prognosis as it is associated with poorer response to treatment and a higher rate of adverse effects and hospital admission. PMID- 20738972 TI - [Clinical research publication by Spanish dermatologists over time and in comparison with other research groups in 2008]. AB - INTRODUCTION: Clinical research is the form of research nearest to clinical practice. MATERIAL AND METHODS: For the years 1992, 1996, 2000, 2004, and 2008, we identified all indexed articles published by Spanish dermatologists and calculated the percentages corresponding to clinical research according to a previously validated definition; we then calculated the proportion of clinical research articles offering higher levels of evidence. For 2008, we compared these percentages to those of French and British dermatologists and Spanish rheumatologists. We also compared these groups' rates of productivity in 2008 in relation to articles providing higher levels of evidence. RESULTS: In 2008, 36% of Spanish dermatologists' publications reported clinical research; 7% were studies offering higher levels of evidence. The proportions did not change significantly over the period studied. Clinical research publications accounted for 35% and 43% of the articles by French and British dermatologists in 2008 and 54% of articles by Spanish rheumatologists in that year. The proportion of publications reporting clinical research was significantly higher for Spanish rheumatologists than for Spanish dermatologists. The proportions of publications offering higher levels of evidence were significantly different in 2008 only for the comparison between Spanish dermatologists and rheumatologists. Other differences were not statistically significant. In the comparison of rates of productivity in clinical research offering higher levels of evidence, British dermatologists were significantly more productive than Spanish dermatologists. CONCLUSIONS: Differences were observed in relation to specialty (Spanish dermatologists vs rheumatologists) and nationality (Spanish vs British dermatologists). The reasons for the differences identified need to be studied in order to improve this situation. PMID- 20738973 TI - [Leonine facies in carcinoid syndrome]. AB - Carcinoid syndrome is a rare disorder caused when elevated levels of vasoactive substances secreted by a carcinoid tumor fail to be metabolized by the liver. This can occur for a variety of reasons including metastatic invasion of the organ. Carcinoid syndrome results in elevated levels of 5-hydroxyindoleacetic acid in the urine. Clinical manifestations include: flushing, diarrhea, bronchospasm, and heart failure. We describe a patient with carcinoid syndrome and hepatic metastases, in whom the key symptom of persistent facial edema resulted in conspicuous leonine facies; there was a partial response to treatment with oral isotretinoin and intramuscular lanreotide. Differential diagnosis was made with other conditions causing facial edema. A review is performed of the various skin manifestations of carcinoid syndrome, highlighting their role in the early diagnosis and treatment of the disorder. PMID- 20738974 TI - [Facial papules and intestinal lipomatosis]. PMID- 20738975 TI - [Papules and plaques grouped on the pectoral region of a patient with hepatitis C virus infection]. PMID- 20738976 TI - [Erythema multiforme due to 5% imiquimod cream]. PMID- 20738977 TI - [Efficacy of etanercept in the treatment of acne conglobata]. PMID- 20738978 TI - [Annular lesions induced by a chlorine tablet]. PMID- 20738979 TI - [Fondaparinux and lepirudin as therapeutic alternatives in a disseminated eczematous skin reaction to low-molecular-weight heparin]. PMID- 20738980 TI - [Sweet syndrome in a pregnant woman]. PMID- 20738981 TI - [Extravasation of vincristine]. PMID- 20738982 TI - [Rapid increase in incidence of melanoma in situ in Girona (Spain), 1994-2005. Effectiveness of public education campaigns about early diagnosis]. PMID- 20738983 TI - [Lichen sclerosus atrophicus at an insulin injection site: an unusual koebner phenomenon]. PMID- 20738984 TI - [Progressive macular hypomelanosis successfully treated with topical clindamycin and benzoyl peroxide]. PMID- 20738985 TI - [Mixed intraepithelial lesion of the vulva]. PMID- 20738986 TI - [Sneddon syndrome associated with urticarial vasculitis and factor V Leiden mutation]. PMID- 20738987 TI - Transverse-section histology for parallel-ridge pattern. PMID- 20738989 TI - General practice out-of-hours service in Ireland provides a new source of syndromic surveillance data on influenza. AB - The use of routinely available electronic sources of healthcare data on the spread of influenza has the potential to enhance current surveillance activities. This study aimed to develop a method for identifying influenza-related records from general practitioner(GP) out-of-hours (OOH) services in Ireland. Data from one such service were interrogated for keywords relating to influenza-like illness (ILI) and a proxy measure of influenza activity in the community setting was developed. Comparison of this syndromic surveillance measure with national data on ILI consultation rates demonstrated a statistically significant temporal correlation.In five out of six influenza seasons investigated,peaks in the GP OOH influenza-related calls appeared at least one week ahead of peaks in the national ILI consultation rates. The method described in this paper has been extended to nine OOH services in Ireland (covering 70% of the Irish population) to provide weekly figures on self-reported illness for influenza in the community and its data have been incorporated into the national weekly influenza reports produced by the Health Protection Surveillance Centre. These data should provide early warnings of both seasonal and pandemic influenza in Ireland. PMID- 20738990 TI - The impact of the pandemic influenza A(H1N1) 2009 virus on seasonal influenza A viruses in the southern hemisphere, 2009. AB - Data collected over winter 2009 by five World Health Organisation National Influenza Centres in the southern hemisphere were used to examine the circulation of pandemic and seasonal influenza A strains during the first pandemic wave in the southern hemisphere.There is compelling evidence that the pandemic influenza A(H1N1) 2009 virus significantly displaced seasonal influenza A(H1N1) and, to a lesser extent, A(H3N2) viruses circulating in the southern hemisphere. Complete replacement of seasonal influenza A strains, however, was not observed during the first pandemic wave. PMID- 20738991 TI - Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010. AB - We report on a case of toxigenic Corynebacterium ulcerans infection in a fully immunised veterinary student, investigated in London, United Kingdom, in May 2010. There was no ongoing transmission in human contacts. Possible animal sources were identified. PMID- 20738992 TI - High prevalence of antibodies to the 2009 pandemic influenza A(H1N1) virus in the Norwegian population following a major epidemic and a large vaccination campaign in autumn 2009. AB - The prevalence of antibodies reactive to the 2009 pandemic influenza A(H1N1) was determined in sera collected before the start of the pandemic, during the early phase, and after the main epidemic wave and nationwide vaccination campaign in Norway. A substantial rise in prevalence of antibodies at protective titres, from 3.2% to 44.9%, was observed between August 2009 and January 2010. The highest prevalence, 65.3%, was seen in the age group of 10-19 year-olds. PMID- 20738993 TI - World Health Organization declares post-pandemic phase. PMID- 20738994 TI - Small pharmacies are more likely to dispense antibiotics without a medical prescription than large pharmacies in Catalonia, Spain. AB - The aim of this study was to explore the relationship between pharmacy size and the likelihood of obtaining antibiotics without medical prescription at a pharmacy. In 2008 in Catalonia, two actors presented three different cases in a randomised sample of pharmacies and asked pharmacists for an antibiotic. Pharmacies were considered as small when having limited space with only one counter and a maximum of two professionals selling medicines, as medium sized with three or four attending professionals, and as large with a large selling space and more than four attending professionals. Of the 197 pharmacies visited, 88 (44.7%) were considered as small while only 25 (12.7%) were large. Antibiotics were obtained without a medical prescription in 89 (45.2%) pharmacies, mainly in small pharmacies (63.6%), followed by medium-sized pharmacies (35.7%) and large pharmacies (12%) (p<0.001). Large pharmacies, that probably have a greater income, more closely followed the prevailing legislation of not selling antibiotics to patients without a medical prescription. This observation should now be confirmed in other countries where over-the-counter sales of antibiotics are prevalent and should be taken into account by programmes aiming at achieving a more prudent use of antibiotics. PMID- 20738995 TI - Ongoing outbreak of aseptic meningitis in South-Eastern Latvia, June - August 2010. AB - An outbreak of aseptic meningitis has been ongoing in several areas of Latgale region, in the south-eastern part of Latvia since the end of June 2010. By 9 August 2010, 114 cases had been notified. Most of the cases were registered in the city and amalgamated municipality of Daugavpils and neighbouring territories. According to current evidence, two types of enteroviruses, coxsackie A-9 virus and echovirus 30, are the causative agents of the outbreak. PMID- 20738996 TI - Ongoing outbreak of aseptic meningitis associated with echovirus type 30 in the City of Novi Sad, Autonomous Province of Vojvodina, Serbia, June - July 2010. AB - Since June 2010, incidence of aseptic meningitis has increased in Novi Sad, Autonomous Province of Vojvodina, Serbia. From 2 June to 25 July 2010, 80 cases of aseptic meningitis were notified, with an incidence rate ranging from 10 to 366 per 100,000 population in different local communities. The majority of cases (n=64) were aged between two and 15 years. Echovirus 30 was cultured from two of four cerebrospinal fluid specimens. The outbreak, for which no common source has yet been identified, is ongoing. PMID- 20738997 TI - The end of the pandemic - what will be the pattern of influenza in the 2010-11 European winter and beyond? PMID- 20738998 TI - Report published on factors contributing to the spread of Campylobacter in the European Union. PMID- 20738999 TI - Value of syndromic surveillance in monitoring a focal waterborne outbreak due to an unusual Cryptosporidium genotype in Northamptonshire, United Kingdom, June - July 2008. AB - The United Kingdom (UK) has several national syndromic surveillance systems. The Health Protection Agency (HPA)/NHS Direct syndromic surveillance system uses pre diagnostic syndromic data from a national telephone helpline, while the HPA/QSurveillance national surveillance system uses clinical diagnosis data extracted from general practitioner (GP)-based clinical information systems. Data from both of these systems were used to monitor a local outbreak of cryptosporidiosis that occurred following Cryptosporidium oocyst contamination of drinking water supplied from the Pitsford Reservoir in Northamptonshire, United Kingdom, in June 2008. There was a peak in the number of calls to NHS Direct concerning diarrhoea that coincided with the incident. QSurveillance data for the local areas affected by the outbreak showed a significant increase in GP consultations for diarrhoea and gastroenteritis in the week of the incident but there was no increase in consultations for vomiting. A total of 33 clinical cases of cryptosporidiosis were identified in the outbreak investigation, of which 23 were confirmed as infected with the outbreak strain. However, QSurveillance data suggest that there were an estimated 422 excess diarrhoea cases during the outbreak, an increase of about 25% over baseline weekly levels. To our knowledge, this is the first time that data from a syndromic surveillance system, the HPA/QSurveillance national surveillance system, have been able to show the extent of such a small outbreak at a local level. QSurveillance, which covers about 38% of the UK population, is currently the only GP database that is able to provide data at local health district (primary care trust) level. The Cryptosporidium contamination incident described demonstrates the potential usefulness of this information, as it is unusual for syndromic surveillance systems to be able to help monitor such a small-scale outbreak. PMID- 20739001 TI - Assessing the risk of a community outbreak of hepatitis A on blood safety in Latvia, 2008. AB - Post-transfusion hepatitis A virus (HAV) infection worldwide is considered a sporadic event. An outbreak of HAV infection occurred in Latvia between the end of 2007 and throughout 2008 with more than 2,800 confirmed cases reported over a 13-month period (incidence of 123 per 100,000 population). The majority of reported HAV infection cases were in people over 18 years of age and in people living in the capitalcity, Riga. We estimated that the crude risk for HAV contamination of whole blood supplies in Riga between February and October 2008 ranged from 1.4 to 10.6 per 10,000 donated units. In people under 40 years of age, the risk of receiving an infectious blood transfusion was more than 3.0 per 10,000 recipients between August and October 2008 during the peak of the outbreak. We conclude that there is a previously under-recognised impact of HAV on blood safety during widespread outbreaks of this disease. Estimating the risk of contamination of blood supplies during an infectious disease outbreak scenario is important for fine tuning risk assessments and potentially improving public health practices. PMID- 20739000 TI - Laboratory-based surveillance for Cryptosporidium in France, 2006-2009. AB - In 2002, the French Food Safety Agency drew attention to the lack of information on the prevalence of human cryptosporidiosis in the country. Two years later, the ANOFEL Cryptosporidium National Network (ACNN) was set up to provide public health authorities with data on the incidence and epidemiology of human cryptosporidiosis in France. Constituted on a voluntary basis, ACNN includes 38 hospital parasitology laboratories (mainly in university hospitals). Each laboratory is engaged to notify new cases of confirmed human cryptosporidiosis, store specimens (e.g. stools, duodenal aspirates or biopsies) and related clinical and epidemiological data, using data sheet forms. From January 2006 to December 2009, 407 cryptosporidiosis cases were notified in France and 364 specimens were collected. Of the notified cases, 74 were children under four years of age, accounting for 18.2%. HIV-infected and immunocompetent patients represented 38.6% (n=157) and 28% (n=114) of cases, respectively. A marked seasonal pattern was observed each year, with increased number of cases in mid to late summer and the beginning of autumn. Genotyping of 345 isolates from 310 patients identified C. parvumin 168 (54.2%) cases, C. hominis in 113 (36.4%) and other species in 29 (9.4%), including C. felis (n=15), C. meleagridis (n=4), C. canis (n=4), Cryptosporidium chipmunk genotype (n=1), Cryptosporidium rabbit genotype (n=1) and new Cryptosporidium genotypes (n=4). These data represent the first multisite report of laboratory-confirmed cases of cryptosporidiosis in France. PMID- 20739002 TI - Influenza antiviral prescribing practices during the 2007-08 and 2008-09 influenza seasons in the setting of increased resistance to oseltamivir among circulating influenza viruses. AB - INTRODUCTION: In December 2008, new interim guidelines on the use of influenza antiviral agents were released in response to a high prevalence of circulating oseltamivir-resistant seasonal influenza A(H1N1) and adamantane-resistant influenza A(H3N2) viruses. Zanamivir, oseltamivir +/- an adamantane, or oseltamivir was recommended, depending on virus type, subtype, and local surveillance data. MATERIALS AND METHODS: Information about antiviral prescribing practices among IDSA Emerging Infections Network (EIN) members was obtained using two web-based questionnaires; one in January 2009 regarding the prior 2007-08 influenza season and one in April 2009 (prepandemic), regarding the concurrent 2008-09 season. RESULTS: In the 2007-08 survey, 646 (52%) of 1249 EIN members responded and in the 2008-09 season survey, 350 (27%) of 1281 responded. In 2008 09 vs. 2007-08: 59% vs. 69% prescribed or recommended antivirals for treatment (p<.0001); 48% vs. 80% prescribed oseltamivir alone and 39% vs. 10% prescribed zanamivir alone (p<.0001 for both). During 2008-09 28% reported treating fewer patients compared with 2007-08; 42% felt antivirals were less effective due to resistance and 40% felt patients had less severe illness. During 2008-09, 42% of respondents reported difficulty providing zanamivir to patients vs. 5% for oseltamivir (p<.0001). Only 11% of respondents could test for influenza A subtype. During both seasons, ~55% used local surveillance data to make treatment decisions. DISCUSSION: A mild winter influenza season, difficulty obtaining recommended agents, and lack of access to subtype diagnosis and surveillance data may have contributed to reduced antiviral use during 2008-09. PMID- 20739003 TI - Partial selective inhibition of HIV-1 reverse transcriptase and human DNA polymerases gamma and beta by thiated 3'-fluorothymidine analogue 5' triphosphates. AB - 3'-Deoxy-3'-fluorothymidine (FLT, alovudine((r))) belongs to the most potent agents inhibiting HIV-1 replication. Its 5'-triphosphate (FLTTP) is a potent inhibitor of HIV-1 reverse transcriptase (HIV RT). Unfortunately, FLT exerts substantial hematologic toxicity both in vitro and in vivo. It was suggested that this toxicity may be related to inhibition of human DNA polymerases, especially mitochondrial DNA polymerase gamma, by nucleoside analogue 5'-triphosphates leading to termination of DNA synthesis and mitochondrial dysfunction. To decrease the toxicity of FLT, its thiated analogues, 4-SFLT and 2-SFLT, were previously synthesized and shown to be potent inhibitors of HIV-1 with low in vitro cytotoxicity. To explain this phenomenon in the present study the synthesis of 5'-triphosphates of thiated FLT analogues was undertaken and their interaction with recombinant HIV-1 RT and human DNA polymerases gamma (pol gamma) and beta (pol beta) was investigated. It was shown that 3'-deoxy-3'-fluoro-4-thiothymidine 5'-triphosphate (4-SFLTTP) and 3'-deoxy-3'-fluoro-2-thiothymidine 5'-triphosphate (2-SFLTTP) were, similarly to FLTTP, potent competitive inhibitors of HIV-1 RT, with K(i)(app) values of 0.091 and 0.022 MUM respectively. It is of interest that 2-SFLTTP, a compound in an unusual syn conformation around the glycosidic bond was an uncompetitive inhibitor of human mitochondrial DNA pol gamma with K(i)(app) of 0.174 MUM, while 4-SFLTTP in anti conformation inhibited this enzyme similarly to FLTTP, i.e., non-competitively, with K(i)(app) of 0.055 MUM. Both 4 SFLTTP and 2-SFLTTP were competitive inhibitors of human DNA pol beta, with K(i)(app) values of 16.84 and 4.04 MUM, respectively. The results point to partially selective inhibition of HIV RT by thiated 3'-fluorothymidine 5' triphosphate analogues. Of special interest is that 2-SFLTTP, showing syn conformation, is a less potent inhibitor of human mitochondrial pol gamma than 4 SFLTTP and FLTTP, both in the anti conformation, and has a higher inhibitory activity against HIV-1 RT than 4-SFLTTP. Moreover, the parent nucleoside 2-SFLT possessing the syn conformation shows a more potent anti-HIV-1 activity and a better selectivity index than its 4-thio isomer in the anti conformation (Matthes et al., 1989; Poopeiko et al., 1995), 2-SFLT is a potent and selective anti-HIV-1 agent with the selectivity index 4-fold higher than that of FLT. Findings regarding the mechanisms of antiviral and cytotoxic activities of FLT and its thioanalogues are discussed. PMID- 20739004 TI - Dynamics and mechanisms of oscillatory photosynthesis. AB - We classify mathematical models that can be used to describe photosynthetic oscillations using ideas from nonlinear dynamics, and discuss potential mechanisms for photosynthetic oscillations in the context of this classification. We then turn our attention to recent experiments with leaves transferred to a low CO2 atmosphere which revealed stochastic oscillations with a period of a few seconds. Rubisco is the enzyme that takes both CO2 and O2 as substrates correspondingly for photosynthetic assimilation and for photorespiration. Photosynthesis depletes CO2 and produces O2 while respiration and photorespiration work in the opposite direction, so the product of one process becomes the reactant of the other coupled process. We examine the possibility of oscillations of CO2 and O2 in the leaf in relation to photorespiration. We suggest that in the cell, oscillations with a period of a few seconds, corresponding to the time between photosynthetic CO2 fixation and photorespiratory CO2 release, underlie the dynamics of metabolism in C3 plants. PMID- 20739006 TI - Internally bridging water molecule in transmembrane alpha-helical kink. AB - There are hundreds of membrane protein atomic coordinates in the Protein Data Bank (PDB), and high-resolution structures of better than 2.5 A enable the visualization of a sizable number of amphiphiles (lipid and/or detergent) and bound water molecules as essential parts of the structure. Upon scrutinizing these high-resolution structures, water molecules were found to 'wedge' and stabilize large kink angle (30-40 degrees) in a simple cylindrical model at the transmembrane helical kinks so as to form an inter-helical cavity to accommodate a ligand binding or active site as a crucial structural feature in alpha-helical integral membrane proteins. Furthermore, some of these water molecules are proposed to play a pivotal role of their conformational change to exert their functional regulation. PMID- 20739005 TI - Substrate and drug binding sites in LeuT. AB - LeuT is a member of the neurotransmitter/sodium symporter family, which includes the neuronal transporters for serotonin, norepinephrine, and dopamine. The original crystal structure of LeuT shows a primary leucine-binding site at the center of the protein. LeuT is inhibited by different classes of antidepressants that act as potent inhibitors of the serotonin transporter. The newly determined crystal structures of LeuT-antidepressant complexes provide opportunities to probe drug binding in the serotonin transporter, of which the exact position remains controversial. Structure of a LeuT-tryptophan complex shows an overlapping binding site with the primary substrate site. A secondary substrate binding site was recently identified, where the binding of a leucine triggers the cytoplasmic release of the primary substrate. This two binding site model presents opportunities for a better understanding of drug binding and the mechanism of inhibition for mammalian transporters. PMID- 20739008 TI - Gestational trophoblastic disease II: classification and management of gestational trophoblastic neoplasia. AB - Gestational trophoblastic neoplasia (GTN) includes invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The overall cure rate in treating these tumors is currently >90%. Thorough evaluation and staging allow selection of appropriate therapy that maximizes chances for cure while minimizing toxicity. Nonmetastatic (stage I) and low-risk metastatic (stages II and III, score <7) GTN can be treated with single agent chemotherapy resulting in a survival rate approaching 100%. High-risk GTN (stages II-IV, score >=7) requires initial multiagent chemotherapy with or without adjuvant radiation and surgery to achieve a survival rate of 80-90%. PMID- 20739007 TI - Unlocking the eukaryotic membrane protein structural proteome. AB - Most of the 231 unique membrane protein structures (as of 3/2010) are of bacterial membrane proteins (MPs) expressed in bacteria, or eukaryotic MPs from natural sources. However eukaryotic membrane proteins, especially those with more than three membrane crossings rarely succumb to any suitable expression in bacterial cells. They typically require expression in eukaryotic cells that can provide appropriate endoplasmic reticulum, chaperones, targeting and post translational processing. In evidence, only approximately 20 eukaryotic MP structures have resulted from heterologous expression. This is required for a general approach to target particular human or pathogen membrane proteins of importance to human health. The first of these appeared in 2005. Our review addresses the special issues that pertain to the expression of eukaryotic and human membrane proteins, and recent advances in the tool kit for crystallization and structure determination. PMID- 20739009 TI - Inadvertent rupture of benign cystic teratoma does not impair future fertility. AB - OBJECTIVE: We sought to investigate the reproductive outcomes of women who underwent laparoscopic removal of benign cystic teratoma with or without intraoperative spillage. STUDY DESIGN: The reproductive outcomes of reproductive age women following laparoscopic removal of benign cystic teratoma from 1997 through 2007 were investigated by a telephone questionnaire. RESULTS: In all, 128 reproductive age women underwent benign cystic teratoma removal, and reproductive outcomes were available for 45. Among those 45 women, intraoperative spillage occurred in 16 (35.6%). The rate of spontaneous pregnancies was significantly lower for the nonspillage compared to the intraoperative spillage groups (20/29 [68.9%] vs 16/16 [100%], respectively; P = .01). However, the median time from surgery to the first pregnancy was similar (22 and 18.5 months, respectively; P = .9). From the 9 remaining women in the nonspillage group, 4 conceived with ovulation induction, 2 conceived with in vitro fertilization, and 3 were infertile. CONCLUSION: Intraoperative spillage of benign cystic teratomas does not lead to long-term infertility. PMID- 20739010 TI - The meaning of intraabdominal bowel dilation in fetuses with gastroschisis. PMID- 20739011 TI - Oral hypoglycemic agents vs insulin in management of gestational diabetes: a systematic review and metaanalysis. AB - OBJECTIVE: The objective of this review was to provide pooled estimates of randomized controlled trials comparing the effects of oral hypoglycemic agents with insulin in achieving glycemic control and to study the maternal and perinatal outcomes in gestational diabetes mellitus. STUDY DESIGN: A protocol for the study was developed. All metaanalyses were performed using Stats Direct statistical software (Stats Direct Ltd, Cheshire, UK). RESULTS: Six studies comprising 1388 subjects were analyzed. No significant differences were found in maternal fasting (weighted mean difference [WMD], 1.31; 95% confidence interval [CI], 0.81-3.43) or postprandial (WMD, 0.80; 95% CI, -3.26 to 4.87) glycemic control. Use of oral hypoglycemic agents (OHAs) was not associated with risk of neonatal hypoglycemia (odds ratio [OR], 1.59; 95% CI, 0.70-3.62), increased birthweight (WMD, 56.11; 95% CI, -42.62 to 154.84), incidence of caesarean section (OR, 0.91; 95% CI, -0.68 to 1.22), or incidence of large-for-gestational age babies (OR, 1.01; 95% CI, 0.61-1.68). CONCLUSION: Our study demonstrates that there are no differences in glycemic control or pregnancy outcomes when OHAs were compared with insulin. PMID- 20739013 TI - Gigantomastia and vulvar lactating adenoma in a patient with myasthenia during pregnancy. AB - We report the association of gigantomastia during pregnancy and a lactating adenoma in ectopic breast tissue of the vulva in a context of myasthenia in a 27 year-old primigravid woman. We discuss the pathophysiologic condition and management of gigantomastia that involves ectopic breast tissue during pregnancy. PMID- 20739012 TI - Current knowledge of obesity's effects in the pre- and periconceptional periods and avenues for future research. AB - The prevalence of obesity is growing among reproductive-age women. This is concerning because obesity has significant health-related consequences. Aside from the long-term risks of diabetes, heart disease, and some types of cancer, obesity poses immediate threats for young women including subfertility and adverse early and late pregnancy outcomes. Epidemiologic and experimental studies demonstrate associations between prepregnancy obesity and poor reproductive outcomes; however, the mechanisms involved are poorly understood. We discuss current knowledge of the pathophysiology of obesity in early reproductive events and how these events may affect reproductive outcomes including fertility and miscarriage risk. We also discuss avenues for future research and interventions to improve reproductive outcomes for obese women. PMID- 20739015 TI - Ambulatory procedures for female pelvic floor disorders in the United States. AB - OBJECTIVE: The aim of this study was to estimate the number of women undergoing ambulatory surgical procedures for female pelvic floor disorders (PFDs) in the United States and to compare age-adjusted ambulatory surgical case rates between 1996 and 2006. STUDY DESIGN: We analyzed data from the 1996 and 2006 National Survey of Ambulatory Surgery, a federal public access de-identified database. Procedures for PFDs were identified using International Classification of Diseases-9th revision Clinical Modification procedure codes for urinary incontinence, fecal incontinence, and pelvic organ prolapse. RESULTS: The number of women undergoing ambulatory surgical procedures for urinary incontinence increased from 34,968 (95% confidence interval, 25,583-44,353) in 1996 to 105,656 (95% confidence interval, 79,033-132,279) in 2006. The age-adjusted ambulatory surgical case rates for all PFDs increased from 7.91 per 10,000 in 1996 to 12.10 per 10,000 in 2006 (P = .0006). CONCLUSION: Ambulatory procedures for urinary incontinence increased between 1996 and 2006, as well as the age-adjusted ambulatory case rate for all PFDs. PMID- 20739016 TI - Head movements during two computer work tasks assessed by accelerometry. AB - We investigated whether potential differences in head inclinations and accelerations for two highly similar computer work tasks could be detected using (1) a triaxial accelerometer and (2) a simulated uniaxial accelerometer. Ten subjects' head movements were registered with a triaxial accelerometer system for two similar document-management tasks at their work place: a fully electronic document-management task and one also involving paper documents. In situations where head movements were small, a triaxial accelerometer was able to discriminate between the different degrees of static work of the neck in terms of range of head inclinations and accelerations. A difference in head acceleration was also found by using a simulated uniaxial accelerometer. Thus, in terms of head movement and for work similar to this office work, potential dynamic differences in observationally similar work tasks can be investigated by using a triaxial accelerometer. For acceleration alone, a uniaxial accelerometer can also be used. PMID- 20739017 TI - Polymorphic variants of genes related to arginine metabolism and the risk of orofacial clefts. AB - OBJECTIVE: Maternal mid-pregnancy low levels of symmetric dimethylarginine and newborn low levels of citrulline are suspected to be risk factors for orofacial clefts. This study was undertaken to investigate the involvement of polymorphic variants of genes related to arginine metabolism in the susceptibility of clefting. DESIGN: PCR-RFLP and HRM analyses were used to analyze single nucleotide polymorphisms (SNPs) of ASS1, ASL, and SLC25A13 in 172 children with non-syndromic cleft lip with or without cleft palate (CL/P) and 188 controls without congenital anomalies. The differences in allele and genotype frequencies between cases and controls were determined using standard Chi-square and Fisher exact tests. The odds ratio (OR) and associated 95% confidence intervals (95% CI) for individuals with CL/P versus controls were also calculated. Associations between the investigated polymorphisms and the risk of being born with an orofacial cleft were tested using the nonparametric and genetic model-free Multifactor Dimensionality Reduction (MDR) approach. RESULTS: Analysis of five SNPs of the ASS1 gene revealed that the G allele of rs7860909 is associated with increased CL/P risk. Compared to individuals with the AA genotype, the G allele carriers had an OR of 1.768 (95% CI: 1.133-2.759; p=0.012). For the remaining SNPs of all analysed genes, there was no overall evidence for cleft association considering the allele and genotype distribution. However, gene-by-gene interaction analysis conducted using the MDR approach revealed a significant interactive genetic effect of ASS1 (rs666174) and SLC25A13 (rs10252573) on the occurrence of clefting (p=0.002). CONCLUSION: Our results demonstrate moderate evidence for the association of polymorphic variants of genes related to arginine metabolism with abnormal palatogenesis. PMID- 20739019 TI - A comparative study on the graft copolymerization of acrylic acid onto rayon fibre by a ceric ion redox system and a gamma-radiation method. AB - Functionalization of rayon fibre has been carried out by grafting acrylic acid (AAC) both by a chemical method using a Ce(4+)-HNO(3) redox initiator and by a mutual irradiation (gamma-rays) method. The reaction conditions affecting the grafting percentage have been optimized for both methods, and the results are compared. The maximum percentage of grafting (50%) by the chemical method was obtained utilizing 18.24 * 10(-3) moles/L of ceric ammonium nitrate (CAN), 39.68 * 10(-2) moles/L of HNO(3), and 104.08 * 10(-2) moles/L of AAc in 20 mL of water at 45 degrees C for 120 min. For the radiation method, the maximum grafting percentage (60%) was higher, and the product was obtained under milder reaction conditions using a lower concentration of AAc (69.38 * 10(-2) moles/L) in 10 mL of water at an optimum total dose of 0.932 kGy. Swelling studies showed higher swelling for the grafted rayon fibre in water (854.54%) as compared to the pristine fibre (407%), while dye uptake studies revealed poor uptake of the dye (crystal violet) by the grafted fibre in comparison with the pristine fibre. The graft copolymers were characterized by IR, TGA, and scanning electron micrographic methods. Grafted fibre, prepared by the radiation-induced method, showed better thermal behaviour. Comparison of the two methods revealed that the radiation method of grafting of acrylic acid onto rayon fibre is a better method of grafting in comparison with the chemical method. PMID- 20739018 TI - Fronto-temporal spontaneous resting state functional connectivity in pediatric bipolar disorder. AB - BACKGROUND: The recent upsurge in interest about pediatric bipolar disorder (BD) has spurred the need for greater understanding of its neurobiology. Structural and functional magnetic resonance imaging studies have implicated fronto-temporal dysfunction in pediatric BD. However, recent data suggest that task-dependent neural changes account for a small fraction of the brain's energy consumption. We now report the first use of task-independent spontaneous resting state functional connectivity (RSFC) to study the neural underpinnings of pediatric BD. METHODS: We acquired task-independent RSFC blood oxygen level-dependent functional magnetic resonance imaging scans while participants were at rest and also a high resolution anatomical image (both at three Tesla) in BD and control youths (n = 15 of each). We focused, on the basis of prior research, on the left dorsolateral prefrontal cortex (DLPFC), amygdala, and accumbens. Image processing and group level analyses followed that of prior work. RESULTS: Our primary analysis showed that pediatric BD participants had significantly greater negative RSFC between the left DLPFC and the right superior temporal gyrus versus control subjects. Secondary analyses using partial correlation showed that BD and control youths had opposite phase relationships between spontaneous RSFC fluctuations in the left DLPFC and right superior temporal gyrus. CONCLUSIONS: Our data indicate that pediatric BD is characterized by altered task-independent functional connectivity in a fronto-temporal circuit that is also implicated in working memory and learning. Further study is warranted to determine the effects of age, gender, development, and treatment on this circuit in pediatric BD. PMID- 20739020 TI - Long-term urinary retention after laparoscopic surgery for deep endometriosis. AB - OBJECTIVE: To report on chronic urinary retention after surgery for deep endometriosis and the possible risk factors for this complication. DESIGN: Descriptive study. SETTING: University hospital. PATIENT(S): Four patients with deep endometriosis who developed this complication. INTERVENTION(S): Laparoscopic surgery, intermittent self-catheterization (ISC). MAIN OUTCOME MEASURE(S): To identify site(s) of lesion associated with this complication. RESULT(S): Four patients developed this complication from damage to the inferior hypogastric plexus involving the sympathetic and/or parasympathetic afferents from the bladder. One patient regained complete bladder function 8 months after surgery, and the others required ISC at the time of writing (13, 24, and 3 months after surgery). Patients with lesions located laterally and deep in the uterosacral ligaments especially near the ischial spines were at high risk. All patients were, however, satisfied with the results of surgery. CONCLUSION(S): Most such injuries are unpredictable, but in our experience, two of three patients with lesions near the ischial spine developed this complication. Chronic urinary retention after radical endometriosis surgery is rare and often under reported. Although most lesions are unilateral and have a potential for improvement, it is not known how long these effects will last. More data from other centers may help in providing additional information. PMID- 20739021 TI - Paediatric pelvic ring fractures and associated injuries. AB - INTRODUCTION: Paediatric pelvic fractures have been infrequently reviewed. The study was performed to highlight the unique features of pelvic fractures in children. PATIENTS AND METHODS: A 14-year retrospective study was undertaken of all patients treated for a pelvic fracture at our institute. RESULTS: Thirty-nine children were included. The mean Injury Severity Score (ISS) was 17.1 (range 4 75). Simple ring fractures were the most common type (46%), dominated by pedestrian versus motor vehicle trauma (58.9%). A pelvic fracture was evident on the initial plain radiographs of all 39 children. Further radiographic investigations (12 CTs and 1 MRI) were undertaken in 13 (33%) of the children. Additional posterior ring fractures were identified in 9. A total of 32 children (82%) sustained one or more associated injuries. Head injuries accounted for 25% and orthopaedic/skeletal injuries for 33% of all associated injuries. Fourteen children required a total of 24 acute surgical procedures. Mean out-pateint clinical follow-up was for 27 months (range 3-85). There was one mortality in this series. Eight children (20%) suffered long term sequale. CONCLUSION: Paediatric pelvic fractures differ from their adult counterpart in aetiology, fracture type, and associated injury pattern. They represent a reliable marker for severe trauma. Prospective studies are required to define optimal treatment guidelines, particularly in older children. PMID- 20739022 TI - The diagnosis of acute urethral trauma. AB - BACKGROUND: During trauma resuscitation, blind catheterization of an injured urethra may aggravate the injury by disrupting a partially torn urethra. In busy trauma centers, retrograde urethrograms (RUG) prior to catheterisation for all patients with unstable pelvic fractures presents a challenge during trauma resuscitation, and the procedure is not commonly practiced despite Advanced Trauma Life Support (ATLS) and World Health Organisation recommendations. The aim of this study was to determine the presenting clinical features of patients with urethral injuries and to predict major trauma patients needing further investigation to exclude this injury. METHODS: A retrospective review of adult major trauma patients diagnosed with urethral injuries during an 8-year period at a major trauma centre, was conducted. RESULTS: There were 998 major trauma patients with fractures of the pelvis over the study period, of whom 223 had pubic symphysis disruption. There were 29 patients with urethral injuries. The sensitivity of any one of the traditional signs of urethral trauma was 66.7% (95% CI: 46.0-82.8). After exclusion of patients with penetrating trauma and iatrogenic injuries, pubic symphysis disruption on initial pelvis AP X-ray and/or the clinical signs of urethral injury had a sensitivity of 100% (95% CI: 84.4 100.0) for urethral trauma. DISCUSSION: Reliance on clinical features alone to predict urethral injury results in a substantial proportion of missed injuries in major trauma patients. RUGs did not appear to be needed in patients with no disruption of the pubic symphysis on initial pelvis X-ray or where no signs of urethral injury are present. In the absence of clinical signs and pubic symphysis disruption, blind urethral catheterisation may be attempted. PMID- 20739023 TI - Gait alterations in rats following attachment of a device and application of altered knee loading. AB - Animal models are widely used to study cartilage degeneration. Experimental interventions to alter contact mechanics in articular joints may also affect the loads borne by the leg during gait and consequently affect the overall loading experienced in the joint. In this study, force plate analyses were utilized to measure parameters of gait in the rear legs of adult rats following application of a varus loading device that altered loading in the knee. Adult rats were assigned to Control, Sham, or Loaded groups (n >= 4/each). Varus loading devices were surgically attached to rats in the Sham and Loaded groups. In the Loaded group, this device applied a controlled compressive overload to the medial compartment of the knee during periods of engagement. Peak ground reaction forces during walking were recorded for each rear leg of each group. Analyses of variance were used to compare outcomes across groups (Control, Sham, and Loaded), leg (contralateral, experimental) and device status (disengaged, engaged) to determine the effects of surgically attaching the device and applying a compressive overload to the joint with the device. The mean peak vertical force in the experimental leg was reduced to 30% in the Sham group in comparison to the contralateral leg and the Control group, indicating an effect of attaching the device to the leg (p<0.01). No differences were found in ground reaction forces between the Sham and Loaded groups with application of compressive overloads with the device. The significant reduction in vertical force due to the surgical attachment of the varus loading device must be considered and accounted for in future studies. PMID- 20739024 TI - A quantitative comparison of a bone remodeling model with dual-energy X-ray absorptiometry and analysis of the inter-individual biological variability of femoral neck T-score. AB - The development of consistent procedures with the inclusion of patient-specific data is essential in the computational modeling of biological processes, in order to achieve clinical relevant data. In this work, these issues are addressed with the development of a methodology that combines the gold standard technique for bone mineral density measurement and osteoporosis diagnosis, Dual energy X-ray absorptiometry (DXA), with a computational model for bone remodeling simulation. The DXA results were divided in three samples constituted from proximal femur DXA exams of patients in different stages of bone mineral density (normal, osteopenia and osteoporosis). These results were quantitatively compared with computational model results. A correlation study was performed between femoral neck T-score and a parameter from the model to ascertain the hypothesis of adjusting the model accordingly to biological variables. The results evidenced the predictive ability of the computational model in the estimation of femoral neck bone mineral content (BMC), with a maximum relative error of 3.92%. On the other hand, a strong correlation (R=-0.862) was found between the variables in study and a mathematical relationship was obtained to estimate the range of values for a model parameter that leads to biological relevant results. The methodology developed and the results obtained represent a solid and reliable basis to further studies on bone quality, ensuring the validity of the computational model in the simulation of bone remodeling process. PMID- 20739025 TI - Solvent-bar microextraction of herbicides combined with non-aqueous field amplified sample injection capillary electrophoresis. AB - Solvent-bar microextraction (SBME) based on two-phase (water-to-organic) extraction was for the first time used as the sample pretreatment method for the non-aqueous capillary electrophoresis (NACE) of herbicides of environmental concern. Due to the compatibility of the extractant organic solvent and the NACE separation system, the extract could be introduced directly to the CE system after SBME. Through investigations of the effect of sample pH, extraction time, agitation speed and salt addition on extraction efficiency, the most suitable extraction conditions were determined: sample solution at a pH of 1, without added salt, and stirring at 700 revolutions per minute for 30 min. SBME as applied here was also compared with single-drop microextraction and hollow fiber protected liquid-phase microextraction. SBME showed the highest extraction efficiency. In addition, field-amplified sample injection with pre-introduced organic solvent plug removal using the electroosmotic flow as a pump (FAEP) was used to enhance the sensitivity further in NACE. Based on studies of the effect of different organic solvents, different lengths of the organic plugs and different volumes of sample injection on stacking efficiency under the most suitable separation conditions, methanol was found to be the most efficient solvent for on-line preconcentration. Combined with SBME, FAEP-NACE achieved limits of detection of between 0.08 ng/mL and 0.14 ng/mL for the studied analytes. This preconcentration approach for NACE was demonstrated to be amenable to aqueous environmental samples by applying it to spiked river water. PMID- 20739026 TI - Hydrodynamic chromatography of polystyrene microparticles in micropillar array columns. AB - We report on the possibility to perform HDC in micropillar array columns and the potential advantages of such a system. The HDC performance of a pillar array column with pillar diameter = 5 microm and an interpillar distance of 2.5 microm has been characterized using both a low MW tracer (FITC) and differently sized polystyrene bead samples (100, 200 and 500 nm). The reduced plate height curves that were obtained for the different investigated markers all overlapped very well, and attained a minimum value of about h(min)=0.3 (reduction based on the pillar diameter), corresponding to 1.6 microm in absolute value and giving good prospects for high efficiency separations. The obtained reduced retention time values were in fair agreement with that predicted by the Di Marzio and Guttman model for a flow between flat plates, using the minimal interpillar distance as characteristic interplate distance. PMID- 20739027 TI - Lexico-semantic processing in children with specific language impairment: the overactivation hypothesis. AB - The hypothesis indicating an overactivation of the lexico-semantic network in children with specific language impairment (SLI) was tested using an auditory pair-primed paradigm (PPP), where participants made a lexical-decision on the second word of a noun pair that could be semantically related, or not, to the first one. Though children with SLI were proven to be as accurate as children matched for receptive vocabulary age, they presented a larger priming effect in the PPP in terms of both reaction time and accuracy. These results preliminarily support the hypothesis of an overactivation of the lexico-semantic network. LEARNING OUTCOMES: As a result of reading this paper the reader will be able to (1) understand how the pair-primed paradigm can contribute to investigate the online spreading of the activation within the lexico-semantic network; (2) be aware of the fact that during development it is unlikely that some cognitive domain are completely typical (residual normality), while others develop atypically; (3) the reader will be aware that children with SLI present some subtle abnormalities in the lexico-semantic network, which appears to be overactive. PMID- 20739028 TI - Early orthographic influences on phonemic awareness tasks: evidence from a preschool training study. AB - Experienced readers show influences of orthographic knowledge on tasks ostensibly tapping phonemic awareness. Here we draw on data from an experimental training study to demonstrate that even preschoolers show influences of their emerging orthographic abilities in such tasks. A total of 40 children were taught some letter-sound correspondences but not others. A selective effect of this training was found on their phonemic awareness task performance for the trained items. These findings point to the multidetermined nature of performance on tasks normally considered as measuring phonemic awareness and have implications for theories of the role of phonemic awareness in reading acquisition. PMID- 20739030 TI - Erythropoietin (EPO) influences colonic anastomotic healing in a rat model by modulating collagen metabolism. AB - INTRODUCTION: Anastomotic failure is one of the most frequent complications in abdominal surgery. During anastomotic healing. the strength of the intestinal tissue nearby is closely related to the accumulation of collagen in interlinked scar tissue. This in turn is influenced, among other things, by single groups of matrixmetalloproteinases, especially collagenases (MMP-1, -8, and -13) and gelatinases (MMP-2 and -9). EPO is known to induce the expression of tissue inhibitor-of-matrixmetalloproteinases-1 (TIMP-1) and thereby to down-regulate MMPs. MATERIALS AND METHODS: We used a rat as an experimental model and applied a high dose of EPO (5U/g BW s.c.), one dose 24 h before operation (as pre conditioning) and one dose directly after performing a colonic anastomosis. After 3 and after 5 d, respectively, immunohistochemical stainings for MMP-2, -8, and 9 as well as TIMP-1 were carried out and evaluated semiquantitatively for each layer of the colonic wall. Sirius-red staining and cross-polarization microscopy were evaluated and the collagen I/III ratio calculated. Anastomotic and colonic tissue distal to the anastomosis were used to determine collagen content. RESULTS: We found increased bursting pressure 5 d post-surgery after applying erythropoietin. It was thus shown that EPO influences collagen metabolism and changes the collagen I/III ratio in the colon distal to the anastomosis. The evaluation of immunohistochemistry did not show the expected ubiquitous up regulation of TIMP-1 and down-regulation of MMPs. Nevertheless, correlations between TIMP-1, MMP-8, and collagen I/III ratio could only be established after the application of EPO. CONCLUSION: Contrary to our hypothesis, the picture of TIMP-1 and of the regulation of the MMPs after the application of EPO is not as clear as expected. EPO improves anastomotic bursting strength and the correlation of TIMP-1, MMP-8, and collagen type I/III ratio can only be seen after the application of EPO. PMID- 20739029 TI - Eczema in early life: genetics, the skin barrier, and lessons learned from birth cohort studies. PMID- 20739031 TI - EPCK1, a vitamin C and E analogue, reduces endotoxin-induced systemic inflammation in mice. AB - BACKGROUND: Phosphate ester of vitamin C and vitamin E (EPCK1), a strong antioxidant, is a water- and lipid-soluble phosphate ester of vitamin C and vitamin E. In the current study, we tested whether EPCK1 inhibits oxidative stress and prevents systemic inflammation. MATERIALS AND METHODS: Mice were randomly divided into a negative control group, a lipopolysaccharide (LPS) induced sepsis group, and a group treated with an intraperitoneal infusion of EPCK1 (10 mg/kg) prior to or following LPS administration. In addition, RAW 264.7 cells were treated with LPS in the presence or absence of EPCK1. We examined levels of high mobility group box 1 (HMGB1) protein and inducible nitric oxide synthase (iNOS) in both in vivo and in vitro experiments, and liver histopathology in the in vivo experiment. RESULTS: Liver histopathology significantly improved in the EPCK1 group compared with the LPS group. Although LPS administration increased HMGB1 and nitric oxide (NO) secretion, EPCK1 decreased the secretion of these mediators in vitro and in vivo. CONCLUSIONS: Our findings suggest that EPCK1 may inhibit inflammation and potentially function as a novel anti-inflammatory therapeutic agent. PMID- 20739032 TI - Effects of pentoxyfilline and heparin on reperfusion injury island skin flaps in rats exposed to tobacco. AB - BACKGROUND: Ischemia-reperfusion injury is believed to be a major cause of transferred skin flap failure. Cigarette smoking is known to be associated with endogenous antioxidant depletion, hypercoagulability, and cutaneous vasoconstriction. This investigation was carried out to study possible effects of pentoxyfilline or heparin on rat skin reperfusion injury under tobacco exposure. MATERIALS AND METHODS: Thirty-six rats were randomized into two major groups: 18 were exposed to cigarette smoke during a 4 wk period prior to surgery; the remaining 18 underwent a sham smoking procedure. Each group was further divided into three equal subgroups: heparin, pentoxyfilline, and saline solution. One identical skin flap was raised in each animal. The vasculature of the flap was clamped for 3 h and reperfused for 5 min. A venous blood sample was obtained from the flap after reperfusion for serum malondialdehyde (MDA) and myeloperoxidase (MPO) analysis. Flap survival was assessed 7 d after the procedure. RESULTS: The lipid peroxidation levels and flap necrosis were significantly higher in the cigarette-smoking group skin flaps. There was also a decrease of MPO activity in this group compared with the non-smoking group. Heparin-treated rats had significantly lower MDA levels and showed the most viable percent area among smoking rats. CONCLUSIONS: These data suggest that heparin had a significant beneficial effect both on flap survival and on the lipid peroxidation reduction after smoke exposure in the rat axial-pattern skin flap subjected to ischemia and reperfusion injury. Pharmacologic therapy may represent an alternative way to counteract tobacco effects in flap surgery in emergency situations. PMID- 20739034 TI - The pre-requisite of a second-generation glioma PET biomarker. AB - Since the introduction of FDG into the field of molecular imaging with positron emission tomography (PET) more than three decades ago, FDG has been the tracer of choice for oncology PET imaging. Despite the relative disadvantages of FDG and the relative benefits of its challengers, FDG remains the most commonly used glioma tracer nowadays. The present article surveys the expectations of the field and gives a concise summary of recent developments; including the issues pertaining to the continued search for an optimal second-generation PET biomarker for glioma. MINI-ABSTRACT: The present article gives a concise summary of recent developments; including the issues pertaining to the continued search for an optimal PET biomarker for glioma. PMID- 20739033 TI - Absence of evidence of translocation of GLUT2 to the apical membrane of enterocytes in everted intestinal sleeves. AB - INTRODUCTION: Traditional models of intestinal glucose absorption confine GLUT2 to the basolateral membrane. Evidence suggests that GLUT2 is translocated to the apical membrane when the enterocyte is exposed to high luminal glucose concentrations. HYPOTHESIS: GLUT2 translocates to the apical membrane by a PKC signaling mechanism dependent on activity of SGLT1 and the cellular cytostructure. METHODS: Transporter-mediated glucose uptake was studied in rat jejunum using everted sleeves under seven conditions: Control, SGLT1 inhibition (phlorizin), GLUT2 inhibition (phloretin), both SGLT1 and GLUT2 inhibition, PKC inhibition (calphostin C or chelerythrine), and disruption of cellular cytostructure (nocodazole). Each condition was tested in iso-osmotic solutions of 1, 20, or 50 mM glucose for 1 or 5 min incubations (n = 6 rats each). RESULTS: Control rats exhibited a saturable pattern of uptake at both durations of incubation. Phlorizin (P <= 0.006 each) inhibited markedly and phloretin (P <= 0.01 each) inhibited partially glucose uptake in all concentrations and time. Phloretin and phlorizin together completely inhibited uptake (P = 0.004 each). Calphostin C, chelerythrine, and nocodazole had little effect on glucose uptake at either 1 or 5 min. Inhibition of SGLT1 led to near complete cessation of transporter-mediated glucose uptake, while GLUT2 inhibition led to partial inhibition, suggesting some constitutive expression of GLUT2 in the apical membrane. Disruption of PKC signaling or cytoskeletal integrity partially inhibited transporter-mediated glucose uptake only in 1 mM glucose, suggesting a non-specific effect. CONCLUSIONS: Under these conditions, it does not appear that GLUT2 is translocated to the apical membrane on the cellular cytostructure in response to PKC signaling. PMID- 20739035 TI - Diel cycles of hydrogen peroxide in marine bathing waters in Southern California, USA: in situ surf zone measurements. AB - Hydrogen peroxide is photochemically produced in natural waters. It has been implicated in the oxidative-induced mortality of fecal indicator bacteria (FIB), a microbial water quality measure. To assess levels and cycling of peroxide in beach waters monitored for FIB, diel studies were carried out in surf zone waters in July 2009 at Crystal Cove State Beach, Southern California, USA. Maximum concentrations of 160-200 nM were obtained within 1h of solar noon. Levels dropped at night to 20-40 nM, consistent with photochemical production from sunlight. Day-time production and night-time dark loss rates averaged 16 +/- 3 nM h(-1) and 12 +/- 4 nM h(-1) respectively. Apparent quantum yields averaged 0.07 +/- 0.02. Production was largely dominated by sunlight, with some dependence on chromophoric dissolved organic matter (CDOM) levels in waters with high absorption coefficients. Peroxide levels measured here are sufficient to cause oxidative-stress-induced mortality of bacteria, affect FIB diel cycling and impact microbial water quality in marine bathing waters. PMID- 20739036 TI - Lead concentrations and isotopes in aerosols from Xiamen, China. AB - To investigate the magnitude and origin of lead (Pb) pollution in the atmosphere of Xiamen, China, 40 aerosol samples were collected from the coast of Xiamen from January to December 2003. All these samples were measured for Pb isotopic compositions ((208)Pb/(206)Pb=2.10897 +/- 0.00297, (207)Pb/(206)Pb=0.85767 +/- 0.00159, n=40) using a Multi-collector-Inductively Coupled Plasma Mass Spectrometer (MC-ICPMS). Thirty-five out of forty samples were also measured for Pb concentrations (79.1 +/- 38.3 ng/m(3), n=35) by Atomic Absorption Spectroscopy (AAS). The results indicate that the Pb concentrations display significant seasonal variations while Pb isotopic ratios remain relatively constant. The Pb concentrations were high in January and February, abruptly decreased in March, remained relatively constant (but low) from April to August, and then gradually increased from September to December. This corresponds to the rainless climate in winter and rain scavenging in summer. The higher Pb concentration of Xiamen aerosols in winter and spring may be also caused by long-range transferred anthropogenic Pb during the northeastern monsoon seasons. Although the use of leaded gasoline in Xiamen was banned in 2000, our new data indicate that the Pb annual concentrations of aerosols in Xiamen increased about 12% when compared to the data measured between 1991 and 1993. Thus, Pb pollution in the atmosphere of Xiamen has not receded even after the phase-out of leaded gasoline. Our results further confirm the previous studies' conclusion that the primary source of atmospheric Pb in China, especially in South China, is the vast combustion of lead-containing coal, not leaded gasoline. PMID- 20739037 TI - [Upper aerodigestive tract erythroplakia]. AB - Erythroplakia is a red mucosal macule with a chronic evolution. It is diagnosed after excluding traumatic, vascular, or inflammatory etiologies. Erythroplakia is rare in the upper aerodigestive tract. It affects middle-aged adults. The main predisposing factors are those of in situ carcinoma. Lesions are mainly located on lips or mucosa. Erythroleukoplakia may also occur. Ninety-one percent of erythroplakia are severe dysplasia, in situ carcinoma, or invasive carcinoma. Excision and histopathological examination are mandatory. PMID- 20739038 TI - [Potentially malignant disorders of the oral mucosa: terminology and classification]. AB - The last WHO expert workgroup recommended abandoning the distinction between potentially malignant lesions and conditions. The term to use is "potentially malignant disorders". Leukoplakia is the most common of these disorders, while erythroplakia is rather rare. The diagnosis is still made by excluding other documented white or red lesions. Despite progress in molecular biology, no marker allows predicting malignant transformation. These lesions are treated surgically with or without dysplasia. It is unknown if this surgery can really prevent transformation into squamous cell carcinoma. The potential malignancy of oral lichen planus is still debated. The risk of malignant transformation is lower than that of leukoplakia. No treatment may prevent this. Other potentially malignant conditions such as oral submucous fibrosis, actinic cheilitis, lupus, and immunodeficiency are rare. PMID- 20739039 TI - [Exophthalmos revealing Tolosa-Hunt syndrome]. PMID- 20739040 TI - [Clinical, radiographic, prognostic and therapeutic aspects of demelinating disease with tumefactive demyelinating lesions]. AB - BACKGROUND: Demyelinating diseases presenting with a tumefactive demyelinating lesion (TDL) raise questions about classification, diagnosis, prognosis, and treatment. Their long-term course is not well described in literature. PATIENTS/METHODS: In a retrospective study, we describe the main characteristics of 29 patients with TDLs. In a case control study, we compared two cohorts of multiple sclerosis (MS) patients: 24 MS patients with TDL versus a reference cohort of patients with relapsing remitting MS. We compared the extended disability status score (EDSS) concerning the first demyelinating event (DE) with TDL, EDSS score at the end of follow-up and treatment intake. The objective was to discuss the prognosis and the management of TDL. RESULTS: In our study, the prognosis was better for patients with non-prevalent TDL (first DE without TDL) compared with patients with prevalent TDL (first DE with TDL) and was not different compared with the MS reference cohort. At the end of follow-up, there was no significant difference between patients treated with immunosuppressors after a first DE with TDL and patients with classical MS. The EDSS at the end of follow-up was statistically more severe for untreated patients after a first DE with TDL than for classical MS patients (P=0.0047). DISCUSSION: The prognosis of patients with TDL is difficult to assess because of its multifactorial nature (underlying disease and treatment impact). In our cohort, outcome of MS patients whose first severe DE involved a TDL was better when they received an early immunosuppressive treatment. PMID- 20739041 TI - [Behavioral disorders in Parkinson's disease: from pathophysiology to the mastery of dopaminergic treatment]. AB - INTRODUCTION: Behavioral changes in Parkinson's disease are complex and their pathophysiology is not yet fully understood. The dopaminergic system seems to play a major role and most of the behavioral disorders in Parkinson's disease can be classified into either hypodopaminergic if related to the disease itself or hyperdopaminergic if related to dopaminergic treatment. STATE OF THE ART: Subthalamic stimulation, which enables withdrawal of dopaminergic medication at an advanced stage in the disease, provides a model for the study of certain nonmotor, dopamine-sensitive symptoms. Such a study has shown that apathy, which is the most frequent behavioral problem in Parkinson's disease, is part of a much broader hypodopaminergic behavioral syndrome which also includes anxiety and depression. Nonmotor fluctuations--essential fluctuations in the patient's psychological state--are an expression of mesolimbic denervation, as shown in positron emission tomography. Drug-induced sensitization of the denervated mesolimbic system accounts for hyperdopaminergic behavioral problems that encompass impulse control disorders that can be alternatively classified as behavioral addictions. The association of impulse control disorders and addiction to the dopaminergic medication has been called dopamine dysregulation syndrome. While L-dopa is the most effective treatment for motor symptoms, dopamine agonists are more effective in improving the nonmotor levodopa-sensitive symptoms. On the other hand, L-dopa induces more motor complications and dopamine agonist more behavioral side effects. There is increasing data and awareness that patients' quality of life appears to be dictated by hypo- and hyperdopaminergic psychological symptoms stemming from mesolimbic denervation and dopaminergic treatment rather than by motor symptoms and motor complications related to nigrostriatal denervation and dopaminergic treatment. PERSPECTIVES: Better management requires knowledge of the clinical syndromes of hyper- and hypodopaminergic behaviors and nonmotor fluctuations, a better understanding of their underlying mechanisms and the development of new evaluation tools for these nonmotor symptoms. CONCLUSIONS: The neurologist who strives to gain mastery of dopaminergic treatment needs to fine tune the dosage of levodopa and dopamine agonists on an individual basis, depending on the presence of motor and nonmotor signs respectively. PMID- 20739042 TI - [Parkinson's disease: Is there a strong environmental contribution?]. AB - Parkinson's disease (PD) is the most common cause of the parkinsonian syndromes and the most frequent neurodegenerative disease after Alzheimer's disease. Only a minority of PD cases is due to a single factor, in particular a genetic mutation. In the large majority of cases, it is considered that PD is a complex or multifactorial disease that results from the effect of multiple risk or protective factors, either genetic or environmental, and, possibly, from their interaction. Epidemiological studies, through a variety of approaches, have brought important evidence in favour of the contribution of environmental factors to the etiology of PD. In this review, we will present current evidence by focusing on specific illustrative examples. PMID- 20739043 TI - Population genetics of Homalodisca vitripennis reovirus validates timing and limited introduction to California of its invasive insect host, the glassy-winged sharpshooter. AB - As RNA viruses evolve rapidly, we hypothesized that a virus could serve as a surrogate to discriminate recently separated populations of an invasive insect species. Homalodisca vitripennis reovirus (HoVRV) was used as a surrogate to assess population structure of glassy-winged sharpshooter (GWSS), an invasive species detected in California ~20 years ago. HoVRV nucleotide sequence polymorphism revealed a bottleneck in the introduced population, yielded population age estimates consistent with timing of GWSS discovery in California, suggested gene flow within the native range but not among native and introduced populations, and could potentially pinpoint source of the introduced population. Collectively, the data support use of a virus surrogate to define critical attributes of invasive species populations, with the caveat that life history of the surrogate must be closely linked to that of the host. PMID- 20739044 TI - Assessing risk to human health from tropical leafy vegetables grown on contaminated urban soils. AB - Fifteen tropical leafy vegetable types were sampled from farmers' gardens situated on nine contaminated sites used to grow vegetables for commercial or subsistence consumption in and around Kampala City, Uganda. Trace metal concentrations in soils were highly variable and originated from irrigation with wastewater, effluent discharge from industry and dumping of solid waste. Metal concentrations in the edible shoots of vegetables also differed greatly between, and within, sites. Gynandropsis gynandra consistently accumulated the highest Cd, Pb and Cu concentrations, while Amaranthus dubius accumulated the highest Zn concentration. Cadmium uptake from soils with contrasting sources and severity of contamination was consistently lowest in Cucurbita maxima and Vigna unguiculata, suggesting these species were most able to restrict Cd uptake from contaminated soil. Concentrations of Pb and Cr were consistently greater in unwashed, than in washed, vegetables, in marked contrast to Cd, Ni and Zn. The risk to human health, expressed as a 'hazard quotient' (HQ(M)), was generally greatest for Cd, followed successively by Pb, Zn, Ni and Cu. Nevertheless, it was apparent that urban cultivation of leafy vegetables could be safely pursued on most sites, subject to site-specific assessment of soil metal burden, judicious choice of vegetable types and adoption of washing in clean water prior to cooking. PMID- 20739045 TI - Multiple site study of recent atmospheric metal (Pb, Zn and Cu) deposition in the NW Iberian Peninsula using peat cores. AB - In order to estimate atmospheric metal deposition in Southern Europe since the beginning of the Industrial Period (~1850 AD), concentration profiles of Pb, Zn and Cu were determined in four (210)Pb-dated peat cores from ombrotrophic bogs in Serra do Xistral (Galicia, NW Iberian Peninsula). Maximum metal concentrations varied by a factor of 1.8 for Pb and Zn (70 to 128MUgg(-1) and 128 to 231MUgg( 1), respectively) and 3.5 for Cu (11 to 37MUgg(-1)). The cumulative metal inventories of each core varied by a factor of 3 for all analysed metals (132 to 329MUgcm(-2) for Pb, 198 to 625MUgcm(-2) for Zn and 22 to 69MUgcm(-2) for Cu), suggesting differences in net accumulation rates among peatlands. Although results suggest that mean deposition rates vary within the studied area, the enhanced (210)Pb accumulation and the interpretation of the inventory ratios ((210)Pb/Pb, Zn/Pb and Cu/Pb) in two bogs indicated that either a record perturbation or post-depositional redistribution effects must be considered. After correction, Pb, Zn and Cu profiles showed increasing concentrations and atmospheric fluxes since the mid-XX(th) century to maximum values in the second half of the XX(th) century. For Pb, maximum fluxes were observed in 1955-1962 and ranged from 16 to 22mgm(-2)yr(-1) (mean of 18+/-1mgm(-2)yr(-1)), two orders of magnitude higher than in the pre-industrial period. Peaks in Pb fluxes in Serra do Xistral before the period of maximum consumption of leaded petrol in Europe (1970s-1980s) suggest the dominance of local pollutant sources in the area (i.e. coal mining and burning). More recent peaks were observed for Zn and Cu, with fluxes ranging from 32 to 52mgm(-2)yr(-1) in 1989-1996, and from 4 to 9mgm(-2)yr( 1) in 1994-2001, respectively. Our results underline the importance of multi-core studies to assess both the integrity and reliability of peat records, and the degree of homogeneity in bog accumulation. We show the usefulness of using the excess (210)Pb inventory to distinguish between differential metal deposition, accumulation or anomalous peat records. PMID- 20739046 TI - Use of the NMP22 BladderChek test in the diagnosis and follow-up of urothelial cancer: a cross-sectional study. AB - OBJECTIVES: To investigate the efficacy of the nuclear matrix protein (NMP) 22 BladderChek test (NMP22BC) in the detection and follow-up of urothelial carcinoma. MATERIAL AND METHODS: A total of 1021 patients who underwent the NMP22BC, cytology, and cystoscopy, were studied. We divided the patients into 2 groups: group I consisted of 597 patients who were being followed up for previous urothelial carcinoma, and group II consisted of 424 patients with hematuria. The sensitivity and specificity of the NMP22BC, cytology, and the combination (NMP22BC + cytology) were compared. RESULTS: Of the 1021 patients, 131 were diagnosed with urothelial cancer. The overall sensitivities for the NMP22BC, cytology, and the combination were 32.1%, 38.2%, and 52.7%, respectively. In group I, the sensitivity of the NMP22BC was lower than the sensitivity of cytology (22.58% vs 35.5%); there was no difference between the sensitivity of the NMP22BC and that of cytology in group II (40.58% vs 40.58%). For the combination, the sensitivity was greater than that of either test alone in both groups (46.77% and 57.97% in groups I and II, respectively). The sensitivity of the NMP22BC was greater than that of cytology (22.6% vs 13.2%) for low-grade bladder cancer. CONCLUSIONS: The NMP22BC has lower sensitivity than cytology. However, the sensitivity of NMP22BC in low-grade tumors was higher than that of cytology. Therefore, when the NMP22BC is combined with cytology, the sensitivity for detecting urothelial carcinoma is increased, which implies that this combination may be useful in the screening and follow-up of urothelial carcinoma. PMID- 20739047 TI - Pyeloureterostomy in the management of the lower pole pelvi-ureteric junction obstruction in incomplete duplicated systems. AB - OBJECTIVES: To report our experience with the pyeloureterostomy (PU) for the treatment of the lower pole PUJO in incomplete duplex systems. The combination of the duplicated collecting system and pelviureteric junction obstruction (PUJO) is a rare association and infrequently reported. Surgical treatment can be challenging in such cases. METHODS: We retrospectively reviewed the medical data of the patients who had surgery from 2001 to 2009, with a diagnosis of PUJO of the lower pole moiety in incomplete duplex system. Demographic, diagnostic, and procedural data were recorded. RESULTS: Seven patients were identified with the lower pole PUJO associated with incomplete duplex systems. Their median age was 49 months (range 2-108 months). Prenatal hydronephrosis was detected in 3 patients, and 4 had a febrile urinary tract infection. PU was performed in 6 patients because of short ureteral length between the ureteropelvic junction and junction of lower and upper pole ureters. One patient was treated with the dismembered pyeloplasty because of sufficient ureteral length of the lower pole. No complications were detected during 14 months of follow-up. CONCLUSIONS: The management of the lower pole PUJO in incomplete duplex systems should be individualized for every patient. PU is a good surgical option in the management of the lower pole PUJO associated with incomplete ureteral duplication. PMID- 20739048 TI - The role of preoperative endo-rectal coil magnetic resonance imaging in predicting surgical difficulty for robotic prostatectomy. AB - OBJECTIVES: To determine whether pelvimetry on endo-rectal coil magnetic resonance imaging (eMRI) predicts surgical difficulty of robot-assisted laparoscopic prostatectomy (RALP). METHODS: Patients' records with preoperative eMRI in our RALP database from April 2008 thru May 2009 were reviewed. Demographic, preoperative clinical data, and eMRI anatomic measurements, including calculated prostate volume (PV) and the pelvic cavity index (PCI), were recorded. PCI is the pelvic inlet multiplied by the interspinous distance and divided by the pelvic depth; PCI estimates the robotic working space. Correlative and multiple regression analyses of clinical and pelvimetric data were performed for prediction of estimated blood loss (EBL), operative time (OT), positive surgical margin (PSM), and transfusion rate as surrogates of surgical difficulty. RESULTS: Prostatic transverse diameter, PV, and the PV-to-PCI ratio were significantly correlated with both OT and EBL (P < .05). Body mass index also correlated with EBL (P < .05). Multiple linear regression analysis demonstrated that the PV-to-PCI ratio significantly predicts OT and EBL. No factor significantly predicted PSM status or transfusion rate on regression analysis. Analysis within the PSM group revealed that those with an apical PSM had statistically narrower and deeper pelvises. CONCLUSIONS: Patients with larger prostates and with narrow, deep pelvises are predicted to have a more difficult RALP. The PV-to-PCI ratio statistically predicts lengthier and bloodier procedures. However, that ratio does not predict PSM or transfusion risk on regression analysis. The eMRI predicts the level of surgical difficulty and is a valuable adjunctive study to obtain before RALP. PMID- 20739049 TI - Body mass index adjusted prostate-specific antigen and its application for prostate cancer screening. AB - OBJECTIVES: The prostate cancer prevention trial (PCPT) prostate cancer risk calculator was developed to aid physicians in counseling men for consideration of prostate biopsy based on prostate-specific antigen (PSA) and other clinical risk factors. This study investigated the role of body mass index (BMI) in this assessment. MATERIALS AND METHODS: BMI category was defined as < 25 (under/normal weight), 25.0-29.9 (overweight), 30.0-34.9 (obese [OB] I), 35.0-39.9 (OB II), and >= 40 (OB III). BMI-adjusted PSA for a man was determined by multiplying his PSA to the ratio of the geometrical mean of PSA for BMI < 25 to the geometrical mean of PSA for his BMI category. Operating characteristics of PSA and BMI-adjusted PSA were compared with PCPT risks using area underneath the receiver operating characteristic curve (AUC). Statistical tests of differences between AUCs for different diagnostic tests were performed with the nonparametric U-statistic method. RESULTS: BMI-adjusted PSA equaled to unadjusted PSA multiplying 1.09, 1.20, 1.50, and 1.71 for men in overweight, OBI, OBII, and OBIII categories, respectively. The AUC for BMI-adjusted PSA values (0.84) did not differ from PSA; that of the PCPT calculator with BMI-adjusted PSA (0.87) did not differ from the calculator with PSA. Of 2816 men with a PSA less than or equal to 2.5 ng/mL who did not undergo biopsy, 126 (4.5%) would have a BMI-adjusted PSA exceeding 2.5 ng/mL. CONCLUSIONS: Because of lower levels of PSA, overweight and obese men may have diminished cancer detection opportunities when undergoing PSA-based screening. PMID- 20739050 TI - Incidence of perioperative urinary tract infection after single-dose antibiotic therapy for midurethal slings. AB - OBJECTIVES: A recent Best Practice Statement published by the American Urological Association (AUA) recommends that antibiotic therapy in patients undergoing midurethral synthetic slings (MUS) should be 24 hours or less. Subjects at our institution are routinely administered a single dose of intravenous antibiotics before MUS surgery. We prospectively evaluated urinary tract infection (UTI) rates and risk factors for UTI in subjects undergoing MUS who receive single-dose antibiotic therapy. METHODS: Adult female patients who were undergoing MUS for stress or mixed urinary incontinence were prospectively included and received a single-dose of an intravenous antibiotic in accordance with the AUA Best Practice Statement. Subjects requiring additional procedures for prolapse were excluded. Baseline characteristics and preoperative and postoperative postvoid residual (PVR) were documented. Subjects were contacted within 1 week of surgery, and seen in the office at 1 month, when a urinalysis was performed, and urine culture sent if subjects were symptomatic. RESULTS: A total of 101 subjects underwent solitary MUS and received a single dose of intravenous antibiotics. Overall, 6 (5.9%) subjects developed a UTI within 1 month of surgery. Patients who developed a UTI were more likely to have elevated PVRs at the preoperative office visit (62.2 vs 26.8 mL, P = .004). CONCLUSIONS: Our study has demonstrated that the rate of perioperative UTI after MUS with one perioperative dose of intravenous antibiotics is low. Patients with an elevated preoperative PVR may be at an increased risk of developing a UTI. Single-dose antibiotic administration is safe and effective at preventing perioperative UTI in subjects undergoing solitary MUS. PMID- 20739051 TI - Surgical technique of diaphragm full-thickness resection and trans-diaphragmatic decompression of pneumothorax during cytoreductive surgery for ovarian cancer. AB - OBJECTIVE: To describe the technique and short-term post-operative outcomes associated with diaphragm full-thickness resection (FTR) and intraoperative trans diaphragmatic decompression of the resultant pneumothorax (TDDP). METHODS: All patients undergoing cytoreductive surgery for primary or recurrent ovarian cancer between 8/1/98 and 7/30/09 were retrospectively identified from the tumor registry database. Patients undergoing diaphragm FTR were selected for detailed review of the operative technique and post-operative outcomes. The operative technique of TDDP using a fenestrated Robinson catheter is described. RESULTS: A total of 45 patients met study inclusion criteria. Diaphragm FTR surgery was performed exclusively by gynecologic oncologists in 73.3% of cases. The median patient age was 60 years, and the majority (75.6%) of cases were performed for primary cytoreduction of Stage IIIC (n=27) or Stage IV (n=18) disease. The two dimensional surface area of tumor involvement ranged from 9 cm(2) to 192 cm(2). The right hemi-diaphragm alone was involved in 71.1% of cases, while both the right and left hemi-diaphragms were involved in 24.4%. TDDP was performed in 41 of the 45 patients undergoing diaphragm FTR, while 4 patients had intraoperative thoracostomy tubes placed. Among the 41 TDDP patients, post-operative days 3-4 radiographic imaging revealed that 56% had a small residual pleural effusion and 9.8% had a residual pneumothorax; however, only 2 patients (4.9%) required post operative thoracostomy tube placement or thoracentesis. CONCLUSION: The technique of TDDP eliminates the need of intraoperative and post-operative thoracostomy tube/thoracentesis in 95.1% of patients undergoing diaphragm FTR as a component of ovarian cancer cytoreductive surgery. PMID- 20739052 TI - Molecular delineation of the Y-borne Sry gene in the Formosan pangolin (Manis pentadactyla pentadactyla) and its phylogenetic implications for Pholidota in extant mammals. AB - The systematic status of Pholidota has been a matter of debate, particularly regarding the apparent inconsistency between morphological and molecular studies. The Sry gene, a master regulator of male sex determination in eutherian mammals, has not yet been used for phylogenetic analyses of extant mammals. The objective of the present study was to clone and characterize the complete gene (1300 base pairs; bp) and amino acid sequences (229 residues) of Sry from the Formosan pangolin (Manis pentadactyla pentadactyla), a member of Pholidota. The Sry amino acid identity between pangolin and other reported species ranged from 42.5% (mouse, Mus musculus) to 84.1% (European hare, Lepus europaeus). Sequence conservation was primarily in the high motility group (HMG) box (234 bp), whereas homology outside the HMG box was low. The cloned Sry was mapped to the pangolin Y chromosome by fluorescence in situ hybridization (FISH); this was confirmed to be the first Y-borne molecular marker identified in Pholidota. Based on Bayesian phylogenetic analysis for Sry HMG sequences from 36 representative taxa, including the Formosan pangolin, Pholidota was more closely related to Carnivora than to Xenarthra, consistent with the emerging molecular tree inferred from markers not located on the Y chromosome. In conclusion, this study characterized the gene structure of Sry of the Formosan pangolin and provided insights into the phylogenetic position of Pholidota. PMID- 20739053 TI - Superior parietal lobule dysfunction in a homogeneous group of dyslexic children with a visual attention span disorder. AB - A visual attention (VA) span disorder has been reported in dyslexic children as potentially responsible for their poor reading outcome. The purpose of the current paper was to identify the cerebral correlates of this VA span disorder. For this purpose, 12 French dyslexic children with severe reading and VA span disorders and 12 age-matched control children were engaged in a categorisation task under fMRI. Two flanked and isolated conditions were designed which both involved multiple-element simultaneous visual processing but taxed visual attention differently. For skilled readers, flanked stimuli processing activated a large bilateral cortical network comprising the superior and inferior parietal cortex, the inferior temporal cortex, the striate and extrastriate visual cortex, the middle frontal cortex and the anterior cingulate cortex while the less attention-demanding task of isolated stimuli only activated the inferior occipito temporal cortex bilaterally. With respect to controls, the dyslexic children showed significantly reduced activation within bilateral parietal and temporal areas during flanked processing, but no difference during the isolated condition. The neural correlates of the processes involved in attention-demanding multi element processing tasks were more specifically addressed by contrasting the flanked and the isolated conditions. This contrast elicited activation of the left precuneus/superior parietal lobule in the controls, but not in the dyslexic children. These findings provide new insights on the role of parietal regions, in particular the left superior parietal lobule, in the visual attention span and in developmental dyslexia. PMID- 20739054 TI - Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. AB - BACKGROUND: Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period. METHODS: We undertook a phase 3, double-blind, placebo controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30,000 per MUL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (<= 15,000 per MUL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50,000-400,000 per MUL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331. FINDINGS: Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8.2, 99% CI 3.59-18.73; p<0.0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0.016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0.001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag. INTERPRETATION: Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment. FUNDING: GlaxoSmithKline. PMID- 20739055 TI - Lymphatic filariasis and onchocerciasis. AB - Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. Most filarial species that infect people co-exist in mutualistic symbiosis with Wolbachia bacteria, which are essential for growth, development, and survival of their nematode hosts. These endosymbionts contribute to inflammatory disease pathogenesis and are a target for doxycycline therapy, which delivers macrofilaricidal activity, improves pathological outcomes, and is effective as monotherapy. Drugs to treat filariasis include diethylcarbamazine, ivermectin, and albendazole, which are used mostly in combination to reduce microfilariae in blood (lymphatic filariasis) and skin (onchocerciasis). Global programmes for control and elimination have been developed to provide sustained delivery of drugs to affected communities to interrupt transmission of disease and ultimately eliminate this burden on public health. PMID- 20739056 TI - Sustaining platelet counts in chronic ITP. PMID- 20739057 TI - Tuneable semi-synthetic network alginate for absorptive encapsulation and controlled release of protein therapeutics. AB - Stimuli-responsive hydrogels swell or contract in response to external pH, ionic strength or temperature, and are of considerable interest as pharmaceutical controlled release devices. Alginate, a mucoadhesive biopolymer, was used as building block in the semi-synthesis of a tetra-functional acetal-linked networked polymer (SNAP) with carboxylate moieties preserved as stimuli responsive sensors and tuneable pore sizes larger than the hydrodynamic radius of model molecules ranging between 1 and 540 kDa. Based on the diffusion coefficients calculated from protein uptake experiments, the networked polymer with pre-designed pore size of 80 nm can allow vitamin B(12), lysozyme, subtilisin, insulin, albumin, and urease to diffuse freely into the hydrogel with diffusivity ratio of D(gel)/D(water) (diffusion coefficients in hydrogel to water) between 0.60 and 0.95. Drying was applied as post-fabrication modification to alter/control the diffusional properties of the gel matrix. Together with the pH-responsive swelling properties, SNAP granules containing acid-labile protein therapeutics such as insulin showed protective characteristics by retaining collapsed/compact state in gastric environment (pH~1.2) while swelling in neutral pH to release the bioactives at near zero-order kinetics. SNAP, a new class of tuneable biomaterial, can be semi-synthesized with desired pore properties, which when applied with the absorptive encapsulation technique, can serve as a technology platform for oral delivery of biomolecules with wide range of molecular sizes. PMID- 20739058 TI - Immobilization of the soluble domain of human complement receptor 1 on agarose encapsulated islets for the prevention of complement activation. AB - The transplantation of islets of Langerhans has been successfully applied to the treatment of insulin-dependent diabetes. However, a shortage of human donors is the hardest obstacle to overcome. We aimed to develop a bioartificial pancreas that can realize xeno-islet transplantation. The islets were encapsulated in agarose microbeads carrying the soluble domain of human complement receptor 1 (sCR1), which is an effective inhibitor of the classical and alternative complement activation pathways. When naked rat islets were cultured in rabbit serum, large amounts of insulin leaked from the damaged islets over the course of a few days incubation, but no damaged cells were observed among islets in sCR1 agarose microbeads cultured in rabbit serum for 4 days. Although low levels of insulin were detected in the rabbit serum, the insulin did not leak from damaged beta-cells, it was physiological insulin secreted by the beta-cells. PMID- 20739059 TI - Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes. AB - Contrast agents based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIO) are internalized by professional phagocytes such as hepatic Kupffer cells, yet their role in phagocyte biology remains largely unknown. Here we investigated the effects of the SPIO ferucarbotran on murine Kupffer cells and human macrophages. Intravenous injection of ferucarbotran into mice led to rapid accumulation of the particles in phagocytes and to long-lasting increased iron deposition in liver and kidneys. Macrophages incorporate ferucarbotran in lysosomal vesicles containing alpha-glucosidase, which is capable of degrading the carboxydextran shell of the ferucarbotran particles. Intravenous injection of ferucarbotran into mice followed by incorporation of the nanoparticles into Kupffer cells triggered apoptosis and the subsequent depletion of Kupffer cells. In macrophages, the proinflammatory cytokine TNF-alpha increased the apoptosis rate, the reactive oxygen species production and the activation of c-Jun N terminal kinase elicited by ferucarbotran, which might be mediated by the induction of cytoplasmic phospholipase A2 by TNF-alpha. Notably, the nanoparticle induced apoptosis of murine Kupffer cells could be prevented by treatment of the mice with the radical scavenger edaravone. Thus, nanosized carboxydextran-coated SPIO-based contrast agents are retained for extended time periods by liver macrophages, where they elicit delayed cell death, which can be antagonized by a therapeutic radical scavenger. PMID- 20739060 TI - Ultraviolet light crosslinking of poly(trimethylene carbonate) for elastomeric tissue engineering scaffolds. AB - A practical method of photocrosslinking high molecular weight poly(trimethylene carbonate)(PTMC) is presented. Flexible, elastomeric and biodegradable networks could be readily prepared by UV irradiating PTMC films containing pentaerythritol triacrylate (PETA) and a photoinitiator. The network characteristics, mechanical properties, wettability, and in vitro enzymatic erosion of the photocrosslinked PTMC films were investigated. Densely crosslinked networks with gel contents up to 98% could be obtained in this manner. Upon photocrosslinking, flexible and tough networks with excellent elastomeric properties were obtained. To illustrate the ease with which the properties of the networks can be tailored, blends of PTMC with mPEG-PTMC or with PTMC-PCL-PTMC were also photocrosslinked. The wettability and the enzymatic erosion rate of the networks could be tuned by blending with block copolymers. Tissue engineering scaffolds were also fabricated using these flexible photocrosslinkable materials. After crosslinking, the fabricated PTMC-based scaffolds showed inter-connected pores and extensive microporosity. Human mesenchymal stem cell (hMSC) culturing studies showed that the photocrosslinked scaffolds prepared from PTMC and PTMC/PTMC-PCL-PTMC blends are well-suited for tissue engineering applications. PMID- 20739061 TI - The mechanical characteristics and in vitro biocompatibility of poly(glycerol sebacate)-bioglass elastomeric composites. AB - Biodegradable elastomeric materials have gained much recent attention in the field of soft tissue engineering. Poly(glycerol sebacate) (PGS) is one of a new family of elastomers which are promising candidates used for soft tissue engineering. However, PGS has a limited range of mechanical properties and has drawbacks, such as cytotoxicity caused by the acidic degradation products of very soft PGS and degradation kinetics that are too fast in vivo to provide sufficient mechanical support to the tissue. However, the development of PGS/based elastomeric composites containing alkaline bioactive fillers could be a method for addressing these drawbacks and thus may pave the way towards wide clinical applications. In this study, we synthesized a new PGS composite system consisting of a micron-sized Bioglass filler. In addition to much improved cytocompatibility, the PGS/Bioglass composites demonstrated three remarkable mechanical properties. First, contrary to previous reports, the addition of microsized Bioglass increases the elongation at break from 160 to 550%, while enhancing the Young's modulus of the composites by up to a factor of four. Second, the modulus of the PGS/Bioglass composites drops abruptly in a physiological environment (culture medium), and the level of drop can be tuned such that the addition of Bioglass does not harden the composite in vivo and thus the desired compliance required for soft tissue engineering are maintained. Third, after the abrupt drop in modulus, the composites exhibited mechanical stability over an extended period. This latter observation is an important feature of the new composites, because they can provide reliable mechanical support to damaged tissues during the lag phase of the healing process. These mechanical properties, together with improved biocompatibility, make this family of composites better candidates than plastic and related composite biomaterials for the applications of tissue engineering. PMID- 20739062 TI - A comparison of bioreactors for culture of fetal mesenchymal stem cells for bone tissue engineering. AB - Bioreactors provide a dynamic culture system for efficient exchange of nutrients and mechanical stimulus necessary for the generation of effective tissue engineered bone grafts (TEBG). We have shown that biaxial rotating (BXR) bioreactor-matured human fetal mesenchymal stem cell (hfMSC) mediated-TEBG can heal a rat critical sized femoral defect. However, it is not known whether optimal bioreactors exist for bone TE (BTE) applications. We systematically compared this BXR bioreactor with three most commonly used systems: Spinner Flask (SF), Perfusion and Rotating Wall Vessel (RWV) bioreactors, for their application in BTE. The BXR bioreactor achieved higher levels of cellularity and confluence (1.4-2.5x, p < 0.05) in large 785 mm(3) macroporous scaffolds not achieved in the other bioreactors operating in optimal settings. BXR bioreactor-treated scaffolds experienced earlier and more robust osteogenic differentiation on von Kossa staining, ALP induction (1.2-1.6*, p < 0.01) and calcium deposition (1.3-2.3*, p < 0.01). We developed a Micro CT quantification method which demonstrated homogenous distribution of hfMSC in BXR bioreactor-treated grafts, but not with the other three. BXR bioreactor enabled superior cellular proliferation, spatial distribution and osteogenic induction of hfMSC over other commonly used bioreactors. In addition, we developed and validated a non-invasive quantitative micro CT-based technique for analyzing neo-tissue formation and its spatial distribution within scaffolds. PMID- 20739063 TI - Activity of the potent dual Abl/Src tyrosine kinase inhibitor FB2 against Bcr-Abl positive cell lines in vitro and in vivo. AB - We have previously shown the inhibition of the small-molecule inhibitor FB2 on imatinib-sensitive and resistance CML cell lines with the wild-type Bcr-Abl fusion gene. Here we report the potent and selective antiproliferation on FB2 on transfected Ba/F3 p210 cell lines expressing various isoforms of Bcr-Abl (wild type, Y253F, T315I). FB2 which orients Bcr-Abl and Src kinase activities, is shown to override imatinib-resistance CML involving Y253F mutation in the Abl kinase domain of the fusion protein except T315I in vivo and in vitro. Thus, we present FB2 that displays potency toward Bcr-Abl and Src as the molecular target, and which could potentially be used to override drug resistance in CML. PMID- 20739064 TI - Relationship between individual cardiovascular risk factors and localization of coronary atherosclerotic lesions. AB - OBJECTIVE: The localization of coronary atherosclerotic lesions in patients with coronary artery disease is important. We investigated the relationship between individual cardiovascular risk factors and lesion localization in the coronary arteries. METHODS: We studied 200 consecutive patients with suspected or known coronary artery disease who were referred for coronary angiography because of chest pain. We assessed the following cardiovascular risk factors: male gender, hypercholesterolemia, smoking, arterial hypertension, positive family history, and diabetes. We evaluated atherosclerotic lesions creating a stenosis >= 50% in the 3 coronary arteries and lesions creating a stenosis >= 30% in the left main stem. RESULTS: Of the 200 study patients, 155 (78%) showed at least 1 coronary artery lesion with a luminal stenosis >= 50%. With an increasing number of risk factors, there was a significant progressive increase of diseased arteries (P < .001). There was a differential association between individual risk factors and lesions in the 3 coronary arteries. Male gender, hypercholesterolemia, and diabetes were predictors of lesions in the left anterior descending artery (odds ratios 2.365, 2.510, and 1.998, respectively). Predictors of left circumflex artery lesions were male gender, smoking, and diabetes (odds ratios 2.581, 1.913, and 2.280, respectively), whereas the only independent predictor of right coronary artery lesions was male gender (odds ratio 2.995). Diabetes was also significantly associated with lesions in the diagonal branches of the left anterior descending artery and the marginal branches of the left circumflex artery. CONCLUSION: Individual cardiovascular risk factors are associated with the localization of atherosclerotic lesions in the coronary circulation. PMID- 20739066 TI - Frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in farmers exposed to pesticides in Canakkale, Turkey. AB - This study aimed to determine the incidence of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in peripheral blood lymphocytes due to direct exposure to pesticides among 46 farmers in Canakkale, Turkey. 48 non exposed individuals living in the same socioeconomic conditions were chosen as control. In addition, a cytokinesis-block proliferation index (CBPI) was calculated. MNi and NBUDs frequencies were significantly higher among the farmers (p < 0.05). Although the NPB frequency of the farmers was higher than the controls, there was no statistical difference. Multiple linear regression analysis showed that apart from gender, no significant effects of various confounding factors were observed. Regarding CBPI, data obtained for the controls were higher than that of the farmers; however, there was no statistically significant difference. PMID- 20739065 TI - 3-Methylcholanthrene (3-MC) and 4-chlorobiphenyl (PCB3) genotoxicity is gender related in Fischer 344 transgenic rats. AB - Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants with myriad biological effects, including carcinogenicity. We present data showing gender-specific genotoxicity in Fischer 344 transgenic BigBlue rodents exposed to 4-chlorobiphenyl (PCB3), a hydroxylated metabolite, and the positive control 3-methylcholanthrene (3-MC) where female rats are more resistant to the genotoxic effects of the test compounds compared to their male counterparts. This difference is further highlighted through our examination of gene expression, organ-specific weight changes, and tissue morphology. The purpose of the present study was to explore the complex and multifaceted issues of lower molecular weight PCBs as initiators of carcinogenesis, by examining the mutagenicity of PCB3, a hydroxylated metabolite (4'-OH-PCB3), and 3-methylcholanthrene (3-MC, positive control) in a transgenic rodent model. Previous findings indicated that PCB3 is mutagenic in the liver of male BigBlue transgenic rats under identical exposure conditions. We expected that female rats would be equally, if not more sensitive than male rats, since a 2-year carcinogenesis bioassay with Sprague Dawley rats and commercial PCB mixtures reported much higher liver cancer rates in female than in male rats. The current study, however, revealed a similar trend in the mutation frequencies across all four treatment groups in females as reported previously in males, but increased variability among animals within each group and a lower overall effect, led to non significant differences in mutation frequencies. A closer analysis of the possible reasons for this negative result using microarray, organ weight and histology data comparisons shows that female Fischer 344 rats 1) had a higher baseline mutation frequency in the corn oil control group and greater variability than male rats; 2) responded with robust gene expression changes, which may also play a role in our observation of 3) highly increased liver, spleen, and lung weight in 3-MC and PCB3-treated female rats and thus changed distribution and kinetics of the test compounds. Our analysis indicates that female transgenic BigBlue Fischer 344 rats are more resistant to PCB3 and 3-MC genotoxicity compared to their male counterparts. PMID- 20739067 TI - CD4 dimerization requires two cysteines in the cytoplasmic domain of the molecule and occurs in microdomains distinct from lipid rafts. AB - CD4 is engaged in APC-mediated T-cell activation and serves as the primary receptor for HIV. CD4 dimerization and location in specific microdomains has been previously suggested to control its pathophysiological activity. In this study, we investigated (i) whether the CD4 cytoplasmic domain contributes to its dimerization by evaluating the dimerization of mutants, bearing deletions or point mutations in their cytoplasmic tail, (ii) whether CD4 monomers and dimers segregate in distinct microdomains by subcellular fractionation, and (iii) how CD4 dimerization is affected by T-cell activation or HIV-1 viral proteins. Our results indicated that within the cytoplasmic tail of CD4, two cysteines played a crucial role in the dimers formation, since point mutations or truncation upstream of these residues prevented dimerization. The solubility of CD4 dimers and monomers in various detergents was different and CD4 dimers were poorly associated with lipid rafts, but strongly interacted with the tetraspanin CD81. Neither cytoskeleton-disrupting drugs nor cholesterol-sequestering agents had an effect on the CD4 dimerization indicating that dimers formation was independent of CD4 association with the cytoskeleton or lipid rafts. Finally, whereas T-cell activation poorly impact on CD4 dimerization, HIV-1 gp120 and Nef drastically reduced the ratio of CD4 dimers/monomers. Together, these findings demonstrate that two cysteines within the CD4 cytoplasmic tail are critical for dimerization, that CD4 dimers locate preferentially in microdomains distinct than classical lipid rafts, likely tetraspanin-enriched microdomains, and that CD4 dimers are implicated in the process of HIV infection. PMID- 20739068 TI - Gender, genetic risk, and criminal behavior. AB - The threshold hypothesis asserts that the prevalence of offending is lower among females because females have a higher threshold for risk than males. As a result, females who do offend should exhibit greater concentrations of genetic and environmental risk than male offenders. In light of these statements, the current study examines the role of genetic factors in the etiology of female offending using data from the National Longitudinal Study of Adolescent Health. The results reveal that the genetic risk threshold is higher for females than for males. However, contrary to the threshold hypothesis, female offenders exhibit fewer genetic risks than male offenders. PMID- 20739069 TI - Molecular cloning, expression in Escherichia coli, and development of monoclonal antibodies to feline cystatin C. AB - Cystatin C is a member of the cystatin superfamily of low-molecular-weight proteins that inhibit the activity of cysteine protease. The full-length cDNA that encodes feline cystatin C (FeCysC) has been cloned from feline white blood cells by the oligo-capping method. The cDNA consists of 796 nucleotides and includes an open reading frame encoding a polypeptide of 146 amino acids. Next, we developed several mouse anti-FeCysC monoclonal antibodies (mAbs). The recombinant FeCysC (rFeCysC) was expressed in Escherichia coli (E. coli) BL21 and used as an antigen to immunise mice. The reactivity of the mAbs to native FeCysC was examined by western blot analysis against the urinary protein from cats with chronic kidney disease (CKD). The three anti-rFeCysC mAbs (3-9G, 7-7C, and 9-12F) were able to recognise native FeCysC. PMID- 20739070 TI - A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection. AB - Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC). Indoleamine 2,3-dioxygenase (IDO), the initial enzyme in the tryptophan catabolism pathway, is upregulated in R. equi infected equine monocyte-derived DC and alveolar macrophages. Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed. Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation of R. equi in equine alveolar macrophages. To investigate an immune-regulatory role for INDO in R. equi infection, IDO(-/-) (B6.129-(Indotm1Alm)/J) (n=22) and strain matched control (C57BL/6J) (n=20) mice were infected with R. equi by intraperitoneal injection, for 3 and 6 days. There was no difference in bacterial counts in liver or spleen between the two groups. Histological sections of liver and spleen were assigned inflammation scores and RT-PCR for interferon-gamma (IFNgamma), tumor necrosis factor-alpha (TNFalpha), IL-4, IL-6, IL-10, IL-12, IL-23, forkhead box P3 (FoxP3), and transforming growth factor-beta (TGFbeta) was performed on liver and spleen. Liver tissue of IDO(-/-) had higher inflammation scores at 6 days post infection (PI) (P=0.05) and had decreased expression of TGFbeta at 3 days PI (P=0.01), and FOXP3 at 3 days (P=0.02) and 6 days (P=0.03) compared to control mice. Immunostaining for FOXP3 showed lower numbers of FOXP3+ regulatory T cells in liver of IDO(-/-) mice 6 days PI. Prolonged inflammation in the liver tissue of IDO(-/-) mice corresponded with lower expression of FOXP3 and TGFbeta in that tissue, and also with lower numbers of FOXP3+ regulatory T cells. We conclude that IDO expression by activated macrophages and DC plays a role in dampening the inflammatory response to R. equi infection in mice. PMID- 20739071 TI - Flow cytometric assessment of antigen-specific proliferation in peripheral chicken T cells by CFSE dilution. AB - Carboxyfluorescein succinimidyl ester (CFSE) dilution is a well established method for analysis of dividing cells by flow cytometry. In other species the method has been extensively used in the study of antigen-specific T cells. The purpose of this study was to apply the method to chicken peripheral mononuclear blood cells (PBMC) and to evaluate and optimize its performance in relation to detection of vaccine-induced chicken T cells specific for Newcastle disease virus (NDV). The method was based on analysis of CFSE dilution upon ex vivo recall stimulation with whole vaccine antigen. Analysis of proliferation was combined with the use of monoclonal antibodies directed against the lymphocyte surface markers CD4 and CD8 in order to phenotype the responding cells. Problems with nonspecific background proliferation especially in the CD8 compartment were significantly reduced by replacing medium containing fetal calf serum with serum free medium. It was rendered probable that antigen-specific cellular immunity can be assessed by this method as NDV-vaccinated chickens showed a significantly higher proliferative capacity than age-matched naive controls. Furthermore it was shown that the recall stimulation lead to a proliferative response in T cells expressing alphabeta-type TCRs but also those expressing the gammadelta-type. In summary, the method was found challenging but nevertheless useful to quantify the proliferative response of chicken antigen-specific T cells. Further investigations though, are needed in order to prove what cell subsets are true antigen-specific responders and what cells are bystander activated. Nevertheless, the method is expected to be a valuable tool to evaluate and quantify vaccine responses to current and new chicken vaccines in the future. PMID- 20739072 TI - Natalizumab treatment reduces endothelial activity in MS patients. AB - Vascular cell adhesion molecule-1 a ligand for leukocyte very late activating antigen-4 is a key player in leukocyte extravasation in MS lesions. Natalizumab a monoclonal antibody against VLA-4 blocks this interaction. VCAM-1 and its soluble form are up-regulated during endothelial activation in MS. We investigated the effect of Natalizumab on sVCAM-1 and VLA-4 on circulating leukocytes in MS patients. Natalizumab reduced levels of sVCAM-1 compared to controls (256 vs. 597 ng/mL). This effect was sustained and only reversed in patients with neutralizing antibodies against Natalizumab. Correspondingly Natalizumab diminished VLA-4 on leukocyte subsets. Our findings indicate that Natalizumab reduces transmigration not only by blocking VLA-4 but also by down-regulating VCAM-1. PMID- 20739073 TI - Acute acidic exposure induces p53-mediated oxidative stress and DNA damage in tilapia (Oreochromis niloticus) blood cells. AB - Acid rain and inputs of acidic effluent can result in increased acidity in aquatic ecosystems, where it is known to have a significant impact and possibly, to cause the decline of some populations of aquatic organisms. In previous studies, intracellular acid-induced oxidative stress has been shown to cause DNA damage, and cooperatively activate the expression of the p53 gene. The acute effects of acidic environments on shrimp and fish have been widely studied. However, the molecular mechanism of acid-induced injury remains largely unknown. In this study, we examined the cellular responses of tilapia to acidic exposure induced oxidative stress and antioxidant enzyme gene expression. Furthermore, we determined how acute acid stress activates the ATM-p53 signal pathway. We measured the upregulation of reactive oxygen species (ROS) production, the intracellular Ca(2)(+) concentration ([Ca(2)(+)](i)), the tail DNA values, the malondialdehyde (MDA) level in the blood cells and the percentage of dead and damaged blood cells. Our results suggest that oxidative stress and DNA damage occurred in tilapia in conditions where the pH was 5.3. Apoptosis was detected by Hoechst staining, which was mainly associated with changes in cell viability. The parameters that we measured were related to acid-induced DNA damage, and all parameters changed in the blood cells through time. The effects of acute acid exposure (pH 5.3) on the expression of ATM, p53, p21, Bax, manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) were investigated in tilapia blood cells. The results showed that acute acid stress induced upregulation of ATM, p53 and p21, associated with increasing of DNA damage and apoptosis in blood cells. Additionally, the expression of Bax was slightly increased. Moreover, consensus p53-binding sequences were identified in tilapia MnSOD and GPx gene promoter regions and increased levels of ROS in the blood cells coincided with increased mRNA expression of p53, MnSOD and GPx. Therefore, it suggests that acid exposure-induced oxidative stress may cause DNA damage or apoptosis, and cooperatively activate ATM-p53 pathway, which may lead to the activation of p21 and regulate transcription of MnSOD and GPx. PMID- 20739074 TI - One-way inhibiting cross-talk between arylhydrocarbon receptor (AhR) and estrogen receptor (ER) signaling in primary cultures of rainbow trout hepatocytes. AB - The aryl hydrocarbon receptor (AhR) and the estrogen receptor (ER) are ligand activated transcription factors, both of which can be activated by environmental pollutants. The AhR regulates cytochrome P450 1A (CYP1A) expression and can be induced by aromatic hydrocarbons. The ER regulates vitellogenin (VTG) expression and can be induced by estrogenic substances. Both receptor responses are established biomarkers used to assess the effects of pollutants in the aquatic environment. The receptors can also be affected in situations of mixed exposure. Cross-talk between these receptor pathways has been suggested, although there are conflicting data in the literature. We investigated cross-talk between ER-VTG and AhR-CYP1A signaling pathways in primary cultures of rainbow trout hepatocytes, using quantitative PCR (qPCR) for mRNA analyses and studies of CYP1A catalytic function and protein expression. The model agonists beta-naphthoflavone (BNF) and 17alpha-ethinylestradiol (EE(2)) were used for AhR and ER activation, respectively. Combined exposure to BNF and EE(2) reduced the EE(2)-mediated induction of VTG mRNA levels by about 40%, but had no effect on the BNF-mediated CYP1A mRNA levels, indicative of a one-way inhibiting AhR-ER cross-talk. However, basal levels of CYP1A mRNA were reduced 40% upon exposure to EE(2) alone, implying different cross-talk mechanism between basal and induced CYP1A mRNA levels. The mammalian ER antagonist fulvestrant (ICI) is commonly described as an absolute ER antagonist. However, ICI failed to reverse the ER activation caused by EE(2) in the present study. The CYP1A-mediated ethoxyresorufin-O-deethylase (EROD) activity was reduced by 80% in cells co-treated with BNF and EE(2), compared to cells exposed to BNF alone. In vitro inhibiting studies suggests that this reduction was a result of inhibition of the CYP1A catalyst by EE(2) since EE(2) acted as a potent inhibitor (IC(50): 4.6MUM) of the EROD activity. In addition, ICI also acted as a potent inhibitor of the EROD enzyme (IC(50): 0.6MUM). Taken together, our data supports a one-way inhibiting AhR-ER cross-talk in rainbow trout hepatocytes exposed to a mixture of BNF and EE(2). PMID- 20739076 TI - Measuring inappropriate medical diagnosis and treatment in survey data: The case of ADHD among school-age children. AB - We exploit the discontinuity in age when children start kindergarten generated by state eligibility laws to examine whether relative age is a significant determinant of ADHD diagnosis and treatment. Using a regression discontinuity model and exact dates of birth, we find that children born just after the cutoff, who are relatively old-for-grade, have a significantly lower incidence of ADHD diagnosis and treatment compared with similar children born just before the cutoff date, who are relatively young-for-grade. Since ADHD is an underlying neurological problem where incidence rates should not change dramatically from one birth date to the next, these results suggest that age relative to peers in class, and the resulting differences in behavior, directly affects a child's probability of being diagnosed with and treated for ADHD. PMID- 20739075 TI - Comparison of outcomes and other variables between conference abstracts and subsequent peer-reviewed papers involving pre-harvest or abattoir-level interventions against foodborne pathogens. AB - Accuracy in the reporting of studies in conference abstracts is important because the majority of studies in such abstracts are never further detailed in peer reviewed publications, and data from such abstracts may be used in systematic reviews. Previous research on interventional studies in human biomedicine indicates that there is no guarantee of consistency between a conference abstract and paper in the reporting of results and other key variables. However, no research has been done to determine if this lack of reporting consistency in abstracts and papers extends to interventional studies in pre-harvest/harvest level food safety. The goal of this study was to compare outcome results and other key variables between conference abstracts and subsequent peer-reviewed publications describing studies of pre-harvest and abattoir-level interventions against foodborne pathogens, and to determine whether the agreement in the results or key variables was associated with the time to full publication. A systematic search identified 59 conference abstracts with matching peer-reviewed papers (matches), and data on variables including outcome measures and results, pathogens, species, interventions, overall efficacy of intervention, sample size and housing were extracted from both the conference abstracts and the papers. The matching of variables between abstracts and papers was described, and logistic regression used to test for associations between variable matching and time to publication. Sample size was only provided for both abstract and paper in 24 matches; the same sample size was reported in 20 of these matches. Most other variables were reported in the majority of abstracts/papers, and with the exception of outcomes and intervention effect, the reporting of variables was relatively consistent. There was no significant difference in the numbers of authors, with the first author the same in 78.3% of matches. Of 231 outcome measures reported in both abstracts and papers, nearly one third (77% or 32.2%) had different results, with 32 changing direction of effect. More than a quarter of matches involved at least one significant change in outcome result. The overall conclusion on the efficacy of the intervention changed in 10.7% of matches. There was a significant association between increased time to publication and differences in the number of authors, and having fewer outcome measures in the abstract reported in the paper. These results suggest that data from conference abstracts should be considered with caution. PMID- 20739077 TI - Morphology and physico-chemical properties of Bacillus spores surrounded or not with an exosporium: consequences on their ability to adhere to stainless steel. AB - This study was designed to elucidate the influence of spore properties such as the presence of an exosporium, on their ability to adhere to materials. This analysis was performed on 17 strains belonging to the B. cereus group and to less related Bacillus species. We first demonstrated that spores of the B. cereus group, surrounded by an exosporium, differed in their morphological features such as exosporium size, number of appendages or hair-like nap length. We also found that the saccharidic composition of exosporium differed among strains, e.g. concerning a newly identified rhamnose derivative: the 2,4-O-dimethyl-rhamnose. Conversely, spores of distant Bacillus species shared morphological and physico chemical properties with B. cereus spores. Some external features were also observed on these spores, such as a thin loose-fitting layer, whose nature is still to be determined, or a thick saccharidic layer (mainly composed of rhamnose and quinovose). The ability of spores to adhere to stainless steel varied among strains, those belonging to the B. cereus group generally being the most adherent. However, the presence of an exosporium is not sufficient to explain the ability of spores to adhere to inanimate surfaces. Indeed, when the 17 strains were compared, hydrophobicity and the number of appendages were the only significant adhesion parameters. Furthermore, the differences in spore adhesion observed within the B. cereus group were related to differences in the number of appendages, the exosporium length and to a lesser extent, the zeta potential. PMID- 20739078 TI - Ageing, telomeres, senescence, and liver injury. AB - Populations in developed countries continue to grow older and an understanding of the ageing process to allow healthy ageing carries important medical implications. Older individuals are more susceptible to most acquired liver disorders and more vulnerable to the consequences of liver disease. Accordingly, age is a critical determinant of outcome for hepatitis C virus infection and liver transplantation. In this review we describe changes in the ageing liver and discuss mechanisms of senescence at the cellular level. In particular, we focus on mechanisms by which inflammation, oxidative stress, and oncogenic stress accelerate cellular senescence. In the setting of chronic hepatic injury and inflammation, cellular senescence functions as an essential stress-response mechanism to limit the proliferation of damaged cells and reduce the risk of malignancy, but this benefit is achieved at the expense of senescence-related organ dysfunction. The dual role of cell senescence in chronic liver disease will make this an intriguing but challenging area for future clinical interventions. PMID- 20739079 TI - Beta-globin mutations are associated with parenchymal siderosis and fibrosis in patients with non-alcoholic fatty liver disease. AB - BACKGROUND & AIMS: Parenchymal liver siderosis is associated with increased fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess whether a panel of genetic variants previously reported to influence iron metabolism, including the C282Y/H63D HFE, the PiZ/PiS alpha1 antitrypsin, the IVS1-24 ferroportin polymorphisms, and the beta-thalassemia trait, may be able to predict the presence of parenchymal siderosis and of progressive fibrosis in NAFLD. METHODS: We considered 274 Italian patients with biopsy-proven NAFLD. Genetic polymorphisms were searched for by sequence allele specific-polymerase chain reaction and restriction analysis, whereas beta-trait was determined according to blood count and HbA(2) determination. RESULTS: Parenchymal iron deposition was predominantly observed in 32 (11.7%) patients. Heterozygosity for the C282Y (OR 1.87, 95% CI 1.04-3.25), homozygosity for the H63D HFE (OR 2.31, 95% CI 1.04-4) mutations, and the beta-thalassemia trait (OR 2.57 95% CI 1.49-4.47) were all predominantly associated with parenchymal siderosis, independently of age, sex, body mass index, alcohol intake, ferritin, and transferrin saturation. Sixty-three percent of patients with hepatocellular siderosis were positive for at least one of the aforementioned genetic variants. The beta-thalassemia trait had the highest positive and the lowest negative likelihood ratios for predominantly parenchymal iron accumulation (5.05 and 0.74, respectively), and was independently associated with moderate/severe fibrosis (OR 2.50, 95% CI 1.26-5.19). CONCLUSIONS: In patients with NAFLD, predominant hepatocellular iron deposition is often related to genetic factors, among which beta-globin mutations play a major role, predisposing to parenchymal iron accumulation and to progressive liver fibrosis. PMID- 20739080 TI - Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C. AB - BACKGROUND & AIMS: The mechanisms of treatment resistance to interferon (IFN) and ribavirin (Rib) combination therapy for hepatitis C virus (HCV) infection are not known. This study aims to gain insight into these mechanisms by exploring hepatic gene expression before and during treatment. METHODS: Liver biopsy was performed in 50 patients before therapy and repeated in 30 of them 1week after initiating combination therapy. The cells in liver lobules (CLL) and the cells in portal areas (CPA) were obtained from 12 patients using laser capture microdissection (LCM). RESULTS: Forty-three patients were infected with genotype 1 HCV, 20 of who were viral responders (genotype 1-Rsp) with treatment outcome of SVR or TR, while 23 were non-responders (genotype 1-nonRsp) with NR. Only seven patients were infected with genotype 2. Before treatment, the expression of IFN and Rib stimulated genes (IRSGs), apoptosis-associated genes, and immune reaction gene pathways was greater in genotype 1-nonRsp than in Rsp. During treatment, IRSGs were induced in genotype 1-Rsp, but not in nonRsp. IRSG induction was irrelevant in genotype 2-Rsp and was mainly impaired in CLL but not in CPA. Pathway analysis revealed that many immune regulatory pathways were induced in CLL from genotype 1 Rsp, while growth factors related to angiogenesis and fibrogenesis were more induced in CPA from genotype 1-nonRsp. CONCLUSIONS: Impaired IRSGs induction in CLL reduces the sensitivity to treatment for genotype 1 HCV infection. CLL and CPA in the liver might be differentially involved in treatment resistance. These findings could be useful for the improvement of therapy for HCV infection. PMID- 20739081 TI - A Yin-Yang balancing act of the lin28/let-7 link in tumorigenesis. PMID- 20739082 TI - Calcium-dependent diuretic system in preascitic liver cirrhosis. AB - BACKGROUND & AIMS: Extracellular Ca(++) activates cell membrane calcium-sensing receptors (CaRs), leading to renal tubule production of prostaglandins E(2) (PGE(2)), which decrease both sodium reabsorption in the thick ascending limb of Henle's loop and free-water reabsorption in collecting ducts. AIMS & METHODS: To assess the activity of this diuretic system in experimental cirrhosis, we evaluated renal function, hormonal status, PGE(2) urinary excretion, and renal tissue concentrations of Na(+)-K(+)-2Cl(-) co-transporters (BSC-1) and CaRs in three groups of rats: one group of controls receiving 5% glucose solution (vehicle) intravenously and two groups of rats with CCl(4)-induced preascitic cirrhosis receiving either vehicle or 0.5mg i.v. Poly-l-Arginine (PolyAg), a CaR selective agonist. RESULTS: Compared to controls, cirrhotic rats showed reduced urine volume and sodium excretion (p<0.05). Western blot analysis revealed reduced CaRs and increased BSC-1 protein content in kidneys of cirrhotic rats compared with controls (all p<0.01). PolyAg-treated cirrhotic rats had their urine and sodium excretion returned to normal; PolyAg also increased renal plasma flow, PGE(2) urinary excretion, and free-water clearance in cirrhotic rats (all p<0.01 v. untreated cirrhotic animals). CONCLUSIONS: In preascitic cirrhosis, sodium retention may be linked to down-regulation of renal CaRs and up-regulation of tubular sodium-retaining channels. Calcimimetic drugs normalize preascitic sodium retention. PMID- 20739083 TI - PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection. AB - BACKGROUND & AIMS: Phosphatidylethanolamine-binding protein 1 (PEBP1, also RKIP) plays a pivotal role in cancer by regulating multiple cellular signaling processes and suppressing metastasis in animal models. We examined whether PEBP1 expression in hepatocellular carcinoma (HCC) correlated with the risk of recurrence and survival after resection. METHODS: A randomly selected cohort of 240 Chinese HCC patients, predominantly hepatitis B related, formed the basis of the study. PEBP1 expression levels were evaluated by immunohistochemistry and real-time reverse-transcriptase PCR. Survival analysis was performed by univariate and multivariate analyses. The results were further validated in an independent series of 403 patients. The relevance of PEBP1 to phospho-ERK was determined by Western blot analysis on clinical samples and hepatoma cell lines. RESULTS: PEBP1, prevalently down-regulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, lack of encapsulation, poor differentiation and large size). Both PEBP1 protein and mRNA levels were independent predictors for tumor recurrence (hazard ratio (HR) = 1.877, p=0.001; HR = 2.633, p = 0.001; respectively), and patient survival (HR = 1.796, p = 0.004; HR = 1.730, p = 0.044; respectively). The prognostic value of PEBP1 was then confirmed in the validation cohort. In addition, Western blot suggested that loss of PEBP1 led to hyperactivity of MAPK signaling. CONCLUSIONS: Down-regulation of PEBP1 in HCC indicated aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify the patients at high risk of post-operative recurrence. PMID- 20739084 TI - Primary isolated hepatic oval cells maintain progenitor cell phenotypes after two year prolonged cultivation. AB - BACKGROUND & AIMS: Although expandable hepatic progenitors provide renewable cell sources for treatment of hepatic disorders, long-term cultivation of hepatic progenitors may affect proliferation and differentiation abilities, and even initiate the formation of malignant cancer stem cells. This study aims to determine characteristics of primary cultured hepatic oval cells after prolonged cultivation in vitro. METHODS: Hepatic oval cells isolated from rats fed with a choline-deficient, ethionine-supplemented diet were continuously propagated every 5-7 days, to 100 passages over two years. Hepatocytic differentiation was induced by sodium butyrate and characterized using western blot, periodic acid Schiff assays, albumin secretion and urea production. Proliferation capacity was evaluated using growth-curve and cell-cycle analysis; anchorage-independent growth and tumorigenicity were determined using soft agar and xenograft assay. RESULTS: After 2 years of serial passages, hepatic oval cells with typical epithelial morphology continuously expressed OV-6, BD-1, BD-2, and Dlk as markers for hepatic progenitors, cytokeratin 19 as a cholangiocyte marker, and alpha fetoprotein and albumin as hepatocyte markers. Furthermore, sodium butyrate could induce these cells to become glycogen-storage cells with the functions of albumin secretion and ureagenesis from ammonia clearance, indicating hepatocytic differentiation. Although proliferation slightly accelerated after the 50th passage, hepatic oval cells stayed diploid cells with features of chromosomal stability, which did not acquire anchorage-independent growth capacity and caused no tumor in immunodeficient mice, suggesting no spontaneous malignant transformation. CONCLUSIONS: Hepatic oval cells retain the progenitor cell features without spontaneous malignant transformation after prolonged cultivation, and thus may serve as an expandable cell source for future exploitation of stem cell technology. PMID- 20739085 TI - Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. AB - BACKGROUND & AIMS: Liver Kupffer cells have been suggested to be heterogeneous macrophage lineage cells. We explored this possibility by classifying the mouse Kupffer cells into subpopulations and characterizing them by their phenotype and function. METHODS: Liver mononuclear cells (MNCs) from C57BL/6 mice were isolated and their phenotypes and functions were analyzed. The effects of clodronate liposomes and gadolinium chloride (GdCl(3)) on Kupffer cells were also investigated. RESULTS: Approximately 25% of liver MNCs were F4/80(+) Kupffer cells. Of these, 46% were CD11b(-)CD68(+), 22% were CD11b(+)CD68(-), and 6% were CD11b(+)CD68(+). CD68(+) cells showed potent phagocytic activity and reactive oxygen species (ROS) production capacity after lipopolysaccharide (LPS) stimulation, whereas CD11b(+) cells did not. CD11b(+) cells showed a strong capacity for the production of cytokines (TNF and IL-12), which was much less prominent in CD68(+) cells. At 24h after LPS or Escherichia coli injection into mice, the proportions of CD11b(+)CD68(-) and CD11b(+)CD68(+) cells increased but that of CD11b(-)CD68(+) cells decreased. The increase in CD11b(+)CD68(+) cells appeared to be derived from the CD11b(+)CD68(-) subset. Although the CD11b(+) cells augmented phagocytic activity after LPS injection, they did not increase ROS production, suggesting their weak lytic activity. Injection of clodronate or GdCl(3) into mice depleted the CD68(+) cells but increased CD11b(+) cells proportionally because CD68(+) cells may phagocytose these toxic reagents and undergo apoptosis. GdCl(3)-treated mice also consistently increased serum TNF after LPS challenge. CONCLUSIONS: Two F4/80(+) Kupffer cell subsets may exist, a CD68(+) subset with phagocytic activity and a CD11b(+) subset with cytokine producing capacity. PMID- 20739086 TI - Characterising adrenal function using directly measured plasma free cortisol in stable severe liver disease. AB - BACKGROUND & AIMS: Adrenal insufficiency (AI) has been reported in patients with advanced liver disease. Diagnosing AI is problematic owing to controversies in using total serum cortisol as a measure of adrenal function. No published data exist on directly measured plasma free cortisol (PFC) in patients with liver disease. METHODS: This prospective study compared serum total and measured plasma free cortisol to evaluate adrenal function in clinically stable cirrhotic patients and healthy controls. Cortisol levels were measured at baseline and following 250 MUg corticotrophin. AI was defined by total cortisol increments (delta cortisol) of less than 250 nmol/L, or a peak total cortisol under 500 nmol/L after cosyntropin. We used a peak plasma free cortisol concentration of 33 nmol/L as the threshold for AI. RESULTS: Forty-three consecutive patients and 10 healthy controls were studied. Cirrhotic patients had significantly lower peak (526 vs. 649 nmol/L, p=0.004) and delta total cortisol (264 vs. 397 nmol/L, p = 0.002) responses compared to healthy controls. However, basal plasma free cortisol was higher in patients (10.9 vs. 6.4 nmol/L, p = 0.03), and there were no differences in peak plasma free cortisol (p = 0.69) between the two groups. The prevalence of AI using total cortisol criteria was 58% compared to 12% using free cortisol (p<0.001). CONCLUSION: In patients with stable severe liver disease, a significant discrepancy exists between the rates of diagnosis of AI using the total and free cortisol criteria. We would advise caution in the interpretation of adrenal function testing using total cortisol measurements in this group. PMID- 20739087 TI - Renal sodium retention in pre-ascitic cirrhosis: the more we know about the puzzle, the more it becomes intricate. PMID- 20739088 TI - Dissecting the evolutionary genetics of iron overload in non-alcoholic fatty liver disease. PMID- 20739089 TI - Secondary metabolic gene clusters: evolutionary toolkits for chemical innovation. AB - Microbes and plants produce a huge array of secondary metabolites that have important ecological functions. These molecules have long been exploited in medicine as antibiotics, anticancer and anti-infective agents and for a wide range of other applications. Gene clusters for secondary metabolic pathways are common in bacteria and filamentous fungi, and examples have now been discovered in plants. Here, current knowledge of gene clusters across the kingdoms is evaluated with the aim of trying to understand the rules behind cluster existence and evolution. Such knowledge will be crucial in learning how to activate the enormous number of 'silent' gene clusters being revealed by whole-genome sequencing and hence in making available a wealth of novel compounds for evaluation as drug leads and other bioactives. It could also facilitate the development of crop plants with enhanced pest or disease resistance, improved nutritional qualities and/or elevated levels of high-value products. PMID- 20739090 TI - Accounting for large deformations in real-time simulations of soft tissues based on reduced-order models. AB - Model reduction techniques have shown to constitute a valuable tool for real-time simulation in surgical environments and other fields. However, some limitations, imposed by real-time constraints, have not yet been overcome. One of such limitations is the severe limitation in time (established in 500Hz of frequency for the resolution) that precludes the employ of Newton-like schemes for solving non-linear models as the ones usually employed for modeling biological tissues. In this work we present a technique able to deal with geometrically non-linear models, based on the employ of model reduction techniques, together with an efficient non-linear solver. Examples of the performance of the technique over some examples will be given. PMID- 20739091 TI - Transdisciplinary research is needed to predict plant invasions in an era of global change. PMID- 20739092 TI - Retention and release of TiO2 nanoparticles in unsaturated porous media during dynamic saturation change. AB - The retention and release of TiO(2) nanoparticles in porous media (packed glass beads) were studied under transient unsaturated conditions as the media were taken through multiple drainage/imbibition (drying/wetting) cycles at three different pH values. The focus of the work was to better understand the role of changing water table levels and rainfall infiltration events on the ultimate mobility of TiO(2) nanoparticles. Results indicate that retention during saturated transport varied considerably, from very strong retention at pH 5 (likely due to electrostatic interactions), to no measurable retention at pH 10. During primary drainage, additional retention (i.e., beyond what was retained during initial saturation) was observed at all pH values. During subsequent imbibition/drainage cycles where nanoparticle-free water was imbibed into the porous medium prior to drainage, the mass of retained TiO(2) remained nearly constant at all three pH values. Final imbibition/drainage and subsequent flushing, both using solution conditions adjusted to favor high mobility, showed very little additional nanoparticle release. These results indicate that the release of TiO(2) nanoparticles following retention by either saturated or unsaturated packed glass beads was difficult to achieve, regardless of the likely initial mechanisms of retention, even when solution conditions were changed to those that should favor high mobility. PMID- 20739093 TI - Sordaria macrospora, a model organism to study fungal cellular development. AB - During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. PMID- 20739094 TI - Transgene expression systems in the Triticeae cereals. AB - The control of transgene expression is vital both for the elucidation of gene function and for the engineering of transgenic crops. Given the dominance of the Triticeae cereals in the agricultural economy of the temperate world, the development of well-performing transgene expression systems of known functionality is of primary importance. Transgenes can be expressed either transiently or stably. Transient expression systems based on direct or virus mediated gene transfer are particularly useful in situations where the need is to rapidly screen large numbers of genes. However, an unequivocal understanding of gene function generally requires that a transgene functions throughout the plant's life and is transmitted through the sexual cycle, since this alone allows its effect to be decoupled from the plant's response to the generally stressful gene transfer event. Temporal, spatial and quantitative control of a transgene's expression depends on its regulatory environment, which includes both its promoter and certain associated untranslated region sequences. While many transgenic approaches aim to manipulate plant phenotype via ectopic gene expression, a transgene sequence can be also configured to down-regulate the expression of its endogenous counterpart, a strategy which exploits the natural gene silencing machinery of plants. In this review, current technical opportunities for controlling transgene expression in the Triticeae species are described. Apart from protocols for transient and stable gene transfer, the choice of promoters and other untranslated regulatory elements, we also consider signal peptides, as they too govern the abundance and particularly the sub cellular localization of transgene products. PMID- 20739095 TI - Cutaneous lupus erythematosus: update of therapeutic options part I. AB - In patients with cutaneous lupus erythematosus (CLE), it is important to provide instructions concerning methods of protection from sunlight and artificial sources of ultraviolet radiation. Topical corticosteroids are the mainstay of treatment for patients with CLE; however, they are of limited value because of their well-known side effects. Recently, calcineurin inhibitors have been shown to be efficient as topical therapy in various CLE subtypes. The first-line treatment for severe and widespread skin manifestations is antimalarials; hydroxychloroquine or chloroquine can each be combined with quinacrine in refractory CLE. Systemic steroids can be used additionally in exacerbations of the disease. In the first part of this review, recent information on topical and first-line systemic treatment is described in detail while providing the reader with up-to-date information on efficacy, side effects, and dosage for the various agents. In the second part, additional systemic agents for the treatment of CLE will be discussed. PMID- 20739096 TI - The association of dermatitis herpetiformis and systemic lupus erythematosus. AB - Dermatitis herpetiformis (DH) is an immune-mediated cutaneous disease occasionally associated with celiac disease, but rarely associated with systemic lupus erythematosus (SLE). The combination of DH and SLE is immunologically mediated and suggests a relationship between the two conditions. We describe a woman with DH and SLE with a novel HLA phenotype. PMID- 20739097 TI - Health care-associated infections studies project: Case 3. PMID- 20739098 TI - Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis. AB - We assessed the spontaneous blood-oxygen-level-dependent signal fluctuations in the resting-state brain networks of amyotrophic lateral sclerosis patients and their relation to physiologically sensitive and disease modified functional magnetic resonance imaging parameters. Resting-state functional magnetic resonance imaging was performed at 3 Tesla on 20 amyotrophic lateral sclerosis patients with minimal frontal cognitive dysfunction and 20 age- and sex-matched healthy volunteers. Resting-state network maps were extracted with independent component analysis and group-level statistical analyses were performed to detect disease and disease-by-age interaction effects. Whole-brain global and regional atrophy measures were obtained from same-session structural scans. The sensori motor network showed significant disease effects, with signals suppressed in patients bilaterally in the primary motor cortex. The default-mode network showed a significant disease-by-age interaction in the posterior cingulate cortex, where signals correlated with age positively in patients and negatively in controls. Both disease and disease-by-age interaction effects were detected in the right fronto-parietal network. Although global atrophy did not show significant differences, regions of reduced gray matter volume were detected in patients compared with controls adjacent to regions of reduced functional connectivity. Our results confirm that resting-state functional magnetic resonance imaging signals in the sensori-motor network are suppressed in amyotrophic lateral sclerosis. A similar suppression is evident in the right fronto-parietal network, possibly reflecting the patients' frontal dysfunction and right-lateralized patterns of regional atrophy. The interaction between disease and aging in the default-mode network unravels a possible mechanism of compensation between motor and extramotor systems emerging as a supplementary functional push to help motor disturbances. PMID- 20739100 TI - Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old. AB - Recently, two large, and independent genome wide association studies of late onset Alzheimer's disease (AD) established association with the same rs11136000 variation in the clusterin (CLU) gene. In addition, one variation, rs3851179, in the phosphatidylinositol binding clathrin assembly protein (PICALM) gene and one variation, rs6656401, in the complement component (3b/4b) receptor 1 (CR) gene were associated with AD. Here, we replicate these associations with cognitive functioning in 1380 individuals from the Danish (1905) birth cohort study of the oldest old (92-93 years at intake) using measures of Mini Mental State Examination (MMSE) and a cognitive composite score. We found a significant association between the highly frequent CLU rs11136000 T allele (38%) and better performance on the cognitive composite score (p = 0.016) explaining 0.5% of the mean variation in cognitive composite score, and for men a significant association between the highly frequent PICALM rs3851179 A allele (38%). Better performance was found (p = 0.024), explaining 1.4% of the mean variation in cognitive composite score in men. These alleles correspond to the minor alleles initially found more frequent in controls than in cases of AD. PMID- 20739101 TI - Association between white matter hyperintensities and executive decline in mild cognitive impairment is network dependent. AB - White matter hyperintensities (WMH) in Mild Cognitive Impairment (MCI) have been associated with impaired executive functioning, although contradictory findings have been reported. The aim of this study was to examine whether WMH location influenced the relation between WMH and executive functioning in MCI participants (55-90 years) in the European multicenter memory-clinic-based DESCRIPA study, who underwent MRI scanning at baseline (N = 337). Linear mixed model analysis was performed to test the association between WMH damage in three networks (frontal parietal, frontal-subcortical and frontal-parietal-subcortical network) and change in executive functioning over a 3-year period. WMH in the frontal-parietal and in the frontal-parietal-subcortical network were associated with decline in executive functioning. However, the frontal-subcortical network was not associated with change in executive functioning. Our results suggest that parietal WMH are a significant contributor to executive decline in MCI and that investigation of WMH in the cerebral networks supporting cognitive functions provide a new way to differentiate stable from cognitive declining MCI individuals. PMID- 20739102 TI - Preparation of new polycyclic compounds derived from benzofurans and furochromones. An approach to novel 1,2,3-thia-, and selena-diazolofurochromones of anticipated antitumor activities. AB - Base catalyzed condensation of enaminoketones (3a,b) with malononitrile yields the respective 7-imino-5[2(substituted)prop-1-enyl]furochromene-6-carbonitriles (4a-d) according to the nature of base used. Compounds (3a, b) condense also with indan-1,3-diketone (5) to give alpha, beta-unsaturated carbonyl compounds (6a) and (6b), respectively. Pyrrolidine-catalyzed condensation of visnaginone (2a) and khellinone (2b) with active methylenes yields the corresponding 1-[7,7 (substituted) furobenzodihydropyrone derivatives (7a-e) which condense with semicarbazide to give the respective semicarbazones (8a-e). Compounds (8b,e) react with thionyl chloride to give the respective 1,2,3-thiadiazoles (9a,b) meanwhile compounds (8a-e) react also with selenium dioxide to give 1,2,3 selenadiazoles (9c-g), respectively. Chalcones (11a,b) were obtained upon condensing (2a,b) with ferrocene-2-carboxaldehyde (10). Compatible elementary and spectroscopic measurements were in good accord with the structures postulated for the new compounds. The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of four (breast: MCF-7, cervix: HELA, colon: HCT116 and liver: HEPG2) human solid tumor cell lines and the structure activity relationship (SAR) was discussed. PMID- 20739099 TI - Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? AB - Normal aging is accompanied by global as well as regional structural changes. While these age-related changes in gray matter volume have been extensively studied, less has been done using newer morphological indexes, such as cortical thickness and surface area. To this end, we analyzed structural images of 216 healthy volunteers, ranging from 18 to 87 years of age, using a surface-based automated parcellation approach. Linear regressions of age revealed a concomitant global age-related reduction in cortical thickness, surface area and volume. Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy. No cortical regions showed more surface area reduction than the global average. The distinction between these morphological measures may provide valuable information to dissect age-related structural changes of the brain, with each of these indexes probably reflecting specific histological changes occurring during aging. PMID- 20739103 TI - Analysis of physico-chemical properties of substrates of ABC and MFS multidrug transporters of pathogenic Candida albicans. AB - In this study, we have explored the structure activity relationships of substrates of two major, promiscuous, multidrug transporters of an opportunistic human pathogen Candida albicans namely, CaCdr1p and CaMdr1p. To differentiate between substrates and non-substrates, the susceptibilities of the Saccharomyces cerevisiae strains over-expressing CaCdr1p or CaMdr1p were determined for 67 structurally diverse xenobiotics. A comparison of physico-chemical indices of these tested compounds enabled identification of molecular descriptors such as, degree of hydrophobicity (MLogP), geometrical descriptor (DISPv), molecular edge descriptor (MDEC.12 and MDEC.13) and 3D-Morse descriptors, that allowed their segregation into substrates and non-substrates for both the transporter proteins. Taken together, present study provides first evidence of chemical basis of substrate specificities of two clinically relevant multidrug transporters of an opportunistic human pathogen C. albicans. PMID- 20739105 TI - [Measles and the internist: a disease to eradicate!]. PMID- 20739104 TI - Synthesis of bioactive polyheterocyclic ring systems as 5alpha-reductase inhibitors. AB - Simple synthetic strategies for the hitherto unreported [1,2,4]triazolo[4,3 a]pyrido[4,3-d]pyrimidines 8 and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5 b][1,6]naphthyridine-5-one 15 are described based on reaction of thione 3 and 12 with hydrazonoyl chloride 1a-h, respectively. The structures of products 8 and 15 were confirmed by spectroscopic and X-ray crystallographic analyses. Also, the mechanism of such reactions was discussed. In addition, reaction of compound 12 with bromoacetic acid and hydrazine hydrate was investigated. Compounds were screened against 5alpha-reductase and showed activities with good LD(50) and LD(90) for all compounds. PMID- 20739106 TI - Emotional intelligence and nursing performance among nursing students. AB - Some scholars have proposed that the educational preparation of nurses can be improved by incorporating emotional intelligence lessons into the nursing curricula. However, the relationship between emotional intelligence and nursing performance in nursing students is unknown. The purpose of the study was to examine this relationship among nursing students. A descriptive correlational design with non-probability sampling methods of 87 nursing students in a university setting was conducted. The variables of focus were emotional intelligence and nursing performance. Emotional intelligence was measured with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Nursing performance was measured using the Six Dimension Scale of Nursing Performance (6 D Scale). The sample was predominately Caucasian (91%), female (93%), mean age 24 years. The mean score for emotional intelligence was 0.53, SD +/- 0.06 indicating moderate emotional intelligence. The mean score for nursing performance was 3.14, SD +/- 0.40 indicating moderate nursing performance. Emotional intelligence was related to nursing performance. Four of the six nursing performance subscale scores were significantly correlated with the total emotional intelligence scores. Implications for nursing education and clinical practice are discussed. PMID- 20739107 TI - Healing of a painful intervertebral disc should not be confused with reversing disc degeneration: implications for physical therapies for discogenic back pain. AB - BACKGROUND: Much is known about intervertebral disc degeneration, but little effort has been made to relate this information to the clinical problem of discogenic back pain, and how it might be treated. METHODS: We re-interpret the scientific literature in order to provide a rationale for physical therapy treatments for discogenic back pain. INTERPRETATION: Intervertebral discs deteriorate over many years, from the nucleus outwards, to an extent that is influenced by genetic inheritance and metabolite transport. Age-related deterioration can be accelerated by physical disruption, which leads to disc "degeneration" or prolapse. Degeneration most often affects the lower lumbar discs, which are loaded most severely, and it is often painful because nerves in the peripheral anulus or vertebral endplate can be sensitised by inflammatory like changes arising from contact with blood or displaced nucleus pulposus. Surgically-removed human discs show an active inflammatory process proceeding from the outside-in, and animal studies confirm that effective healing occurs only in the outer anulus and endplate, where cell density and metabolite transport are greatest. Healing of the disc periphery has the potential to relieve discogenic pain, by re-establishing a physical barrier between nucleus pulposus and nerves, and reducing inflammation. CONCLUSION: Physical therapies should aim to promote healing in the disc periphery, by stimulating cells, boosting metabolite transport, and preventing adhesions and re-injury. Such an approach has the potential to accelerate pain relief in the disc periphery, even if it fails to reverse age-related degenerative changes in the nucleus. PMID- 20739109 TI - Exploring the ambiguities of masculinity in accounts of emotional distress in the military among young ex-servicemen. AB - This paper examines the experiences and perspectives of ex-military servicemen in the UK. It focuses specifically on the complex links between emotional distress and various constructions of 'masculinity' in a military context. Aspects of military culture that exacerbate vulnerability and also those that are protective to mental health are identified and discussed with reference to the theoretical constructs relating to hegemonic masculinity. A qualitative research design using semi-structured interviews provided in-depth accounts of the experiences of 20 ex servicemen aged 23-44, all but one of whom were in the Army. We found that in a military setting hegemonic masculinity is embedded in the construction of a soldier identity and expression of emotion may be seen as inappropriate. As a result soldiers often lack a language with which to express distress (in a context in which they may witness extremely distressing events), which may result in delays in recognising and treating mental health problems. However, constructions of masculinity in this setting to some degree also promote a caring, sharing ethos based on strong inter-dependent bonds. A young soldier who can cope with the stresses of military life 'becomes a man', adopts a masculine/soldier identity and is well-placed to benefit from these protective factors, notably the camaraderie that is part of service life. In this manner a caring ethos in which some admissions of weakness may be permissible is situated within hegemonic masculinity. This seeming paradox between hyper masculinity and caring masculinities appears to be embedded within military culture, perhaps reflecting the flexibility and ambiguity inherent in constructions of hegemonic masculinity. PMID- 20739110 TI - Intraoral dermoid cyst in an infant: a case report. PMID- 20739108 TI - Spatial and socio-behavioral patterns of HIV prevalence in the Democratic Republic of Congo. AB - This study uses a 2007 population-based household survey to examine the individual and community-level factors that increase an individual's risk for HIV infection in the Democratic Republic of Congo (DRC). Using the 2007 DRC Demographic Health Surveillance (DHS) Survey, we use spatial analytical methods to explore sub-regional patterns of HIV infection in the DRC. Geographic coordinates of survey communities are used to map prevalence of HIV infection and explore geographic variables related to HIV risk. Spatial cluster techniques are used to identify hotspots of infection. HIV prevalence is related to individual demographic characteristics and sexual behaviors and community-level factors. We found that the prevalence of HIV within 25 km of an individual's community is an important positive indicator of HIV infection. Distance from a city is negatively associated with HIV infection overall and for women in particular. This study highlights the importance of improved surveillance systems in the DRC and other African countries along with the use of spatial analytical methods to enhance understanding of the determinants of HIV infection and geographic patterns of prevalence, thereby contributing to improved allocation of public health resources in the future. PMID- 20739111 TI - Rationale for early versus late intervention with arthroscopy for treatment of inflammatory/degenerative temporomandibular joint disorders. AB - PURPOSE: The goal of this study was to determine if there were differences in outcomes of arthroscopic surgery in patients with inflammatory/degenerative temporomandibular joint (TMJ) disease who underwent early surgical intervention versus late surgical intervention. MATERIALS AND METHODS: The study population included 44 consecutive patients who met the criteria for TMJ operative arthroscopy who were divided into early and late intervention groups. The time between the onset of symptoms and the performance of arthroscopy was used to determine entry into the early versus late intervention group. All groups were evaluated for changes in preoperative versus postoperative pain levels based on visual analog scale (VAS) scores and maximum interincisal opening distance. Statistical analyses included the Student t test to determine if there were significant differences between preoperative and postoperative assessments in the early and late intervention groups. RESULTS: The mean time between onset of symptoms in the early intervention group (21 patients) was 5.4 months compared with 33 months in the late intervention group (23 patients). All patient groups had statistically significant decreases in pain and improvement in maximum interincisal opening distance after arthroscopy. The early intervention group had a mean decrease in VAS pain scores of 5.14 compared with the late intervention group with a mean decrease in VAS pain scores of 2.84, and this difference was significant (P = .012). The early intervention group had a mean increase in maximum interincisal opening of 12.38 mm compared with the late intervention group with a mean increase of 7.70. Although statistical significance was not achieved for increases in maximum interincisal opening between the early and late intervention groups (P = .089), the difference between the 2 groups was suggestive of a trend. There were no surgical complications for either group; however, 2 patients in the late intervention group developed persistent chronic neuropathic pain, requiring pain management. CONCLUSIONS: TMJ arthroscopy reliably decreased pain and increased the maximum interincisal opening distance in the early and late intervention groups. The early intervention group had better surgical outcomes than the late intervention group. Arthroscopic surgery should be considered early in the management of patients with inflammatory/degenerative TMJ disease. PMID- 20739112 TI - A longitudinal study of functional outcomes after surgical resection and microvascular reconstruction for oral cancer: tongue mobility and swallowing function. AB - PURPOSE: Controversy exists regarding physiologic outcomes related to the tongue after radial forearm free flap (RFFF) reconstruction of hemiglossectomy defects. The purpose of this study is to report swallowing and tongue mobility outcomes for patients with RFFF reconstruction of the anterior two thirds of the tongue. MATERIALS AND METHODS: Swallowing and tongue mobility were assessed at 4 different time points over the course of 1 year of treatment for 15 patients who underwent RFFF reconstruction of the anterior two thirds of the tongue. Preoperative swallowing function in the treatment group was compared with a patient group that had no involvement of the tongue. A comparison group of 14 patients with nasopharyngeal cancer was used to compare preintervention function in patients with and without lesions of the tongue. RESULTS: No differences existed between the experimental and comparison groups before intervention. Two significant differences were found for swallowing ability and tongue mobility in the experimental group. Some of the measures at 1 month postoperatively were significantly different from some of the preoperative measures for liquid swallows and posterior-tongue mobility. All measures returned to baseline by the study's end. CONCLUSION: Although some minor deficits exist in swallowing and tongue mobility after RFFF reconstruction, it appears that these problems are no longer evident 12 months postoperatively. PMID- 20739113 TI - Use of living cell construct to enhance bone reconstruction: preliminary results. PMID- 20739114 TI - Intraoral split-thickness skin grafts: a new approach using vinyl polysiloxane. PMID- 20739115 TI - Use of the internal mammary artery perforator flap for repair of pharyngocutaneous fistulas in the vessel-depleted neck. PMID- 20739116 TI - Relationship between inferior alveolar nerve canal position at mandibular second molar in patients with prognathism and possible occurrence of neurosensory disturbance after sagittal split ramus osteotomy. AB - PURPOSE: To elucidate the relationship between the anatomic position of the inferior alveolar nerve (IAN) at the mandibular second molar and the occurrence of neurosensory disturbances of the IAN after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Also, the present study evaluated the difference in anatomic position of the IAN between patients with and without mandibular prognathism. PATIENTS AND METHODS: Computed tomography images were taken of 28 patients with mandibular prognathism and 30 without prognathism. On these scans, the IANs from the mandibular second molar region to the mandibular foramen in the mandibular ramus were identified. The present study was designed as a cross-sectional study. The distance from the buccal aspect of the IAN canal to the outer buccal cortical margin of the mandible in the mandibular second molar regions was measured on the computed tomography images. Also, the linear distance between the superior aspect of the IAN canal and the alveolar crest in these regions was calculated. In addition, we investigated the presence or absence of contact between the IAN canal and the inner buccal cortical margin of the mandible from the mandibular second molar to the mandibular foramen in the mandibular ramus. Next, we examined whether neurosensory disturbances occurring after SSRO were related to the position of the IAN at the mandibular second molar. RESULTS: A significant difference was found in the occurrence of neurosensory disturbances of the IAN after SSRO between men and women (chi(2) test, P < .05). For the distance from the buccal aspect of the IAN canal to the outer buccal cortical margin of the mandible in the mandibular second molar region, a significant difference was found between groups with and without neurosensory disturbances (Student's t test, P < .01). The shorter the distance from the buccal aspect of the IAN canal to the outer buccal cortical margin, the more frequent the occurrence of neurosensory disturbances of the IAN. CONCLUSIONS: The present results have demonstrated that gender and the anatomic position of the IAN canal at the mandibular second molar are significantly related to the occurrence of neurosensory disturbances of the IAN after SSRO. Therefore, surgeons should clearly inform patients of the increased possibility of neurosensory disturbances after SSRO when the patients are female and are found to have a shorter distance from the buccal aspect of the IAN canal to the outer buccal cortical margin. PMID- 20739118 TI - Of mice and men--viruses and prostate cancer: what is the next step? PMID- 20739117 TI - Leachate characterization in semi-aerobic and anaerobic sanitary landfills: a comparative study. AB - This study analyzes and compares the results of leachate composition at the semi aerobic Pulau Burung Landfill Site (PBLS) (unaerated pond and intermittently aerated pond) and the anaerobic Kulim Sanitary Landfill in the northern region of Malaysia. The raw samples were collected and analyzed for twenty parameters. The average values of the parameters such as phenols (1.2, 6.7, and 2.6 mg/L), total nitrogen (448, 1200, and 300 mg/L N-TN), ammonia-N (542, 1568, and 538 mg/L NH(3) N), nitrite (91, 49, and 52 mg/L NO(2)(-)-N), total phosphorus (21, 17, and 19 mg/L), BOD(5) (83, 243, and 326 mg/L), COD (935, 2345, and 1892 mg/L), BOD(5)/COD (0.096,0.1124,0.205%), pH (8.20, 8.28, and 7.76), turbidity (1546, 180, and 1936 Formazin attenuation units (FAU)), and color (3334, 3347, and 4041 Pt Co) for leachate at the semi-aerobic PBLS (unaerated and intermittently aerated) and the anaerobic Kulim Sanitary Landfill were recorded, respectively. The obtained results were compared with previously published data and data from the Malaysia Environmental Quality Act 1974. The results indicated that Pulau Burung leachate was more stabilized compared with Kulim leachate. Furthermore, the aeration process in PBLS has a considerable effect on reducing the concentration of several pollutants. The studied leachate requires treatment to minimize the pollutants to an acceptable level prior to discharge into water courses. PMID- 20739119 TI - Experimental study on the absorption behaviors of gas phase bivalent mercury in Ca-based wet flue gas desulfurization slurry system. AB - Gas phase oxidation and catalytic oxidation of element mercury (Hg(0)) to bivalent mercury (Hg(2+)) were proposed to improve the mercury removal efficiency in the wet flue gas desulfurization (WFGD) system. However, the re-emission of Hg(0), generated by the reduction of absorbed Hg(2+), would lead to a damping of the total mercury removal efficiency. In this paper, the absorption and reduction behaviors of bivalent mercury in the Ca-based WFGD slurry were evaluated in our purpose-built device. According to our experimental results, the slurry chemistry (such as CaSO(3) content, SO(4)(2-), Cl(-) and pH value) had a strong influence on the reduction of absorbed bivalent mercury. And the inlet concentrations of SO(2) and O(2) contribute little to the mercury absorption. Within the typical pH value range of 4.5-5.5, about 70% of inlet bivalent mercury was converted to Hg(0). The re-emission of Hg would be greatly retarded with the increase of [SO(4)(2-)] due to the formation of HgSO(4) or Hg(3)O(2)SO(4). Moreover, it was found that Cl(-) would also inhibit the reduction of bivalent mercury through the ligands reactions between Cl(-) and Hg(2+). PMID- 20739120 TI - QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis. AB - Aldehydes are a toxic class of chemicals causing severe health hazards. In this background, quantitative structure-toxicity relationship (QSTR) models have been developed in the present study using Extended Topochemical Atom (ETA) indices for a large group of 77 aromatic aldehydes for their acute toxicity against the protozoan ciliate Tetrahymena pyriformis. The ETA models have been compared with those developed using various non-ETA topological indices. Attempt was also made to include the n-octanol/water partition coefficient (logK(o/w)) as an additional descriptor considering the importance of hydrophobicity in toxicity prediction. Thirty different models were developed using different chemometric tools. All the models have been validated using internal validation and external validation techniques. The statistical quality of the ETA models was found to be comparable to that of the non-ETA models. The ETA models have shown the important effects of steric bulk, lipophilicity, presence of electronegative atom containing substituents and functionality of the aldehydic oxygen to the toxicity of the aldehydes. The best ETA model (without using logK(o/w)) shows encouraging statistical quality (Q(int)(2)=0.709,Q(ext)(2)=0.744). It is interesting to note that some of the topological models reported here are better in statistical quality than previously reported models using quantum chemical descriptors. PMID- 20739121 TI - Reduction of VOC emission from natural flours filled biodegradable bio-composites for automobile interior. AB - Various experiments, such as the thermal extract (TE) method, field and emission cell (FLEC) method and 20 L small chamber, were performed to examine the total volatile organic compound (TVOC) emissions from bio-composites. The TVOC of neat poly(lactic acid) (PLA) was ranged from 0.26 mg/m(2)h to 4.11 mg/m(2)h with increasing temperature. For both PLA bio-composites with pineapple flour and destarched cassava flour, the temperature increased from 0.30 mg/m(2)h to 3.72 mg/m(2)h and from 0.19 mg/m(2)h to 8.74 mg/m(2)h, respectively. The TVOC emission factors of all samples increased gradually with increasing temperature. Above 70 degrees C, both PLA-P and PLA-C composites had higher TVOC emission factors than neat PLA due to the rapid emission of natural volatile organic compounds (VOCs), such as furfural (2-furancarboxyaldehyde). PLA composites containing 30 wt% flour had high 1,4-dioxane reduction ability, >50%. The TVOC of poly(butylene succinate) (PBS) was emitted rapidly from 50 degrees C to 90 degrees C due to succinic acid from the pyrolysis of PBS. The TVOC emission factors of PLA bio composite and PBS bio-composites were reduced using the bake-out method (temperature at 70 degrees C and baking time 5h). The initial TVOC emission factors of the PLA and PBS bio-composites with pineapple flour and destarched cassava flour were reduced by the baking treatment using FLEC. The TVOC factors from PLA and PBS decreased until 5 days and were commonly maintained a relatively constant value after 5 days using 20L small chamber. The decrease in TVOC emission showed a similar trend to that of the TE and FLEC method. This method confirmed the beneficial effect of the baking treatment effect for polypropylene and linear density polyethylene (LDPE). PMID- 20739122 TI - Close encounters of the third kind: evidence for contact with TNF-alpha. PMID- 20739123 TI - Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis. AB - Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examined pharmacologic responsiveness and spinal glia activation. Mechanical allodynia developed congruently with joint swelling. Surprisingly, allodynia persisted after resolution of inflammation. At the peak of joint inflammation (days 4-10), hypersensitivity was attenuated with i.p. etanercept, gabapentin, and ketorolac. Following resolution of synovial inflammation (days 19-23), only gabapentin relieved allodynia. The superficial dorsal horn of arthritic mice displayed increased staining of microglia at early and late time points, but astrocyte staining increased only during the inflammatory phase. ATF3, a marker of nerve injury, was significantly increased in the lumbar dorsal root ganglia during the late phase (day 28). Hence, serum transfer in the K/BxN serum transfer arthritis model produces a persistent pain state, where the allodynia during the inflammatory state is attenuated by TNF and prostaglandin inhibitors, and the pharmacology and histochemistry data suggest a transition from an inflammatory state to a state that resembles a neuropathic condition over time. Therefore, the K/BxN serum transfer model represents a multifaceted model for studies exploring pain mechanisms in conditions of joint inflammation and may serve as a platform for exploring novel treatment strategies for pain in human arthritic conditions. PMID- 20739125 TI - A hairy situation - at least in females. PMID- 20739124 TI - Neuronal hyperexcitability in the dorsal horn after painful facet joint injury. AB - Excessive cervical facet capsular ligament stretch has been implicated as a cause of whiplash-associated disorders following rear-end impacts, but the pathophysiological mechanisms that produce chronic pain in these cases remain unclear. Using a rat model of C6-C7 cervical facet joint capsule stretch that produces sustained mechanical hyperalgesia, the presence of neuronal hyperexcitability was characterized 7 days after joint loading. Extracellular recordings of spinal dorsal horn neuronal activity between C6 and C8 (117 neurons) were obtained from anesthetized rats, with both painful and non-painful behavioral outcomes established by the magnitude of capsule stretch. The frequency of neuronal firing during noxious pinch (p<0.0182) and von Frey filaments applications (4-26g) to the forepaw was increased (p<0.0156) in the painful group compared to the non-painful and sham groups. In addition, the incidence and frequency of spontaneous and after discharge firing were greater in the painful group (p<0.0307) relative to sham. The proportion of cells in the deep laminae that responded as wide dynamic range neurons also was increased in the painful group relative to non-painful or sham groups (p<0.0348). These findings suggest that excessive facet capsule stretch, while not producing visible tearing, can produce functional plasticity of dorsal horn neuronal activity. The increase in neuronal firing across a range of stimulus magnitudes observed at day 7 post-injury provides the first direct evidence of neuronal modulation in the spinal cord following facet joint loading, and suggests that facet-mediated chronic pain following whiplash injury is driven, at least in part, by central sensitization. PMID- 20739126 TI - The impact of dietary protein on the pathophysiology of porcine trypanosome infection. AB - The influence of protein nutrition on porcine trypanosomosis was investigated in this study. Thirty six landrace/large white cross weanling pigs were used. Upon purchase, these were divided into two groups of 18 pigs each and these were housed separately to enable them adapt to our animal house management regimen. Post-adaptation, the pigs were divided into 6 groups A(1) and A(2), B(1), and B(2), and C(1) and C(2) (n=6). A(1) and A(2) were fed diet A(1), B(1) and B(2) diet B while C(1) and C(2) were fed diet C with 28%, 20% and 16% crude protein, respectively. Two-week post-adaptation groups A(1), B(1), and C(1) were infected with 3*10(6)Trypanosoma brucei brucei organisms intraperitoneally. Body weight, temperature and Packed Cell Volume of all group members were determined a week prior to infection, on the day of infection and weekly thereafter till end of the study. Serum biochemistry was also concurrently determined. Three days post infection, blood was collected from all the members of A(1), B(1) and C(1) and thoroughly screened microscopically for the presence of trypanosome organisms. This was repeated on subsequent days till all the infected animals developed patency by showing parasitaemia under wet mount. The result of this study showed that infection did not have any significant effect on the rate of weight gain except in group C (p<=0.05). Moreover, infections caused significant hyperthermia in all the infection groups (p<=0.05) with diet A showing the least response and C the most severe. Furthermore, diet did not have any effect on parasite establishment or parasitaemia as the prepatent period was similar in all the infection groups. There was also significant reduction in PCV whose severity also correlated with reduction in the protein dietary quality. Similar observation was also made on the total serum protein where significant hyperproteinaemia correlated with increasing dietary protein and the uninfected controls having higher serum protein relative to the infected. There was in addition parasite induced hypoalbuminaemia whose severity was also graduated in favour of increasing protein level. The study demonstrated the protective influence of dietary protein on some of the pathophysiological features of porcine trypanosomosis. PMID- 20739129 TI - Iron and neurodevelopment in infant. PMID- 20739128 TI - Molecular pathology of wound healing. AB - Skin-wound healing is an orchestrated biological phenomena consisting of three sequential phases, inflammation, proliferation, and maturation. Many biological substances are involved in the process of wound repair, and this short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine. With the development of genetically engineered animals, essential molecules for skin-wound healing have been identified. Especially, cytokines, and growth factors are useful candidates and markers for the determination of wound vitality or age. Moreover, bone marrow-derived progenitor cells would give significant information to wound age determination. In this review article, some interesting observations are presented, possibly contributing to the future practice of forensic pathologists. PMID- 20739127 TI - Extended findings of brain metabolite normalization in MA-dependent subjects across sustained abstinence: a proton MRS study. AB - OBJECTIVE: The goal of the present study was to extend our previous findings on long-term methamphetamine (MA) use and drug abstinence on brain metabolite levels in an expanded group of MA-dependent individuals. METHODS: Seventeen MA abusers with sustained drug abstinence (1-5 years), 30 MA abusers with short-term drug abstinence (1-6 months) and 24 non-substance using controls were studied using MR spectroscopy (MRS). MRS measures of NAA/Cr, Cho/Cr and Cho/NAA were obtained in the anterior cingulate cortex (ACC) and in the primary visual cortex (PVC). RESULTS: ACC-Cho/NAA values were abnormally high in the short-term abstinent group compared to controls [F(1,52) = 18.76, p < 0.0001]. No differences were observed between controls and the long-term abstinent group [F(1,39) = 0.97, p = 0.97]. New evidence of lower ACC-NAA/Cr levels were observed in the short-term abstinent MA abusers compared to controls [F(1,52) = 23.05, p < 0.0001] and long term abstinent MA abusers [F(1,45) = 7.06, p = 0.01]. No differences were observed between long-term abstinent MA abusers and controls [F(1,39) = 0.48, p = 0.49]. CONCLUSIONS: The new findings of relative NAA/Cr normalization across periods of abstinence suggest that adaptive changes following cessation of MA abuse may be broader than initially thought. These changes may contribute to some degree of normalization of neuronal function in the ACC. PMID- 20739130 TI - Sister Mary Joseph's nodule as the sole presenting sign of gastric signet ring cell adenocarcinoma. AB - The Sister Mary Joseph's nodule is a periumbilical metastatic tumor originating from advanced metastatic intra-abdominal and intrapelvic malignancies. It is an inconspicuous and uncommon clinical sign, which not only shows the presence of visceral malignancy but also reveals the poor prognosis of these malignancies. The majority of cases originate from gastrointestinal or ovarian cancer. We present a case of an 80-year-old woman with an umbilical nodule, which was the sole presenting symptom of advanced signet ring cell carcinoma of the stomach with generalized peritoneal carcinomatosis. There are very few cases of gastric signet ring cell adenocarcinoma presenting as a SMJN, a fact rather striking as signet ring cell gastric carcinoma has an increased frequency of peritoneal dissemination and carcinomatosis of the peritoneum. PMID- 20739131 TI - Application of ANAES guidelines for colonoscopy in France: a practical survey. AB - OBJECTIVES: In 2004, the French health authorities published guidelines on the indications for colonoscopy. However, no study has evaluated the awareness of healthcare practitioners of these guidelines. The aim of this study was to determine the level of awareness of the ANAES guidelines among French gastroenterologists. PATIENTS AND METHODS: A questionnaire comprising 20 multiple choice questions (MCQ) was presented to a group of 79 gastroenterologists between February and June in 2008. The questions covered screening tests for colon cancer (one question), endoscopic mucosal resection (two questions) and the ANAES guidelines (17 questions). According to the number of colonoscopies performed per year (less than 100, 100-500, more than 500), the answers to these questions were analyzed separately. RESULTS: Among the practitioners carrying out less than 100, 100-500 and more than 500 colonoscopies per year, the guidelines for colon cancer screening were known by 33, 50 and 56%, respectively, the quality criteria for endoscopic mucosal resection by 0, 0 and 3.7%, respectively, and the ANAES guideline indications for colonoscopy by 34.3, 51.2 and 48.9%, respectively (P<0.001). The ANAES guidelines were significantly better known by practitioners who were performing more than 100 colonoscopies per year, while the indications for control colonoscopy were less often correctly anticipated. No differences were found concerning postponed indications. CONCLUSION: The ANAES guidelines consists of the following elements: (1) awareness of the ANAES guidelines is poor, with control colonoscopy being correctly anticipated in just over a third of the gastroenterologists; (2) performing more than 100 colonoscopies per year improves knowledge of the ANAES guidelines; and (3) the ANAES guidelines need to be simplified and should be covered by continuing medical education. PMID- 20739133 TI - Tubulovillous adenoma of the appendix: a case report and review of the literature. AB - We report the case of a young woman hospitalized for a chronic appendicular syndrome. The histological examination of the resected specimen revealed a rare tumor: tubulovillous adenoma, discovered in 0.02% of all appendectomy procedures. Treatment is most often limited to appendectomy, but in the event of incomplete excision or associated adenocarcinoma, right hemicolectomy may be required. After surgery, a follow-up colonoscopy is recommended due to the higher risk of second gastrointestinal neoplasms in patients with appendicular tumors. PMID- 20739132 TI - Longitudinal study of bone mineral density in children after a diagnosis of Crohn's disease. AB - AIM: The purpose of this study was to measure the bone mineral density (BMD) of children with Crohn's disease (CD) and to prospectively assess its evolution. PATIENTS AND METHODS: A total of 27 children (20 boys, seven girls), aged 12.1+/ 2.5 years, were recruited at the time of CD diagnosis. Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD, expressed as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). One year later, BMD was measured again to identify any correlations with disease activity [group A (active disease) vs group R (remission)]. RESULTS: BMD/CA and BMD/BA were negatively correlated with delay in diagnosis (P<0.0001 and P<0.05, respectively). BMD/CA was less than -2 standard deviation (SD) in nine patients and BMD/BA was less -2 SD in four patients. At the follow-up, the increase in BMD was smaller in group A (n=14), whether expressed as absolute values (-0.002 vs 0.040 g/cm(2) per year; P<0.024) or as percentages (-0.2 vs 6.6%; P<0.041); changes in BMD/CA (-0.5 vs -0.1 SD/year) and BMD/BA (-0.3 vs 0 SD/year) did not differ. CONCLUSION: Diagnostic delay greatly affects BMD in children with CD even prior to corticosteroid therapy. The risk of low BMD increases with persistent CD activity, although the risk is reduced in association with bone maturation delay. PMID- 20739134 TI - Landing sites and intubation may influence helicopter emergency medical services on-scene time. AB - BACKGROUND: Reduced transport time of patients from the scene of an accident to definitive surgical treatment is one important reason to employ ambulance helicopters on trauma missions. However, if the helicopter is unable to land close to the scene, the transport time may be increased compared to transport with ground ambulance, due to time-consuming transfer of the patient between vehicles. OBJECTIVE: The objective of this study was to evaluate how the landing site, as determined by distance from the scene, and rapid sequence intubation (RSI) affected on-scene time (OST). METHODS: This was a prospective observational study performed during a 12-month period in a mixed urban and rural anesthesiologist-staffed Helicopter Emergency Medical Service in Norway. Data regarding the landing sites, the accident, and patient treatment were recorded. RESULTS: A total of 252 primary trauma missions were included in the study. In 75% of the missions, the aircraft landed<50 meters from the scene, and in 7% the distance exceeded 200 meters. Mean OST when the patient was not intubated was 14.5 min (median 14 min). When an RSI was performed, the mean OST was significantly higher (22.7 min, median 20 min; p<0.001). CONCLUSION: Usually, a helicopter can land close to the accident scene and the location of the landing site does not contribute to a delay in arrival of the patient at the hospital. The OST is significantly higher, however, in those patients who receive endotracheal intubation before take-off. This reflects the time needed for intubation, as well as the increased complexity and workload when the patient is severely injured. PMID- 20739136 TI - A qualitative study of caregivers' expectations and communication desires during medical consultation for sick children in Uganda. AB - OBJECTIVE: Little data exist on patients' expectations and communication desires during medical consultation in Non-Western settings. We conducted a qualitative study to compare expectations and communication desires of sick children's caregivers at Mulago Hospital, Uganda, to those of patients in Western countries. METHODS: Three Focus Group Interviews and three Key Informant Interviews were conducted with 24 caregivers of sick children in Mulago Hospital Kampala, Uganda. An interview guide adapted from the Calgary-Cambridge Guide was used to conduct focus group and Key Informant Interviews. Two investigators worked independently to review transcripts and analyse them for content and emerging themes. RESULTS: Caregivers of sick children in Mulago Hospital expect attending doctors to build a relationship with them, by demonstrating the verbal and nonverbal skills outlined in the CCG including maintaining eye contact, using appropriate gestures and voice during communication, and being nonjudgmental. CONCLUSION: The communication needs and expectations of caregivers of sick children in Mulago Hospital are similar to those of patients and caregivers in Western countries. PRACTICE IMPLICATIONS: The CCG can be used as a training guide to enhance the communication skills of current and future doctors in Mulago Hospital. PMID- 20739135 TI - Risky feelings: why a 6% risk of cancer does not always feel like 6%. AB - OBJECTIVE: Emotion plays a strong role in the perception of risk information but is frequently underemphasized in the decision-making and communication literature. We sought to discuss and put into context several lines of research that have explored the links between emotion and risk perceptions. METHODS: In this article, we provide a focused, "state of the science" review of research revealing the ways that emotion, or affect, influences people's cancer-related decisions. We identify illustrative experimental research studies that demonstrate the role of affect in people's estimates of cancer risk, their decisions between different cancer treatments, their perceptions of the chance of cancer recurrence, and their reactions to different methods of presenting risk information. RESULTS: These studies show that people have strong affective reactions to cancer risk information and that the way risk information is presented often determines the emotional gist people take away from such communications. CONCLUSION: Cancer researchers, educators and oncologists need to be aware that emotions are often more influential in decision making about cancer treatments and prevention behaviors than factual knowledge is. PRACTICE IMPLICATIONS: Anticipating and assessing affective reactions is an essential step in the evaluation and improvement of cancer risk communications. PMID- 20739137 TI - [Probable spontaneous amniotic fluid embolism at 28 weeks of term]. PMID- 20739138 TI - [Is there a future for wireless endoscopy?]. PMID- 20739139 TI - Constipation in persons receiving hospice care. AB - CONTEXT: Symptom burden at the end of life is incompletely understood. OBJECTIVES: To estimate the natural history of constipation and the relation of clinical and demographic characteristics to moderate or severe constipation among persons who received hospice care in the United States starting in 2005. METHODS: Data were obtained from a national provider of hospice pharmacy services and included information about the hospice organization, patient demographics and clinical characteristics, constipation intensity, and drugs prescribed. Hospice nurses assessed patients' constipation during the previous 24 hours periodically, using a 0-10 numeric rating scale (NRS; 0=no intensity and 10=worst imaginable; none [NRS 0], mild [NRS 1-3], moderate [NRS 4-6], or severe [NRS 7-10]). Regression models were constructed to identify factors associated with last reported constipation severity scores. RESULTS: Fifty thousand six hundred forty one persons received hospice services, had at least two constipation assessments, and had complete clinical and demographic information; 55.3% of these individuals were female, 87.1% were Caucasian, and mean age was 75.9 years. Constipation was assessed a mean of four times per person; 12% of persons had moderate or severe constipation at their first or last assessment, and 19% of persons who reported moderate or severe constipation at the first assessment also had moderate or severe constipation at the last assessment. First constipation and last pain scores, having cancer, and prescription of a laxative were associated with increased likelihood of moderate or severe constipation at the last assessment. CONCLUSIONS: These data provide insight into a common and potentially distressing symptom and also may be useful as process indicators of the quality of hospice care. PMID- 20739140 TI - Risk factors for common mental disorder in caregiving and bereavement. AB - CONTEXT: Longitudinal studies that have described the trajectory of familial caregiving and bereavement outcomes have often failed to include a comprehensive range of carer and caregiving variables or any patient assessments, and only a few have used a recognized structured interview for psychiatric disorders. OBJECTIVES: To address these limitations, this study aimed to establish links between symptoms of CMD in carers of patients (with advanced disease) during the caregiving phase and their subsequent bereavement. METHODS: To identify the risk factors for poor caregiving and bereavement outcomes, we assessed patients and caregivers using a wide range of measures in a prospectively acquired sample. The main outcome, CMD, was measured through the use of a standardized interview (Revised Clinical Interview Schedule). One hundred carers of patients with advanced disease (more than 95% of patients had a cancer diagnosis) were interviewed shortly after the patient was referred to a U.K. hospice. Interviews were repeated at three and six months after the death of the patient. RESULTS: Multivariate analyses revealed that carers who perceived their caring experience as more burdening had more symptoms of CMD while caring for their loved one. Carer mental health during the caregiving experience was predictive of their mental health at three and six months after death. No relationships were observed between family relations, levels of social support, levels of religious or spiritual beliefs, carers' coping strategies, quality of death in the patient, and caregiving and bereavement outcomes. CONCLUSION: Our findings suggest that much psychological distress detected during caregiving continues into bereavement. PMID- 20739141 TI - Impact of a palliative care consultation team on cancer-related symptoms in advanced cancer patients referred to an outpatient supportive care clinic. AB - CONTEXT: Patients with advanced cancer may develop severe physical and psychosocial symptoms. There are limited data on the impact of an outpatient palliative consultation (PC) team on cancer-related symptoms. OBJECTIVES: To study the impact of the PC on symptoms in patients with advanced cancer receiving outpatient palliative care. METHODS: Four hundred six consecutive patients referred to a supportive care outpatient center (OPC) from January 2006 to June 2007 with complete Edmonton Symptom Assessment Scale (0-10 scale) at the initial and follow-up visits were reviewed. Patient characteristics, change of symptoms at follow-up visit, and response rate were analyzed. Using logistic regression models, the predictors of improvement of pain and fatigue were assessed. RESULTS: Median age was 59 years; 53% were female. Median interval between visits was 15 days. Mean scores at baseline and follow-up visits were fatigue 6.8 and 5.3 (P<0.0001), pain 5.3 and 4.1 (P<0.0001), depression 3.2 and 2.5 (P<0.0001), anxiety 3.7 and 2.8 (P<0.0001), dyspnea 2.7 and 2.5 (P=0.05), sleep 5 and 4 (P<0.0001), and well-being 5.2 and 4.4 (P<0.0001). Dyspnea (odds ratio and P value, 0.90, 0.03), nausea (0.92, 0.06), and depression (0.91, 0.04) were associated with improvement in fatigue; drowsiness (1.10, 0.04), and feeling of well-being (0.87, 0.02) were associated with improvement in pain. CONCLUSION: The initial consult by PC achieved significant symptom improvement in patients receiving treatment in the OPC. Further prospective studies are needed. PMID- 20739142 TI - Existential and supportive care needs among patients with chronic kidney disease. AB - CONTEXT: Living with chronic kidney disease (CKD) is associated with spiritual distress and frequently precipitates a search for meaning and hope; yet, very little is known about these patients' spiritual needs. OBJECTIVES: To describe the nature, prevalence, and predictors of spiritual and supportive care needs in CKD. METHODS: Prospective cohort study of 253 CKD patients who completed a seven item spiritual and seven-item supportive care needs assessment. RESULTS: Patients reported a mean (standard deviation [SD]) number of 2.9 (2.6) spiritual needs, with 69.1% of patients reporting at least one spiritual need. The mean (SD) number of supportive care needs was 3.5 (2.1), with 91.4% of patients reporting at least one of these needs. Thirty-two percent of the patients had high spiritual needs (defined as reporting >=5 of the seven needs). Similarly, 37% of the patients reported high supportive care needs. Neither spiritual nor supportive care needs were associated with age, gender, race, marital status, dialysis modality, time on dialysis, or comorbidity. CONCLUSION: These patients had substantial spiritual and supportive care needs. There were no clear predictors of high spiritual or supportive care needs, highlighting the importance of evaluating all CKD patients for unmet needs. Health professionals will need to better understand and attend to CKD patients' spiritual needs to optimize quality care. PMID- 20739143 TI - Effectiveness of palliative care services in symptom control of patients with advanced terminal cancer: a spanish, multicenter, prospective, quasi experimental, pre-post study. AB - CONTEXT: In implementing the National Strategy of Palliative Care in Spain, there needs to be an evaluation of services, especially of their effectiveness, efficiency, and satisfaction of patients and families. OBJECTIVES: To assess the effectiveness of palliative care services (PCS) in improving symptom control in Spain. METHODS: This multicenter, prospective, quasi-experimental, pre-post intervention study evaluated symptoms, such as pain, breakthrough pain, anorexia, nausea/vomiting, constipation, insomnia, dyspnea at rest and with movement, anxiety, and depression, using patient-reported numeric rating scales on Days 0, 7, and 14 after referral to a PCS. RESULTS: Of the 318 PCSs included in the National Directory for 2004, 105 services in the 17 autonomous regions of Spain were able to report 265 eligible (treatment-naive) patients. Nonparticipation by some centers was because of excessive workload or because their patients were not treatment-naive. Median survival was 42 days. Pain severity and number of crises of breakthrough pain significantly improved, as did other indicators of patient satisfaction. Symptom improvement was independent of type of service (in acute bed hospitals, medium-term stay facilities, hospital support teams, home care support teams, and outpatient clinics). CONCLUSION: Our national plan appears to be successful in reducing symptoms irrespective of the type of organization providing the PCS. An area for improvement could be to lessen the workload of individual teams. PMID- 20739144 TI - Objective vocal quality in children using cochlear implants: a multiparameter approach. AB - OBJECTIVES: The purpose of this study was to determine the objective vocal quality in 36 prelingually deaf children using cochlear implant (CI) with a mean age of 9 years. An additional purpose was to compare the objective vocal quality of these 36 CI users with 25 age-matched children with prelingual severe hearing loss using conventional hearing aids (HAs) and 25 normal hearing (NH) children. STUDY DESIGN: The design for this cross-sectional study was a multigroup posttest only design. METHODS: The objective vocal quality was measured by means of the dysphonia severity index (DSI). Moreover, perceptual voice assessment using the GRBASI scale was performed. RESULTS: CI children have a vocal quality by means of the DSI of +1.8, corresponding with a DSI% of 68%, indicating a borderline vocal quality situated 2% above the limit of normality. The voice was perceptually characterized by the presence of a very slight grade of hoarseness, roughness, strained phonation, and higher pitch and intensity levels. No significant objective vocal quality differences were measured between the voices of the CI children, HA users, and NH children. CONCLUSIONS: According to the results, one aspect of the vocal approach in children with CI and using HAs must be focused on the improvement of the strained vocal characteristic and the use of a lower pitch and intensity level. PMID- 20739145 TI - Left atrial dysfunction as a correlate of heart failure symptoms in hypertrophic cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic process affecting both ventricular and atrial myocardium. We aimed to assess left atrial (LA) function by two-dimensional speckle tracking echocardiography and its relation with left ventricular (LV) function and clinical status in patients with HCM. METHODS: We prospectively enrolled 37 consecutive patients with HCM and 37 normal subjects with similar age and gender distribution. Longitudinal LV strain (epsilon) and LA epsilon and strain rate (Sr) parameters (systolic, early diastolic, and late diastolic during atrial contraction) were assessed. RESULTS: Peak LAepsilon and LA Sr parameters were significantly lower in patients compared with controls (P <= .001 for all). In patients, all LA function parameters correlated with LVepsilon (P < .003 for all). Indexed LA volume, LA function parameters, and mitral regurgitation degree were the main correlates of New York Heart Association class; late diastolic strain rate during atrial contraction was the only independent predictor of symptomatic status. CONCLUSION: In patients with HCM, LA function is significantly reduced and related to LV dysfunction. Moreover, LA booster pump function emerged as an independent correlate of heart failure symptoms in this setting. PMID- 20739146 TI - The Geriatric Nutritional Risk Index predicts increased healthcare costs and hospitalization in a cohort of community-dwelling older adults: results from the MONICA/KORA Augsburg cohort study, 1994-2005. AB - OBJECTIVE: To determine if the Geriatric Nutritional Risk Index (GNRI), an index for the risk of nutrition-related complications, is associated with healthcare costs and risk of hospitalization at baseline and after 10 y. METHODS: Data from a German population-based cohort of 1999 subjects 55 to 74 y of age at baseline were used. Self-reported physician visits, length of hospital stay, and drug intake were used to estimate costs. The GNRI is based on serum albumin values and the discrepancy between real and ideal body weights. Low GNRI values were defined as mean minus 2 times standard deviation. Mean GNRI values were regarded as normal. RESULTS: Low baseline GNRI was consistently associated with increased total costs, probability of hospitalization, inpatient costs, and pharmaceutical costs at baseline and follow-up, after adjustment for socioeconomic characteristics, lifestyle factors, and coexisting conditions. Subjects with low GNRI at baseline had approximately 47% higher total costs, 50% higher risk of hospitalization, 62% higher inpatient costs and 27% higher pharmaceutical costs at follow-up than subjects with normal GNRI values. CONCLUSION: The GNRI risk predicted increased future healthcare costs and higher risk of hospitalization in independent-living older adults. The GNRI is a rapid and low-cost tool that might be routinely used in population-based settings. PMID- 20739147 TI - Treatment with growth hormone, somatostatin, and insulin in combination with hypocaloric parenteral nutrition in gastrointestinal cancer patients after surgery. AB - OBJECTIVE: The metabolic response to gastrointestinal cancer in patients undergoing surgery is associated with hypermetabolism and insulin resistance. The potential use of synergetic anabolic hormones in conjunction with hypocaloric parenteral nutrition (HPN) has become a significant area of investigation. The presented study was performed to determine the clinical efficiency and safety of hormone therapy combined with HPN in patients with gastrointestinal cancer. METHODS: One hundred patients with a Nutrition Risk Screening score of 3 or 4 undergoing surgery for gastrointestinal cancer were randomized into two groups. The patients in the control group received standard total parenteral nutrition and systemic insulin. The patients in the study group received HPN and systemic insulin in addition to pretreatment with recombinant human growth hormone and octreotide. Clinical efficiency and safety were evaluated by the measurement of hormones and protein metabolites, immune function, clinical outcome, and adverse events. Follow-ups were performed to determine the influence on prognosis. RESULTS: Treatment with recombinant human growth hormone, octreotide, and insulin in combination with HPN significantly increased protein synthesis, immune function, and metabolic tolerance, decreased infectious complications, and shortened postoperative hospital stays, but did not increase the risk of tumor development and recurrence in the study group compared with the control group. CONCLUSION: The proper short-term perioperative administration of growth hormone, somatostatin, and insulin in combination with HPN can overcome the postoperative stress response through the increase of protein synthesis to improve immune function in patients with gastrointestinal cancer after surgery. PMID- 20739148 TI - Is glycyrrhizin sensitivity increased in anorexia nervosa and should licorice be avoided? Case report and review of the literature. AB - OBJECTIVE: Hypokalemia is a potentially life-threatening electrolyte disturbance in anorexia nervosa and is most frequently caused by purging behavior. We report a case of severe hypokalemia in anorexia nervosa induced by daily ingestion of approximately 20 g of licorice. METHODS: To confirm the diagnosis of licorice induced pseudohyperaldosteronism, a re-exposure trial was performed. RESULTS: Cessation of the licorice intake normalized plasma potassium, renin, and aldosterone levels and the urine cortisol/cortisone ratio. Re-exposure confirmed the diagnosis. The pronounced response to a relatively low daily dose of licorice suggests high glycyrrhizin sensitivity. CONCLUSION: Patients with anorexia nervosa not only have decreased food intake but also selective and sometimes bizarre eating habits that, in association with increased sensitivity to glycyrrhizin, may cause severe hypokalemia. PMID- 20739149 TI - Intake of marine n-3 fatty acids during pregnancy and risk for epilepsy in the offspring: a population-based cohort study. AB - AIM OF THE STUDY: To estimate if maternal intake of n-3 long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy is related to the risk of epilepsy in the offspring. METHODS: We identified 65,754 live-born singletons from the Danish National Birth Cohort (DNBC, 1996-2002) and followed them for up to 11 years of age. Information on maternal diet in the 4 weeks around the 25th gestational week was obtained from a self-administered food frequency questionnaire and maternal intake of n-3 LCPUFA was estimated from the reported amount and type of fish in diet. Information on epilepsy was obtained from the Danish National Hospital Register. Cox regression models were used to estimate the incidence rate ratios (IRR) of epilepsy. RESULTS: Children born to mothers in the lowest (IRR=1.28, 95% CI: 0.98, 1.67) and highest (IRR=1.33, 95% CI: 1.02, 1.74) quintile of n-3 LCPUFA intake had an increased risk of epilepsy after adjustment for potential confounders compared to children born to mothers with an average intake. The associations may be related to the age of onset of epilepsy. CONCLUSIONS: Maternal deficiency of n-3 LCPUFA and a high intake of n-3 LCPUFA perhaps related to a high consumption of contaminated fish may be associated with an increased risk of epilepsy in early childhood. PMID- 20739150 TI - [Sternal cleft: repair during the neonatal period]. AB - Sternal cleft is a rare congenital abnormality. We report on a neonatal case of sternal cleft with median raphe with a follow-up of 3 years. We review the advantages of surgical repair in the neonatal period because the flexibility of the chest wall is maximal and compression of underlying structures is minimal. PMID- 20739151 TI - Supra-vesical urinary diversion and ureteric re-implantation for malignant disease. AB - Supra-vesical diversion or ureteric reconstruction is indicated for fistulae from the bladder or ureter, urinary incontinence, painful frequency and for end-stage renal failure due to obstructive uropathy. In a palliative setting, conservative measures, such as an indwelling catheter or ureteric stents, should be tried first. Open or laparoscopic surgery should be considered if these measures fail. For a patient who is leaking urine or has a very painful bladder, such surgery may well be justified, even very close to the end of life, as the symptoms are so unpleasant. When the problem is of end-stage renal failure that may be symptomless, the decision is more difficult; the patient may only gain a few months of life with no change in symptoms in return for the major surgery. The options available include cutaneous diversion either by ureterostomy or conduit and reconstruction either by re-implanting a ureter into the bladder or transuretero-ureterostomy. A laparoscopic approach may be possible in many cases. PMID- 20739152 TI - Surgical palliation in malignant disease. PMID- 20739153 TI - HDL and LDL as therapeutic targets for cardiovascular disease prevention: the possible role of niacin. AB - Recently two studies on the effect of addition of extended-release niacin to statin treatment on measures of carotid atherosclerosis were estimated in the ARBITER 6-HALTS study (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies) study and the Oxford Niacin Study were published. Adding niacin to statin treatment significantly diminished carotid atherosclerosis as measured by ultrasound carotid intima-media thickness or magnetic resonance imaging. An inhibitor of niacin induced flushing, laropiprant has been developed and demonstrated to considerably improve the tolerability of niacin therapy without impeding on its effect on lipoproteins. Still however clear evidence for the clinical benefit of long-term niacin treatment on cardiovascular morbidity and mortality is lacking. The development situation for ezetimibe is similar to that of niacin. Long-term interventional studies with hard endpoints of both therapies are ongoing. Also both drugs, when proven efficient and safe, are eagerly needed in the prevention of cardiovascular disease. PMID- 20739154 TI - Nuclear events affecting cell fate: from nuclear mechanisms in cell development, differentiation, and aging to nuclear imaging in three dimensions. PMID- 20739155 TI - Epigenetic control of Hox genes during neurogenesis, development, and disease. AB - The process of mammalian development is established through multiple complex molecular pathways acting in harmony at the genomic, proteomic, and epigenomic levels. The outcome is profoundly influenced by the role of epigenetics through transcriptional regulation of key developmental genes. Epigenetics refer to changes in gene expression that are inherited through mechanisms other than the underlying DNA sequence, which control cellular morphology and identity. It is currently well accepted that epigenetics play central roles in regulating mammalian development and cellular differentiation by dictating cell fate decisions via regulation of specific genes. Among these genes are the Hox family members, which are master regulators of embryonic development and stem cell differentiation and their mis-regulation leads to human disease and cancer. The Hox gene discovery led to the establishment of a fundamental role for basic genetics in development. Hox genes encode for highly conserved transcription factors from flies to humans that organize the anterior-posterior body axis during embryogenesis. Hox gene expression during development is tightly regulated in a spatiotemporal manner, partly by chromatin structure and epigenetic modifications. Here, we review the impact of different epigenetic mechanisms in development and stem cell differentiation with a clear focus on the regulation of Hox genes. PMID- 20739156 TI - Stemona alkaloids, from traditional Thai medicine, increase chemosensitivity via P-glycoprotein-mediated multidrug resistance. AB - P-glycoprotein-mediated drug efflux can cause a multidrug resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy. Through bioassay-guided fractionation, active Stemona alkaloids were isolated from the roots of Stemona aphylla and S. burkillii. The chemical structures of isolated alkaloids were confirmed by HPLC, LC-MS and NMR as stemocurtisine and oxystemokerrine from S. aphylla, and stemofoline from S. burkillii. The isolated alkaloids were evaluated for synergistic growth inhibitory effect with cancer chemotherapeutic agents including vinblastine, paclitaxel and doxorubicin of KB V1 cells (MDR human cervical carcinoma with P-gp expression), but not in KB-3-1 cells (drug sensitive human cervical carcinoma, which lack P-gp expression). Verapamil was employed as a comparative agent. The results showed that among these three isolated alkaloids; stemofoline exhibited the most potent effect in vitro in the reversal of P-gp-mediated MDR. Treatment with stemofoline at the various concentrations up to 72 h was able to significantly increase sensitivity of anticancer drugs including vinblastine, paclitaxel and doxorubicin in dose- and time-dependent manner in KB-V1 cells. The result obtained from this study indicated that Stemona alkaloids may play an important role as a P-gp modulator as used in vitro and may be effective in the treatment of multidrug-resistant cancers. This is the first report of new pharmacological activity of Stemona alkaloids, which could be a new potential MDR chemosensitizer. PMID- 20739157 TI - Anti-asthmatic effects of phenylpropanoid glycosides from Clerodendron trichotomum leaves and Rumex gmelini herbes in conscious guinea-pigs challenged with aerosolized ovalbumin. AB - Clerodendron trichotomum leaves and Rumex aquatica herbs are used as a folk medicine for the treatment of inflammatory diseases, but their active ingredients are not known until now. We isolated caffeic acid and phenylpropanoid glycosides, 1-O-caffeoyl glycoside and acteoside [beta-(3',4'-dihydroxyphenyl) ethyl-O-alpha l-rhamnopyranosyl(1->3)-beta-d-(4-O-caffeoyl)-glucopyranoside] from their ethylacetate fractions, respectively, and evaluated their anti-asthmatic effects on the aerosolized ovalbumin (OA) challenge in the OA-sensitized guinea-pigs measuring the specific airway resistance (sRaw) during the immediate-phase response (IAR) and late-phase response (LAR), and also measured recruitment of leukocytes and chemical mediators on the bronchoalveolar lavage fluids (BALF) in LAR, as well as histopathological survey. Acteoside and 1-O-caffeoyl glycoside (25mg/kg) significantly (P<0.05) inhibited sRaw by 32.14 and 26.79% in IAR, and by 55.88% and 52.94% in LAR, respectively, whereas caffeic acid (25mg/kg) inhibited sRaw by 30.36% in IAR and 44.12% in LAR, compared to control, but with less effective than dexamethasone, disodium cromoglycate, and salbutamol, respectively. In addition, phenylpropanoid glycosides (25mg/kg) significantly inhibited the recruitments of leukocytes, particularly neutrophils and eosinophils into lung, Furthermore, 1-O-caffeoyl glycoside, acteoside and caffeic acid significantly (P<0.05) inhibited protein content at a dose of 25mg/kg, and histamine content and PLA(2) activity at a dose of 50mg/kg, in BALF. Acteoside had more active than caffeic acid and 1-O-caffeoyl glycoside. However, their anti asthmatic effects were less than the reference drugs. These results indicated that caffeic acid and its glycosides (25mg/kg) have anti-asthmatic effect as the same manner with dexamethasone and disodium cromoglycate. PMID- 20739158 TI - Artemisinin inhibits in vitro and in vivo invasion and metastasis of human hepatocellular carcinoma cells. AB - Artemisinin (ART) is isolated from the medicinal plant Artemisia annua L. To determine its effects on the invasion and metastasis of tumors, the human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC-7721 were treated with different concentrations of ART. Starting at 12.5MUM, ART had inhibitory effects in migration and invasion assays that increased at higher concentrations. The inhibitory effect also became stronger with time, from 24 to 72h. ART significantly inhibited the in vivo metastatic abilities of the HepG2 HCC cell line. ART inhibited the invasion and metastasis of HCC cells both in vitro and in vivo by reducing the level of the MMP2 metalloproteinase, and by inducing the TIMP2 protein. ART activated Cdc42, which enhanced E-cadherin activity, resulting in greater cell-cell adhesion, and significantly reduced metastasis. PMID- 20739159 TI - Protective roles of cornuside in acute myocardial ischemia and reperfusion injury in rats. AB - Cornuside is a secoiridoid glucoside isolated from the fruit of Cornus officinalis SIEB. et ZUCC. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of cornuside in vivo and elucidated the potential mechanism. Rat models of myocardial I/R were induced by coronary occlusion followed by reperfusion or by Isoproterenol (ISO), treatment of rats with cornuside (20 and 40 mg/kg, i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with cornuside also attenuated polymorphonuclear leukocytes (PMNs) infiltration, decreased myeloperoxidase (MPO) activity in the heart, lowered serum levels of pro inflammatory factors and reduced phosphorylated IkappaB-alpha and nuclear factor kappa B (NF-kappaB) levels in the heart. Additionally, cornuside was shown to have remarkable antioxidant activity and inhibited ISO-induced myocardial cell necrosis. Thus, cornuside appeared to protect the rat from myocardial I/R injury by acting as an anti-inflammatory agent. These findings suggested that cornuside may be used therapeutically in the setting of myocardial I/R where inflammation and oxidant injury are prominent. PMID- 20739160 TI - The Amazonian herbal Marapuama attenuates cognitive impairment and neuroglial degeneration in a mouse Alzheimer model. AB - Alzheimer's disease (AD) is expected to affect more than 22 million people worldwide by 2025, causing devastating suffering and enormous costs to families and society. AD is a multifactorial disease, with a complex pathological mosaic. In rodents, AD-like dementia can be induced by cerebral microinjection of Abeta peptide, leading to amyloid deposits, amnesia and various features of neurodegeneration. Marapuama (Ptychopetalum olacoides) is regarded as a "brain tonic" in the Amazon region and shows a nootropic profile in rodents. AIM OF THE STUDY: Because a specific extract (POEE) of Marapuama was shown to possess promnesic and anti-amnesic properties, the aim of this study was to verify if POEE is also effective against Abeta(1-42)-induced cognitive deficit in mice. Additionally, Abeta deposits (Congo red), GFAP immunoreactivity (immunohistochemistry), and neurodegenerative changes in the hippocampal pyramidal layer (Nissl) were examined as measures of Abeta(1-42)-induced neurodegeneration. MATERIALS AND METHODS: CF1 mice were subjected to the experimental Alzheimer model with the Abeta(1-42) i.c.v. administration. The effects of POEE 800 mg/kg were evaluated over 14 consecutive days of treatment. RESULTS: The data show that 14 days of oral treatment with POEE (800 mg/kg) was effective in preventing Abeta-induced cognitive impairment, without altering the levels of BDNF and with parallel reductions in Abeta deposits and astrogliosis. CA1 hippocampus loss induced by Abeta(1-42) was also diminished in POEE-treated mice. CONCLUSION: This study offers evidence of functional and neuroprotective effects of two weeks treatment with a Ptychopetalum olacoides extract against Abeta peptide-induced neurotoxicity in mice. Given the multifactorial nature of neurodegeneration, the considerable potential for an AChE inhibitor displaying associated neuroprotective properties such as here reported warrants further clinic evaluation. PMID- 20739162 TI - Activity investigation of pinostrobin towards herpes simplex virus-1 as determined by atomic force microscopy. AB - In the present study, the antiviral activity of pinostrobin towards herpes simplex virus-1 (HSV-1) was investigated by MTT assay and atomic force microscopy. Pinostrobin can inhibit HSV-1 replication with 50% effective concentration (EC(50)) of 22.71 +/- 1.72 MUg/ml. MTT assay showed HSV-1 was significantly inhibited when pretreated with pinostrobin, with the inhibition of 85.69 +/- 2.59%. Significant changes in morphology and size of HSV-1 were observed by atomic force microscopy (AFM) in response to pinostrobin treatment. AFM topography and phase images showed that with increasing time, the envelope was shedded and damaged, finally leading to virus inactivation. With increasing concentration, pinostrobin caused a gradual leakage, also contributing to breakage of the envelope and virus inactivation. Treatment effect of oral pinostrobin in vivo showed that pinostrobin (50mg/kg/dose) possesses definite therapeutical effect in the development of lesion score. In general, the results showed that AFM represents a powerful technique for the investigation of morphology and size of HSV-1 treated by antiviral agents. AFM is applicable to study chemically induced morphological changes at the nanometer level. PMID- 20739161 TI - Hypoglycemic effect of Belamcanda chinensis leaf extract in normal and STZ induced diabetic rats and its potential active faction. AB - Belamcanda chinensis (Iridaceae) belongs to the family of iridaceae and its rhizoma has been widely used for the treatment of throat ailment. Here we report a new pharmacological activity of B. chinensis leaf extract (BCL), that is, the hypoglycemic effect in normal and STZ-induced diabetic rats. Animals either healthy or STZ-induced diabetic show significantly lowered fasting blood glucose levels after treatment with BCL. The serum insulin concentration in normal rats is also enhanced. Additionally, the increase in blood glucose levels after administration of various carbohydrates in normal rats is significantly decreased and the oral glucose tolerance (OGTT) of STZ-induced diabetic rats is largely improved by BCL treatment. However, co-administration of BCL with Nifedipine, a Ca(2+) ion channel blocker, or Nicorandil, an ATP-sensitive K(+) ion channel opener thoroughly abolishes the hypoglycemic effect of BCL. HPLC analysis and compound identification showed that several isoflavone glycosides with antidiabetic activities were contained in BCL while pharmacological experiment showed that the polysaccharide fraction of BCL had no significant hypoglycemic effect on normal rats. Therefore, the isoflavone glycosides but not polysaccharides might be the active fraction of BCL in diabetes treatment. PMID- 20739163 TI - A laccase with antiproliferative activity against tumor cells from an edible mushroom, white common Agrocybe cylindracea. AB - A laccase, with HIV-1 reverse transcriptase inhibitory activity (IC(50)=12.7 MUM) and antiproliferative activity against HepG2 cells (IC(50)=5.6 MUM) and MCF7 cells (IC(50)=6.5 MUM), was purified from fresh fruiting bodies of the edible white common Agrocybe cylindracea mushroom. The laccase, which had a novel N terminal sequence, displayed a molecular mass of 58 kDa within the range reported for most other mushroom laccases. The purification protocol entailed ion exchange chromatography on DEAE-cellulose, SP-Sepharose, and Q-Sepharose and gel filtration on Superdex 75. The laccase was adsorbed on DEAE-cellulose and Q Sepharose, but unadsorbed on SP-Sepharose. Its optimum pH was pH 3-4 and its optimum temperature was 50 degrees C. The activity of the isolated laccase differed from one substrate to another. The ranking was ABTS>N,N-dimethyl-1,4 phenylenediamine>hydroquinone>catechol>2-methylcatechol>pyrogallol. PMID- 20739164 TI - Potential of garlic and its active constituent, S-allyl cysteine, as antihypertensive and cardioprotective in presence of captopril. AB - The purpose of the present study was to investigate the role of fresh garlic homogenate (FGH) and its bioactive sulphur compound S-allyl cysteine sulphoxide (SACS) in potentiating antihypertensive and cardioprotective activities of captopril in rats. SACS was extracted from the fresh garlic using ion exchange resins with yield of 890 mg/kg garlic. The dose of SACS was calculated based on the amount of SACS extracted from 125 to 250 mg of FGH. Albino rats weighing 150 200 g were fed with 10% fructose in fluid for 3 weeks for induction of hypertension and subsequently administered FGH (125 and 250 mg/kg, p.o.) or SACS (0.111 and 0.222 mg/kg/day, p.o.) for the next 3 weeks in their respective groups. In CAP alone and interactive groups (GH+CAP; SACS+CAP), captopril 30 mg/kg was given during sixth week of 10% fructose in fluid. At the end of drug treatment, animals were given isoproterenol 175 mg/kg subcutaneously for two consecutive days. Additionally, varying concentrations of SACS (4, 8, 16, 32 and 64 ng), CAP (1, 2, 4, 8 and 16 ng) and their combination (4:1) were checked for fall in blood pressure in hypertensive rats (10% fructose in fluid without pretreatment) as well as angiotensin-converting enzyme (ACE) inhibiting activity using guinea pig ileum. An isobolographic analysis was used to characterise the interaction between SACS and CAP for fall in blood pressure and ACE inhibiting evaluations. Administration of captopril, low and high doses of FGH (125, 250 mg/kg), either alone or together showed fall in fluid intake and body weight. The combined therapy of FGH 250 mg/kg and CAP was more effective in reducing systolic blood pressure, cholesterol, triglycerides and glucose. The SOD and catalase activities in heart tissue were significantly elevated in groups treated with FGH, SACS, CAP, FGH+CAP and SACS+CAP. Further, combined therapy of FGH 250 mg/kg and CAP caused significant fall in LDH and CK-MB activities in serum and elevation in heart tissue homogenate. SACS in low dose was less effective than low dose of FGH; similarly, high dose of FGH was more efficacious than high dose of SACS. Corroborating with this, combined therapy of garlic (250 mg/kg) with CAP demonstrated higher synergistic action than combination of SACS (0.222 mg/kg) with CAP suggesting the role of additional bioactive constituents apart from SACS, responsible for therapeutic efficacy of garlic. Moreover, combination of SACS and CAP exerted super-additive (synergistic) interaction with respect to fall in blood pressure and ACE inhibition. This study may represent an advertence on concomitant use of garlic or its bioactive constituent, SACS, with captopril. PMID- 20739165 TI - Case reports of adverse effects of herbal medicinal products (HMPs): a quality assessment. AB - BACKGROUND: Case reports provide essential information on adverse effects. Yet there is little consistency in the quality and format of reporting them. AIM: In this study, we aimed to assess the quality of case reports of adverse effect of herbal medicinal products (HMPs) published during three time periods, 1986-1988, 1996-1998, and 2006-2008. METHODS: We conducted literature searches in four major databases: Medline, EMBASE, AMED, and CINALH. Each case report was subject to specific inclusion criteria related to the intervention (i.e. herbal medicine) and outcome measurement (i.e. adverse effect). A 21-item scale was used to assess the quality of all included reports. Each report was categorised into low quality (score between 0 and 14), lower medium quality (score between 15 and 21), upper medium quality (score between 22 and 28), and high quality (score between 29 and 42). RESULTS: In total, 137 case reports were included. The percentage of high quality case reports rose from 0% in 1986-1988 to 27.9% in 1996-1998 and 34.2% in 2006-2008; conversely, the percentages of low quality case reports dropped from 13.3% in 1986-1988 to 0% in 1996-1998 and 2.5% in 2006-2008. CONCLUSION: These findings are consistent with the notion that the quality of case reports is improving. However, due to several caveats, our data should be interpreted with caution. PMID- 20739166 TI - Lycopene and ellagic acid prevent testicular apoptosis induced by cisplatin. AB - The aim of this study was to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cisplatin (CP)-induced testicular apoptosis in male rats. The control group was treated with placebo; LC, EA and CP groups were given alone LC, EA and CP, respectively; the CP+LC group was treated with a combination of CP and LC; and the CP+EA group was treated with a combination of CP and EA. Although CP significantly increased the number of Bax positive (apoptotic) cells it had no effect on the number of Bcl-2-positive (antiapoptotic) cells compared with the control group. Administration of CP caused significant increase in lipid peroxidation and nonsignificant decrease in superoxide dismutase (SOD) activity along with some histopathological lesions in testicular tissue. However, combined treatments of LC or EA in addition to CP tended to prevent the CP-induced testicular apoptosis, histopathological lesions and lipid peroxidation. PMID- 20739167 TI - Cordymin, an antifungal peptide from the medicinal fungus Cordyceps militaris. AB - Cordymin, an antifungal peptide with a molecular mass of 10,906 Da and an N terminal amino acid sequence distinct from those of previously reported proteins, was purified from the medicinal mushroom Cordyceps militaris. The isolation protocol comprised ion exchange chromatography of the aqueous extract on SP Sepharose and Mono S and gel filtration on Superdex 75 by a fast protein liquid chromatography system. Cordymin was adsorbed on both cation exchangers. The peptide inhibited mycelial growth in Bipolaris maydis, Mycosphaerella arachidicola, Rhizoctonia solani and Candida albicans with an IC(50) of 50 MUM, 10 MUM, 80 MUM, and 0.75 mM, respectively. However, there was no effect on Aspergillus fumigatus, Fusarium oxysporum and Valsa mali when tested up to 2 mM. The antifungal activity of the peptide was stable up to 100 degrees C and in the pH range 6-13, and unaffected by 10 mM Zn(2+) and 10 mM Mg(2+). Cordymin inhibited HIV-1 reverse transcriptase with an IC(50) of 55 MUM. Cordymin displayed antiproliferative activity toward breast cancer cells (MCF-7) but there was no effect on colon cancer cells (HT-29). There was no mitogenic activity toward mouse spleen cells and no nitric oxide inducing activity toward mouse macrophages when tested up to 1 mM. PMID- 20739168 TI - Exercise decreases plasma antioxidant capacity and increases urinary isoprostanes of IPF patients. AB - We tested whether markers of systemic oxidant stress were detectable in 29 typical IPF patients, and whether these increased after low level exercise. We obtained resting plasma for measurement of amino terminal pro brain natriuretic peptide (NT-proBNP), and plasma and urine samples for isoprostanes and total nitrite. Total antioxidant capacity (TAC) was measured in plasma, and H(2)O(2) was measured in urine. Subjects exercised at ~50 W on a semi recumbent bicycle until limited by dyspnea. Samples were obtained immediately after exercise for measurement of the same variables. Plasma and urine samples were also obtained at rest from 6 normal individuals over 40 years of age solely to establish comparison values for NT-proBNP, nitrite, H(2)O(2) and TAC assays. Plasma NT proBNP was high at rest and after exercise, suggesting pulmonary arterial hypertension. IPF patients' resting NT-proBNP concentrations apparently exceeded those of normal controls. IPF plasma isoprostanes at rest exceeded the normals. IPF urine isoprostanes increased significantly after exercise (P = 0.047 by signed rank test); and, plasma TAC decreased significantly after exercise (P < 0.001 by signed rank test). Neither plasma nor urine nitrite changed significantly after exercise. H(2)O(2) concentration was quite high after exercise in some IPF subjects' urine. IPF patients demonstrate systemic oxidant stress at rest detectable as increased isoprostanes in the circulation. An increase in urine isoprostanes and a decrease in plasma TAC after exercise suggest that reactive oxygen species (ROS) are produced during low level exercise done by IPF patients. PMID- 20739169 TI - Omalizumab treatment and exercise capacity in severe asthmatics - results from a pilot study. AB - BACKGROUND: In patients with moderate to severe allergic asthma, clinical effectiveness of omalizumab, an approved anti-IgE-reacting substance, is usually assessed by pulmonary function testing (PFT), symptom scores and physicians judgement. AIMS: We postulate that cardiopulmonary exercise testing (CPET) may provide an additional option to verify symptomatic changes in patients with allergic asthma. METHODS: Ten consecutive patients with allergic asthma were treated with omalizumab. Prior to and after 16 weeks of treatment all patients underwent PFT and symptom-limited CPET. Results were compared to 10 asthmatic controls without omalizumab medication. Symptoms were assessed according to investigators judgement (IGETE). RESULTS: All 20 patients showed a significantly impaired exercise capacity at baseline [peak oxygen uptake (VO(2)) 71 +/- 16% predicted]. In patients with omalizumab, peakVO(2) increased from 13.8 (8.4-21.4) to 16.8 (11.2-23.9) ml/kg/min (p < 0.05), VO(2) at anaerobic threshold increased by 22% [9.8 (3.3-15.2) to 12.3 (6.7-14.4) ml/kg/min (p < 0.05)]. There was no improvement in the controls. The increase in VO(2) was significantly correlated to the improvement in symptoms. All patients revealed dynamic hyperinflation under exercise with a decreasing extent with omalizumab treatment. CONCLUSION: This study suggests that CPET may provide additional and useful tools to assess and verify the individual clinical response to omalizumab treatment. An improvement in exercise capacity can reliably mirror changes in quality of life and IGETE. Patients with omalizumab experience significant improvements in their initially impaired exercise capacity. CPET can be safely accomplished in patients with severe asthma. PMID- 20739170 TI - Integration of planar cell polarity and ECM signaling in elongation of the vertebrate body plan. AB - The shaping of the vertebrate embryonic body plan depends heavily on the narrowing and lengthening (convergence and extension) of embryonic tissues by cell intercalation, a process by which cells actively crawl between one another along the axis of convergence to produce a narrower, longer array. We discuss recent evidence that the vertebrate non-canonical Wnt/Planar Cell Polarity (PCP) pathway, known to directly function in polarizing the movements of intercalating cells, is also involved in the localized assembly of extracellular matrix (ECM). These cell-ECM interactions, in turn, are necessary for expression of the oriented, polarized cell intercalation. The mechanism of PCP/ECM interactions, their molecular signaling, and their mechanical consequences for morphogenesis are discussed with the goal of identifying important unsolved issues. PMID- 20739172 TI - A mediator-adapted diaphorase variant for a glucose dehydrogenase-diaphorase biocatalytic system. AB - Biofuel cell is an energy conversion device of the next generation which enables use of safer and higher energy-density fuels such as glucose. We have been developing a biofuel cell that comprises the three enzymes: glucose dehydrogenase (GDH) and diaphorase (DI) on anode, and bilirubin oxidase (BOD) on cathode. In this work, we have developed a DI variant suitable for our biofuel cell by using directed molecular evolution method. A gene library of DI variants was constructed by using error-prone PCR and the variant proteins were expressed in an Escherichia coli system. 8000 isolated variants have been screened with activity against 2-amino-1,4-naphthoquinone (ANQ), and 10 of them have been qualified which were then purified and examined their activities against ANQ. A highest activity was observed in G122D variant of which glycine residue at position 122 is substituted to aspartate. Enzymatic kinetic analyses show that KM for ANQ in G122D is 1/3 of that in wild type (G122D: 356 MUM, wild type: 1.08 mM), whereas kcat and KM for NADH is almost the same, clearly showing that G122D mutation has given DI an improvement in enzymatic activity at lower ANQ concentration. The effect of this mutation was considered electrochemically in solution and in immobilized layer. The results show that G122D variant DI gave a higher current at lower ANQ concentration in solution, as well as in immobilized condition where GDH is co-immobilized within. PMID- 20739171 TI - Tube continued: morphogenesis of the Drosophila tracheal system. AB - The Drosophila respiratory organ (tracheal system) consists of epithelial tubes, the morphogenesis of which is controlled by distinct sets of signaling pathways and transcription factors. The downstream events controlling tube formation and shape are only now beginning to be identified. Here we review recent insight into the communication between neighboring tracheal cells, their interactions with the surrounding matrix, and the impact of these processes on tube morphogenesis. We focus on cell-cell interactions that drive rearrangement of cells within the epithelium and that are essential for maintenance of epithelial integrity, and also on cell-matrix interactions that play key roles in determining and maintaining the size and shape of tube lumens. PMID- 20739173 TI - Photoelectrocatalytic oxidation of NADH in a flow injection analysis system using a poly-hematoxylin modified glassy carbon electrode. AB - A stable electroactive thin film of poly-hematoxylin (poly-HT) was successfully prepared on a glassy carbon electrode (GCE) surface by recording successive cyclic voltammograms of 0.3 mM HT, in a phosphate buffer solution (pH 7.0) containing 0.1 M NaNO3, in the potential range of -0.5 to +2.0 V vs. Ag/AgCl. The deposition of HT on GCE surface can be explained through the electropolymerization process. This poly-HT modified electrode exhibited a good electrocatalytic activity towards the NADH oxidation in a phosphate buffer solution (pH 7.0), and led to a significant decrease in the overpotential by more than 320 mV compared with the bare GCE. In order to perform the photoelectrocatalytic determination of NADH in a flow injection analysis (FIA) system, a home-made flow electrochemical cell with a suitable transparent window for irradiation of the electrode surface was constructed. Flow rate of carrier solution, transmission tubing length, injection volume and applied potential for the amperometric and photoamperometric FIA studies were optimized as 1.3 mL min( 1), 10 cm, 100 MUL and +300 mV vs. Ag/AgCl, respectively. The currents obtained from amperometric and photoamperometric measurements in FIA system at optimum conditions were linearly dependent on the NADH concentration and linear calibration curves were obtained in the range of 1.0*10(-7)-1.5*10(-4) M and in the range of 1.0*10(-7)-2.5*10(-4) M NADH, respectively. The relative standard deviation (RSD) of six replicate injections of 6.0*10(-5) M NADH was calculated as 2.2% and 4.3% for the amperometric and the photoamperometric method, respectively. The limit of detection was found to be 3.0*10(-8) M for the photoamperometric determination of NADH. PMID- 20739174 TI - Advent of innovative chemiluminescent enzyme immunoassay. AB - Using 1,1'-oxalyldiimidazole (ODI) chemiluminescence detection, a new chemiluminescent enzyme immunoassay (CLEIA) was developed to quantify prostate specific antigen (PSA) in human serum. The results observed in ODI CLEIA were compared with those obtained in commercially available enzyme linked immunosorbent assay (ELISA), fluorescence enzyme immunoassay (FEIA), and luminol CLEIA. PSA complex-conjugated horseradish peroxidase (HRP) was formed from one step sandwich immunoreaction of PSA, PSA primary antibody and PSA secondary antibody-conjugated HRP for 15 min in a strip-well at 36.5 degrees C. CL substrate solution (Amplex Red and H2O2 in PBS buffer, pH 7.4) was added in the washed strip-well and incubated for 10 min at room temperature. When resorufin formed in this process was mixed with 1,1'-oxalyldi-4-methylimidazole and H2O2 in a testing tube, rapid and bright CL was observed. Detection limit (0.035 ng/ml) of PSA in ODI CLEIA was much lower than those (0.50 and 0.25 ng/ml) in commercially available ELISA and luminol CLEIA even though total incubation time of the former (25 min) was shorter than those of the latter (45 and 35 min). Also, the dynamic range (0-100 ng/ml, R2=0.9996) of ODI CLEIA was wider than those of other EIAs. In conclusion, the excellent correlation (r=0.9767) between ODI CLEIA and Advia Centaur XP Immunoassay System indicates that the accurate, precise, and rapid ODI CLEIA can be applied as a novel CLEIA capable of diagnosing and monitoring various diseases. PMID- 20739175 TI - Micro-scale and microfluidic devices for neurobiology. AB - The precise spatial and temporal control afforded by microfluidic devices make them uniquely suited as experimental tools for cellular neuroscience. Micro structures have been developed to direct the placement of cells and small organisms within a device. Microfluidics can precisely define pharmacological microenvironments, mimicking conditions found in vivo with the advantage of defined parameters which are usually difficult to control and manipulate in vivo. These devices are compatible with high-resolution microscopy, are simple to assemble, and are reproducible. In this review we will focus on microfluidic devices that have recently been developed for small, whole organisms such as C. elegans and dissociated cultured neurons. These devices have improved control over the placement of cells or organisms and allowed unprecedented experimental access, enabling novel investigations in neurobiology. PMID- 20739176 TI - From structure to cellular mechanism with infrared microspectroscopy. AB - Current efforts in structural biology aim to integrate structural information within the context of cellular organization and function. X-rays and infrared radiation stand at opposite ends of the electromagnetic spectrum and act as complementary probes for achieving this goal. Intense and bright beams are produced by synchrotron radiation, and are efficiently used in the wavelength domain extending from hard X-rays to the far-infrared (or THz) regime. While X ray crystallography provides exquisite details on atomic structure, Fourier transform infrared microspectroscopy (FTIRM) is emerging as a spectroscopic probe and imaging tool for correlating molecular structure to biochemical dynamics and function. In this manuscript, the role of synchrotron FTIRM in bridging the gap towards 'functional biology' is discussed based upon recent achievements, with a critical assessment of the contributions to biological and biomedical research. PMID- 20739177 TI - Communication challenges in surgical oncology. AB - In this essay we set out clinical communication challenges in surgical oncology. We draw directly on relevant examples where they are available. Otherwise, we refer to the more generic surgical and medical literature. We offer 'macro' and 'micro' perspectives on clinical communication. That is, exploring communication challenges at the level of the organization and between individuals, doctors and patients and interprofessionally across different settings. Training content and methods are reported that address the complex communication challenges associated with surgical oncology. Innovations in simulation-based education offer exciting new opportunities for formative and summative assessment. We outline limitations of the essay and finally propose the content of a surgical oncology communication program. PMID- 20739178 TI - Evaluation of methods to extract and quantify lipids from Synechocystis PCC 6803. AB - In order to use the photosynthetic cyanobacterium Synechocystis as a source of feedstock for carbon-neutral, nonpetroleum-based diesel fuel, we evaluated several solvents and solvent systems for their ability to extract lipid from wild type Synechocystis PCC 6803. Chloroform+methanol-based Folch and Bligh & Dyer methods had the highest lipid recoveries. Less toxic solvents, such as methanol and MTBE, or direct trans-esterification of biomass (without pre-extraction step) gave only slightly lower lipid-extraction yields. Ethanol, isopropanol, butanol, hexane, acetic ester, and their combinations were not effective for lipid extraction from Synechocystis (>20% loss), even though they are widely used for non-polar lipid extraction from other feedstock, including algae. We confirmed the success of chloroform+methanol-based extraction by their penetration of the cell membrane system, higher polarity, and stronger interaction with hydrogen bonds. The less-polar solvents not only had lower lipid yield, but also extracted more non-lipid compounds that require extra purification to remove. We also characterized the fatty-acid profile of Synechocystis PCC 6803: C16:0 (~60%), C16:1 (~9.5%), C18:0 (~1.2%), C18:1 (~2%), C18:2 (~9.8%), and C18:3 (~16.5%). PMID- 20739179 TI - Investigation of Cr(VI) adsorption onto chemically treated Helianthus annuus: optimization using response surface methodology. AB - In the present study, chemically treated Helianthus annuus flowers (SHC) were used to optimize the removal efficiency for Cr(VI) by applying Response Surface Methodological approach. The surface structure of SHC was analyzed by Scanning Electron Microscopy (SEM) coupled with Energy Dispersive X-ray Analysis (EDX). Batch mode experiments were also carried out to assess the adsorption equilibrium in aqueous solution. The adsorption capacity (qe) was found to be 7.2 mg/g. The effect of three parameters, that is pH of the solution (2.0-7.0), initial concentration (10-70 mg/L) and adsorbent dose (0.05-0.5 g/100 mL) was studied for the removal of Cr(VI) by SHC. Box-Behnken model was used as an experimental design. The optimum pH, adsorbent dose and initial Cr(VI) concentration were found to be 2.0, 5.0 g/L and 40 mg/L, respectively. Under these conditions, removal efficiency of Cr(VI) was found to be 90.8%. PMID- 20739180 TI - Enhanced hexadecane degradation and low biomass production by Aspergillus niger exposed to an electric current in a model system. AB - The effects of an electric current on growth and hexadecane (HXD) degradation by Aspergillus niger growth were determined. A 450-mL electrochemical cell with titanium ruthenium-oxide coated electrodes and packed with 15 g of perlite (inert biomass support) was inoculated with A. niger (2.0*10(7) spores (g of dry inert support)(-1)) and incubated for 12 days (30 degrees C; constant ventilation). 4.5 days after starting culture a current of 0.42 mA cm(-2) was applied for 24h. The current reduced (52+/-11%) growth of the culture as compared to that of a culture not exposed to current. However, HXD degradation was 96+/-1.4% after 8 days whereas it was 81+/-1.2% after 12 days in control cultures. Carbon balances of cultures not exposed to current suggested an assimilative metabolism, but a non-assimilative metabolism when the current was applied. This change can be related to an increase in total ATP content. The study contributes to the knowledge on the effects of current on the mycelial growth phase of A. niger, and suggests the possibility of manipulating the metabolism of this organism with electric current. PMID- 20739181 TI - The effect of age in the outcome and treatment of older women with ductal carcinoma in situ. AB - The effect of increasing age on outcomes and type of treatment given to older women with ductal carcinoma in situ (DCIS) was assessed. 646 women >=60 years old (654 cases) receiving surgery for DCIS at Memorial Sloan-Kettering Cancer Center between 2000 and 2007 (8 bilateral) had wide local excision (WLE; 37%), WLE plus radiotherapy (WLE+RT; 41%), or mastectomy (22%). 45%, 38%, and 16% of patients 60 69 years, 70-79 years, and >=80 years, respectively, received WLE+RT (P<0.001) and 25%, 20%, and 13%, received mastectomy, respectively (P<0.001). Age (P<0.001), grade (P<0.001), and necrosis (P<0.01) were highly associated with treatment. Four-year local recurrence was 3.6%. Overall local recurrence differed by treatment (mastectomy, 0%; WLE, 5%; WLE+RT, 4%; P<0.00001) but not age. It is possible to identify older women with DCIS in whom the risk of recurrence is acceptably low after WLE alone. WLE alone may be a viable treatment option for select older women with DCIS. PMID- 20739182 TI - The clinical importance of understanding the evolution of papillomaviruses. AB - A significant fraction of human cancers is associated with infections by different papillomaviruses (PVs). In other vertebrates, the presence of specific PVs is also associated with different neoplasias. The popular view of PVs conceives them to be largely static and relies on generalized assumptions that have rarely been rigorously tested such as: virus-host codivergence, strict tissue tropism and host-specificity, their very low mutation rate and the absence of recombination. Here, we want to stress the need and the medical importance of understanding the evolutionary history and present-day dynamics of PVs. Understanding the way that PV genomes have evolved will clarify the link between a given genotype and the phenotypic and clinical outcome of the corresponding viral infection. PMID- 20739183 TI - Comment on "A systematic review of the efficacy of globus pallidus stimulation in the treatment of Parkinson's disease". PMID- 20739184 TI - Nanomechanical analysis of Clostridium tyrobutyricum spores. AB - In this work we report on the measurement of the Young modulus of the external surface of Clostridium tyrobutyricum spores in air with an atomic force microscope. The Young modulus can be reliably measured despite the strong tip spore adhesion forces and the need to immobilize the spores due to their slipping on most substrates. Moreover, we investigate the disturbing factors and consider some practical aspects that influence the measurements of elastic properties of biological objects with the atomic force microscopy indentation techniques. PMID- 20739185 TI - Percutaneous femoral artery access with Prostar device for innovative mitral and aortic interventions. AB - The potential advantages of percutaneous femoral access over a surgical approach are easier recovery and lower inguinal complications rate. This technique can be an asset in disabled patients with high risk of decubitus complications or in surgically challenging patients (obesity). We describe percutaneous access for mitral and aortic minimally invasive valvular interventions in 156 patients (transcatheter aortic valve implantation, n=40; and minimally invasive cardiac surgery, n=116). Severe complications, in two transcatheter aortic valve implantation (TAVI) patients (one retroperitoneal bleeding and one massive superficial bleeding) and in three minimally invasive patients (two retroperitoneal bleeding and one arteriovenous fistula), occurred during first 50 patients versus 0 among 106 following patients (p=0.01). Percutaneous access is possible for innovative cardiac interventions, but severe complications can occur, especially during the learning curve, with serious consequences in high operative risk patients, urging highest caution when initiating this innovative approach. PMID- 20739186 TI - High-concentration glutaraldehyde fixation of bovine pericardium in organic solvent and post-fixation glycine treatment: in vitro material assessment and in vivo anticalcification effect. AB - OBJECTIVE: Glutaraldehdye (GA)-fixed xenografts are widely used in cardiovascular surgery. The objective of this study was to evaluate the anticalcification effect of glycine treatment and high-concentration GA fixation in organic solvent on GA fixed bovine pericardium, and to evaluate the possible synergistic effect of combined treatment. METHODS: Bovine pericardial tissues were divided into four groups according to the methods of treatment. Group 1 consisted of tissues fixed with 0.5% GA (control), group 2 fixed with 0.5% GA and post-treated with glycine, group 3 fixed with 2% GA in organic solvent (65% ethanol+5% octanol), and group 4 fixed with 2% GA in organic solvent and post-treated with glycine. The material characteristics of the treated tissues were assessed by amino acid analysis, thermal stability test, uniaxial mechanical test and light microscopy. The tissues were subcutaneously implanted into 4-week-old rats for 8 weeks, and the calcium contents of the explanted tissues were measured. RESULTS: Differently treated tissues resulted in no significant alterations in material characteristics and morphology as assessed by amino acid analysis, thermal stability test, uniaxial mechanical test, and light microscopy. Median calcium contents of groups 1, 2, 3, and 4 were 80.5 MUg mg(-1), 1.0 MUg mg(-1), 0.5 MUg mg(-1) and 1.7 MUg mg(-1), respectively. The calcium contents of groups 2, 3 and 4 were all significantly lower than that of group 1 (p < 0.05). CONCLUSIONS: Post fixation treatment with glycine, high-concentration GA fixation in organic solvent and combined treatment of these all strongly prevented calcification of GA-fixed bovine pericardium in rat subcutaneous implantation model. PMID- 20739187 TI - Minimally invasive repair of pectus excavatum deformity. AB - This review is trying to address the effectiveness and sustainability of results following minimally invasive repair of pectus excavatum (MIRPE). The aim is to present these results for the benefit of clinicians and the patients. Literature search has revealed 179 hits, which were independently assessed and led to 80 publications being formally reviewed. Studies reporting results from less than 10 patients were excluded. Thirty-five studies were found to be reporting results from patients' and/or surgeons' perspective and they were included in this review. Data from the United Kingdom registry for MIRPE were also included. Results from over 2997 patients (age: <1-85 years) who had MIRPE and 1393 patients who had their metallic bar removed were assessed. The most common indication for surgery was cosmesis. There was a net gain with regard to self esteem for 96-100% of the individuals. A percentage of procedures (0-20%) was assessed by surgeons as having an 'unsatisfactory outcome' and a number of patients (0-25%) reported an 'unsatisfactory end result.' However, these percentages are not necessarily referring to the same patients and an unsatisfactory result does not seem to affect the positive effect on self-esteem. The reported changes in social life, lung capacity, cardiovascular capacity, exercise capacity and general health are based on weak data and significant improvements, if any, are probably seen in a limited number of patients. The metallic bars were removed after 1.5-4.5 years and there is an overall 0-4.5% reported recurrence post-bar removal. In conclusion, MIRPE may improve cosmesis and self-esteem of patients with pectus excavatum deformity. Direct or indirect improvement in other physiological parameters may also help the 'well-being' of these patients and their social integration. There is a clear need for standardisation in the way results are reported in the literature and a socioeconomic analysis with regard to gains, benefits and costs related to MIRPE. PMID- 20739188 TI - Acute kidney injury network classification predicts in-hospital and long-term mortality in patients undergoing elective coronary artery bypass grafting surgery. AB - OBJECTIVE: Acute kidney injury (AKI) is a highly prevalent complication after cardiac surgery. It is associated with substantial morbidity and mortality. However, the definition of AKI has not been well established until the Acute Kidney Injury Network group outlined an easily used consentaneous staging system. The study aims to evaluate the association between this determination and in hospital as well as long-term mortality in patients receiving elective coronary artery bypass grafting (CABG) surgery. METHODS: Patients undergoing elective CABG surgery from January 2003 to December 2007 in a tertiary medical center were studied. The Acute Kidney Injury Network classification was applied for the diagnosis of perioperative AKI. Medical history and intra-operative variables were collected retrospectively. Multivariate analysis was used to identify the independent risk factors of in-hospital and long-term mortality. Long-term survival rates were calculated using the Kaplan-Meier method. RESULTS: This study included 964 patients. The incidence of AKI following elective CABG was 19.8%. Only 7% of the study population developed AKI requiring renal replacement therapy after surgery. The overall in-hospital mortality rate was 5.1%. Significant independent risk factors for in-hospital mortality include increasing age, higher serum uric acid, postoperative requirement of intra-aortic balloon pumping (IABP) and extracorporeal membrane oxygenation (ECMO), perioperative AKI, and chronic dialysis (all p<0.05). Significant independent risk factors for long-term mortality include increasing age, lower serum albumin, higher serum uric acid, postoperative requirement of IABP and ECMO, perioperative AKI, and chronic dialysis (all p < 0.005). CONCLUSIONS: Acute Kidney Injury Network classification is a powerful tool to evaluate the prognostic impact of AKI on both in-hospital and long-term mortality among patients undergoing elective CABG surgery. PMID- 20739189 TI - Dihydrobenzoic acid modified nanoparticle as a MALDI-TOF MS matrix for soft ionization and structure determination of small molecules with diverse structures. AB - Efficient structural characterization is important for quality control when developing novel materials. In this study, we demonstrated the soft ionization capability of the hybrid of immobilized silica and 2,5-dihydrobenzoic acid (DHB) on iron oxide magnetic nanoparticles in MALDI-TOF MS with a clean background. The ratio between SiO(2) and DHB was examined and was found to affect the surface immobilization of DHB on the nanoparticle, critically controlling the ionization efficiency and interference background. Compared with commercial DHB, the functionalized nanoparticle-assisted MALDI-TOF MS provided superior soft ionization with production of strong molecular ions within 5 ppm mass accuracy on a variety of new types of synthetic materials used for solar cells, light emitting devices, dendrimers, and glycolipids, including analytes with either thermally labile structures or poor protonation tendencies. In addition, the enhancements of the molecular ion signal also provided high-quality product-ion spectra allowing structural characterization and unambiguous small molecule identification. Using this technique, the structural differences among the isomers were distinguished through their characteristic fragment ions and comprehensive fragmentation patterns. With the advantages of long-term stability and simple sample preparation by deposition on a regular sample plate, the use of DHB-functionalized nanoparticles combined with high-resolution MALDI-TOF MS provides a generic platform for rapid and unambiguous structure determination of small molecules. PMID- 20739190 TI - Preoperative embolization of the external carotid artery branches as an adjunct to superficial temporal artery-to-middle cerebral artery bypass. AB - When technically feasible, the preferred revascularization procedure in patients with adult moyamoya disease is a superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass. The caliber of the STA has been reported as a prognostic factor for a successful bypass, with smaller-caliber STA being more likely to fail. We describe a novel approach to this circumstance in which preoperative embolization of external carotid artery (ECA) branches is used to augment blood flow through a small STA as a prelude to bypass surgery. We report 2 cases: a 42 year-old female presenting with symptomatic ischemic and radiographically progressive moyamoya disease and a 23-year-old female presenting with advanced moyamoya disease secondary to diabetes. Preoperative angiography demonstrated small-caliber STAs in each case, and primary revascularization was deemed difficult. Preoperative ECA embolization was undertaken to shunt blood toward the STA, thereby increasing its flow and caliber. In both cases, angiography after embolization demonstrated a 20%-45% increase in STA size, and doppler ultrasound indicated a 14%-50% increase in flow. Subsequently, both patients underwent successful STA-MCA bypass combined with encephalomyosynangiosis without complications. Of 167 STA-MCA bypasses performed by the senior author, embolization was performed in 7 unique patients on 9 sides. ECA embolization may be a beneficial adjunct when considering a direct bypass in the setting of a small STA. It can increase blood flow through the STA, making the operation technically easier and enhancing the patency of the bypass. PMID- 20739191 TI - Memory and content. AB - The paper argues that any theory of content has to adopt a "functionalistic core" to concord with the cognitive sciences. This functionalistic core requires that representations are defined as substitutes in functions that describe the flexible behavior to be explained by the representation. The content of a representation can thus only be determined if the representation is "in use", i.e. if it is an argument in such a function. The stored entities in memory are not in use while they are stored, and hence cannot be assigned a specific content. The term "template" is introduced to describe stored entities in memory. The discussion of some implications of this result show that some deep philosophical problems follow from this argument as well as consequences for empirical research on memory. PMID- 20739192 TI - Self-deception as pseudo-rational regulation of belief. AB - Self-deception is a special kind of motivational dominance in belief-formation. We develop criteria which set paradigmatic self-deception apart from related phenomena of auto-manipulation such as pretense and motivational bias. In self deception rational subjects defend or develop beliefs of high subjective importance in response to strong counter-evidence. Self-deceivers make or keep these beliefs tenable by putting prima-facie rational defense-strategies to work against their established standards of rational evaluation. In paradigmatic self deception, target-beliefs are made tenable via reorganizations of those belief sets that relate relevant data to target-beliefs. This manipulation of the evidential value of relevant data goes beyond phenomena of motivated perception of data. In self-deception belief-defense is pseudo-rational. Self-deceivers will typically apply a dual standard of evaluation that remains intransparent to the subject. The developed model of self-deception as pseudo-rational belief-defense is empirically anchored. So, we hope to put forward a promising candidate. PMID- 20739193 TI - A replication of the 5-7 day dream-lag effect with comparison of dreams to future events as control for baseline matching. AB - The dream-lag effect refers to there being, after the frequent incorporation of memory elements from the previous day into dreams (the day-residue), a lower incorporation of memory elements from 2 to 4 days before the dream, but then an increased incorporation of memory elements from 5 to 7 days before the dream. Participants (n=8, all female) kept a daily diary and a dream diary for 14 days and then rated the level of matching between every dream report and every daily diary record. Baseline matching was assessed by comparing all dream reports to all diary records for days that occurred after the dream. A significant dream-lag effect for the 5-7 day period, compared to baseline and compared to the 2-4 day period, was found. This may indicate a memory processing function for sleep, which the dream content may reflect. Participants' and three independent judges' mean ratings also confirmed a significant day-residue effect. PMID- 20739194 TI - Grasping language--a short story on embodiment. AB - The new concept of embodied cognition theories has been enthusiastically studied by the cognitive sciences, by as well as such disparate disciplines as philosophy, anthropology, neuroscience, and robotics. Embodiment theory provides the framework for ongoing discussions on the linkage between "low" cognitive processes as perception and "high" cognition as language processing and comprehension, respectively. This review gives an overview along the lines of argumentation in the ongoing debate on the embodiment of language and employs an ALE meta-analysis to illustrate and weigh previous findings.The collected evidence on the somatotopic activation of motor areas, abstract and concrete word processing, as well as from reported patient and timing studies emphasizes the important role of sensorimotor areas in language processing and supports the hypothesis that the motor system is activated during language comprehension. PMID- 20739195 TI - Selective modulation of PPARgamma activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with Type 2 diabetes. AB - OBJECTIVE: INT131 besylate is a potent non-thiazolidinedione selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulator (SPPARM) designed to improve insulin sensitivity and glucose metabolism while minimizing the side effects of full agonist thiazolidinediones. This study was conducted to determine short-term efficacy and safety of INT131 besylate in patients with Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This was a 4-week randomized, double-blind, placebo-controlled multi-center study with 1 or 10mg INT131 besylate or placebo daily in subjects with T2DM not receiving pharmacotherapy for their hyperglycemia. The primary efficacy analysis was the comparison of treatment groups with respect to least square mean change from baseline to Week 4 of fasting plasma glucose (FPG). RESULTS: Baseline mean (+/- S.D.) FPG for the study population was 171 +/- 42 mg/dl. Change in FPG (+/- S.E., mg/dl) from baseline after 4 weeks was 8 +/- 8 (P=NS) with placebo, -22 +/- 8 with 1mg INT131 besylate (P=.0056) and -46 +/- 7 with 10mg INT131 besylate (P<.0001). Modeling of available data from the literature of the effect of rosiglitazone under similar study conditions suggested that 1 mg of INT131 besylate had a similar reduction in FPG as expected with 8 mg of rosiglitazone. INT131 besylate was well tolerated, and the 1 mg dose demonstrated no evidence of fluid retention or weight gain. CONCLUSIONS: INT131 besylate demonstrated a dose dependent reduction in FPG. The FPG reduction with 1mg INT131 besylate was comparable to the modeled 8 mg dose of rosiglitazone, and did not cause fluid retention or weight gain. These results are consistent with the INT131 SPPARM design. PMID- 20739196 TI - Is lamotrigine a significant human teratogen? Observations from the Australian Pregnancy Register. AB - Lamotrigine (LTG) is increasingly being prescribed in pregnancy for women with epilepsy in place of valproate (VPA), because of the teratogenic risks associated with the latter. It is therefore important to know the teratogenic hazard associated with LTG, relative to VPA and to other commonly used antiepileptic drugs (AEDs). Data from the Australian Register of Antiepileptic Drugs in Pregnancy was examined to determine the incidence of teratogenicity determined 1 year from completion of pregnancy in women who took AEDs in monotherapy during pregnancy. Compared with a 3.4% malformation incidence in women who took no AEDs (N = 118), the incidences for LTG (N = 243), carbamazepine (CBZ) (N = 302) and VPA (N = 224) were, respectively, 4.9%, 5.3% and 15.2%, the latter statistically significantly greater than the risk for no AED therapy in pregnant women with epilepsy. Logistic regression analysis showed no tendency for foetal hazard to increase with increasing LTG dose in pregnancy, unlike the situation for VPA. However, seizure control in pregnancy tended to be not as good in the women taking LTG compared with those taking VPA, though the data examined were not adequate to permit definite conclusions regarding this matter. We conclude that LTG monotherapy in pregnancy is safer than valproate monotherapy from the point of view of foetal malformations, and no more hazardous in this regard than therapy with other commonly used AEDs. PMID- 20739198 TI - Improving quality of life in patients with peripheral arterial disease: an important goal. PMID- 20739197 TI - Drug treatment failures and effectivity in children with newly diagnosed epilepsy. AB - PURPOSE: To determine the percentage of children whom first-line antiepileptic drug treatment failed and the specific reasons for the treatment failure in newly diagnosed epilepsy. METHODS: Hospital records were reviewed for 225 children who were newly diagnosed with epilepsy, started on the first antiepileptic drug, and then monitored for approximately 4.2 years. RESULTS: Of the 225 patients analyzed, the mean age was 7.9 +/- 0.6 years at diagnosis. Most of the patients suffered from primarily generalized tonic-clonic seizures (in 84 patients, 37.3%). 114 patients (50.6%) were classified as having idiopathic epilepsy, 64 (28.4%) had symptomatic epilepsy and 47 (20.8%) has cryptogenic epilepsy. Valproic acid (n: 120, 53.3%), carbamazepine (n: 45, 20%) and oxcarbazepine (n: 31, 13.7%) were the most frequently prescribed antiepileptic drugs. Overall, 67.5% (n: 152) patients were treated successfully with the first antiepileptic drug. Seventy-three patients failed with the first-line antiepileptic drug. Of these patients, 28 discontinued medication because of adverse effects (38.3%), 26 because of lack of efficacy (35.6%) and 19 (26.02%)because of a combination of inefficacy and adverse effects. Age at diagnosis, seizure, etiology and antiepileptic drug selection are considered to be associated with drug treatment failure in childhood epilepsy. There was no statistically significant effect of any of these variables on first-line treatment outcome. CONCLUSION: Approximately one-third of the children with newly diagnosed epilepsy fail the first prescribed antiepileptic drug. Adverse effects and lack of efficacy contributed equally to the treatment failures. PMID- 20739199 TI - Open repair for ruptured abdominal aortic aneurysm and the risk of spinal cord ischemia: review of the literature and risk-factor analysis. AB - OBJECTIVES: Spinal cord ischemia after open surgical repair for rAAA is a rare event. We estimated the current incidence and tried to identify risk factors. We also report a new case. METHODS: Group A consisted of 10 reports on open repair for rAAA from 1980 until 2009. Only series of >=100 patients were considered to estimate the incidence. Thirty three case reports from 1956 until 2009 were identified (group B). Case reports from group B were not encountered in group A. Group B patients were stratified according to the type of neurological deficit as described by Gloviczki (type I complete infarction and type II infarction of the anterior two third). RESULTS: Group A consisted of 1438 patients. In group A 86% were male with a mean age of 72.1 years. The incidence of post-operative paraplegia was 1.2% (range 0-2.8%). In-hospital mortality was 46.9%. Of the 33 patients of group B were 86% male with a mean age of 68.0 years. Most patients developed a type I (42%) or type II (33%) deficit. In-hospital mortality was 51.6%. No significant differences between different types were encountered. CONCLUSION: Spinal cord ischemia after ruptured AAA is a rare complication with an incidence of 1.2% (range 0-2.8%). PMID- 20739200 TI - Use of B-type natriuretic peptide to predict blood pressure improvement after percutaneous revascularisation for renal artery stenosis. AB - OBJECTIVES: The purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA). METHODS: In 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA. RESULTS: BP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml(-1) (interquartile range (IQR) 35-250) and decreased significantly within 1 day of PTRA to 62 pg ml(-1) (IQR 24-182) (p < 0.001), remaining at 75 pg ml(-1) (IQR 31 190) at 6 months. The area under the receiver operating curve for pre intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46-0.67). Pre-intervention BNP >50 pg ml(-1) was seen in 79% of patients with BP improvement compared with 56% in patients without improvement (p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml(-1) was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2-13.2). CONCLUSIONS: BNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml(-1) may be helpful to identify patients in whom PTRA will improve BP. PMID- 20739201 TI - A retrospective study of intravascular ultrasound use in patients undergoing endovascular aneurysm repair: its usefulness and a description of the procedure. AB - OBJECTIVES: To verify the usefulness and limitation of intravascular ultrasound (IVUS) in endovascular aneurysm repair (EVAR). METHODS: A total of 112 consecutive patients, who underwent EVAR to treat abdominal aortic aneurysms, were examined retrospectively. Of these, 33 patients were assigned to the IVUS group because of renal failure, a suspected allergy to contrast agents or anatomical difficulties; the remaining 79 patients were assigned to the non-IVUS group. RESULTS: Patients in the IVUS group required fewer intra-arterial contrast agents (IACAs) than those in the non-IVUS group (67+/-34ml vs. 123+/-50ml; p<0.01). Blood loss and operation time were comparable between the two groups. No patients died within 30 days of the operation. Three major renal complications occurred in the non-IVUS group. Renal deterioration evaluated by chronic kidney disease (CKD) stage was found to a greater extent in the non-IVUS group. CONCLUSIONS: IVUS is a powerful auxiliary method in EVAR for reducing the required volume of contrast agents. The combination of IVUS and IACA usage showed good overall performance; thus, we propose the routine use of IVUS in EVAR procedures. PMID- 20739202 TI - Endovascular repair of a ruptured popliteal artery aneurysm associated with popliteal arteriovenous fistula. AB - Popliteal artery aneurysms (PAAs) represent the most common peripheral arterial aneurysm and are a significant cause of patient morbidity and limb loss. Complications of PAA include distal embolisation, thrombosis and, rarely, rupture. Whereas open surgical repair remains the gold standard, endovascular exclusion has been demonstrated to be a valid alternative in selected patients. We present an unusual case of ruptured PAA associated with popliteal vein arteriovenous fistula that was successfully treated with an endovascular approach. In our opinion, higher-risk patients as well as patients presenting with rupture may constitute a subgroup warranting an endovascular approach whenever possible. PMID- 20739203 TI - Comments regarding 'a new endovascular approach to exclude isolated bilateral common iliac artery aneurysms'. Eur J Vasc Endovasc Surg Extra 2010;19(6) e55-7. PMID- 20739205 TI - Assessing renal function: some significant improvements on the horizon. PMID- 20739204 TI - A model for the preferential delivery of isoflurane to the spinal cord of the goat. AB - To identify the blood supply of the caprine central nervous system, six anaesthetised goats were perfused with coloured suspension into the brachiocephalic artery, the aorta, the iliac artery and the femoral artery. The subsequent distribution indicated that the brain and the main segments of the spinal cord were supplied by the brachiocephalic artery and aorta, respectively. Ten similarly anaesthetised goats then received emulsified isoflurane randomly via either the proximal part of the descending aorta (arterial group) or an ear vein (venous group). In the arterial group, the isoflurane partial pressure (P(iso)) in femoral arterial blood was almost double the P(iso) in jugular venous blood. The model showed that preferential delivery of isoflurane to the goat spinal cord in situ was possible and could be used for further research into the mechanisms of anaesthetic action, particularly factors affecting immobility. PMID- 20739206 TI - Performance on Wechsler intelligence scales in children with Tourette syndrome. AB - BACKGROUND: There is some evidence that Tourette syndrome is associated with cognitive disabilities. AIMS: To examine the cognitive performance of a clinical cohort of children with Tourette syndrome. METHODS: 266 children with Tourette syndrome have been examined with Wechsler Intelligence Scales. The presence of the co-morbidities attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD) was assessed using validated diagnostic instruments. Eighty healthy controls matched a part of the TS cohort. RESULTS: The children with Tourette syndrome had a mean verbal IQ (VIQ) of 92.9, performance IQ (PIQ) of 87.1, and full-scale IQ (FSIQ) of 88.8. We found statistically significant higher PIQ and FSIQ in the control group compared with a matched TS cohort and a trend towards a higher VIQ among the healthy controls. There was a statistically significant influence of age at onset of tics on PIQ. The children with co-morbid OCD scored higher on FSIQ compared with the other groups. The children with co morbid ADHD and OCD showed problems in motor tasks and speed tasks and the children with co-morbid ADHD showed attention deficits. CONCLUSIONS: Children with Tourette syndrome have lower IQ scores than the general population (but less than one standard deviation below) and our control group. Early onset of tics and the presence of co-morbidities might cause specific deficits on cognitive performance. PMID- 20739207 TI - A new simple method for assessing sudomotor function: relevance in type 2 diabetes. AB - AIM: The current sudomotor function tests are too time-consuming to be used for diabetic patients in daily practice. EZSCAN is a new, patented technology that measures electrochemical skin conductance (ESC) through reverse iontophoresis and chronoamperometry. The aim of the present study was to assess the sensitivity, specificity and reproducibility of the method in type 2 diabetic patients in comparison to control subjects with no risk of diabetes. METHODS: A total of 133 type 2 diabetic patients and 41 control subjects were tested. Participants placed their hands and feet on nickel electrodes, and an incremental low direct current was applied to the anode for 2 min. ESC was calculated from the resulting voltage and generated current. ESC diagnostic accuracy was analyzed by ROC curve modeling, and reproducibility was assessed using Bland-Altman analysis. RESULTS: The ESC of hands and feet was significantly reduced in diabetic patients (53+/ 16MUSi and 67+/-14MUSi, respectively) compared with control subjects (68+/-16MUSi and 80+/-7MUSi, respectively; P<0.0001). ESC values had a sensitivity of 75% and specificity of 100%, with an area under the ROC curve of 0.88 at a threshold of 50% on the EZSCAN scale. Coefficients of variation in hand and foot measurements were 15 and 7%, respectively. CONCLUSION: The good sensitivity, specificity and reproducibility of EZSCAN make it a feasible alternative for assessing sudomotor dysfunction, a clinical manifestation of autonomic neuropathy in diabetic patients. The test takes<3 min to perform, and requires neither special patient preparation nor medical personnel training. PMID- 20739208 TI - Correlation of plasma resistin with obesity and insulin resistance in type 2 diabetic patients. AB - AIM: The aim of this case-control study was to assess the relationship between resistin levels and obesity and insulin resistance in type 2 diabetic patients. METHODS: The study involved a sample of the Jordanian population that included 140 type 2 diabetic patients and 125 control subjects. RESULTS: Serum resistin levels were higher in type 2 diabetic patients compared with the controls (P<0.01). Markers of adiposity [body mass index (BMI) and waist circumference (WC)] and insulin resistance, as well as fasting blood glucose, glycated haemoglobin, urea and blood pressure were considerably higher among the studied diabetics than in the controls. When diabetic patients were subdivided into age group categories of 10-year intervals, resistin levels significantly increased with increased age, with a significant proportion in the group aged>60 years (P<0.01). Similarly, there was a significant association between plasma resistin and blood urea with growing older in diabetic patients. Pearson's analysis revealed positive correlations between plasma resistin and age, urea, creatinine, insulin, BMI, WC, body-fat content and homoeostasis model assessment (HOMA). Furthermore, plasma resistin concentrations were higher in type 2 diabetic obese patients than in non-diabetic obese subjects (P<0.01), whereas no such difference was found between overweight and normal-weight controls. CONCLUSION: These results suggest that variations in resistin concentrations are not directly related to susceptibility to type 2 diabetes. However, it may be that resistin plays a role in the pathogenesis of obesity and insulin resistance, both of which could, indirectly, contribute to the development of type 2 diabetes. PMID- 20739209 TI - [Nonsurgical management of hepatocellular carcinoma]. AB - Most of patients with hepatocellular carcinoma (HCC) cannot benefit from surgical therapies. Among nonsurgical options, only radiofrequency can challenge surgery for small size tumours. Conformal radiotherapy is likely highly efficient on solitary tumours, but controlled studies are warranted to conclude. Other options are purely palliative. Transarterial hepatic chemoembolization is the goal standard for multifocal hepatocellular carcinoma and sorafenib for hepatocellular carcinoma with portal vein invasion, leading to modest but significant benefit on survival rates. Yttrium-90 radioembolization is under evaluation through controlled studies, and could be of major interest for multifocal hepatocellular carcinoma with or without portal venous invasion. PMID- 20739210 TI - Proximal row carpectomy in emergency. AB - Proximal row carpectomy (PRC) is a well-accepted procedure for the treatment of early post-traumatic degenerative disease of the wrist. Much less frequently, PRC has been advocated as an emergency procedure for irreparable fracture-dislocation of the wrist. Our objective was to compare the results of PRC in patients having undergone this procedure in the two contexts. We conducted a retrospective analysis of the clinical and radiographic results of six patients treated by emergency PRC as compared to six patients who underwent elective PRC. The mean follow-up was 36 months. Both the patient's satisfaction and the grasp of the wrist joint were significantly better in patients who underwent PRC emergency as compared to those having undergone elective PRC. Quick DASH score, radiographic results, and return to work were also more favourable in these patients, but the difference between the two groups was not significant. This study confirms that PRC is a valuable salvage technique indicated in early posttraumatic wrist collapse. Moreover, when performed in emergency, the procedure shows even better subjective and objective results, allowing a majority of patients to return to their previous job. PMID- 20739211 TI - Assessment of four neural network based classifiers to automatically detect red lesions in retinal images. AB - Diabetic retinopathy (DR) is an important cause of visual impairment in industrialised countries. Automatic detection of DR early markers can contribute to the diagnosis and screening of the disease. The aim of this study was to automatically detect one of such early signs: red lesions (RLs), like haemorrhages and microaneurysms. To achieve this goal, we extracted a set of colour and shape features from image regions and performed feature selection using logistic regression. Four neural network (NN) based classifiers were subsequently used to obtain the final segmentation of RLs: multilayer perceptron (MLP), radial basis function (RBF), support vector machine (SVM) and a combination of these three NNs using a majority voting (MV) schema. Our database was composed of 115 images. It was divided into a training set of 50 images (with RLs) and a test set of 65 images (40 with RLs and 25 without RLs). Attending to performance and complexity criteria, the best results were obtained for RBF. Using a lesion-based criterion, a mean sensitivity of 86.01% and a mean positive predictive value of 51.99% were obtained. With an image-based criterion, a mean sensitivity of 100%, mean specificity of 56.00% and mean accuracy of 83.08% were achieved. PMID- 20739212 TI - The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches. AB - The ability to prospectively isolate breast cancer cells that initiate tumors when transplanted orthotopically into immunocompromised mice has led to an explosion of work characterizing these cells and establishing ways to target them. Microarray studies screening for novel targets and chemical library screens for effective therapies have implicated signaling pathways, tumor-stromal interactions, miRNAs and possible even piwi-interacting (piRNAs) in the regulation of tumor initiating cell self-renewal. Potential targeting agents including the beta-catenin inhibitor sulforaphane, AKT inhibitor perfosine, hedgehog inhibitor cyclopamine, stromal interaction inhibitor repertaxin, multidrug resistance pump poison dofequifar fumarate, as well as targeted the dual epidermal growth factor family inhibitor lapatinib and many more have all been found to have toxicity against purportedly chemotherapy resistant subpopulations of cancer cells often referred to as tumor initiating cells (TICs). Work using clinical samples is emerging and supports the hypothesis that neoadjuvant chemotherapy can enrich for TICs in residual disease, but strong correlation with long-term outcome is yet to be established. This paper reviews current attempts to targeting TICs and discusses the competing hypotheses to explain breast cancer recurrence and therapy resistance. PMID- 20739213 TI - Pleural metastases as a unique entity with dismal outcome of head and neck squamous cell carcinoma. AB - Once distant metastasis occurs, head and neck squamous cell carcinoma (HNSCC) patients generally have a poor prognosis with limited treatment options. A subgroup of patients who developed pleural metastases after curative treatment of localized HNSCC appeared to have worse outcomes. All patients from National Taiwan University Hospital who were diagnosed with localized HNSCC from January 1, 2000 to December 31, 2007 and developed distant metastases were included in this analysis. Medical records were reviewed. Patients with pleura as the first metastatic sites were compared to those with other first metastases for differences in basic demographics, time to distant metastasis (TTM) and overall survival (OS). A total of 198 patients were included, and 52 (26%) had pleural involvement at first diagnosis of distant metastases. Younger age at diagnosis (P=0.002) and buccal mucosa origin (P=0.006) were risk factors for developing pleural metastases. Patients with pleura as the first metastatic sites, compared to those with other first metastases, had significantly shorter TTM (median 7.5 vs. 11.1 months, P<0.001) and OS (median 9.6 vs. 16.5 months, P<0.001). By multivariate analysis, pleural metastases remained an independent predictor for shorter OS. In conclusion, patients with pleural metastases comprise a unique subgroup of HNSCC which rapidly develop distant metastases with poor prognosis. PMID- 20739214 TI - Plant stem cell niches: from signalling to execution. AB - The shoot and root meristems contain small populations of stem cells that constantly renew themselves while providing precursor cells to build all other plant tissues and organs. Cell renewal, growth and differentiation in the meristems are co-ordinated by networks of transcription factors and intercellular signals. The past two years have revealed how auxin and cytokinin signals are integrated with each other and with regulatory genes in the shoot and root meristems. Small RNAs have also emerged as novel intercellular signals. Downstream of meristem regulatory genes, links have been made to cell division control and chromatin function. Protection of genome integrity, partly through programmed cell death after DNA damage, has recently been revealed as a specialised function in plant stem cells. PMID- 20739216 TI - Antiviral treatment for severe EBV infections in apparently immunocompetent patients. AB - BACKGROUND: Infectious mononucleosis usually runs a mild self-limiting course. Complications arise rarely and when so, corticosteroids are the mainstay of their treatment. The role of antivirals in the management of severe EBV infections is debatable. METHODS: We sought to review the usage of antivirals for severe EBV infection in apparently immunocompetent patients. For this reason a search in PubMed and Scopus was performed for the time period from 1982 to 2009. RESULTS: 45 patients with severe manifestations of infectious mononucleosis received antivirals (as an adjunct to steroids in 26 of them). Specifically 21 patients with CNS involvement (meningoencephalitis, cerebellitis), 4 with peripheral nervous system involvement (Guillain-Barre, myeloradiculitis, facial nerve palsy), 5 with hepatitis and 15 with other afflictions (including adult respiratory distress syndrome, thrombocytopenia, aplastic anemia, acute renal failure, ulcerations, myocarditis, and frosted branch vasculitis) received antiviral medications. Thirty-nine out of these 45 patients had a favourable outcome (27 were cured and 12 showed clinical improvement) while 6 patients died. The most commonly prescribed antiviral regimen was acyclovir monotherapy (35 patients). Three patients received combinations of acyclovir with other antivirals and 1 received famciclovir. Three patients received ganciclovir monotherapy, 1 ganciclovir plus foscarnet, 1 foscarnet and 1 vidarabine. CONCLUSION: The available data derive from case reports and case series and thus the deduction of conclusions regarding the effect, if any, of antiviral treatment is debatable. However, physicians may consider using antiviral agents in severe manifestations of EBV infections in immunocompetent patients as an adjunct to steroid treatment. PMID- 20739215 TI - Plant hormone signaling lightens up: integrators of light and hormones. AB - Light is an important environmental signal that regulates diverse growth and developmental processes in plants. In these light-regulated processes, multiple hormonal pathways are often modulated by light to mediate the developmental changes. Conversely, hormone levels in plants also serve as endogenous cues in influencing light responsiveness. Although interactions between light and hormone signaling pathways have long been observed, recent studies have advanced our understanding by identifying signaling integrators that connect the pathways. These integrators, namely PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), PIF4, PIF3 LIKE 5 (PIL5)/PIF1 and LONG HYPOCOTYL 5 (HY5), are key light signaling components and they link light signals to the signaling of phytohormones, such as gibberellin (GA), abscisic acid (ABA), auxin and cytokinin, in regulating seedling photomorphogenesis and seed germination. This review focuses on these integrators in illustrating how light and hormone interact. PMID- 20739217 TI - Peripheral electrical stimulation to induce cortical plasticity: a systematic review of stimulus parameters. AB - Peripheral electrical stimulation (ES) is commonly used as an intervention to facilitate movement and relieve pain in a variety of conditions. It is widely accepted that ES induces rapid plastic change in the motor cortex. This leads to the exciting possibility that ES could be used to drive cortical plasticity in movement disorders, such as stroke, and conditions where pain affects motor control. This paper aimed to critically review the literature to determine which parameters induced cortical plasticity in healthy individuals using ES. A literature search located papers that assessed plasticity in the primary motor cortex of adult humans. Studies that evaluated plasticity using change in the amplitude of potentials evoked by transcranial magnetic stimulation of the motor cortex were included. Details from each study including sample size, ES parameters and reported findings were extracted and compared. Where data were available, Cohen's standardised mean differences (SMD) were calculated. Nineteen studies were located. Of the parameters evaluated, variation of the intensity of peripheral ES appeared to have the most consistent effect on modulation of excitability of corticomotor pathway to stimulated muscles. There was a trend for stimulation above motor threshold to increase excitability (SMD 0.79 mV, CI -0.10 to 1.64). Stimulation below motor threshold, but sufficient to induce sensory perception, produced conflicting results. Further studies with consistent methodology and larger subject numbers are needed before definitive conclusions can be drawn. There also appeared to be a time effect. That is, longer periods of ES induced more sustained changes in cortical excitability. There is insufficient evidence to determine the effect of other stimulation parameters such as frequency and waveform. Further research is needed to confirm whether modulation of these parameters affects plastic change. PMID- 20739218 TI - Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. AB - BACKGROUND: Bortezomib plus melphalan and prednisone (VMP) is significantly better than melphalan plus prednisone alone for elderly patients with untreated multiple myeloma; however, toxic effects are high. We investigated a novel and less intensive bortezomib-based regimen to maintain efficacy and to reduce toxic effects. METHODS: Between March, 2006, and October, 2008, 260 patients with untreated multiple myeloma, 65 years and older, from 63 Spanish centres, were randomly assigned to receive six cycles of VMP (n=130) or bortezomib plus thalidomide and prednisone (VTP; n=130) as induction therapy, consisting of one cycle of bortezomib twice per week for 6 weeks (1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32), plus either melphalan (9 mg/m2 on days 1-4) or daily thalidomide (100 mg), and prednisone (60 mg/m2 on days 1-4). The first cycle was followed by five cycles of bortezomib once per week for 5 weeks (1.3 mg/m2 on days 1, 8, 15, and 22) plus the same doses of melphalan plus prednisone and thalidomide plus prednisone. 178 patients completed the six induction cycles and were randomly assigned to maintenance therapy with bortezomib plus prednisone (n=87) or bortezomib plus thalidomide (n=91), consisting of one conventional cycle of bortezomib for 3 weeks (1.3 mg/m2 on days 1, 4, 8, and 11) every 3 months, plus either prednisone (50 mg every other day) or thalidomide (50 mg per day), for up to 3 years. Treatment codes were generated with a computerised random number generator, and neither participants nor study personnel were masked to treatment. The primary endpoint was response rate in induction and maintenance phases. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00443235. FINDINGS: In the induction phase, 105 (81%) patients in the VTP group and 104 (80%) in the VMP group achieved partial responses or better (p=0.9), including 36 (28%) and 26 (20%) complete remissions, respectively (p=0.2). Treatment with VTP resulted in more serious adverse events (40 [31%] vs 20 [15%], p=0.01) and discontinuations (22 [17%] vs 15 [12%], p=0.03) than did treatment with VMP. The most common toxicities (grade 3 or worse) were infections (one [1%] in the VTP group vs nine [7%] in the VMP group), cardiac events (11 [8%] vs 0), and peripheral neuropathy (nine [7%] vs 12 [9%]). After maintenance therapy, the complete remission rate was 42% (40 [44%] patients in complete remission in the bortezomib plus thalidomide group, 34 [39%] in the bortezomib plus prednisone group). No grade 3 or worse haematological toxicities were recorded during maintenance therapy; two (2%) patients in the bortezomib plus prednisone group and six (7%) in the bortezomib plus thalidomide group developed peripheral neuropathy. INTERPRETATION: Reduced-intensity induction with a bortezomib-based regimen, followed by maintenance, is a safe and effective treatment for elderly patients with multiple myeloma. FUNDING: Pethema (Spanish Program for the Treatment of Hematologic Diseases). PMID- 20739219 TI - Optimising bortezomib in newly diagnosed multiple myeloma. PMID- 20739220 TI - Molecular pathways regulating CD4(+) T cell differentiation, anergy and memory with implications for vaccines. AB - CD4(+) T cells occupy a central role in the induction and regulation of adaptive immune responses. Activated CD4(+) T helper (Th) cells exert immediate effector functions by producing cytokines and chemokines, providing help for the induction of CD8(+) cytotoxic T lymphocyte responses and memory, and providing help for immunoglobulin class switching, affinity maturation of antibody and B cell memory. Inherent in naive CD4(+) T cells is the flexibility to adopt alternate lineage potentials, which depend upon regulatory mechanisms that change with tissue microenvironment and upon infection. Here, we discuss lineage instructive programs that regulate CD4(+) T cell differentiation and memory and how to translate this knowledge into vaccines and immunotherapies that promote protective immune responses. PMID- 20739221 TI - Rheumatoid arthritis progression mediated by activated synovial fibroblasts. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Rheumatoid arthritis synovial fibroblasts (RASFs) are leading cells in joint erosion and contribute actively to inflammation. RASFs show an activated phenotype that is independent of the inflammatory environment and requires the combination of several factors. Although new aspects regarding RASF activation via matrix degradation products, epigenetic modifications, inflammatory factors, Toll-like receptor (TLR) activation and others have recently been uncovered, the primary pathophysiological processes in early arthritis leading to permanent activation are mostly unknown. Here, we review new findings regarding RASF activation and their altered behavior that contribute to matrix destruction and inflammation as well as their potential to spread RA. PMID- 20739222 TI - Chromosome sequence maps of the Giardia lamblia assemblage A isolate WB. AB - Two genotypes, assemblages A and B, of the pathogenic gut protozoan parasite Giardia lamblia infect humans. Symptoms of infection range from asymptomatic to chronic diarrhea. Giardia chromosomes have long been characterized but not until the publication of the first Giardia genome sequence was chromosome mapping work, commenced nearly two decades ago, completed. Initial mapping studies identified and ordered Not I chromosome segments (summating to 1.8 Mb) of the estimated 2 Mb chromosome 3. The resulting map was confirmed with the release of the Giardia genome sequence and this revitalized mapping. The result is that 93% of the WB isolate genome sequence has now been assigned to one of five major chromosomes, and community access to these data has been made available through GiardiaDB, the database for Giardia genomes. PMID- 20739223 TI - The abyssomicin C family as in vitro inhibitors of Mycobacterium tuberculosis. AB - The antimycobacterial efficacy of the abyssomicin C family of natural products, in addition to a key synthetic intermediate, has been investigated given their reported inhibition of Bacillus subtilis p-aminobenzoate biosynthesis. The naturally occurring (-)-abyssomicin C and its atropisomer were found to exhibit low micromolar growth inhibition against the relatively fast-growing and non virulent Mycobacterium smegmatis and the vaccine strain Mycobacterium bovis BCG, while their antipodes were slightly less active. (-)-abyssomicin C and its atropisomer were particularly efficacious against Mycobacterium tuberculosis H37Rv, exhibiting MIC values of 3.6 and 7.2 MUM, respectively. More specifically, (-)-abyssomicin C was bactericidal. This complex natural product and its analogs, thus, hold promise as chemical tools in the study of M. tuberculosis metabolism. PMID- 20739224 TI - Metastatic transitional cell carcinoma of the bladder arising in a patient with bladder autoaugmentation. AB - We report a case of a metastatic transitional cell carcinoma of the bladder in a 20-year-old patient who had previously undergone resection of posterior urethral valves, clean intermittent catheterization, bladder autoaugmentation, and later renal transplantation. To our knowledge, this is the first report of transitional cell carcinoma following bladder autoaugmentation. We also review the literature on bladder autoaugmentation and transitional cell carcinoma. PMID- 20739225 TI - Promoting fusion in minimally invasive lumbar interbody stabilization with low dose bone morphogenic protein-2--but what is the cost? AB - BACKGROUND: Using bone morphogenic protein (BMP) to augment fusion in spine surgery is widespread and lends itself in particular to minimally invasive lumbar fusion, where the surface area for fusion is significantly less than the equivalent open procedure. PURPOSE: Here we described the use of very low-dose BMP in promoting fusion in minimally invasive lumbar interbody fixation but also highlight some of the potential complications of BMP-2 use and techniques available to reduce or avoid them. STUDY DESIGN: Prospective observational study of consecutive patients undergoing minimally invasive lumbar interbody fusion with percutaneous pedicle screws. PATIENT SAMPLE: Thirty patients aged between 22 and 78 years (mean 53 years). OUTCOME MEASURES: Thin-slice lumbar computed tomography scanning with multiplanar reconstruction at 6 and 12 months postoperative. METHODS: Thirty-six spinal levels were instrumented in total, of which four underwent posterior lumbar interbody fusion and 32 underwent transforaminal lumbar interbody fusion. Bone graft harvested locally was placed in the disc space with low-dose BMP-2 (1.4 mg per level). RESULTS: Thirty-three of 36 spinal levels showed complete fusion at a mean postoperative scan time of 7.1 months. Two levels demonstrated partial fusion at 6 months, which was complete at 12 months. There was one case of nonunion at 12 months, which also demonstrated vertebral body osteolysis. Despite very low-dose BMP-2, two cases of asymptomatic heterotopic ossification were observed, and there were two cases of perineural cyst formation, one of whom required revision of the interbody cage. CONCLUSIONS: The use of BMP with autograft in the disc space during minimally invasive lumbar interbody fusion is associated with a high rate of early fusion. Even with very low-dose BMP used in this study, complications related to BMP usage were not avoided completely. PMID- 20739226 TI - Point: the relationship between postimplant dose metrics and biochemical no evidence of disease following low dose rate prostate brachytherapy: is there an elephant in the room? PMID- 20739227 TI - Combined radiofrequency ablation and high-dose rate brachytherapy for early-stage non-small-cell lung cancer. AB - PURPOSE: This retrospective analysis reports the results of patients with early stage inoperable non-small-cell lung cancer treated with radiofrequency ablation (RFA) followed by adjuvant high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS: Seventeen medically inoperable patients with biopsy-proven Stage I non small-cell lung cancer were treated with RFA followed by single fraction HDR brachytherapy. Brachytherapy catheters were inserted immediately after RFA, and one fraction of HDR brachytherapy was delivered on the same day. Doses of brachytherapy ranged from 14.4 to 20 Gy (median, 18 Gy). Patients were followed clinically and radiographically to determine tumor control and toxicity profile. RESULTS: Median followup time was 22 months. Of the 17 patients, 3 patients have recurred locally. Each of the patients with local recurrences was originally treated for T2 disease. In total, three of seven cases with T2N0 disease experienced local recurrences, whereas all 9 patients with T1 disease were controlled locally. Five of the 17 patients required a chest tube posttreatment, and 1 patient developed an empyema. There were no deaths within 1 month of treatment. CONCLUSIONS: RFA followed by HDR brachytherapy yields excellent local control with an acceptable toxicity profile for patients with otherwise inoperable early-stage lung cancer. PMID- 20739228 TI - Two mechanisms underlie the slow noradrenergic depolarization in the rat tail artery in vitro. AB - In rat tail artery, short trains of electrical stimuli evoke both ATP-mediated excitatory junction potentials (EJPs) and a slow noradrenaline (NA)-mediated depolarization (NAD). Here we have investigated the contribution of alpha(1)- and alpha(2)-adrenoceptors to the NAD. The alpha(1)-adrenoceptor antagonist, prazosin (0.1MUM), and the alpha(2)-antagonist, rauwolscine (1MUM), reduced the amplitude of the NAD and in combination these agents virtually abolished the NAD. The K(ATP) channel blocker, glibenclamide (10MUM) abolished the alpha(2)-adrenoceptor mediated component of the NAD, indicating that activation of these receptors produces closure of K(ATP) channels. The alpha(1)-adrenoceptor-mediated component of the NAD was increased in amplitude by glibenclamide. Changes in membrane conductance were monitored by measuring the time constant of decay of EJPs (tauEJP). The tauEJP was increased during alpha(1)-adrenoceptor-mediated depolarization, indicating a decrease in membrane conductance; i.e. closure of K(+) channels. Broad-spectrum K(+) channel blockers (tetraethylammonium, 4 aminopyridine, Ba(2+)) and the TASK-1K(+) channel blocker, anandamide (10MUM), did not reduce the alpha(1)-adrenoceptor-mediated NAD. The alpha(1)-adrenoceptor mediated NAD was unaffected by the Cl(-) channel blockers, 9-anthracene carboxylic acid (100MUM) and niflumic acid (10MUM) or by the non-selective cation channel blocker, SKF 96365 (10MUM). These findings indicate that the NAD is produced by activation of both alpha(1)-and alpha(2)-adrenoceptors. The alpha(2) adrenoceptor-mediated component is produced by closure of K(ATP) channels whereas the alpha(1)-adrenoceptor-mediated component is most likely mediated by closure of another type of K(+) channel. PMID- 20739229 TI - The mitochondrial transcription factor A functions in mitochondrial base excision repair. AB - Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids. TFAM plays an important role in mitochondrial transcription and replication. TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected in mitochondria, whereas base excision repair (BER) has been comprehensively characterized in these organelles. The BER proteins are associated with the inner membrane in mitochondria and thus with the mitochondrial nucleoid, where TFAM is also situated. However, a function for TFAM in BER has not yet been investigated. This study examines the role of TFAM in BER. In vitro studies with purified recombinant TFAM indicate that it preferentially binds to DNA containing 8 oxoguanines, but not to abasic sites, uracils, or a gap in the sequence. TFAM inhibited the in vitro incision activity of 8-oxoguanine DNA glycosylase (OGG1), uracil-DNA glycosylase (UDG), apurinic endonuclease 1 (APE1), and nucleotide incorporation by DNA polymerase gamma (pol gamma). On the other hand, a DNA binding-defective TFAM mutant, L58A, showed less inhibition of BER in vitro. Characterization of TFAM knockdown (KD) cells revealed that these lysates had higher 8oxoG incision activity without changes in alphaOGG1 protein levels, TFAM KD cells had mild resistance to menadione and increased damage accumulation in the mtDNA when compared to the control cells. In addition, we found that the tumor suppressor p53, which has been shown to interact with and alter the DNA binding activity of TFAM, alleviates TFAM-induced inhibition of BER proteins. Together, the results suggest that TFAM modulates BER in mitochondria by virtue of its DNA binding activity and protein interactions. PMID- 20739231 TI - Prolonged thioguanine therapy is well tolerated and safe in the treatment of ulcerative colitis. AB - BACKGROUND: Thioguanine has been used for the treatment of inflammatory bowel disease, in particular for patients who failed conventional thiopurine therapy. To date, thioguanine has been infrequently studied in ulcerative colitis. AIM: To evaluate the tolerability, safety and efficacy of thioguanine in the treatment of ulcerative colitis. METHODS: A database analysis was performed on inflammatory bowel disease patients who had failed conventional thiopurine therapy and were treated with thioguanine. Rates and reasons for treatment failure were assessed. Laboratory values, abdominal ultrasonography, liver biopsy and endoscopic remission rates were evaluated. RESULTS: Forty-six patients were included and median treatment duration was 22 months (range 0.3-72.0). Nine patients failed thioguanine therapy: six due to adverse events, three due to therapy resistance. Concomitant treatment with aminosalicylates protected against thioguanine failure (hazard ratio (HR) 0.11, 95% CI 0.03-0.48). When performed, ultrasonography (n = 21) revealed no suspected therapy-related pathology in all but one patient, in whom hepatomegaly was observed. Liver histology (n = 12) predominantly revealed no abnormalities (n = 4) or non-specific regeneration (n = 4); none showed nodular regenerative hyperplasia. At follow-up, 40% of colonoscopies revealed endoscopic remission as compared with 10% at baseline (P = 0.180). CONCLUSIONS: Long-term use of thioguanine appears to be well tolerated and relatively safe in ulcerative colitis patients who failed conventional thiopurine therapy. PMID- 20739230 TI - An adaptable HPLC method for the analysis of frequently used antibiotics in ocular samples. AB - Four different antibiotics, delivered individually to rabbit eyes via hydrophilic intraocular lenses soaked in the drug solution prior to implantation, were measured in aqueous and vitreous humor samples from the eyes. To meet this analytical need, we developed a sensitive, high performance liquid chromatographic (HPLC) method for measuring the concentrations of moxifloxacin, gatifloxacin, linezolid, and cefuroxime in the ocular tissue. Separations were carried out on a LichroSpher RP-18 column, maintained at room temperature. The fluoroquinolones were eluted with a mobile phase consisting of 20% acetonitrile, in 0.1% trifluoroacetic acid (pH 3.0) with 30 mM tetrabutylammonium chloride. Linezolid and cefuroxime were eluted with 25% acetonitrile in 25 mM Na acetate buffer, pH 5.0. All elutions were isocratic. With ultraviolet detection, the lower limit of quantitation (LLOQ) for these compounds approached 1 ng (on-column injection). By using fluorescence detection, the LLOQ for the fluoroquinolones improved to 200 pg. The overall accuracy of the method was >or=90%. With minor modifications, the method was optimized for each of the agents, and the resulting analytical sensitivity made the method suitable for clinical investigations of the ocular penetration of these drugs. PMID- 20739232 TI - Beyond hereditary hemochromatosis: new insights into the relationship between iron overload and chronic liver diseases. AB - Following the model of hereditary hemochromatosis, the possible role of iron overload as a cofactor for disease progression in acquired liver diseases has been investigated with controversial results. In recent years, progress has been made in understanding the regulation of iron metabolism, thereby allowing the evaluation of the mechanisms linking liver diseases to excessive iron accumulation. Indeed, deregulation of the transcription of hepcidin, emerging as the master regulator of systemic iron metabolism, has been implicated in the pathogenesis of hepatic iron overload in chronic liver diseases. Whatever the cause, hepatocellular iron deposition promotes liver fibrogenesis, while an emerging possible aggravating factor is represented by the strong link between iron stores and insulin resistance, a recently recognized risk factor for the progression of liver diseases. Overall, these pathogenic mechanisms, together with the known proliferative and mutagenic effect of excess iron, converge in determining an increased susceptibility to hepatocellular carcinoma. Finally, an association between serum ferritin levels and mortality in patients with end stage liver disease has recently been reported. Prospective, randomized studies are required to evaluate whether iron depletion may reduce fibrosis progression, hepatocellular carcinoma development, and eventually mortality in patients with chronic liver diseases. PMID- 20739233 TI - Relations among media influence, body image, eating concerns, and sexual orientation in men: A preliminary investigation. AB - The current study explored the relation between sexual orientation, media persuasion, and eating and body image concerns among 78 college men (39 gay; 39 straight). Participants completed measures of sexual orientation, eating disorder symptoms, appearance-related anxiety, perceived importance of physical attractiveness, perceptions of media influence, and media exposure. Gay men scored significantly higher on drive for thinness, body dissatisfaction, and body image-related anxiety than their straight counterparts. Additionally, perceptions of media influence were higher for gay men, and significantly mediated the relation between sexual orientation and eating and body image concerns. Sexual orientation also moderated the relation between perceived media influence and beliefs regarding the importance of physical attractiveness, as this relation was significant for gay men, but not straight men. The current findings suggest that gay men's increased vulnerability to media influence partially accounts for the relatively high rate of eating pathology observed in this population. PMID- 20739234 TI - Early experience in microtia reconstruction: the first 100 cases. AB - Auricular reconstruction in Microtia is a challenging operation with a steep learning curve. In view its rarity attaining a high standard for new surgeons is extremely difficult. This study analyses the first 100 microtia cases looking at complications, technique, pattern of progress and aesthetic outcome. The author performed 100 autologous ear reconstructions for microtia over a period of 4 years utilizing the two stage technique popularised by Nagata and Firmin. In 11 cases a temroparietal fascial flap was utilised because of either a low hairline or scarring. Follow up ranged from 3 to 36 months. Data was collected prospectively. There were 7 cases of partial skin necrosis, 3 of which healed with conservative management. In early cases deficiencies were seen in the proportions of the reconstructed ear and the quality of definition. Better shape and definition were evident as more surgical experience was gained. This occurred as a result of increased appreciation of the ear proportions and improved framework carving. Although two stages were planned 21 cases required further procedures. The series demonstrates the early learning curve in microtia reconstruction and underlines the importance of appropriate training and case availability in achieving high quality results in autologous ear reconstruction. PMID- 20739235 TI - Unique case of 11-fingered polydactyly with cleft hand. AB - Polydactyly is a common congenital extremity deformity in live births. We describe a 3-month-old boy with 11-fingered polydactyly with cleft hand, an extremely rare hand anomaly. The patient was treated with excision of the supernumerary rays and metacarpals, closure of the cleft and removal of excess adipose tissue. Follow-up, lasting 3 years, showed satisfactory functional and aesthetic results. PMID- 20739237 TI - Commentary on: periodontally accelerated osteogenic orthodontics (PAOO) - a clinical dilemma. AB - It is apparent that tooth movement is enhanced by procedures that elevate the remodeling of alveolar bone, and of periodontal and gingival fibrous tissues. The periodontally accelerated osteogenic orthodontics (PAOO) also termed as Wilckodontics, involves full-thickness labial and lingual alveolar flaps accompanied with limited selective labial and lingual surgical scarring of cortical bone (corticotomy). Most of the authors suggest that the RAP is the major stimulus for alveolar bone remodeling, enabling the PAOO. However, we propose that detachment of the bulk of dentogingival and interdental fibers from coronal part of root surfaces by itself should suffice to stimulate alveolar bone resorption mainly on its PDL surfaces, leading to widening of the periodontal ligament space which largely attributes to accelerated osteogenic orthodontics. Moreover this limited fiberotomy also disrupts transiently the positional physical memory of dentition (PPMD), allowing accelerated tooth movement. During retention period, a new biological and physical connectivity is generated that could be termed as new positional memory of the dental arch. PMID- 20739239 TI - Treatment of Class III malocclusions in adults using the Incognito((r)) lingual technique. AB - In orthodontics, as in medicine in general, there is always only one diagnosis. For a given diagnosis, several treatment solutions are available. While these are hard and fast rules, the techniques adopted by orthodontists can vary and yet remain effective, without placing constraints on the practitioner. The lingual technique, originally designed to meet the demands of adult patients for "invisibility" is now comparable or even superior in terms of precision to vestibular techniques. Three clinical Class III cases involving adults and three distinct treatment options are described in this paper. PMID- 20739241 TI - Determination of tooth-size discrepancy and Bolton ratios using Bibliocast Cecile3 digital models. AB - The purpose of this study was to compare digitized models with their current gold standard plaster models for tooth-size discrepancy and Bolton analysis. Fifteen pairs of plaster models were obtained from orthodontic patients with permanent dentition. These were digitized and evaluated using the Bibliocast Cecile3 v2.5 software. Two examiners measured three times the mesiodistal width of all the teeth and the arch length, and determined the tooth-size discrepancy and Boltons ratios. The plaster models were measured using a digital vernier caliper. Interclass correlation (ICC), mean differences and paired t-tests were used for comparisons and statistical analysis. The ICC of the digital models were 0.930 (0.852<=ICC<0.973) for the intra-examiner and 0.929 (0.829<=CCI<0.974) for the inter-examiner. The mean differences between plaster and digital models with respect to the anterior and overall Boltons ratios for examiner 1 was 0.34 mm for both and for examiner 2 were 0.28 mm and 0.21 mm respectively. Although digital model measurements were lower than plaster (p<0.05), these were considered clinically insignificant (differences<0.1mm). The determination of the tooth-size discrepancy and Bolton analysis using digital models and the Bibliocast Cecile3 software are an acceptable alternative to use in clinical practice. PMID- 20739242 TI - European College of Orthodontics: Commission of Affiliation and Titularisation. AB - A. PRETREATMENT RECORDS: 5/12/2004 (12.3 y). DIAGNOSIS: Skeletal Class Il, hypodivergence, Class II division 1, overbite. TREATMENT: Multibracket appliance without extraction of premolars combined with Class II mechanics with HPHG. B. POSTTREATMENT RECORDS: 14/3/2007 (14.7 y). RETENTION: Wire bonded from 33 to 43. Hawley maxillary retainer for night-time wear. C. POSTRETENTION RECORDS: 3/9/2008 (15.2 y). PMID- 20739245 TI - French Board of Orthodontics. AB - A. PRETREATMENT RECORDS: February 2001 (15.11 y). DIAGNOSIS: Molar Class I, skeletal Class I, normodivergent, anterior deficiency: -17 mm, bimaxillary protrusion. TREATMENT: Preparation of arches (alignment, levelling, canine retraction). Correction of arches (space closure). Occlusal finishing (artistic bends). B. POSTTREATMENT RECORDS: February 2003 (17.11 y). RETENTION: Maxillary Hawley plate for nighttime use and bonded lingual wire from 33 to 43. C. POSTRETENTION RECORDS: December 2003 (18.9 y). PMID- 20739246 TI - Investigating quality of life and depressive symptoms in the postpartum period. AB - BACKGROUND: Mood disturbances represent the most frequent form of maternal psychiatric morbidity in the postpartum period. Nevertheless, few studies have examined the impact of postpartum depression on the mother's quality of life. RESEARCH QUESTION OR PROBLEM: The present study aims to assess the quality of life of a sample of mothers in Southern Brazil, in order to investigate the association between postpartum depression and quality of life (QoL) standards. PARTICIPANTS AND METHODS: This study investigates a sample of 101 adult volunteers who completed the Portuguese version World Health Organization Quality of Life Assessment-Bref (WHOQOL-Bref) and Multicultural Quality of Life Index (MQLI) questionnaires. Postnatal depressive symptoms were evaluated through the Postpartum Depression Screening Scale (PDSS) and Edinburgh Postnatal Depression Scale (EPDS). Multiple regression analyses were conducted to predict the overall PDSS and EPDS scores. Pearson Product-Moment Correlation coefficients were computed between the global scores of the quality of life measurements and the screening questionnaires for postnatal depression. RESULTS: Both socio-economic status and quality of life have influenced significantly the depressive symptomatology and correlated epiphenomena. Significant correlations were observed among scores of postpartum depression screening tools and quality of life questionnaires. The socio-economic status of research participants was only significantly correlated to the scores generated by the WHOQOL-Bref questionnaire. CONCLUSIONS: These findings confirm that socio-economic deficiencies and low quality of life can facilitate the expression of depressive symptomatology during the postpartum period. The results also emphasize the salience of psychosocial risk factors in the diathesis of postnatal depression. PMID- 20739247 TI - A qualitative analysis of the content of telephone calls made by women to a dedicated 'Next Birth After Caesarean' antenatal clinic. AB - BACKGROUND: The 'Next Birth After Caesarean' (NBAC) clinic is a dedicated service for women who have had a previous caesarean section. The midwifery-led clinic commenced at a tertiary hospital in Western Australia in 2008. As part of this service, access to a midwife via telephone is available. AIM: This paper aims to provide maternity health care providers with an increased understanding of, and insight into, the different information needs of this specific group of maternity care consumers. METHODS: A qualitative descriptive approach was used to analyse the content of 170 telephone calls made by women to the NBAC clinic over a period of 16 months (July 2008-November 2009). RESULTS: Six distinct categories of calls were elicited from the analysis process with the majority of calls related to women seeking information and support about the option of vaginal birth after caesarean (VBAC). These were labeled: 'Wanting and seeking a VBAC'; 'Is VBAC a possiblility?'; 'Seeking clarification and cross-checking information in the face of opposition'; 'Existing NBAC clients checking in/checking out'; 'Feeling distressed and disappointed; wanting to talk' and 'Professional inquiry about NBAC service'. DISCUSSION: It is acknowledged that women require access to non biased information to be able to make informed decisions about birth after caesarean. However there remains limited evidence on the precise informational needs of these women. It appears from our findings that this particular group of maternity service consumers requires opportunities to discuss their particular needs within the context of their individual childbearing experiences. CONCLUSION: Preliminary evidence is provided that a telephone service led by midwives may be one effective strategy to meet women's informational needs and address decisional conflict in relation to options for birth after a caesarean section. PMID- 20739248 TI - Forensic utilization of familial searches in DNA databases. AB - DNA evidence is widely recognized as an invaluable tool in the process of investigation and identification, as well as one of the most sought after types of evidence for presentation to a jury. In the United States, the development of state and federal DNA databases has greatly impacted the forensic community by creating an efficient, searchable system that can be used to eliminate or include suspects in an investigation based on matching DNA profiles - the profile already in the database to the profile of the unknown sample in evidence. Recent changes in legislation have begun to allow for the possibility to expand the parameters of DNA database searches, taking into account the possibility of familial searches. This article discusses prospective positive outcomes of utilizing familial DNA searches and acknowledges potential negative outcomes, thereby presenting both sides of this very complicated, rapidly evolving situation. PMID- 20739249 TI - Distal quarter leg fractures fixation: The intramedullary nailing alone option. AB - INTRODUCTION: Intramedullary (IM) nailing is the classical treatment for diaphyseal fractures of the tibia. Stabilizing fractures of the distal quarter is recognized as being delicate. We report a continuous, multicenter prospective study of distal tibia-fibula fractures treated with anterograde intramedullary nailing. HYPOTHESIS: The working hypothesis was to identify the problems encountered with IM nailing alone of distal leg fractures. PATIENTS AND METHODS: From May 2007 to November 2008, 51 fractures in 51 patients (19 females and 32 males; mean age, 46.2 years [range, 17-93 years]) were treated with IM nailing. The fractures were classified according to the association pour l'osteosynthese (AO) classification, with most type A1 (29/51). Thirteen fractures presented a distal articular extension treated with screws in five cases. Fixation consisted in intramedullary nailing, reamed in all cases, performed on a standard or orthopaedic surgery table. Nailing was static and distally locked (50/51). The patients were evaluated clinically and radiologically, with AP and lateral images of both legs and the Olerud score. RESULTS: We report one death and eight patients lost to follow-up, providing 42 cases to reviewing at 1 year. The bone union rate was 97.6% in a mean 15.7 weeks. Immediately after surgery, 14 axial deviations greater than 5 degrees were observed, mainly valgus, with only one greater than 10 degrees . The absence of fibular fixation was the only identifiable risk factor for appearance of an initial axial deviation as well as fracture instability over time. Two infections were observed and at 6 months four secondary displacements, one of which can be explained by changing the distal locking due to infection. Four dynamizations were performed. No other risk factor was found. The mean Olerud functional score at 12 months was 83.5 points. DISCUSSION: The clinical results are comparable to those reported in the literature. From a radiological point of view, the rates and times to bone union were identical. However, the rates of malunion were clearly higher. The risk factors for malunion found in the literature are metaphyseal enlargement, fracture comminution, a too distal location of fracture site, young patient age, patient installation on a standard operating table, and technical errors. The absence of supplementary fibular fixation, the subject of debate in the literature, was the only statistically significant point found in the present study. Nailing distal fractures of the leg provides good clinical results. However, with regard to the malunion rates, the technique must be precise and rigorous. We recommend systematic fibular fixation and use of an orthopaedic table. LEVEL OF EVIDENCE: Level IV; cohort type prospective study. PMID- 20739250 TI - Somaesthetic perception of the vertical in spinal cord injured patients: a clinical study. AB - PURPOSE: The perception of verticality results from the integration of vestibular, visual and somatosensory information. Spinal cord injured patients with complete paraplegia have total somatosensory deafferentation below a certain metameric segment. In our study, we were interested in the implication of somatosensory signal in the construction of verticality and in the possible effect of somatosensory loss on spatial representation. METHOD: We analysed haptic and postural aspects of perceived verticality in 14 spinal cord injured patients with complete paraplegia and in an age- and gender-matched group of 13 controls. We also conducted a structured interview on the existence of vertigo or postural instability in daily life. RESULTS: The spinal cord injured patients perceived verticality without any significant directional bias in the orientation of the vertical but with a greater uncertainty than control subjects, both in haptic and postural modalities. If paraplegic did not report vertigo, half described an altered spatial perception without vision. CONCLUSION: The present results confirm the importance of sensory input from the trunk and the lower limbs in the perception of the vertical. However, visual and vestibular information appear to compensate for somatosensory deafferentation. PMID- 20739251 TI - Uptake and resource allocation of ammonium and nitrate in temperate seagrasses Posidonia and Amphibolis. AB - Ecologically relevant estimates of seasonal variability in nitrogen uptake and allocation in two species of temperate seagrasses were obtained using in situ isotope-labelling approach. Significantly higher uptake rates of ammonium by leaves, roots and epiphytes of Amphibolis than Posidonia were observed. Overall, root uptake rates were lower than other components. Effect of season was not significant for leaves, roots or epiphytes of the two species. However, plankton uptake varied seasonally with higher rates in winter (0.98 mg N g(-1)D Wh(-1)). In contrast, nitrate uptake rates for various components were significantly affected by seasons. Uptake rates by plankton were highest ranging from 0.003 mg N g(-1)D Wh(-1) (summer, Amphibolis) to 0.69 mg N g(-1)DWh(-1) (winter, Posidonia). Uptake of nitrate by roots was negligible. Biotic uptake rates for nitrate were an order of magnitude slower than ammonium, demonstrating an affinity for ammonium over nitrate as a preferred inorganic nitrogen source. Adelaide coastal waters have lost over 5000 ha of seagrasses, much of this attributed to nutrient inputs from wastewater, industrial and stormwater. Managing these inputs into future requires better understanding of the fate of nutrients, particularly biological uptake. This study attempts to quantify uptake rates of nitrogen by seagrasses. PMID- 20739252 TI - Forecasting the morbidity and mortality associated with prevalent cases of pre cirrhotic chronic hepatitis C in the United States. AB - BACKGROUND: Without diagnosis and antiviral therapy, many patients with chronic hepatitis C infections will develop end-stage liver disease and die from complications. AIMS: To evaluate the future impacts of preventive interventions and treatment advances, this paper forecasts a baseline estimate of the future morbidity and mortality of prevalent hepatitis C when left untreated. METHODS: We simulated the future disease progression and death for all Americans with prevalent hepatitis C in 2005. To validate the model, we used past seroprevalence to forecast contemporary outcomes. We used the validated model to forecast future cases of end-stage liver disease, transplants, and deaths from 2010 to 2060, and we estimated credible intervals using Monte Carlo simulation. RESULTS: When programmed with past data, our model predicted current levels of hepatitis C outcomes with accuracy between +/-1% and 13%. Morbidity and mortality from hepatitis C will rise from 2010 to a peak between the years 2030 and 2035. We forecasted a peak of 38,600 incident cases of end-stage liver disease; 3200 referrals for transplant; and 36,100 deaths. CONCLUSIONS: Because current rates of screening and treatment are low, future morbidity and mortality from hepatitis C are likely to increase substantially without public health interventions to increase treatment. PMID- 20739253 TI - [Cognition disorders]. PMID- 20739254 TI - [Obstructive sleep apnea and cognitive impairment in the elderly]. AB - Obstructive Sleep Apnea Syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep that result in intermittent hypoxemia and arousal. The prevalence of OSAS increases with aging, occurring in up to 25% of older adults and up to 48% in patients with Alzheimer's disease. OSAS causes hypoxia, fragmented sleep, daytime sleepiness, cognitive dysfunction, functional decline, and brain damage resulting from reduced cerebral blood flow, ischemic brain lesions, microvascular reactivity, white matter lesions, and grey matter loss. OSAS is considered as an independent risk factor for hypertension, stroke and mortality. The treatment of choice for OSAS is continuous positive airway pressure (CPAP). OSAS-related cognitive dysfunction has been shown in a variety of domains including attention, executive functioning, motor efficiency, working memory, and long-term episodic memory. Proposed mechanisms include hypoxemia, sleep fragmentation and inflammatory process, but it remains unclear which mechanisms underlie the relationship between OSAS and disturbances in the different cognitive domains. Recent studies suggest that OSAS may exacerbate cognitive functioning in dementia and that CPAP therapy can be applied to these patients and improve cognitive functioning. PMID- 20739255 TI - [Sleep and depression in elderly people]. AB - Mood disorders and sleep disturbances are closely related. In elderly people, the prevalence of insomnia and depressive symptoms is increased. Moreover, somatic co morbidities associated with aging are known to be risk factors for both insomnia and depression. Assessment of the origin of sleep complaints must consider primary and secondary insomnia, and the existence of associated depression. Causal treatment of insomnia is necessary keeping in consideration that depressive dimension can, afterward, evolve on its own. In presence of intense sleep complaints in inadequacy with somatic examination, and not documented by sleep recordings, depression must be evoked. In patients with a diagnosis of depression, treatment and monitoring of the evolution of insomnia is necessary, because persistent disturbances of sleep are associated with poor prognosis. Concerning the therapeutics, beyond antidepressant treatment and psychotherapy, chronotherapy is a promising, but still not yet evaluated, approach, which presents the advantage to limit the use of psychotropics drugs. PMID- 20739256 TI - [Multiple system atrophy]. AB - Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology. It is the most frequent disorder among atypical parkinsonism with an estimated prevalence of 2 to 5 per 100 000 inhabitants. The clinical symptoms are rapidly progressing with a mean survival ranging between 6 to 9 years. The diagnosis is based on consensus criteria that have been revised in 2008. The diagnostic criteria allow defining "possible", "probable" and "definite" MSA. The latter requires post mortem confirmation of striatonigral and olivopontocerebellar degeneration with alpha-synuclein containing glial cytoplasmic inclusions. The diagnosis of "possible" and "probable" MSA is based on the variable presence and severity of parkinsonism, cerebellar dysfunction, autonomic failure and pyramidal signs. According to the revised criteria, atrophy of putamen, pons, middle cerebellar peduncle (MCP) or cerebellum on brain magnetic resonance imaging are considered to be additional features for the diagnosis of "possible" MSA. T2-weighted brain imaging may further reveal a putaminal hypointensity, a hyperintense lateral putaminal rim, the so called "hot cross bun sign" and MCP hyperintensities. Cardiovascular examination, urodynamic testing and anal sphincter electromyography may be helpful for the diagnosis of autonomic failure. Some patients may respond to levodopa, but usually to a lesser extent than those suffering from Parkinson's disease, and high doses are already required in early disease stages. No specific therapy is available for cerebellar dysfunction, while effective treatments exist for urinary and cardiovascular autonomic failure. Physical therapy may help to improve the difficulties of gait and stance, and to prevent their complications. In later disease stages, speech therapy becomes necessary for the treatment of dysarthria and dysphagia. Percutaneous gastrostomy is sometimes necessary in patients with severe dysphagia. Beyond these strategies, psychological support, social care and occupational therapy to adapt the environment to the patient's disability are prerequisites for improving the quality of life in MSA patients. PMID- 20739257 TI - [Which brakes upon severe dementia clinical research?]. AB - Publications devoted to severe dementia remain limited, whereas several authors underline the need to carry on clinical research in the field. The aim of this paper is to analyze the various technical, psychological and sociological factors that slow down the development of clinical research in severe dementia. To reduce these obstacles seems of main interest considering the economic, medical and human issues related to the severe stage of dementia. PMID- 20739258 TI - [Decision making in the elderly: which tools for its evaluation by the clinician?]. AB - Numerous decision-making situations occur in the activities of daily living. The consequences of the decision-making capacity disturbances may have a great impact on the patient's autonomy, financial management, and his or her reaction to a diagnosis as well as the ability to accept a therapeutic option or give informed consent. Decision-making is a complex and multi-dimensional process and brings into play attention, memory and executive functions, which are processed in the prefrontal cortex, particularly vulnerable in aging. A better comprehension of the mechanisms of decision-making, and of the resulting social consequences of their dysfunction may improve autonomy of the elderly. Unfortunately, we still lack appropriate tools to explore decision-making in routine practice. PMID- 20739259 TI - [Atrial fibrillation and cognitive function]. AB - Atrial fibrillation (AF), which prevalence increases with age, is a growing public health problem and a well known risk factor for stroke. On the other hand, dementia is one of the most important neurological disorders in the elderly, and with aging of the population in developed countries, the number of demented patients will increase in absence of prevention. In the past decade, several vascular risk factors (hypertension, obesity and metabolic syndrome, hypercholesterolemia) have been found, with various degree of evidence, to be associated with vascular dementia but also, surprisingly, with Alzheimer's disease. This review is devoted to the links between atrial fibrillation, cognitive decline and dementia. Globally, transversal studies showed a significant association between atrial fibrillation, cognitive decline and dementia. However, these studies are particularly sensitive to various biases. In this context, recent longitudinal studies of higher level of evidence have been conducted to assess the link between AF and dementia. One study disclosed a high incidence of dementia among patients suffering from atrial fibrillation during a 4.6 years follow-up. Similarly another study showed that atrial fibrillation was significantly associated with conversion from mild cognitive impairment to dementia during a 3 years follow-up. Nevertheless two other longitudinal studies did not find any significant association between AF and dementia, but this discrepancy should be interpreted taking into account that the comparability of all these studies is moderate because they were using different methodologies (population, cognitive testing, and mean follow-up). Possible explanatory mechanisms for the association between AF and the risk of dementia are proposed, such as thrombo-embolic ischemic damage and cerebral hypo perfusion due to fluctuations in the cardiac output. Thus, there is some evidence that FA could be associated with cognitive decline and dementia but this link should be supported by more powerful long term longitudinal studies. PMID- 20739260 TI - [DEX and executive dysfunction in activities of daily living in Alzheimer's disease and frontotemporal dementia]. AB - The questionnaire DEX was designed by Wilson et al. in 1996 to explore the disturbances of executive functions (EF) in activities of daily living (ADL). OBJECTIVE: This study was performed to explore the specificity of the DEX to evaluate executive dysfunction in ADL, and its contribution to the distinction between Alzheimer's disease (AD) and frontotemporal dementia (FTD). SUBJECTS: 13 patients with the frontal variant of FTD, 19 patients with FTD associated with amyotrophic lateral sclerosis, FTD/SLA, 18 patients with Alzheimer's disease, AD, and 24 controlled subjects. METHODS: The scores on the DEX completed by a proxy as well as those on two scales assessing ADL (the Cognitive Difficulties Scale by McNair & Kahn, and a composite scale (NADL) including the evaluation of basic (BADL) and instrumental (IADL) by the Lawton & Brody scales, and of social activities (SADL) from Katz & Lyerly) were compared to neuropsychological tests assessing EF (Behavioural Assessment of Dysexecutive Syndrome (BADS), Wisconsin Card Sorting Test, Stroop test, Trail Making Test B, lexical and categorical verbal fluencies, WAIS-III similarities). RESULTS: No correlation was found between the scores on the DEX or the other ADL scales, and the BADS scores. Scores on DEX showed some weak correlations with some executive tasks, but no stronger than those found with the other ADL scales. Analysis of the most frequently perturbed DEX items failed to show a characteristic profile for EF dysfunction. No significant difference was found between patients with AD and DFT on the scores on the DEX as well as on other ADL scales, when adjusted for dementia severity (assessed by the Mattis Dementia Rating Scale (MDRS)). No difference was found between MA and DFT patients neither in the profile of the most frequently perturbed DEX items, nor in decreased awareness of the disorders assessed by comparison of the scores on the DEX completed by patients and familiars. CONCLUSION: In this study, DEX does not appear as a specific tool for assessing EF dysfunction in ADL compared to other ADL scales. It was more related to global cognitive difficulties as assessed by the CDS and the MDRS. Scores on the DEX as well as on other ADL scales do not contribute to the distinction between AD and FTD. PMID- 20739261 TI - [Treatment of primary hepatocellular carcinoma]. AB - Primary hepatocellular cancer is the fifth most common solid tumor worldwide. Its incidence is the highest in the Third World, however, a risen incidence has been observed recently also in developed countries, due to increasing migration. In Asia and Africa the main etiological factor for HCC is chronic HBV infection, whereas in the Western world HCV etiology predominates. Additional increase in HCC incidence is expected as a consequence of climate change, since risk of aflatoxin contamination in agricultural products increases with hot and dry growing conditions. Aflatoxins are the most potent hepatocarcinogens in nature; therefore minimization of aflatoxin exposition will be a main task of food security in the future. The majority of HCC patients are diagnosed in advanced stages, and treatment possibilities are limited for this patient population. Follow-up of risk populations by means of tumor surveillance is therefore essential. Experience with systemic chemotherapy has been disappointing with low response rates and high toxicity. Recently, novel treatment options have emerged, including the use of specific targeted agents, blockers of signaling pathways involved in hepatocarcinogenesis. Sorafenib, an oral multikinase-inhibitor is the first systemic agent to demonstrate survival benefit in advanced hepatocellular cancer. Several new, promising therapeutic options are being tested in clinical trials. PMID- 20739262 TI - [Symptoms, diagnosis and treatment of radiation-induced enteritis]. AB - The number of radiotherapy in the treatment of malignant diseases is increasing worldwide. During the radiotherapy of tumors in the minor pelvis and abdomen intestinal inflammation of different degree may occur even if special attention is paid. Irradiation to the minor pelvis causes in half of the cases radiation induced acute enteritis, whereas in 25% chronic enteritis and colitis will develop. Chronic enteritis following radiotherapy raises a number of diagnostic and therapeutic problems that can be solved only with cooperation of different specialties. Authors present a short review regarding therapeutical options of radiation induced enteritis. PMID- 20739263 TI - [Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion]. AB - The concentration of deuterium is about 150 ppm (over 16 mmol/L) in surface water and more than 10 mmol/L in living organisms. Experiments with deuterium depleted water (30+/-5 ppm) revealed that due to D-depletion various tumorous cell lines (PC-3, human prostate, MDA, human breast, HT-29, human colon, M14, human melanoma) required longer time to multiply in vitro. DDW caused tumor regression in xenotransplanted mice (MDA and MCF-7, human breast, PC-3) and induced apoptosis in vitro and in vivo. Deuterium depleted water (25+/-5 ppm) induced complete or partial tumor regression in dogs and cats with spontaneous malignancies, it was registered as anticancer for veterinary use in 1999 (Vetera DDW-25 A.U.V., 13/99 FVM). The hypodermic preparation of the registered veterinary drug was successfully tested in clinical investigations. Under the permission of the Hungarian Institute of Pharmacology (No. 5621/40/95) a randomized, double blind controlled, human Phase II clinical trial with prostate cancer was performed, in compliance with GCP principles, which exhibited a significant difference between the control and treated groups with respect to the examined parameters, median survival time and the extension of life-span. We suggest that cells are able to regulate the D/H ratio and the changes in the D/H ratio can trigger certain molecular mechanisms having a key role in cell cycle regulation. We suppose that not the shift in the intracellular pH, but the concomitant increase in the D/H ratio is the real trigger for the cells to enter into S phase. The decrease of D concentration can intervene in the signal transduction pathways thus leading to tumor regression. Deuterium depletion may open new perspectives in cancer treatment and prevention helping to increase the effectiveness of current oncotherapies. PMID- 20739264 TI - [Endangered future: education and replacement of specialists in neurology--a survey, 2010]. AB - Lack of neurologists has become an obvious problem in Hungary recently, not only in small hospitals, but also in major health care centers and university hospitals. With the current survey we set forth to estimate the number of board certified neurologists and to evaluate the foreseeable changes in the next decade. In the beginning of 2010 there were 1310 physicians in Hungary with an official license to practice neurology. During 2009, neurological performance at least once during the year was claimed to the National Health Insurance Fund by 948 board certified neurologists. The number of those neurologists who are routinely involved in neurological patient care was estimated to be around 750. The lack of the young generation is characteristic for the age distribution of neurologists. In 9 out of the 19 counties of Hungary, the number of neurologists below the age of 35 is 1 or zero. In the ten-year period of 2000-2009, the annual mean number of new board certifications in neurology was 22. This number is much lower than that needed to replace those who get employed abroad and who leave the system for other reasons. The number of neurologists in the age range of 40-60 years will drop to 2/3 of the current number by 2020 even if emigration of neurologists will completely halt. If emigration will continue at the current rate and the number of those in neurological training will not increase considerably, then by 2020 only about 300 neurologists will have to cover neurological services throughout Hungary. As this number is insufficient for the task, and the tendency is clearly foreseeable, the health care government should urgently react to this situation to ensure an acceptable level of neurological services in the near future for the population of Hungary. PMID- 20739265 TI - [Tribute to Dr Peter Adler, professor of dentistry, on his birth centenary (1910 1983)]. PMID- 20739266 TI - [Thoughts on the legal history of public health in Hungary]. PMID- 20739268 TI - Prevalence of cardiac diastolic dysfunction in HIV-infected patients: results of the HIV-HEART study. AB - PURPOSE: Antiretroviral therapy has improved the prognosis for many individuals with HIV infection. Consequently, HIV infection has become a chronic and manageable disease with increased risk of cardiovascular disease. Isolated diastolic dysfunction (DD) may be the first indication of underlying cardiac disease and an early marker of coronary artery disease. Our aim was to assess the prevalence of DD in HIV-infected patients. METHODS: In this cross-sectional cohort study, 698 unselected patients were included. All subjects underwent two dimensional transthoracic echocardiography with tissue Doppler imaging. RESULTS: The prevalence of DD among the HIV-infected patients was 48%. Patients with DD were characterized by older age, higher body mass index, higher total cholesterol, arterial hypertension, and diabetes mellitus. Diabetes mellitus and arterial hypertension were associated with approximately four times the risk for DD (odds ratio [OR] 3.9, 95% CI 1.65-9.17; OR 3.8, 95% CI 2.49-5.71, respectively). Persons with hyperlipidemia were approximately one and a half times more likely to have DD than those without hyperlipidemia (OR 1.5, 95% CI 1.12-2.07). CONCLUSIONS: In our study, an impressive high prevalence of DD in HIV infected patients was demonstrated. Traditional cardiovascular risk factors substantially contributed to the development of DD in the HIV-infected cohort. PMID- 20739269 TI - Differences in rapid initiation and termination of voluntary postural sway associated with ageing and falls-risk. AB - The authors examined differences between young adults (n = 25) and healthy older adults (n = 48) in reaction time and the relations between center of pressure (COP) and center of mass (COM) motions during rapid initiation and termination of voluntary postural sway. Older adults were divided into low and high falls-risk groups based on Physiological Profile Assessment scores of sensorimotor function. Low falls-risk older adults had slower reaction times during anteroposterior sway initiation and decreased COP-COM separation during anteroposterior and medialateral sway initiation and anteroposterior continuous voluntary sway compared with young adults. High falls-risk older adults had slower initiation and termination reaction times in all response directions and decreased COP-COM separation during sway initiation and continuous voluntary sway in the anteroposterior and medialateral directions compared with young adults. Compared with low falls-risk older adults, high falls-risk older adults had slower initiation and termination reaction times in all response directions and decreased COP-COM separation during medialateral continuous voluntary sway. Reaction time and COP-COM measures significantly predicted group status in discriminant models with sensitivities and specificities of 72-100%. Overall, these findings highlight important associations of age-related declines in sensorimotor function related to an increased risk of falling with slower postural reaction time and reduced postural stability. PMID- 20739270 TI - No association between music ability and hand preference in children. AB - Hand preference was studied in 2 groups of children-children with musical ability and children without musical ability-to examine whether particular markers that may connect with handedness patterns, such as bias away from dextrality or mixed handedness, stabilize during childhood and are associated with musical ability. Children were administered the Edinburgh Handedness Inventory to determine levels of right, left, and mixed handedness. Results demonstrated no differences in hand preference between both cohorts of children, suggesting the relative independence of musical ability and handedness. However, the inclusion of handedness as a motor marker for musical ability in children in conjunction with other preexisting neurocognitive factors cannot be entirely discounted. PMID- 20739271 TI - Structural analysis of a Synechococcus myovirus S-CAM4 and infected cells by atomic force microscopy. AB - A tailed cyanophage, S-CAM4 (family Myoviridae) from California coastal waters that infects Synechococcus, was characterized by atomic force microscopy. Capsomeric clusters of protein composing the 85 nm diameter icosahedral head were resolved and indicated a triangulation number of T=16. The 140 nm tail assembly, exhibiting a helical appearance with a 13 nm pitch, was seen in both extended and contracted states, the latter exposing the injection tube within. Attached below the base plate were six 50 nm long fibres, and six fibres 275-300 nm in length protruded from the periphery of the base plate. Protein-free DNA was abundant from ruptured heads. Virus attached en masse, in clusters and individually to cells, and cell fragments were recorded, as were perforated cells lysed by the phages. The capsid structure appears most closely related to that of the cyanophage Syn9 and the Bacillus subtilis phage SPO1, which may, in turn, be evolutionarily related to herpesvirus. PMID- 20739272 TI - Complete sequence of Great Island virus and comparison with the T2 and outer capsid proteins of Kemerovo, Lipovnik and Tribec viruses (genus Orbivirus, family Reoviridae). AB - The complete nucleotide sequence of Great Island virus (GIV) genome was determined, along with genome segments (Seg) 1, 2 and 6 of Kemerovo (KEMV), Lipovnik (LIPV) and Tribec (TRBV) viruses. All four viruses, together with Broadhaven virus, are currently classified within the species Great Island virus and have been isolated from ticks, birds or humans. Sequence comparisons showed that Seg-4 of GIV encoded the outer-capsid protein responsible for cell attachment, although it was approximately half the length of its counterpart in the Culicoides or mosquito-transmitted orbiviruses. A second overlapping ORF (in the +2 reading frame) was identified in Seg-9 of GIV, encoding a putative dsRNA binding protein. Phylogenetic analyses of the RNA-dependent RNA polymerase (Pol) and T2 protein amino acid sequences indicated that the tick-borne orbiviruses represent an ancestral group from which the mosquito-borne orbiviruses have evolved. This mirrors the evolutionary relationships between the arthropod vectors of these viruses, supporting a co-speciation hypothesis for these arboviruses and their arthropod-vectors. Phylogenetic analyses of the T2 proteins of KEMV, LIPV, TRBV and GIV (showing 82% amino acid identity) correlated with the early classification of Great Island viruses as two distinct serocomplexes (Great Island and Kemerovo serocomplexes). Amino acid identity levels in the VP1(Pol) and T2 proteins between the two serocomplexes were 73 and 82%, respectively, whilst those between previously characterized Orbivirus species are 53-73% and 26 83%, respectively. These data suggest that, despite limited genome segment reassortment between these two groups, their current classification within the same Orbivirus species could be re-evaluated. PMID- 20739273 TI - p15RS attenuates Wnt/{beta}-catenin signaling by disrupting {beta}-catenin.TCF4 Interaction. AB - The formation of a beta-catenin.TCF4 complex in the nucleus of cells is well known as a prerequisite for the transcription of Wnt target genes. Although many co-factors have been identified to regulate the activity of the beta-catenin.TCF4 complex, it remains unclear how the complex association is negatively regulated. In this study, we report that p15RS, a negative regulator of the cell cycle, blocks beta-catenin.TCF4 complex formation and inhibits Wnt signaling. We observed that p15RS interacts with beta-catenin and TCF4. Interestingly, whereas the interaction of p15RS with beta-catenin is increased, its interaction with TCF4 is decreased upon Wnt1 stimulation. Moreover, overexpression of p15RS reduces the interaction of beta-catenin with TCF4, whereas the depletion of p15RS enhances their interaction. We further demonstrate that overexpression of p15RS suppresses canonical Wnt signaling and results in retarded cell growth, whereas depletion of p15RS shows an enhanced effect on Wnt signaling. We analyzed that inhibition of Wnt signaling by p15RS leads to decreased expression of CYCLIN D1 and c-MYC, two Wnt targeted genes critical for cell growth. Our data suggest that p15RS inhibits Wnt signaling by interrupting beta-catenin.TCF4 complex formation and that Wnt signaling initiates downstream gene expression by removing p15RS from promoters. PMID- 20739274 TI - Epigenetic silencing of beta-spectrin, a TGF-beta signaling/scaffolding protein in a human cancer stem cell disorder: Beckwith-Wiedemann syndrome. AB - Hereditary cancer syndromes provide powerful insights into dysfunctional signaling pathways that lead to sporadic cancers. Beckwith-Wiedemann syndrome (BWS) is a hereditary human cancer stem cell syndrome currently linked to deregulated imprinting at chromosome 11p15 and uniparental disomy. However, causal molecular defects and genetic models have remained elusive to date in the majority of cases. The non-pleckstrin homology domain beta-spectrin (beta2SP) (the official name for human is Spectrin, beta, nonerythrocytic 1 (SPTBN1), isoform 2; the official name for mouse is Spectrin beta 2 (Spnb2), isoform 2), a scaffolding protein, functions as a potent TGF-beta signaling member adaptor in tumor suppression and development. Yet, the role of the beta2SP in human tumor syndromes remains unclear. Here, we report that beta2SP(+/-) mice are born with many phenotypic characteristics observed in BWS patients, suggesting that beta2SP mutant mice phenocopy BWS, and beta2SP loss could be one of the mechanisms associated with BWS. Our results also suggest that epigenetic silencing of beta2SP is a new potential causal factor in human BWS patients. Furthermore, beta2SP(+/-) mice provide an important animal model for BWS, as well as sporadic cancers associated with it, including lethal gastrointestinal and pancreatic cancer. Thus, these studies could lead to further insight into defects generated by dysfunctional stem cells and identification of new treatment strategies and functional markers for the early detection of these lethal cancers that otherwise cannot be detected at an early stage. PMID- 20739275 TI - Regulation of human cytidine triphosphate synthetase 2 by phosphorylation. AB - Cytidine triphosphate synthetase (CTPS) is the rate-limiting enzyme in de novo CTP synthesis and is required for the formation of RNA, DNA, and phospholipids. This study determined the kinetic properties of the individual human CTPS isozymes (hCTPS1 and hCTPS2) and regulation through substrate concentration, oligomerization, and phosphorylation. Kinetic analysis demonstrated that both hCTPS1 and hCTPS2 were maximally active at physiological concentrations of ATP, GTP, and glutamine, whereas the K(m) and IC(50) values for the substrate UTP and the product CTP, respectively, were close to their physiological concentrations, indicating that the intracellular concentrations of UTP and CTP may precisely regulate hCTPS activity. Low serum treatment increased hCTPS2 phosphorylation, and five probable phosphorylation sites were identified in the hCTPS2 C-terminal domain. Metabolic labeling of hCTPS2 with [(32)P]H(3)PO(4) demonstrated that Ser(568) and Ser(571) were two major phosphorylation sites, and additional studies demonstrated that Ser(568) was phosphorylated by casein kinase 1 both in vitro and in vivo. Interestingly, mutation of Ser(568) (S568A) but not Ser(571) significantly increased hCTPS2 activity, demonstrating that Ser(568) is a major inhibitory phosphorylation site. The S568A mutation had a greater effect on the glutamine than ammonia-dependent activity, indicating that phosphorylation of this site may influence the glutaminase domain of hCTPS2. Deletion of the C terminal regulatory domain of hCTPS1 also greatly increased the V(max) of this enzyme. In summary, this is the first study to characterize the kinetic properties of hCTPS1 and hCTPS2 and to identify Ser(568) as a major site of CTPS2 regulation by phosphorylation. PMID- 20739276 TI - Nucleosome interactions and stability in an ordered nucleosome array model system. AB - Although it is well established that the majority of eukaryotic DNA is sequestered as nucleosomes, the higher-order structure resulting from nucleosome interactions as well as the dynamics of nucleosome stability are not as well understood. To characterize the structural and functional contribution of individual nucleosomal sites, we have developed a chromatin model system containing up to four nucleosomes, where the array composition, saturation, and length can be varied via the ordered ligation of distinct mononucleosomes. Using this system we find that the ligated tetranucleosomal arrays undergo intra-array compaction. However, this compaction is less extensive than for longer arrays and is histone H4 tail-independent, suggesting that well ordered stretches of four or fewer nucleosomes do not fully compact to the 30-nm fiber. Like longer arrays, the tetranucleosomal arrays exhibit cooperative self-association to form species composed of many copies of the array. This propensity for self-association decreases when the fraction of nucleosomes lacking H4 tails is systematically increased. However, even tetranucleosomal arrays with only two octamers possessing H4 tails recapitulate most of the inter-array self-association. Varying array length shows that systems as short as dinucleosomes demonstrate significant self-association, confirming that relatively few determinants are required for inter-array interactions and suggesting that in vivo multiple interactions of short runs of nucleosomes might contribute to complex fiber-fiber interactions. Additionally, we find that the stability of nucleosomes toward octamer loss increases with array length and saturation, suggesting that in vivo stretches of ordered, saturated nucleosomes could serve to protect these regions from histone ejection. PMID- 20739277 TI - Novel mechanisms in the regulation of G protein-coupled receptor trafficking to the plasma membrane. AB - beta(2)-adrenergic receptors (beta(2)-AR) are low abundance, integral membrane proteins that mediate the effects of catecholamines at the cell surface. Whereas the processes governing desensitization of activated beta(2)-ARs and their subsequent removal from the cell surface have been characterized in considerable detail, little is known about the mechanisms controlling trafficking of neo synthesized receptors to the cell surface. Since the discovery of the signal peptide, the targeting of the integral membrane proteins to plasma membrane has been thought to be determined by structural features of the amino acid sequence alone. Here we report that localization of translationally silenced beta(2)-AR mRNA to the peripheral cytoplasmic regions is critical for receptor localization to the plasma membrane. beta(2)-AR mRNA is recognized by the nucleocytoplasmic shuttling RNA-binding protein HuR, which silences translational initiation while chaperoning the mRNA-protein complex to the cell periphery. When HuR expression is down-regulated, beta(2)-AR mRNA translation is initiated prematurely in perinuclear polyribosomes, leading to overproduction of receptors but defective trafficking to the plasma membrane. Our results underscore the importance of the spatiotemporal relationship between beta(2)-AR mRNA localization, translation, and trafficking to the plasma membrane, and establish a novel mechanism whereby G protein-coupled receptor (GPCR) responsiveness is regulated by RNA-based signals. PMID- 20739278 TI - Crystal structure of an Exo-1,5-{alpha}-L-arabinofuranosidase from Streptomyces avermitilis provides insights into the mechanism of substrate discrimination between exo- and endo-type enzymes in glycoside hydrolase family 43. AB - Exo-1,5-alpha-L-arabinofuranosidases belonging to glycoside hydrolase family 43 have strict substrate specificity. These enzymes hydrolyze only the alpha-1,5 linkages of linear arabinan and arabino-oligosaccharides in an exo-acting manner. The enzyme from Streptomyces avermitilis contains a core catalytic domain belonging to glycoside hydrolase family 43 and a C-terminal arabinan binding module belonging to carbohydrate binding module family 42. We determined the crystal structure of intact exo-1,5-alpha-L-arabinofuranosidase. The catalytic module is composed of a 5-bladed beta-propeller topologically identical to the other family 43 enzymes. The arabinan binding module had three similar subdomains assembled against one another around a pseudo-3-fold axis, forming a beta-trefoil fold. A sugar complex structure with alpha-1,5-L-arabinofuranotriose revealed three subsites in the catalytic domain, and a sugar complex structure with alpha L-arabinofuranosyl azide revealed three arabinose-binding sites in the carbohydrate binding module. A mutagenesis study revealed that substrate specificity was regulated by residues Asn-159, Tyr-192, and Leu-289 located at the aglycon side of the substrate-binding pocket. The exo-acting manner of the enzyme was attributed to the strict pocket structure of subsite -1, formed by the flexible loop region Tyr-281-Arg-294 and the side chain of Tyr-40, which occupied the positions corresponding to the catalytic glycon cleft of GH43 endo-acting enzymes. PMID- 20739279 TI - N-glycosylation at the SynCAM (synaptic cell adhesion molecule) immunoglobulin interface modulates synaptic adhesion. AB - Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses. The regulation of these trans-synaptic interactions is an important neurobiological question. We have previously shown that the synaptic cell adhesion molecules (SynCAMs) 1 and 2 engage in homo- and heterophilic interactions and bridge the synaptic cleft to induce presynaptic terminals. Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions. Through crystallographic analysis of SynCAM 2, we identified within the adhesive interface of its Ig1 domain an N glycan on residue Asn(60). Structural modeling of the corresponding SynCAM 1 Ig1 domain indicates that its glycosylation sites Asn(70)/Asn(104) flank the binding interface of this domain. Mass spectrometric and mutational studies confirm and characterize the modification of these three sites. These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner. Although glycosylation of SynCAM 2 at Asn(60) reduces adhesion, N-glycans at Asn(70)/Asn(104) of SynCAM 1 increase its interactions. The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding. Functionally, N glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction. These results demonstrate that N-glycosylation of SynCAM proteins differentially affects their binding interface and implicate post translational modification as a mechanism to regulate trans-synaptic adhesion. PMID- 20739280 TI - Mutational insights into the roles of amino acid residues in ligand binding for two closely related family 16 carbohydrate binding modules. AB - Carbohydrate binding modules (CBMs) are specialized proteins that bind to polysaccharides and oligosaccharides. Caldanaerobius polysaccharolyticus Man5ACBM16-1/CBM16-2 bind to glucose-, mannose-, and glucose/mannose-configured substrates. The crystal structures of the two proteins represent the only examples in CBM family 16, and studies that evaluate the roles of amino acid residues in ligand binding in this family are lacking. In this study, we probed the roles of amino acids (selected based on CBM16-1/ligand co-crystal structures) on substrate binding. Two tryptophan (Trp-20 and Trp-125) and two glutamine (Gln 81 and Gln-93) residues are shown to be critical in ligand binding. Additionally, several polar residues that flank the critical residues also contribute to ligand binding. The CBM16-1 Q121E mutation increased affinity for all substrates tested, whereas the Q21G and N97R mutants exhibited decreased substrate affinity. We solved CBM/substrate co-crystal structures to elucidate the molecular basis of the increased substrate binding by CBM16-1 Q121E. The Gln-121, Gln-21, and Asn-97 residues can be manipulated to fine-tune ligand binding by the Man5A CBMs. Surprisingly, none of the eight residues investigated was absolutely conserved in CBM family 16. Thus, the critical residues in the Man5A CBMs are either not essential for substrate binding in the other members of this family or the two CBMs are evolutionarily distinct from the members available in the current protein database. Man5A is dependent on its CBMs for robust activity, and insights from this study should serve to enhance our understanding of the interdependence of its catalytic and substrate binding modules. PMID- 20739281 TI - In vitro and in vivo analysis of the binding of the C terminus of the HDL receptor scavenger receptor class B, type I (SR-BI), to the PDZ1 domain of its adaptor protein PDZK1. AB - The PDZ1 domain of the four PDZ domain-containing protein PDZK1 has been reported to bind the C terminus of the HDL receptor scavenger receptor class B, type I (SR BI), and to control hepatic SR-BI expression and function. We generated wild-type (WT) and mutant murine PDZ1 domains, the mutants bearing single amino acid substitutions in their carboxylate binding loop (Lys(14)-Xaa(4)-Asn(19)-Tyr-Gly Phe-Phe-Leu(24)), and measured their binding affinity for a 7-residue peptide corresponding to the C terminus of SR-BI ((503)VLQEAKL(509)). The Y20A and G21Y substitutions abrogated all binding activity. Surprisingly, binding affinities (K(d)) of the K14A and F22A mutants were 3.2 and 4.0 MUM, respectively, similar to 2.6 MUM measured for the WT PDZ1. To understand these findings, we determined the high resolution structure of WT PDZ1 bound to a 5-residue sequence from the C terminal SR-BI ((505)QEAKL(509)) using x-ray crystallography. In addition, we incorporated the K14A and Y20A substitutions into full-length PDZK1 liver specific transgenes and expressed them in WT and PDZK1 knock-out mice. In WT mice, the transgenes did not alter endogenous hepatic SR-BI protein expression (intracellular distribution or amount) or lipoprotein metabolism (total plasma cholesterol, lipoprotein size distribution). In PDZK1 knock-out mice, as expected, the K14A mutant behaved like wild-type PDZK1 and completely corrected their hepatic SR-BI and plasma lipoprotein abnormalities. Unexpectedly, the 10-20 fold overexpressed Y20A mutant also substantially, but not completely, corrected these abnormalities. The results suggest that there may be an additional site(s) within PDZK1 that bind(s) SR-BI and mediate(s) productive SR-BI-PDZK1 interaction previously attributed exclusively to the canonical binding of the C-terminal SR BI to PDZ1. PMID- 20739282 TI - Identification of protein-protein and protein-ribosome interacting regions of the C-terminal tail of human mitochondrial inner membrane protein Oxa1L. AB - The mammalian mitochondrial inner membrane protein Oxa1L is involved in the insertion of a number of mitochondrial translation products into the inner membrane. During this process, the C-terminal tail of Oxa1L (Oxa1L-CTT) binds mitochondrial ribosomes and is believed to coordinate the synthesis and membrane insertion of the nascent chains into the membrane. The C-terminal tail of Oxa1L does not contain any Cys residues. Four variants of this protein with a specifically placed Cys residue at position 4, 39, 67, or 94 of Oxa1L-CTT have been prepared. These Cys residues have been derivatized with a fluorescent probe, tetramethylrhodamine-5-maleimide, for biophysical studies. Oxa1L-CTT forms oligomers cooperatively with a binding constant in the submicromolar range. Fluorescence anisotropy and fluorescence lifetime measurements indicate that contacts near a long helix close to position 39 of Oxa1L-CTT occur during oligomer formation. Fluorescence correlation spectroscopy measurements demonstrate that all of the Oxa1L-CTT derivatives bind to mammalian mitochondrial ribosomes. Steady-state fluorescence quenching and fluorescence lifetime data indicate that there are extensive contacts between Oxa1L-CTT and the ribosome encompassing regions around positions 39, 67, and 94. The results of this study suggest that Oxa1L-CTT undergoes conformational changes and induced oligomer formation when it binds to the ribosome. PMID- 20739283 TI - Implications for collagen binding from the crystallographic structure of fibronectin 6FnI1-2FnII7FnI. AB - Collagen and fibronectin (FN) are two abundant and essential components of the vertebrate extracellular matrix; they interact directly with cellular receptors and affect cell adhesion and migration. Past studies identified a FN fragment comprising six modules, (6)FnI(1-2)FnII(7-9)FnI, and termed the gelatin binding domain (GBD) as responsible for collagen interaction. Recently, we showed that the GBD binds tightly to a specific site within type I collagen and determined the structure of domains (8-9)FnI in complex with a peptide from that site. Here, we present the crystallographic structure of domains (6)FnI(1-2)FnII(7)FnI, which form a compact, globular unit through interdomain interactions. Analysis of NMR titrations with single-stranded collagen peptides reveals a dominant collagen interaction surface on domains (2)FnII and (7)FnI; a similar surface appears involved in interactions with triple-helical peptides. Models of the complete GBD, based on the new structure and the (8-9)FnI.collagen complex show a continuous putative collagen binding surface. We explore the implications of this model using long collagen peptides and discuss our findings in the context of FN interactions with collagen fibrils. PMID- 20739284 TI - Crystal structures of phosphoketolase: thiamine diphosphate-dependent dehydration mechanism. AB - Thiamine diphosphate (ThDP)-dependent enzymes are ubiquitously present in all organisms and catalyze essential reactions in various metabolic pathways. ThDP dependent phosphoketolase plays key roles in the central metabolism of heterofermentative bacteria and in the pentose catabolism of various microbes. In particular, bifidobacteria, representatives of beneficial commensal bacteria, have an effective glycolytic pathway called bifid shunt in which 2.5 mol of ATP are produced per glucose. Phosphoketolase catalyzes two steps in the bifid shunt because of its dual-substrate specificity; they are phosphorolytic cleavage of fructose 6-phosphate or xylulose 5-phosphate to produce aldose phosphate, acetyl phosphate, and H(2)O. The phosphoketolase reaction is different from other well studied ThDP-dependent enzymes because it involves a dehydration step. Although phosphoketolase was discovered more than 50 years ago, its three-dimensional structure remains unclear. In this study we report the crystal structures of xylulose 5-phosphate/fructose 6-phosphate phosphoketolase from Bifidobacterium breve. The structures of the two intermediates before and after dehydration (alpha,beta-dihydroxyethyl ThDP and 2-acetyl-ThDP) and complex with inorganic phosphate give an insight into the mechanism of each step of the enzymatic reaction. PMID- 20739285 TI - Structure of Rpn10 and its interactions with polyubiquitin chains and the proteasome subunit Rpn12. AB - Schizosaccharomyces pombe Rpn10 (SpRpn10) is a proteasomal ubiquitin (Ub) receptor located within the 19 S regulatory particle where it binds to subunits of both the base and lid subparticles. We have solved the structure of full length SpRpn10 by determining the crystal structure of the von Willebrand factor type A domain and characterizing the full-length protein by NMR. We demonstrate that the single Ub-interacting motif (UIM) of SpRpn10 forms a 1:1 complex with Lys(48)-linked diUb, which it binds selectively over monoUb and Lys(63)-linked diUb. We further show that the SpRpn10 UIM binds to SpRpn12, a subunit of the lid subparticle, with an affinity comparable with Lys(48)-linked diUb. This is the first observation of a UIM binding other than a Ub fold and suggests that SpRpn12 could modulate the activity of SpRpn10 as a proteasomal Ub receptor. PMID- 20739287 TI - Integrin {beta}3 phosphorylation dictates its complex with the Shc phosphotyrosine-binding (PTB) domain. AB - Adaptor protein Shc plays a key role in mitogen-activated protein kinase (MAPK) signaling pathway, which can be mediated through a number of different receptors including integrins. By specifically recognizing the tyrosine-phosphorylated integrin beta(3), Shc has been shown to trigger integrin outside-in signaling, although the structural basis of this interaction remains nebulous. Here we present the detailed structural analysis of Shc phosphotyrosine-binding (PTB) domain in complex with the bi-phosphorylated beta(3)integrin cytoplasmic tail (CT). We show that this complex is primarily defined by the phosphorylation state of the integrin C-terminal Tyr(759), which fits neatly into the classical PTB pocket of Shc. In addition, we have identified a novel binding interface which concurrently accommodates phosphorylated Tyr(747) of the highly conserved NPXY motif of beta(3). The structure represents the first snapshot of an integrin cytoplasmic tail bound to a target for mediating the outside-in signaling. Detailed comparison with the known Shc PTB structure bound to a target TrkA peptide revealed some significant differences, which shed new light upon the PTB domain specificity. PMID- 20739286 TI - Allostery is an intrinsic property of the protease domain of DegS: implications for enzyme function and evolution. AB - DegS is a periplasmic Escherichia coli protease, which functions as a trimer to catalyze the initial rate-limiting step in a proteolytic cascade that ultimately activates transcription of stress response genes in the cytoplasm. Each DegS subunit consists of a protease domain and a PDZ domain. During protein folding stress, DegS is allosterically activated by peptides exposed in misfolded outer membrane porins, which bind to the PDZ domain and stabilize the active protease. It is not known whether allostery is conferred by the PDZ domains or is an intrinsic feature of the trimeric protease domain. Here, we demonstrate that free DegS(DeltaPDZ) equilibrates between active and inactive trimers with the latter species predominating. Substrate binding stabilizes active DegS(DeltaPDZ) in a positively cooperative fashion. Mutations can also stabilize active DegS(DeltaPDZ) and produce an enzyme that displays hyperbolic kinetics and degrades substrate with a maximal velocity within error of that for fully activated, intact DegS. Crystal structures of multiple DegS(DeltaPDZ) variants, in functional and non-functional conformations, support a two-state model in which allosteric switching is mediated by changes in specific elements of tertiary structure in the context of an invariant trimeric base. Overall, our results indicate that protein substrates must bind sufficiently tightly and specifically to the functional conformation of DegS(DeltaPDZ) to assist their own degradation. Thus, substrate binding alone may have regulated the activities of ancestral DegS trimers with subsequent fusion of the protease domain to a PDZ domain, resulting in ligand-mediated regulation. PMID- 20739288 TI - Flap endonuclease 1 mechanism analysis indicates flap base binding prior to threading. AB - FEN1 cleaves 5' flaps at their base to create a nicked product for ligation. FEN1 has been reported to enter the flap from the 5'-end and track to the base. Current binding analyses support a very different mechanism of interaction with the flap substrate. Measurements of FEN1 binding to a flap substrate show that the nuclease binds with similar high affinity to the base of a long flap even when the 5'-end is blocked with biotin/streptavidin. However, FEN1 bound to a blocked flap is more sensitive to sequestration by a competing substrate. These results are consistent with a substrate interaction mechanism in which FEN1 first binds the flap base and then threads the flap through an opening in the protein from the 5'-end to the base for cleavage. Significantly, when the unblocked flap length is reduced from five to two nucleotides, FEN1 can be sequestered from the substrate to a similar extent as a blocked, long flap substrate. Apparently, interactions related to threading occur only when the flap is greater than two to four nucleotides long, implying that short flaps are cleaved without a threading requirement. PMID- 20739289 TI - Pseudomonas aeruginosa Homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl- secretion by human airway epithelia. AB - The ubiquitous bacterium Pseudomonas aeruginosa frequently causes hospital acquired infections. P. aeruginosa also infects the lungs of cystic fibrosis (CF) patients and secretes N-(3-oxo-dodecanoyl)-S-homoserine lactone (3O-C12) to regulate bacterial gene expression critical for P. aeruginosa persistence. In addition to its effects as a quorum-sensing gene regulator in P. aeruginosa, 3O C12 elicits cross-kingdom effects on host cell signaling leading to both pro- or anti-inflammatory effects. We find that in addition to these slow effects mediated through changes in gene expression, 3O-C12 also rapidly increases Cl(-) and fluid secretion in the cystic fibrosis transmembrane regulator (CFTR) expressing airway epithelia. 3O-C12 does not stimulate Cl(-) secretion in CF cells, suggesting that lactone activates the CFTR. 3O-C12 also appears to directly activate the inositol trisphosphate receptor and release Ca(2+) from the endoplasmic reticulum (ER), lowering [Ca(2+)] in the ER and thereby activating the Ca(2+)-sensitive ER signaling protein STIM1. 3O-C12 increases cytosolic [Ca(2+)] and, strikingly, also cytosolic [cAMP], the known activator of CFTR. Activation of Cl(-) current by 3O-C12 was inhibited by a cAMP antagonist and increased by a phosphodiesterase inhibitor. Finally, a Ca(2+) buffer that lowers [Ca(2+)] in the ER similar to the effect of 3O-C12 also increased cAMP and I(Cl). The results suggest that 3O-C12 stimulates CFTR-dependent Cl(-) and fluid secretion in airway epithelial cells by activating the inositol trisphosphate receptor, thus lowering [Ca(2+)] in the ER and activating STIM1 and store operated cAMP production. In CF airways, where CFTR is absent, the adaptive ability to rapidly flush the bacteria away is compromised because the lactone cannot affect Cl(-) and fluid secretion. PMID- 20739290 TI - Kv7-type channel currents in spiral ganglion neurons: involvement in sensorineural hearing loss. AB - Alterations in K(v)7-mediated currents in excitable cells result in several diseased conditions. A case in DFNA2, an autosomal dominant version of progressive hearing loss, involves degeneration of hair cells and spiral ganglion neurons (SGNs) from basal to apical cochlea, manifesting as high-to-low frequency hearing loss, and has been ascribed to mutations in K(v)7.4 channels. Analyses of the cellular mechanisms of K(v)7.4 mutations and progressive degeneration of SGNs have been hampered by the paucity of functional data on the role K(v)7 channels play in young and adult neurons. To understand the cellular mechanisms of the disease in SGNs, we examined temporal (young, 0.5 months old, and senescent, 17 months old) and spatial (apical and basal) roles of K(v)7-mediated currents. We report that differential contribution of K(v)7 currents in mice SGNs results in distinct and profound variations of the membrane properties of basal versus apical neurons. The current produces a major impact on the resting membrane potential of basal neurons. Inhibition of the current promotes membrane depolarization, resulting in activation of Ca(2+) currents and a sustained rise in intracellular Ca(2+). Using TUNEL assay, we demonstrate that a sustained increase in intracellular Ca(2+) mediated by inhibition of K(v)7 current results in significant SGN apoptotic death. Thus, this study provides evidence of the cellular etiology and mechanisms of SGN degeneration in DFNA2. PMID- 20739291 TI - ATP-binding cassette transporter A1 mediates the beneficial effects of the liver X receptor agonist GW3965 on object recognition memory and amyloid burden in amyloid precursor protein/presenilin 1 mice. AB - The cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) moves lipids onto apolipoproteins including apolipoprotein E (apoE), which is the major cholesterol carrier in the brain and an established genetic risk factor for late onset Alzheimer disease (AD). In amyloid mouse models of AD, ABCA1 deficiency exacerbates amyloidogenesis, whereas ABCA1 overexpression ameliorates amyloid load, suggesting a role for ABCA1 in Abeta metabolism. Agonists of liver X receptors (LXR), including GW3965, induce transcription of several genes including ABCA1 and apoE, and reduce Abeta levels and improve cognition in AD mice. However, the specific role of ABCA1 in mediating beneficial responses to LXR agonists in AD mice is unknown. We evaluated behavioral and neuropathogical outcomes in GW3965-treated female APP/PS1 mice with and without ABCA1. Treatment of APP/PS1 mice with GW3965 increased ABCA1 and apoE protein levels. ABCA1 was required to observe significantly elevated apoE levels in brain tissue and cerebrospinal fluid upon therapeutic (33 mg/kg/day) GW3965 treatment. At 33 mg/kg/day, GW3965 was also associated with a trend toward redistribution of Abeta to the carbonate-soluble pool independent of ABCA1. APP/PS1 mice treated with either 2.5 or 33 mg/kg/day of GW3965 showed a clear trend toward reduced amyloid burden in hippocampus and whole brain, whereas APP/PS1-treated mice lacking ABCA1 failed to display reduced amyloid load in the whole brain and showed trends toward increased hippocampal amyloid. Treatment of APP/PS1 mice with either dose of GW3965 completely restored novel object recognition memory to wild-type levels, which required ABCA1. These results suggest that ABCA1 contributes to several beneficial effects of the LXR agonist GW3965 in APP/PS1 mice. PMID- 20739292 TI - Apolipoprotein A-I deficiency increases cerebral amyloid angiopathy and cognitive deficits in APP/PS1DeltaE9 mice. AB - A hallmark of Alzheimer disease (AD) is the deposition of amyloid beta (Abeta) in brain parenchyma and cerebral blood vessels, accompanied by cognitive decline. Previously, we showed that human apolipoprotein A-I (apoA-I) decreases Abeta(40) aggregation and toxicity. Here we demonstrate that apoA-I in lipidated or non lipidated form prevents the formation of high molecular weight aggregates of Abeta(42) and decreases Abeta(42) toxicity in primary brain cells. To determine the effects of apoA-I on AD phenotype in vivo, we crossed APP/PS1DeltaE9 to apoA I(KO) mice. Using a Morris water maze, we demonstrate that the deletion of mouse Apoa-I exacerbates memory deficits in APP/PS1DeltaE9 mice. Further characterization of APP/PS1DeltaE9/apoA-I(KO) mice showed that apoA-I deficiency did not affect amyloid precursor protein processing, soluble Abeta oligomer levels, Abeta plaque load, or levels of insoluble Abeta in brain parenchyma. To examine the effect of Apoa-I deletion on cerebral amyloid angiopathy, we measured insoluble Abeta isolated from cerebral blood vessels. Our data show that in APP/PS1DeltaE9/apoA-I(KO) mice, insoluble Abeta(40) is increased more than 10 fold, and Abeta(42) is increased 1.5-fold. The increased levels of deposited amyloid in the vessels of cortices and hippocampi of APP/PS1DeltaE9/apoA-I(KO) mice, measured by X-34 staining, confirmed the results. Finally, we demonstrate that lipidated and non-lipidated apoA-I significantly decreased Abeta toxicity against brain vascular smooth muscle cells. We conclude that lack of apoA-I aggravates the memory deficits in APP/PS1DeltaE9 mice in parallel to significantly increased cerebral amyloid angiopathy. PMID- 20739293 TI - Expanding role of the jumonji C domain as an RNA hydroxylase. AB - JmjC (Jumonji C) domain-containing proteins are known to be an extensive family of Fe(II)/2-oxoglutarate-dependent oxygenases involved in epigenetic regulation of gene expression by catalyzing oxidative demethylation of methylated histones. We report here that a human JmjC protein named Tyw5p (TYW5) unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxywybutosine, in tRNA(Phe) by catalyzing hydroxylation. The finding provides an insight into the expanding role of JmjC protein as an RNA hydroxylase. PMID- 20739294 TI - Involvement of 9-O-Acetyl GD3 ganglioside in Mycobacterium leprae infection of Schwann cells. AB - Mycobacterium leprae (ML), the etiologic agent of leprosy, mainly affects the skin and peripheral nerves, leading to demyelization and loss of axonal conductance. Schwann cells (SCs) are the main cell population infected by ML in the nerves, and infection triggers changes in the SC phenotype from a myelinated to a nonmyelinated state. In the present study, we show that expression of 9-O acetyl GD3, a ganglioside involved in cellular anti-apoptotic signaling and nerve regeneration, increases in SCs following infection with ML. Observation by confocal microscopy together with coimmunoprecipitation suggested that this ganglioside participates in ML attachment and internalization by SC. Immunoblockage of 9-O-acetyl GD3 in vitro significantly reduced adhesion of ML to SC surfaces. Finally, we show that activation of the MAPK (ERK 1/2) pathway and SC proliferation, two known effects of ML on SCs that result in demyelization, are significantly reduced when the 9-O-acetyl GD3 ganglioside is immunoblocked. Taken together, these data suggest the involvement of 9-O-acetyl GD3 in ML infection on SCs. PMID- 20739295 TI - The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-kappaB from the synapse to the nucleus. AB - Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB) out of dendritic spines (where NF kappaB is activated by excitatory synaptic input) and supports a high level of active NF-kappaB in neuronal nuclei (where NF-kappaB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD. PMID- 20739301 TI - Subcellular sites of the signal transduction and degradation of phytochrome A. AB - Phytochrome regulates various physiological and developmental processes throughout the life cycle of plants. Among the members of the phytochrome family, phytochrome A (phyA) exclusively mediates the far-red light high irradiance response (FR-HIR), which is elicited by continuous far-red light. In FR-HIR, nuclear accumulation of phyA, which precedes physiological responses, is proposed to be required for the response. In contrast to FR, red light induces rapid degradation of phyA to suppress undesirable long-term photomorphogenic responses of phyA. In the present study, we compared biological activities between phyA derivatives to which either a nuclear localization (NLS) or export (NES) signal sequence was attached. Those derivatives were expressed under the control of the PHYA promoter in the Arabidopsis phyA mutant. Detailed microscopic observation revealed that the phyA-green fluorescent protein (GFP) without a signal sequence is localized exclusively in the cytoplasm in darkness. Rapid nuclear entry was observed after exposure to both red and far-red light. Interestingly, both phyA GFP-NLS and phyA-GFP-NES were rapidly degraded under continuous red light. Furthermore, a proteasome inhibitor delayed degradation equally under these two conditions. Therefore, similar mechanisms for phyA degradation may exist in the cytoplasm and nucleus. As expected from previous reports, phyA-GFP-NLS, but not phyA-GFP-NES, mediated different aspects of FR-HIR, such as inhibition of hypocotyl elongation and rapid induction of gene expression, confirming that phyA nuclear localization is required for FR-HIR. In addition, a detailed time course analysis of phyA-GFP and phyA-GFP-NLS responses revealed that they were almost indistinguishable, raising the question of the physiological relevance of phyA cytoplasmic retention in darkness. PMID- 20739302 TI - A role for AUXIN RESISTANT3 in the coordination of leaf growth. AB - The characteristically flat structure of Arabidopsis thaliana vegetative leaves requires coordinating the growth of the epidermal, palisade mesophyll, spongy mesophyll and vascular tissues. Mutations disrupting such coordination or the specific growth properties of any of these tissues can cause hyponasty, epinasty, waviness or other deviations from flatness. Here, we show that the incurvata6 (icu6) semi-dominant allele of the AUXIN RESISTANT3 (AXR3) gene causes leaf hyponasty. Cotyledons and leaves of icu6/AXR3 plants exhibited reduced size of adaxial pavement cells, and abnormal expansion of palisade mesophyll cells. Enhanced auxin responses in the adaxial domain of icu6/AXR3 developing cotyledons and leaves correlated with increased cell divisions in the adaxial epidermis. Leaf incurvature in icu6/AXR3 leaves was alleviated by loss-of-function alleles of the ASYMMETRIC LEAVES1 (AS1) and AS2 genes, which restrict the expression of class I KNOX genes to the shoot apical meristem and regulate cell proliferation in leaf primordia. Taken together, our results suggest that an interaction between auxin responses and the AS1-AS2 pathway coordinates tissue growth during Arabidopsis thaliana leaf expansion. PMID- 20739296 TI - Genetic background impacts developmental potential of enteric neural crest derived progenitors in the Sox10Dom model of Hirschsprung disease. AB - Abnormalities in the development of enteric neural crest-derived progenitors (ENPs) that generate the enteric nervous system (ENS) can lead to aganglionosis in a variable portion of the distal gastrointestinal tract. Cumulative evidence suggests that variation of aganglionosis is due to gene interactions that modulate the ability of ENPs to populate the intestine; however, the developmental processes underlying this effect are unknown. We hypothesized that differences in enteric ganglion deficits could be attributable to the effects of genetic background on early developmental processes, including migration, proliferation, or lineage divergence. Developmental processes were investigated in congenic Sox10(Dom) mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B6) and C3HeB/FeJ (C3Fe). Immuno-staining on whole-mount fetal gut tissue and dissociated cell suspensions was used to assess migration and proliferation. Flow cytometry utilizing the cell surface markers p75 and HNK-1 was used to isolate live ENPs for analysis of developmental potential. Frequency of ENPs was reduced in Sox10(Dom) embryos relative to wild type embryos, but was unaffected by genetic background. Both migration and developmental potential of ENPs in Sox10(Dom) embryos were altered by inbred strain background with the most highly significant differences seen for developmental potential between strains and genotypes. In vivo imaging of fetal ENPs and postnatal ganglia demonstrates that altered lineage divergence impacts ganglia in the proximal intestine. Our analysis demonstrates that genetic background alters early ENS development and suggests that abnormalities in lineage diversification can shift the proportions of ENP populations and thus may contribute to ENS deficiencies in vivo. PMID- 20739303 TI - Microbial volatile emissions promote accumulation of exceptionally high levels of starch in leaves in mono- and dicotyledonous plants. AB - Microbes emit volatile compounds that affect plant growth and development. However, little or nothing is known about how microbial emissions may affect primary carbohydrate metabolism in plants. In this work we explored the effect on leaf starch metabolism of volatiles released from different microbial species ranging from Gram-negative and Gram-positive bacteria to fungi. Surprisingly, we found that all microbial species tested (including plant pathogens and species not normally interacting with plants) emitted volatiles that strongly promoted starch accumulation in leaves of both mono- and dicotyledonous plants. Starch content in leaves of plants treated for 2 d with microbial volatiles was comparable with or even higher than that of reserve organs such as potato tubers. Transcriptome and enzyme activity analyses of potato leaves exposed to volatiles emitted by Alternaria alternata revealed that starch overaccumulation was accompanied by up-regulation of sucrose synthase, invertase inhibitors, starch synthase class III and IV, starch branching enzyme and glucose-6-phosphate transporter. This phenomenon, designated as MIVOISAP (microbial volatiles-induced starch accumulation process), was also accompanied by down-regulation of acid invertase, plastidial thioredoxins, starch breakdown enzymes, proteins involved in internal amino acid provision and less well defined mechanisms involving a bacterial- type stringent response. Treatment of potato leaves with fungal volatiles also resulted in enhanced levels of sucrose, ADPglucose, UDPglucose and 3-phosphoglycerate. MIVOISAP is independent of the presence of sucrose in the culture medium and is strongly repressed by cysteine supplementation. The discovery that microbial volatiles trigger starch accumulation enhancement in leaves constitutes an unreported mechanism for the elicidation of plant carbohydrate metabolism by microbes. PMID- 20739304 TI - AGC kinase OsOxi1 positively regulates basal resistance through suppression of OsPti1a-mediated negative regulation. AB - OsPti1a, a functional ortholog of tomato SlPti1, negatively regulates both basal resistance and R-gene-mediated resistance in rice. To investigate the molecular function of OsPti1a in defense responses, we searched for components interacting with OsPti1a using a yeast two-hybrid system. One of the interacting proteins is a Ser/Thr kinase that directly phosphorylates OsPti1a in vitro. This protein belongs to the AGC kinase family and is highly similar to AtOxi1, which is induced in response to a wide range of reactive oxygen species (ROS)-generating stimuli in Arabidopsis. Thus, it was designated OsOxi1. OsOxi1 was transiently phosphorylated in response to ROS and chitin elicitor. Both OsOxi1-overexpressing transgenic lines and the ospti1a mutant were highly sensitive to ROS treatment, indicating that OsOxi1 and OsPti1a are involved in ROS-mediated signaling in opposing ways. OsOxi1 is specifically expressed at infection sites where ROS are produced after inoculation with a blast fungus, Magnaporthe oryzae. Overexpression of OsOxi1 enhanced basal resistance to the blast fungus, indicating that OsOxi1 positively regulates disease resistance. OsOxi1 phosphorylates Thr-233 of OsPti1a and a point mutation of Thr-233 enhanced disease susceptibility to a bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), suggesting that the phosphorylation of OsPti1a by OsOxi1 is essential for basal resistance to Xoo. Taken together, our data suggest that OsOxi1 positively regulates defense responses through the phosphorylation of OsPti1a, causing the release from an OsPti1a-dependent inhibition of the responses. PMID- 20739305 TI - Functional identification of Arabidopsis ATSIP2 (At3g57520) as an alkaline alpha galactosidase with a substrate specificity for raffinose and an apparent sink specific expression pattern. AB - Arabidopsis ATSIP2 has recently been suggested to be a raffinose synthase gene. However, it has high amino acid identity to functionally characterized alkaline alpha-galactosidases from Cucumis melo and Zea mays. Using the Sf9 insect cell expression system, we demonstrate that recombinant ATSIP2 is a genuine alkaline alpha-galactosidase with a distinct substrate specificity for raffinose, and not a raffinose synthase. A beta-glucuronidase reporter construct using the ATSIP2 promoter shows that ATSIP2 is strongly expressed in sink tissues of Arabidopsis, i.e. sink leaves and non-xylem parts of the root stele, suggesting a physiological function in raffinose phloem unloading. PMID- 20739306 TI - Cytosolic alkalization and cytosolic calcium oscillation in Arabidopsis guard cells response to ABA and MeJA. AB - Abscisic acid (ABA)- and methyl jasmonate (MeJA)-induced stomatal closure are accompanied by cytosolic alkalization in guard cells. However, it remains to be clarified how the alkalization functions in not only ABA signaling but also MeJA. We investigated cytosolic alkalization in guard cells during ABA-, MeJA- and Ca(2+)-induced stomatal closure of wild type, abi1-1, abi2-1, ost1-2 and coi1 using a pH-sensitive fluorescent dye, BCECF-AM. ABA induced cytosolic alkalization in guard cells of wild-type and coi1 but not in ost1-2 guard cells whereas MeJA elicited cytosolic alkalization in wild-type and ost1-2 guard cells but not in coi1. Neither ABA nor MeJA induced cytosolic alkalization in abi1-1 and abi2-1 guard cells. Exogenous Ca(2+) induced stomatal closure accompanied by cytosolic alkalization in guard cells of wild-type, abi1-1, abi2-1, ost1-2 and coi1 plants. An agent to acidify cytosol, butyrate, suppressed Ca(2+)-induced cytosolic alkalization and ABA-, MeJA- and Ca(2+)-induced cytosolic Ca(2+) oscillation in wild-type guard cells to prevent stomatal closure. These results indicate that cytosolic alkalization and cytosolic Ca(2+) oscillation coordinately function in ABA and MeJA signaling in Arabidopsis guard cells. PMID- 20739307 TI - BioRuby: bioinformatics software for the Ruby programming language. AB - SUMMARY: The BioRuby software toolkit contains a comprehensive set of free development tools and libraries for bioinformatics and molecular biology, written in the Ruby programming language. BioRuby has components for sequence analysis, pathway analysis, protein modelling and phylogenetic analysis; it supports many widely used data formats and provides easy access to databases, external programs and public web services, including BLAST, KEGG, GenBank, MEDLINE and GO. BioRuby comes with a tutorial, documentation and an interactive environment, which can be used in the shell, and in the web browser. AVAILABILITY: BioRuby is free and open source software, made available under the Ruby license. BioRuby runs on all platforms that support Ruby, including Linux, Mac OS X and Windows. And, with JRuby, BioRuby runs on the Java Virtual Machine. The source code is available from http://www.bioruby.org/. CONTACT: katayama@bioruby.org PMID- 20739308 TI - 2Struc: the secondary structure server. AB - SUMMARY: The defined secondary structure of proteins method is often considered the gold standard for assignment of secondary structure from three-dimensional coordinates. However, there are alternative methods. '2Struc: The Secondary Structure Server' has been created as a single point of access for eight different secondary structure assignment methods. It has been designed to enable comparisons between methods for analyzing the secondary structure content for a single protein. It also includes a second functionality, 'Compare-the-Protein' to enable comparisons of the secondary structure features from any one method to be made within a collection of nuclear magnetic resonance models, or between the crystal structures of two different proteins. AVAILABILITY: http://2struc.cryst.bbk.ac.uk CONTACT: r.w.janes@qmul.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20739309 TI - Structural genomics of histone tail recognition. AB - SUMMARY: The structural genomics of histone tail recognition web server is an open access resource that presents within mini articles all publicly available experimental structures of histone tails in complex with human proteins. Each article is composed of interactive 3D slides that dissect the structural mechanism underlying the recognition of specific sequences and histone marks. A concise text html-linked to interactive graphics guides the reader through the main features of the interaction. This resource can be used to analyze and compare binding modes across multiple histone recognition modules, to evaluate the chemical tractability of binding sites involved in epigenetic signaling and design small molecule inhibitors. AVAILABILITY: http://www.thesgc.org/resources/histone_tails/ CONTACT: matthieu.schapira@utoronto.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20739310 TI - GASSST: global alignment short sequence search tool. AB - MOTIVATION: The rapid development of next-generation sequencing technologies able to produce huge amounts of sequence data is leading to a wide range of new applications. This triggers the need for fast and accurate alignment software. Common techniques often restrict indels in the alignment to improve speed, whereas more flexible aligners are too slow for large-scale applications. Moreover, many current aligners are becoming inefficient as generated reads grow ever larger. Our goal with our new aligner GASSST (Global Alignment Short Sequence Search Tool) is thus 2-fold-achieving high performance with no restrictions on the number of indels with a design that is still effective on long reads. RESULTS: We propose a new efficient filtering step that discards most alignments coming from the seed phase before they are checked by the costly dynamic programming algorithm. We use a carefully designed series of filters of increasing complexity and efficiency to quickly eliminate most candidate alignments in a wide range of configurations. The main filter uses a precomputed table containing the alignment score of short four base words aligned against each other. This table is reused several times by a new algorithm designed to approximate the score of the full dynamic programming algorithm. We compare the performance of GASSST against BWA, BFAST, SSAHA2 and PASS. We found that GASSST achieves high sensitivity in a wide range of configurations and faster overall execution time than other state-of-the-art aligners. AVAILABILITY: GASSST is distributed under the CeCILL software license at http://www.irisa.fr/symbiose/projects/gassst/ CONTACT: guillaume.rizk@irisa.fr; dominique.lavenier@irisa.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20739311 TI - TFInfer: a tool for probabilistic inference of transcription factor activities. AB - SUMMARY: TFInfer is a novel open access, standalone tool for genome-wide inference of transcription factor activities from gene expression data. Based on an earlier MATLAB version, the software has now been extended in a number of ways. It has been significantly optimised in terms of performance, and it was given novel functionality, by allowing the user to model both time series and data from multiple independent conditions. With a full documentation and intuitive graphical user interface, together with an in-built data base of yeast and Escherichia coli transcription factors, the software does not require any mathematical or computational expertise to be used effectively. AVAILABILITY: http://homepages.inf.ed.ac.uk/gsanguin/TFInfer.html CONTACT: gsanguin@staffmail.ed.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 20739313 TI - Macromolecular dynamics in red blood cells investigated using neutron spectroscopy. AB - We present neutron scattering measurements on the dynamics of haemoglobin (Hb) in human red blood cells (RBCs) in vivo. Global and internal Hb dynamics were measured in the ps to ns time and A length scales using quasi-elastic neutron backscattering spectroscopy. We observed the cross over from global Hb short-time to long-time self-diffusion. Both short- and long-time diffusion coefficients agree quantitatively with predicted values from the hydrodynamic theory of non charged hard-sphere suspensions when a bound water fraction of around 0.23 gram H(2)O per gram Hb is taken into account. The higher amount of water in the cells facilitates internal protein fluctuations in the ps time scale when compared with fully hydrated Hb powder. Slower internal dynamics of Hb in RBCs in the ns time range were found to be rather similar to results obtained with fully hydrated protein powders, solutions and Escherichia coli cells. PMID- 20739314 TI - Predator diversity stabilizes and strengthens trophic control of a keystone grazer. AB - Despite the global vulnerability of predators to extinction, and the critical functional role they play in many ecosystems, there have been few realistic tests of the consequences of predator species deletion (conversely, predator diversity) in natural ecosystems. We performed a four-month field experiment in a southeastern United States salt marsh to test the role of predatory crab diversity in regulating populations of a keystone grazer that can decimate marsh vegetation at high densities. Our results revealed that a combination of this system's two resident predator species, in comparison to individual species, both stabilize and strengthen predation rates on the potent grazer. Monthly monitoring of predation rates from intense, hot summer months into the cooler autumn indicate this diversity benefit arises from predators responding differentially to changing environmental conditions across seasons. This study provides some of the first experimental field support for the insurance hypothesis from marine ecosystems, suggests that predator temporal complementarity may be more common than currently perceived, and argues for conservation of predator diversity to ensure reliable and effective control of potentially habitat-destroying grazers. PMID- 20739315 TI - Infant anticipatory stress. AB - In humans, anticipatory stress involves activation of the limbic-hypothalamic pituitary-adrenal axis, which releases stress hormones such as cortisol in response to an impending stressor. Conditioning of the stress response to anticipate and prepare for future challenges is a hallmark of adaptation. It is unknown whether human infants in the first year of life have developed the neural circuitry to support the anticipation of stressful events in an attachment context. Here, we show that human infants at six months of age produce an anticipatory stress response, as indicated by the release of stress hormones, when re-exposed after 24 h to a context in which they demonstrated a stress response to a disruption in the parent-infant relationship. Although infant stress response (cortisol elevation) was greater to the stressful event (parent unresponsiveness) than to the second exposure to the stress context (room, chair, presence of parent and experimenter, etc.), it was greater in the stress group than in the control group on both days. Results suggest that human infants have the capacity to produce an anticipatory stress response that is based on expectations about how their parents will treat them in a specific context. PMID- 20739316 TI - Hepatic coenzyme Q redox balance of fishes as a potential bioindicator of environmental contamination by polycyclic aromatic hydrocarbons. AB - In this communication, we introduce a novel biomarker of aquatic contamination based on the xenobiotic-induced response of the hepatic coenzyme Q (CoQ) redox balance of fishes to polycyclic aromatic hydrocarbons (PAHs). The method is demonstrated by comparing changes in the liver CoQ redox balance with that measured using the CYP1A-based, 7-ethoxyresofurin-O-deethylase activity assay, on administration of benzo[a]pyrene (BaP) and beta-naphthoflavone (BNF) to Barramundi (Lates calcarifer). Both assays showed comparable dose-dependent effects in fish treated with BaP or BNF. Perturbation in the constitutive hepatic CoQ redox balance of fishes may thus provide a simple biomarker of aquatic PAH contamination. PMID- 20739312 TI - Biological characteristics of stem cells from foetal, cord blood and extraembryonic tissues. AB - Foetal stem cells (FSCs) can be isolated during gestation from many different tissues such as blood, liver and bone marrow as well as from a variety of extraembryonic tissues such as amniotic fluid and placenta. Strong evidence suggests that these cells differ on many biological aspects such as growth kinetics, morphology, immunophenotype, differentiation potential and engraftment capacity in vivo. Despite these differences, FSCs appear to be more primitive and have greater multi-potentiality than their adult counterparts. For example, foetal blood haemopoietic stem cells proliferate more rapidly than those found in cord blood or adult bone marrow. These features have led to FSCs being investigated for pre- and post-natal cell therapy and regenerative medicine applications. The cells have been used in pre-clinical studies to treat a wide range of diseases such as skeletal dysplasia, diaphragmatic hernia and respiratory failure, white matter damage, renal pathologies as well as cancers. Their intermediate state between adult and embryonic stem cells also makes them an ideal candidate for reprogramming to the pluripotent status. PMID- 20739317 TI - Trade-offs limiting the evolution of coloniality: ecological displacement rates used to measure small costs. AB - Multicellular organisms that benefit from division of labour are presumably descended from colonial species that initially derived benefits from larger colony size, before the evolution of specialization. Life in a colony can have costs as well as benefits, but these can be hard to measure. We measured physiological costs to life in a colony using a novel method based on population dynamics, comparing growth rates of unicells and kairomone-induced colonies of a green alga Desmodesmus subspicatus against a reference co-occurring species. Coloniality negatively affected growth during the initial log growth phase, while no adverse effect was detected under nutrient-limited competitive conditions. The results point to costs associated with traits involved in rapid growth rather than those associated with efficient growth under resource scarcity. Some benefits of coloniality (e.g. defence from herbivory) may be different from when this trait evolved, but our approach shows how costs would have depended on conditions. PMID- 20739318 TI - Insulin signalling regulates remating in female Drosophila. AB - Mating rate is a major determinant of female lifespan and fitness, and is predicted to optimize at an intermediate level, beyond which superfluous matings are costly. In female Drosophila melanogaster, nutrition is a key regulator of mating rate but the underlying mechanism is unknown. The evolutionarily conserved insulin/insulin-like growth factor-like signalling (IIS) pathway is responsive to nutrition, and regulates development, metabolism, stress resistance, fecundity and lifespan. Here we show that inhibition of IIS, by ablation of Drosophila insulin-like peptide (DILP)-producing median neurosecretory cells, knockout of dilp2, dilp3 or dilp5 genes, expression of a dominant-negative DILP-receptor (InR) transgene or knockout of Lnk, results in reduced female remating rates. IIS mediated regulation of female remating can occur independent of virgin receptivity, developmental defects, reduced body size or fecundity, and the receipt of the female receptivity-inhibiting male sex peptide. Our results provide a likely mechanism by which females match remating rates to the perceived nutritional environment. The findings suggest that longevity-mediating genes could often have pleiotropic effects on remating rate. However, overexpression of the IIS-regulated transcription factor dFOXO in the fat body-which extends lifespan-does not affect remating rate. Thus, long life and reduced remating are not obligatorily coupled. PMID- 20739319 TI - Grandmothering and natural selection. AB - Humans are unique among primates in that women regularly outlive their reproductive period by decades. The grandmother hypothesis proposes that natural selection increased the length of the human post-menopausal period-and, thus, extended longevity-as a result of the inclusive fitness benefits of grandmothering. However, it has yet to be demonstrated that the inclusive fitness benefits associated with grandmothering are large enough to warrant this explanation. Here, we show that the inclusive fitness benefits are too small to affect the evolution of longevity under a wide range of conditions in simulated populations. This is due in large part to the relatively weak selection that applies to women near or beyond the end of their reproductive period. However, we find that grandmothers can facilitate the evolution of a shorter reproductive period when their help decreases the weaning age of their matrilineal grandchildren. Because selection favours a shorter reproductive period in the presence of shorter interbirth intervals, this finding holds true for any form of allocare that helps mothers resume cycling more quickly. We conclude that while grandmothering is unlikely to explain human-like longevity, allocare could have played an important role in shaping other unique aspects of human life history, such as a later age at first birth and a shorter female reproductive period. PMID- 20739320 TI - Nutritional state and collective motion: from individuals to mass migration. AB - In order to move effectively in unpredictable or heterogeneous environments animals must make appropriate decisions in response to internal and external cues. Identifying the link between these components remains a challenge for movement ecology and is important in understanding the mechanisms driving both individual and collective motion. One accessible way of examining how internal state influences an individual's motion is to consider the nutritional state of an animal. Our experimental results reveal that nutritional state exerts a relatively minor influence on the motion of isolated individuals, but large group level differences emerge from diet affecting inter-individual interactions. This supports the idea that mass movement in locusts may be driven by cannibalism. To estimate how these findings are likely to impact collective migration of locust hopper bands, we create an experimentally parametrized model of locust interactions and motion. Our model supports our hypothesis that nutrient dependent social interactions can lead to the collective motion seen in our experiments and predicts a transition in the mean speed and the degree of coordination of bands with increasing insect density. Furthermore, increasing the interaction strength (representing greater protein deprivation) dramatically reduces the critical density at which this transition occurs, demonstrating that individuals' nutritional state could have a major impact on large-scale migration. PMID- 20739321 TI - On the coevolution of social responsiveness and behavioural consistency. AB - Recent research focuses on animal personalities, that is individual differences in behaviour that are consistent across contexts and over time. From an adaptive perspective, such limited behavioural plasticity is surprising, since a more flexible structure of behaviour should provide a selective advantage. Here, we argue that consistency can be advantageous because it makes individuals predictable. Predictability, however, can only be advantageous if at least some individuals in the population respond to individual differences. Consequently, the evolution of consistency and responsiveness are mutually dependent. We present a general analysis of this coevolutionary feedback for scenarios that can be represented as matrix games with two pure strategies (e.g. hawk-dove game, snowdrift game). We first show that responsive strategies are favoured whenever some individual differences are present in the population (e.g. due to mutation and drift). We then show that the presence of responsive individuals can trigger a coevolutionary process between responsiveness and consistency that gives rise to populations in which responsive individuals coexist with unresponsive individuals who show high levels of adaptive consistency in their behaviour. Next to providing an adaptive explanation for consistency, our results also link two key features associated with personalities, individual differences in responsiveness and behavioural consistency. PMID- 20739322 TI - Sequences, stratigraphy and scenarios: what can we say about the fossil record of the earliest tetrapods? AB - Past research on the emergence of digit-bearing tetrapods has led to the widely accepted premise that this important evolutionary event occurred during the Late Devonian. The discovery of convincing digit-bearing tetrapod trackways of early Middle Devonian age in Poland has upset this orthodoxy, indicating that current scenarios which link the timing of the origin of digited tetrapods to specific events in Earth history are likely to be in error. Inspired by this find, we examine the fossil record of early digit-bearing tetrapods and their closest fish like relatives from a statistical standpoint. We find that the Polish trackways force a substantial reconsideration of the nature of the early tetrapod record when only body fossils are considered. However, the effect is less drastic (and often not statistically significant) when other reliably dated trackways that were previously considered anachronistic are taken into account. Using two approaches, we find that 95 per cent credible and confidence intervals for the origin of digit-bearing tetrapods extend into the Early Devonian and beyond, spanning late Emsian to mid Ludlow. For biologically realistic diversity models, estimated genus-level preservation rates for Devonian digited tetrapods and their relatives range from 0.025 to 0.073 per lineage-million years, an order of magnitude lower than species-level rates for groups typically considered to have dense records. Available fossils of early digited tetrapods and their immediate relatives are adequate for documenting large-scale patterns of character acquisition associated with the origin of terrestriality, but low preservation rates coupled with clear geographical and stratigraphic sampling biases caution against building scenarios for the origin of digits and terrestrialization tied to the provenance of particular specimens or faunas. PMID- 20739323 TI - Counterbalancing clinical supervision and independent practice: case studies in learning thoracic epidural catheter insertion. AB - BACKGROUND: Thoracic epidural catheter placement is an example of a demanding and high-risk clinical skill that junior anaesthetists need to learn by experience and under the supervision of consultants. This learning is known to present challenges that require further study. METHODS: Ten consultant and 10 trainee anaesthetists in a teaching hospital were interviewed about teaching and learning this skill in the operating theatre, and a phenomenological analysis of their experience was performed. RESULTS: Trainee participation was limited by time pressure, lack of familiarity with consultants, and consultants' own need for clinical experience. There was a particular tension between safe and effective consultant practice and permitting trainees' independence. Three distinct stages of participation and assistance were identified from reports of ideal practice: early (part-task or basic procedure, consultant always present giving instruction and feedback), middle (independent practice with straightforward cases without further instruction), and late (skill extension and transfer). Learning assistance provided by consultants varied, but it was often not matched to the trainees' stages of learning. Negotiation of participation and assistance was recognized as being useful, but it did not happen routinely. CONCLUSIONS: There are many obstacles to trainees' participation in thoracic epidural catheter insertion, and learning assistance is not matched to need. A more explicit understanding of stages of learning is required to benefit the learning of this and other advanced clinical skills. PMID- 20739324 TI - Evaluation of nationwide health promotion campaigns in The Netherlands: an exploration of practices, wishes and opportunities. AB - Nationwide health promotion campaigns are an important part of government-funded health promotion efforts. Valid evaluation is important, but difficult because gold standard research designs are not applicable and the allocation of budget and time for evaluation is often very tight. In The Netherlands, Health Promotion Institutes (HPIs) are responsible for these campaigns. We conducted an exploratory study among the HPIs to gain better insight into goals, practices, conditions and perceived barriers regarding evaluation of these campaigns. Data were obtained through personal interviews with representatives of HPIs who had direct management responsibility for the evaluation of their campaigns. The HPIs typically made use of a pre-test-post-test design with single measurements before and after the campaign without a control group. In campaign preparations, HPIs used qualitative research to pre- and pilot-test some campaign materials, but true formative evaluation was rare. Besides, accountability to their sponsors, peers and the population at large, the most important reason to evaluate was to learn for future campaigns. In terms of the RE-AIM framework, evaluation was mostly restricted to Reach and Effects; hardly any evaluation of adoption, implementation or maintenance was reported. Budget and time constraints were reported as the main barriers for more extensive formative and effect evaluation. Evaluation of nationwide campaigns is standard procedure, but the applied research designs are weak, due to lack of time, budget and research methodology expertise. Next to additional budget and a longer-term planning, input from external experts regarding evaluation research designs are needed for evaluation improvement. PMID- 20739326 TI - Taxing soft drinks in the Pacific: implementation lessons for improving health. AB - A tax on soft drinks is often proposed as a health promotion strategy for reducing their consumption and improving health outcomes. However, little is known about the processes and politics of implementing such taxes. We analysed four different soft drink taxes in Pacific countries and documented the lessons learnt regarding the process of policy agenda-setting and implementation. While local social and political context is critically important in determining policy uptake, these case studies suggest strategies for health promotion practitioners that can help to improve policy uptake and implementation. The case studies reveal interaction between the Ministries of Health, Finance and Revenue at every stage of the policy making process. In regard to agenda-setting, relevance to government fiscal priorities was important in gaining support for soft drink taxes. The active involvement of health policy makers was also important in initiating the policies, and the use of existing taxation mechanisms enabled successful policy implementation. While the earmarking of taxes for health has been widely recommended, the revenue may be redirected as government priorities change. Health promotion practitioners must strategically plan for agenda setting, development and implementation of intersectoral health-promoting policies by engaging with stakeholders in finance at an early stage to identify priorities and synergies, developing cross-sectoral advocacy coalitions, and basing proposals on existing legislative mechanisms where possible. PMID- 20739325 TI - How to promote healthy behaviours in patients? An overview of evidence for behaviour change techniques. AB - To identify the evidence for the effectiveness of behaviour change techniques, when used by health-care professionals, in accomplishing health-promoting behaviours in patients. Reviews were used to extract data at a study level. A taxonomy was used to classify behaviour change techniques. We included 23 systematic reviews: 14 on smoking cessation, 6 on physical exercise, and 2 on healthy diets and 1 on both exercise and diets. None of the behaviour change techniques demonstrated clear effects in a convincing majority of the studies in which they were evaluated. Techniques targeting knowledge (n = 210 studies) and facilitation of behaviour (n = 172) were evaluated most frequently. However, self monitoring of behaviour (positive effects in 56% of the studies), risk communication (52%) and use of social support (50%) were most often identified as effective. Insufficient insight into appropriateness of technique choice and quality of technique delivery hinder precise conclusions. Relatively, however, self-monitoring of behaviour, risk communication and use of social support are most effective. Health professionals should avoid thinking that providing knowledge, materials and professional support will be sufficient for patients to accomplish change and consider alternative strategies which may be more effective. PMID- 20739327 TI - How to be a department chair of epidemiology: a survival guide. AB - As former chairs of 3 of the largest departments of epidemiology in the country, the authors provide "lessons learned" on how to be an epidemiology chair. To start, they suggest discussing strategic visioning with faculty, staff, and students; evaluating existing operational and governance structures; setting a predictable style; and considering which traditions to keep and which to modernize. Next, the authors consider key administrative issues. Recruitment and retention of the best faculty and students are critical to a successful department's future. A great department requires a great vision. To manage the change a new vision creates, the chair must attain buy-in and proceed with persistence. Chairs must promote the interests of the department to higher administration, a job best accomplished by being a team player and picking your battles. Keeping an eye on the mission involves balancing quality education with research and always striving to improve public health. Finally, a chair must continuously assess whether he or she is doing the best job. Eventually, the chair must know when to quit and how to quit well. Although being chair is demanding and sometimes difficult, it is a position that can be rewarding to both the individual and the department. PMID- 20739332 TI - Asking people directly about preferred health-seeking behaviour yields invalid response: an experiment in south-east Nigeria. AB - BACKGROUND: Various factors determine health-seeking behaviour in south-east Nigeria. This study compared the hypothetical and actual health-seeking behaviour using where people sought malaria treatment as proxy for health-seeking behaviour and determinant of health service utilization. METHODS: The study was conducted in an urban area and a rural area in the Anambra state, south-east, Nigeria. Multistage sampling method was used to select a minimum sample size of 400 households in each community. Datawere collected on where people would prefer to be treated for malaria if they had malaria and where they actually sought for malaria treatment. RESULTS: Hypothetically majority of the people would prefer to use public and private hospitals for treatment of malaria but in reality majority of respondents in both rural and urban areas sought treatment at patent medicine dealers (PMDs) for both adult and childhood malaria. CONCLUSION: There were divergences between what people stated they would have ideally done in treating malaria and what they actually did when malaria occurred. Since PMDs were actually used by consumers of malaria treatment over other providers mainly because of low cost, there is the need to train PMDs to improve the quality of their services. PMID- 20739333 TI - The empowerment of women and the population dynamics of climate change. PMID- 20739334 TI - Investigating variability in patient response to treatment--a case study from a replicate cross-over study. AB - It is a common belief that individual variation in response to treatment is an important explanation for the variation in observed outcomes in clinical trials. If such variation is large, it seems reasonable to suppose that progress in treating disease will be advanced by classifying patients according to their abilities or not to 'respond' to particular treatments. We consider that there is currently a lost opportunity in drug development. There is a great deal of talk about individual response to treatment and tailor-made drugs. However, relatively little work is being done to formally investigate, using suitable designs, where individual response to treatment may be important. Through a case study from a replicate cross-over study we show how, given suitable replication, it is possible to isolate the component of variation corresponding to patient-by treatment interaction and hence investigate the possibility of individual response to treatment. PMID- 20739335 TI - Evaluation of the symbol digit modalities test (SDMT) and MS neuropsychological screening questionnaire (MSNQ) in natalizumab-treated MS patients over 48 weeks. AB - BACKGROUND AND OBJECTIVES: Brief cognitive tests to monitor cognitive impairment in patients with multiple sclerosis (MS) are needed. METHODS: Performance on monthly administrations of the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Questionnaire (MSNQ) was assessed in 660 patients with MS in 21 countries (109 sites) for 48 weeks in an open-label, safety-extension study of natalizumab. RESULTS: At baseline, the cohort's mean age was 40.1 years, 67.6% were female and the median Expanded Disability Status Scale score was 2.5. Test retest correlations were high for both SDMT (range 0.89 for weeks 0-4 to 0.96 for weeks 44-48) and MSNQ (0.82 for weeks 0-4 to 0.93 for weeks 44-48). There were no statistically significant effects of geographic region. While SDMT scores improved by 15 points over 48 weeks (p < 0.0001), incremental monthly changes were small (effect size d < 0.3). Similar results were obtained on the MSNQ except that scores moved downward, suggesting fewer cognitive complaints over 48 weeks (p < 0.0001), but again the incremental monthly changes were small (d < 0.2). CONCLUSIONS: These results replicate earlier work in a smaller cohort treated with conventional disease-modifying therapy, and support the reliability of the SDMT and MSNQ as potential screening for monitoring tools for cognition over time. PMID- 20739336 TI - Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis. AB - In order to evaluate the effects of vitamin D3 on monocyte-derived dendritic cells (DCs) of relapsing-remitting multiple sclerosis patients, DCs differentiation and maturation were evaluated in vitro based on surface phenotypic changes. The expression of CD14, CD83, CD1a, CD80, CD86, CD206 and C209 was analysed by fluorescence-activated cell sorting. The results reveal that vitamin D3 inhibits both the differentiation and maturation of DCs. Moreover, inhibits the secretion of IL 23/12p40 and increases the secretion of CCL2. The data suggest that one of the mechanisms of the beneficial action of vitamin D3 in multiple sclerosis may be associated with its influence on DCs. PMID- 20739337 TI - Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. AB - BACKGROUND: Neuromyelitis optica (NMO) is assumed to be immunologically distinct from multiple sclerosis (MS). Adequate studies about cytokines and chemokines in NMO have been lacking. OBJECTIVE: To investigate the contribution of cytokines/chemokines in the pathogenesis of NMO. METHODS: We measured 27 cytokines/chemokines and Th17 cell-associated cytokines in the cerebrospinal fluid (CSF) of 31 NMO, 29 MS and 18 other non-inflammatory neurological disorders patients. The serum levels of some cytokines/ chemokines were also measured. The correlations between clinical characteristics/laboratory findings and levels of cytokines/chemokines in NMO were examined. RESULTS: The CSF levels of interleukin (IL)-1 receptor antagonist, IL-6, IL-8, IL-13 and granulocyte colony-stimulating factor were significantly increased in NMO, while IL-9, fibroblast growth factor basic, granulocyte macrophage colony-stimulating factor, macrophage inflammatory protein-1-beta and tumor necrosis factor-alpha were increased in MS. IL-10 and interferon-gamma-inducible protein-10 were elevated in NMO and MS. In serum analyses, only the IL-6 level showed significant elevation in NMO. The CSF IL-6 level had a significant correlation with the CSF glial fibrillary acidic protein level and CSF cells, and a weak correlation with anti-aquaporin-4 antibody titers. CONCLUSIONS: Different immunological status and pathophysiologies exist between NMO and MS, and IL-6 may play important roles in the pathogenesis of NMO. PMID- 20739338 TI - High-resolution black-blood contrast-enhanced T1 weighted images for the diagnosis and follow-up of intracranial arteritis. AB - Primary arteritis of the central nervous system (CNS) comprises a heterogeneous group of CNS disorders, which is characterised by non-atheromatous inflammation and necrosis of the arterial wall. The clinical presentation is highly variable, with stroke being the most common manifestation. Conventional angiography is considered to be the best imaging tool for diagnosing the disease. However, angiographic findings, which usually show lumen irregularities and stenosis, are often unspecific and can occur with a variety of other vascular disorders, such as atherosclerosis and arterial dissection. Therefore, brain biopsies are often needed to confirm the diagnosis. Recent reports have shown that MRI is able to visualise contrast enhancement in subjects with known primary CNS arteritis. PMID- 20739339 TI - Colonic transformation of ileal pouch-anal anastomosis and of the distal ileum: MRI findings. AB - Colonic metaplasia of the ileal reservoir in patients after ileal pouch-anal anastomosis (IPAA) is described in pathological and histochemical studies. So far, there are no reports on the imaging presentation of colonic transformation. We describe the distinctive post-operative MRI features found in a 28-year-old patient with IPAA after failed conservative treatment of chronic ulcerative colitis. These distinct MRI features of colonic transformation of ileum mimicking normal colon are important to know for radiologists reading MR examinations of patients with IPAA. PMID- 20739340 TI - Gastric calcifying fibrous pseudotumour associated with an ulcer: report of one case with a literature review. AB - Calcifying fibrous pseudotumour (CFPT) is a rare lesion that has only recently been reported in the literature. Usually, the lesion develops in subcutaneous tissue, deep soft tissues or viscera. It appears as a uniform, hypocellular and well-circumscribed mass without a capsule. Only nine cases of gastric CFPT have been reported in the literature so far. Here, we report a new case of gastric CFPT, which was, surprisingly, associated with an ulcer. To our knowledge, a gastric CFPT with an ulcer has not been previously reported in the literature. The patient (a healthy 49-year-old man) had vomited approximately 300 g brown liquid and developed syncope once. CT scan and gastroscopy revealed a polypoid mass at the great curvature of the gastric body with a larger ulcer on its top. The mass was removed by surgery. During a follow-up of 5 months, the patient was asymptomatic with no recurrence. We discuss the imaging findings, as well as the clinicopathological features of this unusual case and review the related literature. PMID- 20739341 TI - Gadolinium enhancement of cauda equina after combined spinal-epidural anaesthesia. AB - The occurrence of neurological symptoms after spinal anaesthesia has been reported with several local anaesthetics including lidocaine, prilocaine, mepivacaine, tetracaine and bupivacaine. Although hyperbaric bupivacaine is known to induce neurological symptoms less frequently than lidocaine, a few cases of cauda equina syndrome (CES) following the intraspinal injection of bupivacaine have been reported in the English literature. We describe lumbar MRI findings for a 29-year-old woman presenting with CES after caesarean section. PMID- 20739342 TI - A new interventional technique for percutaneous treatment of drainage-resistant liver abscess. AB - The objective of this case report is to describe a device that can be used as a minimally invasive alternative for the treatment of drainage-resistant liver abscess. The device uses pulse lavage to fragment and evacuate the semi-solid contents of a liver abscess. The treatment of liver abscesses consists of percutaneous drainage, antibiotics and treatment of the underlying cause. This approach can be ineffective if the contents of the abscess cavity are not liquid, and in those cases open surgery is often needed. Here, we describe for the first time a new minimally invasive technique for treating persistent liver abscesses. A patient developed a liver abscess after a hepatico-jejunostomy performed as a palliative treatment for an unresectable pancreatic head carcinoma. Simple drainage by a percutaneously placed pig-tail catheter was insufficient because of inadequate removal of the contents of the abscess cavity. After dilatation of the drain tract the persistent semi-solid necrotic contents were fragmented by a pulsed lavage device, after which the abscess healed uneventfully. The application of pulsed lavage for debridement of drainage-resistant liver abscesses proved to be an effective and minimally invasive alternative to open surgery. PMID- 20739343 TI - Molecular biology: the key to personalised treatment in radiation oncology? AB - We know considerably more about what makes cells and tissues resistant or sensitive to radiation than we did 20 years ago. Novel techniques in molecular biology have made a major contribution to our understanding at the level of signalling pathways. Before the "New Biology" era, radioresponsiveness was defined in terms of physiological parameters designated as the five Rs. These are: repair, repopulation, reassortment, reoxygenation and radiosensitivity. Of these, only the role of hypoxia proved to be a robust predictive and prognostic marker, but radiotherapy regimens were nonetheless modified in terms of dose per fraction, fraction size and overall time, in ways that persist in clinical practice today. The first molecular techniques were applied to radiobiology about two decades ago and soon revealed the existence of genes/proteins that respond to and influence the cellular outcome of irradiation. The subsequent development of screening techniques using microarray technology has since revealed that a very large number of genes fall into this category. We can now obtain an adequately robust molecular signature, predicting for a radioresponsive phenotype using gene expression and proteomic approaches. In parallel with these developments, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) can now detect specific biological molecules such as haemoglobin and glucose, so revealing a 3D map of tumour blood flow and metabolism. The key to personalised radiotherapy will be to extend this capability to the proteins of the molecular signature that determine radiosensitivity. PMID- 20739344 TI - Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy. AB - The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35+/-0.2 Gy) than the calculated equivalent whole-body dose (0.07+/-0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2+/-0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1+/-0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate. PMID- 20739345 TI - Significance of manipulating tumour hypoxia and radiation dose rate in terms of local tumour response and lung metastatic potential, referring to the response of quiescent cell populations. AB - The purpose of this study was to evaluate the influence of manipulating intratumour oxygenation status and radiation dose rate on local tumour response and lung metastases following radiotherapy, referring to the response of quiescent cell populations within irradiated tumours. B16-BL6 melanoma tumour bearing C57BL/6 mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. They received gamma-ray irradiation at high dose rate (HDR) or reduced dose rate (RDR) following treatment with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the quiescent (Q) and total (proliferating + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Following HDR irradiation, nicotinamide and MTH enhanced the sensitivity of the total and Q-cell populations, respectively. The decrease in sensitivity at RDR irradiation compared with HDR irradiation was slightly inhibited by MTH, especially in Q cells. Without gamma-ray irradiation, nicotinamide treatment tended to reduce the number of lung metastases. With gamma rays, in combination with nicotinamide or MTH, especially the former, HDR irradiation decreased the number of metastases more remarkably than RDR irradiation. Manipulating both tumour hypoxia and irradiation dose rate have the potential to influence lung metastasis. The combination with the acute hypoxia releasing agent nicotinamide may be more promising in HDR than RDR irradiation in terms of reducing the number of lung metastases. PMID- 20739346 TI - Post-traumatic acute abdominal pain. PMID- 20739347 TI - Short echo time proton magnetic resonance spectroscopy in Alzheimer's disease: a longitudinal multiple time point study. AB - Short echo time localized proton magnetic resonance spectroscopy provides quantification of brain metabolites, including N-acetyl-aspartate, myo-inositol, creatine/phosphocreatine and choline-containing compounds, which may be useful biomarkers for monitoring Alzheimer's disease. We aimed to quantify the rate of metabolite change in Alzheimer's disease, to assess factors influencing changes and to investigate the potential for serial magnetic resonance spectroscopy as an Alzheimer's disease trial biomarker. A total of 42 patients and 22 controls each had up to six magnetic resonance spectroscopy examinations over a 2-year period, using a midline posterior cingulate single-voxel point resolved spectroscopy sequence (1.5 T; time to repetition = 2000 ms; echo time = 30 ms; 192 averages). Metabolite ratios N-acetyl-aspartate:creatine/phosphocreatine, choline-containing compounds:creatine/phosphocreatine, and myo-inositol:creatine/phosphocreatine were measured using online software (PROBE-Q) and the N-acetyl-aspartate:myo inositol ratio was derived. Baseline ratios were compared between patients and controls. A linear mixed model was used to quantify longitudinal changes and extended to assess the effect of age, disease severity and baseline use of acetylcholinesterase inhibitors. Patients and controls were matched for age (patients: 68.9 +/- 7.2 years; controls: 69.1 +/- 6.7 years); 71% of the patients were on acetylcholinesterase inhibitors at baseline; mean Mini-Mental State Examination for patients was 19.4 +/- 4.1. A total of 307 spectra were acquired. In cross-sectional analyses, patients were significantly different from controls for N-acetyl-aspartate:creatine/phosphocreatine (11% lower, P < 0.001), N-acetyl aspartate:myo-inositol (24% lower, P < 0.001), and myo inositol:creatine/phosphocreatine (17% higher, P < 0.001). After adjustment for N acetyl-aspartate:myo-inositol, none of the other variables differed significantly. In patients there was significant decline in N-acetyl aspartate:creatine/phosphocreatine (mean: 2.2%/year; 95% confidence interval: 0.9 3.5) and N-acetyl-aspartate:myo-inositol (mean: 3.7%/year; 95% confidence interval: 1.7-5.7), with no evidence for influence by age, disease severity or acetylcholinesterase inhibitor use. There was significant excess decline in patients compared with controls only in N-acetyl-aspartate:myo-inositol (mean: 3.6%/year; 95% confidence interval: 0.8-6.4; P = 0.014). Between-subject standard deviation for N-acetyl-aspartate:myo-inositol was 0% for controls and 3.5%/year for patients; within-subject standard deviation for a 1 year, two-time-point study was 9.2%/year for both patients and controls. These results confirm that magnetic resonance spectroscopy can be used to quantify excess metabolite decline in Alzheimer's disease, which may provide a useful measure of disease progression. We found no evidence that age, disease severity or acetylcholinesterase inhibitor use influenced rate of decline, although numbers were small. The substantial variability in longitudinal measurements that drives sample size requirements is principally within-subject and technique related: technical developments to reduce this variability may make serial magnetic resonance spectroscopy a viable biomarker in clinical trials for Alzheimer's disease. PMID- 20739348 TI - Detection of Epstein-Barr virus and B-cell follicles in the multiple sclerosis brain: what you find depends on how and where you look. PMID- 20739349 TI - Larger temporal volume in elderly with high versus low beta-amyloid deposition. AB - beta-Amyloid deposition is one of the main hallmarks of Alzheimer's disease thought to eventually cause neuronal death. Post-mortem and neuroimaging studies have consistently reported cases with documented normal cognition despite high beta-amyloid burden. It is of great interest to understand what differentiates these particular subjects from those without beta-amyloid deposition or with both beta-amyloid deposition and cognitive deficits, i.e. what allows these subjects to resist the damage of the pathological lesions. [11C]Pittsburgh compound B positron emission tomography and magnetic resonance brain scans were obtained in 149 participants including healthy controls and patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease. Magnetic resonance data were compared between high versus low-[11C]Pittsburgh compound B cases, and between high-[11C]Pittsburgh compound B cases with versus those without cognitive deficits. Larger temporal (including hippocampal) grey matter volume, associated with better episodic memory performance, was found in high- versus low-[11C]Pittsburgh compound B healthy controls. The same finding was obtained using different [11C]Pittsburgh compound B thresholds, correcting [11C]Pittsburgh compound B data for partial averaging, using age, education, Mini Mental State Examination, apolipoprotein E4 and sex-matched subsamples, and using manual hippocampal delineation instead of voxel-based analysis. By contrast, in participants with subjective cognitive impairment, significant grey matter atrophy was found in high-[11C]Pittsburgh compound B cases compared to low [11C]Pittsburgh compound B cases, as well as in high-[11C]Pittsburgh compound B cases with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease compared to high-[11C]Pittsburgh compound B healthy controls. Larger grey matter volume in high-[11C]Pittsburgh compound B healthy controls may reflect either a tissue reactive response to beta-amyloid or a combination of higher 'brain reserve' and under-representation of subjects with standard/low temporal volume in the high-[11C]Pittsburgh compound B healthy controls. Our complementary analyses tend to support the latter hypotheses. Overall, our findings suggest that the deleterious effects of beta-amyloid on cognition may be delayed in those subjects with larger brain (temporal) volume. PMID- 20739351 TI - Aortic arch replacement and elephant trunk procedure: an interdisciplinary approach to surgical reconstruction, perfusion strategies and blood management. AB - Surgical treatment of patients who present with large aneurysms of the ascending aorta, transverse arch and descending aorta, including the thoracic and abdominal aorta typically consists of a two-staged elephant trunk procedure. Typically, these operations are lengthy, requiring long cardiopulmonary bypass times, deep hypothermic circulatory arrest and multiple anastamotic suture lines, which increases the risks for coagulopathic bleeding and the need for massive transfusions. The purpose of this report is to describe our approach, involving advanced surgical techniques and the innovative perfusion considerations as well as modified blood management strategies to minimize perioperative blood loss and the need for transfusions. All of the above will highlight critical cardiac team communications. An ever-evolving case requires forward thinking, revised judgments, open discussion and the continued involvement of all team members. In turn, this ensures evidence-based medical and perfusion practices that lead to achieving a positive peri-operative course, with optimal blood conservation. PMID- 20739352 TI - Improved deoxyribozymes for synthesis of covalently branched DNA and RNA. AB - A covalently branched nucleic acid can be synthesized by joining the 2'-hydroxyl of the branch-site ribonucleotide of a DNA or RNA strand to the activated 5' phosphorus of a separate DNA or RNA strand. We have previously used deoxyribozymes to synthesize several types of branched nucleic acids for experiments in biotechnology and biochemistry. Here, we report in vitro selection experiments to identify improved deoxyribozymes for synthesis of branched DNA and RNA. Each of the new deoxyribozymes requires Mn2(+) as a cofactor, rather than Mg2(+) as used by our previous branch-forming deoxyribozymes, and each has an initially random region of 40 rather than 22 or fewer combined nucleotides. The deoxyribozymes all function by forming a three-helix-junction (3HJ) complex with their two oligonucleotide substrates. For synthesis of branched DNA, the best new deoxyribozyme, 8LV13, has k(obs) on the order of 0.1 min-1, which is about two orders of magnitude faster than our previously identified 15HA9 deoxyribozyme. 8LV13 also functions at closer-to-neutral pH than does 15HA9 (pH 7.5 versus 9.0) and has useful tolerance for many DNA substrate sequences. For synthesis of branched RNA, two new deoxyribozymes, 8LX1 and 8LX6, were identified with broad sequence tolerances and substantial activity at pH 7.5, versus pH 9.0 for many of our previous deoxyribozymes that form branched RNA. These experiments provide new, and in key aspects improved, practical catalysts for preparation of synthetic branched DNA and RNA. PMID- 20739353 TI - Structural basis of microRNA length variety. AB - The biogenesis of human microRNAs (miRNAs) includes two RNA cleavage steps in which the activities of the RNases Drosha and Dicer are involved. miRNAs of diverse lengths are generated from different genes, and miRNAs that are heterogeneous in length are produced from a single miRNA gene. We determined the solution structures of many miRNA precursors and analysed the structural basis of miRNA length diversity using a new measure: the weighted average length of diced RNA (WALDI). We found that asymmetrical structural motifs present in precursor hairpins are primarily responsible for the length diversity of miRNAs generated by Dicer. High-resolution northern blots of miRNAs and their precursors revealed that both Dicer and Drosha cleavages of imperfect specificity contributed to the miRNA length heterogeneity. The relevance of these findings to the dynamics of the dicing complex, mRNA regulation by miRNA, RNA interference and miRNA technologies are discussed. PMID- 20739355 TI - Patient safety and quality of care continue to improve in NHS North West following early implementation of the European Working Time Directive. AB - OBJECTIVES: NHS North West aimed to fully implement the European Working Time Directive (EWTD) 1 year ahead of the August 2009 national deadline. Significant debate has taken place concerning the implications of the EWTD for patient safety. This study aims to directly address this issue by comparing parameters of patient safety in NHS North West to those nationally prior to EWTD implementation, and during 'North West-only' EWTD implementation. DESIGN: Hospital standardised mortality ratio (HSMR), average length of stay (ALOS) and standardised readmission rate (SRR) in acute trusts across all specialties were calculated retrospectively throughout NHS North West for the three financial years from 2006/2007 to 2008/2009. These figures were compared to national data for the same parameters. RESULTS: The analysis of HSMR, ALOS and SRR reveal no significant difference in trend across three financial years when NHS North West is compared to England. HSMR and SRR within NHS North West continued to improve at a similar rate to the England average after August 2008. The ALOS analysis shows that NHS North West performed better than the national average for the majority of the study period, with no significant change in this pattern in the period following August 2008. When the HSMRs for NHS North West and England are compared against a fixed benchmark year (2005), the data shows a continuing decrease. The NHS North West figures follow the national trend closely at all times. CONCLUSION: The data presented in this study quantitatively demonstrates, for the first time, that implementation of the EWTD in NHS North West in August 2008 had no obvious adverse impact on key outcomes associated with patient safety and quality of care. Continued efforts will be required to address the challenge posed nationally by the restricted working hour's schedule. PMID- 20739354 TI - In situ proteomic analysis of human breast cancer epithelial cells using laser capture microdissection: annotation by protein set enrichment analysis and gene ontology. AB - Identification of molecular signatures that allow detection of the transition from normal breast epithelial cells to malignant invasive cells is a critical component in the development of diagnostic, therapeutic, and preventative strategies for human breast cancer. Substantial efforts have been devoted to deciphering breast cancer etiology at the genome level, but only a limited number of studies have appeared at the proteome level. In this work, we compared individual in situ proteome profiles of nonpatient matched nine noncancerous, normal breast epithelial (NBE) samples with nine estrogen receptor (ER)-positive (luminal subtype), invasive malignant breast epithelial (MBE) samples by combining laser capture microdissection (LCM) and quantitative shotgun proteomics. A total of 12,970 unique peptides were identified from the 18 samples, and 1623 proteins were selected for quantitative analysis using spectral index (SpI) as a measure of protein abundance. A total of 298 proteins were differentially expressed between NBE and MBE at 95% confidence level, and this differential expression correlated well with immunohistochemistry (IHC) results reported in the Human Protein Atlas (HPA) database. To assess pathway level patterns in the observed expression changes, we developed protein set enrichment analysis (PSEA), a modification of a well-known approach in gene expression analysis, Gene Set Enrichment Analysis (GSEA). Unlike single gene-based functional term enrichment analyses that only examines pathway overrepresentation of proteins above a given significance threshold, PSEA applies a weighted running sum statistic to the entire expression data to discover significantly enriched protein groups. Application of PSEA to the expression data in this study revealed not only well-known ER-dependent and cellular morphology-dependent protein abundance changes, but also significant alterations of downstream targets for multiple transcription factors (TFs), suggesting a role for specific gene regulatory pathways in breast tumorigenesis. A parallel GOMiner analysis revealed both confirmatory and complementary data to PSEA. The combination of the two annotation approaches yielded extensive biological feature mapping for in depth analysis of the quantitative proteomic data. PMID- 20739356 TI - Diabetes and cancer. AB - Diabetes and cancer are common conditions, and their co-diagnosis in the same individual is not infrequent. A link between the two conditions has been postulated for almost 80 years, but only in the past decade has significant epidemiological evidence been amassed to suggest that diabetes and cancer are associated, and the link appears causal. Hyperinsulinaemia, adipocytokines, growth factors and epigenetic changes may be implicated in the pathogenesis of cancer amongst patients with diabetes, and recently, diabetes therapies have also been implicated. There is reasonable circumstantial evidence that metformin may decrease the risk of cancer amongst diabetic patients. Much more research is required to elucidate the link between diabetes and cancer, particularly the potential link with diabetes treatments. PMID- 20739357 TI - Management of paediatric burns. PMID- 20739361 TI - Voting and mental capacity. PMID- 20739360 TI - Management of hypertensive disorders during pregnancy: summary of NICE guidance. PMID- 20739362 TI - Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. AB - OBJECTIVES: Toll-like receptor 9 (TLR9), which recognizes hypomethylated DNA [cytosine-phosphate-guanine (CpG)], plays a role in the maintenance of serological memory and has been recently implicated in the pathogenesis of SLE. We previously reported that in vitro TLR9 triggers memory B-cell differentiation into antibody-producing cells, and that the MyD88-inhibitor ST2825 blocks TLR9 induced plasma cell (PC) generation. Here, we investigated whether memory B cells produce autoantibodies in SLE patients with active disease or in clinical remission, and whether ST2825 could inhibit PC generation in SLE patients. METHODS: Peripheral blood mononuclear cells from 10 SLE patients in clinical remission and 2 with active SLE were cultured in the presence of CpG with or without ST2825. Phenotypical analysis of CpG-stimulated cells was performed by flow cytometry. Supernatants were collected to measure antibody production by ELISA and to detect autoantibodies by IF. RESULTS: CpG-induced TLR9 stimulation caused autoantibody secretion in patients with active disease and in the majority of patients in clinical remission. Inhibition of MyD88 completely blocked the de novo generation of PCs and the secretion of autoantibodies. CONCLUSIONS: Autoreactive B cells persist in SLE patients during disease remission in the circulating B-cell memory pool. TLR9-dependent activation of memory B cells by pathogens could be one of the mechanisms triggering relapses in SLE. Compounds targeting the TLR/MyD88 pathway may be used as novel therapeutic tools to treat acute disease and to prevent relapses in SLE patients. PMID- 20739363 TI - Diagnosis and management of adults with chronic heart failure: summary of updated NICE guidance. PMID- 20739364 TI - Should treatment for heart failure with preserved ejection fraction differ from that for heart failure with reduced ejection fraction? PMID- 20739372 TI - New UK figures show further rise in sexually transmitted infections. PMID- 20739373 TI - Risk of cot death in babies of British teen mothers is still high. PMID- 20739374 TI - The expression of renin-angiotensin system components in the human gastric mucosa. AB - INTRODUCTION: The aim of the present study was to map the distribution of representative protein components of the renin-angiotensin system (RAS) in the human gastric mucosa. MATERIALS AND METHODS: Biopsies from the antral and corporal mucosa of healthy Helicobacter pylori negative and positive volunteers were assessed by histology, Western blot and immunohistochemistry for angiotensin II subtype 1 and 2 receptors (AT1R, AT2R) and other RAS components (angiotensinogen, renin, angiotensin converting enzyme, and neprilysin). Mucosal levels of myeloperoxidase (MPO) served as a protein marker of neutrophil infiltration. RESULTS: AT1R and AT2R were located in a variety of cells in the human gastric mucosa, including AT1R on a subpopulation of endocrine cells in the antral mucosa. Angiotensinogen and renin were expressed by resident mesenchymal cells in lamina propria. All investigated RAS components were found in vascular endothelial cells. The AT1R protein expression was 3-4 times higher in the gastric mucosa of H. pylori positive subjects compared to the gastric mucosa of H. pylori negative subjects (p < 0.05). Gastric mucosal AT1R protein expression correlated positively with neutrophil infiltration (r = 0.7, p < 0.05). CONCLUSIONS: Protein components of RAS are present in the human gastric mucosa. The results suggest an angiotensin II mediated impact on mucosal epithelial functions, antral endocrine properties, microvascular permeability, and gastric inflammation. PMID- 20739375 TI - The midgestational maternal blood pressure decline is absent in mice lacking expression of the angiotensin II AT2 receptor. AB - The midgestational maternal blood pressure (BP) decrease is absent in mice treated with an angiotensin II AT2 receptor blocker. We tested the hypotheses that there would be 1) no midgestational decrease in maternal systolic BP (SBP) in AT2-/- mice, and 2) a pattern of increased AT2 and/or decreased AT1a mRNA expression in tissues from normal (wild-type, WT) mice, corresponding with SBP changes. Heart, aorta, placenta and kidney tissue were obtained from WT and AT2-/ mice before pregnancy and on gestational days (Gd) 5-6, 12-13 and 18-19. AT1a and AT2 mRNA expression was quantified. SBP was measured. SBP was significantly decreased in WT Gd12-13 mice, but did not change during pregnancy in AT2-/- mice. In WT mice, aortic AT1a mRNA expression levels were significantly higher at Gd12 13 and Gd18-19 compared with before pregnancy. AT1a kidney and heart mRNA did not change during pregnancy. There were no changes in AT2 mRNA expression. There was no distinct pattern of change in AT1a expression in AT2-/mice. Placental AT1a and AT2 expression levels increased markedly between Gd12-13 and Gd18-19 in WT mice. We conclude that the AT2 receptor is essential for the midgestational SBP decline in WT mice. There is no consistent relationship between changes in tissue angiotensin II receptor mRNA expression and SBP in WT mice. PMID- 20739376 TI - Changes in expression of bone morphogenetic proteins (BMPs), their receptors and inhibin co-receptor betaglycan during bovine antral follicle development: inhibin can antagonize the suppressive effect of BMPs on thecal androgen production. AB - We reported previously that bone morphogenetic proteins (BMPs) potently suppress CYP17 expression and androgen production by bovine theca interna cells (TC) in vitro. In this study, real-time PCR was used to analyse gene expression in TC and granulosa cell (GC) layers from developing bovine antral follicles (1-18 mm). Abundance of mRNA transcripts for four BMPs (BMP2, BMP4, BMP6, and BMP7) and associated type I (BMPR1A, BMPR1B, ACVR1 and ACVR1B) and type II (BMPR2, ACVR2A and ACVR2B) receptors showed relatively modest, though significant, changes during follicle development. BMP2 was selectively expressed in GC, while BMP6, BMP7 and betaglycan (TGFBR3) were more abundant in TC. Abundance of betaglycan mRNA (inhibin co-receptor) in TC increased progressively (fivefold; P<0.001) as follicles grew from 1-2 to 9-10 mm. This suggests a shift in thecal responsiveness to GC-derived inhibin, produced in increasing amounts as follicles achieve dominance. This prompted us to investigate whether inhibin can function as a physiological antagonist of BMP action on bovine TC in vitro, in a manner comparable to that for activin signalling. BMP4, BMP6 and BMP7 abolished LH induced androstenedione secretion and suppressed CYP17 mRNA >200-fold (P<0.001), while co-treatment with inhibin-A reversed the suppressive action of BMP in each case (P<0.001). Results support a physiological role for granulosa-derived inhibin as an antagonist of BMP action on thecal androgen synthesis. A shift in intrafollicular balance between thecal BMP signalling (inhibitory for androgen synthesis) and betaglycan-dependent inhibin signalling (stimulatory for androgen synthesis) accords with the physiological requirement to deliver an adequate supply of aromatase substrate to GC of developing follicles. PMID- 20739377 TI - Progesterone receptor membrane component 1 expression and putative function in bovine oocyte maturation, fertilization, and early embryonic development. AB - Although the mRNA that encodes progesterone receptor membrane component 1 (PGRMC1) is present in mammalian oocytes, nothing is known about either PGRMC1's expression pattern or function in oocytes during maturation, fertilization, and subsequent embryonic development. As PGRMC1 associates with the mitotic spindle in somatic cells, we hypothesized that PGRMC1 is involved in oocyte maturation (meiosis). Western blot analysis confirmed the presence of PGRMC1 in bovine oocytes. This study also shows that PGRMC1 is present at the germinal vesicle (GV)- and MII-stage oocytes and is associated with male and female pronucleus formation of the zygote and is highly expressed in blastocysts. A more detailed examination of PGRMC1 localization using confocal imaging demonstrated that in GV stage oocytes, PGRMC1 was concentrated throughout the GV but did not localize to the chromatin. With the resumption of meiosis in vitro, PGRMC1 concentrated in the centromeric region of metaphase I chromosomes, while in the anaphase I/telophase I stages the majority of PGRMC1 concentrated between the separating chromosomes. At the metaphase II stage, PGRMC1 re-associated with the centromeric region of the chromosomes. A colocalization study demonstrated that PGRMC1 associated with the phosphorylated form of aurora kinase B, which localizes to the centromeres at metaphase. Finally, PGRMC1 antibody injection significantly lowered the percentage of oocytes that matured and reached the metaphase II stage after 24 h of culture. The majority of the PGRMC1 antibody-injected oocytes arrested in the prometaphase I stage of meiosis. Furthermore, in most of the PGRMC1 antibody-injected oocytes, the chromosomes were disorganized and scattered. Taken together, these data demonstrate that PGRMC1 is expressed in bovine oocytes and its localization changes at specific stages of oocyte maturation. These observations suggest an important role for PGRMC1 in oocyte maturation, which may be specifically related to the mechanism by which chromosomes segregate. PMID- 20739378 TI - Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. AB - CONTEXT: Glucokinase plays a key role in glucose homeostasis. Glucokinase activators can lower glucose levels in both animal and human type 2 diabetes, but their mechanism of action has never been explored in humans. OBJECTIVE: The objective of the study was to investigate the effects of the glucokinase activator piragliatin (RO4389620) on beta-cell function and glucose fluxes in both fasting and fed (oral glucose tolerance test) states in patients with type 2 diabetes. DESIGN: This was a phase Ib randomized, double-blind, placebo controlled crossover trial of two (25 and 100 mg) doses of piragliatin. SETTING: This study was conducted at a clinical research center. PATIENTS: Patients included 15 volunteer ambulatory patients with mild type 2 diabetes. INTERVENTIONS: Interventions included three 10-h (-300' to +300') studies, with an interval of at least 14 d. Administration of a single dose of placebo or piragliatin 25 mg or piragliatin 100 mg at -120'. Oral glucose tolerance test (at 0') with dual (iv and oral routes) tracer dilution technique was conducted. MAIN OUTCOME MEASURES: The primary measure was plasma glucose concentration. The secondary measure was model assessed beta-cell function and tracer-determined glucose fluxes. RESULTS: Piragliatin caused a dose-dependent reduction of glucose levels in both fasting and fed states (P < 0.01). In the fasting state, piragliatin caused a dose-dependent increase in beta-cell function, a fall in endogenous glucose output, and a rise in glucose use (all P < 0.01). In the fed state, the primary effects of piragliatin were on beta-cell function (P < 0.01). CONCLUSIONS: The glucokinase activator piragliatin has an acute glucose-lowering action in patients with mild type 2 diabetes, mainly mediated through a generalized enhancement of beta-cell function and through fasting restricted changes in glucose turnover. PMID- 20739379 TI - Cushing's disease and idiopathic intracranial hypertension: case report and review of underlying pathophysiological mechanisms. AB - CONTEXT: Several studies have reported an association between idiopathic intracranial hypertension (IIH) and deficits of the hypothalamic-pituitary adrenal (HPA) axis. CASE ILLUSTRATION: A 33-yr-old woman with Cushing's disease underwent successful surgical resection of a pituitary adenoma and developed IIH 11 months later after inadvertent withdrawal of oral glucocorticoids. METHODS: A review of the literature was conducted to identify previous studies pertaining to IIH in association with neuroendocrine disease, focusing on reports related to HPA axis dysfunction. RESULTS: A number of patients developing IIH due to a relative deficiency in glucocorticoids, after surgical or medical management for Cushing's disease, withdrawal from glucocorticoid replacement, or as an initial presentation of Addison's disease, have been reported. Hypotheses regarding the underlying pathophysiology of IIH in this context and, in particular, the role of cortisol and its relationship to other neuroendocrine and inflammatory mediators that may regulate the homeostasis of cerebrospinal fluid production and absorption are reviewed. CONCLUSION: In a subset of patients, dysfunction of the HPA axis appears to play a role in the development of IIH. Hormonal control of cerebrospinal fluid production and absorption may be regulated by inflammatory mediators and the enzyme 11beta-hydroxysteroid dehydrogenase type 1. Further study of neuroendocrine markers in the serum and cerebrospinal fluid may be an avenue for further research in IIH. PMID- 20739380 TI - Familial longevity is associated with decreased thyroid function. AB - CONTEXT: A relation between low thyroid activity and prolonged life span in humans has been observed. Several studies have demonstrated hereditary and genetic influences on thyroid function. OBJECTIVE: The objective of the study was to test whether low thyroid activity associated with extreme longevity constitutes a heritable phenotype, which could contribute to the familial longevity observed in the Leiden Longevity Study. DESIGN: This was a cross sectional study. SETTING: The study was conducted at a university hospital in the city of Leiden, The Netherlands. PARTICIPANTS: Eight hundred fifty-nine nonagenarian siblings (median age 92.9 yr) from 421 long-lived families participated in the study. Families were recruited from the entire Dutch population if at least two long-lived siblings were alive and fulfilled the age criterion of age of 89 yr or older for males and 91 yr or older for females. There were no selection criteria on health or demographic characteristics. INTERVENTION: Blood samples were taken for determination of serum parameters of thyroid function. MAIN OUTCOME MEASURE: We calculated the family mortality history score of the parents of the nonagenarian siblings and related this to thyroid function parameters in the nonagenarian siblings. RESULTS: We found that a lower family mortality history score (less mortality) of the parents of nonagenarian siblings was associated with higher serum TSH levels (P = 0.005) and lower free T(4) levels (P = 0.002) as well as lower free T(3) levels (P = 0.034) in the nonagenarian siblings. CONCLUSIONS: Our findings support the previous observation that low thyroid activity in humans constitutes a heritable phenotype that contributes to exceptional familial longevity observed in the Leiden Longevity Study. PMID- 20739381 TI - New diagnostic criteria for diabetes: is the change from glucose to HbA1c possible in all populations? AB - AIM: Recently, a change of the diagnostic tool for diabetes from an oral glucose tolerance test (OGTT) to hemoglobin A1c (HbA1c) has been suggested. The aim of the study was to assess whether ethnicity modified the association between glucose levels and HbA1c and to compare diabetes prevalence according to diagnostic method among Greenland Inuit, Inuit migrants in Denmark, and a general Danish population. METHODS: Data from two population-based surveys conducted from 1999-2002 were compared with a total of 7957 individuals, 1173 Inuit participants from the Greenland Population Study, including 256 Inuit migrants in Denmark, and 6784 Danish participants in the Inter99 study. The participants received a standard 75-g OGTT. HbA1c was analyzed by an ion-exchange HPLC Bio-Rad variant (Hercules, California). All analyses were performed in the laboratory at Steno Diabetes Centre. RESULTS: The Inuit had significantly higher levels of HbA1c than the Danish participants at any given level of fasting and 2-h glucose and for each category of glucose tolerance: normal glucose tolerance, impaired fasting glycemia, and impaired glucose tolerance. The prevalence of diabetes diagnosed by OGTT was 11.2% among Inuit residents in Greenland, 9.8% among Inuit migrants, and 4.2% among Danes vs. 31.7% among Inuit residents in Greenland, 21.3% among Inuit migrants, and 6.7% among Danes diagnosed by HbA1c. OGTT-defined diabetes was associated with increased cardiovascular risk factors compared to HbA1c-defined diabetes. CONCLUSION: The association between glucose and HbA1c is not the same in the two populations. The mechanism behind this difference is unknown, and studies on long-term consequences associated with HbA1c are needed. PMID- 20739382 TI - Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. AB - CONTEXT: Transsphenoidal surgery is considered first-line therapy for acromegaly; however, there is often a need for adjunctive therapy. Somatostatin analogs (SSA) have greatly improved the effectiveness of medical treatment, but one third of patients are resistant. OBJECTIVE: The aim was to evaluate whether magnetic resonance imaging (MRI) signal could predict long-term response to SSA in patients with active acromegaly after neurosurgery. PATIENTS AND METHODS: Sixty two patients who were active acromegalic after surgery were included in this retrospective study. Remaining pituitary tumor was classified as hyper-, iso-, or hypointense by evaluating T2-weighted MRI signal. Treatment with SSA at maximal effective doses was prescribed and evaluated at 6 and 12 months by monitoring IGF I, GH, and T2 MRI. RESULTS: Complete response to SSA treatment (defined as normal IGF-I) at 6 months was observed in 30%, partial response (defined as IGF-I between 2 and 3 sd score) in 15%, and no response in 55% of patients. At 12 months, 28, 20, and 52% were observed, respectively. MRI signal was hypointense in 40%, hyperintense in 48%, and isointense in 12%. At 6 months, complete response to SSA was observed in 71% of cases having hypointense MRI signal and in 20% of hyperintense (P = 0.04). At 12 months, 62% of hypointense remained well controlled, whereas in the hyperintense group, good, partial, or no response results did not change from that observed at 6 months (P = 0.04). CONCLUSION: In active acromegalic patients after surgery, a hypointense T2-weighted MRI signal is associated with a better response to SSA treatment at 6 and 12 months. PMID- 20739383 TI - Overexpression and functional relevance of somatostatin receptor-1, -2, and -5 in endometrium and endometriotic lesions. AB - CONTEXT: Somatostatin plays a role in physiological and pathological cell proliferation and angiogenesis. Five subtypes of somatostatin receptors have been identified, and the therapeutic use of somatostatin receptor-selective agonists has been reported in several diseases. OBJECTIVES: The aim was to describe the expression and the functional relevance of three human somatostatin receptors (sst1, sst2, and sst5) in tissues of women with and without endometriosis. PATIENTS AND METHODS: This pilot study analyzed endometrium, ovarian endometriomata, and peritoneal lesions in 15 patients affected by endometriosis and the endometrium of five women without endometriosis. 111In-pentetreotide scintigraphy was used to detect endometriotic lesions; real-time RT-PCR and immunohistochemistry for sst1, sst2, and sst5 were performed. Migration and proliferation assays were performed on human endometrial stromal cells (ESC) treated with somatostatin and octreotide for 48 h. RESULTS: 111In-pentetreotide scintigraphy was able to correctly identify and locate pelvic endometriotic lesions as confirmed by computed tomography scans. The endometrium of women with endometriosis expressed significantly more sst1, sst2, and sst5 in comparison to that of control women. Moreover, sst1, sst2, and sst5 were highly expressed in ovarian endometriomata and peritoneal lesions. The sst receptor ligand octreotide significantly inhibited ESC migration and proliferation with a maximum effect at 10(-6) m, whereas somatostatin was effective only on ESC growth. CONCLUSIONS: This is the first report characterizing the overexpression and functional relevance of somatostatin receptors in eutopic endometrium and lesions of patients affected by endometriosis. Thus, the use of these receptors may provide new strategies for the diagnosis and treatment of endometriosis. PMID- 20739384 TI - Urinary cortisol and six-year risk of all-cause and cardiovascular mortality. AB - CONTEXT: The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality are largely absent. OBJECTIVE: The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons. DESIGN AND SETTING: Participants were part of the InCHIANTI study, a prospective cohort study in the older general population with 6 yr of follow-up. PARTICIPANTS: We studied 861 participants aged 65 yr and older. MAIN OUTCOME MEASURE: Twenty-four-hour urinary cortisol levels were assessed at baseline. In the following 6 yr, all-cause and cardiovascular mortality was ascertained from death certificates. Cardiovascular mortality included deaths due to ischemic heart disease and cerebrovascular disease. RESULTS: During a mean follow-up of 5.7 (sd = 1.2) yr, 183 persons died, of whom 41 died from cardiovascular disease. After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease (hazard ratio = 5.00; 95% confidence interval = 2.02-12.37). This effect was found to be consistent across persons with and without cardiovascular disease at baseline (p interaction = 0.78). CONCLUSIONS: High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system. PMID- 20739385 TI - DHEA-S levels and cardiovascular disease mortality in postmenopausal women: results from the National Institutes of Health--National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE). AB - CONTEXT: Dehydroepiandrosterone sulfate (DHEA-S), a major circulating sex steroid prohormone, declines with age. Low levels have been associated with increased cardiovascular disease (CVD) risk and all-cause mortality, although these results have not been consistently replicated, particularly in women. OBJECTIVE: Our objective was to examine the association of circulating DHEA-S levels, CVD, and mortality risk among postmenopausal women with suspected myocardial ischemia. DESIGN: In the Women's Ischemia Syndrome Evaluation, 270 postmenopausal women underwent coronary angiography and blood hormone levels for suspected ischemia and were followed annually. The primary outcome of interest was CVD mortality; secondary analyses included all-cause mortality and nonfatal CVD events (myocardial infarction, stroke, and congestive heart failure) and angiographic obstructive coronary artery disease (CAD). RESULTS: Women in the lowest DHEA-S tertile had higher CVD mortality (17% 6-yr mortality rate vs. 8%; log-rank P = 0.011), and all-cause mortality (21 vs. 10%; P = 0.011) compared with women with higher DHEA-S levels. The increased CVD mortality risk [hazard ratio (HR) = 2.55; 95% confidence interval (CI) = 1.19-5.45] remained unchanged after adjustment for multiple CVD risk factors (HR = 2.43; 95% CI = 1.06-5.56) but became nonsignificant when further adjusting for the presence or severity of angiographic obstructive CAD (HR = 1.99; 95% CI = 0.87-4.59). Results were similar for all-cause mortality. Lower DHEA-S levels were only marginally but not independently associated with obstructive CAD. CONCLUSIONS: Among postmenopausal women with coronary risk factors undergoing coronary angiography for suspected myocardial ischemia, lower DHEA-S levels were linked with higher CVD mortality and all-cause mortality. Our study provides valuable feasibility data useful for future investigations and possible mechanistic pathways. PMID- 20739387 TI - Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia. AB - INTRODUCTION: Adult hypophosphatasia (HPP) is characterized by low serum alkaline phosphatase (S-ALP) and poorly healing fractures due to ALPL gene mutations. Increased S-ALP and fracture repair were reported in two patients treated with teriparatide, PTH 1-34. The effects of full-length PTH 1-84 have not been studied. METHODS: Two 56- and 64-yr-old sisters (patients 1 and 2) with HPP and with long-standing, painful femur fractures received PTH 1-84 (Preotact, 100 MUg/d sc) for 7 and 18 months, respectively. Patient 1 had another treatment 8 months later because of new femur fractures. We characterized the underlying mutation(s) and treatment effects according to S-ALP, bone markers, serum ionized calcium, plasma phosphate (P-Pi), pain, mobility, and fracture healing. RESULTS: Both patients were compound heterozygotes for a p.G339R and p.E191K ALPL mutation. S-ALP increased significantly, 4.9- and 6.8-fold in patient 1 and 2.7 fold in patient 2. Responses decreased at 6 months but remained higher than basal activity. Serum N-terminal propeptide of type I procollagen and urinary N telopeptide of type I collagen increased 14- to 19-fold and 9-5-fold in patient 1, respectively, and 9- and 3-fold in patient 2. P-Pi fluctuated in patient 1 and increased in patient 2. Pain and mobility improved promptly. Fractures healed after 7-8 months of treatment in patient 1 and at 15 months in patient 2. CONCLUSION: PTH 1-84 improves pain, mobility, and fracture repair in adult HPP, even after repeat treatment. Residual activity of the p.E191K ALPL gene mutation could explain why PTH can stimulate S-ALP. P-Pi concentrations may modulate the response. PMID- 20739388 TI - Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer. AB - CONTEXT: Antiangiogenic therapies have shown potential in the treatment of advanced thyroid cancer, but it is uncertain which patients are most likely to benefit from therapy. OBJECTIVE: This prespecified exploratory analysis investigated whether baseline levels and/or changes in circulating biomarkers could predict tumor response and/or progression-free survival (PFS) among patients enrolled in a phase 2 study of motesanib in advanced thyroid cancer. DESIGN/SETTING/PATIENTS: Patients with progressive locally advanced or metastatic medullary or differentiated thyroid cancer received motesanib 125 mg once daily for up to 48 wk in a phase 2 interventional study. Samples for assessment of circulating biomarkers of angiogenesis or apoptosis were collected at study wk 1 (baseline), 2, 4, 8, 16, 24, 32, 40, 48, and 4 wk after cessation of motesanib treatment. Tumor response was assessed per Response Evaluation Criteria in Solid Tumors by independent review. RESULTS: Change from baseline in serum placental growth factor (PlGF) after 1 wk of treatment correlated with best tumor response (Kendall rank correlation, 0.28; P < 0.0001). Using a Fisher exact test, the most significant separation between patients who had an objective response and those who did not was at a 4.7-fold increase in PlGF. The response rate among patients with a greater than 4.7-fold increase in PlGF was 30% compared with 3% below this threshold. There was also a significant separation between responders and nonresponders at a 1.6-fold decrease in soluble vascular endothelial growth factor (VEGF) receptor 2 after 3 wk of treatment. Patients with baseline serum VEGF less than 671 pg/ml had significantly longer PFS times than the remainder of patients. CONCLUSIONS: Changes in PlGF and soluble VEGF receptor 2 levels after initiation of therapy predicted response to motesanib in patients with advanced differentiated thyroid cancer or metastatic medullary thyroid cancer. Lower baseline VEGF levels were associated with longer PFS. PMID- 20739389 TI - Targeting beta-cell function early in the course of therapy for type 2 diabetes mellitus. AB - OBJECTIVE: This report examines current perspectives regarding likely mechanisms of beta-cell failure in type 2 diabetes and their clinical implications for protecting or sparing beta-cells early in the disease progression. In addition, it considers translation strategies to incorporate relevant scientific findings into educational initiatives targeting clinical practice behavior. PARTICIPANTS: On January 10, 2009, a working group of basic researchers, clinical endocrinologists, and primary care physicians met to consider whether current knowledge regarding pancreatic beta-cell defects justifies retargeting and retiming treatment for clinical practice. Based on this meeting, a writing group comprised of four meeting participants subsequently prepared this consensus statement. The conference was convened by The Endocrine Society and funded by an unrestricted educational grant from Novo Nordisk. EVIDENCE: Participants reviewed and discussed published literature, plus their own unpublished data. CONSENSUS PROCESS: The summary and recommendations were supported unanimously by the writing group as representing the consensus opinions of the working group. CONCLUSIONS: Workshop participants strongly advocated developing new systems to address common barriers to glycemic control and recommended several initial steps toward this goal. These recommendations included further studies to establish the clinical value of pharmacological therapies, continuing basic research to elucidate the nature and mechanisms of beta-cell failure in type 2 diabetes mellitus, and exploring new educational approaches to promote pathophysiology based clinical practices. The Endocrine Society has launched a new website to continue the discussion between endocrinologists and primary care physicians on beta-cell pathophysiology in type 2 diabetes and its clinical implications. Join the conversation at http://www.betacellsindiabetes.org PMID- 20739390 TI - Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis. AB - Mesenchymal stem cells (MSC) have been reported to be an attractive therapeutic cell source for the treatment of renal diseases. Recently, we reported that transplantation of allogenic fetal membrane-derived MSC (FM-MSC), which are available noninvasively in large amounts, had a therapeutic effect on a hindlimb ischemia model (Ishikane S, Ohnishi S, Yamahara K, Sada M, Harada K, Mishima K, Iwasaki K, Fujiwara M, Kitamura S, Nagaya N, Ikeda T. Stem Cells 26: 2625-2633, 2008). Here, we investigated whether allogenic FM-MSC administration could ameliorate renal injury in experimental glomerulonephritis. Lewis rats with anti Thy1 nephritis intravenously received FM-MSC obtained from major histocompatibility complex-mismatched ACI rats (FM-MSC group) or a PBS (PBS group). Nephritic rats exhibited an increased urinary protein excretion in the PBS group, whereas the FM-MSC group rats had a significantly lower level of increase (P < 0.05 vs. PBS group). FM-MSC transplantation significantly reduced activated mesangial cell (MC) proliferation, glomerular monocyte/macrophage infiltration, mesangial matrix accumulation, as well as the glomerular expression of inflammatory or extracellular matrix-related genes including TNF-alpha, monocyte chemoattractant protein 1 (MCP-1), type I collagen, TGF-beta, type 1 plasminogen activator inhibitor (PAI-1) (P < 0.05 vs. PBS group). In vitro, FM MSC-derived conditioned medium significantly attenuated the expression of TNF alpha and MCP-1 in rat MC through a prostaglandin E(2)-dependent mechanism. These data suggest that transplanted FM-MSC contributed to the healing process in injured kidney tissue by producing paracrine factors. Our results indicate that allogenic FM-MSC transplantation is a potent therapeutic strategy for the treatment of acute glomerulonephritis. PMID- 20739391 TI - p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway. AB - p66Shc, a promoter of apoptosis, modulates oxidative stress response and cellular survival, but its role in the progression of diabetic nephropathy is relatively unknown. In this study, mechanisms by which p66Shc modulates high-glucose (HG)- or angiotensin (ANG) II-induced mitochondrial dysfunction were investigated in renal proximal tubular cells (HK-2 cells). Expression of p66Shc and its phosphorylated form (p-p66Shc, serine residue 36) and apoptosis were notably increased in renal tubules of diabetic mice, suggesting an increased reactive oxygen species production. In vitro, HG and ANG II led to an increased expression of total and p-p66Shc in HK-2 cells. These changes were accompanied with increased production of mitochondrial H(2)O(2), reduced mitochondrial membrane potential, increased translocation of mitochondrial cytochrome c from mitochondria into cytosol, upregulation of the expression of caspase-9, and ultimately reduced cell survival. Overexpression of a dominant-negative Ser36 mutant p66Shc (p66ShcS36A) or treatment of p66Shc- or PKC-beta-short interfering RNAs partially reversed these changes. Treatment of HK-2 cells with HG and ANG II also increased the protein-protein association between p-p66Shc and Pin1, an isomerase, in the cytosol, and with cytochrome c in the mitochondria. These interactions were partially disrupted with the treatment of PKC-beta inhibitor or Pin1-short interfering RNA. These data suggest that p66Shc mediates HG- and ANG II-induced mitochondrial dysfunctions via PKC-beta and Pin1-dependent pathways in renal tubular cells. PMID- 20739392 TI - Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice. AB - ATRAP [ANG II type 1 receptor (AT1R)-associated protein] is a molecule which directly interacts with AT1R and inhibits AT1R signaling. The aim of this study was to examine the effects of continuous ANG II infusion on the intrarenal expression and distribution of ATRAP and to determine the role of AT1R signaling in mediating these effects. C57BL/6 male mice were subjected to vehicle or ANG II infusions at doses of 200, 1,000, or 2,500 ng.kg(-1).min(-1) for 14 days. ANG II infusion caused significant suppression of ATRAP expression in the kidney but did not affect ATRAP expression in the testis or liver. Although only the highest ANG II dose (2,500 ng.kg(-1).min(-1)) provoked renal pathological responses, such as an increase in the mRNA expression of angiotensinogen and the alpha-subunit of the epithelial sodium channel, ANG II-induced decreases in ATRAP were observed even at the lowest dose (200 ng.kg(-1).min(-1)), particularly in the outer medulla of the kidney, based on immunohistochemical staining and Western blot analysis. The decrease in renal ATRAP expression by ANG II infusion was prevented by treatment with the AT1R-specific blocker olmesartan. In addition, the ANG II mediated decrease in renal ATRAP expression through AT1R signaling occurred without an ANG II-induced decrease in plasma membrane AT1R expression in the kidney. On the other hand, a transgenic model increase in renal ATRAP expression beyond baseline was accompanied by a constitutive reduction of renal plasma membrane AT1R expression and by the promotion of renal AT1R internalization as well as the decreased induction of angiotensinogen gene expression in response to ANG II. These results suggest that the plasma membrane AT1R level in the kidney is modulated by intrarenal ATRAP expression under physiological and pathophysiological conditions in vivo. PMID- 20739393 TI - Fibroblast growth factor 23 production in bone is directly regulated by 1{alpha},25-dihydroxyvitamin D, but not PTH. AB - Fibroblast growth factor 23 (FGF23), which is primarily produced by osteocytes in bone, regulates renal phosphate excretion and 1alpha,25-dihydroxyvitamin D [1,25(OH)(2)D(3)] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating serum FGF23, but the direct effect on circulating FGF23 levels in renal insufficiency is still unclear. To identify the major regulator of FGF23 synthesis in renal insufficiency, we compared the effect of parathyroid hormone (PTH) and 1,25(OH)(2)D(3) on FGF23 synthesis in the calvariae of normal rats with that of uremic rats in vitro. 1,25(OH)(2)D(3) treatment significantly increased the FGF23 concentration in the medium from both groups, but the degree of increase in the uremic group was markedly higher than in the control group. A significant increase in FGF23 mRNA expression occurred as early as 4 h after treatment and reached the maximum within 8 h in the uremic group, whereas in the normal group a significant increase in FGF23 mRNA expression was observed only at 8 h. In addition, the expression of vitamin D receptor (VDR) mRNA in the calvariae of uremic rats was markedly higher than in normal rats. However, in neither group did PTH treatment affect the medium FGF23 concentration or the FGF23 mRNA levels. These results suggest that FGF23 synthesis in bone is regulated by 1,25(OH)(2)D(3) directly, not by PTH, and that increased VDR mRNA expression induced the relatively swift and strong response in the uremic group. PMID- 20739394 TI - TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion. AB - The hypothesis that TNF receptor 1-deficient (TNFR1(-/-)) mice display blood pressure (BP) and renal functional responses that differ from wild-type (WT) mice was tested in an angiotensin II (ANG II)-dependent model of hypertension. Basal systolic BP (SBP), mean arterial pressure, diastolic BP, heart rate (HR), and pulse pressure were similar in WT and TNFR1(-/-) mice. Infusion of ANG II for 7 days elevated SBP to a greater extent in TNFR1(-/-) compared with WT mice; pulse pressure was also elevated in TNFR1(-/-). HR decreased in TNFR1(-/-) mice infused with ANG II, an effect prominent on day 1. Basal urinary albumin excretion was similar in WT and TNFR1(-/-) mice but was higher in TNFR1(-/-) in response to ANG II infusion. Water intake and urine volume were increased by ANG II infusion; this increase was higher in TNFR1(-/-) vs. WT mice, whereas body weight and food intake were unaffected. Baseline creatinine clearance (Ccr), urinary sodium excretion, and fractional excretion of sodium (FE(Na)%) were similar in vehicle treated WT and TNFR1(-/-) mice. ANG II infusion for 7 days increased Ccr and filtered load of sodium in TNFR1(-/-) but not WT mice, whereas it elicited an increase in FE(Na)% and urinary sodium excretion in WT but not TNFR1(-/-) mice. ANG II also inhibited renal TNFR1 mRNA accumulation while increasing that of TNFR2. These findings indicate deletion of TNFR1 is associated with an exacerbated SBP response, decrease in HR, and altered renal function in ANG II dependent hypertension. PMID- 20739395 TI - Effector memory T lymphocytes in renal disease. PMID- 20739396 TI - TRB3: an oxidant stress-induced pseudokinase with a potential to negatively modulate MCP-1 cytokine in diabetic nephropathy. PMID- 20739398 TI - C1q/TNF-related protein-3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue. AB - Proteins secreted by adipocytes (adipokines) play an important role in the pathophysiology of type 2 diabetes mellitus and the associated chronic and low grade state of inflammation. It was the aim to characterize the antiinflammatory potential of the new adipocytokine, C1q/TNF-related protein-3 (CTRP-3), which shows structural homologies to the pleiotropic adipocytokine adiponectin. mRNA and protein expression of CTRP-3 was analyzed by RT-PCR and Western blot. Recombinant CTRP-3 and small interfering RNA-based strategies were used to investigate the effect of CTRP-3 on toll-like receptor (TLR) ligand, lipopolysaccharide (LPS)-, and lauric acid-induced chemokine release of monocytes and adipocytes. Together with complex ELISA-based techniques, a designed TLR4/myeloid differentiation protein-2 fusion molecule shown to bind LPS was used to prove the ability of CTRP-3 to act as endogenous LPS antagonist. CTRP-3 is synthesized in monocytes and adipocytes. The recombinant protein dose-dependently inhibits the release of chemokines in monocytes and adipocytes that were induced by lauric acid, LPS, and other TLR ligands in vitro and ex vivo. CTRP-3 inhibits monocyte chemoattractant protein-1 release in adipocytes, whereas small interfering RNA-mediated knockdown of CTRP-3 up-regulates monocyte chemoattractant protein-1 release, reduces lipid droplet size, and decreases intracellular triglyceride concentration in adipocytes, causing a dedifferentiation into a more proinflammatory and immature phenotype. By using a designed TLR4/MD-2 fusion molecule, it is shown by different techniques that CTRP 3 specifically and effectively inhibits the binding of LPS to its receptor, TLR4/MD-2. CTRP-3 inhibits three basic and common proinflammatory pathways involved in obesity and type 2 diabetes mellitus (adipo-inflammation) by acting as an endogenous LPS antagonist of the adipose tissue. PMID- 20739397 TI - Defective gonadotropin-dependent ovarian folliculogenesis and granulosa cell gene expression in inhibin-deficient mice. AB - Inhibin-alpha knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins (FSH and LH) are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH. These studies suggest that in the absence of inhibins, granulosa cells differentiate abnormally and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling contributing to tumor development. To test this hypothesis, we stimulated immature wild-type and Inha-/- female mice with gonadotropin analogs prior to tumor formation and subsequently examined gonadotropin-induced ovarian follicle development as well as preovulatory and human chorionic gonadotropin-induced gene expression changes in granulosa cells. We find that at 3 wk of age, inhibin-deficient ovaries do not show further antral development or undergo cumulus expansion. In addition, there are widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells, with significant changes in genes involved in extracellular matrix and cell-cell communication. These data indicate the gonadotropins initiate an improper program of cell differentiation prior to tumor formation in the absence of inhibins. PMID- 20739399 TI - Tissue distribution and cardiac metabolism of 3-iodothyronamine. AB - 3-iodothyronamine (T1AM) is a novel relative of thyroid hormone, able to interact with specific G protein-coupled receptors, known as trace amine-associated receptors. Significant functional effects are produced by exogenous T1AM, including a negative inotropic and chronotropic effect in cardiac preparations. This work was aimed at estimating endogenous T1AM concentration in different tissues and determining its cardiac metabolism. A novel HPLC tandem mass spectrometry assay was developed, allowing detection of T1AM, thyronamine, 3 iodothyroacetic acid, and thyroacetic acid. T1AM was detected in rat serum, at the concentration of 0.3+/-0.03 pmol/ml, and in all tested organs (heart, liver, kidney, skeletal muscle, stomach, lung, and brain), at concentrations significantly higher than the serum concentration, ranging from 5.6+/-1.5 pmol/g in lung to 92.9+/-28.5 pmol/g in liver. T1AM was also identified for the first time in human blood. In H9c2 cardiomyocytes and isolated perfused rat hearts, significant Na+-dependent uptake of exogenous T1AM was observed, and at the steady state total cellular or tissue T1AM concentration exceeded extracellular concentration by more than 20-fold. In both preparations T1AM underwent oxidative deamination to 3-iodothyroacetic acid. T1AM deamination was inhibited by iproniazid but not pargyline or semicarbazide, suggesting the involvement of both monoamine oxidase and semicarbazide-sensitive amine oxidase. Thyronamine and thyroacetic acid were not detected in heart. Finally, evidence of T1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low. PMID- 20739400 TI - GADD45gamma: a new vitamin D-regulated gene that is antiproliferative in prostate cancer cells. AB - 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits proliferation of normal and malignant prostate epithelial cells at least in part through inhibition of G1 to S phase cell cycle progression. The mechanisms of the antiproliferative effects of 1,25-(OH)2D3 have yet to be fully elucidated but are known to require the vitamin D receptor. We previously developed a 1,25-(OH)2D3-resistant derivative of the human prostate cancer cell line, LNCaP, which retains active vitamin D receptors but is not growth inhibited by 1,25-(OH)2D3. Gene expression profiling revealed two novel 1,25-(OH)2D3-inducible genes, growth arrest and DNA damage inducible gene gamma (GADD45gamma) and mitogen induced gene 6 (MIG6), in LNCaP but not in 1,25-(OH)2D3-resistant cells. GADD45gamma up-regulation was associated with growth inhibition by 1,25-(OH)2D3 in human prostate cancer cells. Ectopic expression of GADD45gamma in either LNCaP or ALVA31 cells resulted in G1 accumulation and inhibition of proliferation equal to or greater than that caused by 1,25-(OH)2D3 treatment. In contrast, ectopic expression of MIG6 had only minimal effects on cell cycle distribution and proliferation. Whereas GADD45gamma has been shown to be induced by androgens in prostate cancer cells, up-regulation of GADD45gamma by 1,25-(OH)2D3 was not dependent on androgen receptor signaling, further refuting a requirement for androgens/androgen receptor in vitamin D mediated growth inhibition. These data introduce two novel 1,25-(OH)2D3-regulated genes and establish GADD45gamma as a growth-inhibitory protein in prostate cancer. Furthermore, the induction of GADD45gamma gene expression by 1,25-(OH)2D3 may mark therapeutic response in prostate cancer. PMID- 20739402 TI - Osteoclastic metabolism of 25(OH)-vitamin D3: a potential mechanism for optimization of bone resorption. AB - The extrarenal synthesis of 1alpha,25 dihydroxyvitamin D3 (1,25D) has been demonstrated in a number of cell types including osteoblasts and cells of the monocyte/macrophage lineage. The skeleton appears responsive to serum levels of the 1,25D precursor, 25 hydroxyvitamin D3 (25D), in terms of bone mineralization parameters. The effect of metabolism of 25D into active 1,25D by osteoclast lineage cells is unknown. We found that CYP27B1 mRNA expression increased with exposure of human peripheral blood mononuclear cells (PBMCs) to macrophage colony stimulating factor in the presence or absence of receptor activator of nuclear factor-kappaB ligand. Consistent with this, human osteoclast cultures incubated with 25D produced measurable quantities of 1,25D. Osteoclast formation from either mouse RAW264.7 cells or human PBMCs in the presence of physiological concentrations of 25D resulted in significant up-regulation of the key osteoclast transcription factor, nuclear factor of activated T cells-c1 in PBMCs and a number of key osteoclast marker genes in both models. The expression of the osteoblast coupling factor, ephrin-b2, was also increased in the presence of 25D. Levels of CYP27B1 and nuclear factor of activated T cells-1 mRNA correlated during osteoclastogenesis and also in a cohort of human bone samples. CYP27B1 short-hairpin RNA knockdown in RAW264.7 cells decreased their osteoclastogenic potential. 25D dose dependently reduced the resorptive capacity of PBMC-derived osteoclasts without compromising cell viability. 25D also reduced resorption by RAW264.7- and giant cell tumor-derived osteoclasts. Conversely, osteoclasts formed from vitamin D receptor-null mouse splenocytes had increased resorptive activity compared with wild-type cells. We conclude that 25D metabolism is an important intrinsic mechanism for optimizing osteoclast differentiation, ameliorating osteoclast activity, and potentially promoting the coupling of bone resorption to formation. PMID- 20739401 TI - Progesterone treatment inhibits and dihydrotestosterone (DHT) treatment potentiates voltage-gated calcium currents in gonadotropin-releasing hormone (GnRH) neurons. AB - GnRH neurons are central regulators of fertility, and their activity is modulated by steroid feedback. In normal females, GnRH secretion is regulated by estradiol and progesterone (P). Excess androgens present in hyperandrogenemic fertility disorders may disrupt communication of negative feedback signals from P and/or independently stimulate GnRH release. Voltage-gated calcium channels (VGCCs) are important in regulating excitability and hormone release. Estradiol alters VGCCs in a time-of-day-dependent manner. To further elucidate ovarian steroid modulation of GnRH neuron VGCCs, we studied the effects of dihydrotestosterone (DHT) and P. Adult mice were ovariectomized (OVX) or OVX and treated with implants containing DHT (OVXD), estradiol (OVXE), estradiol and DHT (OVXED), estradiol and P (OVXEP), or estradiol, DHT, and P (OVXEDP). Macroscopic calcium current (I(Ca)) was recorded in the morning or afternoon 8-12 d after surgery using whole-cell voltage-clamp. I(Ca) was increased in afternoon vs. morning in GnRH neurons from OVXE mice but this increase was abolished in cells from OVXEP mice. I(Ca) in cells from OVXD mice was increased regardless of time of day; there was no additional effect in OVXED mice. P reduced N-type and DHT potentiated N- and R-type VGCCs; P blocked the DHT potentiation of N-type mediated current. These data suggest P and DHT have opposing actions on VGCCs in GnRH neurons, but in the presence of both steroids, P dominates. VGCCs are targets of ovarian steroid feedback modulation of GnRH neuron activity and, more specifically, a potential mechanism whereby androgens could activate GnRH neuronal function. PMID- 20739403 TI - DHT selectively reverses Smad3-mediated/TGF-beta-induced responses through transcriptional down-regulation of Smad3 in prostate epithelial cells. AB - Androgens suppress TGF-beta responses in the prostate through mechanisms that are not fully explored. We have recently reported that 5alpha-dihydrotestosterone (DHT) suppresses the ability of TGF-beta to inhibit proliferation and induce apoptosis of prostatic epithelial cells and provided evidence that such suppression was fueled by transcriptional down-regulation of TGF-beta receptor II (TaubetaRII). We now show that androgen receptor (AR) activated by DHT suppresses the TGF-beta-induced phosphorylation of Sma- and Mad-related protein (Smad)3 in LNCaP cells overexpressing TbetaRII under the control of a cytomegalovirus promoter, which is not regulated by DHT, suggesting that transcriptional repression of TbetaRII alone does not fully account for the impact of DHT on TGF beta responses. Instead, we demonstrate that such suppression occurs through loss of total Smad3, resulting from transcriptional suppression of Smad3. We provide evidence that DHT down-regulates the promoter activity of Smad3 in various prostate cancer cell lines, including NRP-154+AR, DU145+AR, LNCaP, and VCaP, at least partly through androgen-dependent inactivation of Sp1. Moreover, we show that overexpression of Smad3 reverses the ability of DHT to protect against TGF beta-induced apoptosis in NRP-154+AR, supporting our model that loss of Smad3 by DHT is involved in the protection against TGF-beta-induced apoptosis. Together, these findings suggest that deregulated/enhanced expression and activation of AR in prostate carcinomas may intercept the tumor suppressor function of TGF-beta through transcriptional suppression of Smad3, thereby providing new mechanistic insight into the development of castration-resistant prostate cancer. PMID- 20739404 TI - The thyroid hormone receptor alpha1 protein is expressed in embryonic postmitotic neurons and persists in most adult neurons. AB - Thyroid hormone is essential for brain development where it acts mainly through the thyroid hormone receptor alpha1 (TRalpha1) isoform. However, the potential for the hormone to act in adult neurons has remained undefined due to difficulties in reliably determining the expression pattern of TR proteins in vivo. We therefore created a mouse strain that expresses TRalpha1 and green fluorescent protein as a chimeric protein from the Thra locus, allowing examination of TRalpha1 expression during fetal and postnatal development and in the adult. Furthermore, the use of antibodies against other markers enabled identification of TRalpha1 expression in subtypes of neurons and during specific stages of their maturation. TRalpha1 expression was first detected in postmitotic cells of the cortical plate in the embryonic telencephalon and preceded the expression of the mature neuronal protein NeuN. In the cerebellum, TRalpha1 expression was absent in proliferating cells of the external granular layer, but switched on as the cells migrated towards the internal granular layer. In addition, TRalpha1 was expressed transiently in developing Purkinje cells, but not in mature cells. Glial expression was found in tanycytes in the hypothalamus and in the cerebellum. In the adult brain, TRalpha1 expression was detected in essentially all neurons. Our data demonstrate that thyroid hormone, unexpectedly, has the capacity to play an important role in virtually all developing and adult neurons. Because the role of TRalpha1 in most neuronal cell types in vivo is largely unknown, our findings suggest that novel functions for thyroid hormone remain to be identified in the brain. PMID- 20739405 TI - Do patients with liver cirrhosis undergoing cardiac surgery have acceptable outcomes? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether patients with liver cirrhosis have acceptable outcomes after undergoing cardiac surgery. Altogether 97 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, year, journal, country of study, study type, patient group studied, relevant outcomes, results and study weaknesses were tabulated. One prospective and another eight retrospective studies involving adult population of patients with liver cirrhosis undergoing various cardiac surgical procedures were selected. In these studies, the overall mortality was 17.1% and combined mean mortality for Child-Pugh class A, B and C was 5.2%, 35.4% and 70%, respectively. The major morbidity ranged from 20 to 60% in group A and 50 to 100% in the patients with more advanced hepatic disease. Some studies have demonstrated that thrombocytopenia, decreased serum cholinesterase and high preoperative total bilirubin levels are significantly associated with worse clinical outcomes. These studies, although with small samples, collectively demonstrate that patients with Child-Pugh class A cirrhosis tolerated cardiac surgical procedures with a mild increase in mortality and morbidity. However, the risk of mortality in patients with Child-Pugh class B and C or MELD score>13 is extremely high. Nevertheless, even if these patients underwent successful surgery, their long-term survival was significantly poorer and their health status remains compromised even well after cardiac surgery because of persistent liver dysfunction. PMID- 20739406 TI - Facilitated anastomosis using a reverse thermo-sensitive polymer for temporary coronary occlusion in off-pump minimally invasive direct coronary artery bypass surgery. AB - To evaluate the safety and efficacy of a novel, reverse thermo-sensitive polymer (LeGooTM) for its ability to provide temporary coronary occlusion and hemostasis during minimally invasive direct coronary artery bypass (MIDCAB) surgery. Between January 2009 and March 2009, 20 consecutive MIDCAB patients were studied. Ten patients received a conventional MIDCAB procedure using proximal vessel loops and CO2 blower (control group). The following 10 patients were operated by an otherwise identical procedure, except that intracoronary administration of LeGooTM was used instead of vessel snares (LeGooTM group). Left internal mammary artery (LIMA) bypass flow, peri- and postoperative events and perioperative creatinine kinase-MB fraction (CK-MB) release were prospectively analyzed. CO2 blower use was required in three of 10 of the LeGooTM patients. Procedural time was identical, with a trend of shorter anastomosis time in the LeGooTM group (12.3 vs. 10.7 min, P=0.11). LIMA-LAD flow was also not different (control 35.8 vs. LeGooTM 42.5 ml/min, P=0.541). CK-MB values were not statistically different on postoperative days 1 and 2. However, the level of CK-MB 4 h postoperatively was lower in LeGooTM patients (18.3+/-6.1 vs. 13.2+/-2.9 U/l, P=0.006). No major adverse cerebral or cardiovascular event occurred postoperatively and during follow-up of 317+/-21 days. Using LeGooTM to achieve temporary coronary artery occlusion is easier to work with during MIDCAB due to the absence of vessel snares and less need of blowing to eliminate blood from the operative field. There were no negative postoperative events associated with the use of LeGooTM. PMID- 20739407 TI - Acute myocardial infarction caused by coronary embolization of a papillary fibroelastoma of the thoracic ascending aorta. AB - Papillary fibroelastomas (PFE) are benign endocardial masses and generally originate from the cardiac valves, while PFE arising from the ascending thoracic aorta are an uncommon clinical finding. We report the case of a 78-year-old female who presented to the emergency department with an acute ST segment elevation myocardial infarction. Urgent coronary angiography showed no significant coronary artery obstructive disease but left ventriculography revealed the presence of a highly mobile mass located in the proximal portion of the ascending thoracic aorta. We postulated that the clinical symptoms were caused by embolization from the aortic mass and surgical excision of the peduncle was performed. Histopathological examination revealed a PFE with thrombotic material. Nowadays, surgical excision of PFE remains, the treatment of choice for symptomatic patients with excellent short- and long-term results but recurrence of PFE following surgical excision has not been reported. PMID- 20739408 TI - Severe left atrium compression after percutaneous coronary intervention with perforation of a circumflex branch of the left coronary artery. AB - Coronary artery perforation is a rare complication of percutaneous coronary intervention, but can result in cardiac tamponade and is thus potentially life threatening. This report describes a rare case of epimyocardial haematoma formation after coronary perforation resulting in a functional mitral stenosis in a patient with coronary bypass grafting in his history. Coronary artery perforations in patients who had previously undergone a coronary bypass grafting procedure, may lead to uncommon haematoma localizations with significant functional implications. A rapid surgical intervention can be life saving. PMID- 20739409 TI - Primary arterial switch operation for transposition of the great arteries with intact ventricular septum--is it safe after three weeks of age? AB - In patients with transposition of the great arteries with intact ventricular septum (TGA-IVS), late presentation for surgical treatment is not uncommon. Earlier experience suggested an excess mortality for the primary arterial switch operation (ASO) when performed after the third week of life in such patients. The true age limit for the primary ASO, however, remains speculative. A best evidence topic was written to determine the safety of extending the age limit of the primary ASO for TGA-IVS beyond three weeks of age. Eight of 74 relevant papers constituted the best evidence to address the issue. Sufficient level II evidence was found to suggest that in experienced institutions in the current era, the ASO for TGA-IVS may be performed primarily in infants three to eight weeks of age with comparable early outcomes to younger patients. Kang et al. investigated 275 neonates (younger than 21 days) and 105 infants (age range 21-185 days) undergoing the primary ASO for TGA-IVS. They found no significant difference in terms of in-hospital mortality (5.5% vs. 3.8%) or need for mechanical left ventricular (LV) support (3.6% vs. 5.7%) between the younger and older groups, respectively. Of the younger group, 3.8% developed postoperative LV failure leading to death or mechanical LV support. All nine patients older than two months (age range 61-185 days) survived to discharge although two (aged 69 and 86 days) required mechanical LV support for postoperative LV failure. The postoperative course of the late ASO group, however, was significantly prolonged as reflected in the duration of postoperative ventilation (4.9 vs. 7.1 days, P=0.012) and length of postoperative stay (12.5 vs. 18.9 days, P=0.001). In the report of Sarris et al., 52 patients with TGA-IVS who were older than four weeks of age (36 were older than eight weeks) underwent a primary ASO with early mortality comparable with younger patients (2% vs. 3%, respectively). For infants between the ages of two and six months, the strength of the evidence favoring this management approach is limited by the small sample size of reported series and the increased requirement for mechanical circulatory support for postoperative LV failure. PMID- 20739410 TI - Risk factors and mortality associated with deep sternal wound infections following coronary bypass surgery with or without concomitant procedures in a UK population: a basis for a new risk model? AB - Deep sternal wound infection (DSWI) is a rare but serious complication following coronary artery bypass surgery. Our study investigates the risk factors and mortality associated with DSWI with other risk models for DSWI. Data was collected prospectively on 7602 patients undergoing coronary artery bypass grafting+/-concomitant surgery between April 1999 and September 2009 including DSWI. All 13 Society for Thoracic Surgeons (STS) risk scoring variables were assessed using logistic regression in relation to developing DSWI. The STS risk scores were evaluated using the area under the receiver operating curve. A total of 44 (0.59%) patients developed DSWI. These patients had a higher mortality (9.1%) than patients without DSWI (2.6%) (P=0.03). The mean preoperative and combined STS scores were significantly higher in the DSWI patient group compared to the non-DSWI group (9.46+/-4.30 and 8.76+/-3.86 vs. 7.07+/-4.25 and 6.51+/ 4.11, P=0.0003 and P=0.0005, respectively). Logistic regression identified age [odds ratio (OR)=1.055], body mass index (OR=1.076), diabetes (OR=2.00) and chronic lung disease (OR=2.47) as the significant independent determinants of DSWI from the variables considered. Mortality rates and mean STS scores are higher in patients requiring re-opening for DSWI. Not all the STS risk factors were predictors of DSWI in our population. PMID- 20739411 TI - Cell biology of prokaryotic organelles. AB - Mounting evidence in recent years has challenged the dogma that prokaryotes are simple and undefined cells devoid of an organized subcellular architecture. In fact, proteins once thought to be the purely eukaryotic inventions, including relatives of actin and tubulin control prokaryotic cell shape, DNA segregation, and cytokinesis. Similarly, compartmentalization, commonly noted as a distinguishing feature of eukaryotic cells, is also prevalent in the prokaryotic world in the form of protein-bounded and lipid-bounded organelles. In this article we highlight some of these prokaryotic organelles and discuss the current knowledge on their ultrastructure and the molecular mechanisms of their biogenesis and maintenance. PMID- 20739412 TI - Hormone action in the mammary gland. AB - A woman's breast cancer risk is affected by her reproductive history. The hormonal milieu also influences the course of the disease. The female reproductive hormones, estrogens, progesterone, and prolactin, have a major impact on breast cancer and control postnatal mammary gland development. Analysis of hormone receptor mutant mouse strains combined with tissue recombination techniques and proteomics revealed that sequential activation of hormone signaling in the mammary epithelium is required for progression of morphogenesis. Hormones impinge on a subset of luminal mammary epithelial cells (MECs) that express hormone receptors and act as sensor cells translating and amplifying systemic signals into local stimuli. Proliferation is induced by paracrine mechanisms mediated by distinct factors at different stages. Tissue and stage specificity of hormonal signaling is achieved at the molecular level by different chromatin contexts and differential recruitment of coactivators and corepressors. PMID- 20739413 TI - Odyssey of auxin. AB - The history of plant biology is inexorably intertwined with the conception and discovery of auxin, followed by the many decades of research to comprehend its action during growth and development. Growth responses to auxin are complex and require the coordination of auxin production, transport, and perception. In this overview of past auxin research, we limit our discourse to the mechanism of auxin action. We attempt to trace the almost epic voyage from the birth of the hormonal concept in plants to the recent crystallographic studies that resolved the TIR1 auxin receptor complex, the first structural model of a plant hormone receptor. The century-long endeavor is a beautiful illustration of the power of scientific reasoning and human intuition, but it also brings to light the fact that decisive progress is made when new technologies emerge and disciplines unite. PMID- 20739414 TI - The X as model for RNA's niche in epigenomic regulation. AB - The X-linked region now known as the "X-inactivation center" (Xic) was once dominated by protein-coding genes but, with the rise of Eutherian mammals some 150-200 million years ago, became infiltrated by genes that produce long noncoding RNA (ncRNA). Some of the noncoding genes have been shown to play crucial roles during X-chromosome inactivation (XCI), including the targeting of chromatin modifiers to the X. The rapid establishment of ncRNA hints at a possible preference for long transcripts in some aspects of epigenetic regulation. This article discusses the role of RNA in XCI and considers the advantages RNA offers in delivering allelic, cis-limited, and locus-specific control. Unlike proteins and small RNAs, long ncRNAs are tethered to the site of transcription and effectively tag the allele of origin. Furthermore, long ncRNAs are drawn from larger sequence space than proteins and can mark a unique region in a complex genome. Thus, like their small RNA cousins, long ncRNAs may emerge as versatile and powerful regulators of the epigenome. PMID- 20739417 TI - High prevalence of genu varum/valgum in European children with low vitamin D status and insufficient dairy products/calcium intakes. AB - OBJECTIVE: The prevalence of lower limb deformities physiologically decreases after 5 years of age. It remains high in some tropical and subtropical regions where it has been associated with severe vitamin D deficiency, low calcium/milk intakes, malnutrition, and/or fluoride overexposure. Very little data is available in apparently healthy Caucasian children and adolescents. DESIGN: We evaluated the prevalence of genu varum/valgum and other clinical symptoms, and assessed vitamin D status and markers of calcium metabolism in 226 apparently healthy European full-time boarders (7-16 years) seen during winter-spring and fed a cereal-based diet with little access to meat, milk, and dairy products. A cohort of 71 white children and adolescents hospitalized for acute illness served as age-matched controls. RESULTS: Association studies showed a high prevalence of lower limb deformities (36%) and higher alkaline phosphate activities in the 21% of children and adolescent full-time boarders with serum 25-(OH)D levels <= 30 nmol/l, and low serum calcium in the 74% of boarders with 25-(OH)D levels <= 50 nmol/l, compared with boarders with higher vitamin D status. No such anomalies were found in the control cohort despite lower serum 25-(OH)D levels. CONCLUSIONS: Low 25-(OH)D levels, at least during winter-spring, combined with additional risk factors such as very low calcium/milk intakes and possibly digestive disorders, are associated with an increased risk of genu varum/valgum in European children and adolescents. Thus, dietary fortification, or supplementation with vitamin D, may be recommended, at least during the winter, to European children and adolescents with either none or insufficient calcium/dairy product intakes. PMID- 20739415 TI - The origins of the RNA world. AB - The general notion of an "RNA World" is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein based life. However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imagined that all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules. A thorough consideration of this "RNA-first" view of the origin of life must reconcile concerns regarding the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth. Perhaps these concerns will eventually be resolved, and recent experimental findings provide some reason for optimism. However, the problem of the origin of the RNA World is far from being solved, and it is fruitful to consider the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA. PMID- 20739416 TI - RNA reactions one molecule at a time. AB - Much of the dynamics information is lost in bulk measurements because of the population averaging. Single-molecule methods measure one molecule at a time; they provide knowledge not obtainable by other means. In this article, we review the application of the two most widely used single-molecule methods--fluorescence resonance energy transfer (FRET) and force versus extension measurements--to several RNA reactions. First, we discuss folding/unfolding studies on a hairpin ribozyme that revealed multiple conformations of the RNA with distinct kinetics, and on a series of RNA pseudoknots, whose mechanical stabilities were found to show a strong correlation with their frameshifting efficiency during translation. We also discuss several RNA-related molecular motors. Single-molecule experiments revealed detailed mechanisms for the interaction of HIV reverse transcriptase and nucleic acid helicases (NS3 and RIG-1) with their substrates. Optical tweezers studies showed that translation of a single messenger RNA by a ribosome occurs by successive translocation-and-pause cycles. Single-molecule FRET experiments yielded important information on ribosome conformational changes and tRNA dynamics during translation. Overall, single-molecule experiments have been very valuable for understanding RNA reactions. PMID- 20739419 TI - Dietary intake of stearidonic acid-enriched soybean oil increases the omega-3 index: randomized, double-blind clinical study of efficacy and safety. AB - BACKGROUND: The benefits of omega-3 (n-3) long-chain polyunsaturated fatty acids to heart health are well established. Stearidonic acid (SDA, 18:4n-3) may contribute to these benefits. OBJECTIVE: The objective was to evaluate the ability of SDA-containing soybean oil to increase the omega-3 index [erythrocyte eicosapentaenoic acid (EPA) + docosahexaenoic acid, as a percentage of total fatty acids] and to affect other cardiovascular disease risk markers compared with EPA and regular soy oil (control). DESIGN: This was a randomized, placebo controlled, double-blind multicenter study in which 252 overweight subjects were randomly assigned to 1 of 3 treatments for 12 wk: 1 g encapsulated soybean oil/d plus 14.7 g liquid soybean oil/d to be mixed in food (control group), 1 g encapsulated EPA/d plus 14.7 g liquid soybean oil/d (EPA group), and 1 g encapsulated soybean oil/d plus 14.7 g liquid SDA-enriched soybean oil/d, providing 4.2 g SDA (SDA group). Subjects consumed treatment oils in exchange for other oils in their diet. RESULTS: The mean (+/-SE) baseline omega-3 index was similar between treatments, but after 12 wk of treatment values for this index were 4.15 +/- 0.12%, 4.84 +/- 0.13%, and 4.69 +/- 0.15% for control, EPA, and SDA groups, respectively. Values for the EPA and SDA groups were greater than those for control subjects in the intent-to-treat population (P < 0.001 and P = 0.006, respectively). No adverse treatment-related effects of SDA-enriched soybean oil were reported. CONCLUSIONS: SDA-enriched soybean oil increased the omega-3 index by raising erythrocyte EPA concentrations. SDA-enriched soybean oil is a land based n-3 fatty acid that is a sustainable approach to increasing tissue concentrations of long-chain polyunsaturated n-3 fatty acids. PMID- 20739420 TI - The contribution of malabsorption to the reduction in net energy absorption after long-limb Roux-en-Y gastric bypass. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) restricts food intake, and when the Roux limb is elongated to 150 cm, the procedure is believed to induce malabsorption. OBJECTIVE: Our objective was to measure total reduction in intestinal absorption of combustible energy after RYGB and the extent to which this was due to restriction of food intake or malabsorption of ingested macronutrients. DESIGN: Long-limb RYGB was performed in 9 severely obese patients. Dietary intake and intestinal absorption of fat, protein, carbohydrate, and combustible energy were measured before and at 2 intervals after bypass. By using coefficients of absorption to measure absorptive function, equations were developed to calculate the daily gram and kilocalorie quantities of ingested macronutrients that were not absorbed because of malabsorption or restricted food intake. RESULTS: Coefficients of fat absorption were 92 +/- 1.3% before bypass, 72 +/- 5.5% 5 mo after bypass, and 68 +/- 8.7% 14 mo after bypass. There were no statistically significant effects of RYGB on protein or carbohydrate absorption coefficients, although protein coefficients decreased substantially in some patients. Five months after bypass, malabsorption reduced absorption of combustible energy by 124 +/- 57 kcal/d, whereas restriction of food intake reduced energy absorption by 2062 +/- 271 kcal/d. Fourteen months after bypass, malabsorption reduced energy absorption by 172 +/- 60 kcal/d compared with 1418 +/- 171 kcal/d caused by restricted food intake. CONCLUSION: On average, malabsorption accounted for ~6% and 11% of the total reduction in combustible energy absorption at 5 and 14 mo, respectively, after this gastric bypass procedure. PMID- 20739418 TI - Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial. AB - BACKGROUND: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain. OBJECTIVE: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome. DESIGN: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets. RESULTS: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 * 10(-4) mL . MUU(-1) . min(-1) (interquartile range: 2.0, 4.2 * 10(-4) mL . MUU(-1) . min(-1)), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, -4% (-12.7%, 5.3%); for the HM/HGI group, 2.1% (-5.8%, 10.7%); for the HM/LGI group, -3.5% (-10.6%, 4.3%); for the LF/HGI group, -8.6% (-15.4%, 1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations. CONCLUSIONS: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298. PMID- 20739421 TI - Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake. AB - BACKGROUND: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. OBJECTIVE: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. DESIGN: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. RESULTS: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. CONCLUSIONS: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control. This trial was registered at clinicaltrials.gov as NCT00390637. PMID- 20739423 TI - Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians. AB - BACKGROUND: Understanding folate intakes after folic acid fortification of the food supply will help to establish dietary and supplement recommendations that balance health benefits and risks. OBJECTIVES: The objectives were to estimate the prevalence of folate inadequacy (POFI) and intakes above the Tolerable Upper Intake Level (UL) among Canadians and to estimate the supplemental dose that, with diet, provides reproductive-aged women with 400 MUg folic acid/d to prevent neural tube defects. DESIGN: Twenty-four-hour recall and supplement (prior 30 d) data from the 2004 Canadian Community Health Survey (n = 35,107) were used to calculate the POFI and intakes above the UL with and without adjustment for fortification overages. POFI was also estimated by risk factors thought to be related to low folate intake. The Software for Intake Distribution Evaluation (SIDE program; Department of Statistics and Center for Agricultural and Rural Development, Iowa State University) was used to estimate usual dietary intakes in all analyses. RESULTS: Except for women aged >70 y, POFI was <20% after adjustment for fortification overages. For children aged <14 y, POFI approached zero, even when supplement use was excluded. POFI among adults was unaffected by supplement use, except for women aged >70 y. Only 18% of reproductive-aged women consumed 400 MUg folic acid/d from diet and supplements. Modeling showed that supplements containing 325-700 MUg folic acid would provide adult women with 400 MUg/d but not more than the UL. Diabetes was associated with POFI. CONCLUSIONS: Innovative strategies are needed to ensure that the subgroups of Canadians who could still benefit from improved folate intake are targeted. Consideration should be given to removing folic acid from supplements designed for young children and men. PMID- 20739422 TI - Maternal serum folate species in early pregnancy and risk of preterm birth. AB - BACKGROUND: Poor maternal folate status has been associated with an increased risk of preterm birth. However, major gaps remain in our understanding of how individual folate species relate to preterm birth. OBJECTIVE: Our objective was to assess the association between maternal folate status as measured by 5 methyltetrahydrofolate (5MeTHF), 5-formyltetrahydrofolate (5FoTHF), and folic acid concentrations, which are the 3 primary folate species in serum, and the risk of preterm birth and spontaneous preterm birth (sPTB). DESIGN: A cohort of 313 pregnant women who received care at resident antepartum clinics at Magee Womens Hospital (Pittsburgh, PA) (2003-2007) was enrolled at <16 wk gestation. We analyzed nonfasting blood samples that were drawn from subjects at enrollment for the 3 folate species by using HPLC-tandem mass spectrometry. RESULTS: Serum 5MeTHF and 5FoTHF concentrations comprised 65% and 33% of total folate concentrations, respectively. In confounder-adjusted, multivariable, log-binomial regression models, 1-SD increases in serum total folate and serum 5MeTHF concentrations were associated with significant reductions in the risk of sPTB (P < 0.05). There was a significant interaction between serum 5MeTHF and 5FoTHF concentrations and risk of preterm birth (P = 0.01). When serum 5MeTHF concentrations were low, there was a positive linear relation between 5FoTHF and risk of preterm birth. When 5MeTHF concentrations were high, there was a strong negative relation between 5FoTHF and preterm birth. CONCLUSIONS: Our results imply that the relative concentrations of folate species may be more critical than total folate in preventing preterm birth. An improved understanding of folate metabolism during pregnancy may lead to targeted intervention strategies that decrease the rate of preterm birth. PMID- 20739425 TI - Ethnic differences in blood lipids and dietary intake between UK children of black African, black Caribbean, South Asian, and white European origin: the Child Heart and Health Study in England (CHASE). AB - BACKGROUND: Ischemic heart disease (IHD) rates are lower in UK black Africans and black Caribbeans and higher in South Asians when compared with white Europeans. Ethnic differences in lipid concentrations may play a part in these differences. OBJECTIVE: The objective was to investigate blood lipid and dietary patterns in UK children from different ethnic groups. DESIGN: This was a cross-sectional study in 2026 UK children (including 285 black Africans, 188 black Caribbeans, 534 South Asians, and 512 white Europeans) attending primary schools in London, Birmingham, and Leicester. We measured fasting blood lipid concentrations and collected 24-h dietary recalls. RESULTS: In comparison with white Europeans, black African children had lower total cholesterol (-0.14 mmol/L; 95% CI: -0.25, 0.04 mmol/L), LDL-cholesterol (-0.10 mmol/L; 95% CI: -0.20, -0.01 mmol/L), and triglyceride concentrations (proportional difference: -0.11 mmol/L; 95% CI: 0.16, -0.06 mmol/L); HDL-cholesterol concentrations were similar. Lower saturated fat intakes (-1.4%; 95% CI: -1.9%, -0.9%) explained the differences between total and LDL cholesterol. Black Caribbean children had total, LDL-cholesterol, HDL cholesterol, and triglyceride concentrations similar to those for white Europeans, with slightly lower saturated fat intakes. South Asian children had total and LDL-cholesterol concentrations similar to those for white Europeans, lower HDL-cholesterol concentrations (-0.7 mmol/L; 95% CI: -0.11, -0.03 mmol/L), and elevated triglyceride concentrations (proportional difference: 0.14 mmol/L; 95% CI: 0.09, 0.20 mmol/L); higher polyunsaturated and monounsaturated fat intakes did not explain these lipid differences. CONCLUSIONS: Only black African children had a blood lipid profile and associated dietary pattern likely to protect against future IHD. The loss of historically lower LDL-cholesterol concentrations among UK black Caribbeans and South Asians may have important adverse consequences for future IHD risk in these groups. PMID- 20739424 TI - Coffee consumption and risk of incident gout in women: the Nurses' Health Study. AB - BACKGROUND: Coffee is one of the most widely consumed beverages in the world and may affect the risk of gout via various mechanisms, but prospective data on the relation between coffee intake and the risk of incident gout are limited. DESIGN: Over a 26-y period, we prospectively examined the relation between coffee intake and risk of incident gout in 89,433 female participants in the Nurses' Health Study. We assessed the consumption of coffee, decaffeinated coffee, tea, and total caffeine in participants every 2-4 y through validated questionnaires. We used a supplementary questionnaire to ascertain whether participants met the survey criteria of the American College of Rheumatology for gout. RESULTS: During the 26 y of follow-up, we documented 896 confirmed incident cases of gout. There was an inverse association between higher coffee intake and the risk of gout. The multivariate relative risks (RRs) for incident gout according to coffee consumption categories [ie, 0, 1-237, 238-947, and >=948 mL coffee/d (237 mL = one 8-ounce cup)] were 1.00, 0.97, 0.78 (95% CI: 0.64, 0.95), and 0.43 (95% CI: 0.30, 0.61; P for trend < 0.0001), respectively. For decaffeinated coffee, the multivariate RRs according to consumption categories (0, 1-237, and >=237 mL decaffeinated coffee/d) were 1.00, 1.02, and 0.77 (95% CI: 0.63, 0.95; P for trend = 0.02), respectively. There was an inverse association between total caffeine from all sources and the risk of gout; the multivariate RR of the highest quintile compared with the lowest quintile was 0.52 (95% CI: 0.41, 0.68; P for trend <0.0001). CONCLUSION: These prospective data suggest that long-term coffee consumption is associated with a lower risk of incident gout in women. PMID- 20739427 TI - High nitrogen fertilization and stem leaning have overlapping effects on wood formation in poplar but invoke largely distinct molecular pathways. AB - Previous studies indicated that high nitrogen fertilization may impact secondary xylem development and alter fibre anatomy and composition. The resulting wood shares some resemblance with tension wood, which has much thicker cell walls than normal wood due to the deposition of an additional layer known as the G-layer. This report compares the short-term effects of high nitrogen fertilization and tree leaning to induce tension wood, either alone or in combination, upon wood formation in young trees of Populus trichocarpa (Torr. & Gray) * P. deltoides Bartr. ex Marsh. Fibre anatomy, chemical composition and transcript profiles were examined in newly formed secondary xylem. Each of the treatments resulted in thicker cell walls relative to the controls. High nitrogen and tree leaning had overlapping effects on chemical composition based on Fourier transform infrared analysis, specifically indicating that secondary cell wall composition was shifted in favour of cellulose and hemicelluloses relative to lignin content. In contrast, the high-nitrogen trees had shorter fibres, whilst the leaning trees had longer fibres that the controls. Microarray transcript profiling carried out after 28 days of treatment identified 180 transcripts that accumulated differentially in one or more treatments. Only 10% of differentially expressed transcripts were affected in all treatments relative to the controls. Several of the affected transcripts were related to carbohydrate metabolism, secondary cell wall formation, nitrogen metabolism and osmotic stress. RT-qPCR analyses at 1, 7 and 28 days showed that several transcripts followed very different accumulation profiles in terms of rate and level of accumulation, depending on the treatment. Our findings suggest that high nitrogen fertilization and tension wood induction elicit largely distinct and molecular pathways with partial overlap. When combined, the two types of environmental cue yielded additive effects. PMID- 20739426 TI - Effect of vitamin supplements on HIV shedding in breast milk. AB - BACKGROUND: Supplementation in lactating HIV-1-infected women with preformed vitamin A and beta-carotene (VA/BC) increases the risk of mother-to-child transmission of HIV through breastfeeding. Identifying a biological mechanism to explain this unexpected finding would lend support to a causal effect. OBJECTIVE: The aim of the study was to evaluate the effect of VA/BC or multivitamin (B complex, vitamin C, and vitamin E) supplementation of HIV-infected women on HIV shedding in breast milk during the first 2 y postpartum. DESIGN: We quantified viral (cell-free) and proviral (cell-associated) HIV loads in breast-milk samples collected <=15 d after delivery and every 3 mo thereafter from 594 Tanzanian HIV 1-infected women who participated in a randomized trial. Women received 1 of the following 4 daily oral regimens in a 2 * 2 factorial fashion during pregnancy and throughout the first 2 y postpartum: multivitamin, VA/BC, multivitamin including VA/BC, or placebo. RESULTS: The proportion of breast-milk samples with detectable viral load was significantly higher in women who received VA/BC (51.3%) than in women who were not assigned to VA/BC (44.8%; P = 0.02). The effect was apparent >=6 mo postpartum (relative risk: 1.34; 95% CI: 1.04, 1.73). No associations with proviral load were observed. The multivitamin had no effects. In observational analyses, beta-carotene but not retinol breast-milk concentrations were significantly associated with an increased viral load in milk. CONCLUSIONS: VA/BC supplementation in lactating women increases the HIV load in breast milk. This finding contributes to explaining the adverse effect of VA/BC on mother-to-child transmission. beta-Carotene appears to have an effect on breast-milk viral load, independent of preformed vitamin A. This trial was registered at clinicaltrials.gov as NCT00197756. PMID- 20739428 TI - Volatile organic compound emissions induced by the aphid Myzus persicae differ among resistant and susceptible peach cultivars and a wild relative. AB - Little is known on aphid-induced emissions of volatile organic compounds (VOCs) from trees and particularly on their intraspecific variability in association with resistance traits. We compared VOC emissions from five peach cultivars (Prunus persica (L.) Batsch) and a wild relative (Prunus davidiana (Carriere) Franch) that differ in their level (susceptible/resistant) and type (antixenosis, antibiosis) of resistance to the green peach aphid, Myzus persicae (Sulzer). Additionally, the kinetics of VOC induction in response to aphids was compared with that by mechanical wounding. Qualitative and overall quantitative differences among peach genotypes were found in VOC emissions that were mainly composed of methyl-salicylate, farnesenes, (E)-beta-ocimene and (E)-4,8-dimethyl 1,3,7-nonatriene. Irrespective of the type of resistance, all resistant genotypes had increased VOC emissions upon aphid attack, while in susceptible genotypes emissions remained low. Emission increases were highest in the genotypes that express increased aphid resistance during second infestations, which had also the highest proportions of methyl-salicylate in their emissions. VOC induction by aphids proceeded slowly with a delay of several hours. Artificial wounding of leaves did not result in emissions of aphid-induced VOCs but caused an immediate burst of green leaf volatiles and benzaldehyde. We conclude that VOC induction in resistant peach cultivars is part of a general defence syndrome that is being avoided or suppressed by M. persicae in the susceptible genotypes. The induction likely involves an aphid-specific elicitor and (methyl)-salicylate in the subsequent signalling and regulation processes that should include gene activation due to the marked delay in the emission response. The results are compared with those of the literature and discussed in view of their ecological and environmental significance. PMID- 20739429 TI - The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster. AB - Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired. PMID- 20739431 TI - A phase I/II trial combining high-dose melphalan and autologous transplant with bortezomib for multiple myeloma: a dose- and schedule-finding study. AB - PURPOSE: We did a randomized phase I/II trial designed to evaluate the safety and efficacy of combining the proteasome inhibitor bortezomib with high-dose melphalan as the conditioning for high-dose therapy and autologous transplant for myeloma. EXPERIMENTAL DESIGN: Enrolled patients were limited to those who did not achieve a very good partial remission (VGPR) following one or more induction regimens, and were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m(2)) either 24 hours before or 24 hours after high-dose melphalan. Dose escalation was based on the escalation with overdose control (EWOC), a Bayesian statistical model. Bone marrow aspirates were collected before initiation of therapy and at the time of transplant to evaluate which sequence resulted in maximal plasma cell apoptosis, and response to transplant was assessed by the International Myeloma Working Group criteria. RESULTS: Among 39 randomized patients, 20 received bortezomib after melphalan and 19 received bortezomib before melphalan. Toxicities and posttransplant hematopoietic recovery rates were similar between arms. The overall response rate for all patients was 87%, with 51% achieving a VGPR or better. Pharmacodynamic studies showed greater plasma cell apoptosis among patients who received bortezomib following melphalan. CONCLUSIONS: The use of bortezomib in conjunction with high-dose melphalan is safe, with data suggesting improved efficacy. A single dose of bortezomib administered after high-dose melphalan is the recommended dose and schedule for future clinical investigation. PMID- 20739430 TI - Calcium signaling in taste cells: regulation required. AB - Peripheral taste receptor cells depend on distinct calcium signals to generate appropriate cellular responses that relay taste information to the central nervous system. Some taste cells have conventional chemical synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release from stores to formulate an output signal through a hemichannel. Despite the importance of calcium signaling in taste cells, little is known about how these signals are regulated. This review summarizes recent studies that have identified 2 calcium clearance mechanisms expressed in taste cells, including mitochondrial calcium uptake and sodium/calcium exchangers (NCXs). These studies identified a unique constitutive calcium influx that contributes to maintaining appropriate calcium homeostasis in taste cells and the role of the mitochondria and exchangers in this process. The additional role of NCXs in the regulation of evoked calcium responses is also discussed. Clearly, calcium signaling is a dynamic process in taste cells and appears to be more complex than has previously been appreciated. PMID- 20739433 TI - Folotyn (pralatrexate injection) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma: U.S. Food and Drug Administration drug approval summary. AB - PURPOSE: On September 24, 2009, the U.S. Food and Drug Administration granted accelerated approval for Folotyn (pralatrexate injection, Allos Therapeutics, Inc.) as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL); it is the first drug approved for this indication. EXPERIMENTAL DESIGN: This review was based on study PDX-008, a phase II, single-arm, nonrandomized, open-label, international, multicenter trial, designed to evaluate the safety and efficacy of pralatrexate when administered concurrently with vitamin B(12) and folic acid supplementation in patients with relapsed or refractory PTCL. RESULTS: The overall response rate was 27% in 109 evaluable patients [95% confidence interval (CI), 19-36%]. Twelve percent of 109 evaluable patients (95% CI, 7-20%)] had a response duration of >=14 weeks. Six of these 13 patients achieved a complete response, and one patient had complete response unconfirmed. The most common grade 3 and 4 toxicities were thrombocytopenia, mucositis, and neutropenia. CONCLUSION: This accelerated approval was based on a response rate that is reasonably likely to predict clinical benefit in this heavily pretreated patient population with this rare disease. The applicant has committed to conducting postmarketing clinical trials to assess clinical benefit. The recommended starting dose of pralatrexate in patients with relapsed or refractory PTCL is 30 mg/m(2) via intravenous push over 3 to 5 min weekly for 6 weeks followed by a one-week rest (one cycle). Intramuscular injection of 1 mg vitamin B(12) should be administered every 8 to 10 weeks along with 1.0 mg folic acid given orally once a day. PMID- 20739432 TI - Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. AB - PURPOSE: Plexiform neurofibromas (pNF) are Schwann cell tumors found in a third of individuals with neurofibromatosis type 1 (NF1). pNF can undergo transformation to malignant peripheral nerve sheath tumors (MPNST). There are no identified serum biomarkers of pNF tumor burden or transformation to MPNST. Serum biomarkers would be useful to verify NF1 diagnosis, monitor tumor burden, and/or detect transformation. EXPERIMENTAL DESIGN: We used microarray gene expression analysis to define 92 genes that encode putative secreted proteins in neurofibroma Schwann cells, neurofibromas, and MPNST. We validated differential expression by quantitative reverse transcription-PCR, Western blotting, and ELISA assays in cell conditioned medium and control and NF1 patient sera. RESULTS: Of 13 candidate genes evaluated, only adrenomedullin (ADM) was confirmed as differentially expressed and elevated in serum of NF1 patients. ADM protein concentrati on was further elevated in serum of a small sampling of NF1 patients with MPNST. MPNST cell conditioned medium, containing ADM and hepatocyte growth factor, stimulated MPNST migration and endothelial cell proliferation. CONCLUSIONS: Thus, microarray analysis identifies potential serum biomarkers for disease, and ADM is a serum biomarker of NF1. ADM serum levels do not seem to correlate with the presence of pNFs but may be a biomarker of transformation to MPNST. PMID- 20739434 TI - Prognostic gene expression signature for squamous cell carcinoma of lung. AB - PURPOSE: This study aimed to identify and validate a gene expression signature for squamous cell carcinoma of the lung (SQCC). EXPERIMENTAL DESIGN: A published microarray dataset from 129 SQCC patients was used as a training set to identify the minimal gene set prognostic signature. This was selected using the MAximizing R Square Algorithm (MARSA), a novel heuristic signature optimization procedure based on goodness-of-fit (R square). The signature was tested internally by leave one-out-cross-validation (LOOCV), and then externally in three independent public lung cancer microarray datasets: two datasets of non-small cell lung cancer (NSCLC) and one of adenocarcinoma (ADC) only. Quantitative-PCR (qPCR) was used to validate the signature in a fourth independent SQCC cohort. RESULTS: A 12-gene signature that passed the internal LOOCV validation was identified. The signature was independently prognostic for SQCC in two NSCLC datasets (total n = 223) but not in ADC. The lack of prognostic significance in ADC was confirmed in the Director's Challenge ADC dataset (n = 442). The prognostic significance of the signature was validated further by qPCR in another independent cohort containing 62 SQCC samples (hazard ratio, 3.76; 95% confidence interval, 1.10-12.87; P = 0.035). CONCLUSIONS: We identified a novel 12-gene prognostic signature specific for SQCC and showed the effectiveness of MARSA to identify prognostic gene expression signatures. PMID- 20739435 TI - Directed and conditional deceased donor organ donations: laws and misconceptions. PMID- 20739436 TI - Risky business? The risks and benefits of umbilical cord blood collection. PMID- 20739437 TI - The trouble with paediatricians. PMID- 20739438 TI - Take this medicine: the legality of prescription incentive schemes. PMID- 20739439 TI - The need for balancing the reproductive rights of women and the unborn in the Mexican courtroom. PMID- 20739440 TI - Changes in alcohol availability, price and alcohol-related problems and the collectivity of drinking cultures: what happened in southern and northern Sweden? AB - AIMS: The aims of this study were to study whether alcohol-related self-reported problems follow the same pattern of changes in alcohol consumption in southern Sweden, assumed to be affected by a decrease in Danish spirits tax and by an increase in Swedish travellers' import quotas, and to study whether the results obtained for southern and northern Sweden follow the predictions of Skog's theory of collectivity of drinking cultures. METHODS: Analysis was carried out on a sample from the Swedish general population from southern and northern Sweden separately. Two indices such as impaired self-control/dependent behaviour and extrinsic problems for alcohol-related problems were computed and analysed in terms of sex, age, income and alcohol consumption level. RESULTS: Although there were no huge changes in the number of persons reporting alcohol-related problems, the general trend in data for various subpopulations was a decrease in the southern site and an increase in the northern site. In the northern site, the increase in alcohol consumption among men also showed an increase in alcohol related problems. However, various population subgroups changed in different directions and did not move in concert over the population distribution. CONCLUSIONS: Analysis confirmed that alcohol-related problems, according to the two indices used, followed a similar pattern to alcohol consumption, but less divergent. A version of Skog's theory applied on alcohol-related problems could not confirm that alcohol-related problems did not change collectively within the population. PMID- 20739441 TI - The impact of alcohol marketing on youth drinking behaviour: a two-stage cohort study. AB - AIM: To examine whether awareness of, and involvement with alcohol marketing at age 13 is predictive of initiation of drinking, frequency of drinking and units of alcohol consumed at age 15. METHODS: A two-stage cohort study, involving a questionnaire survey, combining interview and self-completion, was administered in respondents' homes. Respondents were drawn from secondary schools in three adjoining local authority areas in the West of Scotland, UK. From a baseline sample of 920 teenagers (aged 12-14, mean age 13), in 2006, a cohort of 552 was followed up 2 years later (aged 14-16, mean age 15). Data were gathered on multiple forms of alcohol marketing and measures of drinking initiation, frequency and consumption. RESULTS: At follow-up, logistic regression demonstrated that, after controlling for confounding variables, involvement with alcohol marketing at baseline was predictive of both uptake of drinking and increased frequency of drinking. Awareness of marketing at baseline was also associated with an increased frequency of drinking at follow-up. CONCLUSIONS: Our findings demonstrate an association between involvement with, and awareness of, alcohol marketing and drinking uptake or increased drinking frequency, and we consider whether the current regulatory environment affords youth sufficient protection from alcohol marketing. PMID- 20739442 TI - Asking the right questions about substitution and complementarity: a comment on Moore's paper. PMID- 20739443 TI - Effects of changes in availability of alcohol: unexpected results can stimulate theory development and research. PMID- 20739444 TI - Postprandial lipid-related metabolites are altered in dogs fed dietary diacylglycerol and low glycemic index starch during weight loss. AB - In this study, we investigated a combination of a low glycemic index starch (LGIS) and diacylglycerol (DAG) on lipid, lipoprotein (LP) metabolism, and weight management. Obese, intact female adult Beagle dogs were assigned to 1 of 4 starch/oil combination diets [LGIS/DAG (LD); LGIS/triacylglycerol (TAG); high glycemic index starch (HGIS)/DAG; and HGIS/TAG (HT)] and fed for 9 wk (n = 6/group) using an incomplete 4 * 4 Latin square design. Each dog was fed 1 of 2 opposite starch/oil combination diets (e.g. LD and HT). At wk 1 and 8, postprandial blood was collected for plasma triacylglycerol (TG), beta hydroxybutyrate (BHB), total cholesterol (TC), and LP analyses. During the same week, dogs were overnight feed-deprived and post-heparin blood was collected for LP lipase and hepatic lipase activity determinations. At wk 1, 4, and 8, blood was drawn from overnight feed-deprived dogs for plasma TG, BHB, TC, LP, leptin, and adiponectin measurements. Feces were collected at wk 3 for digestibility calculations. The LGIS diets resulted in lower carbohydrate, protein, total tract dry matter digestibilities, and metabolizable energy compared with the HGIS diet groups (P < 0.05). Thus, the LGIS groups lost more body weight (P = 0.001), which was positively correlated with plasma leptin concentrations (r(2) = 0.427; P < 0.001). Moreover, the LGIS diet lowered TC concentrations in combination with DAG. The DAG diet groups decreased postprandial TG and increased BHB concentrations (P < 0.05). Starch/oil types did not alter lipase activities or adiponectin concentrations. In conclusion, the LGIS diet demonstrated potential as a weight management tool in dogs by decreasing postprandial TG and increasing BHB in combination with DAG. PMID- 20739445 TI - Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. AB - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = -16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = -27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC. PMID- 20739446 TI - A one-year intervention has modest effects on energy and macronutrient intakes of overweight and obese Swedish children. AB - To decrease BMI in overweight and obese children, improved dietary intake and increased physical activity are key elements. Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children. A randomized open trial was conducted with 92 overweight or obese 10.4 +/- 1.08-y-old children. The intervention included 14 group sessions with different themes regarding food and physical activity. Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations. The control group participated in the same measurements as the intervention group but did not take part in group sessions. After 1 y, both groups had decreased their energy intake (EI) relative to total energy expenditure, but the effect was more pronounced for the intervention group than for the control group. At 1 y follow-up, a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar (P = 0.019). However, the groups did not differ in the proportion children who met the recommended intake of dietary fiber. Further, SFA intake relative to total EI did not differ between the groups at 1 y follow-up. In conclusion, despite a rather comprehensive intervention, only modest effects were achieved with respect to reduced EI and improved macronutrient intake. PMID- 20739447 TI - Vitamin supplementation increases risk of subclinical mastitis in HIV-infected women. AB - Subclinical mastitis is common in HIV-infected women and is a risk factor for mother-to-child transmission of HIV. The purpose of this study was to examine the effect of vitamin supplementation [vitamin A + beta-carotene, multivitamins (B complex, C, and E), or multivitamins, including vitamin A + beta-carotene] on the risk of subclinical mastitis during the first 2 y postpartum among HIV-infected women. The study was a randomized, placebo-controlled, clinical trial including 674 HIV-infected, antiretroviral naive Tanzanian women who were recruited during pregnancy and followed-up after delivery. Breast milk samples were obtained approximately every 3 mo. Any subclinical mastitis was defined as a ratio of the sodium to potassium (Na:K) breast milk concentrations > 0.6 and further classified as either moderate (Na:K >= 0.6 and <= 1) or severe (Na:K > 1.0). Fifty-eight percent of women had at least 1 episode of any subclinical mastitis. Women assigned to multivitamins (B complex, C, and E) had a 33% greater risk of any subclinical mastitis (P = 0.005) and a 75% greater risk of severe subclinical mastitis (P = 0.0006) than women who received the placebo. Vitamin A + beta carotene also increased the risk of severe subclinical mastitis by 45% (P = 0.03). Among women with CD4+ T-cell counts >= 350 cells/MUL, multivitamin intake resulted in a 49% increased risk of any subclinical mastitis (P = 0.006); by contrast, there were no treatment effects among women with CD4+ T-cell counts < 350 cells/MUL (P- interaction for treatment * CD4+ T-cell count = 0.10). Supplementation of HIV-infected women with vitamins increased the risk of subclinical mastitis. PMID- 20739448 TI - Low calcium intake is related to increased risk of tooth loss in men. AB - Our aim was to investigate the association between calcium (Ca) intake and number of teeth and tooth loss. The Danish Monica (Monitoring Trends and Determinants in Cardiovascular Disease) study is a prospective observational study from 1982-83 to 1993-94. The study population included 1602 adults (30-60 y) with information on dietary Ca intake and number of teeth and a subset of 511 participants with information on tooth loss from 1987-88 to 1993-94. Ca intake less than the recommendations, estimated by a 7-d food record or a diet history interview in 1982-83, was more frequent among females (55%) than males (45%; P < 0.001). Low Ca intake was associated with low number of teeth (1-25 vs. 26-32 teeth) in males [odds ratio (OR) = 1.57 (95% CI = 1.10-2.29)] and females [OR = 1.44 (95% CI = 1.10-2.05)] after adjustment for age, education, smoking, alcohol and sucrose consumption, subjective oral dryness, and time since last dental care visit. The reference group (26-32 teeth) and edentulous participants did not significantly differ. A Ca intake below recommendations was significantly associated with increased risk of subsequent tooth loss in males [incidence-rate ratio = 1.70 (95% CI = 1.15-2.48)]. There was no association in women. Ca intake below recommendations was significantly associated with fewer teeth in both sexes. However, there was a significant, negative association between Ca intake below recommendations and tooth loss in males only. Given the high percentage of individuals with Ca intake below recommendations, consumption of foods rich in Ca should be promoted to preserve oral health. PMID- 20739449 TI - Dietary dried plum increases bone mass in adult and aged male mice. AB - Bone is progressively lost with advancing age. Therapies are limited and the only effective proanabolic regimen presently available to restore bone is intermittent treatment with teriparatide (parathyroid hormone 1-34). Recent evidence suggests that dietary supplementation with dried plum (DP) can prevent bone loss due to estrogen deficiency. To determine whether dietary DP supplementation can prevent the loss of bone with aging and whether bone that has already been lost can be restored, adult (6 mo) and old (18 mo) male mice were fed a normal diet or isoenergetic, isonitrogenous diets supplemented with DP (0, 15, and 25% DP by weight) for 6 mo. MicroCT analysis and bone histomorphometry were used to assess bone volume, structure, and metabolic activity before, during, and after dietary supplementation. Mice fed the 0% DP diet (control diet) lost bone, whereas both adult and old mice fed the 25% DP-supplemented diet gained bone. Adult but not old mice fed the 15% diet also gained bone. Cancellous bone volume in mice receiving 25% DP exceeded baseline levels by 40-50%. Trabecular structure varied with diet and age and responses in old mice were generally blunted. Trabecular, but not cortical, mineral density varied with age and measures of bone anabolic activity were lower in aged mice. Our findings suggest that DP contains proanabolic factors that can dramatically increase bone volume and restore bone that has already been lost due to aging. In turn, DP may provide effective prophylactic and therapeutic agents for the treatment of osteoporosis. PMID- 20739450 TI - Targeted analysis of conjugated and microbial-derived phenolic metabolites in human urine after consumption of an almond skin phenolic extract. AB - A single-blind, placebo-controlled, and randomized trial study was carried out with 16 healthy volunteers (7 men and 5 women). The test group ingested an encapsulated almond skin phenolic extract (884 mg of total polyphenols/dose) containing flavan-3-ols, flavonols, and flavanones, whereas the placebo group ingested microcrystalline cellulose. Our aim in this study was to determine changes in the urinary excretion of conjugated and microbial-derived phenolic metabolites before (-2 to 0 h) and after (0-2, 2-6, 6-10, and 10-24 h) intake of the almond polyphenols compared with the placebo group. For the test group, maximum urinary excretion of (epi)catechin and naringenin conjugates derived from phase II metabolism was attained at 2-6 h after consumption of the almond skin extract and excretions differed from the placebo group during this time period (P <= 0.0001). However, excretion of conjugated metabolites of isorhamnetin was highest at 10-24 h and did not differ from the placebo group during this time (P > 0.05). Hydroxyphenylvalerolactones reached maximum urinary levels at 6-10 h after consumption of almond polyphenols, and excretion differed from the placebo group during this time period (P = 0.0004). For the test group, excretions of phenolic acids (hydroxyphenylpropionic, hydroxyphenylacetic, hydroxybenzoic, and hydroxycinnamic acids) did not differ from the placebo group at any time period of urine collection (P > 0.05). The findings presented in this work provide evidence concerning the bioavailability of almond skin polyphenols considering the effects of both phase II and microbial metabolism. PMID- 20739451 TI - Keto-carotenoids are the major metabolites of dietary lutein and fucoxanthin in mouse tissues. AB - Fucoxanthin, a xanthophyll present in brown algae consumed in Eastern Asia, can suppress carcinogenesis and obesity in rodents. We investigated the metabolism, tissue distribution, and depletion of fucoxanthin in ICR mice by comparison with those of lutein. The experiments comprised 14-d dietary supplementation with lutein esters or fucoxanthin, followed by 41- or 28-d, respectively, depletion periods with carotenoid-free diets. After lutein ester supplementation, 3' hydroxy-epsilon,epsilon-caroten-3-one and lutein were the predominant carotenoids in plasma and tissues, accompanied by epsilon,epsilon-carotene-3,3'-dione. The presence of these keto-carotenoids in mouse tissues is reported here for the first time, to our knowledge. Lutein and its metabolites accumulated most in the liver (7.51 MUmol/kg), followed by plasma (2.11 MUmol/L), adipose tissues (1.01 1.44 MUmol/kg), and kidney (0.87 MUmol/kg). The half-life of the depletion (t(1/2)) of lutein metabolites varied as follows: plasma (1.16 d) < liver (2.63 d) < kidney (4.44 d) < < < adipose tissues (>41 d). Fucoxanthinol and amarouciaxanthin A were the main metabolites in mice fed fucoxanthin and partitioned more into adipose tissues (3.13-3.64 MUmol/kg) than into plasma, liver, and kidney (1.29-1.80 MUmol/kg). Fucoxanthin metabolites had shorter t(1/2) in plasma, liver, and kidneys (0.92-1.23 d) compared with those of adipose tissues (2.76-4.81 d). The tissue distribution of lutein and fucoxanthin metabolites was not associated with their lipophilicity, but depletion seemed to be slower for more lipophilic compounds. We concluded that mice actively convert lutein and fucoxanthin to keto-carotenoids by oxidizing the secondary hydroxyl groups and accumulate them in tissues. PMID- 20739452 TI - Dietary patterns in Mexican adults are associated with risk of being overweight or obese. AB - Our objective was to identify and describe the major dietary patterns in the Mexican adult population and their association with being overweight or obese. Dietary intake was evaluated by a FFQ that was completed by 15,890 Mexican adults who participated in the National Health and Nutrition Survey 2006. Dietary patterns were generated by cluster analysis based on the percent contribution to total energy intake from 30 food groups. We identified 3 major dietary patterns: refined foods and sweets (RS), traditional (T), and diverse (D). The T pattern was characterized by low dietary diversity, with maize and maize foods accounting for ~47% of energy intake. This pattern had the lowest contribution of most food groups, with the exception of beans (~4.0%). The RS pattern had the highest contribution of alcohol (9.4%), soft drinks (9.4%), white bread (7.7%), fast food, sweets, and snacks. The D pattern had the lowest contribution of maize (15.5%) and the highest contribution of whole-fat dairy (8.0%), rice and pasta, meat, poultry, eggs, saturated fat, fruits, and vegetables. After adjusting for age, gender, physical activity, socioeconomic status, area, and region, the RS and D dietary patterns were associated with 14 and 17% increased risk of being overweight (P < 0.01) and 20% increased risk of being obese, respectively, compared with the T dietary pattern (P < 0.001). These findings support an association of dietary patterns with being overweight or obese in a nationally representative sample of Mexican adults. PMID- 20739453 TI - Human pregnane X receptor agonism by Ginkgo biloba extract: assessment of the role of individual ginkgolides. AB - Ginkgo biloba extract activates pregnane X receptor (PXR), but how this occurs is not known. Therefore, we investigated the mechanism of PXR activation by the extract and the role of five individual terpene trilactones in the activation. In a cell-based reporter gene assay, G. biloba extract activated human PXR (hPXR), and at a concentration present in the extract, ginkgolide A, but not ginkgolide B, ginkgolide C, ginkgolide J, or bilobalide was partially responsible for the increase in hPXR activity of the extract. Likewise, in cultured human hepatocytes, only ginkgolide A contributed to the increase in hPXR target gene expression (CYP3A4 mRNA and CYP3A-mediated testosterone 6beta-hydroxylation). The extract, but none of the terpene trilactones, bound to hPXR ligand-binding domain, as analyzed by a time-resolved fluorescence resonance energy transfer competitive binding assay. Only the extract and ginkgolide A recruited steroid receptor coactivator-1, as determined by a mammalian two-hybrid assay. Compared with hPXR, rat PXR (rPXR) was activated to a lesser extent by G. biloba extract. Similar to hPXR, only ginkgolide A contributed to rPXR activation by the extract. In contrast to the effect of G. biloba extract on PXR function, it did not affect hPXR expression. Overall, the main conclusions are that G. biloba extract is an hPXR agonist, and among the five terpene trilactones investigated, only ginkgolide A contributes to the actions of the extract. Our findings provide insights into the biological and chemical mechanisms of hPXR activation by G. biloba extract. PMID- 20739454 TI - Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor. AB - Histone deacetylases (HDACs) are validated targets for anticancer therapy as attested by the approval of suberoylanilide hydroxamic acid (SAHA) and romidepsin (FK228) for treating cutaneous T cell lymphoma. We recently described the bioassay-guided isolation, structure determination, synthesis, and target identification of largazole, a marine-derived antiproliferative natural product that is a prodrug that releases a potent HDAC inhibitor, largazole thiol. Here, we characterize the anticancer activity of largazole by using in vitro and in vivo cancer models. Screening against the National Cancer Institute's 60 cell lines revealed that largazole is particularly active against several colon cancer cell types. Consequently, we tested largazole, along with several synthetic analogs, for HDAC inhibition in human HCT116 colon cancer cells. Enzyme inhibition strongly correlated with the growth inhibitory effects, and differential activity of largazole analogs was rationalized by molecular docking to an HDAC1 homology model. Comparative genomewide transcript profiling revealed a close overlap of genes that are regulated by largazole, FK228, and SAHA. Several of these genes can be related to largazole's ability to induce cell cycle arrest and apoptosis. Stability studies suggested reasonable bioavailability of the active species, largazole thiol. We established that largazole inhibits HDACs in tumor tissue in vivo by using a human HCT116 xenograft mouse model. Largazole strongly stimulated histone hyperacetylation in the tumor, showed efficacy in inhibiting tumor growth, and induced apoptosis in the tumor. This effect probably is mediated by the modulation of levels of cell cycle regulators, antagonism of the AKT pathway through insulin receptor substrate 1 down-regulation, and reduction of epidermal growth factor receptor levels. PMID- 20739456 TI - Productivity shortfalls in drug discovery: contributions from the preclinical sciences? AB - An inverse relationship between human and financial investment and productivity, in the form of new drug approvals, has been a consistent theme in drug discovery for more than a decade. There appear to be many causes and solutions for this, but few tangible outcomes. Although Food and Drug Administration regulators, the constraints resulting from short-term business decisions, and the harvesting of all "low-hanging fruit," have been cited as the major causes for the decreased productivity, a change in the preclinical research culture is equally culpable. Current trends in biomedical research have led to a decreased emphasis on the null hypothesis/data-driven approach; a trend toward qualitative rather than quantitative science; an implicit assumption that all targets represent a viable starting point for drug discovery efforts; and the replacement of the creativity, objectivity, passion, and logic characteristic of the drug hunter with consensus dependent, technology-driven research cultures. In addition, the euphoria following the mapping of the human genome and its implicit potential as a source for new drug targets has given way to disillusionment as the relevance, tractability, and complexity of novel disease-associated targets have become recognized as significant challenges. Biomedical research efforts directed toward drug discovery, both in academia and industry, must prioritize genuine innovation over technology and thus allow efforts in preclinical research to play a key role in the solution to the shortfall in new drug applications. PMID- 20739455 TI - Tolerance to the antinociceptive effect of morphine in the absence of short-term presynaptic desensitization in rat periaqueductal gray neurons. AB - Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic MU-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D(50) = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol] enkephalin was decreased in morphine-tolerant (EC(50) = 708 nM) compared with saline-pretreated rats (EC(50) = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, beta-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization. PMID- 20739457 TI - Effects of a positive allosteric modulator of group II metabotropic glutamate receptors, LY487379, on cognitive flexibility and impulsive-like responding in rats. AB - Orthosteric group II metabotropic glutamate receptor (mGluR) agonists are regarded as novel, effective medications for all major symptom domains of schizophrenia, including cognitive disturbances. mGluR2s also can be affected in a more subtle way by positive allosteric modulators (PAMs) characterized by a unique degree of subtype selectivity and neuronal frequency-dependent activity. Because currently available treatments for schizophrenia do not improve cognitive dysfunction, the main aim of the present study was to examine the effects of a mGluR2 PAM, N-(4-(2-methoxyphenoxy)-phenyl-N-(2,2,2-trifluoroethylsulfonyl)-pyrid 3-ylmethylamine (LY487379), on rat cognitive flexibility and impulsive-like responding, assessed in an attentional set-shifting task (ASST) and a differential reinforcement of low-rate 72 s (DRL72) schedule of food reinforcement. In addition, in vivo microdialysis was used to assess the drug's impact on cortical levels of dopamine, norepinephrine, serotonin, and glutamate. Rats treated with LY487379 (30 mg/kg) required significantly fewer trials to criteria during the extradimensional shift phase of the ASST. Under a DRL72 schedule, LY487379 (30 mg/kg) decreased the response rate and increased the number of reinforcers obtained. These effects were accompanied by the shift of the frequency distribution of responses toward longer inter-response time durations. LY487379 significantly enhanced extracellular norepinephrine and serotonin levels in the medial prefrontal cortex. In summary, the present study demonstrates that a mGluR2 PAM, LY487379, promotes cognitive flexibility and facilitates behavioral inhibition. These procognitive effects may contribute to the therapeutic efficacy of agents stimulating mGluR2 in schizophrenia. PMID- 20739458 TI - Contextual and subjective antecedents of smoking in a college student sample. AB - INTRODUCTION: College is a time when individuals are at risk for initiating or increasing their smoking behavior. Little is known, however, about the contexts in which college students smoke. Identifying antecedents to smoking would provide insights into motivation and stimulus control of smoking in this population. METHOD: In a sample of 50 college student smokers, situational, behavioral, and subjective state variables were compared between prompted interviews (N = 2,095) and participant-initiated smoking interviews (N = 865) using electronic handheld diaries. RESULTS: The strongest predictors of smoking were recently inhabiting an outside location (odds ratio [OR] = 4.19, p < .001), the presence of others smoking (OR = 3.93, p < .001), and being where smoking was permitted (OR = 3.26, p < .001), indicating situational control over smoking. Less cue control over smoking was found for daily than nondaily smokers. Craving was the most robust subjective antecedent of smoking behavior (OR = 1.32, p < .001). DISCUSSION: These results suggest that smoking among college students is largely opportunistic, craving is important and may develop early in the progression of smoking, and stimulus control may erode with greater smoking experience. PMID- 20739459 TI - Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration. AB - Tissue inflammation induces rapid mobilization of antigen-charged dendritic cells (DCs), which migrate to draining lymph nodes via afferent lymphatics to elicit the immune response. This increase in DC trafficking has been shown to require integrin-dependent adhesion to ICAM-1 and VCAM-1, expressed on inflamed lymphatic endothelium. In addition, both constitutive- and inflammation-induced DC migration involves the chemokine CCL21, which most likely triggers integrin activation on DC via its receptor CCR7. Recently, however, conflicting evidence has suggested that DC entry occurs independently of integrins, implying that the role of CCL21 in lymphatics is purely chemotactic. Hence, while CCL21 is reported to be inducible during inflammation, the details of this induction and the role of CCL21 during initial DC trafficking are unclear. Here, we have characterized both the production of CCL21 and the mechanism of its action in DC transmigration using primary human dermal lymphatic endothelial cells (HDLECs) and a mouse model of skin contact hypersensitivity. We showed that CCL21 is constitutively expressed intracellularly but rapidly secreted after exposure to the inflammatory cytokine tumour necrosis factor (TNF) alpha following de novo RNA and protein synthesis. Furthermore, using in vitro transmigration assays, we showed that endogenous HDLEC-derived CCL21 stimulates DC translymphatic migration by a predominantly chemotactic mechanism in resting HDLEC and by a beta2 integrin mediated mechanism in TNFalpha-stimulated HDLEC. These results imply a direct role for CCL21 in lymphatic transmigration that involves the selective use of integrin activation in inflammation. PMID- 20739460 TI - Neutrophil activation and survival are modulated by interaction with NK cells. AB - It is increasingly evident that neutrophils are able to cross-talk with other leukocytes to shape ongoing inflammatory and immune responses. In this study, we analyzed whether human NK cells may influence the survival and activation of neutrophils under co-culture conditions. We report that NK cells exposed to either IL-15 or IL-18 alone strongly protect the survival of neutrophils via the release of IFNgamma and granulocyte macrophage colony-stimulating factor (GM-CSF) plus IFNgamma, respectively, and cause a slight up-regulation of neutrophil CD64 and CD11b expression. In comparison, NK cells exposed to both IL-15 and IL-18 show a lesser ability to increase the survival of neutrophils but can more potently up-regulate CD64 and CD11b expression, as well as induce the de novo surface expression of CD69, in neutrophils. Analysis of the events occurring in neutrophil/NK co-cultures exposed to IL-15 plus IL-18 revealed that (i) neutrophil survival is positively affected by NK-derived GM-CSF but negatively influenced by a CD18-dependent neutrophil/NK contact, (ii) NK-derived IFNgamma is almost entirely responsible for the induction of CD64, (iii) both soluble factors (primarily GM-CSF) and direct cell-cell contact up-regulate CD11b and CD69 and (iv) NK-derived GM-CSF induces the expression of biologically active heparin binding EGF-like growth factor (HB-EGF) in neutrophils. Finally, we demonstrate that NK cells can also express HB-EGF when stimulated with either IL-2 or IL-15, yet independently of endogenous GM-CSF. Altogether, our results define a novel interaction within the innate immune system whereby NK cells, by directly modulating neutrophil functions, might contribute to the pathogenesis of inflammatory diseases. PMID- 20739461 TI - Alpha-arrestins Aly1 and Aly2 regulate intracellular trafficking in response to nutrient signaling. AB - Extracellular signals regulate trafficking events to reorganize proteins at the plasma membrane (PM); however, few effectors of this regulation have been identified. beta-Arrestins relay signaling cues to the trafficking machinery by controlling agonist-stimulated endocytosis of G-protein-coupled receptors. In contrast, we show that yeast alpha-arrestins, Aly1 and Aly2, control intracellular sorting of Gap1, the general amino acid permease, in response to nutrients. These studies are the first to demonstrate association of alpha arrestins with clathrin and clathrin adaptor proteins (AP) and show that Aly1 and Aly2 interact directly with the gamma-subunit of AP-1, Apl4. Aly2-dependent trafficking of Gap1 requires AP-1, which mediates endosome-to-Golgi transport, and the nutrient-regulated kinase, Npr1, which phosphorylates Aly2. During nitrogen starvation, Npr1 phosphorylation of Aly2 may stimulate Gap1 incorporation into AP-1/clathrin-coated vesicles to promote Gap1 trafficking from endosomes to the trans-Golgi network. Ultimately, increased Aly1-/Aly2-mediated recycling of Gap1 from endosomes results in higher Gap1 levels within cells and at the PM by diverting Gap away from trafficking pathways that lead to vacuolar degradation. This work defines a new role for arrestins in membrane trafficking and offers insight into how alpha-arrestins coordinate signaling events with protein trafficking. PMID- 20739462 TI - Deficiency in the multicopy Sycp3-like X-linked genes Slx and Slxl1 causes major defects in spermatid differentiation. AB - The human and mouse sex chromosomes are enriched in multicopy genes required for postmeiotic differentiation of round spermatids into sperm. The gene Sly is present in multiple copies on the mouse Y chromosome and encodes a protein that is required for the epigenetic regulation of postmeiotic sex chromosome expression. The X chromosome carries two multicopy genes related to Sly: Slx and Slxl1. Here we investigate the role of Slx/Slxl1 using transgenically-delivered small interfering RNAs to disrupt their function. We show that Slx and Slxl1 are important for normal sperm differentiation and male fertility. Slx/Slxl1 deficiency leads to delay in spermatid elongation and sperm release. A high proportion of delayed spermatids are eliminated via apoptosis, with a consequent reduced sperm count. The remaining spermatozoa are abnormal with impaired motility and fertilizing abilities. Microarray analyses reveal that Slx/Slxl1 deficiency affects the metabolic processes occurring in the spermatid cytoplasm but does not lead to a global perturbation of sex chromosome expression; this is in contrast with the effect of Sly deficiency which leads to an up-regulation of X and Y chromosome genes. This difference may be due to the fact that SLX/SLXL1 are cytoplasmic while SLY is found in the nucleus and cytoplasm of spermatids. PMID- 20739463 TI - Expression of the Salmonella spp. virulence factor SifA in yeast alters Rho1 activity on peroxisomes. AB - The Salmonella typhimurium effector protein SifA regulates the assembly and tubulation of the Salmonella phagosome. SifA localizes to the phagosome and interacts with the membrane via its prenylated tail. SifA is a structural homologue of another bacterial effector that acts as a GTP-exchange factor for Rho family GTPases and can bind GDP-RhoA. When coexpressed with a bacterial lipase that is activated by RhoA, SifA can induce tubulation of mammalian endosomes. In an effort to develop a genetic system to study SifA function, we expressed SifA and characterized its activity in yeast. GFP-SifA predominantly localized to yeast peroxisomal membranes. Under peroxisome-inducing conditions, GFP-SifA reduced the number of free peroxisomes and promoted the formation of large peroxisomes with membrane invaginations. GFP-SifA activity depended on the recruitment to peroxisomes of wild-type Rho1p and Pex25p, a receptor for Rho1p. GFP-SifA could also rescue the actin organization defects in pex25Delta and rho1 mutants, suggesting that SifA may recruit and potentiate Rho1p activity. We reexamined the distribution of GFP-SifA in mammalian cells and found the majority colocalizing with LAMP1-positive compartment and not with the peroxisomal marker PMP70. Together, these data suggest that SifA may use a similar mode of action via Rho proteins to alter yeast peroxisomal and mammalian endosomal membranes. Further definition of SifA activity on yeast peroxisomes could provide more insight into its role in regulating host membrane dynamics and small GTPases. PMID- 20739464 TI - Arp2/3- and cofilin-coordinated actin dynamics is required for insulin-mediated GLUT4 translocation to the surface of muscle cells. AB - GLUT4 vesicles are actively recruited to the muscle cell surface upon insulin stimulation. Key to this process is Rac-dependent reorganization of filamentous actin beneath the plasma membrane, but the underlying molecular mechanisms have yet to be elucidated. Using L6 rat skeletal myoblasts stably expressing myc tagged GLUT4, we found that Arp2/3, acting downstream of Rac GTPase, is responsible for the cortical actin polymerization evoked by insulin. siRNA mediated silencing of either Arp3 or p34 subunits of the Arp2/3 complex abrogated actin remodeling and impaired GLUT4 translocation. Insulin also led to dephosphorylation of the actin-severing protein cofilin on Ser-3, mediated by the phosphatase slingshot. Cofilin dephosphorylation was prevented by strategies depolymerizing remodeled actin (latrunculin B or p34 silencing), suggesting that accumulation of polymerized actin drives severing to enact a dynamic actin cycling. Cofilin knockdown via siRNA caused overwhelming actin polymerization that subsequently inhibited GLUT4 translocation. This inhibition was relieved by reexpressing Xenopus wild-type cofilin-GFP but not the S3E-cofilin-GFP mutant that emulates permanent phosphorylation. Transferrin recycling was not affected by depleting Arp2/3 or cofilin. These results suggest that cofilin dephosphorylation is required for GLUT4 translocation. We propose that Arp2/3 and cofilin coordinate a dynamic cycle of actin branching and severing at the cell cortex, essential for insulin-mediated GLUT4 translocation in muscle cells. PMID- 20739465 TI - TRPV1 activation is required for hypertonicity-stimulated inflammatory cytokine release in human corneal epithelial cells. AB - PURPOSE: To determine whether hypertonic stress promotes increases in inflammatory cytokine release through transient receptor potential vanilloid channel type 1 (TRPV1) signaling pathway activation in human corneal epithelial cells (HCECs). METHODS: Hyperosmotic medium was prepared by supplementing isotonic Ringers solution with sucrose. Ca2+ signaling was measured in fura2-AM loaded HCECs using a single-cell fluorescence imaging system. Western blot analysis evaluated the phosphorylation status of EGFR, ERK, p38 MAPK, and nuclear factor (NF)-kappaB. ELISA assessed the effect of TRPV1 activation on the release of IL-6 and IL-8. RESULTS: A 450 mOsm hypertonic stress elicited 2-fold Ca2+ transients that were suppressed by the TRPV1-selective antagonists capsazepine and JYL 1421. Such transients were enhanced by PGE2. Hypertonicity-induced EGF receptor (EGFR) transactivation was suppressed by preincubating HCECs with capsazepine, matrix metalloproteinase 1 (MMP1) inhibitor TIMP-1, broad-spectrum MMP inhibitor GM 6001, heparin-bound (HB)-EGF inhibitor CRM 197, or EGFR inhibitor AG 1478. ERK and p38 MAPK and NF-kappaB activation after EGFR transactivation occurred in tonicity and in a time-dependent manner. Hypertonicity-induced increases in IL-6 and IL-8 releases were suppressed by exposure to capsazepine, AG 1478, ERK inhibitor PD 98059, p38 inhibitor SB 203580, or NF-kappaB inhibitor PDTC. CONCLUSIONS: Hypertonic stress-elicited TRPV1 channel stimulation mediates increases in a proinflammatory cytokine IL-6 and a chemoattractant IL-8 by eliciting EGFR transactivation, MAPK, and NF-kappaB activation. Selective drug modulation of either TRPV1 activity or its signaling mediators may yield a novel approach to suppressing inflammatory responses occurring in dry eye syndrome. PMID- 20739466 TI - Spontaneous lymphatic vessel formation and regression in the murine cornea. AB - PURPOSE: Lymphatic dysfunctions are associated with many diseases, ranging from cancer metastasis to transplant rejection, for which there is little effective treatment. To date, there is no natural model with which to study lymphatic regression. This study was conducted to investigate whether murine cornea, an extensively exploited tissue for vascular studies, derives its lymphatic-free status from a natural regression mechanism. The differential behaviors between the lymphatic and blood vessels under normal development and inflammation conditions are also compared. METHODS: Normal mouse eyeballs or whole-mount corneas encompassing the entire course of corneal development and maturation and adult inflamed corneas were used for immunofluorescent microscopic studies. RESULTS: The data demonstrated, for the first time, that mouse cornea was endowed with a significant number of lymphatic vessels that underwent spontaneous formation and regression during a critical period after birth, which was not observed for blood vessels. Because lymphatic growth can be reactivated in the adult cornea after inflammatory stimulation, the cornea thereby becomes the first tissue ever identified to have a full range of lymphatic plasticity. CONCLUSIONS: These novel findings not only provide a new concept in defining the cornea and its related diseases, they also reveal a completely natural model with which to study both lymphatic regression and formation. It is hoped that further studies will divulge novel and potent pro- or anti-lymphatic factors to treat lymphatic disorders inside and outside the eye. PMID- 20739467 TI - Comparison of candidate materials for a synthetic osteo-odonto keratoprosthesis device. AB - PURPOSE: Osteo-odonto keratoprosthesis is one of the most successful forms of keratoprosthesis surgery for end-stage corneal and ocular surface disease. There is a lack of detailed comparison studies on the biocompatibilities of different materials used in keratoprosthesis. The aim of this investigation was to compare synthetic bioinert materials used for keratoprosthesis surgery with hydroxyapatite (HA) as a reference. METHODS: Test materials were sintered titanium oxide (TiO(2)), aluminum oxide (Al(2)O(3)), and yttria-stabilized zirconia (YSZ) with density >95%. Bacterial adhesion on the substrates was evaluated using scanning electron microscopy and the spread plate method. Surface properties of the implant discs were scanned using optical microscopy. Human keratocyte attachment and proliferation rates were assessed by cell counting and MTT assay at different time points. Morphologic analysis and immunoblotting were used to evaluate focal adhesion formation, whereas cell adhesion force was measured with a multimode atomic force microscope. RESULTS: The authors found that bacterial adhesion on the TiO(2), Al(2)O(3), and YSZ surfaces were lower than that on HA substrates. TiO(2) significantly promoted keratocyte proliferation and viability compared with HA, Al(2)O(3,) and YSZ. Immunofluorescent imaging analyses, immunoblotting, and atomic force microscope measurement revealed that TiO(2) surfaces enhanced cell spreading and cell adhesion compared with HA and Al(2)O(3). CONCLUSIONS: TiO(2) is the most suitable replacement candidate for use as skirt material because it enhanced cell functions and reduced bacterial adhesion. This would, in turn, enhance tissue integration and reduce device failure rates during keratoprosthesis surgery. PMID- 20739469 TI - Correlations between M-CHARTS and PHP findings and subjective perception of metamorphopsia in patients with macular diseases. AB - PURPOSE: To assess the correlations between a patient's subjective perception of metamorphopsia and the clinical measurements of metamorphopsia by M-CHARTS and PreView PHP (PHP). METHODS: The authors designed a 10-item questionnaire focusing on the symptoms of metamorphopsia and verified its validity with a Rasch analysis. M-CHARTS measured the minimum visual angle of a dotted line needed to detect metamorphopsia, and PHP used the hyperacuity function for detection. Subjects were 39 patients with idiopathic epiretinal membrane (ERM), 22 patients with idiopathic macular hole (M-hole), 19 patients with age-related macular degeneration (AMD), and 51 healthy controls. RESULTS: Rasch analysis suggested the elimination of one question. The nine-item questionnaire score significantly correlated to the M-CHARTS score in ERM (r = 0.59; P = 0.0004) but not in M-hole and to the PHP result in AMD (r = -0.29; P = 0.04) but not in ERM. Eighty percent of ERM patients with greater horizontal M-CHARTS score subjectively perceived horizontal metamorphopsia more often. M-CHARTS showed better sensitivities than PHP in both ERM (89% vs. 42%) and AMD (74% vs. 68%) and better specificity (100% vs. 71%) in healthy controls. Rasch analysis indicated that the present form of the questionnaire is better suited for moderate to severe cases of metamorphopsia than for mild cases. CONCLUSIONS: The questionnaire appears to be a valid assessment of patient subjective perception of metamorphopsia and can be used to supplement the clinical measurements of metamorphopsia by M-CHARTS and PHP in patients with macular diseases. PMID- 20739468 TI - Microarray analysis of iris gene expression in mice with mutations influencing pigmentation. AB - PURPOSE: Several ocular diseases involve the iris, notably including oculocutaneous albinism, pigment dispersion syndrome, and exfoliation syndrome. To screen for candidate genes that may contribute to the pathogenesis of these diseases, genome-wide iris gene expression patterns were comparatively analyzed from mouse models of these conditions. METHODS: Iris samples from albino mice with a Tyr mutation, pigment dispersion-prone mice with Tyrp1 and Gpnmb mutations, and mice resembling exfoliation syndrome with a Lyst mutation were compared with samples from wild-type mice. All mice were strain (C57BL/6J), age (60 days old), and sex (female) matched. Microarrays were used to compare transcriptional profiles, and differentially expressed transcripts were described by functional annotation clustering using DAVID Bioinformatics Resources. Quantitative real-time PCR was performed to validate a subset of identified changes. RESULTS: Compared with wild-type C57BL/6J mice, each disease context exhibited a large number of statistically significant changes in gene expression, including 685 transcripts differentially expressed in albino irides, 403 in pigment dispersion-prone irides, and 460 in exfoliative-like irides. CONCLUSIONS: Functional annotation clusterings were particularly striking among the overrepresented genes, with albino and pigment dispersion-prone irides both exhibiting overall evidence of crystallin-mediated stress responses. Exfoliative like irides from mice with a Lyst mutation showed overall evidence of involvement of genes that influence immune system processes, lytic vacuoles, and lysosomes. These findings have several biologically relevant implications, particularly with respect to secondary forms of glaucoma, and represent a useful resource as a hypothesis-generating dataset. PMID- 20739470 TI - Role of the adrenergic system in a mouse model of oxygen-induced retinopathy: antiangiogenic effects of beta-adrenoreceptor blockade. AB - PURPOSE: Oxygen-induced retinopathy (OIR) is a model for human retinopathy of prematurity (ROP). In OIR mice, this study determined whether blockade of beta adrenergic receptors (beta-ARs) with propranolol influences retinal levels of proangiogenic factors, retinal vascularization, and blood-retinal barrier (BRB) breakdown. METHODS: Propranolol was administered subcutaneously and picropodophyllin (PPP) intraperitoneally. Intravitreal injections of vascular endothelial growth factor (VEGF) were performed. Messengers of beta-ARs, VEGF, its receptors, IGF-1 and IGF-1R were measured with quantitative RT-PCR. VEGF content was determined with ELISA. beta-ARs, hypoxia-inducible factor (HIF) 1alpha, occludin, and albumin were measured with Western blot. Retinal localization of beta3-ARs was determined by immunohistochemistry. Retinopathy was assessed by scoring fluorescein-perfused retinas, and plasma extravasation was visualized by Evans blue dye. RESULTS: Hypoxia did not influence beta-AR expression, except that it increased beta3-AR protein with dense beta3-AR immunoreactivity localized to engorged retinal tufts. Hypoxia upregulated VEGF, IGF-1, their receptors, and HIF-1alpha. Propranolol dose-dependently reduced upregulated VEGF and decreased hypoxic levels of IGF-1 mRNA and HIF-1alpha. Blockade of IGF-1R activity with PPP did not influence propranolol's effects on VEGF. Retinal VEGF in normoxic mice or VEGF in brain, lungs, and heart of the OIR mice were unaffected by propranolol. Propranolol ameliorated the retinopathy score, restored occludin and albumin, and reduced hypoxia-induced plasma extravasation without influencing the vascular permeability induced by intravitreal VEGF. CONCLUSIONS: This is the first demonstration that beta-AR blockade is protective against retinal angiogenesis and ameliorates BRB dysfunction in OIR. Although the relevance of these results to infant ROP is uncertain, the findings may help to establish potential pharmacologic targets based on beta3-AR pharmacology. PMID- 20739472 TI - An antiviral small-interfering RNA simultaneously effective against the most prevalent enteroviruses causing acute hemorrhagic conjunctivitis. AB - PURPOSE: Acute hemorrhagic conjunctivitis (AHC), a highly contagious eye disease, is caused primarily by either enterovirus 70 (EV70) or coxsackievirus A24 (CVA24) infection. Yet methods to prevent or cure AHC are not available. Recent evidence has shown that small-interfering RNAs (siRNAs), mediators of posttranscriptional gene knockdown, can act as effective antiviral agents. Thus, the authors attempted to develop a novel siRNA-based anti-AHC agent effective against both EV70 and CVA24. METHODS: Concurrent screening of the entire viral genome sequences of EV70 and CVA24 using the CAPSID program identified five different siRNA candidates complementary to genome regions of both viruses. The antiviral potentials of these siRNAs were assessed by treating MRC5 and primary human conjunctival cells with the siRNAs and following this with viral challenge. RESULTS: Among the five siRNAs, AHCe-3D-3 siRNA showed excellent cytoprotective effects and dramatic decreases in virus replication and virus protein synthesis. This siRNA, targeting the virus polymerase 3D gene, also induced similar antiviral effects in primary human conjunctival cells. CONCLUSIONS: These findings strongly suggest that the AHCe-3D-3 siRNA, homologous to two different AHC-associated enteroviruses, can provide equivalent antiviral activities against both AHC-causing enteroviruses. Such an siRNA may be developed as a clinically valuable AHC control agent. PMID- 20739471 TI - Static and dynamic measurements of accommodation in individuals with down syndrome. AB - PURPOSE: To identify whether static and dynamic aspects of accommodation other than accuracy are deficient in individuals with Down syndrome (DS) and whether poor accommodation is related to sensory or motor pathway deficits. METHODS: Static aspects of accommodation (maximum accommodative response and lag) were measured with an autorefractor for both proximal and minus lens demands. Dynamic aspects of accommodation (latency, peak velocity, microfluctuations) were recorded at 30 Hz with a custom-built photorefractor as subjects viewed a movie switching between 11 m and 50, 33, 25, or 20 cm. Thirty-six subjects with DS were recruited (age 3 to 39 years), and 24 (67%) had useable responses for at least one study measurement for comparison with 140 controls (3 to 40 years) from a previously published cohort. RESULTS: DS subjects had lower maximum accommodative responses (mean = 2.52 +/- 1.66 D) and higher lags (1.81 +/- 1.30 D for 33 cm demand) than controls for both proximal and minus lens stimuli. DS subjects had greater microfluctuations (one-way ANCOVA, P < 0.001), and a small percentage of the total number of latency measurements (17% accommodative and 16% disaccommodative) were longer than controls. Peak velocities of accommodation and disaccommodation were not different between groups (one-way ANCOVA, P = 0.143). CONCLUSIONS: Peak velocities of accommodation and disaccommodation (primarily motor aspects) did not differ between controls and DS subjects; however, latencies (primarily sensory) and microfluctuations (combined motor and sensory) were poorer in DS subjects. These results suggest that poor accommodative accuracy in individuals with DS may be predominantly related to sensory deficits. PMID- 20739473 TI - SOX2 is required for adult human muller stem cell survival and maintenance of progenicity in vitro. AB - PURPOSE: SOX2, a high-mobility group transcription factor, is expressed by retinal progenitors during development. It has been associated with the ability of progenitor cells to differentiate into retinal neurons and is highly expressed by human Muller stem cells (hMSCs) in culture. The authors investigated the role of this factor in the maintenance of progenicity and neural differentiation of hMSCs in vitro. METHODS: SOX2 silencing was induced by transfection of hMSCs in culture with two pGSU6-GFP SOX2 silencing constructs and a scrambled control vector. Silencing was confirmed by examination of gene and protein expression coding for SOX2. Effects of SOX2 downregulation were investigated by expression of proliferation (Ki67) and apoptotic (TUNEL, caspase) cell markers and by the expression of markers of retinal neurons (HuD, betaIII tubulin, rhodopsin, BRN3B, ISL1), glia (vimentin), and the progenitor marker PAX6. RESULTS: SOX2 silencing caused hMSCs to rapidly adopt a neural-like morphology and was accompanied by the upregulation of specific markers of retinal neurons, including betaIII tubulin, rhodopsin, BRN3B, and ISL1, and by the downregulation of the neural progenitor marker PAX6 and the glial cell marker vimentin. Interestingly, SOX2 silencing induced apoptosis, suggesting a crucial role of this factor on hMSC survival in vitro. CONCLUSIONS: These in vitro results parallel that seen when Sox2 is silenced in neural stem cells of lower species during development, and they suggest that Sox2 may have an important role in adult hMSC differentiation into retinal neurons in vitro. PMID- 20739474 TI - Imaging reveals optic tract degeneration in hemianopia. AB - PURPOSE: To investigate whether there is transsynaptic degeneration in the human optic tract in hemianopia. To consider how the degeneration varies with duration of hemianopia and location of insult. METHODS: Seven patients with damage to the primary visual cortex (V1), the lateral geniculate nucleus (LGN), or the optic tract were scanned with structural MRI. The volume and cross-sectional area of the left and right optic tracts were computed based on the intensity values of the T1-weighted image. High values correspond to voxels with high white matter content, and the values decrease as the white matter content drops (indicating degeneration). A laterality index to compare the tract size in the two hemispheres was calculated at different intensity values. RESULTS: The three hemianopic patients with longstanding damage to either V1 or LGN showed laterality indices greater than 0.5 at the highest intensity values, indicating significant optic tract degeneration. Those with recent damage to the optic tract had even higher laterality indices due to direct degeneration. Even 18 months after V1 lesion, there was a significant correlation between the cross-section and volume indices at different intensity thresholds, whereas no control subject showed any correlation. CONCLUSIONS: Transsynaptic degeneration had already begun 18 months after lesion. Although there was no visible decrease in volume at this stage, the white matter integrity was compromised. Significant decrease in volume could be visualized at longer durations of hemianopia. This method of objectively assessing structural images provides an effective, noninvasive approach to monitor the timescale of optic tract degeneration. PMID- 20739475 TI - Generation of bioengineered corneas with decellularized xenografts and human keratocytes. AB - PURPOSE: Decellularization of animal corneas is a promising method for the development of artificial human corneas by tissue engineering. In this study, two different decellularization protocols were evaluated to determine which one is able to best preserve the histologic structure, composition, and optical behavior of decellularized porcine corneas. Then, these corneas were recellularized with human keratocytes to obtain a partial human corneal substitute. METHODS: Two different decellularization protocols were applied, using NaCl and SDS, to determine which one is able to best preserve the histologic structure, composition, and optical behavior of the decellularized corneas. Then, those decellularized corneas that showed the most appropriate results were recellularized with human keratocytes and evaluated at the histologic, biochemical, and optical levels for use in regenerative medicine. RESULTS: The results showed that 1.5 M NaCl treatment of porcine corneas is able to generate an acellular corneal stroma with adequate histologic and optical properties and that human keratocytes are able to penetrate and spread within this scaffold with proper levels of cell differentiation. In contrast, 0.1% SDS treatment of porcine corneas resulted in high levels of fibril disorganization and poor optical behavior of these corneas. CONCLUSIONS: In conclusion, the authors suggest that the decellularization of animal corneas with 1.5 M NaCl represents a useful method for the development of human bioengineered corneas with therapeutic potential. PMID- 20739476 TI - Relative peripheral refractive error and the risk of onset and progression of myopia in children. AB - PURPOSE: To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression. METHODS: The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age +/- SD = 8.8 +/- 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30 degrees in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography. RESULTS: The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.30; African American children OR = 0.75, 95% CI = 0.58-0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (-0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity. CONCLUSIONS: Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation. PMID- 20739478 TI - CREB-Dependent Regulation of GAD65 Transcription by BDNF/TrkB in Cortical Interneurons. AB - In the cerebral cortex, the functional output of projection neurons is fine-tuned by inhibitory neurons present in the network, which use gamma-aminobutyric acid (GABA) as their main neurotransmitter. Previous studies have suggested that the expression levels of the rate-limiting GABA synthetic enzyme, GAD65, depend on brain derived neurotrophic factor (BDNF)/TrkB activation. However, the molecular mechanisms by which this neurotrophic factor and its receptor controls GABA synthesis are still unknown. Here, we show a direct regulation of the GAD65 gene by BDNF-TrkB signaling via CREB in cortical interneurons. Conditional ablation of TrkB in cortical interneurons causes a cell-autonomous decrease in the synaptically enriched GAD65 protein and its transcripts levels, suggesting that transcriptional regulation of the GAD65 gene is altered. Dissection of the intracellular pathway that underlies this process revealed that BDNF/TrkB signaling controls the transcription of GAD65 in a Ras-ERK-CREB-dependent manner. Our study reveals a novel molecular mechanism through which BDNF/TrkB signaling may modulate the maturation and function of cortical inhibitory circuits. PMID- 20739477 TI - The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture. AB - The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations. PMID- 20739479 TI - Rodent cortical astroglia express in situ functional P2X7 receptors sensing pathologically high ATP concentrations. AB - ATP is an important neuronal and astroglial signaling molecule in the brain. In the present study, brain slices were prepared from the prefrontal cortex (PFC) of Wistar rats and 2 lines of mice. P2X7 receptor immunoreactivity was colocalized with astro- and microglial but not neuronal markers. Whole-cell patch-clamp recordings showed that, in astroglial cells, dibenzoyl-ATP (BzATP) and ATP caused inward currents, near the resting membrane potential. The inactivity of alpha,beta-methylene ATP, as well as the potency increases of BzATP and ATP in a low divalent cation (X2(+))-containing superfusion medium suggested the involvement of P2X7 receptors. This idea was corroborated by the inhibition of these current responses by PPADS, Brilliant Blue G, A 438079, and calmidazolium. Ivermectin, trinitrophenyl-adenosine-5'-triphosphate, and cyclopentyl dipropylxanthine did not alter the agonist effects. The reversal potential of BzATP was near 0 mV, indicating the opening of cationic receptor channels. In a low X2(+) superfusion medium, ATP-induced current responses in PFC astroglial cells of wild-type mice but not of the P2X7 knockouts. Hence, cortical astroglia of rats and mice possess functional P2X7 receptors. These receptors may participate in necrotic/apoptotic or proliferative reactions after stimulation by large quantities of ATP released by central nervous system injury. PMID- 20739480 TI - Efficiency of fine-needle aspiration compared with other sampling techniques for laboratory diagnosis of Buruli ulcer disease. AB - In accordance with recent WHO recommendations, this study evaluates the sensitivities of PCR and microscopy for fine-needle aspiration (FNA) versus techniques involving swabs and punch biopsy specimens and suggests that FNA can replace punch biopsies for nonulcerative lesions and may serve as an alternative for ulcerative lesions in cases where scarred edges prevent the collection of swabs. PMID- 20739481 TI - Rapid detection of respiratory tract viral infections and coinfections in patients with influenza-like illnesses by use of reverse transcription-PCR DNA microarray systems. AB - We prospectively tested 95 nasal swabs or nasopharyngeal aspirates taken from 56 adults and 39 children visiting the Reims University Medical Centre (northern France) for influenza-like illnesses (ILI) during the early stage of the French influenza A/H1N1v pandemic (October 2009). Respiratory samples were tested using a combination of two commercially available reverse transcription-PCR (RT-PCR) DNA microarray systems allowing rapid detection of influenza A virus strains, including the new A/H1N1v strain as well as 20 other common or newly discovered respiratory viruses. Concomitantly, a generic and classical real-time RT-PCR assay was performed to detect all circulating influenza A virus strains in the same samples. Of the 95 respiratory samples tested, 30 (31%) were positive for the detection of influenza A/H1N1v virus infection by both RT-PCR DNA microarray and classical real-time RT-PCR detection assays. Among the infections, 25 (83%) were monoinfections, whereas 5 (17%) were multiple infections associating influenza A/H1N1v virus with coronavirus (CoV), human bocavirus (HBoV), respiratory syncytial virus (RSV), or human rhinoviruses (HRVs). Of the 95 respiratory samples tested, 35 (37%) were positive for respiratory viruses other than influenza A/H1N1v virus. Among these infections, we observed 30 monoinfections (HRVs [63%], parainfluenza viruses [PIVs] [20%]), influenza A/H3N2 virus [6%], coronavirus [4%], and HBoV [4%]) and 5 multiple infections, in which HRVs and PIVs were the most frequently detected viruses. No specific single or mixed viral infections appeared to be associated significantly with secondary hospitalization in infectious disease or intensive care departments during the study period (P > 0.5). The use of RT-PCR DNA microarray systems in clinical virology practice allows the rapid and accurate detection of conventional and newly discovered viral respiratory pathogens in patients suffering from ILI and therefore could be of major interest for development of new epidemiological survey systems for respiratory viral infections. PMID- 20739482 TI - Improved identification of epidemiologically related strains of Salmonella enterica by use of a fusion algorithm based on pulsed-field gel electrophoresis and multiple-locus variable-number tandem-repeat analysis. AB - Pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem repeat analysis (MLVA) are used to assess genetic similarity between bacterial strains. There are cases, however, when neither of these methods quantifies genetic variation at a level of resolution that is well suited for studying the molecular epidemiology of bacterial pathogens. To improve estimates based on these methods, we propose a fusion algorithm that combines the information obtained from both PFGE and MLVA assays to assess epidemiological relationships. This involves generating distance matrices for PFGE data (Dice coefficients) and MLVA data (single-step stepwise-mutation model) and modifying the relative distances using the two different data types. We applied the algorithm to a set of Salmonella enterica serovar Typhimurium isolates collected from a wide range of sampling dates, locations, and host species. All three classification methods (PFGE only, MLVA only, and fusion) produced a similar pattern of clustering relative to groupings of common phage types, with the fusion results being slightly better. We then examined a group of serovar Newport isolates collected over a limited geographic and temporal scale and showed that the fusion of PFGE and MLVA data produced the best discrimination of isolates relative to a collection site (farm). Our analysis shows that the fusion of PFGE and MLVA data provides an improved ability to discriminate epidemiologically related isolates but provides only minor improvement in the discrimination of less related isolates. PMID- 20739483 TI - Herbaspirillum species bacteremia in a pediatric oncology patient. AB - Herbaspirillum species, an organism commonly found in soil, has only recently been linked to disease in humans. We report Herbaspirillum bacteremia in a 2-year old female patient following a hematopoietic stem cell transplant for relapsed acute lymphoblastic leukemia. PMID- 20739484 TI - Spoligotypes of Mycobacterium tuberculosis from different Provinces of China. AB - A total of 2,346 Mycobacterium tuberculosis isolates from 13 provinces in China were genotyped by spoligotyping. Two hundred seventy-eight spoligotypes were identified: 2,153 isolates were grouped into 85 clusters, and the remaining 193 isolates were orphans. Comparison with the SpolDB4.0 database revealed that 118 spoligotypes had shared international type numbers in the database and the other 160 were novel. These 160 novel spoligotypes were assigned to families and subfamilies using the SpotClust program. The most prevalent family was the Beijing family (74.08%), followed by the T family (14.11%). CAS family strains were found only in the Xinjiang and Tibet regions, while EAI family strains were found only in Fujian Province. In conclusion, the present study of the M. tuberculosis population in China demonstrated that Beijing family isolates are the most prevalent strains in China and that they exhibit geographical variation. Furthermore, many new spoligotypes were found in this study. PMID- 20739485 TI - Diagnostic limitations to accurate diagnosis of cholera. AB - The treatment regimen for diarrhea depends greatly on correct diagnosis of its etiology. Recent diarrhea outbreaks in Bangladesh showed Vibrio cholerae to be the predominant cause, although more than 40% of the suspected cases failed to show cholera etiology by conventional culture methods (CMs). In the present study, suspected cholera stools collected from every 50th patient during an acute diarrheal outbreak were analyzed extensively using different microbiological and molecular tools to determine their etiology. Of 135 stools tested, 86 (64%) produced V. cholerae O1 by CMs, while 119 (88%) tested positive for V. cholerae O1 by rapid cholera dipstick (DS) assay; all but three samples positive for V. cholerae O1 by CMs were also positive for V. cholerae O1 by DS assay. Of 49 stools that lacked CM-based cholera etiology despite most being positive for V. cholerae O1 by DS assay, 25 (51%) had coccoid V. cholerae O1 cells as confirmed by direct fluorescent antibody (DFA) assay, 36 (73%) amplified primers for the genes wbe O1 and ctxA by multiplex-PCR (M-PCR), and 31 (63%) showed El Tor specific lytic phage on plaque assay (PA). Each of these methods allowed the cholera etiology to be confirmed for 97% of the stool samples. The results suggest that suspected cholera stools that fail to show etiology by CMs during acute diarrhea outbreaks may be due to the inactivation of V. cholerae by in vivo vibriolytic action of the phage and/or nonculturability induced as a host response. PMID- 20739486 TI - Detection of hepatitis B and C viruses in almost all hepatocytes by modified PCR based in situ hybridization. AB - Although PCR-based in situ hybridization (PCR-ISH) can be used to determine the distribution and localization of pathogens in tissues, this approach is hampered by its low specificity. Therefore, we used a highly specific and sensitive PCR ISH method to reveal the lobular distribution and intracellular localization of hepatitis B virus (HBV) and HCV in chronic liver disease and to clarify the state of persistent HBV and HCV infection in the liver. HBV genomic DNA was detected in almost all hepatocytes, whereas HBV RNA or protein was differentially distributed only in a subset of the HBV DNA-positive region. Further, HCV genomic RNA was detected in almost all hepatocytes and was localized to the cytoplasm. HCV RNA was also detected in the epithelium of the large bile duct but not in endothelial cells, portal tracts, or sinusoidal lymphocytes. In patients with HBV and HCV coinfection, HCV RNA was localized to the noncancerous tissue, whereas HBV DNA was found only in the cancerous tissue. Using this novel PCR-ISH method, we could visualize the staining pattern of HBV and HCV in liver sections, and we obtained results consistent with those of real-time detection (RTD)-PCR analysis. In conclusion, almost all hepatocytes are infected with HBV or HCV in chronic liver disease; this finding implies that the viruses spreads throughout the liver in the chronic stage. PMID- 20739487 TI - Complication of corticosteroid treatment by acute Plasmodium malariae infection confirmed by small-subunit rRNA sequencing. AB - We report a case of acute Plasmodium malariae infection complicating corticosteroid treatment for membranoproliferative glomerulonephritis in a patient from an area where P. malariae infection is not endemic. A peripheral blood smear showed typical band-form trophozoites compatible with P. malariae or Plasmodium knowlesi. SSU rRNA sequencing confirmed the identity to be P. malariae. PMID- 20739488 TI - Ureaplasma urealyticum continuous ambulatory peritoneal dialysis-associated peritonitis diagnosed by 16S rRNA gene PCR. AB - In some patients with peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD), a causative organism is never identified. We report a case of Ureaplasma urealyticum CAPD-associated peritonitis diagnosed by 16S rRNA gene PCR. Ureaplasma may be an underrecognized cause of peritonitis because it cannot be recovered using routine culture methods. PMID- 20739489 TI - Improved safety for molecular diagnosis of classical rabies viruses by use of a TaqMan real-time reverse transcription-PCR "double check" strategy. AB - To improve the diagnosis of classical rabies virus with molecular methods, a validated, ready-to-use, real-time reverse transcription-PCR (RT-PCR) assay was developed. In a first step, primers and 6-carboxyfluorescien-labeled TaqMan probes specific for rabies virus were selected from the consensus sequence of the nucleoprotein gene of 203 different rabies virus sequences derived from GenBank. The selected primer-probe combination was highly specific and sensitive. During validation using a sample set of rabies virus strains from the virus archives of the Friedrich-Loeffler-Institut (FLI; Germany), the Veterinary Laboratories Agency (VLA; United Kingdom), and the DTU National Veterinary Institute (Lindholm, Denmark), covering the global diversity of rabies virus lineages, it was shown that both the newly developed assay and a previously described one had some detection failures. This was overcome by a combined assay that detected all samples as positive. In addition, the introduction of labeled positive controls (LPC) increased the diagnostic safety of the single as well as the combined assay. Based on the newly developed, alternative assay for the detection of rabies virus and the application of LPCs, an improved diagnostic sensitivity and reliability can be ascertained for postmortem and intra vitam real-time RT-PCR analyses in rabies reference laboratories. PMID- 20739490 TI - Genotypic and phenotypic correlations of multidrug-resistant Acinetobacter baumannii-A. calcoaceticus complex strains isolated from patients at the National Naval Medical Center. PMID- 20739491 TI - Diagnosis of bacteriuria and leukocyturia by automated flow cytometry compared with urine culture. AB - Urinary tract infection (UTI) is a widespread disease, and thus, the most common samples tested in diagnostic microbiology laboratories are urine samples. The "gold standard" for diagnosis is still bacterial culture, but a large proportion of samples are negative. Unnecessary culture can be reduced by an effective screening test. We evaluated the performance of a new urine cytometer, the Sysmex UF-1000i (Dasit), on 703 urine samples submitted to our laboratory for culture. We compared bacteria and leukocyte (WBC) counts performed with the Sysmex UF 1000i to CFU-per-milliliter quantification on CPS agar to assess the best cutoff values. Different cutoff values of bacteria/ml and WBC/ml were compared to give the best discrimination. On the basis of the results obtained in this study, we suggest that when the Sysmex UF-1000i analyzer is used as a screening test for UTI the cutoff values should be 65 bacteria/ml and 100 WBC/ml. Diagnostic performance in terms of sensitivity (98.2%), specificity (62.1%), negative predictive value (98.7%), positive predictive value (53.7%), and diagnostic accuracy (73.3%) were satisfactory. Screening with the Sysmex UF-1000i is acceptable for routine use. In our laboratory, we have reduced the number of bacterial cultures by 43%, speeded up their reporting, and decreased the inappropriate use of antibiotics. PMID- 20739492 TI - Evaluation of BBL CHROMagar VanRE for detection of vancomycin-resistant Enterococci in rectal swab specimens. AB - A study was performed on 517 surveillance rectal swabs to evaluate a selective and differential chromogenic medium, the BBL CHROMagar VanRE (CVRE), which enables recovery and identification of VanA- and VanB-containing Enterococcus faecium (ENFM) and Enterococcus faecalis (ENFS) isolates. Compared to BBL Enterococcosel agar, a bile-esculin-azide-vancomycin (BEAV) agar, the initial overall sensitivity, specificity, and positive and negative predictive values of CVRE for the detection of vancomycin-resistant ENFM and ENFS were 99.1% and 94.8% and 84.2% and 99.7%, respectively. Among our patient population, more vancomycin resistant enterococci (VRE) were recovered with CVRE than BEAV. PMID- 20739493 TI - Evaluation of a chromogenic culture medium for isolation of Clostridium difficile within 24 hours. AB - Rapid and effective methods for the isolation of Clostridium difficile from stool samples are desirable to obtain isolates for typing or to facilitate accurate diagnosis of C. difficile-associated diarrhea. We report on the evaluation of a prototype chromogenic medium (ID C. difficile prototype [IDCd]) for isolation of C. difficile. The chromogenic medium was compared using (i) 368 untreated stool samples that were also inoculated onto CLO medium, (ii) 339 stool samples that were subjected to alcohol shock and also inoculated onto five distinct selective agars, and (iii) standardized suspensions of 10 C. difficile ribotypes (untreated and alcohol treated) that were also inoculated onto five distinct selective agars. Two hundred thirty-six isolates of C. difficile were recovered from 368 untreated stool samples, and all but 1 of these strains (99.6%) were recovered on IDCd within 24 h, whereas 74.6% of isolates were recovered on CLO medium after 48 h. Of 339 alcohol-treated stool samples cultured onto IDCd and five other selective agars, C. difficile was recovered from 218 samples using a combination of all media. The use of IDCd allowed recovery of 96.3% of isolates within 24 h, whereas 51 to 83% of isolates were recovered within 24 h using the five other media. Finally, when they were challenged with pure cultures, all 10 ribotypes of C. difficile generated higher colony counts on IDCd irrespective of alcohol pretreatment or duration of incubation. We conclude that IDCd is an effective medium for isolation of C. difficile from stool samples within 24 h. PMID- 20739494 TI - Propionibacterium acnes and Staphylococcus epidermidis isolated from refractory endodontic lesions are opportunistic pathogens. AB - The predominant cultivable microbiota from 20 refractory endodontic lesions (9 with abscesses and 11 without abscesses) were determined, and Propionibacterium acnes and Staphylococcus epidermidis were among the most predominant organisms. The number of species identified from lesions with abscesses (14.1 +/- 2.6) was significantly greater (P < 0.001) than the number from lesions without abscesses (7.4 +/- 5.9). Comparison of perioral isolates using repetitive extragenic palindromic PCR of the same species from the same subjects demonstrated that the endodontic and skin populations were significantly different. The P. acnes isolates were typed on the basis of recA gene sequence comparison, and only three types (types I, II, and III) were identified among 125 isolates examined. However, we found that type I (type IA and IB) isolates were primarily isolated from the skin, while types II and III were significantly more likely to be isolated from the endodontic lesions (P < 10(-10)). We found that the robustness of the recA phylotypes was not strong by comparing the partial gene sequences of six putative virulence determinants, PAmce, PAp60, PA-25957, PA-5541, PA-21293, and PA-4687. The resulting neighbor-joining trees were incongruent, and significant (phi test; P = 2.2 * 10(-7)) evidence of recombination was demonstrated, with significant phylogenetic heterogeneity being apparent within the clusters. P. acnes and S. epidermidis isolated from refractory endodontic infections, with or without periapical abscesses, are likely to be nosocomial infections. PMID- 20739495 TI - Molecular epidemiology of multidrug-resistant Acinetobacter baumannii in a single institution over a 10-year period. AB - Multidrug-resistant Acinetobacter baumannii is a worldwide nosocomial menace. We sought to better understand its behavior through studying the molecular epidemiology of this organism at the Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia, over a 10-year period. Multilocus sequence typing (MLST), semiautomated repetitive sequence-based PCR (rep-PCR), and pulsed field gel electrophoresis (PFGE) were performed on a selection of 31 A. baumannii isolates collected over the 10-year period to determine their relationships to one another. MLST also allowed us to put this information in a global context. The presence or absence of bla(OXA-23) was also established. The presence of bla(OXA-23) closely correlated with carbapenem resistance in our collection. Sequence type 92 (ST92) was the dominant sequence type and was present in the hospital for 9 years. There was also evidence of the spread of ST69, ST73, and ST125 (novel) within the hospital, but this was not sustained over long periods. There were only single examples of the novel sequence types ST126 and ST127. The different typing methods clustered the isolates similarly; however, PFGE and rep PCR were more discriminatory than MLST. Worldwide, ST92 and the associated clonal complex 92 represent the most sampled and widespread sequence type(s) and are also known as European clone 2 and worldwide clonal lineage 2. Antibiotic susceptibility within ST92 is variable, suggesting a role for mechanisms other than antibiotic resistance in its success. PMID- 20739496 TI - Neisseria meningitidis serogroup X sequence type 767 in Turkey. PMID- 20739497 TI - The clinical microbiology laboratory director in the United States hospital setting. AB - Clinical microbiology laboratory directors come from diverse backgrounds with overlapping but not identical training experiences. Although director responsibilities are defined by CLIA legislation, there is no standardization of job descriptions among hospital or university settings. One job that would make the microbiology director indispensable, if done well, is clinical consultation. Other challenges include attracting and educating future directors, expanding income opportunities through novel business plans and research funding, increasing doctoral-level professional staffing to provide clinical, administrative, educational, and scientific competencies, cooperating with fellow laboratory directors to merge novel technical methods with appropriate clinical interpretation, and participating in the political process to drive legislation toward excellence in patient care. Conversation among medical microbiologists is needed to focus efforts on defining, standardizing, and improving our performance as CML directors. PMID- 20739498 TI - Characterization of vancomycin-resistant Enterococcus faecium isolated from swine in three Michigan counties. AB - Vancomycin-resistant enterococci are a major cause of nosocomial infections but are rarely found in humans in the community and have not been identified in food animals in the United States. We evaluated a total of 360 fecal specimens from humans and their animals being raised for exhibit at three county fairs in Michigan. Fecal samples from 158 humans, 55 swine, 50 cattle, 25 horses, 57 sheep, 14 goats, and 1 llama were obtained and plated onto Enterococcosel agar containing 16 MUg/ml of vancomycin. Vancomycin-resistant Enterococcus faecium (VREF) was isolated from six pigs but not from humans or any animal other than pigs. All six VREF isolates had a MIC to vancomycin of >=256 MUg/ml and contained the vanA gene. Pulsed-field gel electrophoresis (PFGE) patterns of the six VREF isolates were >=80% similar. Multilocus sequence typing (MLST) revealed sequence type 5 (ST5) (n = 2), ST6 (n = 3), and ST185 (n = 1), which are E. faecium sequence types belonging to clonal complex 5 (CC5). These findings show the dissemination of VREF strains among pigs in three Michigan counties. This is the first report of VRE found in food animals in the United States. PMID- 20739499 TI - Technical and diagnostic performance of five commercial anti-diphtheria toxoid IgG enzyme-linked immunosorbent assay kits. AB - The technical and diagnostic performances of five commercially available enzyme linked immunosorbent assays for the measurement of anti-diphtheria toxoid IgG antibodies were evaluated. There was good agreement between the relative sensitivities of the five assays, but the relative specificity of one of the assays differed from that of the other four assays. Three of the five assays possessed recoveries of the international reference material NIBSC 00/496 within the range of 90% to 110% at antibody levels >0.1 IU/ml. The data suggest that there are manufacture-dependent differences in relative sensitivity, specificity, and accuracy for the determination of anti-diphtheria toxoid IgG antibodies that could result in different diagnostic interpretations. PMID- 20739500 TI - Vaccination of rhesus macaques with the anthrax vaccine adsorbed vaccine produces a serum antibody response that effectively neutralizes receptor-bound protective antigen in vitro. AB - Anthrax toxin (ATx) is composed of the binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor and lethal factor) but have the same binding protein, protective antigen (PA). PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to the target cell surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell). To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (noncomplexed [NC] and receptor-bound [RB] TNA assays). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated rhesus macaques (Macaca mulatta) that survived an aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was prebound to cells. Neutralization titers in surviving versus nonsurviving animals and between prechallenge and postchallenge activities were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support the idea that the full-length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines. PMID- 20739501 TI - Improved diagnosis of Strongyloides stercoralis using recombinant antigen-based serologies in a community-wide study in northern Argentina. AB - The serodiagnosis of Strongyloides stercoralis infection by enzyme-linked immunosorbent assays based on crude antigen (CrAg-ELISA), while useful, has been limited by the reliance on crude parasite extracts. Newer techniques such as the luciferase immunoprecipitation system assay (LIPS), based on a 31-kDa recombinant antigen (termed NIE) from S. stercoralis and/or the recombinant antigen S. stercoralis immunoreactive antigen (SsIR), or the NIE-ELISA have shown promise in controlled settings. We compared each of these serologic assays in individuals from both regions of the world in which S. stercoralis is endemic and those in which it is not. A comprehensive stool evaluation (sedimentation concentration, Baermann concentration with charcoal cultures, agar plate, and Harada-Mori) and four different serologic techniques using CrAg-ELISA or recombinant NIE-ELISA as well as LIPS using NIE alone or in combination with a second recombinant antigen (NIE/SsIR-LIPS) were compared among individuals with parasitologically proven infection (n = 251) and healthy controls from regions of the world in which the infection is nonendemic (n = 11). Accuracy was calculated for each assay. The prevalence of S. stercoralis infection was 29.4% among Argentinean stool samples (n = 228). Sedimentation concentration and Baermann were the most sensitive stool based methods. NIE-LIPS showed the highest sensitivity (97.8%) and specificity (100%) of the serologic assays. The calculated negative predictive value was highest for both the NIE-LIPS and CrAg-ELISA (>97%) irrespective of disease prevalence. No cross-reactivity with soil-transmitted helminths was noted. NIE LIPS compares favorably against the current CrAg-ELISA and stool evaluation, providing additional accuracy and ease of performance in the serodiagnosis of S. stercoralis infections irrespective of disease prevalence. PMID- 20739502 TI - Immunogenicity of an autogenous Streptococcus suis bacterin in preparturient sows and their piglets in relation to protection after weaning. AB - Streptococcus suis is an important porcine pathogen causing meningitis and other invasive diseases in piglets of different ages. Application of S. suis serotype 2 bacterins to specific-pathogen-free (SPF) weaning piglets has been demonstrated to protect against the homologous serotype. However, autogenous S. suis bacterins are also applied to sows and suckling piglets in the field. Therefore, comparative evaluation of different bacterin immunization regimes, including sow vaccination, was performed in this study. The main objectives were to determine the immunogenicity of an S. suis bacterin in sows prepartum and its influence on active immunization of piglets. Experimental infection of 6- and 8-week-old weaning piglets was performed to elucidate protective efficacies. Humoral immune responses were investigated by an enzyme-linked immunosorbent assay (ELISA) measuring muramidase-released protein (MRP)-specific IgG titers and by opsonophagocytosis assays. Bacterin application elicited high MRP-specific IgG titers in the serum and colostrum of sows, as well as opsonizing antibodies. Piglets from vaccinated sows had significantly higher MRP-specific titers than respective piglets from nonvaccinated sows until 6 weeks postpartum. Vaccination of suckling piglets did not result in high MRP-specific titers nor in induction of opsonizing antibodies. Furthermore, neither vaccination of suckling nor of weaning piglets from immunized sows was associated with a prominent active immune response and protection at 8 weeks postpartum. However, protection was observed in respective 6-week-old weaning piglets, most likely because of protective maternal immunity. In conclusion, this study provides the first results suggesting protective passive maternal immunity for S. suis serotype 2 after bacterin vaccination of sows and a strong inhibitory effect on active immunization of suckling and weaning piglets, leading to highly susceptible growers. PMID- 20739503 TI - Development of human-murine chimeric immunoglobulin G for use in the serological detection of human flavivirus and alphavirus antibodies. AB - Diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the indirect IgG ELISA. Broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, West Nile, yellow fever, Japanese encephalitis, Saint Louis encephalitis, and Powassan viruses), or alphaviruses (e.g., Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis, and chikungunya viruses) that can cause human disease. We have created human-murine chimeric monoclonal antibodies (cMAbs) by combining the variable regions of flavivirus (6B6C-1) or alphavirus (1A4B-6) broadly cross-reactive murine MAbs (mMAbs) with the constant region of human IgG1. These cMAbs may be used as standardized reagents capable of replacing human infection-immune-positive control sera in indirect IgG ELISA for diagnosis of all human flaviviral or alphaviral infections. The IgG cMAbs secreted from plasmid transformed Sp2/0-Ag14 cells had serological activity identical to that of the parent mMAbs, as measured by ELISA using multiple flaviviruses or alphaviruses. PMID- 20739504 TI - Serological evidence of human klassevirus infection. AB - Klassevirus is a proposed new genus of picornavirus that has been associated with pediatric diarrhea. In this study, we used recombinant klassevirus 3C protease as the capture antigen for an indirect serological enzyme-linked immunosorbent assay (ELISA). Four of six klassevirus reverse transcription (RT)-PCR-positive individuals demonstrated seroconversion against the 3C protease, suggesting that klassevirus infection and replication occur in humans. Additional screening of 353 samples from an age-banded serological cohort from two St. Louis hospitals indicated a seroprevalence of 6.8%. PMID- 20739505 TI - Immune responses and therapeutic antitumor effects of an experimental DNA vaccine encoding human papillomavirus type 16 oncoproteins genetically fused to herpesvirus glycoprotein D. AB - Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV 1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8(+) T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells). In the present report, we characterized some previously uncovered aspects concerning the induction of CD8(+) T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells. Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4(+) T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8(+) T-cell responses. In addition, we determined the priming/boosting properties of pgD-E7E6E5 when used in combination with a recombinant serotype 68 adenovirus (AdC68) vector encoding the same chimeric antigen. Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8(+) T-cell responses, measured by intracellular gamma interferon (IFN-gamma) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2D(b)-restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein. Up to 70% of the mice challenged with 5 * 10(5) TC-1 cells and immunized with pgD-E7E6E5 controlled tumor development even after 3 days of tumor cell challenge. In addition, coadministration of pgD E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells. In conclusion, the present results expand our previous knowledge on the immune modulation properties of the pgD-E7E6E5 vector and demonstrate, for the first time, the strong antitumor effects of the DNA vaccine, raising promising perspectives regarding the development of immunotherapeutic reagents for the control of HPV-16-associated tumors. PMID- 20739507 TI - Glucose-induced ERM protein activation and translocation regulates insulin secretion. AB - A key step in regulating insulin secretion is insulin granule trafficking to the plasma membrane. Using live-cell time-lapse confocal microscopy, we observed a dynamic association of insulin granules with filamentous actin and PIP2-enriched structures. We found that the scaffolding protein family ERM, comprising ezrin, radixin, and moesin, are expressed in beta-cells and target both F-actin and PIP2. Furthermore, ERM proteins are activated via phosphorylation in a glucose- and calcium-dependent manner. This activation leads to a translocation of the ERM proteins to sites on the cell periphery enriched in insulin granules, the exocyst complex docking protein Exo70, and lipid rafts. ERM scaffolding proteins also participate in insulin granule trafficking and docking to the plasma membrane. Overexpression of a truncated dominant-negative ezrin construct that lacks the ERM F-actin binding domain leads to a reduction in insulin granules near the plasma membrane and impaired secretion. Conversely, overexpression of a constitutively active ezrin results in more granules near the cell periphery and an enhancement of insulin secretion. Diabetic mouse islets contain less active ERM, suggestive of a novel mechanism whereby impairment of insulin granule trafficking to the membrane through a complex containing F-actin, PIP2, Exo70, and ERM proteins contributes to defective insulin secretion. PMID- 20739506 TI - NF-kappaB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions. AB - NF-kappaB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-kappaB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-kappaB activity in muscle. The effect that exercise has on NF-kappaB activity/signaling also is not clear. We measured NF-kappaB DNA-binding activity and the mRNA level of putative NF-kappaB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-kappaB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-kappaB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-kappaB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-kappaB activity in muscle. Acute exercise stimulates NF-kappaB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-kappaB activity, which could be explained by the already elevated NF-kappaB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-kappaB activity, suggesting that other factors promote gene expression of these cytokines during exercise. PMID- 20739509 TI - Methods to quantify sex steroid hormones in bone: applications to the study of androgen ablation and administration. AB - Bone may contain an intraskeletal reservoir of sex steroids that is capable of producing biological effects. The purposes of these experiments were to 1) establish and validate methods to extract and measure intraskeletal sex hormones, 2) compare serum and intraskeletal sex hormone abundance, and 3) determine the impact of testosterone-enanthate administration and orchiectomy on intraskeletal sex hormone concentrations. Tibiae from male F344 rats were crushed, suspended in an aqueous buffer, disrupted mechanically and sonically, extracted with organic solvents, dried, and reconstituted in assay buffer appropriate for measurement of testosterone, dihydrotestosterone, and estradiol by immunoassay. Prior to extraction, bone homogenate was spiked with [3H]testosterone, [3H]dihydrotestosterone, or [3H]estradiol, and >80% of each 3H-labeled sex hormone was recovered. Extracted bone samples were also assayed with and without known amounts of unlabeled sex hormones, and >97% of the expected hormone concentrations were measured. Administration of testosterone-enanthate increased intraskeletal testosterone 11-fold and intraskeletal dihydrotestosterone by 82% without altering intraskeletal estradiol (P < 0.01). Conversely, orchiectomy did not alter intraskeletal testosterone or estradiol but increased intraskeletal dihydrotestosterone by 39% (P < 0.05). In intact rats, intraskeletal testosterone and dihydrotestosterone were directionally higher than in serum, whereas intraskeletal estradiol was directionally lower than serum. Serum androgens were positively correlated with intraskeletal androgens (r = 0.74-0.96, P < 0.001); however, neither serum nor intraskeletal androgens nor serum estradiol were correlated with intraskeletal estradiol. We report the validation of a novel method for measuring intraskeletal sex hormones. Our findings demonstrate that the intraskeletal sex steroid reservoirs are modifiable and only partially influenced by circulating sex hormones. PMID- 20739508 TI - Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium. AB - The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased >=2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase (Fasn), insulin-induced gene 1 (Insig1), mitochondrial citrate transporter (Slc25a1), and stearoyl-CoA desaturase 2 (Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1alpha (Acaca) and ATP citrate lyase (Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein. PMID- 20739510 TI - Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men. AB - Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity. PMID- 20739511 TI - An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart. AB - Adiponectin promotes cardioprotection by various mechanisms, and this study used primary cardiomyocytes and the isolated working perfused heart to investigate cardiometabolic effects. We show in adult cardiomyocytes that adiponectin increased CD36 translocation and fatty acid uptake as well as insulin-stimulated glucose transport and Akt phosphorylation. Coimmunoprecipitation showed that adiponectin enhanced association of AdipoR1 with APPL1, subsequent binding of APPL1 with AMPKalpha2, which led to phosphorylation and inhibition of ACC and increased fatty acid oxidation. Using siRNA to effectively knockdown APPL1 in neonatal cardiomyocytes, we demonstrated an essential role for APPL1 in mediating increased fatty acid uptake and oxidation by adiponectin. Importantly, enhanced fatty acid oxidation in conjunction with AMPK and ACC phosphorylation was also observed in the isolated working heart. Despite increasing fatty acid oxidation and myocardial oxygen consumption, adiponectin increased hydraulic work and maintained cardiac efficiency. In summary, the present study documents several beneficial metabolic effects mediated by adiponectin in the heart and provides novel insight into the mechanisms behind these effects, in particular the importance of APPL1. PMID- 20739513 TI - Human cytomegalovirus induces the endoplasmic reticulum chaperone BiP through increased transcription and activation of translation by using the BiP internal ribosome entry site. AB - The endoplasmic reticulum (ER) chaperone BiP (immunoglobulin binding protein) plays a major role in the control of the unfolded protein response. We have previously shown that BiP levels are dramatically increased during human cytomegalovirus (HCMV) infection, where BiP performs unique roles in viral assembly and egress. We show that BiP mRNA levels increase during infection due to activation of the BiP promoter by the major immediate-early (MIE) proteins. The BiP promoter, like other ER stress-activated promoters, contains endoplasmic reticulum stress elements (ERSEs), which are activated by unfolded protein response (UPR)-induced transcription factors. However, these elements are not needed for MIE protein-mediated transcriptional activation; thus, a virus specific transcriptional activation mechanism is used. Transcriptional activation results in only a 3- to 4-fold increase in BiP mRNA, suggesting that additional mechanisms for BiP production are utilized. The BiP mRNA contains an internal ribosome entry site (IRES) which increases the level of BiP mRNA translation. We show that utilization of the BiP IRES is dramatically increased in HCMV-infected cells. Utilization of the BiP IRES can be activated by the La autoantigen, also called Sjogren's syndrome antigen B (SSB). We show that SSB/La levels are significantly increased during HCMV infection, and SSB/La depletion causes the loss of BiP IRES utilization and lowers endogenous BiP levels in infected cells. Our data show that BiP levels increase in HCMV-infected cells through the combination of increased BiP gene transcription mediated by the MIE proteins and increased BiP mRNA translation due to SSB/La-induced utilization of the BiP IRES. PMID- 20739512 TI - Impact of viral-mediated IGF-I gene transfer on skeletal muscle following cast immobilization. AB - Insulin-like growth factor I (IGF-I) is a potent myogenic factor that plays a critical role in muscle regeneration and muscle hypertrophy. The purpose of this study was to evaluate the effect of IGF-I overexpression on the recovery of muscle size and function during reloading/reambulation after a period of cast immobilization in predominantly fast twitch muscles. In addition, we investigated concomitant molecular responses in IGF-I receptor and binding proteins (BPs). Recombinant adeno-associated virus vector for IGF-I (rAAV-IGF-IA) was injected into the anterior compartment of one of the hindlimbs of young (3 wk) C57BL6 female mice. At 20 wk of age, both hindlimbs were cast immobilized in a shortened position for 2 wk to unload the tibialis anterior (TA) and extensor longus digitorum (EDL) muscles. The TA and EDL muscles were removed bilaterally after 2 wk of cast immobilization and after 1 and 3 wk of free cage reambulation. Increases in IGF-I mRNA and protein levels with IGF-I overexpression were associated with significant increases in muscle wet weight, fiber size, and tetanic force, although overexpression did not protect against cast immobilization-induced muscle atrophy. After 1 wk of reambulation, evidence of enhanced muscle regeneration was noted in IGF-I-overexpressing muscles with an increased prevalence of central nuclei, embryonic myosin, and Pax7 positive fibers. We also observed larger relative gains in muscle size (wet weight and fiber area), but not force, during the 3-wk reambulation period in hindlimb muscles overexpressing IGF-I compared with contralateral control legs. Changes in IGFBP-5 mRNA expression during cast immobilization and reambulation paralleled those of IGF-I, whereas IGFBP-3 expression changed inversely to IGFBP-5. PMID- 20739514 TI - Pathogenesis and immune response of Crimean-Congo hemorrhagic fever virus in a STAT-1 knockout mouse model. AB - Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation. PMID- 20739515 TI - Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. AB - The type I alpha/beta interferons (IFN-alpha/beta) are known to play an important role in host defense against influenza A virus infection, but we have now discovered that the recently identified type III IFNs (IFN-lambda) constitute the major response to intranasal infection with this virus. Type III IFNs were present at much higher levels than type I IFNs in the lungs of infected mice, and the enhanced susceptibility of STAT2-/- animals demonstrated that only signaling through the IFN-alpha/beta or IFN-lambda pathways was sufficient to mediate protection. This finding offers a possible explanation for the similar levels of antiviral protection found in wild-type (WT) mice and in animals lacking a functional type I IFN receptor (IFNAR-/-) but also argues that our current understanding of type III IFN induction is incomplete. While murine IFN-lambda production is thought to depend on signaling through the type I IFN receptor, we demonstrate that intranasal influenza A virus infection leads to the robust type III IFN induction in the lungs of both WT and IFNAR-/- mice. This is consistent with previous studies showing that IFNAR-mediated protection is redundant for mucosal influenza virus infection and with data showing that the type III IFN receptor is expressed primarily by epithelial cells. However, the overlapping effects of these two cytokine families are limited by their differential receptor expression, with a requirement for IFN-alpha/beta signaling in combating systemic disease. PMID- 20739516 TI - NS reassortment of an H7-type highly pathogenic avian influenza virus affects its propagation by altering the regulation of viral RNA production and antiviral host response. AB - Highly pathogenic avian influenza viruses (HPAIV) with reassorted NS segments from H5- and H7-type avian virus strains placed in the genetic background of the A/FPV/Rostock/34 HPAIV (FPV; H7N1) were generated by reverse genetics. Virological characterizations demonstrated that the growth kinetics of the reassortant viruses differed from that of wild-type (wt) FPV and depended on whether cells were of mammalian or avian origin. Surprisingly, molecular analysis revealed that the different reassortant NS segments were not only responsible for alterations in the antiviral host response but also affected viral genome replication and transcription as well as nuclear ribonucleoprotein (RNP) export. RNP reconstitution experiments demonstrated that the effects on accumulation levels of viral RNA species were dependent on the specific NS segment as well as on the genetic background of the RNA-dependent RNA polymerase (RdRp). Beta interferon (IFN-beta) expression and the induction of apoptosis were found to be inversely correlated with the magnitude of viral growth, while the NS allele, virus subtype, and nonstructural protein NS1 expression levels showed no correlation. Thus, these results demonstrate that the origin of the NS segment can have a dramatic effect on the replication efficiency and host range of HPAIV. Overall, our data suggest that the propagation of NS reassortant influenza viruses is affected at multiple steps of the viral life cycle as a result of the different effects of the NS1 protein on multiple viral and host functions. PMID- 20739517 TI - Host insect inhibitor-of-apoptosis SfIAP functionally replaces baculovirus IAP but is differentially regulated by Its N-terminal leader. AB - The inhibitor-of-apoptosis (IAP) proteins encoded by baculoviruses bear a striking resemblance to the cellular IAP homologs of their invertebrate hosts. By virtue of the acquired selective advantage of blocking virus-induced apoptosis, baculoviruses may have captured cellular IAP genes that subsequently evolved for virus-specific objectives. To compare viral and host IAPs, we defined antiapoptotic properties of SfIAP, the principal cellular IAP of the lepidopteran host Spodoptera frugiperda. We report here that SfIAP prevented virus-induced apoptosis as well as viral Op-IAP3 (which is encoded by the Orgyia pseudotsugata nucleopolyhedrovirus) when overexpressed from the baculovirus genome. Like Op IAP3, SfIAP blocked apoptosis at a step prior to caspase activation. Both of the baculovirus IAP repeats (BIRs) were required for SfIAP function. Moreover, deletion of the C-terminal RING motif generated a loss-of-function SfIAP that interacted and dominantly interfered with wild-type SfIAP. Like Op-IAP3, wild type SfIAP formed intracellular homodimers, suggesting that oligomerization is a functional requirement for both cellular and viral IAPs. SfIAP possesses a ~100 residue N-terminal leader domain, which is absent among all viral IAPs. Remarkably, deletion of the leader yielded a fully functional SfIAP with dramatically increased protein stability. Thus, the SfIAP leader contains an instability motif that may confer regulatory options for cellular IAPs that baculovirus IAPs have evolved to bypass for maximal stability and antiapoptotic potency. Our findings that SfIAP and viral IAPs have common motifs, share multiple biochemical properties including oligomerization, and act at the same step to block apoptosis support the hypothesis that baculoviral IAPs were derived by acquisition of host insect IAPs. PMID- 20739518 TI - The noncanonical Gag domains p8 and n are critical for assembly and release of mouse mammary tumor virus. AB - The mouse mammary tumor virus (MMTV) Gag contains the unique domains pp21, p3, p8, and n. We investigated the contribution of these domains to particle assembly and found that the region spanning the p8 and n domains is critical for shape determination and assembly. Deletion of pp21 and p3 reduced the number of released particles, but deletion of the n domain resulted in frequent formation of aberrant particles, while deletion of p8 severely impaired assembly. Further investigation of p8 revealed that both the basic and the proline-rich motifs within p8 contribute to MMTV assembly. PMID- 20739519 TI - Early innate recognition of herpes simplex virus in human primary macrophages is mediated via the MDA5/MAVS-dependent and MDA5/MAVS/RNA polymerase III-independent pathways. AB - Innate recognition of viruses is mediated by pattern recognition receptors (PRRs) triggering expression of antiviral interferons (IFNs) and proinflammatory cytokines. In mice, Toll-like receptor 2 (TLR2) and TLR9 as well as intracellular nucleotide-sensing pathways have been shown to recognize herpes simplex virus (HSV). Here, we describe how human primary macrophages recognize early HSV infection via intracellular pathways. A number of inflammatory cytokines, IFNs, and IFN-stimulated genes were upregulated after HSV infection. We show that early recognition of HSV and induction of IFNs and inflammatory cytokines are independent of TLR2 and TLR9, since inhibition of TLR2 using TLR2 neutralizing antibodies did not affect virus-induced responses and the macrophages were unresponsive to TLR9 stimulation. Instead, HSV recognition involves intracellular recognition systems, since induction of tumor necrosis factor alpha (TNF-alpha) and IFNs was dependent on virus entry and replication. Importantly, expression of IFNs was strongly inhibited by small interfering RNA (siRNA) knockdown of MAVS, but this MAVS-dependent IFN induction occurred independently of the recently discovered polymerase III (Pol III)/RIG-I DNA sensing system. In contrast, induction of TNF-alpha was largely independent of MAVS, suggesting that induction of inflammatory cytokines during HSV infection proceeds via a novel pathway. Transfection with ODN2006, a broad inhibitor of intracellular nucleotide recognition, revealed that nucleotide-sensing systems are employed to induce both IFNs and TNF-alpha. Finally, using siRNA knockdown, we found that MDA5, but not RIG-I, was the primary mediator of HSV recognition. Thus, innate recognition of HSV by human primary macrophages occurs via two distinct intracellular nucleotide sensing pathways responsible for induction of IFNs and inflammatory cytokine expression, respectively. PMID- 20739520 TI - Pathogenesis of hepatitis E virus and hepatitis C virus in chimpanzees: similarities and differences. AB - The chimpanzee is the only animal model for investigating the pathogenesis of viral hepatitis types A through E in humans. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human based reagents. In this study, the host responses to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), were compared in multiple experimentally infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. Respecting the limitations of microarray probes designed for human target transcripts to effectively assay chimpanzee transcripts, we conducted probe-level analysis of the microarray data in conjunction with a custom mapping of the probe sequences to the most recent human and chimpanzee genome sequences. Time points for statistical comparison were chosen based on independently measured viremia levels. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust in the magnitude and number of differentially expressed genes compared to HEV infection. PMID- 20739522 TI - Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation. AB - Type I interferons (IFNs) IFN-alpha/beta play an important role in innate immunity against viral infections by inducing antiviral responses. Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the synthesis of type I IFNs. However, whether PRRSV can inhibit IFN signaling is less well understood. In the present study, we found that PRRSV interferes with the IFN signaling pathway. The transcript levels of IFN-stimulated genes ISG15 and ISG56 and protein level of signal transducer and activator of transcription 2 (STAT2) in PRRSV VR2385-infected MARC-145 cells were significantly lower than those in mock-infected cells after IFN-alpha treatment. IFN-induced phosphorylation of both STAT1 and STAT2 and their heterodimer formation in the PRRSV-infected cells were not affected. However, the majority of the STAT1/STAT2/IRF9 (IFN regulatory factor 9) heterotrimers remained in the cytoplasm of PRRSV-infected cells, which indicates that the nuclear translocation of the heterotrimers was blocked. Overexpression of NSP1beta of PRRSV VR2385 inhibited expression of ISG15 and ISG56 and blocked nuclear translocation of STAT1, which suggests that NSP1beta might be the viral protein responsible for the inhibition of IFN signaling. PRRSV infection in primary porcine pulmonary alveolar macrophages (PAMs) also inhibited IFN-alpha-stimulated expression of the ISGs and the STAT2 protein. In contrast, a licensed low-virulence vaccine strain, Ingelvac PRRS modified live virus (MLV), activated expression of IFN-inducible genes, including those of chemokines and antiviral proteins, in PAMs without the addition of external IFN and had no detectable effect on IFN signaling. These findings suggest that PRRSV interferes with the activation and signaling pathway of type I IFNs by blocking ISG factor 3 (ISGF3) nuclear translocation. PMID- 20739521 TI - Tracking the evolution of multiple in vitro hepatitis C virus replicon variants under protease inhibitor selection pressure by 454 deep sequencing. AB - Resistance to hepatitis C virus (HCV) inhibitors targeting viral enzymes has been observed in in vitro replicon studies and during clinical trials. The factors determining the emergence of resistance and the changes in the viral quasispecies population under selective pressure are not fully understood. To assess the dynamics of variants emerging in vitro under various selective pressures with TMC380765, a potent macrocyclic HCV NS3/4A protease inhibitor, HCV genotype 1b replicon-containing cells were cultured in the presence of a low, high, or stepwise-increasing TMC380765 concentration(s). HCV replicon RNA from representative samples thus obtained was analyzed using (i) population, (ii) clonal, and (iii) 454 deep sequencing technologies. Depending on the concentration of TMC380765, distinct mutational patterns emerged. In particular, culturing with low concentrations resulted in the selection of low-level resistance mutations (F43S and A156G), whereas high concentrations resulted in the selection of high-level resistance mutations (A156V, D168V, and D168A). Clonal and 454 deep sequencing analysis of the replicon RNA allowed the identification of low-frequency preexisting mutations possibly contributing to the mutational pattern that emerged. Stepwise-increasing TMC380765 concentrations resulted in the emergence and disappearance of multiple replicon variants in response to the changing selection pressure. Moreover, two different codons for the wild-type amino acids were observed at certain NS3 positions within one population of replicons, which may contribute to the emerging mutational patterns. Deep sequencing technologies enabled the study of minority variants present in the HCV quasispecies population present at baseline and during antiviral drug pressure, giving new insights into the dynamics of resistance acquisition by HCV. PMID- 20739523 TI - Diverging affinity of tospovirus RNA silencing suppressor proteins, NSs, for various RNA duplex molecules. AB - The tospovirus NSs protein was previously shown to suppress the antiviral RNA silencing mechanism in plants. Here the biochemical analysis of NSs proteins from different tospoviruses, using purified NSs or NSs containing cell extracts, is described. The results showed that all tospoviral NSs proteins analyzed exhibited affinity to small double-stranded RNA molecules, i.e., small interfering RNAs (siRNAs) and micro-RNA (miRNA)/miRNA* duplexes. Interestingly, the NSs proteins from tomato spotted wilt virus (TSWV), impatiens necrotic spot virus (INSV), and groundnut ringspot virus (GRSV) also showed affinity to long double-stranded RNA (dsRNA), whereas tomato yellow ring virus (TYRV) NSs did not. The TSWV NSs protein was shown to be capable of inhibiting Dicer-mediated cleavage of long dsRNA in vitro. In addition, it suppressed the accumulation of green fluorescent protein (GFP)-specific siRNAs during coinfiltration with an inverted-repeat-GFP RNA construct in Nicotiana benthamiana. In vivo interference of TSWV NSs in the miRNA pathway was shown by suppression of an enhanced GFP (eGFP) miRNA sensor construct. The ability to stabilize miRNA/miRNA* by different tospovirus NSs proteins in vivo was demonstrated by increased accumulation and detection of both miRNA171c and miRNA171c* in tospovirus-infected N. benthamiana. All together, these data suggest that tospoviruses interfere in the RNA silencing pathway by sequestering siRNA and miRNA/miRNA* molecules before they are uploaded into their respective RNA-induced silencing complexes. The observed affinity to long dsRNA for only a subset of the tospoviruses studied is discussed in light of evolutional divergence and their ancestral relation to the animal-infecting members of the Bunyaviridae. PMID- 20739524 TI - The coronavirus nucleocapsid protein is dynamically associated with the replication-transcription complexes. AB - The coronavirus nucleocapsid (N) protein is a virion structural protein. It also functions, however, in an unknown way in viral replication and localizes to the viral replication-transcription complexes (RTCs). Here we investigated, using recombinant murine coronaviruses expressing green fluorescent protein (GFP) tagged versions of the N protein, the dynamics of its interactions with the RTCs and the domain(s) involved. Using fluorescent recovery after photobleaching, we showed that the N protein, unlike the nonstructural protein 2, is dynamically associated with the RTCs. Recruitment of the N protein to the RTCs requires the C terminal N2b domain, which interacts with other N proteins in an RNA-independent manner. PMID- 20739525 TI - Identification of a previously unrecognized promoter that drives expression of the UXP transcription unit in the human adenovirus type 5 genome. AB - We previously identified an adenovirus (Ad) protein named U exon protein (UXP) encoded by a leftward-strand (l-strand) transcription unit. Here we identify and characterize the UXP promoter. Primer extension and RNase protection assays mapped the transcription initiation site at 32 nucleotides upstream of the UXP gene initiation codon. A series of viral mutants with mutations at two putative inverted CCAAT (I-CCAAT) boxes and two E2F sites were generated. With mutants lacking the proximal I-CCAAT box, the UXP mRNA level decreased significantly to 30% of the Ad type 5 (Ad5) mRNA level as measured by quantitative reverse transcription-PCR. Decreased UXP was also observed by immunoblotting and immunofluorescence. UXP mRNA and protein levels were similar to those of Ad5 for mutants lacking the distal I-CCAAT box or both putative E2F sites. Ad DNA levels were similar in mutant- and wild-type Ad5-infected cells during the late stage of infection, strongly suggesting that the decreased UXP mRNA and protein from mutants lacking the proximal I-CCAAT box was due to decreased promoter activity. Electrophoretic mobility shift assays (EMSA) indicated that a cellular factor binds specifically to the proximal I-CCAAT box of the UXP promoter. An in vitro luciferase reporter assay demonstrated that basal promoter activity lies between bp -158 and +30 of the transcription initiation site. No E1A-mediated promoter transactivation was observed in 293 cells compared with A549 cells. Thus, we propose that there is a previously unidentified Ad5 promoter that drives expression of the UXP transcription unit. This promoter is embedded within the gene for fiber, and it contains a proximal I-CCAAT box critical for UXP mRNA transcription. PMID- 20739526 TI - Structural evidence of glycoprotein assembly in cellular membrane compartments prior to Alphavirus budding. AB - Membrane glycoproteins of alphavirus play a critical role in the assembly and budding of progeny virions. However, knowledge regarding transport of viral glycoproteins to the plasma membrane is obscure. In this study, we investigated the role of cytopathic vacuole type II (CPV-II) through in situ electron tomography of alphavirus-infected cells. The results revealed that CPV-II contains viral glycoproteins arranged in helical tubular arrays resembling the basic organization of glycoprotein trimers on the envelope of the mature virions. The location of CPV-II adjacent to the site of viral budding suggests a model for the transport of structural components to the site of budding. Thus, the structural characteristics of CPV-II can be used in evaluating the design of a packaging cell line for replicon production. PMID- 20739527 TI - HLA-Cw*03-restricted CD8+ T-cell responses targeting the HIV-1 gag major homology region drive virus immune escape and fitness constraints compensated for by intracodon variation. AB - The potential importance of HLA-C-restricted CD8+ cytotoxic T lymphocytes (CTL) in HIV infection remains undetermined. We studied the dominant HLA-Cw*03 restricted CTL response to YVDRFFKTL(296-304) (YL9), within the conserved major homology region (MHR) of the Gag protein, in 80 HLA-Cw*03-positive individuals with chronic HIV infection to better define the efficacy of the YL9 HLA-C restricted response. The HLA-Cw*03 allele is strongly associated with HIV sequence changes from Thr-303 to Val, Ile, or Ala at position 8 within the YL9 epitope (P=1.62*10(-10)). In vitro studies revealed that introduction of the changes T303I and T303A into the YL9 epitope both significantly reduced CTL recognition and substantially reduced the viral replicative capacity. However, subsequent selection of the Val-303 variant, via intracodon variation from Ile 303 (I303V) or Ala-303 (A303V), restored both viral fitness and CTL recognition, as supported by our in vivo data. These results illustrate that HLA-C-restricted CTL responses are capable of driving viral immune escape within Gag, but in contrast to what was previously described for HLA-B-restricted Gag escape mutants, the common Cw*03-Gag-303V variant selected resulted in no detectable benefit to the host. PMID- 20739528 TI - NFX1 plays a role in human papillomavirus type 16 E6 activation of NFkappaB activity. AB - High-risk human papillomavirus (HR HPV) requires differentiating epithelial cells to continue to divide in order to replicate the viral DNA. To achieve this, HPV perturbs several regulatory pathways, including cellular apoptosis and senescence signals. HPV E6 has been identified as a regulator of the NFkappaB signaling pathway, a pathway important in many cellular processes, as well as regulation of virus-host cell interactions. We report here that NFX1-91, an endogenously expressed transcriptional regulator of human telomerase reverse transcriptase (hTERT) that is targeted by HPV type 16 (HPV16) E6/E6-associated protein (E6AP) for degradation, is also critical for regulation of the NFkappaB pathway by HPV16 E6. Microarray analysis revealed induction of NFkappaB-responsive genes and reduction of NFkappaB inhibitors with knockdown of NFX1-91. Knockdown of NFX1-91 induced downregulation of p105, an NFkappaB inhibitor in both primary human foreskin keratinocytes (HFKs) and HCT116 cells. Chromatin immunoprecipitation assays further confirmed that NFX1-91 bound to the p105 promoter and upregulated its expression. Similarly, in HPV16 E6-positive cells, reduction of p105 expression was observed, paralleling knockdown of NFX1-91 expression. Overall, our data suggest a mechanism for HPV16 E6 activation of the NFkappaB pathway through NFX1-91. Also, it provides evidence that NFX1-91 can function as a dual regulator, not only a transcriptional repressor, but also a transcriptional activator, when bound to DNA. PMID- 20739529 TI - Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase. AB - Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication. PMID- 20739530 TI - CD8+ T cell recognition of cryptic epitopes is a ubiquitous feature of AIDS virus infection. AB - Vaccines designed to elicit AIDS virus-specific CD8+ T cells should engender broad responses. Emerging data indicate that alternate reading frames (ARFs) of both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode CD8+ T cell epitopes, termed cryptic epitopes. Here, we show that SIV specific CD8+ T cells from SIV-infected rhesus macaques target 14 epitopes in eight ARFs during SIV infection. Animals recognized up to five epitopes, totaling nearly one-quarter of the anti-SIV responses. The epitopes were targeted by high frequency responses as early as 2 weeks postinfection and in the chronic phase. Hence, previously overlooked ARF-encoded epitopes could be important components of AIDS vaccines. PMID- 20739531 TI - Partial functional rescue of Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus infectivity by replacement of F protein with GP64 from Autographa californica multicapsid nucleopolyhedrovirus. AB - Two distinct envelope fusion proteins (EFPs) (GP64 and F) have been identified in members of the Baculoviridae family of viruses. F proteins are found in group II nucleopolyhedroviruses (NPVs) of alphabaculoviruses and in beta- and deltabaculoviruses, while GP64 occurs only in group I NPVs of alphabaculoviruses. It was proposed that an ancestral baculovirus acquired the gp64 gene that conferred a selective advantage and allowed it to evolve into group I NPVs. The F protein is a functional analogue of GP64, as evidenced from the rescue of gp64 null Autographa californica multicapsid nucleopolyhedrovirus (MNPV) (AcMNPV) by F proteins from group II NPVs or from betabaculoviruses. However, GP64 failed to rescue an F-null Spodoptera exigua MNPV (SeMNPV) (group II NPV). Here, we report the successful generation of an infectious gp64-rescued group II NPV of Helicoverpa armigera (vHaBacDeltaF-gp64). Viral growth curve assays and quantitative real-time PCR (Q-PCR), however, showed substantially decreased infectivity of vHaBacDeltaF-gp64 compared to the HaF rescue control virus vHaBacDeltaF-HaF. Electron microscopy further showed that most vHaBacDeltaF-gp64 budded viruses (BV) in the cell culture supernatant lacked envelope components and contained morphologically aberrant nucleocapsids, suggesting the improper BV envelopment or budding of vHaBacDeltaF-gp64. Bioassays using pseudotyped viruses with a reintroduced polyhedrin gene showed that GP64-pseudotyped Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HearNPV) significantly delayed the mortality of infected H. armigera larvae. PMID- 20739532 TI - Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models. AB - Oseltamivir is routinely used worldwide for the treatment of severe influenza A virus infection, and should drug-resistant pandemic 2009 H1N1 viruses become widespread, this potent defense strategy might fail. Oseltamivir-resistant variants of the pandemic 2009 H1N1 influenza A virus have been detected in a substantial number of patients, but to date, the mutant viruses have not moved into circulation in the general population. It is not known whether the resistance mutations in viral neuraminidase (NA) reduce viral fitness. We addressed this question by studying transmission of oseltamivir-resistant mutants derived from two different isolates of the pandemic H1N1 virus in both the guinea pig and ferret transmission models. In vitro, the virus readily acquired a single histidine-to-tyrosine mutation at position 275 (H275Y) in viral neuraminidase when serially passaged in cell culture with increasing concentrations of oseltamivir. This mutation conferred a high degree of resistance to oseltamivir but not zanamivir. Unexpectedly, in guinea pigs and ferrets, the fitness of viruses with the H275Y point mutation was not detectably impaired, and both wild type and mutant viruses were transmitted equally well from animals that were initially inoculated with 1:1 virus mixtures to naive contacts. In contrast, a reassortant virus containing an oseltamivir-resistant seasonal NA in the pandemic H1N1 background showed decreased transmission efficiency and fitness in the guinea pig model. Our data suggest that the currently circulating pandemic 2009 H1N1 virus has a high potential to acquire drug resistance without losing fitness. PMID- 20739533 TI - Compromised spindle assembly checkpoint due to altered expression of Ubch10 and Cdc20 in human papillomavirus type 16 E6- and E7-expressing keratinocytes. AB - Cells expressing human papillomavirus type 16 (HPV-16) E6 and E7 proteins exhibit deregulation of G2/M genes, allowing bypass of DNA damage arrest signals. Normally, cells with DNA damage that override the G2 damage checkpoint would precociously enter mitosis and ultimately face mitotic catastrophe and apoptotic cell death. However, E6/E7-expressing cells (E6/E7 cells) have the ability to enter and exit mitosis in the presence of DNA damage and continue with the next round of the cell cycle. Little is known about the mechanism that allows these cells to gain entry into and exit from mitosis. Here, we show that in the presence of DNA damage, E6/E7 cells have elevated levels of cyclin B, which would allow entry into mitosis. Also, as required for exit from mitosis, cyclin B is degraded in these cells, permitting initiation of the next round of DNA synthesis and cell cycle progression. Proteasomal degradation of cyclin B by anaphase promoting complex/cyclosome (APC/C) is, in part, due to elevated levels of the E2 conjugating enzyme, Ubch10, and the substrate recognition protein, Cdc20, of APC/C. Also, in E6/E7 cells with DNA damage, while Cdc20 is complexed with BubR1, indicating an active checkpoint, it is also present in complexes free of BubR1, presumably allowing APC/C activity and slippage through the checkpoint. PMID- 20739534 TI - Hepatitis C virus egress and release depend on endosomal trafficking of core protein. AB - Hepatitis C virus (HCV) assembly is known to occur in juxtaposition to lipid droplets, but the mechanisms of nascent virion transport and release remain poorly understood. Here we demonstrate that HCV core protein targets to early and late endosomes but not to mitochondria or peroxisomes. Further, by employing inhibitors of early and late endosome motility in HCV-infected cells, we demonstrate that the movement of core protein to the early and late endosomes and virus production require an endosome-based secretory pathway. We also observed that this way is independent of that of the internalization of endocytosed virus particles during virus entry. PMID- 20739535 TI - Novel Nipah virus immune-antagonism strategy revealed by experimental and computational study. AB - Nipah virus is an emerging pathogen that causes severe disease in humans. It expresses several antagonist proteins that subvert the immune response and that may contribute to its pathogenicity. Studies of its biology are difficult due to its high pathogenicity and requirement for biosafety level 4 containment. We integrated experimental and computational methods to elucidate the effects of Nipah virus immune antagonists. Individual Nipah virus immune antagonists (phosphoprotein and V and W proteins) were expressed from recombinant Newcastle disease viruses, and the responses of infected human monocyte-derived dendritic cells were determined. We developed an ordinary differential equation model of the infectious process that that produced results with a high degree of correlation with these experimental results. In order to simulate the effects of wild-type virus, the model was extended to incorporate published experimental data on the time trajectories of immune-antagonist production. These data showed that the RNA-editing mechanism utilized by the wild-type Nipah virus to produce immune antagonists leads to a delay in the production of the most effective immune antagonists, V and W. Model simulations indicated that this delay caused a disconnection between attenuation of the antiviral response and suppression of inflammation. While the antiviral cytokines were efficiently suppressed at early time points, some early inflammatory cytokine production occurred, which would be expected to increase vascular permeability and promote virus spread and pathogenesis. These results suggest that Nipah virus has evolved a unique immune antagonist strategy that benefits from controlled expression of multiple antagonist proteins with various potencies. PMID- 20739536 TI - Environmental sources of scrapie prions. AB - Ovine scrapie and cervine chronic wasting disease show considerable horizontal transmission. Here we report that a scrapie-affected sheep farm has a widespread environmental contamination with prions. Prions were amplified by protein misfolding cyclic amplification (sPMCA) from seven of nine environmental swab samples taken, including those from metal, plastic, and wooden surfaces. Sheep had been removed from the areas from which the swabs were taken up to 20 days prior to sampling, indicating that prions persist for at least that long. These data implicate inanimate objects as environmental reservoirs for prion infectivity that are likely to contribute to facile disease transmission. PMID- 20739538 TI - A determinant of Sindbis virus neurovirulence enables efficient disruption of Jak/STAT signaling. AB - Previous studies with Venezuelan equine encephalitis virus and Sindbis virus (SINV) indicate that alphaviruses are capable of suppressing the cellular response to type I and type II interferons (IFNs) by disrupting Jak/STAT signaling; however, the relevance of this signaling inhibition toward pathogenesis has not been investigated. The relative abilities of neurovirulent and nonneurovirulent SINV strains to downregulate Jak/STAT signaling were compared to determine whether the ability to inhibit IFN signaling correlates with virulence potential. The adult mouse neurovirulent strain AR86 was found to rapidly and robustly inhibit tyrosine phosphorylation of STAT1 and STAT2 in response to IFN-gamma and/or IFN-beta. In contrast, the closely related SINV strains Girdwood and TR339, which do not cause detectable disease in adult mice, were relatively inefficient inhibitors of STAT1/2 activation. Decreased STAT activation in AR86-infected cells was associated with decreased activation of the IFN receptor-associated tyrosine kinases Tyk2, Jak1, and Jak2. To identify the viral factor(s) involved, we infected cells with several panels of AR86/Girdwood chimeric viruses. Surprisingly, we found that a single amino acid determinant, threonine at nsP1 position 538, which is required for AR86 virulence, was also required for efficient disruption of STAT1 activation, and this determinant fully restored STAT1 inhibition when it was introduced into the avirulent Girdwood background. These data indicate that a key virulence determinant plays a critical role in downregulating the response to type I and type II IFNs, which suggests that the ability of alphaviruses to inhibit Jak/STAT signaling relates to their in vivo virulence potential. PMID- 20739537 TI - Murine coronavirus receptors are differentially expressed in the central nervous system and play virus strain-dependent roles in neuronal spread. AB - Coronavirus infection of the murine central nervous system (CNS) provides a model for studies of viral encephalitis and demyelinating disease. Mouse hepatitis virus (MHV) neurotropism varies by strain: MHV-A59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain JHM.SD (MHV-4) causes fatal encephalitis with extensive neuronal spread of virus. In addition, while neurons are the predominant CNS cell type infected in vivo, the canonical receptor for MHV, the carcinoembryonic antigen family member CEACAM1a, has been demonstrated only on endothelial cells and microglia. In order to investigate whether CEACAM1a is also expressed in other cell types, ceacam1a mRNA expression was quantified in murine tissues and primary cells. As expected, among CNS cell types, microglia expressed the highest levels of ceacam1a, but lower levels were also detected in oligodendrocytes, astrocytes, and neurons. Given the low levels of neuronal expression of ceacam1a, primary neurons from wild-type and ceacam1a knockout mice were inoculated with MHV to determine the extent to which CEACAM1a independent infection might contribute to CNS infection. While both A59 and JHM.SD infected small numbers of ceacam1a knockout neurons, only JHM.SD spread efficiently to adjacent cells in the absence of CEACAM1a. Quantification of mRNA for the ceacam1a-related genes ceacam2 and psg16 (bCEA), which encode proposed alternative MHV receptors, revealed low ceacam2 expression in microglia and oligodendrocytes and psg16 expression exclusively in neurons; however, only CEACAM2 mediated infection in human 293T cells. Therefore, neither CEACAM2 nor PSG16 is likely to be an MHV receptor on neurons, and the mechanism for CEACAM1a independent neuronal spread of JHM.SD remains unknown. PMID- 20739540 TI - Modification of human papillomavirus minor capsid protein L2 by sumoylation. AB - The human papillomavirus (HPV) minor capsid protein L2 plays important roles in the generation of infectious viral particles and in the initial steps of infection. Here we show that HPV-16 L2 protein is sumoylated at lysine 35 and that sumoylation affects its stability. Interestingly, the sumoylated form of L2 cannot bind to the major capsid protein L1, suggesting a mechanism by which capsid assembly may be modulated in an infected cell. Additionally, L2 appears to modulate the overall sumoylation status of the host cell. These observations indicate a complex interplay between the HPV L2 protein and the host sumoylation machinery. PMID- 20739539 TI - An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. AB - Cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic RNA that is colinear with the distal part of the viral 3'-untranslated region (UTR). This small subgenomic flavivirus RNA (sfRNA) results from the incomplete degradation of the viral genome by the host 5'-3' exonuclease XRN1. Production of the sfRNA is important for the pathogenicity of the virus. This study not only presents a detailed description of the yellow fever virus (YFV) sfRNA but, more importantly, describes for the first time the molecular characteristics of the stalling site for XRN1 in the flavivirus genome. Similar to the case for West Nile virus, the YFV sfRNA was produced by XRN1. However, in contrast to the case for other arthropod-borne flaviviruses, not one but two sfRNAs were detected in YFV-infected mammalian cells. The smaller of these two sfRNAs was not observed in infected mosquito cells. The larger sfRNA could also be produced in vitro by incubation with purified XRN1. These two YFV sfRNAs formed a 5'-nested set. The 5' ends of the YFV sfRNAs were found to be just upstream of the previously predicted RNA pseudoknot PSK3. RNA structure probing and mutagenesis studies provided strong evidence that this pseudoknot structure was formed and served as the molecular signal to stall XRN1. The sequence involved in PSK3 formation was cloned into the Sinrep5 expression vector and shown to direct the production of an sfRNA-like RNA. These results underscore the importance of the RNA pseudoknot in stalling XRN1 and also demonstrate that it is the sole viral requirement for sfRNA production. PMID- 20739541 TI - In vitro analysis of virus particle subpopulations in candidate live-attenuated influenza vaccines distinguishes effective from ineffective vaccines. AB - Two effective (vac+) and two ineffective (vac-) candidate live-attenuated influenza vaccines (LAIVs) derived from naturally selected genetically stable variants of A/TK/OR/71-delNS1[1-124] (H7N3) that differed only in the length and kind of amino acid residues at the C terminus of the nonstructural NS1 protein were analyzed for their content of particle subpopulations. These subpopulations included total physical particles (measured as hemagglutinating particles [HAPs]) with their subsumed biologically active particles of infectious virus (plaque forming particles [PFPs]) and different classes of noninfectious virus, namely, interferon-inducing particles (IFPs), noninfectious cell-killing particles (niCKPs), and defective interfering particles (DIPs). The vac+ variants were distinguished from the vac- variants on the basis of their content of viral subpopulations by (i) the capacity to induce higher quantum yields of interferon (IFN), (ii) the generation of an unusual type of IFN-induction dose-response curve, (iii) the presence of IFPs that induce IFN more efficiently, (iv) reduced sensitivity to IFN action, and (v) elevated rates of PFP replication that resulted in larger plaques and higher PFP and HAP titers. These in vitro analyses provide a benchmark for the screening of candidate LAIVs and their potential as effective vaccines. Vaccine design may be improved by enhancement of attributes that are dominant in the effective (vac+) vaccines. PMID- 20739542 TI - Open reading frame E3-10.9K of subspecies B1 human adenoviruses encodes a family of late orthologous proteins that vary in their predicted structural features and subcellular localization. AB - Subspecies B1 human adenoviruses (HAdV-B1s) are important causative agents of acute respiratory disease, but the molecular bases of their distinct pathobiology are still poorly understood. Marked differences in genetic content between HAdV B1s and the well-characterized HAdV-Cs that may contribute to distinct pathogenic properties map to the E3 region. Between the highly conserved E3-19K and E3 10.4K/RIDalpha open reading frames (ORFs), and in the same location as the HAdV-C ADP/E3-11.6K ORF, HAdV-B1s carry ORFs E3-20.1K and E3-20.5K and a polymorphic third ORF, designated E3-10.9K, that varies in the size of its predicted product among HAdV-B1 serotypes and genomic variants. As an initial effort to define the function of the E3-10.9K ORF, we carried out a biochemical characterization of E3 10.9K-encoded orthologous proteins and investigated their expression in infected cells. Sequence-based predictions suggested that E3-10.9K orthologs with a hydrophobic domain are integral membrane proteins. Ectopically expressed, C terminally tagged (with enhanced green fluorescent protein [EGFP]) E3-10.9K and E3-9K localized primarily to the plasma membrane, while E3-7.7K localized primarily to a juxtanuclear compartment that could not be identified. EGFP fusion proteins with a hydrophobic domain were N and O glycosylated. EGFP-tagged E3 4.8K, which lacked the hydrophobic domain, displayed diffuse cellular localization similar to that of the EGFP control. E3-10.9K transcripts from the major late promoter were detected at late time points postinfection. A C terminally hemagglutinin-tagged version of E3-9K was detected by immunoprecipitation at late times postinfection in the membrane fraction of mutant virus-infected cells. These data suggest a role for ORF E3-10.9K-encoded proteins at late stages of HAdV-B1 replication, with potentially important functional implications for the documented ORF polymorphism. PMID- 20739543 TI - The carboxy-terminal segment of the human cytomegalovirus DNA polymerase accessory subunit UL44 is crucial for viral replication. AB - The amino-terminal 290 residues of UL44, the presumed processivity factor of human cytomegalovirus DNA polymerase, possess all of the established biochemical activities of the full-length protein, while the carboxy-terminal 143 residues contain a nuclear localization signal (NLS). We found that although the amino terminal domain was sufficient for origin-dependent synthesis in a transient transfection assay, the carboxy-terminal segment was crucial for virus replication and for the formation of DNA replication compartments in infected cells, even when this segment was replaced with a simian virus 40 NLS that ensured nuclear localization. Our results suggest a role for this segment in viral DNA synthesis. PMID- 20739545 TI - Impaired orthotopic glioma growth and vascularization in transgenic mouse models of Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common form of dementia among the aging population and is characterized pathologically by the progressive intracerebral accumulation of beta-amyloid (Abeta) peptides and neurofibrillary tangles. The level of proangiogenic growth factors and inflammatory mediators with proangiogenic activity is known to be elevated in AD brains which has led to the supposition that the cerebrovasculature of AD patients is in a proangiogenic state. However, angiogenesis depends on the balance between proangiogenic and antiangiogenic factors and the brains of AD patients also show an accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic. To determine whether angiogenesis is compromised in the brains of two transgenic mouse models of AD overproducing Abeta peptides (Tg APPsw and Tg PS1/APPsw mice), we assessed the growth and vascularization of orthotopically implanted murine gliomas since they require a high degree of angiogenesis to sustain their growth. Our data reveal that intracranial tumor growth and angiogenesis is significantly reduced in Tg APPsw and Tg PS1/APPsw mice compared with their wild-type littermates. In addition, we show that Abeta inhibits the angiogenesis stimulated by glioma cells when cocultured with human brain microvascular cells on a Matrigel layer. Altogether our data suggest that the brain of transgenic mouse models of AD does not constitute a favorable environment to support neoangiogenesis and may explain why vascular insults synergistically precipitate the cognitive presentation of AD. PMID- 20739546 TI - Development and regeneration of sensory transduction in auditory hair cells requires functional interaction between cadherin-23 and protocadherin-15. AB - Tip links are extracellular filaments that connect pairs of hair cell stereocilia and convey tension to mechanosensitive channels. Recent evidence suggests that tip links are formed by calcium-dependent interactions between the N-terminal domains of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). Mutations in either CDH23 or PCDH15 cause deafness in mice and humans, indicating the molecules are required for normal inner ear function. However, there is little physiological evidence to support a direct role for CDH23 and PCDH15 in hair cell mechanotransduction. To investigate the contributions of CDH23 and PCDH15 to mechanotransduction and tip-link formation, we examined outer hair cells of mouse cochleas during development and after chemical disruption of tip links. We found that tip links and mechanotransduction with all the qualitative properties of mature transduction recovered within 24 h after disruption. To probe tip-link formation, we measured transduction currents after extracellular application of recombinant CDH23 and PCDH15 fragments, which included putative interaction domains (EC1). Both fragments inhibited development and regeneration of transduction but did not disrupt transduction in mature cells. PCDH15 fragments that carried a mutation in EC1 that causes deafness in humans did not inhibit transduction development or regeneration. Immunolocalization revealed wild-type fragments bound near the tips of hair cell stereocilia. Scanning electron micrographs revealed that hair bundles exposed to fragments had a reduced number of linkages aligned along the morphological axis of sensitivity of the bundle. Together, the data provide direct evidence implicating CDH23 and PCDH15 proteins in the formation of tip links during development and regeneration of mechanotransduction. PMID- 20739547 TI - Beta-band activity during motor planning reflects response uncertainty. AB - It has been known for many years that the power of beta-band oscillatory activity in motor-related brain regions decreases during the preparation and execution of voluntary movements. However, it is not clear yet whether the amplitude of this desynchronization is modulated by any parameter of the motor task. Here, we examined whether the degree of uncertainty about the upcoming movement direction modulated beta-band desynchronization during motor preparation. To this end, we recorded whole-head neuromagnetic signals while human subjects performed an instructed-delay reaching task with one, two, or three possible target directions. We found that the reduction of power of beta-band activity (16-28 Hz) during motor preparation was scaled relative to directional uncertainty. Furthermore, we show that the change of beta-band power correlates with the change of latency of response associated with response uncertainty. Finally, we show that the main source of beta-band desynchronization was located in the peri Rolandic region. The results establish directional uncertainty as an important determinant of beta-band power during motor preparation and indicate that neural activity in the sensorimotor cortex during motor preparation covaries with directional uncertainty. PMID- 20739548 TI - Direct innervation and modulation of orexin neurons by lateral hypothalamic LepRb neurons. AB - Leptin, the adipose-derived hormonal signal of body energy stores, acts via the leptin receptor (LepRb) on neurons in multiple brain regions. We previously identified LepRb neurons in the lateral hypothalamic area (LHA), which are distinct from neighboring leptin-regulated melanin-concentrating hormone (MCH)- or orexin (OX)-expressing cells. Neither the direct synaptic targets of LHA LepRb neurons nor their potential role in the regulation of other LHA neurons has been determined, however. We thus generated several adenoviral and transgenic systems in which cre recombinase promotes the expression of the tracer, WGA (wheat germ agglutinin), and used these in combination with LepRb(cre) mice to determine the neuronal targets of LHA LepRb neurons. This analysis revealed that, although some LHA LepRb neurons project to dopamine neurons in the ventral tegmental area, LHA LepRb neurons also densely innervate the LHA where they directly synapse with OX, but not MCH, neurons. Indeed, few other LepRb neurons in the brain project to the OX-containing region of the mouse LHA, and direct leptin action via LHA LepRb neurons regulates gene expression in OX neurons. These findings thus reveal a major role for LHA leptin action in the modulation of OX neurons, suggesting the importance of LHA LepRb neurons in the regulation of OX signaling that is crucial to leptin action and metabolic control. PMID- 20739549 TI - In vivo NMDA receptor activation accelerates motor unit maturation, protects spinal motor neurons, and enhances SMN2 gene expression in severe spinal muscular atrophy mice. AB - Spinal muscular atrophy (SMA), a lethal neurodegenerative disease that occurs in childhood, is caused by the misexpression of the survival of motor neuron (SMN) protein in motor neurons. It is still unclear whether activating motor units in SMA corrects the delay in the postnatal maturation of the motor unit resulting in an enhanced neuroprotection. In the present work, we demonstrate that an adequate NMDA receptor activation in a type 2 SMA mouse model significantly accelerated motor unit postnatal maturation, counteracted apoptosis in the spinal cord, and induced a marked increase of SMN expression resulting from a modification of SMN2 gene transcription pattern. These beneficial effects were dependent on the level of NMDA receptor activation since a treatment with high doses of NMDA led to an acceleration of the motor unit maturation but favored the apoptotic process and decreased SMN expression. In addition, these results suggest that the NMDA induced acceleration of motor unit postnatal maturation occurred independently of SMN. The NMDA receptor activating treatment strongly extended the life span in two different mouse models of severe SMA. The analysis of the intracellular signaling cascade that lay downstream the activated NMDA receptor revealed an unexpected reactivation of the CaMKII/AKT/CREB (cAMP response element-binding protein) pathway that induced an enhanced SMN expression. Therefore, pharmacological activation of spinal NMDA receptors could constitute a useful strategy for both increasing SMN expression and limiting motor neuron death in SMA spinal cord. PMID- 20739550 TI - Direction opponency, not quadrature, is key to the 1/4 cycle preference for apparent motion in the motion energy model. AB - Sensitivity to visual motion is a fundamental property of neurons in the visual cortex and has received wide attention in terms of mathematical models. A key feature of many popular models for cortical motion sensors is the use of pairs of functions that are related by a 90 degrees phase shift. This phase relationship, known as quadrature, is the hallmark of the motion energy model and played an important role in the development of a class of model dubbed elaborated Reichardt detectors. For decades, the literature has supported a link between quadrature and the observation that motion detectors and human observers often prefer a 1/4 cycle displacement of an apparent motion stimulus that consists of a pair of sinusoidal gratings. We show that there is essentially no link between quadrature and this preference. Quadrature is neither necessary nor sufficient for a motion sensor to prefer 1/4 cycle displacement, and motion energy is not maximized for a 1/4 cycle step. Other properties of motion sensors are the key: the opponent subtraction of two oppositely tuned stages that individually have sinusoidal displacement tuning curves. Thus, psychophysical and neurophysiological data revealing a preference at or near 1/4 cycle displacement do not offer specific support for common quadrature or energy-based motion models. Instead, they point to a broader class of model. PMID- 20739552 TI - The NADPH oxidase NOX2 controls glutamate release: a novel mechanism involved in psychosis-like ketamine responses. AB - Subanesthetic doses of NMDA receptor antagonist ketamine induce schizophrenia like symptoms in humans and behavioral changes in rodents. Subchronic administration of ketamine leads to loss of parvalbumin-positive interneurons through reactive oxygen species (ROS), generated by the NADPH oxidase NOX2. However, ketamine induces very rapid alterations, in both mice and humans. Thus, we have investigated the role of NOX2 in acute responses to subanesthetic doses of ketamine. In wild-type mice, ketamine caused rapid (30 min) behavioral alterations, release of neurotransmitters, and brain oxidative stress, whereas NOX2-deficient mice did not display such alterations. Decreased expression of the subunit 2A of the NMDA receptor after repetitive ketamine exposure was also precluded by NOX2 deficiency. However, neurotransmitter release and behavioral changes in response to amphetamine were not altered in NOX2-deficient mice. Our results suggest that NOX2 is a major source of ROS production in the prefrontal cortex controlling glutamate release and associated behavioral alterations after acute ketamine exposure. Prolonged NOX2-dependent glutamate release may lead to neuroadaptative downregulation of NMDA receptor subunits. PMID- 20739553 TI - Dynamics of the Parkinsonian striatal microcircuit: entrainment into a dominant network state. AB - Neuronal synchronization in basal ganglia circuits plays a key role in the encoding of movement, procedural memory storage and habit formation. Striatal dopamine (DA) depletion during Parkinsonism causes abnormal synchronization in corticobasal ganglia loops resulting in motor dysfunction. However, the dynamics of the striatal microcircuit underlying abnormal synchronization in Parkinsonism is poorly understood. Here we used targeted whole-cell recordings, calcium imaging allowing the recording from dozens of cells simultaneously and analytical approaches, to describe the striking alterations in network dynamics that the striatal microcircuit undergoes following DA depletion in a rat model of Parkinson disease (PD): In addition to a significant enhancement of basal neuronal activity frequent periods of spontaneous synchronization were observed. Multidimensional reduction techniques of vectorized network dynamics revealed that increased synchronization resulted from a dominant network state that absorbed most spontaneously active cells. Abnormal synchronous activity can be virtually abolished by glutamatergic antagonists, while blockade of GABAergic transmission facilitates the engagement of striatal cell assemblies in the dominant state. Finally, a dopaminergic receptor agonist was capable of uncoupling neurons from the dominant state. Abnormal synchronization and "locking" into a dominant state may represent the basic neuronal mechanism that underlies movement disorders at the microcircuit level. PMID- 20739551 TI - Insulin reveals Akt signaling as a novel regulator of norepinephrine transporter trafficking and norepinephrine homeostasis. AB - Noradrenergic signaling in the CNS plays an essential role in circuits involving attention, mood, memory, and stress as well as providing pivotal support for autonomic function in the peripheral nervous system. The high-affinity norepinephrine (NE) transporter (NET) is the primary mechanism by which noradrenergic synaptic transmission is terminated. Data indicate that NET function is regulated by insulin, a hormone critical for the regulation of metabolism. Given the high comorbidity of metabolic disorders such as diabetes and obesity with mental disorders such as depression and schizophrenia, we sought to determine how insulin signaling regulates NET function and thus noradrenergic homeostasis. Here, we show that acute insulin treatment, through the downstream kinase protein kinase B (Akt), significantly decreases NET surface expression in mouse hippocampal slices and superior cervical ganglion neuron boutons (sites of synaptic NE release). In vivo manipulation of insulin/Akt signaling, with streptozotocin, a drug that induces a type 1-like diabetic state in mice, also results in aberrant NET function and NE homeostasis. Notably, we also demonstrate that Akt inhibition or stimulation, independent of insulin, is capable of altering NET surface availability. These data suggest that aberrant states of Akt signaling such as in diabetes and obesity have the potential to alter NET function and noradrenergic tone in the brain. Furthermore, they provide one potential molecular mechanism by which Akt, a candidate gene for mood disorders such as schizophrenia and depression, can impact brain monoamine homeostasis. PMID- 20739554 TI - Dependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction. AB - Normal termination of signaling is essential to reset signaling cascades, especially those such as phototransduction that are turned on and off with great rapidity. Genetic approaches in Drosophila led to the identification of several proteins required for termination, including protein kinase C (PKC), NINAC (neither inactivation nor afterpotential C) p174, which consists of fused protein kinase and myosin domains, and a PDZ (postsynaptic density-95/Discs Large/zona occludens-1) scaffold protein, INAD (inactivation no afterpotential D). Here, we describe a mutation affecting a poorly characterized but evolutionarily conserved protein, Retinophilin (Retin), which is expressed primarily in the phototransducing compartment of photoreceptor cells, the rhabdomeres. Retin and NINAC formed a complex and were mutually dependent on each other for expression. Loss of retin resulted in an age-dependent impairment in termination of phototransduction. Mutations that affect termination of the photoresponse typically lead to a reduction in levels of the major rhodopsin (Rh1) to attenuate signaling. Consistent with the slower termination in retin(1), the mutant photoreceptor cells exhibited increased endocytosis of Rh1 and a decline in Rh1 protein. The slower termination in retin(1) was a consequence of a cascade of defects, which began with the reduction in NINAC p174 levels. The diminished p174 concentration caused a decrease in INAD. Because PKC requires interaction with INAD for protein stability, this leads to reduction in PKC levels. The decline in PKC was age dependent and paralleled the onset of the termination phenotype in retin(1) mutant flies. We conclude that the slower termination of the photoresponse in retin(1) resulted from a requirement for the Retin/NINAC complex for stability of INAD and PKC. PMID- 20739555 TI - Rats markedly escalate their intake and show a persistent susceptibility to reinstatement only when cocaine is injected rapidly. AB - When drugs enter the brain rapidly, liability for addiction is increased, but why this is the case is not well understood. Here we examined the influence of varying the speed of intravenous cocaine delivery on self-administration behavior in rats given limited or extended opportunity to take drug. The speed of cocaine delivery had no effect on self-administration behavior when rats were given only 1 h each day to take cocaine. When given sixfold more time to take cocaine, rats that received cocaine rapidly (5-45 s) increased their total intake eightfold. However, rats that received cocaine more slowly (>90 s) did not avail themselves of the opportunity to take much more drug: they increased their intake only twofold. Furthermore, when tested 45 d after the last self-administration session, a drug-priming injection reinstated drug-seeking behavior only in rats that in the past had cocaine injected rapidly (5 s), and this was associated with a persistent suppression in the ability of cocaine to induce immediate early gene expression. Cocaine may be potentially more addictive when it reaches the brain rapidly because (1) this promotes a marked escalation in intake and (2) it renders individuals more susceptible to relapse long after the discontinuation of drug use. This is presumably because the rapid uptake of drug to the brain preferentially promotes persistent changes in brain systems that regulate motivation for drug, and continuing exposure to large amounts of drug produces a vicious cycle of additional maladaptive changes in brain and behavior. PMID- 20739556 TI - Theta oscillations reflect the dynamics of interference in episodic memory retrieval. AB - Selectively retrieving episodic information from a cue often induces interference from related episodes. To promote successful retrieval of the target episode, such interference is resolved by inhibition, causing retrieval-induced forgetting of the related but irrelevant information. Passively studying the episodic information again (reexposure) does not show this effect. This study examined the hypothesis that brain oscillations in the theta band (5-9 Hz) reflect the dynamics of interference in selective memory retrieval, analyzing EEG data from 24 healthy human subjects (21 women, 3 men). High versus low levels of interference were investigated by comparing the effects of selective retrieval with the effects of reexposure of material, with the former, but not the latter, inducing interference. Moreover, we analyzed repeated cycles of selective retrieval and reexposure, assuming that interference is reduced by inhibition across retrieval cycles, but not across reexposure cycles. We found greater theta band activity in selective retrieval than in reexposure, and a reduction in theta amplitude from the first to the second cycle of retrieval predicting the amount of retrieval-induced forgetting; the sources of theta amplitude reduction across retrieval cycles were located in the anterior cingulate cortex. No difference in theta activity was found across repeated cycles of reexposure. The results suggest that higher levels of interference in episodic memory are indexed by more theta band activity, and that successful interference resolution via inhibition causes a reduction in theta amplitude. Thus, theta band activity can serve as a neural marker of the dynamics of interference in selective episodic retrieval. PMID- 20739557 TI - Insular cortex activity is associated with effects of negative expectation on nociceptive long-term habituation. AB - It is generally accepted that acute painful experience is influenced by context information shaping expectation and modulating attention, arousal, stress, and mood. However, little is known about the nature, duration, and extent of this effect, particularly regarding the negative expectation. We used a standardized longitudinal pain paradigm and painful heat test stimuli in healthy participants over a time course of 8 consecutive days, inducing nociceptive habituation over time. Thirty-eight healthy volunteers were randomly assigned to two different groups. One group received the information that the investigators expected the pain intensity to increase over time (context group). The other group was not given any information (control group). All participants rated the pain intensity of the daily standardized pain paradigm on a visual analog scale. In agreement with previous studies the pain ratings in the control group habituated over time. However, the context group reported no change of pain ratings over time. Functional imaging data showed a difference between the two groups in the right parietal operculum. These data suggest that a negative context not only has an effect on immediate pain but can modulate perception of pain in the future even without experience/conditioning. Neuronally, this process is mediated by the right opercular region. PMID- 20739559 TI - Development of a large-scale functional brain network during human non-rapid eye movement sleep. AB - Graph theoretical analysis of functional magnetic resonance imaging (fMRI) time series has revealed a small-world organization of slow-frequency blood oxygen level-dependent (BOLD) signal fluctuations during wakeful resting. In this study, we used graph theoretical measures to explore how physiological changes during sleep are reflected in functional connectivity and small-world network properties of a large-scale, low-frequency functional brain network. Twenty-five young and healthy participants fell asleep during a 26.7 min fMRI scan with simultaneous polysomnography. A maximum overlap discrete wavelet transformation was applied to fMRI time series extracted from 90 cortical and subcortical regions in normalized space after residualization of the raw signal against unspecific sources of signal fluctuations; functional connectivity analysis focused on the slow frequency BOLD signal fluctuations between 0.03 and 0.06 Hz. We observed that in the transition from wakefulness to light sleep, thalamocortical connectivity was sharply reduced, whereas corticocortical connectivity increased; corticocortical connectivity subsequently broke down in slow-wave sleep. Local clustering values were closest to random values in light sleep, whereas slow-wave sleep was characterized by the highest clustering ratio (gamma). Our findings support the hypothesis that changes in consciousness in the descent to sleep are subserved by reduced thalamocortical connectivity at sleep onset and a breakdown of general connectivity in slow-wave sleep, with both processes limiting the capacity of the brain to integrate information across functional modules. PMID- 20739558 TI - Defects in mitochondrial axonal transport and membrane potential without increased reactive oxygen species production in a Drosophila model of Friedreich ataxia. AB - Friedreich ataxia, a neurodegenerative disorder resulting from frataxin deficiency, is thought to involve progressive cellular damage from oxidative stress. In Drosophila larvae with reduced frataxin expression (DfhIR), we evaluated possible mechanisms of cellular neuropathology by quantifying mitochondrial axonal transport, membrane potential (MMP), and reactive oxygen species (ROS) production in the DfhIR versus wild-type nervous system throughout development. Although dying-back neuropathy in DfhIR larvae did not occur until late third instar, reduced MMP was already apparent at second instar in the cell bodies, axons and neuromuscular junctions (NMJs) of segmental nerves. Defects in axonal transport of mitochondria appeared late in development in distal nerve of DfhIR larvae, with retrograde movement preferentially affected. As a result, by late third instar the neuromuscular junctions (NMJs) of DfhIR larvae accumulated a higher density of mitochondria, many of which were depolarized. Notably, increased ROS production was not detected in any neuronal region or developmental stage in DfhIR larvae. However, when challenged with antimycin A, neurons did respond with a larger increase in ROS. We propose that pathology in the frataxin deficient nervous system involves decreased MMP and ATP production followed by failures of mitochondrial transport and NMJ function. PMID- 20739561 TI - Microstructural brain differences predict functional hemodynamic responses in a reward processing task. AB - Many aspects of human behavior are driven by rewards, yet different people are differentially sensitive to rewards and punishment. In this study, we show that white matter microstructure in the uncinate/inferior fronto-occipital fasciculus, defined by fractional anisotropy values derived from diffusion tensor magnetic resonance images, correlates with both short-term (indexed by the fMRI blood oxygenation level-dependent response to reward in the nucleus accumbens) and long term (indexed by the trait measure sensitivity to punishment) reactivity to rewards. Moreover, trait measures of reward processing were also correlated with reward-related functional activation in the nucleus accumbens. The white matter tract revealed by the correlational analysis connects the anterior temporal lobe with the medial and lateral orbitofrontal cortex and also supplies the ventral striatum. The pattern of strong correlations suggests an intimate relationship between white matter structure and reward-related behavior that may also play a role in a number of pathological conditions, such as addiction and pathological gambling. PMID- 20739560 TI - Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice. AB - Misexpression and cytosolic retention of peripheral myelin protein 22 (PMP22) within Schwann cells (SCs) is associated with a genetically heterogeneous group of demyelinating peripheral neuropathies. PMP22 overproducer C22 and spontaneous mutant Trembler J (TrJ) mice display neuropathic phenotypes and affected nerves contain abnormally localized PMP22. Nutrient deprivation-induced autophagy is able to suppress the formation of PMP22 aggregates in a toxin-induced cellular model, and improve locomotor performance and myelination in TrJ mice. As a step toward therapies, we assessed whether pharmacological activation of autophagy by rapamycin (RM) could facilitate the processing of PMP22 within neuropathic SCs and enhance their capacity to myelinate peripheral axons. Exposure of mouse SCs to RM induced autophagy in a dose- and time-dependent manner and decreased the accumulation of poly-ubiquitinated substrates. The treatment of myelinating dorsal root ganglion (DRG) explant cultures from neuropathic mice with RM (25 nm) improved the processing of PMP22 and increased the abundance and length of myelin internodes, as well as the expression of myelin proteins. Notably, RM is similarly effective in both the C22 and TrJ model, signifying that the benefit overlaps among distinct genetic models of PMP22 neuropathies. Furthermore, lentivirus-mediated shRNA knockdown of the autophagy-related gene 12 (Atg12) abolished the activation of autophagy and the increase in myelin proteins, demonstrating that autophagy is critical for the observed improvement. Together, these results support the potential use of RM and other autophagy-enhancing compounds as therapeutic agents for PMP22-associated demyelinating neuropathies. PMID- 20739562 TI - Characterization of the intracellular localization, processing, and secretion of two glial cell line-derived neurotrophic factor splice isoforms. AB - Endocrine and neuronal cells have highly developed secretion mechanisms, and the secretion can be either constitutive or regulated by physiological stimuli. In the constitutive pathway, intracellular transport vesicles undergo immediate fusion reactions after arrival at the target. In regulated secretion, vesicles accumulate near the target membrane until triggered to fuse, typically by a local rise in free Ca(2+). In the present study, we characterize the processing and secretion mechanisms of the glial cell line-derived neurotrophic factor (GDNF). Although the function of GDNF has been extensively studied, very little is known about the basic cell biology of GDNF and its precursor forms (alpha)pro-GDNF and (beta)pro-GDNF that have different pro-regions. Our results show that both (alpha)pro-GDNF and (beta)pro-GDNF are secreted. We demonstrate that KCl-induced depolarization increases the secretion of (beta)pro-GDNF and corresponding mature GDNF, but not (alpha)pro-GDNF and corresponding mature GDNF, to the cell medium in a Ca(2+)-dependent manner. In parallel with this, immunofluorescence analysis of cells show that (alpha)pro-GDNF/GDNF is localized mostly in the Golgi complex, whereas (beta)pro-GDNF/GDNF is localized primarily in secretogranin II and Rab3A positive vesicles of the regulated secretory pathway. In addition, we find that matrix metalloproteinases and plasmin that cleave pro-BDNF and pro-NGF are not responsible for the cleavage of pro-GDNF, whereas furin endoproteinase, PACE4, and proprotein convertases PC5A, PC5B, and PC7 can cleave pro-GDNF into mature GDNF. Thus, the processing and secretion mechanisms of GDNF are different from those of BDNF and NGF. PMID- 20739564 TI - Id gene regulation and function in the prosensory domains of the chicken inner ear: a link between Bmp signaling and Atoh1. AB - Bone morphogenetic proteins (Bmps) regulate the expression of the proneural gene Atoh1 and the generation of hair cells in the developing inner ear. The present work explored the role of Inhibitor of Differentiation genes (Id1-3) in this process. The results show that Id genes are expressed in the prosensory domains of the otic vesicle, along with Bmp4 and Bmp7. Those domains exhibit high levels of the phosphorylated form of Bmp-responding R-Smads (P-Smad1,5,8), and of Bmp dependent Smad transcriptional activity as shown by the BRE-tk-EGFP reporter. Increased Bmp signaling induces the expression of Id1-3 along with the inhibition of Atoh1. Conversely, the Bmp antagonist Noggin or the Bmp-receptor inhibitor Dorsomorphin elicit opposite effects, indicating that Bmp signaling is necessary for Id expression and Atoh1 regulation in the otocyst. The forced expression of Id3 is sufficient to reduce Atoh1 expression and to prevent the expression of hair cell differentiation markers. Together, these results suggest that Ids are part of the machinery that mediates the regulation of hair cell differentiation exerted by Bmps. In agreement with that, during hair cell differentiation Bmp4 expression, P-Smad1,5,8 levels and Id expression are downregulated from hair cells. However, Ids are also downregulated from the supporting cells which contrarily to hair cells exhibit high levels of Bmp4 expression, P-Smad1,5,8, and BRE-tk-EGFP activity, suggesting that in these cells Ids escape from Bmp/Smad signaling. The differential regulation of Ids in time and space may underlie the multiple functions of Bmp signaling during sensory organ development. PMID- 20739563 TI - Microglial receptor for advanced glycation end product-dependent signal pathway drives beta-amyloid-induced synaptic depression and long-term depression impairment in entorhinal cortex. AB - Overproduction of beta-amyloid (Abeta) is a pathologic feature of Alzheimer's disease, leading to cognitive impairment. Here, we investigated the impact of cell-specific receptor for advanced glycation end products (RAGE) on Abeta induced entorhinal cortex (EC) synaptic dysfunction. We found both a transient depression of basal synaptic transmission and inhibition of long-term depression (LTD) after the application of Abeta in EC slices. Synaptic depression and LTD impairment induced by Abeta were rescued by functional suppression of RAGE. Remarkably, the rescue was only observed in slices from mice expressing a defective form of RAGE targeted to microglia, but not in slices from mice expressing defective RAGE targeted to neurons. Moreover, we found that the inflammatory cytokine IL-1beta (interleukin-1beta) and stress-activated kinases [p38 MAPK (p38 mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase)] were significantly altered and involved in RAGE signaling pathways depending on RAGE expression in neuron or microglia. These findings suggest a prominent role of microglial RAGE signaling in Abeta-induced EC synaptic dysfunction. PMID- 20739565 TI - Alternative splicing of neuroligin regulates the rate of presynaptic differentiation. AB - Neuroligins (NLGs) and Neurexins (NRXs) are important adhesion molecules that promote synapse formation. Multiple splice variants of NLG and NRX exist, but their specific functions are unclear. Here we report that a surrogate postsynaptic cell expressing full-length NLG-1 triggers slow presynaptic differentiation in a contacting axon. In contrast, a version of NLG-1, which lacks insert B (NLG-1DeltaB), induces rapid presynaptic differentiation, reaching the rate seen at native neuronal synapses. We show that this acceleration is attributed to the removal of the N-linked glycosylation site within insert B. NLG 1DeltaB also increases synaptic density at neuro-neuronal synapses more than does full-length NLG-1. Other postsynaptic adhesion proteins, such as N-cadherin, EphB2, and SynCAM-1, alone or in combination with full-length NLG-1, do not trigger fast differentiation, suggesting that rapid presynaptic differentiation depends on a unique interaction of NLG-1DeltaB with axonal proteins. Indeed, we find that NLG-1DeltaB recruits more axonal alpha-NRX. Our results suggest that the engagement of alpha-NRX is a key to rapid induction of synapses at new sites of axo-dendritic contact. PMID- 20739566 TI - Reward prediction error coding in dorsal striatal neurons. AB - In the current theory of learning, the reward prediction error (RPE), the difference between expected and received reward, is thought to be a key factor in reward-based learning, working as a teaching signal. The activity of dopamine neurons is known to code RPE, and the release of dopamine is known to modify the strength of synaptic connectivity in the target neurons. A fundamental interest in current neuroscience concerns the origin of RPE signals in the brain. Here, we show that a group of rat striatal neurons show a clear parametric RPE coding similar to that of dopamine neurons when tested under probabilistic pavlovian conditioning. Together with the fact that striatum and dopamine neurons have strong direct and indirect fiber connections, the result suggests that the striatum plays an important role in coding RPE signal by cooperating with dopamine neurons. PMID- 20739567 TI - Neural predictors of within-subject fluctuations in attentional control. AB - Whether salient objects automatically capture attention has long been the subject of considerable controversy. A possible resolution, investigated in this functional magnetic resonance imaging (fMRI) study, is that observers vacillate between periods when attention capture is robust and when it is minimal. Human observers searched static displays for a target circle among nontarget squares; an irrelevant color singleton distractor appeared on 50% of trials. Behavioral results showed a distraction effect in which response times to distractor-present trials were slower than for distractor-absent trials. fMRI results confirmed that this distraction effect not only fluctuated within experimental sessions, but the momentary degree of distraction could be predicted in advance by pretrial activity in middle frontal gyrus. A second experiment ruled out an alternative account by which participants achieved resistance to capture by trading off search efficiency. Together, these data reveal that observers frequently exert the capacity to resist attentional distraction, although they do not to sustain this capacity for long periods of time. PMID- 20739568 TI - Developmental mechanisms for suppressing the effects of delayed release at the endbulb of Held. AB - Delayed release of neurotransmitter, also called asynchronous release, is commonly observed at synapses, yet its influence on transmission of spike information is unknown. We examined this issue at endbulb of Held synapses, which are formed by auditory nerve fibers onto bushy cells in the cochlear nucleus. Endbulbs from CBA/CaJ mice aged P6-P49 showed prominent delayed release when driven at physiologically relevant rates. In bushy cells from mice before the onset of hearing (P6-P12), spikes were driven by delayed release up to 100 ms after presynaptic activity. However, no such spikes were observed in bushy cells from mice after the onset of hearing (>P14). Dynamic-clamp experiments indicated that delayed release can drive spikes in older bushy cells provided synchronous release is absent, suggesting that activity normally suppresses these spikes. Application of apamin or alpha-dendrotoxin revealed late spikes in older bushy cells, suggesting that postsynaptic activation of K(V)1.x and SK channels during spiking suppresses the subsequent effects of delayed release. The developmental upregulation of these potassium channels would be highly adaptive for temporally precise auditory processing. Furthermore, delayed release appeared to influence synchronous neurotransmitter release. Enhancement of delayed release using strontium was correlated with lower firing probability in current clamp and smaller synchronous EPSCs in voltage clamp. EGTA-AM had the opposite effects. These effects were consistent with delayed and synchronous release competing for a single vesicle pool. Thus delayed release apparently has negative presynaptic and postsynaptic consequences at the endbulb, which are partly mitigated by postsynaptic potassium channel expression. PMID- 20739570 TI - Hippocampal ripple-contingent training accelerates trace eyeblink conditioning and retards extinction in rabbits. AB - There are at least two distinct oscillatory states of the hippocampus that are related to distinct behavioral patterns. Theta (4-12 Hz) oscillation has been suggested to indicate selective attention during which the animal concentrates on some features of the environment while suppressing reactivity to others. In contrast, sharp-wave ripples ( approximately 200 Hz) can be seen in a state in which the hippocampus is at its most responsive to any kind of afferent stimulation. In addition, external stimulation tends to evoke and reset theta oscillation, the phase of which has been shown to modulate synaptic plasticity in the hippocampus. Theoretically, training on a hippocampus-dependent learning task contingent upon ripples could enhance learning rate due to elevated responsiveness and enhanced phase locking of the theta oscillation. We used a brain-computer interface to detect hippocampal ripples in rabbits to deliver trace eyeblink conditioning and extinction trials selectively contingent upon them. A yoked control group was trained regardless of their ongoing neural state. Ripple-contingent training expedited acquisition of the conditioned response early in training and evoked stronger theta-band phase locking to the conditioned stimulus. Surprisingly, ripple-contingent training also resulted in slower extinction in well trained animals. We suggest that the ongoing oscillatory activity in the hippocampus determines the extent to which a stimulus can induce a phase reset of the theta oscillation, which in turn is the determining factor of learning rate in trace eyeblink conditioning. PMID- 20739569 TI - Transcranial electric stimulation entrains cortical neuronal populations in rats. AB - Low intensity electric fields have been suggested to affect the ongoing neuronal activity in vitro and in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performed in vivo extracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity. PMID- 20739571 TI - Target-specific encoding of response inhibition: increased contribution of AMPA to NMDA receptors at excitatory synapses in the prefrontal cortex. AB - Impulse control suppresses actions that are inappropriate in one context, but may be beneficial in others. The medial prefrontal cortex (mPFC) mediates this process by providing a top-down signal to inhibit competing responses, although the mechanism by which the mPFC acquires this ability is unknown. To that end, we examined synaptic changes in the mPFC associated with learning to inhibit an incorrect response. Rats were trained in a simple response inhibition task to withhold responding until a signal was presented. We then measured synaptic plasticity of excitatory synapses in the mPFC, using whole-cell patch-clamp recordings, in brain slices prepared from trained rats. Response inhibition training significantly increased the relative contribution of AMPA receptors to the overall EPSC in prelimbic, but not infralimbic, neurons of the mPFC. This potentiation of synaptic transmission closely paralleled the acquisition and extinction of response inhibition. Using a retrograde fluorescent tracer, we observed that these plastic changes were selective for efferents projecting to the ventral striatum, but not the dorsal striatum or amygdala. Therefore, we suggest that response inhibition is encoded by a selective strengthening of a subset of corticostriatal projections, uncovering a synaptic mechanism of impulse control. This information could be exploited in therapeutic interventions for disorders of impulse control, such as addiction, attention deficit-hyperactivity disorder, and schizophrenia. PMID- 20739572 TI - Excitatory glycine responses of CNS myelin mediated by NR1/NR3 "NMDA" receptor subunits. AB - NMDA receptors are typically excited by a combination of glutamate and glycine. Here we describe excitatory responses in CNS myelin that are gated by a glycine agonist alone and mediated by NR1/NR3 "NMDA" receptor subunits. Response properties include activation by d-serine, inhibition by the glycine-site antagonist CNQX, and insensitivity to the glutamate-site antagonist d-APV. d Serine responses were abrogated in NR3A-deficient mice. Our results suggest the presence of functional NR1/NR3 receptors in CNS myelin. PMID- 20739573 TI - Periodicity and evoked responses in motor cortex. AB - Spiking in primary motor cortex (MI) exhibits a characteristic beta frequency periodicity, but the functional relevance of this rhythmic firing is controversial. We simultaneously recorded multiple single units and local field potentials in MI in two monkeys (Macaca mulatta) during continuous, self-paced movements to serially presented targets. We find that the appearance of each new target evokes precisely timed spiking in MI at a characteristic latency but that the exact timing of this response varies depending on its relationship to the phase of the ongoing beta range oscillation. As a result of this interaction between evoked spiking and endogenous beta periodicity, we find that the amount of information about target location encoded in the spiking of MI neurons is not simply a function of elapsed time but depends also on oscillatory phase. Our results suggest that periodicity may be an important feature of the early stages of sensorimotor processing in the cortical motor system. PMID- 20739575 TI - Movement-related cortical stimulation can induce human motor plasticity. AB - Repeated paired associative stimulation combining peripheral nerve stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can produce human motor plasticity. However, previous studies used paired artificial stimuli, so that it is not known whether repetitive natural M1 activity associated with TMS can induce plasticity or not. To test this hypothesis, we developed a movement-related cortical stimulation (MRCS) protocol, in which the left M1 was stimulated by TMS at specific timing with respect to the mean expected reaction time (RT) of voluntary movement during a simple reaction time task using the right abductor pollicis brevis (APB) muscle. Seventeen normal volunteers were subjected to repeated MRCS intervention (0.2 Hz, 240 pairs). Motor function was assessed before and after MRCS. When TMS was given 50 ms before the RT of movement [MRCS(-50)], motor-evoked potential (MEP) amplitude of the right APB, but not other muscles, increased for up to 15 min post-MRCS. The RT of the right APB was also shortened. However, spinal excitability measured by F-wave did not change. When TMS was given 100 ms after the RT [MRCS(+100)], MEP amplitude was decreased. These findings show that this new MRCS protocol can produce timing-dependent motor associative plasticity, which may be clinically useful. PMID- 20739574 TI - Unexpected survival of neurons of origin of the pyramidal tract after spinal cord injury. AB - There is continuing controversy about whether the cells of origin of the corticospinal tract (CST) undergo retrograde cell death after spinal cord injury (SCI). All previous attempts to assess this have used imaging and/or histological techniques to assess upper motoneurons in the cerebral cortex. Here, we address the question in a novel way by assessing Wallerian degeneration and axon numbers in the medullary pyramid of Sprague Dawley rats after both acute SCI, either at cervical level 5 (C5) or thoracic level 9 (T9), and chronic SCI at T9. Our findings demonstrate that only a fraction of a percentage of the total axons in the medullary pyramid exhibit any sign of degeneration at any time after SCI--no more so than in uninjured control rats. Moreover, design-based counts of myelinated axons revealed no decrease in axon number in the medullary pyramid after SCI, regardless of injury level, severity, or time after injury. Spinal cord-injured rats had fewer myelinated axons in the medullary pyramid at 1 year after injury than aged matched controls, suggesting that injury may affect ongoing myelination of axons during aging. We conclude that SCI does not cause death of the CST cell bodies in the cortex; therefore, therapeutic strategies aimed at promoting axon regeneration of the CST in the spinal cord do not require a separate intervention to prevent retrograde degeneration of upper motoneurons in the cortex. PMID- 20739576 TI - Genetic targeting of ERK1 suggests a predominant role for ERK2 in murine pain models. AB - The extracellular signal-regulated kinase (ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies using inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase (MEK), and transgenic mice expressing a dominant-negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the function of each isoform in pain, we used mice with a targeted genetic deletion of ERK1 [ERK1 knock-out (KO)] to test the hypothesis that ERK1 is required for behavioral sensitization in rodent pain models. Despite activation (phosphorylation) of ERK1 after acute noxious stimulation and in models of chronic pain, we found that ERK1 was not required for formalin-induced spontaneous behaviors, complete Freund's adjuvant-induced heat and mechanical hypersensitivity, and spared nerve injury-induced mechanical hypersensitivity. However, ERK1 deletion did delay formalin-induced long-term heat hypersensitivity, without affecting formalin-induced mechanical hypersensitivity, suggesting that ERK1 partially shapes long-term responses to formalin. Interestingly, ERK1 deletion resulted in elevated basal ERK2 phosphorylation. However, this did not appear to influence nociceptive processing, since inflammation-induced ERK2 phosphorylation and pERK1/2 immunoreactivity in spinal cord were not elevated in ERK1 KO mice. Additionally, systemic MEK inhibition with SL327 (alpha-[amino[(4-aminophenyl)thio]methylene]-2 (trifluoromethyl)benzeneacetonitrile) attenuated formalin-induced spontaneous behaviors similarly in wild-type and ERK1 KO mice, indicating that unrelated signaling pathways do not functionally compensate for the loss of ERK1. Together, these results suggest that ERK1 plays a limited role in nociceptive sensitization and support a predominant role for ERK2 in these processes. PMID- 20739577 TI - New models of self-management education for minority ethnic groups: pilot randomized trial of a story-sharing intervention. AB - OBJECTIVE: no model of self-management education or peer support has yet achieved widespread reach and acceptability with minority ethnic groups. We sought to refine and test a new complex intervention in diabetes education: informal story sharing groups facilitated by bilingual health advocates. METHODS: pilot randomized trial with in-depth process evaluation in a socioeconomically deprived area. 157 people referred for diabetes education were randomized by concealed allocation to an intervention (story-sharing group in their own language) or control ('usual care' self-management education, through an interpreter if necessary) arm. Story-sharing groups were held in five ethnic languages and English (for African Caribbeans), and ran fortnightly for six months. Primary outcome was UKPDS (UK Prospective Diabetes Study) risk score. Secondary outcomes included attendance, HbA1c, well-being and enablement. Process measures included ethnographic observation, and qualitative interviews with staff and patients. RESULTS: some follow-up data were obtained on 87% of participants. There was no significant difference between intervention and control arms in biomedical outcomes. Attendance was 79% in the story-sharing arm and 35% in the control arm (p < 0.0001), and patient enablement scores were significantly higher (8.3 compared to 5.9, p < 0.005). The model was very popular with clinicians, managers and patients, which helped overcome numerous challenges to its successful embedding in a busy public sector diabetes service. CONCLUSION: people from minority ethnic groups in a socioeconomically deprived area were keen to attend informal story-sharing groups and felt empowered by them, but clinical outcomes were no better than with conventional education. Further research is needed to maximize the potential and evaluate the place of this appealing service model before it is introduced as a part of mainstream diabetes services. PMID- 20739578 TI - The effect of age on the outcomes of arthroscopic repair of type II superior labral anterior and posterior lesions. AB - BACKGROUND: The majority of clinical outcome studies of type II superior labral anterior and posterior (SLAP) repair assess patients younger than age 40. Biceps tenotomy or tenodesis is often recommended for patients older than age 40 with superior labrum-biceps complex injury. HYPOTHESIS: There is no difference in patient clinical outcomes comparing arthroscopic type II SLAP repair in patients younger or older than age 40. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Fifty-two patients stratified to groups younger than age 40 (21 patients; average age, 32.9 years) and older than age 40 (31 patients; average age, 55.1 years) were identified at a minimum 2-year follow-up (average, 28 months) after type II SLAP repair by a single surgeon using suture anchors. Outcome scores included American Shoulder and Elbow Society scores (ASES), Short Form-12 scores, Simple Shoulder Test scores, and visual analog pain scale. RESULTS: At follow-up, there was no statistical difference in visual analog pain scale (P = .16), ASES scores (P = .07), Simple Shoulder Test scores (P =.41), Short Form-12 testing, or range of motion testing. Patients older than age 40 noted their shoulder to be 87% of normal; 26 of 31 (84%) were satisfied to completely satisfied, and 28 of 31 (90%) would have the surgery again. Patients younger than 40 noted their shoulder to be approximately 89% of normal; 20 of 21 (95%) were satisfied to completely satisfied, and 18 of 21 (86%) would have the same procedure performed again. CONCLUSION: Our findings support that arthroscopic treatment of isolated type II SLAP repair using suture anchors can yield good to excellent results in patients older and younger than age 40. We found no statistically significant difference in patient outcome scores, satisfaction levels, or willingness to have the same procedure again when comparing arthroscopic SLAP repair in patients younger or older than age 40. PMID- 20739579 TI - Intramedullary acromioclavicular ligament reconstruction strengthens isolated coracoclavicular ligament reconstruction in acromioclavicular dislocations. AB - BACKGROUND: Techniques for reconstruction of the dislocated acromioclavicular (AC) joint abound. Most, however, do not address the injured AC ligaments and capsule. Evidence exists supporting the horizontal stabilizing effect of these ligaments on the AC joint. A novel AC and coracoclavicular (CC) reconstruction technique with an intramedullary free-tissue graft secured by suture buttons is low-profile, technically straightforward, and reproducible. HYPOTHESIS: A novel intramedullary AC reconstruction will strengthen an isolated free-tissue reconstruction of the CC ligaments. STUDY DESIGN: Controlled laboratory study. METHODS: Six cadaveric matched pair shoulders were tested with a custom testing system. Anterior-posterior and superior-inferior AC joint displacements (mm) were measured with AC joint compressions of 10 N, 20 N, and 30 N, and with translational loads of 10 N and 15 N. The same measurements were made after performing either a free-tissue tendon allograft CC reconstruction, or a free tissue graft reconstruction of the CC and AC ligamentous complexes in the corresponding contralateral matched shoulder. The AC ligamentous complex was reconstructed with an intramedullary free-tissue graft secured by suture buttons. Load-to-failure testing was then performed on each construct. A paired t test was used for statistical analysis (P < .05). RESULTS: Mean anterior-posterior translation of the reconstruction of the CC and AC ligamentous complexes was 50% or less than that of the CC reconstruction in all loading conditions (P < .05). Mean superior-inferior translation did not differ among the groups. Overall load to-failure testing did not differ between groups. CONCLUSION: Intramedullary AC complex reconstruction utilizing free-tissue graft for reconstruction of both the CC and AC ligaments demonstrates significantly greater initial horizontal stability than a free tissue isolated CC reconstruction and is similar to intact specimens. CLINICAL RELEVANCE: This novel intramedullary AC ligament reconstruction may be considered when seeking to improve horizontal stability in an anatomical CC ligament reconstruction. PMID- 20739580 TI - Evidence of multiple virulence subtypes in nosocomial and community-associated MRSA genotypes in companion animals from the upper midwestern and northeastern United States. AB - OBJECTIVE: Not much is known about the zoonotic transmission of methicillin resistant Staphylococcus aureus (MRSA) in companion animals in the United States. We report the rate of prevalence of S. aureus and MRSA recovered from clinical samples of animals requiring treatment at veterinary clinics throughout the upper midwestern and northeastern United States. DESIGN: We compared phenotypes, genotypes, and virulence profiles of the MRSA isolates identified in companion animals, such as cats, dogs, horses, and pigs, with typical human nosocomial and community-associated MRSA (CA-MRSA) genotypes to assess implied zoonotic transmission or zooanthroponosis. Five hundred thirty-three coagulase-positive staphylococci (CPS) isolates recovered between 2006 and 2008 from a variety of animal-source samples were screened for S. aureus by S. aureus-specific 16S rDNA primers and were screened for methicillin-resistance. All MRSA isolates were genotyped by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and spa typing. They were also screened for common staphylococcal enterotoxin and adhesion genes by multiplex and singleplex PCR. RESULTS: Among the 533 CPS isolates recovered, 66 (12.4%) were determined to be S. aureus and 24 (4.5%) were MRSA. The percent of animals that were positive for S. aureus were as follows: 6.6% (32 of 487) dogs, 39.6% (19 of 48) cats, 83.3% (10 of 12) horses, and 100% of pigs, rabbits, hamsters and rats. Notably, 36.4% of all S. aureus identified were MRSA. Methicillin-resistant S. aureus was present in clinical samples from 12 of 487 dogs (2.5%), 6 of 48 cats (12.5%), 5 of 12 horses (42%), and 1 of 2 pigs (50%). The 24 MRSA isolates resolved into 4 PFGE clones: USA100 (50%), USA300 (16.7%), USA500 (20.8%) and USA800 (12.5%) and 6 sequence types (ST5, ST8, ST105, ST830, and ST986) or 2 clonal complexes, CC5 and CC8. Five major virulence profiles (clusters A to E) were observed in these MRSA isolates. Genotypic and virulence profiles of cats and dogs were more similar to each other than to those of horses. A Panton-Valentine leukocidin positive isolate with ST8:USA300 background was identified in a pig causing skin and soft infection. CONCLUSION: The presence of human MRSA clones in these animals suggests possible reverse zoonotic transmission. This study reports the first case of a USA300 genotype in a pig. Presence of multiple virulence profiles within a MRSA genotype in these animals suggests the potential of emergence of new MRSA clones by gaining or losing additional virulence genes. PMID- 20739581 TI - Thyroxine suppression therapy for benign, non-functioning solitary thyroid nodules: a quality-effects meta-analysis. AB - Levothyroxine (LT4) suppressive therapy for solitary thyroid nodules is not popularly advocated presently because its clinical efficacy and safety are currently considered controversial. This meta-analysis aims to address efficacy issues by using rigorous methods to arrive at a pooled estimate. On the basis of the analysis, it is estimated that LT4 therapy is clearly associated with up to a two-fold increase in the chance of nodule reduction. This translates to a number needed to treat (NNT) of 6 or a 50% decrease in the risk of cancer given nodule reduction. Keeping this definition of efficacy in mind and a low incidence of adverse events with low level LT4 suppression, such an intervention might be appropriate in patients selected on the basis of a low risk for adverse effects. PMID- 20739582 TI - Virchow's contribution to the understanding of thrombosis and cellular biology. PMID- 20739583 TI - Jean-Martin Charcot: the father of neurology. PMID- 20739584 TI - The impact of overreporting on MMPI-2-RF substantive scale score validity. AB - This study examined the impact of overreporting on the validity of Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) substantive scale scores by comparing correlations with relevant external criteria (i.e., validity coefficients) of individuals who completed the instrument under instructions to (a) feign psychopathology or (b) feign somatic complaints, with validity findings for a control group of individuals who completed the MMPI-2-RF under standard instructions. Validity coefficients for MMPI-2-RF substantive scale scores were much weaker for feigners than for controls. The authors also found mean profiles to be more elevated for feigners than for controls. Effects were more extreme for psychopathology feigners than for somatic feigners. The results demonstrate the detrimental effect that overreporting psychopathology or somatic problems has on the validity of MMPI-2-RF scale scores. The findings illustrate the need for validity indices in self-report measures of personality and psychopathology. PMID- 20739585 TI - Childhood experiences of cancer: an interpretative phenomenological analysis approach. AB - Pediatric oncology has emerged as one of the great medical success stories of the last 4 decades. The cure rate of childhood cancer has increased from approximately 25% in the 1960's to more than 75% in more recent years. However, very little is known about how children actually experience the diagnosis and treatment of their illness. A total of 9 families in which a child was diagnosed with cancer were interviewed twice over a 12-month period. Using the qualitative methodology of interpretative phenomenological analysis (IPA), children's experiences of being patients with a diagnosis of cancer were explicated. The results revealed 5 significant themes: the experience of illness, the upside of being sick, refocusing on what is important, acquiring a new perspective, and the experience of returning to well-being. Changes over time were noted because children's experiences' were often pertinent to the stage of treatment the child had reached. These results revealed rich and intimate information about a sensitive issue with implications for understanding child development and medical and psychosocial treatment. PMID- 20739586 TI - Changes in children's reports of symptom occurrence and severity during a course of myelosuppressive chemotherapy. AB - The purposes of this study in children who underwent a cycle of myelosuppressive chemotherapy were to describe changes in symptom occurrence and severity during the chemotherapy cycle. Patients (N = 66) 10 to 18 years of age completed the Memorial Symptom Assessment Scale for 10- to 18-year-olds (MSAS 10-18) at the start of a chemotherapy cycle (T1) and weekly for the next 2 weeks (T2 and T3). More than 30% of children reported 10 or more symptoms at all 3 time points. Symptom occurrence trajectories were tested with multilevel logistic regression. In all, 6 symptoms (ie, fatigue, sadness, irritability, worrying, weight loss, sweating) showed a decreasing linear trend. Significant quadratic patterns of change were found for feeling drowsy, nausea, and vomiting. Changes in symptom severity over time were evaluated with multilevel negative binomial regression. No significant differences over time were found in any of the symptom severity scores on the MSAS. Children experienced a high number of symptoms at the initiation of a chemotherapy cycle that persisted over the subsequent 2 weeks. PMID- 20739587 TI - The development of an instrument to assess the unmet needs of young people who have a sibling with cancer: piloting the Sibling Cancer Needs Instrument (SCNI). AB - The psychosocial needs of young people (aged 12-24) who have a sibling with cancer are still comparatively underresearched and largely underserviced. Steps taken in the development of a needs-based measure, the Sibling Cancer Needs Instrument (SCNI), are presented, involving a qualitative exploration of needs (focus group with 4 young people, telephone interviews with 7 young people, and a staff survey) and a quantitative piloting of the resulting first version of the SCNI on 71 young people. Results are explored in relation to the 10 identified domains of need (information, peer support [friends], peer support [similar experience], sibling relationship/support, expressing/coping with feelings, access to support services, respite/recreation, acknowledgement/attention for self, instrumental support, and involvement in the cancer experience). The survey data showed that 75% of young people endorsed 10 or more needs, whereas 50% endorsed more than half of all 80 needs, and on average, participants reported 10 unmet needs. Correlations between needs and psychological distress scores are also explored. Initial reliability, and face and content validity for the SCNI encourage further development of the instrument to assist in better monitoring and to meet the various needs of this underserviced population. PMID- 20739588 TI - Social performance and secret ritual: battling against obsessive-compulsive disorder. AB - This autoethnography offers an account of my experience with mental illness and provides an analysis of the performative aspects of obsessive-compulsive disorder (OCD). OCD is a genetic disorder triggered by environmental stressors involving a chemical imbalance in the brain. The resulting biologically altered state leaves individuals to steer themselves among and between "appropriate" performance and secret rituals. Analyzing my own communication practices through a performance lens highlights the importance of image management for people struggling with disability. In telling my own story, this article provides readers an in-depth look at OCD as a traumatic brain disorder whose sufferers rely on communicative performance to maintain their public and private identities, and as a disease that impedes social life for its sufferers. Implications of this account for those struggling with mental disability and for practitioners aiming to help them are discussed. PMID- 20739589 TI - Self- and other-diagnosis in user-led mental health online communities. AB - This article consists of a qualitative analysis of discussion forums in online mental health communities whose members routinely write about diagnosis. The analysis concerns the function of diagnosis from the perspective of personal identity, with particular focus on the status of official diagnosis, as well as community members' discussions of symptoms and psychiatric syndromes that amount to informal diagnosis or consultation. Self-diagnosis sometimes takes the form of recommended "quizzes" and other online quasi-diagnostic tools. Other-diagnosis, in which a third party is discussed by community members, is also considered. We discuss the implications of such online discourse for Internet users themselves as well the challenges for the health and medical professions. PMID- 20739590 TI - Hepatic non-Hodgkin's lymphoma with lactic acidosis in HIV-infected patients: report of 2 cases. AB - We report 2 patients with HIV-associated non-Hodgkin's lymphoma with massive hepatic involvement and lactic acidosis. The lactic acidosis was likely caused by excessive tumor lactate production coupled with impaired hepatic clearance. Although 1 patient died rapidly, the other survived for 7 months after receiving urgent combination chemotherapy. Clinicians should be aware of this condition and the importance of its early diagnosis and treatment. PMID- 20739591 TI - Sexual practice among Thai HIV-infected patients: prevalence and risk factors for unprotected sex. AB - Positive prevention which focuses on prevention of HIV transmission from those already infected to those uninfected is an important issue for HIV prevention. A self-administered questionnaire on sexual practice survey of HIV-infected patients attending HIV clinics was undertaken. Of the 1160 patients, 53% knew their HIV status after being ill and 59% believed that they got infection from their regular sexual partner. In 3 months prior to the survey, 18% reported unprotected sex. Unprotected sex significantly decreased in people having adequate condoms but increased in those who believed that their sexual partners were already infected. Effect of disclosure of HIV status on unprotected sex depended on whether patients were men or women. Non-disclosure HIV-positive men claimed to have less unprotected sex than their counterpart, HIV-positive women. Factors related to unprotected sex should be addressed and sexual health must be integrated and promoted in HIV health care. PMID- 20739592 TI - Differential contributions of thalamic nuclei in the generation of antisaccades. AB - Our knowledge of thalamus function comes largely from anatomical studies showing, for example, that the ventroanterior (VA) and ventrolateral (VL) nuclei are connected to "motor" regions, whereas the mediodorsal (MD) nucleus is connected to prefrontal "executive" regions. Interestingly, Kunimatsu and Tanaka recently showed that preparatory signals for antisaccades (a motor response requiring executive control) were enhanced compared with prosaccades in the VA/VL but not in the MD, which is surprising given MD's connection to executive regions. PMID- 20739593 TI - Activity-dependent regulation of the binomial parameters p and n at the mouse neuromuscular junction in vivo. AB - Block of neurotransmission at the mammalian neuromuscular junction triggers an increase in the number of vesicles released (quantal content). The increase occurs whether nerve and muscle activity are both blocked by placement of a tetrodotoxin (TTX) containing cuff on the nerve or whether muscle activity is selectively blocked by injection of alpha-bungarotoxin (BTX). We used ANOVA to examine whether the mechanism underlying the increase in quantal content differed between the two types of activity blockade. We found that TTX-induced blockade increased the probability of release (p), whereas BTX-induced blockade increased the number of releasable vesicles (n). The lack of increase in p when postsynaptic activity was blocked with BTX suggests that block of presynaptic activity triggers the increase. To determine whether n is regulated by mismatch of pre- and postsynaptic activity introduced by BTX injection we combined BTX and TTX and still found an increase in n. We conclude that block of acetylcholine binding to acetylcholine receptors during spontaneous release triggers the increase in n. PMID- 20739594 TI - A neural representation of sequential states within an instructed task. AB - In the study of the neural basis of sensorimotor transformations, it has become clear that the brain does not always wait to sense external events and afterward select the appropriate responses. If there are predictable regularities in the environment, the brain begins to anticipate the timing of instructional cues and the signals to execute a response, revealing an internal representation of the sequential behavioral states of the task being performed. To investigate neural mechanisms that could represent the sequential states of a task, we recorded neural activity from two oculomotor structures implicated in behavioral timing- the supplementary eye fields (SEF) and the lateral intraparietal area (LIP)- while rhesus monkeys performed a memory-guided saccade task. The neurons of the SEF were found to collectively encode the progression of the task with individual neurons predicting and/or detecting states or transitions between states. LIP neurons, while also encoding information about the current temporal interval, were limited with respect to SEF neurons in two ways. First, LIP neurons tended to be active when the monkey was planning a saccade but not in the precue or intertrial intervals, whereas SEF neurons tended to have activity modulation in all intervals. Second, the LIP neurons were more likely to be spatially tuned than SEF neurons. SEF neurons also show anticipatory activity. The state selective and anticipatory responses of SEF neurons support two complementary models of behavioral timing, state dependent and accumulator models, and suggest that each model describes a contribution SEF makes to timing at different temporal resolutions. PMID- 20739595 TI - Mechanisms of direction selectivity in cat primary visual cortex as revealed by visual adaptation. AB - In contrast to neurons of the lateral geniculate nucleus (LGN), neurons in the primary visual cortex (V1) are selective for the direction of visual motion. Cortical direction selectivity could emerge from the spatiotemporal configuration of inputs from thalamic cells, from intracortical inhibitory interactions, or from a combination of thalamic and intracortical interactions. To distinguish between these possibilities, we studied the effect of adaptation (prolonged visual stimulation) on the direction selectivity of intracellularly recorded cortical neurons. It is known that adaptation selectively reduces the responses of cortical neurons, while largely sparing the afferent LGN input. Adaptation can therefore be used as a tool to dissect the relative contribution of afferent and intracortical interactions to the generation of direction selectivity. In both simple and complex cells, adaptation caused a hyperpolarization of the resting membrane potential (-2.5 mV, simple cells, -0.95 mV complex cells). In simple cells, adaptation in either direction only slightly reduced the visually evoked depolarization; this reduction was similar for preferred and null directions. In complex cells, adaptation strongly reduced visual responses in a direction dependent manner: the reduction was largest when the stimulus direction matched that of the adapting motion. As a result, adaptation caused changes in the direction selectivity of complex cells: direction selectivity was reduced after preferred direction adaptation and increased after null direction adaptation. Because adaptation in the null direction enhanced direction selectivity rather than reduced it, it seems unlikely that inhibition from the null direction is the primary mechanism for creating direction selectivity. PMID- 20739596 TI - Supplementary eye field encodes option and action value for saccades with variable reward. AB - We recorded neuronal activity in the supplementary eye field (SEF) while monkeys made saccades to targets that yielded rewards of variable amount and uncertainty of delivery. Some SEF cells (29%) represented the anticipated value of the saccade target. These neurons encoded the value of the reward option but did not reflect the action necessary to obtain the reward. A plurality of cells (45%) represented both saccade direction and value. These neurons reflect action value, i.e., the value that is expected to follow from a specific saccade. Other cells (13%) represented only saccade direction. The SEF neurons matched the monkey's risk-seeking behavior by responding more strongly to the uncertain reward options than would be expected based on their response to the sure options and the cued outcome probability. Thus SEF neurons represented subjective, not expected, value. Across the SEF population, option-value signals developed early, ~120 ms prior to saccade execution. Action-value and saccade direction signals developed ~60 ms later. These results suggest that the SEF is involved in transforming option-value signals into action-value signals. However, in contrast to other oculomotor neurons, SEF neurons did not reach a constant level of activity before saccade onset. Instead the activity level of many (52%) SEF neurons still reflected value at the time just before saccade initiation. This suggests that SEF neurons guide the selection of a saccade based on value information but do not participate in the initiation of that saccade. PMID- 20739597 TI - Multiple somatotopic representations of heat and mechanical pain in the operculo insular cortex: a high-resolution fMRI study. AB - Whereas studies of somatotopic representation of touch have been useful to distinguish multiple somatosensory areas within primary (SI) and secondary (SII) somatosensory cortex regions, no such analysis exists for the representation of pain across nociceptive modalities. Here we investigated somatotopy in the operculo-insular cortex with noxious heat and pinprick stimuli in 11 healthy subjects using high-resolution (2 * 2 * 4 mm) 3T functional magnetic resonance imaging (fMRI). Heat stimuli (delivered using a laser) and pinprick stimuli (delivered using a punctate probe) were directed to the dorsum of the right hand and foot in a balanced design. Locations of the peak fMRI responses were compared between stimulation sites (hand vs. foot) and modalities (heat vs. pinprick) within four bilateral regions of interest: anterior and posterior insula and frontal and parietal operculum. Importantly, all analyses were performed on individual, non-normalized fMRI images. For heat stimuli, we found hand-foot somatotopy in the contralateral anterior and posterior insula [hand, 9 +/- 10 (SD) mm anterior to foot, P < 0.05] and in the contralateral parietal operculum (SII; hand, 7 +/- 10 mm lateral to foot, P < 0.05). For pinprick stimuli, we also found somatotopy in the contralateral posterior insula (hand, 9 +/- 10 mm anterior to foot, P < 0.05). Furthermore, the response to heat stimulation of the hand was 11 +/- 12 mm anterior to the response to pinprick stimulation of the hand in the contralateral (left) anterior insula (P < 0.05). These results indicate the existence of multiple somatotopic representations for pain within the operculo-insular region in humans, possibly reflecting its importance as a sensory-integration site that directs emotional responses and behavior appropriately depending on the body site being injured. PMID- 20739598 TI - Modulation of firing rate by background synaptic noise statistics in rat visual cortical neurons. AB - It has been shown previously that background synaptic noise modulates the response gain of neocortical neurons. However, the role of the statistical properties of the noise in modulating firing rate is not known. Here, the dependence of firing rate on the statistical properties of the excitatory to inhibitory balance (EI) in cortical pyramidal neurons was studied. Excitatory glutamatergic and inhibitory GABAergic synaptic conductances were simulated as two stochastic processes and injected into individual neurons in vitro through use of the dynamic-clamp system. Response gain was significantly modulated as a function of the statistical interactions between excitatory and inhibitory synaptic conductances. Firing rates were compared for noisy synaptic conductance steps by varying either the EI correlation or the relative delay between correlated E and I. When inhibitory synaptic conductances exhibited a short temporal delay (5 ms) relative to correlated excitatory synaptic conductances, the response gain was increased compared with noise with no temporal delay but with an equivalent degree of correlation. The dependence of neuronal firing rate on the EI delay of the noisy background synaptic conductance suggests that individual excitatory pyramidal neurons are sensitive to the EI balance of the synaptic conductance. Therefore the statistical EI interactions encoded within the synaptic subthreshold membrane fluctuations are able to modulate neuronal firing properties. PMID- 20739599 TI - Decoding and cortical source localization for intended movement direction with MEG. AB - Magnetoencephalography (MEG) enables a noninvasive interface with the brain that is potentially capable of providing movement-related information similar to that obtained using more invasive neural recording techniques. Previous studies have shown that movement direction can be decoded from multichannel MEG signals recorded in humans performing wrist movements. We studied whether this information can be extracted without overt movement of the subject, because the targeted users of brain-controlled interface (BCI) technology are those with severe motor disabilities. The objectives of this study were twofold: 1) to decode intended movement direction from MEG signals recorded during the planning period before movement onset and during imagined movement and 2) to localize cortical sources modulated by intended movement direction. Ten able-bodied subjects performed both overt and imagined wrist movement while their cortical activities were recorded using a whole head MEG system. The intended movement direction was decoded using linear discriminant analysis and a Bayesian classifier. Minimum current estimation (MCE) in combination with a bootstrapping procedure enabled source-space statistical analysis, which showed that the contralateral motor cortical area was significantly modulated by intended movement direction, and this modulation was the strongest ~100 ms before the onset of overt movement. These results suggest that it is possible to study cortical representation of specific movement information using MEG, and such studies may aid in presurgical localization of optimal sites for implanting electrodes for BCI systems. PMID- 20739600 TI - Auditory nerve fibers excite targets through synapses that vary in convergence, strength, and short-term plasticity. AB - Auditory nerve fibers are the major source of excitation to the three groups of principal cells of the ventral cochlear nucleus (VCN), bushy, T stellate, and octopus cells. Shock-evoked excitatory postsynaptic currents (eEPSCs) in slices from mice showed systematic differences between groups of principal cells, indicating that target cells contribute to determining pre- and postsynaptic properties of synapses from spiral ganglion cells. Bushy cells likely to be small spherical bushy cells receive no more than three, most often two, excitatory inputs; those likely to be globular bushy cells receive at least four, most likely five, inputs. T stellate cells receive 6.5 inputs. Octopus cells receive >60 inputs. The N-methyl-d-aspartate (NMDA) components of eEPSCs were largest in T stellate, smaller in bushy, and smallest in octopus cells, and they were larger in neurons from younger than older mice. The average AMPA conductance of a unitary input is 22 +/- 15 nS in both groups of bushy cells, <1.5 nS in octopus cells, and 4.6 +/- 3 nS in T stellate cells. Sensitivity to philanthotoxin (PhTX) and rectification in the intracellular presence of spermine indicate that AMPA receptors that mediate eEPSCs in T stellate cells contain more GluR2 subunits than those in bushy and octopus cells. The AMPA components of eEPSCs were briefer in bushy (0.5 ms half-width) than in T stellate and octopus cells (0.8-0.9 ms half-width). Widening of eEPSCs in the presence of cyclothiazide (CTZ) indicates that desensitization shortens eEPSCs. CTZ-insensitive synaptic depression of the AMPA components was greater in bushy and octopus than in T stellate cells. PMID- 20739602 TI - Temporal shift from velocity to position proprioceptive feedback control during reaching movements. AB - Reaching movements to a target usually have stereotypical kinematics. Although this suggests that the desired kinematics of a movement might be planned, does it also mean that deviations from the planned kinematics are corrected by proprioceptive feedback control? To answer this question, we designed a task in which the subjects made center-forward movements to a target while holding the handle of a robot. Subjects were instructed to make movements at a peak velocity of 1 m/s. No further instructions were given with respect to the movement trajectory or the velocity time profile. In randomly chosen trials the robot imposed servo-controlled deviations from the previously computed unperturbed velocity and position time profiles. The duration of the velocity deviations and the magnitude of accumulated position deviations were manipulated. The subjects were instructed to either "Attempt to correct" or "Do not correct" the movement. The responses to the imposed deviations in the surface electromyograms in the elbow and shoulder agonist muscles consisted of an initial burst followed by a sharp decrease in the "Do not correct" condition or by sustained activity in the "Attempt to correct" condition. The timing and magnitude of the initial response burst reflected those of the velocity deviations and were not affected by the instruction. The timing and magnitude of the late response activity reflected position feedback control and were strongly affected by the instruction. We suggest that proprioceptive feedback control is suppressed in the beginning of the movement, then velocity feedback control is activated in the middle of the movement to control a desired velocity, whereas position feedback control is facilitated late in the movement to acquire the final position. PMID- 20739601 TI - Facial injections of pruritogens and algogens excite partly overlapping populations of primary and second-order trigeminal neurons in mice. AB - Intradermal cheek injection of pruitogens or algogens differentially elicits hindlimb scratching or forelimb wiping, suggesting that these behaviors distinguish between itch and pain. We studied whether pruritogens and algogens excite separate or overlapping populations of primary afferent and second-order trigeminal neurons in mice. Calcium imaging of primary sensory trigeminal ganglion (TG) cells showed that 15.4% responded to histamine, 5.8% to the protease-activated receptor (PAR)-2 agonist, 13.4% to allyl isothiocyanate (AITC), and 36.7% to capsaicin. AITC and/or capsaicin activated the vast majority of histamine- and PAR-2 agonist-sensitive TG cells. A chemical search strategy identified second-order neurons in trigeminal subnucleus caudalis (Vc) responsive to histamine, the PAR-2 agonist, or AITC. A minority of histamine or PAR-2 agonist-responsive Vc neurons responded to the other pruritogen, whereas a large majority of puritogen-responsive Vc neurons responded to capsaicin and/or AITC. A minority of AITC-responsive Vc neurons responded to pruritogens, whereas most responded to capsaicin. These data indicate that most primary and higher-order trigeminal sensory neurons are activated by both pruritic and algesic stimuli, although a minority exhibit selectivity. The results are discussed in terms of population codes for itch and pain that result in distinct behavioral responses of hindlimb scratching and forelimb wiping that are mediated at lumbar and cervical segmental levels, respectively. PMID- 20739603 TI - Solution structure of the HRDC domain of human Bloom syndrome protein BLM. AB - Bloom syndrome is a rare genetic disorder characterized by severe growth retardation and cancer predisposition. The disease is caused by a loss of function of the Bloom syndrome protein (BLM), a member of the RecQ family of DNA helicases. Here we report on the first 3D structure of a BLM fragment, a solution structure of the C-terminal helicase-and-ribonuclease D-C-terminal (HRDC) domain from human BLM. The structure reveals unique features of BLM HRDC that are distinct from the HRDC domain of Werner syndrome protein. In particular, BLM HRDC retains many acidic residues exposed to the solvent, which makes the domain surface extensively electronegative. Consistent with this, fluorescence polarization assays showed an inability of isolated BLM HRDC to interact with DNA substrates. Analyses employing ultracentrifugation, gel-filtration, CD spectroscopy and dynamic light scattering showed that the BLM HRDC domain exists as a stable monomer in solution. The results show that BLM HRDC is a compact, robust and acidic motif which may play a distinct role apart from DNA binding. PMID- 20739604 TI - Drinking and arterial blood pressure responses to ANG II in young and old rats. AB - We investigated water drinking and arterial blood pressure responses to intravenous infusions of ANG II in young (4 mo), middle-aged adult (12 mo), and old (29 mo) male Brown Norway rats. Infusions of ANG II began with arterial blood pressure either at control levels or at reduced levels following injection of the vasodilator minoxidil. Under control conditions, mean arterial pressure (MAP) in response to ANG II rose to the same level for all groups, and middle-aged and old rats drank as much or more water in response to ANG II compared with young rats, depending on whether intakes were analyzed using absolute or body weight-adjusted values. When arterial blood pressure first was reduced with minoxidil, MAP in response to ANG II stabilized at significantly lower levels compared with control conditions for all groups. Young rats drank significantly more water under reduced pressure conditions compared with control conditions, while middle-aged and old rats did not. Urine volume in response to ANG II was lower, while water balance was higher, under conditions of reduced pressure compared with control conditions. Baroreflex control of heart rate was substantially reduced in old rats compared with young and middle-aged animals. In summary, young rats appear to be more sensitive to the inhibitory effects of increased arterial blood pressure on water drinking than are older animals. PMID- 20739605 TI - Diaphragm muscle shortening modulates kinematics of lower rib cage in dogs. AB - We tested the hypothesis that diaphragm muscle shortening modulates volume displacement and kinematics of the lower rib cage in dogs and that posture and mode of ventilation affect such modulation. Radiopaque markers were surgically attached to the lower three ribs of the rib cage and to the midcostal region of the diaphragm in six dogs of ~8 kg body masses, and the locations of these markers were determined by a biplane fluoroscopy system. Three-dimensional software modeling techniques were used to compute volume displacement and surface area of the midcostal diaphragm and the lower three ribs during quiet spontaneous breathing, mechanical ventilation, and bilateral phrenic nerve stimulation at different lung volumes spanning the vital capacity. Volume displaced by the diaphragm relative to that displaced by the lower ribs is disproportionately greater under mechanical ventilation than during spontaneous breathing in the supine position (P < 0.05). At maximal stimulation, diaphragm volume displacement grows disproportionately larger than rib volume displacement as lung volume increases (P < 0.05). Surface area of both the diaphragm and the lower ribs during maximal stimulation of the diaphragm is reduced compared with that at spontaneous breathing (P < 0.05). In the prone posture, mechanical ventilation results in a smaller change in diaphragm surface area than spontaneous breathing (P < 0.05). Our data demonstrate that during inspiration the lower rib cage moves not only through the pump- and bucket-handle motion, but also rotates around the spine. Taken together, these data support the observation that the kinematics of the lower rib cage and its mechanical interaction with the diaphragm are more complex than previously known. PMID- 20739606 TI - Cloning and characterization of a zebrafish homologue of human AQP1: a bifunctional water and gas channel. AB - The mammalian aquaporins AQP1, AQP4, and AQP5 have been shown to function not only as water channels but also as gas channels. Zebrafish have two genes encoding an AQP1 homologue, aqp1a and aqp1b. In the present study, we cloned the cDNA that encodes the zebrafish protein Aqp1a from the 72-h postfertilization (hpf) embryo of Danio rerio, as well as from the swim bladder of the adult. The deduced amino-acid sequence of aqp1a consists of 260 amino acids and is 59% identical to human AQP1. By analyzing the genomic DNA sequence, we identified four exons in the aqp1a gene. By in situ hybridization, aqp1a is expressed transiently in the developing vasculature and in erythrocytes from 16 to 48 h of development. Later, at 72 hpf, aqp1a is expressed in dermal ionocytes and in the swim bladder. Western blot analysis of adult tissues reveals that Aqp1a is most highly expressed in the eye and swim bladder. Xenopus oocytes expressing aqp1a have a channel-dependent (*) osmotic water permeability (P(f)(*)) that is indistinguishable from that of human AQP1. On the basis of the magnitude of the transient change in surface pH (DeltapH(S)) that were recorded as the oocytes were exposed to either CO(2) or NH(3), we conclude that zebrafish Aqp1a is permeable to both CO(2) and NH(3). The ratio (DeltapH(S)(*))((CO)2)/P(f)(*) is about half that of human AQP1, and the ratio (DeltapH(S)(*))(NH3)/P(f)(*) is about one-quarter that of human AQP1. Thus, compared with human AQP1, zebrafish Aqp1a has about twice the selectivity for CO(2) over NH(3). PMID- 20739607 TI - High-protein-induced glomerular hyperfiltration is independent of the tubuloglomerular feedback mechanism and nitric oxide synthases. AB - A high protein intake is associated with increased glomerular filtration rate (GFR), which has been suggested to be mediated by reduced signaling of the tubuloglomerular feedback (TGF) mechanism. Nitric oxide (NO) has been shown to contribute to high protein-induced glomerular hyperfiltration, but the specific NO synthase (NOS) isoform responsible is not clear. In this study, a model for high-protein-induced hyperfiltration in conscious mice was developed. Using this model, we investigated the role of TGF using adenosine A(1)-receptor knockout mice lacking the TGF mechanism. Furthermore, the role of the different NOS isoforms was studied using neuronal-, inducible-, and endothelial-NOS knockout mice, and furthermore, wild-type mice acutely administered with the unspecific NOS inhibitor N(omega)-nitro-l-arginine methyl ester (100 mg/kg). GFR was measured consecutively in mice given a low-protein diet (8% casein) for 10 days, followed by a high-protein diet (50% casein) for 10 days. All mice developed high protein-induced hyperfiltration to a similar degree. These results demonstrate that high protein-induced glomerular hyperfiltration is independent of the TGF mechanism and NOS isoforms. PMID- 20739608 TI - Functional elucidation of a key contact between tRNA and the large ribosomal subunit rRNA during decoding. AB - The selection of cognate tRNAs during translation is specified by a kinetic discrimination mechanism driven by distinct structural states of the ribosome. While the biochemical steps that drive the tRNA selection process have been carefully documented, it remains unclear how recognition of matched codon:anticodon helices in the small subunit facilitate global rearrangements in the ribosome complex that efficiently promote tRNA decoding. Here we use an in vitro selection approach to isolate tRNA(Trp) miscoding variants that exhibit a globally perturbed tRNA tertiary structure. Interestingly, the most substantial distortions are positioned in the elbow region of the tRNA that closely approaches helix 69 (H69) of the large ribosomal subunit. The importance of these specific interactions to tRNA selection is underscored by our kinetic analysis of both tRNA and rRNA variants that perturb the integrity of this interaction. PMID- 20739609 TI - Plant cell growth in tissue. AB - Cell walls are part of the apoplasm pathway that transports water, solutes, and nutrients to cells within plant tissue. Pressures within the apoplasm (cell walls and xylem) are often different from atmospheric pressure during expansive growth of plant cells in tissue. The previously established Augmented Growth Equations are modified to evaluate the turgor pressure, water uptake, and expansive growth of plant cells in tissue when pressures within the apoplasm are lower and higher than atmospheric pressure. Analyses indicate that a step-down and step-up in pressure within the apoplasm will cause an exponential decrease and increase in turgor pressure, respectively, and the rates of water uptake and expansive growth each undergo a rapid decrease and increase, respectively, followed by an exponential return to their initial magnitude. Other analyses indicate that pressure within the apoplasm decreases exponentially to a lower value after a step-down in turgor pressure, which simulates its behavior after an increase in expansive growth rate. Also, analyses indicate that the turgor pressure decays exponentially to a constant value that is the sum of the critical turgor pressure and pressure within the apoplasm during stress relaxation experiments in which pressures within the apoplasm are not atmospheric pressure. Additional analyses indicate that when the turgor pressure is constant (clamped), a decrease in pressure within the apoplasm elicits an increase in elastic expansion followed by an increase in irreversible expansion rate. Some analytical results are supported by prior experimental research, and other analytical results can be verified with existing experimental methods. PMID- 20739610 TI - SHORT-ROOT and SCARECROW regulate leaf growth in Arabidopsis by stimulating S phase progression of the cell cycle. AB - SHORT-ROOT (SHR) and SCARECROW (SCR) are required for stem cell maintenance in the Arabidopsis (Arabidopsis thaliana) root meristem, ensuring its indeterminate growth. Mutation of SHR and SCR genes results in disorganization of the quiescent center and loss of stem cell activity, resulting in the cessation of root growth. This paper reports on the role of SHR and SCR in the development of leaves, which, in contrast to the root, have a determinate growth pattern and lack a persistent stem cell niche. Our results demonstrate that inhibition of leaf growth in shr and scr mutants is not a secondary effect of the compromised root development but is caused by an effect on cell division in the leaves: a reduced cell division rate and early exit of the proliferation phase. Consistent with the observed cell division phenotype, the expression of SHR and SCR genes in leaves is closely associated with cell division activity in most cell types. The increased cell cycle duration is due to a prolonged S-phase duration, which is mediated by up-regulation of cell cycle inhibitors known to restrain the activity of the transcription factor, E2Fa. Therefore, we conclude that, in contrast to their specific roles in cortex/endodermis differentiation and stem cell maintenance in the root, SHR and SCR primarily function as general regulators of cell proliferation in leaves. PMID- 20739612 TI - An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II. AB - Fluid balance is critical to life and hence is tightly controlled in the body. Angiotensin II (ANGII), one of the most important components of this regulatory system, is recognized as a dipsogenic hormone that stimulates vasopressin (VP) expression and release. However, detailed mechanisms regarding how ANGII brings about these changes are not fully understood. In the present study, we show initially that the osmoregulatory functions of secretin (SCT) in the brain are similar to those of ANGII in mice and, more important, we discovered the role of SCT as the link between ANGII and its downstream effects. This was substantiated by the use of two knockout mice, SCTR(-/-) and SCT(-/-), in which we show the absence of an intact SCT/secretin receptor (SCTR) axis resulted in an abolishment or much reduced ANGII osmoregulatory functions. By immunohistochemical staining and in situ hybridization, the proteins and transcripts of SCT and its receptor are found in the paraventricular nucleus (PVN) and lamina terminalis. We propose that SCT produced in the circumventricular organs is transported and released in the PVN to stimulate vasopressin expression and release. In summary, our findings identify SCT and SCTR as novel elements of the ANGII osmoregulatory pathway in maintaining fluid balance in the body. PMID- 20739611 TI - alpha-Conotoxin BuIA[T5A;P6O]: a novel ligand that discriminates between alpha6beta4 and alpha6beta2 nicotinic acetylcholine receptors and blocks nicotine stimulated norepinephrine release. AB - alpha6* (asterisk indicates the presence of additional subunits) nicotinic acetylcholine receptors (nAChRs) are broadly implicated in catecholamine dependent disorders that involve attention, motor movement, and nicotine self administration. Different molecular forms of alpha6 nAChRs mediate catecholamine release, but receptor differentiation is greatly hampered by a paucity of subtype selective ligands. alpha-Conotoxins are nAChR-targeted peptides used by Conus species to incapacitate prey. We hypothesized that distinct conotoxin-binding kinetics could be exploited to develop a series of selective probes to enable study of native receptor subtypes. Proline6 of alpha-conotoxin BuIA was found to be critical for nAChR selectivity; substitution of proline6 with 4-hydroyxproline increased the IC(50) by 2800-fold at alpha6/alpha3beta2beta3 but only by 6-fold at alpha6/alpha3beta4 nAChRs (to 1300 and 12 nM, respectively). We used conotoxin probes together with subunit-null mice to interrogate nAChR subtypes that modulate hippocampal norepinephrine release. Release was abolished in alpha6-null mutant mice. alpha-Conotoxin BuIA[T5A;P6O] partially blocked norepinephrine release in wild-type controls but failed to block release in beta4(-/-) mice. In contrast, BuIA[T5A;P6O] failed to block dopamine release in the wild-type striatum known to contain alpha6beta2* nAChRs. BuIA[T5A;P6O] is a novel ligand for distinguishing between closely related alpha6* nAChRs; alpha6beta4* nAChRs modulate norepinephrine release in hippocampus but not dopamine release in striatum. PMID- 20739613 TI - p63RhoGEF--a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells. AB - The purpose of our study was to investigate the role of endogenous p63RhoGEF in G(q/11)-dependent RhoA activation and signaling in rat aortic smooth muscle cells (RASMCs). Therefore, we studied the expression and subcellular localization in freshly isolated RASMCs and performed loss of function experiments to analyze its contribution to RhoGTPase activation and functional responses such as proliferation and contraction. By this, we could show that p63RhoGEF is endogenously expressed in RASMCs and acts there as the dominant mediator of the fast angiotensin II (ANG II)-dependent but not of the sphingosine-1-phosphate (S(1)P)-dependent RhoA activation. p63RhoGEF is not an activator of the concomitant Rac1 activation and functions independently of caveolae. The knockdown of endogenous p63RhoGEF significantly reduced the mitogenic response of ANG II, abolished ANG II-induced stress fiber formation and cell elongation in 2 D culture, and impaired the ANG II-driven contraction in a collagen-based 3-D model. In conclusion, our data provide for the first time evidence that p63RhoGEF is an important mediator of ANG II-dependent RhoA activation in RASMCs and therewith a leading actor in the subsequently triggered cellular processes, such as proliferation and contraction. PMID- 20739614 TI - Acquired von Willebrand syndrome in patients with an axial flow left ventricular assist device. AB - BACKGROUND: Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy. METHODS AND RESULTS: Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified. CONCLUSIONS: A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device. PMID- 20739615 TI - The development of aortic insufficiency in left ventricular assist device supported patients. AB - BACKGROUND: Aortic insufficiency (AI) following left ventricular assist device (LVAD) placement can affect device performance. The aim of this study was to examine AI development following LVAD implantation. METHODS AND RESULTS: Echocardiograms (n=315) from 78 subjects undergoing HeartMate-XVE (n=25 [32%]) or HeartMate-II (n=53 [68%]) implantations from 2004 to 2008 were reviewed. Studies were obtained preoperatively and at 1, 3, 6, 12, 18, and 24 months after surgery. AI was graded on an interval scale (0=none, 0.5=trivial, 1=mild, 1.5=mild moderate, 2=moderate, 2.5=moderate-severe, 3=severe), and the change in AI at follow-up was analyzed with significance tests. Kaplan-Meier estimates for freedom from moderate or worse AI at follow-up were generated. Mixed-model linear regression was used to identify correlates of AI progression during LVAD support. The median (25th, 75th percentile) duration of LVAD support was 239 (112, 455) days, and preoperative AI grade was 0.0 (0.0, 0.0). At 6 months, 89+/-4% of subjects (n=49 at risk) were free from moderate or worse AI, but this was reduced to 74+/-7% (n=29 at risk) and 49+/-13% (n=13 at risk) by 12 and 18 months, respectively. Correlates (slope+/-SE) of AI progression included female sex (0.002+/-0.001; P=0.01), smaller body surface area (-0.003+/-0.001 per m(2); P=0.0017), and HeartMate-II model type (0.002+/-0.001; P=0.039). Correlates (beta+/-SE) of progressive AI on postoperative echocardiogram included increasing aortic sinus diameter (0.04+/-0.01 per mm; P=0.001), an aortic valve that remained closed (0.42+/-0.06; P<0.001) or only intermittently opened (0.34+/ 0.09; P<0.001), and lower left ventricular diastolic (-0.002+/-0.0004 per cm(3); P<0.001) and systolic (-0.002+/-0.0004 per cm(3); P<0.001) volumes. CONCLUSIONS: AI progresses over time in LVAD-supported patients. As we move toward an era of long-term cardiac support, more studies are needed to determine the clinical significance of these findings. PMID- 20739616 TI - Technical Advance: Function and efficacy of an {alpha}4-integrin antagonist using bioluminescence imaging to detect leukocyte trafficking in murine experimental colitis. AB - Leukocyte trafficking is a therapeutic target in IBD. The integrins alpha4beta and alpha4beta1 regulate leukocyte migration into tissues and lymphoid organs. Current strategies rely on biologics, such as mAb, to inhibit leukocyte recruitment. Here we show the in vivo therapeutic effects of a small molecule alpha4-integrin antagonist (GSK223618A) in a leukocyte-trafficking model and a murine model of colitis. Leukocytes isolated from MLNs of transgenic beta-actin luc+ mice were injected i.v. into recipients with DSS-induced colitis. Recipient mice were orally gavaged with vehicle or an alpha4-integrin antagonist 1 h pre adoptive transfer, followed by bioluminescence whole body and ex vivo organ imaging 4 h post-transfer. To confirm its therapeutic effect, the alpha4-integrin antagonist was given orally twice daily for 6 days to mice with DSS-induced colitis, starting on Day 3. Clinical, macroscopic, and histological signs of inflammation were assessed and gene-expression profiles analyzed. Using bioluminescence imaging, we tracked and quantified leukocyte migration to the inflamed gut and demonstrated its inhibition by a small molecule alpha4-integrin antagonist. Additionally, the therapeutic effect of the antagonist was confirmed in DSS-induced colitis in terms of clinical, macroscopic, and histological signs of inflammation. Gene expression analysis suggested enhancement of tissue healing in compound-treated animals. Inhibition of leukocyte trafficking using small molecule integrin antagonists is a promising alternative to large molecule biologics. Furthermore, in vivo bioluminescence imaging is a valuable strategy for preclinical evaluation of potential therapeutics that target leukocyte trafficking in inflammatory diseases. PMID- 20739617 TI - PD-L1(hi) retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells. AB - We previously reported that after exposure to inflammatory cytokines, such as IL 17 and IFN-gamma, RPE cells express increased amounts of suppressor of cytokine signaling, leading to general suppression of the inflammatory response. Here, we demonstrate that RPE cells expressed increased levels of PD-L1 in response to IL 17, IFN-gamma, or Poly I:C. These PD-L1(hi) RPE cells inhibited the pathogenic activities of IRBP-specific T cells, which usually induced uveitis when injected into naive mice (EAU). The suppressed pathogenicity of these uveitogenic T cells after exposure to PD-L1(hi) RPE cells could be partially reversed by anti-PD-L1 antibodies. Nevertheless, IRBP-specific T cells pre-exposed to PD-L1(hi) RPE cells displayed substantial suppressor activity, which strongly inhibited the activation of fresh IRBP-Teffs in response to subsequent antigenic challenge and when transferred into naive mice, inhibited the induction of EAU by IRBP-Teff transfer. These findings suggest that inflammatory cytokine-triggered up regulation of PD-L1 on RPE constitutes a critical factor for inducing infiltrated uveitogenic T cells with regulatory activities, which may accelerate the natural resolution of T cell-mediated intraocular inflammation. PMID- 20739619 TI - Small conductance Ca2+-activated K+ channels regulate firing properties and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus. AB - Small conductance Ca(2+)-activated K(+) channels (SK) regulate action potential (AP) firing properties and excitability in many central neurons. However, the functional roles of SK channels of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal days 7-9. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. With the use of whole cell current clamp, single APs and spike trains of different frequencies were evoked by current injections. We found that 1) PCMNs have two different firing patterns: the majority of PCMNs (90%) exhibited spike frequency adaptation (SFA) and the rest (10%) showed less or no adaptation; 2) application of the specific SK channel blocker apamin significantly increased spike half width in single APs and trains and reduced the spike frequency-dependent AP broadening in trains; 3) SK channel blockade suppressed afterhyperpolarization (AHP) amplitude following single APs and trains and abolished spike-frequency dependence of AHP in trains; and 4) SK channel blockade increased the spike frequency but did not alter the pattern of SFA. Using whole cell voltage clamp, we measured outward currents and afterhyperpolarization current (I(AHP)). SK channel blockade revealed that SK-mediated outward currents had both transient and persistent components. After bath application of apamin and Ca(2+)-free solution, we found that apamin-sensitive and Ca(2+)-sensitive I(AHP) were comparable, confirming that SK channels may contribute to a major portion of Ca(2+)-activated K(+) channel-mediated I(AHP). These results suggest that PCMNs have SK channels that significantly regulate AP repolarization, AHP, and spike frequency but do not affect SFA. We conclude that activation of SK channels underlies one of the mechanisms for negative control of PCMN excitability. PMID- 20739620 TI - Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue. AB - Fatty acid reesterification in adipose tissue is dependent on the generation of glycerol 3-phosphate, and, at least in rodent adipose tissue, this appears to occur primarily through glyceroneogenesis. A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4). PDK4 is induced in white adipose tissue by thiazolidinediones (TZDs) and the inhibition or knockdown of PDK4 inhibits TZD induced increases in glyceroneogenesis. Since TZDs have many unwanted side effects, we were interested in identifying alternative mechanisms that could regulate PDK4 mRNA expression in white adipose tissue. In this regard we hypothesized that exercise, fasting, and epinephrine would increase PDK4 mRNA levels in rat epididymal adipose tissue. We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5'-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue. Exercise, fasting, and in or ex vivo epinephrine treatment increased PDK4 mRNA levels. These perturbations did not increase the expression of PDK1, -2, or 3. Pyruvate dehydrogenase phosphorylation was increased after an overnight fast and 4 h after the cessation of exercise. In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels. The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine induced increases in lipolysis. Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression. The inhibition of peroxisome proliferator activated receptor-gamma (PPARgamma) also attenuated the induction of PDK4. Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARgamma could be involved in this pathway. PMID- 20739621 TI - Imaging signal transduction during phagocytosis: phospholipids, surface charge, and electrostatic interactions. AB - Together with the development of genetically encoded fluorescent probes, digital imaging has provided great impetus to the study of cell signaling by providing enhanced sensitivity and much-improved spatial and temporal resolution. We have used phagocytosis as a paradigm of signal transduction, taking advantage of the generous size of phagosomes and of their comparatively leisurely rate of formation. Aided by the design of specific probes, we demonstrated a highly localized and elegantly choreographed sequence of changes in the level of several phosphoinositides and were able to also monitor the fate of phosphatidylserine. The net changes in the content of these anionic phospholipids are accompanied by marked alterations in the surface charge of the membrane of nascent phagosomes. These, in turn, cause the relocation of proteins that associate with the membrane by electrostatic interactions. Our studies suggest that anionic lipids control protein targeting not only through stereospecific recognition by specialized domains but also by electrostatic association mediated by polycationic motifs. The "electrostatic switch" can be turned on or off by altering the charge of the protein ligand (e.g., by phosphorylation) or, alternatively, by modifying the lipid composition of the target membrane. PMID- 20739622 TI - Rapid downregulation of the rat glutamine transporter SNAT3 by a caveolin dependent trafficking mechanism in Xenopus laevis oocytes. AB - The glutamine transporter SNAT3 is involved in the uptake and release of glutamine in the brain, liver, and kidney. Substrate transport is accompanied by Na(+) cotransport and H(+) antiport. In this study, treatment of Xenopus laevis oocytes expressing rat SNAT3 with the phorbol ester PMA resulted in a rapid downregulation of glutamine uptake in less than 20 min. PMA treatment of oocytes coexpressing SNAT3 and the monocarboxylate transporter MCT1 reduced SNAT3 activity only, demonstrating the specificity of the regulatory mechanism. Single or combined mutations of seven putative phosphorylation sites in the SNAT3 sequence did not affect the regulation of SNAT3 by PMA. Expression of an EGFP SNAT3 fusion protein in oocytes established that the downregulation was caused by the retrieval of the transporter from the plasma membrane. Coexpression of SNAT3 with dominant-negative mutants of dynamin or caveolin revealed that SNAT3 trafficking occurs in a dynamin-independent manner and is influenced by caveolin. Although system N activity was not affected by PMA in cultured astrocytes, a downregulation was observed in HepG2 cells. PMID- 20739623 TI - Regulation of serum response factor activity and smooth muscle cell apoptosis by chromodomain helicase DNA-binding protein 8. AB - Serum response factor (SRF) is a widely expressed protein that plays a key role in the regulation of smooth muscle differentiation, proliferation, migration, and apoptosis. It is generally accepted that one mechanism by which SRF regulates these diverse functions is through pathway-specific cofactor interactions. A novel SRF cofactor, chromodomain helicase DNA binding protein 8 (CHD8), was isolated from a yeast two-hybrid screen using SRF as bait. CHD8 is highly expressed in adult smooth muscle tissues. Coimmunoprecipitation assays from A10 smooth muscle cells demonstrated binding of endogenous SRF and CHD8. Data from GST-pulldown assays indicate that the NH(2)-terminus of CHD8 can interact directly with the MADS domain of SRF. Adenoviral-mediated knockdown of CHD8 in smooth muscle cells resulted in attenuated expression of SRF-dependent, smooth muscle-specific genes. Knockdown of CHD8, SRF, or CTCF, a previously described binding partner of CHD8, in A10 VSMCs also resulted in a marked induction of apoptosis. Mechanistically, apoptosis induced by CHD8 knockdown was accompanied by attenuated expression of the anti-apoptotic proteins, Birc5, and CARD10, whereas SRF knockdown attenuated expression of CARD10 and Mcl-1, but not Birc5, and CTCF knockdown attenuated expression of Birc5. These data suggest that CHD8 plays a dual role in smooth muscle cells modulating SRF activity toward differentiation genes and promoting cell survival through interactions with both SRF and CTCF to regulate expression of Birc5 and CARD10. PMID- 20739624 TI - Functional NMDA receptors with atypical properties are expressed in podocytes. AB - N-methyl-D-aspartate (NMDA) receptors are essential for normal nervous system function, but their excessive activation can lead to neuronal degeneration. NMDA receptors are also expressed in peripheral tissues, where their properties and significance are not well understood. Here we show that functional NMDA receptors are expressed in podocytes, polarized cells that form an essential component of the glomerular filtration apparatus. Application of NMDA to podocyte cell lines or primary cultures of mouse podocytes evoked macroscopic currents mediated by cation channels, with significant permeability to Ca2(+). Podocyte NMDA receptors do not desensitize with prolonged exposure to NMDA. They are blocked by supraphysiological concentrations of external or internal Mg2(+) and, also, by the prototype antagonists MK-801 and D-2-aminophosphonovaleric acid. NMDA responses in podocytes were strongly potentiated by D-serine, but not by glycine, even at high concentrations. D-Aspartate and L-homocysteate are effective agonists of podocyte NMDA receptors. Surprisingly, L-glutamate and L-aspartate did not evoke robust ionic currents in podocytes, regardless of the concentration or membrane potential at which these amino acids were tested. NMDA application for 2 h caused activation of secondary signals through Erk and Akt pathways and, at higher concentrations, caused activation of RhoA. Exposure to NMDA for 6 h did not cause loss of cultured podocytes but did lead to a reduction in nephrin expression. NMDA receptors that respond to circulating ligands may play a role in regulation of glomerular function or dysfunction, but they are unlikely to be components of a local glutamate signaling system in glomeruli. PMID- 20739626 TI - Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern. AB - The beneficial effects of caloric restriction in increasing longevity and forestalling age-related diseases are well known. Dietary restriction of methionine also renders similar benefits. We recently showed in a renal epithelial cell culture system that reduction of culture medium methionine by 80% resulted in altered tight junctional (TJ) claudin composition and also improved epithelial barrier function (51). In the current study, we examined the effect of dietary restriction of methionine on TJ barrier function in rat gastrointestinal tissue to see whether this phenomenon also holds true in a tissue model and for a different epithelial cell type. After 28 days on methionine-restricted (MR) diet, rats showed small but significant reductions in the plasma and (intracellular) colonocyte levels of methionine. Colon mucosal sheets from rats on the MR diet showed increased transepithelial electrical resistance with concomitant decrease in paracellular diffusion of (14)C-D-mannitol, suggesting improved barrier function relative to rats on control diet. This improved barrier function could not be explained by changes in colon crypt length or frequency. Neither was the colonocyte mitotic index nor the apoptotic frequency altered significantly. However, TJ composition/structure was being altered by the MR diet. RT-PCR and Western blot analysis showed an increase in the abundance of claudin-3 and an apparent change in the posttranslational modification of occludin, data reinforcing a paracellular barrier alteration. Overall, our data suggest that reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition. PMID- 20739625 TI - Orai1 interacts with STIM1 and mediates capacitative Ca2+ entry in mouse pulmonary arterial smooth muscle cells. AB - Previous studies in mouse pulmonary arterial smooth muscle cells (PASMCs) showed that cannonical transient receptor potential channel TRPC1 and stromal interaction molecule 1 (STIM1) mediate the sustained component of capacitative Ca(2+) entry (CCE), but the molecular candidate(s) that mediate the transient component of CCE remain unknown. The aim of the present study was to examine whether Orai1 mediates the transient component of CCE through activation of STIM1 in mouse PASMCs. In primary cultured mouse PASMCs loaded with fura-2, cyclopiazonic acid (CPA) caused a transient followed by a sustained rise in intracellular Ca(2+) concentration ([Ca(2+)](i)). The transient but not the sustained rise in [Ca(2+)](i) was partially inhibited by nifedipine. The nifedipine-insensitive transient rise in [Ca(2+)](i) and the increase in Mn(2+) quench of fura-2 fluorescence caused by CPA were both reduced in cells treated with Orai1 siRNA. These responses to CPA were further reduced in cells treated with Orai1 and STIM1 small interfering (si)RNA. Moreover, overexpression of STIM1 enhanced the rise in [Ca(2+)](i) and the increase in Mn(2+) quench of fura-2 fluorescence caused by CPA, and these responses were reduced in cells treated with Orai1 siRNA. RT-PCR revealed Orai1 and STIM1 mRNAs, and Western blot analysis identified Orai1 and STIM1 proteins in mouse PASMCs. Furthermore, Orai1 was found to coimmunoprecipitate with STIM1, and the precipitation level of Orai1 was increased in cells subjected to store-depletion. Immunostaining revealed colocalization of Orai1 and STIM1 proteins, and the colocalization of these proteins was more apparent after store-depletion. These data provide direct evidence that the transient component of CCE is mediated by Orai1 channel as a result of STIM1 activation in mouse PASMCs. PMID- 20739627 TI - Nicotinic receptor signaling in nonexcitable epithelial cells: paradigm shifting from ion current to kinase cascade. Focus on "Upregulation of nuclear factor kappaB expression by SLURP-1 is mediated by alpha7-nicotinic acetylcholine receptor and involves both ionic events and activation of protein kinases". PMID- 20739628 TI - Transmembrane helices 1 and 6 of the human breast cancer resistance protein (BCRP/ABCG2): identification of polar residues important for drug transport. AB - The human breast cancer resistance protein (BCRP/ABCG2) mediates efflux of drugs and xenobiotics. In this study, we investigated the role of polar residues within or near the predicted transmembrane alpha-helices 1 and 6 of BCRP in drug transport. We substituted Asn(387), Gln(398), Asn(629), and Thr(642) with Ala, Thr(402) with Ala and Arg, and Tyr(645) with Phe, and the mutants were stably expressed in human embryonic kidney-293 or Flp-In-293 cells. Immunoblotting and confocal microscopy analysis revealed that all of the mutants were well expressed and predominantly targeted to the plasma membrane. While T402A and T402R showed a significant global reduction in the efflux of mitoxantrone, Hoechst 33342, and BODIPY-prazosin, N629A exhibited significantly increased efflux activities for all of the substrates. N387A and Q398A displayed significantly impaired efflux for mitoxantrone and Hoechst 33342, but not for BODIPY-prazosin. In contrast, T642A and Y645F showed a moderate reduction in Hoechst 33342 efflux only. Drug resistance profiles of human embryonic kidney-293 cells expressing the mutants generally correlated with the efflux data. Furthermore, N629A was associated with a marked increase, and N387A and T402A with a significant reduction, in BCRP ATPase activity. Mutations of some of the polar residues may cause conformational changes, as manifested by the altered binding of the 5D3 antibody to BCRP in the presence of prazosin. The inward-facing homology model of BCRP indicated that Thr(402) within transmembrane 1 may be important for helical interactions, and Asn(629) may be involved in BCRP-substrate interaction. In conclusion, we have demonstrated the functional importance of some of these polar residues in BCRP activity. PMID- 20739629 TI - Reproductive factors, hormone use, and risk for lung cancer in postmenopausal women, the Nurses' Health Study. AB - BACKGROUND: There is increasing evidence suggesting that female hormones may play a significant role in lung cancer development. We evaluated the associations between reproductive factors, exogenous hormone use, and lung cancer incidence in the Nurses' Health Study. METHODS: We assessed age at menopause, age at menarche, type of menopause, parity, age at first birth, postmenopausal hormone (PMH) use, and past oral contraceptive use in 107,171 postmenopausal women. Cox models were used to estimate the hazard ratios for each exposure, adjusting for smoking and other covariates. RESULTS: We identified 1,729 lung cancer cases during follow-up from 1984 to 2006. Menopause onset before 44 years of age (hazard ratio, 1.39; 95% confidence interval, 1.14-1.70) and past oral contraceptive use for >5 years (hazard ratio, 1.22; 95% confidence interval, 1.05-1.42) were associated with increased lung cancer risk. These associations were strongest in current smokers and small cell histology. In never smokers, increased parity was associated with decreased risk among parous women (P trend = 0.03), whereas in current smokers, older age at first birth was associated with increased risk (P trend = 0.02). PMH use was not associated with overall lung cancer incidence. However, nonsignificant results of increased risk in adenocarcinoma were seen with current PMH use. CONCLUSIONS: Our findings suggest female hormones may influence lung carcinogenesis, although the effect is likely modest, varied by histologic subtype, and altered by smoking. IMPACT: Further investigation of the pathophysiology of female hormones in lung cancer subtypes and their interaction with smoking will lead to better understanding of lung carcinogenesis. PMID- 20739630 TI - Identification of adults with developmental language impairments. AB - PURPOSE: To assess the utility of a wide range of language measures (phonology, morphology, syntax, and semantics) for the identification of adults with developmental language impairment. METHOD: Measures were administered to 3 groups of adults, each representing a population expected to demonstrate high levels of language impairment, and to matched control groups. RESULTS: Three measures were the strongest contributors to identification of language impairment in the 3 groups of adults. These measures, combined, maximized identification of members of the clinical groups as having impaired language (sensitivity) and members of the control groups as having typical language (specificity). CONCLUSION: This suggests that a relatively brief battery could have utility for identifying developmental language impairment during the adult years. PMID- 20739631 TI - Establishing validity of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). AB - PURPOSE: The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) was developed to provide a protocol and form for clinicians to use when assessing the voice quality of adults with voice disorders (Kempster, Gerratt, Verdolini Abbott, Barkmeier-Kramer, & Hillman, 2009). This study examined the reliability and the empirical validity of the CAPE-V when used by experienced voice clinicians judging normal and disordered voices. METHOD: The validity of the CAPE V was examined in 2 ways. First, we compared judgments made by 21 raters of 22 normal and 37 disordered voices using the CAPE-V and the GRBAS (grade, roughness, breathiness, asthenia, strain; see Hirano, 1981) scales. Second, we compared our raters' judgments of overall severity to a priori consensus judgments of severity for the 59 voices. RESULTS: Intrarater reliability coefficients for the CAPE-V ranged from .82 for breathiness to .35 for strain; interrater reliability ranged from .76 for overall severity to .28 for pitch. CONCLUSIONS: Although both CAPE-V and GRBAS reliability coefficients varied across raters and parameters, this study reports slightly improved rater reliability using the CAPE-V to make perceptual judgments of voice quality in comparison to the GRBAS scale. The results provide evidence for the empirical (concurrent) validity of the CAPE-V. PMID- 20739632 TI - Interventions targeting attention in young children with autism. AB - PURPOSE: The ability to focus and sustain one's attention is critical for learning. Children with autism demonstrate unusual characteristics of attention from infancy. It is reasonable to assume that early anomalies in attention influence a child's developmental trajectories. Therapeutic interventions for autism often focus on core features of autism such as communication and socialization, while very few interventions specifically address attention. The purpose of this article is to provide clinicians a description of attention characteristics in children with autism and discuss interventions thought to improve attention. METHOD: Characteristics of attention in children with autism are presented. Intervention studies featuring measures of attention as an outcome variable for young children with autism are reviewed to present interventions that have empirical evidence for improvements in attention. Results are synthesized by strategy, specific feature of attention targeted, and results for both habilitative goals and accommodations for attention. CONCLUSION: Although research is not extensive, several strategies to support attention in young children with autism have been investigated. The empirical findings regarding these strategies can inform evidence-based practice. PMID- 20739633 TI - Script training treatment for adults with apraxia of speech. AB - PURPOSE: Outcomes of script training for individuals with apraxia of speech (AOS) and mild anomic aphasia were investigated. Script training is a functional treatment that has been successful for individuals with aphasia but has not been applied to individuals with AOS. Principles of motor learning were incorporated into training to promote long-term retention of scripts. METHOD: Three individuals with AOS completed script training. A multiple-baseline, across behaviors design examined acquisition of client-selected scripts. Errors and speaking rates were also analyzed. Random practice and delayed feedback were incorporated into training to promote motor learning. Probes for long-term retention were elicited up to 6 months after treatment. RESULTS: All clients successfully acquired their scripts, and probes demonstrated script retention 6 months after treatment. Errors generally decreased but remained variable even during maintenance and retention probes. Speaking rate increased for 2 clients but also remained variable. CONCLUSIONS: Script training was successful and functional for clients with AOS. Clients reported increased confidence, speaking ease, and speech naturalness. Although scripts did not become errorless, clients retained their scripts and reported using them frequently. Whether principles of motor learning may have promoted the long-term retention of scripts exhibited by participants must be determined through future research. PMID- 20739634 TI - Bar codes may have poorer error rates than commonly believed. PMID- 20739635 TI - Peptide lost and found: internal standards and the mass spectrometric quantification of peptides. PMID- 20739636 TI - The relationship between cholesteryl ester transfer protein and cardiovascular risk. PMID- 20739637 TI - Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders. AB - BACKGROUND: Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility. METHODS: We developed a competitive (c)-ELISA and an immunocapture TOF mass-spectrometry (IC-TOF-MS) assay. Exploiting these 2 methods and our previously described weak cation exchange (WCX)-TOF-MS assay, we measured serum hepcidin concentrations in 186 patients with various disorders of iron metabolism and in 23 healthy controls. RESULTS: We found that (a) the relative differences in median hepcidin concentrations in various diseases to be similar, although the absolute concentrations measured with c-ELISA and WCX-TOF-MS differed; (b) hepcidin isoforms contributed to differences in hepcidin concentrations between methods, which were most prominent in patients with chronic kidney disease; and (c) hepcidin concentrations measured by both the c-ELISA and IC-TOF-MS correlated with ferritin concentrations <60 MUg/L, and were suitable for distinguishing between iron deficiency anemia (IDA) and the combination of IDA and anemia of chronic disease. CONCLUSIONS: c-ELISA is the method of choice for the large-scale quantification of serum hepcidin concentrations, because of its low limit of detection, low cost, and high-throughput. Because of its specificity for bioactive hepcidin-25, WCX-TOF-MS can be regarded as a valuable special-purpose assay for disorders with variable concentrations of hepcidin isoforms, such as chronic kidney disease. PMID- 20739638 TI - Plasma renin activity by LC-MS/MS: development of a prototypical clinical assay reveals a subpopulation of human plasma samples with substantial peptidase activity. AB - BACKGROUND: For management and treatment of secondary hypertension, plasma renin activity (PRA) assay is considered an essential diagnostic tool. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based approach to PRA offering improvements in laboratory workflow and throughput. During development, we observed a substantial number of clinical samples that have strong degradation activity toward angiotensin (Ang) I during generation. A preliminary characterization of this degradation activity was performed, and we provide here a method by which this degradation can be monitored via the addition of an isotope-labeled degradation standard. METHODS: Automated online sample extraction coupled with HPLC was used to isolate Ang I and internal standard from plasma. The effluent from the analytical column was directed to a triple quadrupole MS operated in selected reaction monitoring mode, monitoring the a(5) and b(5) product ions from the [M+3H](+3) precursors. Routine analysis could be achieved with as little as 150 MUL plasma. RESULTS: We identified both C-terminal and N terminal degradation products of Ang I using isotope-labeled peptides as controls and substrates. In 2%-5% of patient samples, the degradation essentially eliminated any Ang I produced during generation. CONCLUSIONS: Our method requires reduced sample handling when compared with an RIA and eliminates the need for extended generation times for samples with low renin activity. Degradation of Ang I during generation appears to be a confounding variable in the interpretation of results from some clinical samples. Samples with profound degradation activity can be identified using a degradation standard that is added at the start of generation. PMID- 20739639 TI - Metabolism of vabicaserin in mice, rats, dogs, monkeys, and humans. AB - Vabicaserin is a potent 5-hydroxytryptamine(2C) agonist that is currently being developed for the treatment of the psychotic symptoms of schizophrenia. In this study, in vitro and in vivo metabolism of vabicaserin was evaluated in mice, rats, dogs, monkeys, and humans, and the structures of the metabolites were characterized by liquid chromatography/mass spectrometry and NMR spectroscopy. Vabicaserin underwent three major metabolic pathways in vitro: NADPH-dependent hydroxylation, NADPH-independent imine formation, and carbamoyl glucuronidation. After a single oral dose, vabicaserin was extensively metabolized in animals and humans, and its metabolites were mainly excreted via the urine in mice and rats. Along with the metabolites observed in vitro, secondary metabolism via oxidation and conjugation of the primary metabolites generated from the above-mentioned three pathways yielded a number of additional metabolites in vivo. Carbamoyl glucuronidation was the major metabolic pathway in humans but a minor pathway in rats. Although carbamoyl glucuronidation was a major metabolic pathway in mice, dogs, and monkeys, oxidative metabolism was also extensive in these species. Hydroxylation occurred in all species, although different regional selectivity was apparent. The imine pathway also appeared to be common to several species, because vabicaserin imine was observed in humans and hydroxyl imine metabolites were observed in mice, rats, and dogs. A nitrone metabolite of vabicaserin was observed in dogs and humans but not in other species. In conclusion, the major metabolic pathways for vabicaserin in humans and nonclinical safety species include carbamoyl glucuronidation, hydroxylation, formation of an imine, and a nitrone. PMID- 20739641 TI - Biomarkers of PD progression: is CSF the answer? PMID- 20739640 TI - Involvement and mechanism of DGAT2 upregulation in the pathogenesis of alcoholic fatty liver disease. AB - The mechanisms involved in the development of alcoholic liver disease (ALD) are not well established. We investigated the involvement of acyl-CoA: diacylglycerol acyltransferase 2 (DGAT2) upregulation in mediating hepatic fat accumulation induced by chronic alcohol consumption. Chronic alcohol feeding caused fatty liver and increased hepatic DGAT2 gene and protein expression, concomitant with a significant suppression of hepatic MAPK/ERK kinase/extracellular regulated kinase 1/2 (MEK/ERK1/2) activation. In vitro studies demonstrated that specific inhibitors of the MEK/ERK1/2 pathway increased DGAT2 gene expression and triglyceride (TG) contents in HepG2 cells, whereas epidermal growth factor, a strong ERK1/2 activator, had the opposite effect. Moreover, chronic alcohol feeding decreased hepatic S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio, an indicator of disrupted transmethylation reactions. Mechanistic investigations revealed that N-acetyl-S-farnesyl-L-cysteine, a potent inhibitor of isoprenylcysteine carboxyl methyltransferase, suppressed ERK1/2 activation, followed by an enhanced DGAT2 expression and an elevated TG content in HepG2 cells. Lastly, we demonstrated that the beneficial effects of betaine supplementation in ALD were associated with improved SAM/SAH ratio, alleviated ERK1/2 inhibition, and attenuated DGAT2 upregulation. In conclusion, our data suggest that upregulation of DGAT2 plays an important role in the pathogenesis of ALD, and that abnormal methionine metabolism contributes, at least partially, to DGAT2 upregulation via suppression of MEK/ERK1/2 activation. PMID- 20739642 TI - Clinical applicability and the perfusion-diffusion mismatch theory: not yet a perfect match. PMID- 20739643 TI - Toward understanding cortical lesions in multiple sclerosis. PMID- 20739644 TI - Imaging distribution and frequency of cortical lesions in patients with multiple sclerosis. AB - BACKGROUND: The presence of cortical lesions (CLs) and their topographic distribution in the brains of patients with multiple sclerosis (MS) have been clearly shown by recent histopathologic studies. CLs can also be assessed in vivo, with less sensitivity, by using specific MRI sequences. MRI-based lesion probability maps (LPMs) may partially overcome this lack of sensitivity and provide unique information on the spatial distribution and frequency of CLs in MS. METHODS: A total of 149 patients with MS (103 relapsing-remitting [RR] and 46 primary progressive [PP]) underwent an MRI examination, which included the double inversion recovery (DIR) sequence for CL assessment. CL masks were then obtained for each patient and a cortical LPM (cLPM) was created for each MS subtype. RESULTS: CLs were mainly distributed in the frontal (RR = 51.8%; PP = 50.5%) and temporal (RR = 30.4%; PP = 35.5%) lobes, with a prominent involvement of the motor (RR = 37.8%; PP = 30.6%) and anterior cingulate (RR = 9.2%; PP = 10.6%) cortices. The extent of brain lobe affected by CLs was higher in RR than in PP patients. The frequency of CL occurrence was higher in PP than in RR patients. Both measurements, however, did not show differences between the 2 MS subtypes at voxel-wise analysis. CONCLUSIONS: Patients with RRMS and PPMS share more similarities than differences in terms of CL number, volume, topographic distribution, and frequency. The similarities between histopathologic data and the findings reported here suggest that DIR images can accurately illustrate the focal pathology occurring in the cortical regions of patients with MS, providing clinically relevant information. PMID- 20739645 TI - Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. AB - OBJECTIVE: To investigate the relation of diabetes to dementia, Alzheimer disease (AD), and vascular dementia (VaD), through analyses of incidence, mortality, and neuropathologic outcomes in a prospective population-based study of the oldest old. METHODS: The Vantaa 85+ study included 553 residents living in the city of Vantaa, Finland, and aged >=85 years on April 1, 1991. Survivors were reexamined in 1994, 1996, 1999, and 2001. Autopsies were performed in 291 persons who died during the follow-up (48% of total population). Diabetes was assessed according to self-report, medical record of physician-diagnosed diabetes, or use of antidiabetic medication. Macroscopic infarcts were identified from 1-cm coronal slices of cerebral hemispheres, 5-mm transverse brainstem slices, and sagittal cerebellum slices. Methenamine silver staining was used for beta-amyloid, methenamine silver-Bodian staining for neurofibrillary tangles, and modified Bielschowsky method for neuritic plaques. Cox proportional hazards and multiple logistic regression models were used to analyze the association of diabetes with dementia and neuropathology, respectively. RESULTS: Diabetes at baseline doubled the incidence of dementia, AD, and VaD, and increased mortality. Individuals with diabetes were less likely to have beta-amyloid (hazard ratio [HR] [95% confidence interval (CI)] was 0.48 [0.23-0.98]) and tangles (HR [95% CI] 0.72 [0.39-1.33]) but more likely to have cerebral infarcts (HR [95% CI] 1.88 [1.06-3.34]) after all adjustments. CONCLUSION: Elderly patients with diabetes develop more extensive vascular pathology, which alone or together with AD-type pathology (particularly in APOE epsilon4 carriers) results in increased dementia risk. PMID- 20739646 TI - Neurologic disease burden in treated HIV/AIDS predicts survival: a population based study. AB - BACKGROUND: Combination antiretroviral therapy (cART) has improved the survival of patients with HIV/AIDS but its impact remains uncertain on the changing prevalence and incidence of neurologic disorders with ensuing effects on mortality. METHODS: The prevalence and incidence of neurologic disorders were examined in patients receiving active care in a regional HIV care program from 1998 to 2008. The mortality hazard ratio (HR) was calculated by Cox proportional hazard models with adjustment for demographic and clinical variables. RESULTS: Of 1,651 HIV-infected patients assessed, 404 (24.5%) were identified as having one or more neurologic disorders, while 41% of AIDS-affected persons exhibited neurologic disease. Symptomatic distal sensory polyneuropathy (DSP, 10.0%) and HIV-associated neurocognitive disorder (HAND, 6.2%) represented the most prevalent disorders among 53 recognized neurologic disorders. Patients with at least one neurologic disorder exhibited higher mortality rates (17.6% vs 8.0%, p < 0.0001), particularly AIDS-related deaths (9.7% vs 3.2%, p < 0.0001), compared with those without neurologic disorders. The highest mortality HR was associated with opportunistic infections of CNS (HR 5.3, 95% confidence interval [CI] 2.5 11.2), followed by HAND (HR 3.1, 95% CI 1.8-5.3) and the presence of any neurologic disorder (HR 2.0, 95% CI 1.2-3.2). The risk of AIDS-related death with a neurologic disorder was increased by 13.3% per 100 cells/mm(3) decrement in blood CD4+ T-cell levels or by 39% per 10-fold increment in plasma viral load. CONCLUSIONS: The burden and type of HIV-related neurologic disease have evolved over the past decade and despite the availability of cART, neurologic disorders occur frequently and predict an increased risk of death. PMID- 20739647 TI - Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. AB - OBJECTIVE: There have been few treatment trials for psychogenic nonepileptic seizures (PNES). Some psychotherapies have been shown to improve PNES and comorbid symptom outcomes. We evaluated a pharmacologic intervention to test the hypothesis that sertraline would reduce PNES. METHODS: We conducted a pilot, double-blind, randomized, placebo-controlled trial in an academic medical hospital with epilepsy center outpatients. Subjects aged 18 to 65 years diagnosed with video-EEG-confirmed PNES were treated with flexible-dose sertraline or placebo over 12 weeks. Seizure calendars and symptom scales were charted prospectively. Secondary outcome measures included psychiatric symptom scales and psychosocial variables. RESULTS: Thirty-eight subjects enrolled, and 26 (68%) completed the trial. Thirty-three subjects with nonzero nonepileptic seizure rates at baseline were included in intent-to-treat analysis of the primary outcome. Subjects assigned to the sertraline arm experienced a 45% reduction in seizure rates from baseline to final visit (p = 0.03) vs an 8% increase in placebo (p = 0.78). Secondary outcome scales revealed no significant between group differences in change scores from baseline to final visit, after adjustment for differences at baseline. CONCLUSIONS: PNES were reduced in patients treated with a serotonin selective reuptake inhibitor, whereas those treated with placebo slightly increased. This study provides feasibility data for a larger-scale study. LEVEL OF EVIDENCE: This study provides Class II evidence that flexible dose sertraline up to a maximum dose of 200 mg is associated with a nonsignificant reduction in PNES rate compared with a placebo control arm (risk ratio 0.51, 95% confidence interval 0.25-1.05, p = 0.29), adjusting for differences at baseline. PMID- 20739648 TI - Insulin resistance, type 2 diabetes, and AD: cerebrovascular disease or neurodegeneration? PMID- 20739649 TI - Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. AB - OBJECTIVE: We examined the association between diabetes-related factors and pathology of Alzheimer disease (AD) to evaluate how diabetes affects the pathogenic process of AD. METHODS: This study included specimens from a series of 135 autopsies of residents of the town of Hisayama in Fukuoka prefecture (74 men and 61 women) performed between 1998 and 2003, who underwent a 75-g oral glucose tolerance test in clinical examinations in 1988. We measured diabetes-related factors including fasting glucose, 2-hour post-load plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 1988. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines and neurofibrillary tangles (NFTs) were assessed according to Braak stage. The associations between each factor and AD pathology were examined by analysis of covariance and logistic regression analyses. RESULTS: Higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were associated with increased risk for NPs after adjustment for age, sex, systolic blood pressure, total cholesterol, body mass index, habitual smoking, regular exercise, and cerebrovascular disease. However, there were no relationships between diabetes-related factors and NFTs. Regarding the effects of APOE genotype on the risk of AD pathology, the coexistence of hyperglycemia and APOE epsilon4 increased the risk for NP formation. A similar enhancement was observed for hyperinsulinemia and high HOMA-IR. CONCLUSION: The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon4. PMID- 20739650 TI - FDA increases focus on postmarketing studies. PMID- 20739651 TI - MicroRNAs as Onco-miRs, drivers of cancer. PMID- 20739652 TI - Early breast cancer: single dose of radiation during surgery gains support. PMID- 20739653 TI - Will the pediatric regimen work for adolescents with ALL? PMID- 20739654 TI - StatBite. FDA-required postmarketing studies, 1992-2008. PMID- 20739655 TI - Pharicin B stabilizes retinoic acid receptor-alpha and presents synergistic differentiation induction with ATRA in myeloid leukemic cells. AB - All-trans retinoic acid (ATRA), a natural ligand for the retinoic acid receptors (RARs), induces clinical remission in most acute promyelocytic leukemia (APL) patients through the induction of differentiation and/or eradication of leukemia initiating cells. Here, we identify a novel natural ent-kaurene diterpenoid derived from Isodon pharicus leaves, called pharicin B, that can rapidly stabilize RAR-alpha protein in various acute myeloid leukemic (AML) cell lines and primary leukemic cells from AML patients, even in the presence of ATRA, which is known to induce the loss of RAR-alpha protein. Pharicin B also enhances ATRA dependent the transcriptional activity of RAR-alpha protein in the promyelocytic leukemia-RARalpha-positive APL cell line NB4 cells. We also showed that pharicin B presents a synergistic or additive differentiation-enhancing effect when used in combination with ATRA in several AML cell lines and, especially, some primary leukemic cells from APL patients. In addition, pharicin B can overcome retinoid resistance in 2 of 3 NB4-derived ATRA-resistant subclones. These findings provide a good example for chemical biology-based investigations of pathophysiological and therapeutic significances of RAR-alpha and PML-RAR-alpha proteins. The effectiveness of the ATRA/pharicin B combination warrants further investigation on their use as a therapeutic strategy for AML patients. PMID- 20739656 TI - Prognosis of Binet stage A chronic lymphocytic leukemia patients: the strength of routine parameters. AB - Recent developments in the management of chronic lymphocytic leukemia (CLL) patients have made necessary the availability of dependable prognostic factors. We have developed a prognostic index derived from the multivariate analysis of 339 stage A patients at diagnosis, exhaustively studied for classical and recent predictive markers. Only 4 biologic parameters were found to be independent predictors of progression-free survival (PFS): serum thymidine kinase (sTK), lymphocytosis, beta2-microglobulin, and CD38 expression. Two groups were distinguishable: cases with no or 1 risk factor (among whom 85% did not progress after 7 years), and cases with 2 or more factors showing a median PFS of 20 months. Finally, we propose an easy, fast, cost-effective strategy for a trustworthy prognostication in stage A patients, who currently represent more than 80% of the CLL population, allowing physicians to adapt follow-up individually. PMID- 20739658 TI - Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin clearance phenotype with enhanced heme-iron recycling and antioxidant capacity. AB - Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb. PMID- 20739657 TI - The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. AB - The Ataxia Telangiectasia Mutated (ATM) gene is frequently inactivated in lymphoid malignancies such as chronic lymphocytic leukemia (CLL), T prolymphocytic leukemia (T-PLL), and mantle cell lymphoma (MCL) and is associated with defective apoptosis in response to alkylating agents and purine analogues. ATM mutant cells exhibit impaired DNA double strand break repair. Poly (ADP ribose) polymerase (PARP) inhibition that imposes the requirement for DNA double strand break repair should selectively sensitize ATM-deficient tumor cells to killing. We investigated in vitro sensitivity to the poly (ADP-ribose) polymerase inhibitor olaparib (AZD2281) of 5 ATM mutant lymphoblastoid cell lines (LCL), an ATM mutant MCL cell line, an ATM knockdown PGA CLL cell line, and 9 ATM-deficient primary CLLs induced to cycle and observed differential killing compared with ATM wildtype counterparts. Pharmacologic inhibition of ATM and ATM knockdown confirmed the effect was ATM-dependent and mediated through mitotic catastrophe independently of apoptosis. A nonobese diabetic/severe combined immunodeficient (NOD/SCID) murine xenograft model of an ATM mutant MCL cell line demonstrated significantly reduced tumor load and an increased survival of animals after olaparib treatment in vivo. Addition of olaparib sensitized ATM null tumor cells to DNA-damaging agents. We suggest that olaparib would be an appropriate agent for treating refractory ATM mutant lymphoid tumors. PMID- 20739659 TI - Tissue transglutaminase contributes to the all-trans-retinoic acid-induced differentiation syndrome phenotype in the NB4 model of acute promyelocytic leukemia. AB - Treatment of acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA) results in terminal differentiation of leukemic cells toward neutrophil granulocytes. Administration of ATRA leads to massive changes in gene expression, including down-regulation of cell proliferation-related genes and induction of genes involved in immune function. One of the most induced genes in APL NB4 cells is transglutaminase 2 (TG2). RNA interference-mediated stable silencing of TG2 in NB4 cells (TG2-KD NB4) coupled with whole genome microarray analysis revealed that TG2 is involved in the expression of a large number of ATRA-regulated genes. The affected genes participate in granulocyte functions, and their silencing lead to reduced adhesive, migratory, and phagocytic capacity of neutrophils and less superoxide production. The expression of genes related to cell-cycle control also changed, suggesting that TG2 regulates myeloid cell differentiation. CC chemokines CCL2, CCL3, CCL22, CCL24, and cytokines IL1B and IL8 involved in the development of differentiation syndrome are expressed at significantly lower level in TG2-KD NB4 than in wild-type NB4 cells upon ATRA treatment. Based on our results, we propose that reduced expression of TG2 in differentiating APL cells may suppress effector functions of neutrophil granulocytes and attenuate the ATRA induced inflammatory phenotype of differentiation syndrome. PMID- 20739660 TI - Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization. AB - Recently, we reported a novel system whereby human pericytes are recruited to endothelial cell (EC)-lined tubes in 3-dimensional (3D) extracellular matrices to stimulate vascular maturation including basement membrane matrix assembly. Through the use of this serum-free, defined system, we demonstrate that pericyte motility within 3D collagen matrices is dependent on the copresence of ECs. Using either soluble receptor traps consisting of the extracellular ligand-binding domains of platelet-derived growth factor receptor beta, epidermal growth factor receptor (EGFR), and ErbB4 receptors or blocking antibodies directed to platelet derived growth factor (PDGF)-BB, or heparin-binding EGF-like growth factor (HB EGF), we show that both of these EC-derived ligands are required to control pericyte motility, proliferation, and recruitment along the EC tube ablumenal surface. Blockade of pericyte recruitment causes a lack of basement membrane matrix deposition and, concomitantly, increased vessel widths. Combined inhibition of PDGF-BB and HB-EGF-induced signaling in quail embryos leads to reduced pericyte recruitment to EC tubes, decreased basement membrane matrix deposition, increased vessel widths, and vascular hemorrhage phenotypes in vivo, in support of our findings in vitro. In conclusion, we report a dual role for EC derived PDGF-BB and HB-EGF in controlling pericyte recruitment to EC-lined tubes during developmental vascularization events. PMID- 20739661 TI - Time-lapse cinematography-compatible polystyrene-based microwell culture system: a novel tool for tracking the development of individual bovine embryos. AB - We have developed a polystyrene-based well-of-the-well (WOW) system using injection molding to track individual embryos throughout culture using time-lapse cinematography (TLC). WOW culture of bovine embryos following in vitro fertilization was compared with conventional droplet culture (control). No differences between control- and WOW-cultured embryos were observed during development to the blastocyst stage. Morphological quality and inner cell mass (ICM) and trophectoderm (TE) cell numbers were not different between control- and WOW-derived blastocysts; however, apoptosis in both the ICM and TE cells was reduced in WOW culture (P < 0.01). Oxygen consumption in WOW-derived blastocysts was closer to physiological level than that of control-derived blastocysts. Moreover, WOW culture improved embryo viability, as indicated by increased pregnancy rates at Days 30 and 60 after embryo transfer (P < 0.05). TLC monitoring was performed to evaluate the cleavage pattern and the duration of the first cell cycle of embryos from oocytes collected by ovum pickup; correlations with success of pregnancy were determined. Logistic regression analysis indicated that the cleavage pattern correlated with success of pregnancy (P < 0.05), but cell cycle length did not. Higher pregnancy rates (66.7%) were observed for animals in which transferred blastocysts had undergone normal cleavage, identified by the presence of two blastomeres of the same size without fragmentation, than among those with abnormal cleavage (33.3%). These results suggest that our microwell culture system is a powerful tool for producing and selecting healthy embryos and for identifying viability biomarkers. PMID- 20739663 TI - A male-specific role for p38 mitogen-activated protein kinase in germ cell sex differentiation in mice. AB - Germ cell sex differentiation in the mouse embryo is denoted by meiosis entry in females and mitotic arrest in males. Because p38 mitogen-activated protein kinase (MAPK) signaling initiates mitotic arrest in other differentiating cell types, we investigated its potential role in XY germ cell differentiation in mice. We report that p38 MAPK is phosphorylated and therefore activated only in XY germ cells around the time of sex differentiation. Quantitative RT-PCR analysis showed that 14 known targets of p38 MAPK signaling are expressed in the embryonic gonads at this time and that five of these targets (Mapkapk5, Max, Myc, Hbp1, and Cebpa) have expression profiles similar to that of activated p38 MAPK. Inhibition of p38 MAPK signaling in XY germ cells ex vivo reduced expression of the pluripotency marker POU5F1 and increased the expression of Stra8 and SYCP3, premeiosis and meiosis markers, respectively, to levels approaching those observed in XX germ cells. These data suggest that p38 MAPK signaling antagonizes entry into meiosis in XY germ cells, instead directing them toward mitotic quiescence and a spermatogenic fate. PMID- 20739662 TI - Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep. AB - Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ~147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64-66, 87 90, and 139-140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep. PMID- 20739664 TI - GATA depletion impacts insulin-like growth factor 1 mRNA and protein levels in luteinizing porcine granulosa cells. AB - GATA4 and GATA6 are zinc-finger transcription factors that regulate specific genes involved in steroidogenesis. Using RNA interference (RNAi)-mediated reduction of GATA4 and/or GATA6 with microarray analysis, we aimed to identify novel GATA target genes in luteinizing porcine granulosa cells under vehicle- and cAMP-treated conditions. Microarray analysis identified IGF1 mRNA to be cAMP- and GATA-responsive, and real-time PCR demonstrated that the cAMP-induced increase in IGF1 mRNA was reduced under conditions of GATA6 depletion and GATA4 plus GATA6 depletion, but not GATA4 depletion. Insulin-like growth factor 1 protein levels in media were also decreased by GATA6 or GATA4 plus GATA6 reduction. IGFBP2 and IGFBP4 mRNAs were increased and IGFBP5 mRNA decreased with vehicle and cAMP treatment under GATA4 plus GATA6 RNAi conditions. GATA6 reduction alone increased basal IGFBP4 and decreased IGFBP5 with both vehicle and cAMP, and GATA4 reduction alone lowered cAMP IGFBP5 levels with cAMP. No changes in IGFBP3 mRNA were observed with GATA reduction relative to the control RNAi condition. Levels of insulin-like growth factor binding proteins 2-5 in media as assessed by Western ligand blotting were not altered by GATA reduction. Electromobility gel shift assays with two GATA-containing oligonucleotides of the IGF1 5'-regulatory region showed GATA4 and GATA6 could bind the more proximal GATA-B site. These studies indicate that although GATA4 and GATA6 can bind the porcine IGF1 5'-region, GATA6 is functionally most important for cAMP-stimulated mRNA levels. Using microarray analysis, we identified other mRNAs that were altered by GATA-reduced conditions, including ALDH1, DIO2, and EDNRB. Our findings further support GATA as a coordinator of endocrine/paracrine/autocrine signals in the ovary. PMID- 20739666 TI - HER1 signaling mediates extravillous trophoblast differentiation in humans. AB - This study examines the role of HER1 signaling in the differentiation of proliferative extravillous trophoblast (EVT) into invasive EVT. Using the JAR choriocarcinoma cell line and placental villous explants as experimental models and immunohistochemical assessment of protein markers of EVT differentiation (downregulation of HER1 and Cx40 and upregulation of HER2 and alpha1 integrin), we show that the ability of decidual conditioned medium (DCM) to induce HER1/2 switching was abrogated in the presence of the HER1 antagonist, AG1478. Similarly, epidermal growth factor (EGF) treatment resulted in the downregulation of HER1 and an upregulation of HER2 expression, whereas co-incubation of EGF with AG1478 inhibited this response. However, EGF did not downregulate Cx40 or induce migration of EVT. In contrast, heparin-binding epidermal-like growth factor (HBEGF) stimulated dose-dependent JAR cell migration, which was inhibited by both AG1478 and AG825 (HER2 antagonist). Western blot analysis of HER1 activation demonstrated that HBEGF-mediated phosphorylation of the HER1 Tyr992 and Tyr1068 sites, while EGF activated the Tyr1045 site. Moreover, HBEGF induced a stronger and more sustained activation of both the mitogen-activated protein kinase and phosphoinositol 3 kinase (PIK3) signaling pathways. Migration assays using a panel of signaling pathway inhibitors demonstrated that the HBEGF-mediated migration was dependent on the PIK3 pathway. These results demonstrate that HBEGF mediated HER1 signaling through PIK3 is an important component of EVT invasion. PMID- 20739665 TI - Current concepts of follicle-stimulating hormone receptor gene regulation. AB - Follicle-stimulating hormone (FSH), a pituitary glycoprotein hormone, is an integral component of the endocrine axis that regulates gonadal function and fertility. To transmit its signal, FSH must bind to its receptor (FSHR) located on Sertoli cells of the testis and granulosa cells of the ovary. Thus, both the magnitude and the target of hormone response are controlled by mechanisms that determine FSHR levels and cell-specific expression, which are supported by transcription of its gene. The present review examines the status of FSHR/Fshr gene regulation, emphasizing the importance of distal sequences in FSHR/Fshr transcription, new insights gained from the influx of genomics data and bioinformatics, and emerging trends that offer direction in deciphering the FSHR/Fshr regulatory landscape. PMID- 20739667 TI - BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice. AB - During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis. PMID- 20739668 TI - Gene expression in the fetal mouse ovary is altered by exposure to low doses of bisphenol A. AB - Evidence from experimental studies suggests that fetal exposure to the endocrine disrupting chemical bisphenol A (BPA) has adverse reproductive effects in both males and females. Studies from our laboratory suggest that exposure to the developing female fetus produces a unique, multigenerational effect. Specifically, maternal exposure affects the earliest stages of oogenesis in the developing fetal ovary, and the resulting subtle meiotic defects increase the likelihood that embryos produced by the exposed female in adulthood (i.e., the grandchildren) will be chromosomally abnormal. To understand the impact of BPA on the developing ovary, we conducted expression studies to characterize gene expression changes in the fetal ovary that result from BPA exposure. We first tested the validity of the approach, asking whether we could reliably detect temporal changes in expression levels of meiotic genes in controls. As anticipated, we were able to identify appropriate increases in expression in meiotic, but in few other, genes. Intriguingly, this analysis provided data on a small set of genes for which timing and expression changes suggest that they may have important and heretofore unrecognized meiotic roles. After verifying the utility of our approach, we focused our analysis on BPA-exposed animals. We found modest, but significant, changes in gene expression in the fetal ovaries from exposed fetuses. The first changes were evident within 24 h of exposure, and the most extensive changes correlated with the onset of meiosis. Furthermore, gene ontology analysis suggested that BPA acts to down-regulate mitotic cell-cycle genes, raising the possibility that fetal BPA exposure may act to limit expansion of the primordial germ cell population. PMID- 20739669 TI - Transformation-related protein 53 expression in the early mouse embryo compromises preimplantation embryonic development by preventing the formation of a proliferating inner cell mass. AB - The developmental viability of the preimplantation embryo requires the successful formation of a cluster of pluripotent stem cells called the inner cell mass. Development is variably compromised by a range of exogenous stressors (including their production by assisted reproductive technologies). Inbred C57BL/6 strain embryos are particularly susceptible to the stresses associated with embryo culture, whereas hybrid embryos are more resistant, and this is accounted for in part by the overexpression of transformation-related protein 53 in cultured inbred embryos compared with similarly treated hybrid embryos or embryos not subjected to culture. We show here that this loss of viability is a consequence of the Trp53-dependent reduction in the capacity of blastocysts to form a proliferating inner cell mass. Formation of the trophectodermal line was not adversely affected by these stresses. PMID- 20739671 TI - Thin-slicing divorce: thirty seconds of information predict changes in psychological adjustment over 90 days. PMID- 20739670 TI - Effect of decreasing intraluteal progesterone on sensitivity of the early porcine corpus luteum to the luteolytic actions of prostaglandin F2alpha. AB - Prostaglandin F2alpha (PGF) causes luteolysis of the pig corpus luteum (CL) only after Day 12 of the estrous cycle. Recent evidence indicates that progesterone (P4) may protect the CL from cell death. The present study tested the hypothesis that acute inhibition of P4 by treatment with epostane (EPO; 3betaHSD inhibitor) in CL lacking luteolytic capacity (Day 9 CL) will allow PGF to induce responses associated with luteolysis. Multiple PGF-induced responses were evaluated, including genes involved in production of PGF and estradiol-17beta, apoptosis (caspase 3), and transcription (FOSB). These responses are associated with PGF induced luteolysis and do not normally occur in CL lacking luteolytic capacity. Animals on Day 7 after estrus were divided into four groups: 1) control (C), 2) PGF, 3) EPO, and 4) PGF plus EPO (PGF+EPO). Treatment with EPO (10 mg/kg) or vehicle was given every 12 h for 36 h. Treatment with PGF (25 mg) or vehicle was given at 38 h, and CL were collected from all animals at 48 h. Some CL from each animal were frozen in liquid nitrogen for mRNA and protein analysis. Remaining CL were incubated in media for 2 h for determination of P4 and PGF production. EPO dramatically decreased production of P4 by luteal tissue (ng/mg tissue) by 90% and 95% in EPO and PGF+EPO groups, respectively, compared to C (P < 0.01). Low production of PGF by luteal tissue was found in C, PGF, and EPO groups; however, treatment with PGF+EPO dramatically increased (782%) luteal PGF production. Similar to intraluteal PGF production, increased mRNA for cyclooxygenase 2 (PTGS2) and phospholipase A2 (group IB; PLA2G1B) was found in the PGF+EPO, but not in the EPO or PGF, group. Aromatase (CYP19A1) mRNA was not induced by PGF or EPO; however, PGF+EPO caused a more than 40-fold increase in CYP19A1 mRNA (P < 0.01). CASP3 mRNA was increased (P < 0.01) by EPO (3.4-fold) and by PGF (2.7 fold) but was most dramatically increased by PGF+EPO (5.3-fold), whereas caspase activity was only increased by PGF (1.5-fold) or PGF+EPO (2.2-fold). Thus, these data support the hypothesis that elimination of the protective effect of intraluteal P4 does not directly cause luteolysis of the early CL but allows PGF to induce luteolytic responses in CL lacking luteolytic capacity. PMID- 20739672 TI - Explaining the effect of education on health: a field study in Ghana. AB - Higher education (or more years of formal schooling) is widely associated with better health, but the underlying causes of this association are unclear. In this study, we tested our schooling-decision-making model, which posits that formal education fosters intellectual ability, which in turn provides individuals with enduring competencies to support better health-related behaviors. Using data from a field study on formal education in 181 adults in rural Ghana, we examined health-protective behaviors related to HIV/AIDS infection, a critical health issue in Ghana. As expected, individuals with more education practiced more protective health behaviors. Our structural equation modeling analysis showed that cognitive abilities, numeracy, and decision-making abilities increased with exposure to schooling, and that these enhanced abilities (and not HIV/AIDS knowledge) mediated the effects of education on health-protective behavior. Research and policy implications for HIV prevention efforts in sub-Saharan Africa are discussed. PMID- 20739673 TI - Comparing gains and losses. AB - Loss aversion in choice is commonly assumed to arise from the anticipation that losses have a greater effect on feelings than gains, but evidence for this assumption in research on judged feelings is mixed. We argue that loss aversion is present in judged feelings when people compare gains and losses and assess them on a common scale. But many situations in which people judge and express their feelings lack these features. When judging their feelings about an outcome, people naturally consider a context of similar outcomes for comparison (e.g., they consider losses against other losses). This process permits gains and losses to be normed separately and produces psychological scale units that may not be the same in size or meaning for gains and losses. Our experiments show loss aversion in judged feelings for tasks that encourage gain-loss comparisons, but not tasks that discourage them, particularly those using bipolar scales. PMID- 20739674 TI - The outcast-lash-out effect in youth: alienation increases aggression following peer rejection. AB - Although there are good theoretical reasons to believe that youth who are high in alienation (i.e., estranged from society, significant others, and themselves) are prone to behave aggressively, empirical evidence is lacking. The present experiment tested whether alienation moderates the effects of acute peer rejection on aggression in youth. Participants (N = 121; mean age = 11.5 years) completed a personal profile (e.g., "How do you describe yourself?") that was allegedly evaluated online by a panel of peer judges. After randomly receiving negative or positive feedback from peer judges, participants were given the opportunity to aggress against them (i.e., by reducing their monetary reward and by posting negative comments about them online). As predicted, alienation increased participants' aggression against peers who had rejected them, but not against peers who had praised them, even after controlling for peer-nominated chronic rejection and peer-nominated aggression. Thus, alienated youth are more aggressive than others when they experience acute peer rejection. PMID- 20739675 TI - Unique requirements for reactivation of virus-specific memory B lymphocytes. AB - Memory B cells (MBCs) are rapidly activated upon Ag re-exposure in vivo, but the precise requirements for this process are still elusive. To address these requirements, T cell-independent reactivation of MBCs against virus-like particles was analyzed. As few as 25 MBCs are sufficient for a measurable Ab response after adoptive transfer. We found that MBCs were reactivated upon antigenic challenge to normal levels after depletion of macrophages, CD11c(+) dendritic cells, and matured follicular dendritic cells. Furthermore, MBC responses were possible in TNF/lymphotoxin alpha double-deficient mice after partial normalization of lymphoid architecture by means of long-term reconstitution with wild-type bone marrow. Activation did not occur when chimeric mice, which still lack all lymph nodes and Peyer's patches, were splenectomized prior to MBC transfer. Together with our finding that MBC responses are weak when Ag was administered within minutes after adoptive MBC transfer, these results strongly suggest that MBCs have to occupy specific niches within secondary lymphoid tissue to become fully Ag-responsive. We provide clear evidence that MBCs are not preferentially resident within the splenic marginal zones and show that impaired homing to lymphoid follicles resulted in significantly diminished activation, suggesting that reactivation of MBCs occurred inside lymphoid follicles. Furthermore, comparison of virus-specific MBC T cell-independent reactivation versus primary T cell-independent type II B cell activation revealed unique requirements of MBC activation. PMID- 20739676 TI - Notch1 deficiency results in decreased inflammation during wound healing and regulates vascular endothelial growth factor receptor-1 and inflammatory cytokine expression in macrophages. AB - We investigated whether Notch signaling plays a role in regulating macrophage responses to inflammation. In a wound healing assay, macrophage recruitment was decreased in Notch1(+/-) mice, and the wounds were characterized by decreased TNF alpha expression. As wound healing progressed, Notch1(+/-) wounds had increased vascularization and collagen deposition compared with wild-type wounds. In mice with myeloid-specific Notch1 deletion, wounds had decreased macrophage recruitment as well as decreased TNF-alpha expression, indicating the specific role of Notch1 in the inflammatory response in these cells. In vitro, we found that vascular endothelial growth factor receptor-1 (VEGFR-1) was upregulated in macrophages in response to LPS/IFN-gamma and that this upregulation depended on Notch signaling. Furthermore, macrophages from Notch1(+/-) mice had decreased expression of VEGFR-1 compared with macrophages from wild-type mice, whereas VEGFR-1 expression in Notch4(-/-) macrophages was normal. Inhibition of Notch signaling decreased induction of the inflammatory cytokines IL-6, IL-12, CXCL10, MCP-1, monokine induced by IFN-gamma, and TNF-alpha in macrophages in response to LPS/IFN-gamma. Additionally, macrophages from Notch1(+/-) mice demonstrated decreased induction of IL-6, IL-12, and TNF-alpha in response to stimulation compared with wild-type mice. Thus, both pharmacological inhibition of Notch and genetic analysis demonstrate that Notch1 regulates VEGFR-1 and cytokine expression in macrophages. We have also established that Notch1 is important for the inflammatory response during wound healing in mice. PMID- 20739677 TI - Late B cell depletion with a human anti-human CD20 IgG1kappa monoclonal antibody halts the development of experimental autoimmune encephalomyelitis in marmosets. AB - Depletion of CD20(+) B cells has been related to reduced clinical activity in relapsing-remitting multiple sclerosis. The underlying mechanism is not understood, because serum IgG levels were unaltered by the treatment. We report the effect of late B cell depletion on cellular and humoral immune mechanisms in a preclinical multiple sclerosis model (i.e., experimental autoimmune encephalomyelitis [EAE] in the common marmoset). We used a novel human anti-human CD20 IgG1kappa mAb (HuMab 7D8) that cross-reacts with marmoset CD20. EAE was induced in 14 marmosets by immunization with recombinant human myelin oligodendrocyte glycoprotein (MOG) in CFA. After 21 d, B cells were depleted in seven monkeys by HuMab 7D8, and seven control monkeys received PBS. The Ab induced profound and long-lasting B cell depletion from PBMCs and lymphoid organs throughout the observation period of 106 d. Whereas all of the control monkeys developed clinically evident EAE, overt neurologic deficits were reduced substantially in three HuMab 7D8-treated monkeys, and four HuMab 7D8-treated monkeys remained completely asymptomatic. The effect of HuMab 7D8 was confirmed on magnetic resonance images, detecting only small lesions in HuMab 7D8-treated monkeys. The infusion of HuMab 7D8 arrested the progressive increase of anti-MOG IgG Abs. Although CD3(+) T cell numbers in lymphoid organs were increased, their proliferation and cytokine production were impaired significantly. Most notable were the substantially reduced mRNA levels of IL-7 and proinflammatory cytokines (IL-6, IL-17A, IFN-gamma, and TNF-alpha). In conclusion, B cell depletion prevents the development of clinical and pathological signs of EAE, which is associated with impaired activation of MOG-reactive T cells in lymphoid organs. PMID- 20739678 TI - Advancing science, promoting peace. PMID- 20739680 TI - Recommendations for biomarker identification and qualification in clinical proteomics. AB - Clinical proteomics has yielded some early positive results-the identification of potential disease biomarkers-indicating the promise for this analytical approach to improve the current state of the art in clinical practice. However, the inability to verify some candidate molecules in subsequent studies has led to skepticism among many clinicians and regulatory bodies, and it has become evident that commonly encountered shortcomings in fundamental aspects of experimental design mainly during biomarker discovery must be addressed in order to provide robust data. In this Perspective, we assert that successful studies generally use suitable statistical approaches for biomarker definition and confirm results in independent test sets; in addition, we describe a brief set of practical and feasible recommendations that we have developed for investigators to properly identify and qualify proteomic biomarkers, which could also be used as reporting requirements. Such recommendations should help put proteomic biomarker discovery on the solid ground needed for turning the old promise into a new reality. PMID- 20739681 TI - A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. AB - Corneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage. PMID- 20739682 TI - Drug reaction with eosinophilia and systemic symptoms (DRESS): a multiorgan antiviral T cell response. AB - Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, drug induced reaction that involves both the skin and the viscera. Evidence for reactivation of herpes family viruses has been seen in some DRESS patients. To understand the immunological components of DRESS and their relationship to viral reactivation, we prospectively assessed 40 patients exhibiting DRESS in response to carbamazepine, allopurinol, or sulfamethoxazole. Peripheral blood T lymphocytes from the patients were evaluated for phenotype, cytokine secretion, and repertoire of CD4+ and CD8+ and for viral reactivation. We found Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), or HHV-7 reactivation in 76% of the patients. In all patients, circulating CD8+ T lymphocytes were activated, exhibited increased cutaneous homing markers, and secreted large amounts of tumor necrosis factor-alpha and interferon-gamma. The production of these cytokines was particularly high in patients with the most severe visceral involvement. In addition, expanded populations of CD8+ T lymphocytes sharing the same T cell receptor repertoire were detected in the blood, skin, liver, and lungs of patients. Nearly half of these expanded blood CD8+ T lymphocytes specifically recognized one of several EBV epitopes. Finally, we found that the culprit drugs triggered the production of EBV in patients' EBV-transformed B lymphocytes. Thus, cutaneous and visceral symptoms of DRESS are mediated by activated CD8+ T lymphocytes, which are largely directed against herpes viruses such as EBV. PMID- 20739683 TI - Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of eNOS, p38 MAPK, and AMPK pathways. AB - OBJECTIVE: Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice. RESEARCH DESIGN AND METHODS: The effects of selective CB1 agonist arachidonyl-2-chloroethanolamide (ACEA) and endocannabinoids anandamide and 2-arachidonoylglycerol on endothelial nitric oxide synthase (eNOS) expression were examined, as were mitochondrial DNA amount and mitochondrial biogenesis parameters in cultured mouse and human white adipocytes. These parameters were also investigated in white adipose tissue (WAT), muscle, and liver of mice chronically treated with ACEA. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation was investigated in WAT and isolated mature adipocytes from eNOS(-/-) and wild-type mice. eNOS, p38 MAPK, adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial biogenesis were investigated in WAT, muscle, and liver of HFD mice chronically treated with ACEA. RESULTS: ACEA decreased mitochondrial biogenesis and eNOS expression, activated p38 MAPK, and reduced AMPK phosphorylation in white adipocytes. The ACEA effects on mitochondria were antagonized by nitric oxide donors and by p38 MAPK silencing. White adipocytes from eNOS(-/-) mice displayed higher p38 MAPK phosphorylation than wild-type animals under basal conditions, and ACEA was ineffective in cells lacking eNOS. Moreover, mitochondrial biogenesis was downregulated, while p38 MAPK phosphorylation was increased and AMPK phosphorylation was decreased in WAT, muscle, and liver of ACEA-treated mice on a HFD. CONCLUSIONS: CB1 receptor stimulation decreases mitochondrial biogenesis in white adipocytes, through eNOS downregulation and p38 MAPK activation, and impairs mitochondrial function in metabolically active tissues of dietary obese mice. PMID- 20739684 TI - Effect of HLA class I and class II alleles on progression from autoantibody positivity to overt type 1 diabetes in children with risk-associated class II genotypes. AB - OBJECTIVE: Class II alleles define the main HLA effect on type 1 diabetes, but there is an independent effect of certain class I alleles. Class II and class I molecules are differently involved in the initiation and effector phases of the immune response, suggesting that class I alleles would be important determinants in the rate of beta-cell destruction. To test this hypothesis we analyzed the role of HLA class I and class II gene polymorphisms in the progression from diabetes-associated autoimmunity to clinical disease. RESEARCH DESIGN AND METHODS: The effect of HLA-DR-DQ haplotypes and a panel of class I HLA-A and -B alleles on the progression from autoantibody seroconversion to clinical diabetes was studied in 249 children persistently positive for at least one biochemical diabetes-associated autoantibody in addition to islet cell autoantibody. RESULTS: The progression to clinical disease was separately analyzed after the appearance of the first and the second persistent biochemical autoantibody using Cox regression. Multivariate analysis demonstrated a significant protective effect of the A*03 allele (odds ratio [OR] 0.61, P = 0.042 after the first and OR 0.55, P = 0.027 after the second autoantibody), whereas the B*39 allele had a promoting effect after seroconversion for the second autoantibody (OR 2.4, P = 0.014). When children with the DR3/DR4 genotype were separately analyzed, HLA-B*39 had a strong effect (OR 6.6, P = 0.004 and OR 7.5, P = 0.007, after the appearance of the first and the second autoantibody, respectively). The protective effect of A*03 was seen only among children without the DR3/DR4 combination. CONCLUSIONS: These results confirm that class I alleles affect the progression of diabetes associated autoimmunity and demonstrate interactions between class I and class II alleles. PMID- 20739686 TI - Use of a shared medical record with secure messaging by older patients with diabetes. AB - OBJECTIVE: Evaluate use of a web-based shared medical record (SMR) between older patients with diabetes and providers. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study. Health records and SMR use patterns of 6,185 enrollees aged >=65 years with diabetes were analyzed from implementation of a SMR in August 2003 through December 2007. We analyzed baseline predictors of age, sex, distance from clinic, socioeconomic status, insulin use, morbidity, and associated primary care provider's (PCP) secure messaging use on patients' initial and subsequent use of the SMR. Changes in morbidity, PCP, or diabetes treatment were evaluated for impact on outcomes. RESULTS: A total of 32.2% of enrollees used the SMR; median rate was 1.02 user-days/month. Numbers of users and rate of use continued to increase. In adjusted analyses, likelihood of SMR use was associated with younger age, male sex, and higher socioeconomic status neighborhood, as well as clinical characteristics of overall morbidity and assigned PCP's use of secure messaging. Initial SMR use was more likely within 3 months of an increase in morbidity (hazard ratio 1.61, 95% CI 1.28-2.01) and within 1 month of changing to a PCP with higher use (3.02, 1.66-5.51). CONCLUSIONS: Four years after implementation, one-third of older individuals with diabetes had used the web-based SMR. Higher morbidity predicted initial and continued use of SMR services. Providers' use of the communication feature was associated with higher likelihood of SMR engagement by their patients. Web-based SMRs may be an effective form of non-visit-based health care for older individuals with diabetes. PMID- 20739685 TI - Cause-specific mortality trends in a large population-based cohort with long standing childhood-onset type 1 diabetes. AB - OBJECTIVE: Little is known concerning the primary cause(s) of mortality in type 1 diabetes responsible for the excess mortality seen in this population. RESEARCH DESIGN AND METHODS: The Allegheny County (Pennsylvania) childhood-onset (age < 18 years) type 1 diabetes registry (n = 1,075) with diagnosis from 1965 to 1979 was used to explore patterns in cause-specific mortality. Cause of death was determined by a mortality classification committee of at least three physician epidemiologists, based on the death certificate and additional records surrounding the death. RESULTS: Vital status for 1,043 (97%) participants was ascertained as of 1 January 2008, revealing 279 (26.0%) deaths overall (141 females and 138 males). Within the first 10 years after diagnosis, the leading cause of death was acute diabetes complications (73.6%), while during the next 10 years, deaths were nearly evenly attributed to acute (15%), cardiovascular (22%), renal (20%), or infectious (18%) causes. After 20 years' duration, chronic diabetes complications (cardiovascular, renal, or infectious) accounted for >70% of all deaths, with cardiovascular disease as the leading cause of death (40%). Women (P < 0.05) and African Americans (P < 0.001) have significantly higher diabetes-related mortality rates than men and Caucasians, respectively. Standardized mortality ratios (SMRs) for non-diabetes-related causes do not significantly differ from the general population (violent deaths: SMR 1.2, 95% CI 0.6-1.8; cancer: SMR 1.2, 0.5-2.0). CONCLUSIONS: The excess mortality seen in type 1 diabetes is almost entirely related to diabetes and its comorbidities but varies by duration of diabetes and particularly affects women and African Americans. PMID- 20739687 TI - All-cause mortality risk among a national sample of individuals with diabetes. AB - OBJECTIVE: Little is known about the relative contributions of modifiable risk factors to overall diabetes mortality. The purpose of the current study is to 1) assess the association between modifiable risk factors and all-cause mortality among a nationally representative sample of individuals with diabetes and 2) determine the population-attributable risk percent (PAR%) for these factors. RESEARCH DESIGN AND METHODS: We analyzed data from a nationally representative sample of 1,507 adults over the age of 17 years with a self-reported diagnosis of diabetes from the Third National Health and Nutrition Examination Survey (NHANES III) mortality study. Our main outcome measures were all-cause mortality and PAR%. We used the Cox proportional hazard analysis to determine hazard ratios (HRs) for known diabetes risks and calculated PAR%. RESULTS: Among adults with diabetes, the HRs for all-cause mortality were significant for individuals who had an A1C>=8% (HR 1.65, 95% CI 1.11-2.45) or reported no regular physical activity (1.58, 1.24-2.02) or current tobacco use (1.77, 1.15-2.73). The population-attributable risk was 15.3% for A1C value>=8%, 16.4% for no regular physical activity, and 7.5% for current tobacco use. CONCLUSIONS: Health systems may consider prioritizing care to include smoking cessation, increasing physical activity, and moderate glycemic control among patients with diabetes. This study suggests that focusing on these areas may result in significant reductions in mortality in individuals with diabetes. PMID- 20739688 TI - Impact of chronic kidney disease on survival after amputation in individuals with diabetes. AB - OBJECTIVE: To identify factors that influence survival after diabetes-related amputations. RESEARCH DESIGN AND METHODS: We abstracted medical records of 1,043 hospitalized subjects with diabetes and a lower-extremity amputation from 1 January to 31 December 1993 in six metropolitan statistical areas in south Texas. We identified mortality in the 10-year period after amputation from death certificate data. Diabetes was verified using World Health Organization criteria. Amputations were identified by ICD-9-CM codes 84.11-84.18 and categorized as foot, below-knee amputation, and above-knee amputation and verified by reviewing medical records. We evaluated three levels of renal function: chronic kidney disease (CKD), hemodialysis, and no renal disease. We defined CKD based on a glomerular filtration rate<60 ml/min and hemodialysis from Current Procedural Terminology (CPT) codes (90921, 90925, 90935, and 90937). We used chi2 for trend and Cox regression analysis to evaluate risk factors for survival after amputation. RESULTS: Patients with CKD and dialysis had more below-knee amputations and above-knee amputations than patients with no renal disease (P<0.01). Survival was significantly higher in patients with no renal impairment (P<0.01). The Cox regression indicated a 290% increase in hazard for death for dialysis treatment (hazard ratio [HR] 3.9, 95% CI 3.07-5.0) and a 46% increase for CKD (HR 1.46, 95% CI 1.21-1.77). Subjects with an above-knee amputation had a 167% increase in hazard (HR 2.67, 95% CI 2.14-3.34), and below-knee amputation patients had a 67% increase in hazard for death. CONCLUSIONS: Survival after amputation is lower in diabetic patients with CKD, dialysis, and high-level amputations. PMID- 20739689 TI - What psychosocial factors influence adolescents' oral health? AB - Few studies have examined, comprehensively and prospectively, determinants of oral-health-related quality of life. The aim of this study was to examine the relationships between psychosocial factors and oral health status, health perceptions, and quality of life. Measures of symptom and functional status, health perceptions, quality of life, oral health beliefs, and psychological (sense of coherence, self-esteem, health locus of control) and social factors (parents' income and education) were collected from 439 12- and 13-year-olds at baseline and six-month follow-up, together with a clinical examination at baseline. Structural equation modeling indicated that increased levels of caries and more symptoms predicted more functional limitations, and, cross-sectionally, greater functional impact was associated with worse health perceptions, which were linked to lower quality of life. Sense of coherence was the most important psychosocial predictor. These factors are important in understanding how oral health affects young people's daily lives. PMID- 20739690 TI - Assessing tooth color differences in digital facial portraits. AB - Although a large body of scientific literature shows that background color and luminance affect color perception, previous measurements of tooth color difference thresholds have not taken the effects of viewing context into account. The present study tested the hypothesis that differences in skin/gingival color influence individuals' judgments of tooth color differences. Perceptibility and acceptability thresholds were determined in 10 individuals using a signal detection paradigm. They evaluated 500 pseudo-random presentations of two facial portraits: an African-American and a Caucasian. These portraits varied trial-to trial only in the direction (CIELAB +L*, +a*, or +b*) or magnitude of the color difference between a portrait's two central incisors. The individuals were significantly less sensitive to tooth color differences in the +L* direction in the Caucasian portrait than for any other combination of color direction or portrait type. Furthermore, comparable perceptibility and acceptability thresholds were generally not statistically significant from each other. PMID- 20739691 TI - Randomized clinical trial of treatment for TMJ disc displacement. AB - Of the various conservative treatment modalities available for temporomandibular disorders, we believe that therapeutic exercise has a good prognosis, especially for anterior disc displacement without reduction. Since its effectiveness has not been extensively evaluated, we conducted a comparative study to verify the hypothesis that treatment efficacy would not differ for exercise and occlusal splints. Fifty-two individuals with anterior disc displacement without reduction were randomly assigned to a splint or a joint mobilization self-exercise treatment group. Four outcome variables were evaluated: (i) maximum mouth-opening range without and (ii) with pain, (iii) current maximum daily pain intensity, and (iv) limitation of daily functions. All outcome variables significantly improved after 8 weeks of treatment in both groups. In particular, the mouth opening range increased more in the exercise group than in the splint group. This result demonstrates that therapeutic exercise brings earlier recovery of jaw function compared with splints. PMID- 20739692 TI - The rgg gene is a specific marker for Streptococcus oralis. AB - Although the pathogenesis of Streptococcus oralis may be different from that of other viridans group streptococci, S. oralis shares a high degree of DNA sequence similarity with these streptococci. As a result, discrimination of S. oralis from its close relatives has long been considered difficult. This study was conducted to find specific genes that allow for the in vitro identification of S. oralis, but not other oral commensals. Four hundred ninety S. oralis clones obtained by suppressive subtractive hybridization were used for Southern hybridization, and positive clones were sequenced. Of 5 S. oralis-specific clones, newly designed primer sets based on the glucosyltransferase regulatory gene amplified genomic DNA only from S. oralis strains, but not from any of the other 125 strains tested. Our findings may be useful for the future development of efficient diagnostic tools for the rapid identification and differentiation of S. oralis from other oral streptococci strains. PMID- 20739694 TI - The use of nanoparticles to control oral biofilm formation. AB - Nanoparticles are normally considered to be of a size no greater than 100 nm, and the exploitation of their unique attributes to combat infection has increased markedly over the past decade. The potential of nanoparticles to control the formation of biofilms within the oral cavity, as a function of their biocidal, anti-adhesive, and delivery capabilities, is now coming under close scrutiny. Possible uses as constituents of prosthetic device coatings, as topically applied agents, and within dental materials are being explored. The latest insights into the application of nanoparticles in the control of oral infections, including their use in photodynamic therapy, will be discussed in this review. In particular, the use of nanoparticulate silver, copper, zinc, silicon, and their oxides will be considered in relation to their effects on bacterial populations. The recent interest in the applications of nanoparticulate polymers and calcium phosphates will also be assessed. Particular attention will be paid to the toxicity issues surrounding the potential impact of nanoparticles on oral and other tissues. PMID- 20739693 TI - Comparative human salivary and plasma proteomes. AB - The protein compositions, or the proteomes, found in human salivary and plasma fluids are compared. From recent experimental work by many laboratories, a catalogue of 2290 proteins found in whole saliva has been compiled. This list of salivary proteins is compared with the 2698 proteins found in plasma. Approximately 27% of the whole-saliva proteins are found in plasma. However, despite this apparent low degree of overlap, the distribution found across Gene Ontological categories, such as molecular function, biological processes, and cellular components, shows significant similarities. Moreover, nearly 40% of the proteins that have been suggested to be candidate markers for diseases such as cancer, cardiovascular disease, and stroke can be found in whole saliva. These comparisons and correlations should encourage researchers to consider the use of saliva to discover new protein markers of disease and as a diagnostic non proximal fluid to detect early signs of disease throughout the body. PMID- 20739695 TI - TGF-beta signaling in gingival fibroblast-epithelial interaction. AB - The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-beta has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-beta signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-beta inhibition. A novel three dimensional (3D) gel-culture system consisting of primary human gingival fibroblasts (GF) and gingival epithelial (GE) cells in collagen gels was applied. GF populations from patients with severe periodontitis degraded collagen gels, which was reduced by TGF-beta-receptor kinase inhibition. Up-regulation of TGF beta-responsive genes was evident in GF/GE co-cultures. Furthermore, the TGF-beta downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-beta signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful in vitro model for therapeutic drug screening for periodontitis. PMID- 20739696 TI - Oxidative stress, systemic inflammation, and severe periodontitis. AB - Periodontal infections have been associated with a state of chronic inflammation. To ascertain whether severe periodontitis and its treatment are associated with oxidative stress, we recruited 145 cases (periodontitis) and 56 controls in a case-control study. A further pilot intervention study of 14 cases (periodontal therapy) was performed. Blood samples were taken at baseline (case-control) and 1, 3, 5, 7, and 30 days after treatment (intervention). Diacron-reactive oxygen metabolites (D-ROM), anti-oxidant potential, C-reactive protein (CRP), interleukin-6, and lipid profiles were determined with high-sensitivity assays in serum. Patients with severe periodontitis exhibited higher D-ROM levels (P < 0.001) and lower total anti-oxidant capacity (P < 0.001) compared with healthy control individuals. These findings were independent of age, gender, smoking habits, ethnicity, and standard lipids differences. D-ROM levels were positively correlated with CRP (R = 0.4, P < 0.001) and clinical periodontal parameters (R = 0.20, P < 0.05). Acute increases of D-ROM (P < 0.01) were observed following periodontal therapy. Analysis of these data suggests a positive association between severe periodontitis and oxidative stress. PMID- 20739697 TI - Infiltrants inhibit progression of natural caries lesions in vitro. AB - To define the optimized material properties of caries-infiltrating resins (infiltrants), we evaluated the effects of infiltrant composition and penetration coefficient (PC) on the inhibition of the progression of natural approximal caries lesions in vitro. Non-cavitated natural enamel lesions were etched (15% HCl gel) and infiltrated for 5 min with experimental resins varying in PC (cm/sec): PC63, PC185, PC204, and PC391. As a positive control (PosC), lesions were covered with flowable composite resin, whereas untreated lesions served as negative controls (NegC). Specimens were exposed to a demineralizing solution (pH 4.95) for 400 days. Progression of mineral loss was analyzed by transverse wavelength-independent microradiography. Percentage progressions of NegC [median (25th/75th percentile), 24 (10/56)], PC63 [9 (3/39)], and PC185 [12 (9/24)] were significantly higher compared with those of PosC [1 (-8/8)], PC204 [-2 (-4/2)], and PC391 [0 (-5/9)] (p < 0.05). Thus, infiltrants with PC > 200 cm/sec are capable of inhibiting lesion progression. PMID- 20739698 TI - New approaches to enhanced remineralization of tooth enamel. AB - Dental caries is a highly prevalent diet-related disease and is a major public health problem. A goal of modern dentistry is to manage non-cavitated caries lesions non-invasively through remineralization in an attempt to prevent disease progression and improve aesthetics, strength, and function. Remineralization is defined as the process whereby calcium and phosphate ions are supplied from a source external to the tooth to promote ion deposition into crystal voids in demineralized enamel, to produce net mineral gain. Recently, a range of novel calcium-phosphate-based remineralization delivery systems has been developed for clinical application. These delivery systems include crystalline, unstabilized amorphous, or stabilized amorphous formulations of calcium phosphate. These systems are reviewed, and the technology with the most scientific evidence to support its clinical use is the remineralizing system utilizing casein phosphopeptides to stabilize and deliver bioavailable calcium, phosphate, and fluoride ions. The recent clinical evidence for this technology is presented and the mechanism of action discussed. Biomimetic approaches to stabilization of bioavailable calcium, phosphate, and fluoride ions and the localization of these ions to non-cavitated caries lesions for controlled remineralization show promise for the non-invasive management of dental caries. PMID- 20739700 TI - Dental development in hemifacial microsomia. AB - Hemifacial microsomia (HFM) is a congenital disorder marked by facial asymmetry. Whether facial asymmetry accounts for asymmetrical dental development is unknown. There are few data on dental development relative to mandibular development or severity of HFM, or on development over time. We hypothesized that when mandibular development was severely disturbed, local dental development was also affected. We compared dental development scores between affected and non-affected mandibular sides in patients with HFM (n = 84) and compared these data with those collected from Dutch control children (n = 451). Logistic functions were constructed for dental age over time for all four Pruzansky/Kaban types. The results showed a tendency toward delayed dental development in Pruzansky/Kaban types IIb and III at younger ages. The temporary delay of tooth formation in patients with severe forms of HFM and the distribution of agenic teeth suggest an interaction between mandibular and dental development. PMID- 20739699 TI - Characterization of progenitor cells in pulps of murine incisors. AB - The continuous growth of rodent incisors requires the presence of stem cells capable of generating ameloblasts and odontoblasts. While epithelial stem cells giving rise to ameloblasts have been well-characterized, cells giving rise to the odontoblasts in incisors have not been fully characterized. The goal of this study was to gain insight into the potential population in dental pulps of unerupted and erupted incisors that give rise to odontoblasts. We show that pulps from unerupted incisors contain a significant mesenchymal-stem-cell (MSC)-like population (cells expressing CD90+/CD45-, CD117+/CD45-, Sca-1+/CD45-) and few CD45+ cells. Our in vitro studies showed that these cells displayed extensive osteo-dentinogenic potential, but were unable to differentiate into chondrocytes and adipocytes. Dental pulps from erupted incisors displayed increased percentages of CD45+ and decreased percentages of cells expressing markers of an MSC-like population. Despite these differences, pulps from erupted incisors also displayed extensive osteo-dentinogenic potential and inability to differentiate into chondrocytes and adipocytes. These results provide evidence that continuous generation of odontoblasts and dentin on the labial and lingual sides of unerupted and erupted incisors is supported by a progenitor population and not multipotent MSCs in the dental pulp. PMID- 20739702 TI - Subgingival microbial profiles of smokers with periodontitis. AB - The subgingival microbiome is largely uncultivated, and therefore, cultivation based and targeted molecular approaches have limited value in examining the effect of smoking on this community. We tested the hypothesis that the subgingival biofilm is compositionally different in current and never-smokers by using an open-ended molecular approach for bacterial identification. Subgingival plaque from deep sites of current and never-smokers matched for disease was analyzed by 16S sequencing. Smokers demonstrated greater abundance of Parvimonas, Fusobacterium, Campylobacter, Bacteroides, and Treponema and lower levels of Veillonella, Neisseria, and Streptococcus. Several uncultivated Peptostreptococci, Parvimonas micra, Campylobacter gracilis, Treponema socranskii, Dialister pneumosintes, and Tannerella forsythia were elevated in this group, while Veillonella sp. oral clone B2, Neisseria sp. oral clone 2.24, Streptococcus sanguinis, and Capnocytophaga sp. clone AH015 were at lower levels. The microbial profile of smoking-associated periodontitis is distinct from that of non-smokers, with significant differences in the prevalence and abundance of disease-associated and health-compatible organisms. PMID- 20739701 TI - Polymorphisms in the Matrilin-1 gene and risk of mandibular prognathism in Koreans. AB - Previous linkage analysis of an Asian population proposed possible candidate genes for mandibular prognathism, such as Matrilin-1 (cartilage matrix protein). To investigate the association between the single-nucleotide polymorphisms (SNPs) in Matrilin-1 and mandibular prognathism, we investigated three sequence variants (-158 T>C, 7987 G>A, 8572 C>T) in 164 mandibular prognathism patients and 132 control individuals with a normal occlusion. The results showed that the 8572 TT genotypes in Matrilin-1 showed increased risk of mandibular prognathism (OR = 9.28, 95% Cl = 1.19~197.57, P < 0.05), whereas the 7987 AA genotype showed a protective effect for mandibular prognathism (OR = 0.16, 95% Cl = 0.05~0.47, P < 0.05). Genotyping results showed that the Matrilin-1 polymorphism haplotype TGC (ht4; 158T, 7987G, and 8572C alleles) had a pronounced risk effect for mandibular prognathism compared with controls (OR = 5.16, 95% Cl = 2.03~13.93, P < 0.01). The results suggest that polymorphisms in Matrilin-1 could be used as a marker for genetic susceptibility to mandibular prognathism. PMID- 20739703 TI - Neuron-immune interactions in the sensitized thalamus induced by mustard oil application to rat molar pulp. AB - We have reported that mustard oil application to the rat dental pulp induces neuronal activation in the thalamus. To address the mechanisms involved in the thalamic changes, we performed neuronal responsiveness recording, immunohistochemistry, and molecular biological analysis. After mustard oil application, neuronal responsiveness was increased in the mediodorsal nucleus. When MK801 (an N-methyl-D-aspartate receptor antagonist) was applied to the mediodorsal nucleus, the enhanced responsiveness was decreased. N-methyl-D aspartate receptor 2D, glial fibrillary acidic protein, and antigen-presenting cell-related gene mRNAs in the contralateral thalamus were up-regulated at 10 minutes after mustard oil application, but were down-regulated within 10 minutes after the antagonist application. OX6-expressing microglia and glial fibrillary acidic protein-expressing astrocytes did not increase until 60 minutes after mustard oil application. These results suggested that the thalamic neurons play some roles in regulating the glial cell activation in the mediodorsal nucleus via N-methyl-D-aspartate receptor 2D during pulp inflammation-induced central sensitization. PMID- 20739704 TI - Cognitive status in persons with amalgam-related complaints. AB - Self-reported cognitive symptoms are frequent in persons with amalgam-related complaints, but few studies have focused on their cognitive function. The aim was to examine a symptom profile and whether participants with amalgam-related complaints have cognitive deficits in comparison with control individuals. We drew 342 participants with amalgam-related complaints and 342 one-to-one matched control individuals from a longitudinal population-based study. For 81 of the participants with amalgam-related complaints and controls, data were available approximately five years before the onset of complaints, making a longitudinal analysis possible. All participants were assessed by a self-reported health questionnaire and a comprehensive cognitive test battery. The participants with amalgam-related complaints reported more symptoms, mainly musculoskeletal and neuropsychological, compared with control individuals (p < 0.001). The results revealed no significant difference between the amalgam and control group, either cross-sectionally or longitudinally, for any of the cognitive tests. These results suggest that cognitive decline is not associated with amalgam-related complaints. PMID- 20739705 TI - Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. AB - Periodontal diseases (PD) are chronic infectious inflammatory diseases characterized by the destruction of tooth-supporting structures, being the presence of periodontopathogens required, but not sufficient, for disease development. As a general rule, host inflammatory mediators have been associated with tissue destruction, while anti-inflammatory mediators counteract and attenuate disease progression. With the discovery of several T-cell subsets bearing distinct immunoregulatory properties, this pro- vs. anti-inflammatory scenario became more complex, and a series of studies has hypothesized protective or destructive roles for Th1, Th2, Th17, and Treg subpopulations of polarized lymphocytes. Interestingly, the "protective vs. destructive" archetype is usually considered in a framework related to tissue destruction and disease progression. However, it is important to remember that periodontal diseases are infectious inflammatory conditions, and recent studies have demonstrated that cytokines (TNF alpha and IFN-gamma) considered harmful in the context of tissue destruction play important roles in the control of periodontal infection. Therefore, in this review, the state-of-the-art knowledge concerning the protective and destructive roles of host inflammatory immune response will be critically evaluated and discussed from the tissue destruction and control-of-infection viewpoints. PMID- 20739706 TI - Connecting world youth with tobacco brands: YouTube and the internet policy vacuum on Web 2.0. AB - BACKGROUND: The internet is an ideal forum for tobacco marketing, as it is largely unregulated and there is no global governing body for controlling content. Nevertheless, tobacco companies deny advertising on the internet. OBJECTIVE: To assess the extent and nature of English language videos available on the Web 2.0 domain 'YouTube' that contain tobacco brand images or words. METHODS: The authors conducted a YouTube search using five leading non-Chinese cigarette brands worldwide. The themes and content of up to 40 of the most viewed videos returned for each search were analysed: a total of 163 videos. RESULTS: A majority of the 163 tobacco brand-related videos analysed (71.2%, 95% CI 63.9 to 77.7) had pro-tobacco content, versus a small minority (3.7%) having anti-tobacco content (95% CI 1.4 to 7.8). Most of these videos contained tobacco brand content (70.6%), the brand name in the title (71.2%) or smoking imagery content (50.9%). One pro-smoking music video had been viewed over 2 million times. The four most prominent themes of the videos were celebrity/movies, sports, music and 'archive', the first three of which represent themes of interest to a youth audience. CONCLUSIONS: Pro-tobacco videos have a significant presence on YouTube, consistent with indirect marketing activity by tobacco companies or their proxies. Since content may be removed from YouTube if it is found to breach copyright or if it contains offensive material, there is scope for the public and health organisations to request the removal of pro-tobacco content containing copyright or offensive material. Governments should also consider implementing Framework Convention on Tobacco Control requirements on the internet, to further reduce such pro-tobacco content. PMID- 20739707 TI - Improving drug safety surveillance: lessons from rosiglitazone. PMID- 20739708 TI - The role of doctors' religious faith and ethnicity in taking ethically controversial decisions during end-of-life care. AB - BACKGROUND AND AIMS: The prevalence of religious faith among doctors and its relationship with decision-making in end-of-life care is not well documented. The impact of ethnic differences on this is also poorly understood. This study compares ethnicity and religious faith in the medical and general UK populations, and reports on their associations with ethically controversial decisions taken when providing care to dying patients. METHOD: A postal survey of 3733 UK medical practitioners, of whom 2923 reported on the care of their last patient who died. FINDINGS: Specialists in care of the elderly were somewhat more likely to be Hindu or Muslim than other doctors; palliative care specialists were somewhat more likely to be Christian, religious and 'white' than others. Ethnicity was largely unrelated to rates of reporting ethically controversial decisions. Independently of speciality, doctors who described themselves as non-religious were more likely than others to report having given continuous deep sedation until death, having taken decisions they expected or partly intended to end life, and to have discussed these decisions with patients judged to have the capacity to participate in discussions. Speciality was independently related to wide variations in the reporting of decisions taken with some intent to end life, with doctors in 'other hospital' specialities being almost 10 times as likely to report this when compared with palliative medicine specialists, regardless of religious faith. CONCLUSIONS: Greater acknowledgement of the relationship of doctors' values with clinical decision-making is advocated. PMID- 20739709 TI - Functional dissection of IME1 transcription using quantitative promoter-reporter screening. AB - Transcriptional regulation is a key mechanism that controls the fate and response of cells to diverse signals. Therefore, the identification of the DNA-binding proteins, which mediate these signals, is a crucial step in elucidating how cell fate is regulated. In this report, we applied both bioinformatics and functional genomic approaches to scrutinize the unusually large promoter of the IME1 gene in budding yeast. Using a recently described fluorescent protein-based reporter screen, reporter-synthetic genetic array (R-SGA), we assessed the effect of viable deletion mutants on transcription of various IME1 promoter-reporter genes. We discovered potential transcription factors, many of which have no perfect consensus site within the IME1 promoter. Moreover, most of the cis-regulatory sequences with perfect homology to known transcription factor (TF) consensus were found to be nonfunctional in the R-SGA analysis. In addition, our results suggest that lack of conservation may not discriminate against a TF regulatory role at a specific promoter. We demonstrate that Sum1 and Sok2, which regulate IME1, bind to nonperfect consensuses within nonconserved regions in the sensu stricto Saccharomyces strains. Our analysis supports the view that although comparative analysis can provide a useful guide, functional assays are required for accurate identification of TF-binding site interactions in complex promoters. PMID- 20739710 TI - Novel acid phosphatase in Candida glabrata suggests selective pressure and niche specialization in the phosphate signal transduction pathway. AB - Evolution through natural selection suggests unnecessary genes are lost. We observed that the yeast Candida glabrata lost the gene encoding a phosphate repressible acid phosphatase (PHO5) present in many yeasts including Saccharomyces cerevisiae. However, C. glabrata still had phosphate starvation inducible phosphatase activity. Screening a C. glabrata genomic library, we identified CgPMU2, a member of a three-gene family that contains a phosphomutase like domain. This small-scale gene duplication event could allow for sub- or neofunctionalization. On the basis of phylogenetic and biochemical characterizations, CgPMU2 has neofunctionalized to become a broad range, phosphate starvation-regulated acid phosphatase, which functionally replaces PHO5 in this pathogenic yeast. We determined that CgPmu2, unlike ScPho5, is not able to hydrolyze phytic acid (inositol hexakisphosphate). Phytic acid is present in fruits and seeds where S. cerevisiae grows, but is not abundant in mammalian tissues where C. glabrata grows. We demonstrated that C. glabrata is limited from an environment where phytic acid is the only source of phosphate. Our work suggests that during evolutionary time, the selection for the ancestral PHO5 was lost and that C. glabrata neofunctionalized a weak phosphatase to replace PHO5. Convergent evolution of a phosphate starvation-inducible acid phosphatase in C. glabrata relative to most yeast species provides an example of how small changes in signal transduction pathways can mediate genetic isolation and uncovers a potential speciation gene. PMID- 20739712 TI - A genetic survey of fluoxetine action on synaptic transmission in Caenorhabditis elegans. AB - Fluoxetine is one of the most commonly prescribed medications for many behavioral and neurological disorders. Fluoxetine acts primarily as an inhibitor of the serotonin reuptake transporter (SERT) to block the removal of serotonin from the synaptic cleft, thereby enhancing serotonin signals. While the effects of fluoxetine on behavior are firmly established, debate is ongoing whether inhibition of serotonin reuptake is a sufficient explanation for its therapeutic action. Here, we provide evidence of two additional aspects of fluoxetine action through genetic analyses in Caenorhabditis elegans. We show that fluoxetine treatment and null mutation in the sole SERT gene mod-5 eliminate serotonin in specific neurons. These neurons do not synthesize serotonin but import extracellular serotonin via MOD-5/SERT. Furthermore, we show that fluoxetine acts independently of MOD-5/SERT to regulate discrete properties of acetylcholine (Ach), gamma-aminobutyric acid (GABA), and glutamate neurotransmission in the locomotory circuit. We identified that two G-protein-coupled 5-HT receptors, SER 7 and SER-5, antagonistically regulate the effects of fluoxetine and that fluoxetine binds to SER-7. Epistatic analyses suggest that SER-7 and SER-5 act upstream of AMPA receptor GLR-1 signaling. Our work provides genetic evidence that fluoxetine may influence neuronal functions and behavior by directly targeting serotonin receptors. PMID- 20739711 TI - Cooperation between the septins and the actomyosin ring and role of a cell integrity pathway during cell division in fission yeast. AB - A major question about cytokinesis concerns the role of the septin proteins, which localize to the division site in all animal and fungal cells but are essential for cytokinesis only in some cell types. For example, in Schizosaccharomyces pombe, four septins localize to the division site, but deletion of the four genes produces only a modest delay in cell separation. To ask if the S. pombe septins function redundantly in cytokinesis, we conducted a synthetic-lethal screen in a septin-deficient strain and identified seven mutations. One mutation affects Cdc4, a myosin light chain that is an essential component of the cytokinetic actomyosin ring. Five others cause frequent cell lysis during cell separation and map to two loci. These mutations and their dosage suppressors define a signaling pathway (including Rho1 and a novel arrestin) for repairing cell-wall damage. The seventh mutation affects the poorly understood RNA-binding protein Scw1 and severely delays cell separation when combined either with a septin mutation or with a mutation affecting the septin interacting, anillin-like protein Mid2, suggesting that Scw1 functions in a pathway parallel to that of the septins. Taken together, our results suggest that the S. pombe septins participate redundantly in one or more pathways that cooperate with the actomyosin ring during cytokinesis and that a septin defect causes septum defects that can be repaired effectively only when the cell integrity pathway is intact. PMID- 20739714 TI - 18F-fluorodeoxyglucose-positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group. AB - BACKGROUND: In non-cutaneous T-cell/natural killer (T/NK) lymphomas, the prognostic value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG PET) during or after therapy is unknown. PATIENTS AND METHODS: In this retrospective study, 54 T/NK lymphoma patients were assessed using FDG-PET before (n = 40), during (n = 44) and/or after therapy (n = 31). RESULTS: FDG-PET showed an abnormal FDG uptake in all cases. Interim FDG-PET was negative in 25 of 44 cases. After completion of therapy, 19 of 31 patients reached complete remission with negative FDG-PET. In ALK+ anaplastic large cell lymphomas, the 4-year progression-free survival (PFS) was 80% and the negative predictive value of post therapy FDG-PET was 83% (n = 9). In ALK- T/NK lymphomas, the 4-year PFS was 59% for patients with a negative interim FDG-PET versus 46% for patients with a positive interim FDG-PET (P = 0.28, n = 35). Similarly, there was no statistical difference in 4-year PFS between negative and positive post-therapy FDG-PET in these lymphomas (51% and 67%, respectively, P = 0.96). The 4-year cumulative incidence of relapse from a negative post-therapy FDG-PET was 53% in ALK- T/NK lymphomas. CONCLUSIONS: Although T/NK lymphomas are FDG-avid at diagnosis, a negative interim or post-therapy FDG-PET does not translate into an improved PFS in ALK- T/NK lymphomas. PMID- 20739713 TI - The confounding effects of population structure, genetic diversity and the sampling scheme on the detection and quantification of population size changes. AB - The idea that molecular data should contain information on the recent evolutionary history of populations is rather old. However, much of the work carried out today owes to the work of the statisticians and theoreticians who demonstrated that it was possible to detect departures from equilibrium conditions (e.g., panmictic population/mutation-drift equilibrium) and interpret them in terms of deviations from neutrality or stationarity. During the last 20 years the detection of population size changes has usually been carried out under the assumption that samples were obtained from populations that can be approximated by a Wright-Fisher model (i.e., assuming panmixia, demographic stationarity, etc.). However, natural populations are usually part of spatial networks and are interconnected through gene flow. Here we simulated genetic data at mutation and migration-drift equilibrium under an n-island and a stepping stone model. The simulated populations were thus stationary and not subject to any population size change. We varied the level of gene flow between populations and the scaled mutation rate. We also used several sampling schemes. We then analyzed the simulated samples using the Bayesian method implemented in MSVAR, the Markov Chain Monte Carlo simulation program, to detect and quantify putative population size changes using microsatellite data. Our results show that all three factors (genetic differentiation/gene flow, genetic diversity, and the sampling scheme) play a role in generating false bottleneck signals. We also suggest an ad hoc method to counter this effect. The confounding effect of population structure and of the sampling scheme has practical implications for many conservation studies. Indeed, if population structure is creating "spurious" bottleneck signals, the interpretation of bottleneck signals from genetic data might be less straightforward than it would seem, and several studies may have overestimated or incorrectly detected bottlenecks in endangered species. PMID- 20739715 TI - Aerobic exercise training-induced decrease in plasma visfatin and insulin resistance in obese female adolescents. AB - The purpose of this study was to assess differences in the levels of plasma visfatin among female adolescents and changes in plasma visfatin and insulin resistance in obese female adolescents after 12 wk of aerobic exercise training. Twenty normal-weight female students (body-mass index [BMI] < 22.9 kg/m2 and body fat <= 29.9) and 18 obese female students (BMI >= 25 kg/ m2 and body fat >= 30%) participated in this study. Eleven obese students were assigned to an exercise group and completed a 12-wk aerobic exercise-training program that included four 40- to 50-min sessions per wk with an energy expenditure of 300-400 kcal/d. Seven obese students were assigned to a control group that received no exercise sessions or dietary restriction. The plasma visfatin levels of obese female adolescents were significantly higher (p < .05) than those of the normal-weight female adolescents. The plasma visfatin levels (294.00 +/- 124.74 ng/ml to 185.55 +/- 67.30 ng/ml, p < .01) and insulin resistance (p < .05) were significantly reduced after 12 wk of aerobic exercise. The results suggest that aerobic exercise resulting in an energy expenditure of 1,200-1,600 kcal/wk for 12 wk decreases plasma visfatin and insulin resistance in obese female adolescents. PMID- 20739716 TI - Molecular responses to moderate endurance exercise in skeletal muscle. AB - This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 +/- 1 yr, body mass 80 +/- 2 kg, and VO(2peak) 45 +/- 1 ml x kg-1 x min-1) immediately (0 hr) and 3 hr after a 60 min bout of cycle exercise (60% +/- 5% VO(2peak)). Corresponding muscle biopsies were also obtained under resting conditions. The phosphorylation status of insulin/IGF-PI3K molecular-signaling proteins, ubiquitin-proteasome-related gene expression, FOXO transcription factors, and myogenic regulatory factors in muscle samples was analyzed using multiplex analysis, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). A condition-time interaction was observed for Akt phosphorylation (p < .05) with multiplexing. Regardless of endurance exercise, Akt phosphorylation decreased and ERK phosphorylation increased at 3 hr compared with 0 hr (p < .05). Levels of p70(S6K) phosphorylation were 110% greater (p < .05) at 3 hr than at 0 hr using Western blots. MuRF mRNA expression postexercise increased; levels were 4.7- and 5.7-fold greater (p < .05) at 0 hr and 3 hr, respectively, than at rest with qRT-PCR. Atrogin mRNA expression was up-regulated 3.2-fold 3 hr postexercise compared with rest. These findings demonstrate modest changes in the molecular responses to moderate endurance exercise in the absence of nutrition. This study provides the groundwork for future investigations designed to optimize the metabolic conditions necessary to positively influence the cellular mechanisms specific to skeletal-muscle protein turnover during recovery from endurance exercise. PMID- 20739717 TI - Altered antioxidant and trace-element status in adolescent female gymnasts. AB - Physical activity is associated with the generation of reactive oxygen species and may lead to decreased levels of plasma antioxidants and increased oxidant stress. Some studies have reported that antioxidant supplements can reduce the consequences of oxidative stress during exercise. In this study the authors aimed to assess the chronic effects of exercise on endogenous serum antioxidant enzyme concentrations. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were measured in adolescent girls who were either competitive gymnasts or sedentary controls. The relationship between age, body-mass index, dietary intake, trace-element status, and serum GPx and SOD was determined. The participants in the study were part of a 3-yr longitudinal investigation of exercise and peak bone-mass development in 38 competitive gymnasts and 40 healthy sedentary adolescent females 8-17 yr of age. Serum GPx and SOD were measured using colorimetric assays, and trace elements were measured using inductively coupled plasma mass spectrometry. The mean serum GPx concentrations were significantly higher in the gymnasts than in the sedentary females (157 +/- 11.1 vs. 126 +/- 8.8 U/ml, p < .05). In contrast, serum SOD concentrations were significantly lower in the gymnasts than in the sedentary group (7.24 +/- 2.6 vs. 8.57 +/- 2.3 U/ml, p < .05). Serum selenium, zinc, and copper were higher in the physically active group than in the inactive group (0.89 +/- 0.03, 10.86 +/- 0.39, 14.50 +/- 0.50 vs. 0.81 +/- 0.03, 10.32 +/- 0.28, and 14.38 +/- 0.42 umol/L, respectively), although only serum selenium reached statistical significance (p < .05). The findings show that young female gymnasts have an altered antioxidant enzyme profile compared with their less physically active peers. PMID- 20739718 TI - Race-day carbohydrate intakes of elite triathletes contesting olympic-distance triathlon events. AB - The aim of this study was to investigate the prerace and during-race carbohydrate intakes of elite-level triathletes contesting draft-legal Olympic-distance triathlon (ODT) events. Self-reported prerace and during-race nutrition data were collected at 3 separate ODT events from 51 elite senior and under-23 triathletes. One hundred twenty-nine observations of food and fluid intake representing actual prerace (n = 62) and during-race (n = 67) nutrition practices from 36 male and 15 female triathletes were used in the final analysis of this study. Female triathletes consumed significantly more carbohydrate on the morning before race start when corrected for body mass and race start time than their male counterparts (p < .05). Male and female triathletes consumed 26% more energy (kJ/kg) and 24% more carbohydrate (g/kg) when commencing a race after midday (1:00-1:30 p.m.) than for a late morning (11:00-11:15 a.m.) race start. During the race, triathletes consumed less than 60 g of carbohydrate on 66% of occasions, with average total race intakes of 48 +/- 25 and 49 +/- 25 g carbohydrate for men and women, respectively. Given average race times of 1:57:07 hr and 2:08:12 hr, hourly carbohydrate intakes were ~25 g and ~23 g for men and women, respectively. Although most elite ODT triathletes consume sufficient carbohydrate to meet recommended prerace carbohydrate intake guidelines, during race carbohydrate intakes varied considerably, with many failing to meet recommended levels. PMID- 20739720 TI - The effect of acute taurine ingestion on endurance performance and metabolism in well-trained cyclists. AB - This study examined whether acute taurine (T) ingestion before prolonged cycling would improve time-trial (TT) performance and alter whole-body fuel utilization compared with a control (CON) trial and a placebo (PL) trial in which participants were told they received taurine but did not. Eleven endurance trained male cyclists (27.2 +/- 1.5 yr, 74.3 +/- 2.3 kg, 59.9 +/- 2.3 ml . kg-1 . min-1; M +/- SEM) completed 3 trials in a randomized, crossover, blinded design in which they consumed a noncaloric sweetened beverage with either 1.66 g of T or nothing added (CON, PL) 1 hr before exercise. Participants then cycled at 66.5% +/- 1.9% VO(2max) for 90 min followed immediately by a TT (doing 5 kJ of work/kg body mass as fast as possible). Data on fluid administration, expired gas, heart rate, and ratings of perceived exertion were collected at 15-min intervals during the 90-min cycling ride, but there were no differences recorded between trials. There was no difference in TT performance between any of the 3 trials (1,500 +/- 87 s). Average carbohydrate (T 2.73 +/- 0.21, CON 2.88 +/- 0.19, PL 2.89 +/- 0.20 g/min) and fat (T 0.45 +/- 0.05, CON 0.39 +/- 0.04, PL 0.39 +/- 0.05 g/min) oxidation rates were unaffected by T supplementation. T ingestion resulted in a 16% increase (5 g, ~84 kJ; p < .05) in total fat oxidation over the 90-min exercise period compared with CON and PL. The acute ingestion of 1.66 g of T before exercise did not enhance TT performance but did result in a small but significant increase in fat oxidation during submaximal cycling in endurance trained cyclists. PMID- 20739719 TI - Increased blood pH but not performance with sodium bicarbonate supplementation in elite rugby union players. AB - PURPOSE: This study investigated the effect of ingesting 0.3 g/kg body weight (BW) of sodium bicarbonate (NaHCO3) on physiological responses, gastrointestinal (GI) tolerability, and sprint performance in elite rugby union players. METHODS: Twenty-five male rugby players, age 21.6 (2.6) yr, participated in a randomized, double-blind, placebo-controlled crossover trial. Sixty-five minutes after consuming 0.3 g/kg BW of either NaHCO3 or placebo, participants completed a 25 min warm-up followed by 9 min of high-intensity rugby-specific training followed by a rugby-specific repeated-sprint test (RSRST). Whole-blood samples were collected to determine lactate and bicarbonate concentrations and pH at baseline, after supplement ingestion, and immediately after the RSRST. Acute GI discomfort was assessed by questionnaire throughout the trials, and chronic GI discomfort was assessed during the 24 hr postingestion. RESULTS: After supplement ingestion and immediately after the RSRST, blood HCO3- concentration and pH were higher for the NaHCO3 condition than for the placebo condition (p < .001). After the RSRST, blood lactate concentrations were significantly higher for the NaHCO3 than for the placebo condition (p < .001). There was no difference in performance on the RSRST between the 2 conditions. The incidence of belching, stomachache, diarrhea, stomach bloating, and nausea was higher after ingestion of NaHCO3 than with placebo (all p < .050). The severity of stomach cramps, belching, stomachache, bowel urgency, diarrhea, vomiting, stomach bloating, and flatulence was rated worse after ingestion of NaHCO3 than with placebo (p < .050). CONCLUSIONS: NaHCO3 supplementation increased blood HCO3- concentration and attenuated the decline in blood pH compared with placebo during high-intensity exercise in well-trained rugby players but did not significantly improve exercise performance. The higher incidence and greater severity of GI symptoms after ingestion of NaHCO3 may negatively affect physical performance, and the authors strongly recommend testing this supplement during training before use in competitive situations. PMID- 20739721 TI - Relationship between changes in upon-waking urinary indices of hydration status and body mass in adolescent Singaporean athletes. AB - This study investigated the relationship between changes in upon-waking body mass (BM) and changes in urine specific gravity (U(sg)) and urine color (U(col)) from 1 day to the next. Throughout the 5-day investigation, healthy adolescent Singaporean athletes (n = 66) had their upon-waking, bladder-voided BM measured. A small aliquot of the first bladder void each day was collected and analyzed for U(sg) and U(col), the latter by both an investigator (IU(col)) and individual participants (SU(col)). Results revealed a significant inverse relationship between changes in BM and changes in U(sg) (p = .003) and U(col) (p = .001). On average, U(sg) and U(col) changed by ~0.003 units and ~1 color (across a 9-unit scale), respectively, with every 1% change in BM from 1 day to the next. There was a stronger relationship between U(sg) and IU(col) (r = .82, p < .001) than between U(sg) and SU(col) (r = .60, p < .001). These results suggest that the degree of fluid deficit may be predicted from the U(sg) measurements among moderately hypohydrated athletes. In addition, training athletes to interpret and use the U(col) chart is recommended. PMID- 20739723 TI - Lack of effect of exercise time of day on acute energy intake in healthy men. AB - Although the manipulation of exercise and dietary intake to achieve successful weight loss has been extensively studied, it is unclear how the time of day that exercise is performed may affect subsequent energy intake. The purpose of the current study was to investigate the effect of an acute bout of exercise performed in the morning compared with an equivalent bout of exercise performed in the afternoon on short-term energy intake. Nine healthy male participants completed 3 trials: morning exercise (AM), afternoon exercise (PM), or control (no exercise; CON) in a randomized counterbalanced design. Exercise consisted of 45 min of treadmill running at 75% VO(2peak). Energy intake was assessed over a 26-hr period with the participants eating ad libitum from a standard assortment of food items of known quantity and composition. There was no significant difference in overall energy intake (M +/- SD; CON 23,505 +/- 6,938 kJ, AM 24,957 +/- 5,607 kJ, PM 24,560 +/- 5,988 kJ; p = .590) or macronutrient preferences during the 26-hr period examined between trials. Likewise, no differences in energy intake or macronutrient preferences were observed at any of the specific individual meal periods examined (i.e., breakfast, lunch, dinner) between trials. These results suggest that the time of day that exercise is performed does not significantly affect short-term energy intake in healthy men. PMID- 20739722 TI - Excess postexercise oxygen consumption after aerobic exercise training. AB - Literature examining the effects of aerobic exercise training on excess postexercise oxygen consumption (EPOC) is sparse. In this study, 9 male participants (19-32 yr) trained (EX) for 12 wk, and 10 in a control group (CON) maintained normal activity. VO(2max), rectal temperature (T(re)), epinephrine, norepinephrine, free fatty acids (FFA), insulin, glucose, blood lactate (BLA), and EPOC were measured before (PRE) and after (POST) the intervention. EPOC at PRE was measured for 120 min after 30 min of treadmill running at 70% VO(2max). EX completed 2 EPOC trials at POST, i.e., at the same absolute (ABS) and relative (REL) intensity; 1 EPOC test for CON served as both the ABS and REL trial because no significant change in VO(2max) was noted. During the ABS trial, total EPOC decreased significantly (p < .01) from PRE (39.4 +/- 3.6 kcal) to POST (31.7 +/- 2.2 kcal). T(re), epinephrine, insulin, glucose, and BLA at end-exercise or during recovery were significantly lower and FFA significantly higher after training. Training did not significantly affect EPOC during the REL trial; however, epinephrine was significantly lower, and norepinephrine and FFA, significantly higher, at endexercise after training. Results indicate that EPOC varies as a function of relative rather than absolute metabolic stress and that training improves the efficiency of metabolic regulation during recovery from exercise. Mechanisms for the decreased magnitude of EPOC in the ABS trial include decreases in BLA, T(re), and perhaps epinephrine-mediated hepatic glucose production and insulin-mediated glucose uptake. PMID- 20739724 TI - Treatment considerations for primary myelofibrosis. PMID- 20739725 TI - Thalidomide and lenalidomide in primary myelofibrosis. AB - Primary myelofibrosis is a clonal haematopoietic stem cell disease, characterised by marrow stromal fibrosis, extramedullary haematopoiesis, splenomegaly, hepatomegaly and progressive cytopenia. Therapeutic options once cytopenia has developed are limited to supportive care, such as erythrocyte transfusions and growth factors. The aetiology has become more clear, especially since JAK-2 mutations were found, resulting in increased production of cytokines. The immune modulating drug thalidomide and its derivative lenalidomide have shown to be effective in reducing cytopenia, most probably by inhibiting the cytokine responses. In some patients the bone marrow fibrosis disappears. We describe the experience with these drugs in a cohort of 14 patients for thalidomide and seven for lenalidomide (in six patients lenalidomide was given after thalidomide and one patient received lenalidomide upfront). Thalidomide gave clinical improvement in 6/14 patients, but its use was limited mainly due to toxicity, especially the development of neuropathy. The drug could be given for a median period of 15.5 months in responding patients. Lenalidomide was effective in 4/7 of the patients, in some patients with no response on thalidomide. Due to the more favourable toxicity profile, the median duration of therapy was 19 months, with 3/4 patients on therapy longer than 19 months. These data are discussed in view of the clinical studies published. We conclude that lenalidomide is preferred in myelofibrosis, given a higher response rate and more favourable toxicity profile. If no response the addition of prednisone can be considered. In some patients it can normalise haemoglobin and make them transfusion independent. PMID- 20739726 TI - Dilemmas in treatment of women with familial hypercholesterolaemia during pregnancy. AB - Familial hypercholesterolaemia (FH) is a co-dominant monogenic disorder of lipoprotein metabolism, characterised by severely elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth onwards. Treatment of FH patients with cholesterol-lowering medication is mandatory to prevent premature cardiovascular disease (CVD). As a result of a nationwide screening in the Netherlands, a large group of women with FH in the child-bearing age range has been identified. Physicians are faced with a treatment dilemma if these females present either with a wish for pregnancy or an established pregnancy, since all systemically absorbed lipid-lowering medication is contraindicated during pregnancy. Currently, no evidence-based guidelines exist on the optimal clinical approach in these patients. Animal studies have shown conflicting data on potential teratogenicity of statins. In humans, there is no strong adverse safety signal, but prospective studies are lacking. The consequences of maternal hypercholesterolaemia during pregnancy for both mother and child are not well determined, although it has been suggested that it may increase the risk of CVD in the offspring. This review describes two representative cases from clinical practice, and discusses clinical considerations for treating pregnant FH patients supplemented with what is known from the literature. PMID- 20739727 TI - Novel therapies for hypereosinophilic syndromes. AB - BACKGROUND: Conventional therapies (corticosteroids, cytotoxic agents or interferon-a) or newer compounds such imatinib are used specifically in subsets of hypereosinophilic syndromes (HES). However other therapies are still needed in this condition. OBJECTIVE: To review the novel therapies for HES discussing their advantages and shortcomings. METHODS AND RESULTS: Preclinical and clinical data on novel tyrosine kinase inhibitors, anti-IL -5 antibodies or anti-CD52 antibodies (alemtuzumab) are analysed. The former might represent appropriate options in case of imatinib resistance; the efficacy of anti-IL-5 monoclonal antibodies therapy is limited by the occurrence of rebound eosinophilia and alemtuzumab might be a promising anti-eosinophil therapy for all HES subsets. CONCLUSION: Some of the novel therapies might become appropriate therapeutic options for HES. PMID- 20739728 TI - Self-monitoring of blood glucose in tablet-treated type 2 diabetic patients (ZODIAC). AB - BACKGROUND: Whether self-monitoring of blood glucose (SMBG) improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) not using insulin is questionable. Our aim was to investigate the effects of SMBG in patients with T2DM who were in persistent moderate glycaemic control whilst not using insulin. METHODS: Patients were eligible when between 18 and 70 years of age, with an HbA1c between 7 and 8.5%, using one or two oral blood glucose lowering agents. Forty-one of the anticipated 52 patients were randomly assigned to receive either SMBG added to usual care, or to continue with usual care for one year. A fasting glucose value and three postprandial glucose values were measured twice weekly (including a Saturday or a Sunday). The primary efficacy parameter was HbA1c. Furthermore, health-related quality of life and treatment satisfaction were assessed using the Short-form 36 Health Survey Questionnaire (SF-36), the Type 2 Diabetes Symptom Checklist (DSC-r), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the WHO -Wellbeing Index (WHO-5). RESULTS: Change in HbA1c between groups was -0.05% (95% CI: -0.51, 0.41; p=0.507). Also, there were no significant changes between groups on the DTSQ , DSC type 2, WHO-5 or SF -36, except for the SF -36 dimension 'health change' which was lower in the SBMG group (mean difference: -12 (95% CI: -20.9, -3.1). CONCLUSION: On top of the absence of a clinical benefit, tablet-treated T2DM patients experienced some worsening of their health perception. We therefore argue that the use of SMBG in this patient group is questionable, and its unlimited use and promotion should be reconsidered. PMID- 20739729 TI - Rhabdomyolysis following pandemic influenza A (H1N1) infection. AB - Rhabdomyalysis is uncommon but potentially life-threatening. We present a 17-year old patient who developed rhabdomyalysis following pandemic influenza A (H1N1/09) infection. With aggressive hydration her renal function remained normal throughout the entire disease course, and she steadily improved clinically. Although pneumonia and acute respiratory distress syndrome are the most common severe complications of H1N1/09 infection, clinicians should be aware that H1N1/09 infection may be complicated by rhabdomyolysis. PMID- 20739731 TI - An adult with vague abdominal complaints and atypical colonoscopic findings. PMID- 20739730 TI - Falsely elevated lactate in severe ethylene glycol intoxication. AB - A 29-year-old male presented at the emergency department of our hospital in a confused state. He had a history of psychoses and substance abuse. Physical examination revealed hyperventilation and abdominal tenderness. Blood gas analysis in the emergency department using an ABL 725 Radiometer analyser showed a severe metabolic acidosis with massive lactate elevation. Lactate acidosis due to mesenteric ischaemia was suspected. However, toxicology screening demonstrated ethylene glycol intoxication. Treatment with ethanol infusion and acute haemodialysis was started. Repeated laboratory measurements using a clinical chemistry analyser showed minimal plasma lactate elevation. Falsely elevated lactate measurement is a little known phenomenon that can occur in ethylene glycol intoxication and can cause serious delay in diagnosis. Therefore, elevated lactate concentrations measured on intensive care unit and emergency department blood gas analysers should be confirmed by a clinical chemistry analyser in the main laboratory in case of suspected ethylene glycol intoxication. PMID- 20739732 TI - A tropical surprise? PMID- 20739733 TI - An unusual cause of constipation by a rectal mass. PMID- 20739734 TI - The influence of a soiled finger in capillary blood glucose monitoring. PMID- 20739735 TI - Five-year incidence of type 2 diabetes mellitus in patients with familial combined hyperlipidaemia. PMID- 20739736 TI - Ascertainment and verification of diabetes in the EPIC-NL study. AB - BACKGROUND: The objectives of this study were to describe in detail the ascertainment and verification of prevalent and incident diabetes in the Dutch contributor to the European Prospective Investigation into Cancer and Nutrition (EPIC-NL cohort) and to examine to what extent ascertained diabetes agreed with general practitioner (GP) and pharmacy records. METHODS: In total, 40,011 adults, aged 21 to 70 years at baseline, were included. Diabetes was ascertained via self report, linkage to registers of hospital discharge diagnoses (HDD) and a urinary glucose strip test. Ascertained diabetes cases were verified against GP or pharmacist information using mailed questionnaires. RESULTS: At baseline, 795 (2.0%) diabetes cases were ascertained, and 1494 (3.7%) during a mean follow-up of ten years. The majority was ascertained via self-report only (56.7%), or self report in combination with HDD (18.0%). After verification of ascertained diabetes cases, 1532 (66.9%) [corrected] were defined as having diabetes , 495 (21.6%) as non-diabetic individuals, and 262 (11.5%) as uncertain. Of the 1538 cases ascertained by self-report, 1350 (positive predictive value: 87.8%) were confirmed by GP or pharmacist. Cases ascertained via self-report in combination with HDD were most often confirmed (334 (positive predictive value: 96.0%)). CONCLUSIONS: Two out of three ascertained diabetes cases were confirmed to have been diagnosed with diabetes by their GP or pharmacist. Diabetes cases ascertained via self-report in combination with HDD had the highest confirmation. PMID- 20739738 TI - Towards strain gauges based on a self-assembled nanoparticle monolayer--SAXS study. AB - An in situ small-angle x-ray scattering study of the nanoparticle displacement in a self-assembled monolayer as a function of a supporting membrane strain is presented. The average nanoparticle spacing is 6.7 nm in the unstrained state and increases in the applied force direction, following linearly the membrane strain which reaches the maximum value of 11%. The experimental results suggest a continuous mutual shift of the nanoparticles and their gradual separation with the growing stress rather than nanoparticle islands formation. No measurable shift of the nanoparticles was observed in the direction perpendicular to the applied stress. PMID- 20739739 TI - A theoretical model for Schottky diodes for excluding the sneak current in cross bar array resistive memory. AB - Kirchhoff's law was used to examine the electrical specifications of selection diodes, which are essential for suppressing the read interference problems in nano-scale resistive switching cross bar arrays with a high block density. The diode in the cross bar array with a 100 Mb block density should have a reverse/forward resistance ratio of > 10(8), and a forward current density of > 10(5) A cm(-2) for stable reading and writing operation. Whilst normal circuit simulators are heavily overloaded when the number of cells (m) connected to one bit and word line is larger (m >> 100), which is the desired range for high density cross bar arrays, the present model can provide a simple simulation. The validity of this new method was confirmed by a comparison with the previously reported method based on a voltage estimation. PMID- 20739737 TI - Nutrient withdrawal rescues growth factor-deprived cells from mTOR-dependent damage. AB - Deregulated nutrient signaling plays pivotal roles in body ageing and in diabetic complications; biochemical cascades linking energy dysmetabolism to cell damage and loss are still incompletely clarified, and novel molecular paradigms and pharmacological targets critically needed. We provide evidence that in the retrovirus-packaging cell line HEK293-T Phoenix, massive cell death in serum-free medium is remarkably prevented or attenuated by either glucose or aminoacid withdrawal, and by the glycolysis inhibitor 2-deoxy-glucose. A similar protection was also elicited by interference with mitochondrial function, clearly suggesting involvement of energy metabolism in increased cell survival. Oxidative stress did not account for nutrient toxicity on serum-starved cells. Instead, nutrient restriction was associated with reduced activity of the mTOR/S6 Kinase cascade. Moreover, pharmacological and genetic manipulation of the mTOR pathway modulated in an opposite fashion signaling to S6K/S6 and cell viability in nutrient repleted medium. Additionally, stimulation of the AMP-activated Protein Kinase concomitantly inhibited mTOR signaling and cell death, while neither event was affected by overexpression of the NAD+ dependent deacetylase Sirt-1, another cellular sensor of nutrient scarcity. Finally, blockade of the mTOR cascade reduced hyperglycemic damage also in a more pathophysiologically relevant model, i.e. in human umbilical vein endothelial cells (HUVEC) exposed to hyperglycemia. Taken together these findings point to a key role of the mTOR/S6K cascade in cell damage by excess nutrients and scarcity of growth-factors, a condition shared by diabetes and other ageing-related pathologies. PMID- 20739740 TI - Photoluminescence, white light emitting properties and related aspects of ZnO nanoparticles admixed with graphene and GaN. AB - ZnO nanoparticles exhibit a broad band centred around 530 nm in the photoluminescence (PL) spectrum due to the presence of oxygen vacancies. Composites of ZnO nanoparticles with graphenes show marked changes in the PL spectrum with broad bands covering the entire visible region, making them candidates for solid state lighting, while graphene prepared by arc discharge of graphite in a hydrogen atmosphere (HG) containing 2-3 layers as well as boron doped (BHG) and nitrogen-doped (NHG) samples of HG give white light when admixed with ZnO nanoparticles; excellent results are obtained with the addition of just 7 wt% of BHG to the ZnO nanoparticles. Mixtures of ZnO and GaN nanoparticles also exhibit white light emission. The quantum yields of these ZnO nanoparticle based white light sources are in the 4-6% range. Photoconductivity characteristics of ZnO nanoparticles are affected by the addition of even a small amount of graphene (<0.5 wt%). PMID- 20739741 TI - Parallel fabrication of polymer-protected nanogaps. AB - A method to create an array of sub-5 nm nanogaps with self-aligned holes in a protective polymer overlayer is presented. The parallel formation of the nanogaps, intended for electrical sensing of biomolecules in an aqueous environment, is achieved by electromigration using a simple voltage ramp across parallel-connected electrode patterns with individual constrictions. It was observed that the nanogap always formed on the cathode side of a bowtie electrode, with corresponding hillocks on the anode side, with the distance of the gap/hillock formation from the constriction depending on the ambient temperature. This technique provides a practical means to fabricate a series of polymer-protected nanogaps with considerably higher efficiency than afforded by the normally slow serial process of electromigration. PMID- 20739742 TI - Inhibited cell spreading on polystyrene nanopillars fabricated by nanoimprinting and in situ elongation. AB - Polymer nanopillars (40-80 nm in diameter and 100 nm in pitch) were fabricated at high density over large areas directly on bulk tissue culture polystyrene plates using nanoimprint lithography. Nanoporous Si molds for imprinting were generated by transfer from an anodic alumina membrane. Ultrahigh aspect ratio polymer nanopillars were formed in a novel procedure using controlled elongation of the imprinted pillars during mold release. The resulting nanopillar arrays show significant changes in surface wettability upon brief O(2) plasma treatment. Human dermal fibroblasts were cultured on the nanopillar surfaces in order to study cell-substrate interaction at the nanoscale. The nanopillar topography shows strong effects on the cell morphology, with pillars of widely varying aspect ratios and surface energies resisting cell spreading. This effect on cell behavior can be rationalized in terms of the cells' requirement to form micron scale focal adhesions. The study indicates that at the nanoscale, physical factors can supersede the effects of chemical factors on the cell-substratum interaction. PMID- 20739743 TI - Magnetism and perfect spin filtering effect in graphene nanoflakes. AB - Magnetic and spin-polarized transport properties in zigzag-edged graphene nanoflakes were investigated from first-principles calculations. Ferrimagnetic structure was found to be the ground state for triangular shaped graphene flakes. Magnetism is weakened by doping B or N atoms into the flakes, and it is enhanced if F atoms are doped in certain sublattices of the flakes. The magnetic properties can be rationalized by the behaviors of dopants as well as interactions between dopants and the host atoms. A perfect (100%) spin filtering effect was achieved for the pure or B doped graphene flake sandwiched between two gold electrodes. The orientation of the spin current is found to be flipped if the flake is doped with N, O, or F atoms. The orientation-tunable spin filtering effect is potentially useful in practical applications. PMID- 20739744 TI - The effect of surface modifications of carbon nanotubes on the electrical properties of inkjet-printed SWNT/PEDOT-PSS composite line patterns. AB - We prepared nanocomposite inks of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT-PSS) filled with single-walled carbon nanotubes (SWNTs) purified by acidic treatment, carboxylated by chemical oxidation and carboxyl-functionalized nanotubes physically modified with a natural gum, gum arabic. Inkjet printing of line patterns with a feature size of 100 microm width and lengths ranging from 1 to 5 cm was performed on glass substrates with a piezoelectric inkjet printer. The carboxyl-functionalized SWNT-based composite demonstrated a significant decrease (fourfold) of electrical resistance for the line patterns compared to that with a purified CNT-based composite due to improved dispersability of nanotubes in the polymer matrix. The use of gum arabic for the dispersion of carboxyl-functionalized nanotubes demonstrated a further drastic decrease (18-fold) of the resistance compared with a purified CNT-based composite owing to the formation of an extended continuous network within the line pattern. The inkjet-printed conductive patterns can be applied in various fields, such as flexible high speed transistors, high efficiency solar cells and transparent electrodes. PMID- 20739745 TI - Novel SiOC nanocomposites for high-yield preparation of ultra-large-scale SiC nanowires. AB - Novel SiOC nanocomposites were successfully synthesized from commercial silica sol and sucrose via a simply designed route. The formation of SiOC nanocomposites was studied using thermogravimetry and differential scanning calorimetry. The synthesized nanocomposites were characterized by Fourier transform infrared spectroscopy, x-ray fluorescence spectrometer, x-ray photoelectron spectroscopy, x-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The results indicate that the synthesized composites are amorphous in nature and homogeneous with the microstructure of close packed SiO(2) and carbon at nanoscale. The SiOC nanocomposites exhibit very high reactivity and can be annealed to produce SiC nanocrystals at 1200 degrees C which is about 300 degrees C lower than the value obtained by thermodynamic calculation. Ultra-large-scale beta-SiC nanowires with high quality were prepared by directly annealing the synthesized SiOC nanocomposites at 1500 degrees C under Ar atmosphere, where the yield of SiC nanowires was up to 59%. The SiC nanowires grow along the [111] direction with highly uniform diameters of about 100 nm. Experimental results indicate that the close contact between SiO(2) and carbon at nanoscale plays a vital role in the high yield of SiC nanowires. The present work provides an efficient strategy for the large scale production of high-quality SiC nanowires. PMID- 20739746 TI - Transgenic animals may help resolve a sticky situation in cystic fibrosis. AB - Cystic fibrosis (CF) is caused by defects in the CFTR, a cAMP-activated Cl- channel of epithelia. The resulting reduction in epithelial fluid transport creates abnormally viscous secretions from airway mucous glands that may be a major factor in CF pathology. Mouse airways have few mucous glands, and the mouse model of CF exhibits no significant airway disease. Pigs and ferrets, however, have approximately the same number of airway mucous glands as humans. In this issue of the JCI, three independent research groups conclude that changes in airway mucous gland function in CFTR-deficient animals of these species resemble the changes seen in human CF. It is expected, therefore, that these animals will develop lung disease similar to human CF and prove to be valuable models on which to test potential therapies. PMID- 20739747 TI - From skin cells to hepatocytes: advances in application of iPS cell technology. AB - The discovery several years ago that fibroblasts and other somatic cells from mice and humans can be reprogrammed to become inducible pluripotent stem (iPS) cells has created enthusiasm for their potential applications in regenerative medicine and for modeling human diseases. Two independent studies in this issue of the JCI provide evidence that iPS cells represent a promising source of hepatocytes for a wide range of applications, including cell transplantation, drug toxicity testing, patient-specific disease modeling, and even ex vivo gene therapy. But how far have we come? PMID- 20739748 TI - Fitness and freezing: vector biology and human health. AB - Microbes transmitted to mammals by arthropods contend with many factors that could impede survival. To survive, host fitness with infection must outweigh costs. In this issue of the JCI, Neelakanta et al. demonstrate that ticks infected with Anaplasma phagocytophilum show enhanced fitness against freezing injury owing to induced expression of tick "antifreeze glycoprotein." This allows A. phagocytophilum to successfully propagate and survive to cause disease in nonnatural hosts, such as humans. How an intracellular microbe with a small genome subverts host cell function for survival provides insight into the control of some cellular function programs and underscores how vector biology can have an impact on human health. PMID- 20739749 TI - Why antibodies disobey the Hippocratic Oath and end up doing harm: a new clue. AB - The appearance of methicillin-resistant Staphylococcus aureus (MRSA) as an endemic microbe, first in hospital and health care settings and more recently in the community, has led to a disastrous situation in which use of the available antibiotic armamentarium is increasingly ineffective and spawns further antibiotic resistance. This vicious cycle highlights the pressing need for an S. aureus vaccine. However, to date, clinical trials with S. aureus vaccines have not demonstrated sustained efficacy. In this issue of the JCI, Skurnik and colleagues report that specific antibodies to two different S. aureus surface polysaccharides, which independently promote effector cell killing of S. aureus in vitro and protection against S. aureus in animal models, bind to and abrogate the activity of one another when they are combined. This fascinating finding suggests a new paradigm to explain the failure of antibody immunity to S. aureus. PMID- 20739750 TI - Too much PABP, too little translation. AB - Posttranscriptional regulation is of critical importance during mammalian spermiogenesis. A set of mRNAs that encode proteins critical to normal sperm formation are synthesized early in the process of male germ cell differentiation and are stored in a repressed state. These mRNAs are subsequently translationally activated during the process of spermatid elongation and maturation. Of note, the translationally repressed mRNAs contain long poly(A) tails that are dramatically shortened during the translational activation process. Understanding the mechanisms that underlie this process of mRNA storage and subsequent translational activation has been a long-standing goal. The relationship of the poly(A) tail to translational control is intimately related to the functions of the cognate poly(A)-binding proteins (PABPs). In this issue of the JCI, Yanagiya and colleagues use a set of knockout mice to demonstrate a novel functional role for a particular modulator of PABP function, PABP-interacting protein 2a (PAIP2A), in the normal terminal differentiation of male germ cells. PMID- 20739751 TI - Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. AB - Human induced pluripotent stem (iPS) cells hold great promise for advancements in developmental biology, cell-based therapy, and modeling of human disease. Here, we examined the use of human iPS cells for modeling inherited metabolic disorders of the liver. Dermal fibroblasts from patients with various inherited metabolic diseases of the liver were used to generate a library of patient-specific human iPS cell lines. Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions. The resulting cells exhibited properties of mature hepatocytes, such as albumin secretion and cytochrome P450 metabolism. Moreover, cells generated from patients with 3 of the inherited metabolic conditions studied in further detail (alpha1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease type 1a) were found to recapitulate key pathological features of the diseases affecting the patients from which they were derived, such as aggregation of misfolded alpha1-antitrypsin in the endoplasmic reticulum, deficient LDL receptor-mediated cholesterol uptake, and elevated lipid and glycogen accumulation. Therefore, we report a simple and effective platform for hepatocyte generation from patient-specific human iPS cells. These patient derived hepatocytes demonstrate that it is possible to model diseases whose phenotypes are caused by pathological dysregulation of key processes within adult cells. PMID- 20739752 TI - Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis. AB - Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments. PMID- 20739753 TI - Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice. AB - New prophylactic approaches are needed to control infection with the Gram positive bacterium Staphylococcus aureus, which is a major cause of nosocomial and community-acquired infections. To develop these, greater understanding of protective immunity against S. aureus infection is needed. Human immunity to extracellular Gram-positive bacterial pathogens is primarily mediated by opsonic killing (OPK) via antibodies specific for surface polysaccharides. S. aureus expresses two such antigens, capsular polysaccharide (CP) and poly-N-acetyl glucosamine (PNAG). Here, we have shown that immunization-induced polyclonal animal antisera and monoclonal antibodies specific for either CP or PNAG antigens have excellent in vitro OPK activity in human blood but that when mixed together they show potent interference in OPK activity. In addition, reductions in antibody binding to the bacterial surface, complement deposition, and passive protection were seen in two mouse models of S. aureus infection. Electron microscopy, isothermal calorimetry, and surface plasmon resonance indicated that antibodies to CP and PNAG bound together via an apparent idiotype-anti-idiotype interaction. This interaction was also found in sera from humans with S. aureus bacteremia. These findings suggest that the lack of effective immunity to S. aureus infections in humans could be due, in part, to interference in OPK when antibodies to CP and PNAG antigens are both present. This information could be used to better design S. aureus vaccine components. PMID- 20739754 TI - Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. AB - The ability to generate induced pluripotent stem (iPS) cells from a patient's somatic cells has provided a foundation for organ regeneration without the need for immune suppression. However, it has not been established that the differentiated progeny of iPS cells can effectively reverse failure of a vital organ. Here, we examined whether iPS cell-derived hepatocytes have both the functional and proliferative capabilities needed for liver regeneration in mice with fumarylacetoacetate hydrolase deficiency. To avoid biases resulting from random genomic integration, we used iPS cells generated without viruses. To exclude compensation by hepatocytes not derived from iPS cells, we generated chimeric mice in which all hepatocytes were iPS cell derived. In vivo analyses showed that iPS cells were intrinsically able to differentiate into fully mature hepatocytes that provided full liver function. The iPS cell-derived hepatocytes also replicated the unique proliferative capabilities of normal hepatocytes and were able to regenerate the liver after transplantation and two-thirds partial hepatectomy. Thus, our results establish the feasibility of using iPS cells generated in a clinically acceptable fashion for rapid and stable liver regeneration. PMID- 20739755 TI - Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the cold. AB - In the United States, Ixodes scapularis ticks overwinter in the Northeast and Upper Midwest and transmit the agent of human granulocytic anaplasmosis, Anaplasma phagocytophilum, among other pathogens. We now show that the presence of A. phagocytophilum in I. scapularis ticks increases their ability to survive in the cold. We identified an I. scapularis antifreeze glycoprotein, designated IAFGP, and demonstrated via RNAi knockdown studies the importance of IAFGP for the survival of I. scapularis ticks in a cold environment. Transfection studies also show that IAFGP increased the viability of yeast cells subjected to cold temperature. Remarkably, A. phagocytophilum induced the expression of iafgp, thereby increasing the cold tolerance and survival of I. scapularis. These data define a molecular basis for symbiosis between a human pathogenic bacterium and its arthropod vector and delineate what we believe to be a new pathway that may be targeted to alter the life cycle of this microbe and its invertebrate host. PMID- 20739756 TI - cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways. AB - Cystic fibrosis (CF), which is caused by mutations in CFTR, affects many tissues, including the lung. Submucosal gland serous acinar cells are primary sites of fluid secretion and CFTR expression in the lung. Absence of CFTR in these cells may contribute to CF lung pathogenesis by disrupting fluid secretion. Here, we have isolated primary serous acinar cells from wild-type and CFTR-/- pigs and humans without CF to investigate the cellular mechanisms and regulation of fluid secretion by optical imaging. Porcine and human serous cells secrete fluid in response to vasoactive intestinal polypeptide (VIP) and other agents that raise intracellular cAMP levels; here, we have demonstrated that this requires CFTR and a cAMP-dependent rise in intracellular Ca2+ concentration ([Ca2+]i). Importantly, cAMP induced the release of Ca2+ from InsP3-sensitive Ca2+ stores also responsive to cAMP-independent agonists such as cholinergic, histaminergic, and purinergic agonists that stimulate CFTR-independent fluid secretion. This provides two types of synergism that strongly potentiated cAMP-mediated fluid secretion but differed in their CFTR dependencies. First, CFTR-dependent secretion was strongly potentiated by low VIP and carbachol concentrations that individually were unable to stimulate secretion. Second, higher VIP concentrations more strongly potentiated the [Ca2+]i responses, enabling ineffectual levels of cholinergic stimulation to strongly activate CFTR-independent fluid secretion. These results identify important molecular mechanisms of cAMP-dependent secretion, including a requirement for Ca2+ signaling, and suggest new therapeutic approaches to correct defective submucosal gland secretion in CF. PMID- 20739759 TI - Specific Learning Disability and the Right to Education 2009 Act: call for action. PMID- 20739758 TI - Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs. AB - Cystic fibrosis (CF) results from mutations that disrupt CF transmembrane conductance regulator (CFTR), an anion channel found mainly in apical membranes of epithelial cells. CF leads to chronic infection of the airways with normally innocuous bacteria and fungi. Hypotheses to explain the pathophysiology of CF airways have been difficult to test because mouse models of CF do not develop human-like airway disease. The recent production of pigs lacking CFTR and pigs expressing the most common CF-causing CFTR mutant, DeltaF508, provide another model that might help clarify the pathophysiology of CF airway disease. Here, we studied individual submucosal glands from 1-day-old piglets in situ in explanted tracheas, using optical methods to monitor mucus secretion rates from multiple glands in parallel. Secretion rates from control piglets (WT and CFTR+/-) and piglets with CF-like disease (CFTR-/- and CFTR-/DeltaF508) were measured under 5 conditions: unstimulated (to determine basal secretion), stimulated with forskolin, stimulated with carbachol, stimulated with substance P, and, as a test for synergy, stimulated with forskolin and a low concentration of carbachol. Glands from piglets with CF-like disease responded qualitatively to all agonists like glands from human patients with CF, producing virtually no fluid in response to stimulation with forskolin and substantially less in response to all other agonists except carbachol. These data are a step toward determining whether gland secretory defects contribute to CF airway disease. PMID- 20739757 TI - The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice. AB - Translational control plays a key role in late spermiogenesis. A number of mRNAs encoding proteins required for late spermiogenesis are expressed in early spermatids but are stored as translationally inactive messenger ribonucleoprotein particles (mRNPs). The translation of these mRNAs is associated with shortening of their poly(A) tail in late spermiogenesis. Poly(A)-binding protein (Pabp) plays an important role in mRNA stabilization and translation. Three Pabp interacting proteins, Paip1, Paip2a, and Paip2b, have been described. Paip2a is expressed in late spermatids. To investigate the role of Paip2 in spermiogenesis, we generated mice with knockout of either Paip2a or Paip2b and double-KO (DKO) mice lacking both Paip2a and Paip2b. Paip2a-KO and Paip2a/Paip2b-DKO mice exhibited male infertility. Translation of several mRNAs encoding proteins essential to male germ cell development was inhibited in late spermiogenesis in Paip2a/Paip2b-DKO mice, resulting in defective elongated spermatids. Inhibition of translation in Paip2a/Paip2b-DKO mice was caused by aberrant increased expression of Pabp, which impaired the interaction between eukaryotic initiation factor 4E (eIF4E) and the cap structure at the 5' end of the mRNA. We therefore propose a model whereby efficient mRNA translation in late spermiogenesis occurs at an optimal concentration of Pabp, a condition not fulfilled in Paip2a/Paip2b DKO mice. PMID- 20739760 TI - Apolipoprotein E gene polymorphism and total serum cholesterol level in Iranian population. AB - BACKGROUND: Apolipoprotein E (APOE) is known as a major regulator of blood lipid levels in humans. A number of APOE gene allelic variants have been reported including E2, E3 and E4. Recent studies suggested a role for APOE in obesity and increased Body Mass Index (BMI) and plasma lipid levels in obese children. AIM: The aim of this study was to examine the association between APOE genetic variants and the BMI and lipid profile in an Iranian cohort. SETTING AND DESIGN: Samples were obtained from subjects who participated in a study based on the WHO designed MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study for coronary artery disease risk assessment in Zone 17 of Tehran. The study was approved by the local ethical committee. Informed consent was obtained from all subjects included in this study. MATERIALS AND METHODS: Subjects (n=320) were recruited. The level of triglyceride (TG) and total serum cholesterol was tested for all subjects in this study. Genotyping for APOE was carried using polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP)technique. STATISTICAL ANALYSIS: Levels of significance were determined using contingency tables by either Chi-square or Fisher exact analysis using the STATA (v8) software. The analysis of regression and significance of differences for level of cholesterol and TG was established by one-way analysis of variance followed by Dunnett post hoc multiple comparison tests using SPSS software Version 11.5. RESULTS: The frequency of allele E2 was significantly higher in patients with total serum cholesterol level <200 mg/dl (P 0.01 OR 2.1 95% CI 1.1-4.2). CONCLUSION: The association found in this study between allele E2 and lower total cholesterol level had been reported in previous studies. We have also observed that the frequency of genotype E2/E3 and E2/E4 was significantly higher in patients with normal total serum cholesterol level compared to patients with abnormal cholesterol (P=0.003 OR 2.4 95% CI; 1.3-4.6). Our data needs to be repeated in a larger population with more information for serum LDL and HDL levels and their subgroups. PMID- 20739761 TI - Association of glutathione S-transferase (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north Indian population. AB - BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM). The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST) family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. AIMS: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. SETTINGS AND DESIGN: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. MATERIALS AND METHODS: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR) and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP). STATISTICAL ANALYSIS: Fisher's exact test and chi2 statistics using SPSS software (Version-15.0). RESULTS: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325) and GSTP1 (I/V) (P=0.001, OR= 0.397, 95%CI=0.225-0.701) with T2DM and no significant association with GSTT1 (P=0.493). The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I) demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496). CONCLUSIONS: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V) and multiple association in GSTM1 null, T1 present and P1 (I/I), these polymorphisms can be screened in the population to determine the diabetic risk. PMID- 20739762 TI - Detection of inducible clindamycin resistance among Staphylococcal isolates from different clinical specimens in western India. AB - BACKGROUND: Macrolide (MLS B ) resistance is the most widespread and clinically important mechanism of resistance encountered with Gram-positive organisms. Resistance may be constitutive (cMLS B phenotype) or inducible (iMLS B phenotype). The iMLS B phenotypes are not differentiated by using standard susceptibility test methods, but can be distinguished by erythromycin-clindamycin disk approximation test (D-test) and demonstration of resistance genes by molecular methods. AIMS: To demonstrate in vitro inducible clindamycin resistance (iMLS B ) in erythromycin-resistant (ER) and clindamycin-susceptible (CLI-S) clinical isolates of Staphylococci spp., and interpretation of susceptibility tests to guide therapy. MATERIALS AND METHODS: Eight hundred and fifty-one isolates of Staphylococci spp. were recovered from various clinical specimens. All the Staphylococcal spp. were identified by conventional microbiological methods including colony morphology, Gram stain, catalase, slide coagulase and tube coagulase. Antibiotic susceptibility testing was performed by Kirby Bauer disc diffusion method. Erythromycin-resistant isolates were examined for inducible clindamycin resistance (iMLS B ) by using double disk approximation test (D-test) at 15 mm disk separation. RESULTS: The Staphylococci spp. isolated were 379 S. aureus [31.60% methicillin-resistant S. aureus (MRSA), 12.92% methicillin-sensitive S. aureus (MSSA)] and 472 coagulase-negative Staphylococci (CNS) [37.60% methicillin-resistant coagulase-negative Staphylococci (MRCNS), 17.86% methicillin-sensitive coagulase-negative Staphylococci (MSCNS)]. Four hundred and thirty (50.52%) Staphylococcal spp. isolates showed erythromycin resistance. Constitutive resistance was demonstrated in 202 (46.97%), inducible clindamycin resistance (iMLS B ) in 101 (23.48%), and non-inducible (MS) in 127 (29.53%). Two distinct induction phenotypes, D (18.13%) and D + (5.34%) were observed. All iMLS B isolates were susceptible to linezolid and vancomycin while 78.78% to ciprofloxacin. CONCLUSIONS: Fifty percent of Staphylococcal spp. were ER among which 23.48% were iMLS B phenotypes. Eighty-seven per cent of iMLS B phenotypes were observed to be methicillin-resistant. The high frequency of methicillin resistance isolates (87.12%) with in vitro inducible clindamycin resistance at our institute raises concern of clindamycin treatment failures with methicillin-resistant infections. So we recommend that microbiology laboratories should include the D-test for inducible resistance to clindamycin in the routine antibiotic susceptibility testing. PMID- 20739763 TI - Potentially inappropriate medication use in elderly patients: a study of prevalence and predictors in two teaching hospitals. AB - BACKGROUND: Geriatrics is an emerging clinical specialty in India. Information about the appropriateness of prescription medication use among the elderly in India is limited. AIMS: To determine the prevalence and predictors of potentially inappropriate medication (PIM) use, and assess the relationship between PIM use and adverse drug reactions (ADRs) in the hospitalized elderly. SETTINGS: Medicine wards at two teaching hospitals. DESIGN: Prospective observational study. MATERIALS AND METHODS: Patients aged > 60 years admitted to medicine wards between January 2008 and June 2009 were included and reviewed for PIM use according to the Beers Criteria 2003 (BC). Severity of PIM use was classified as per BC as 'high' or 'low'. ADRs observed in the study patients were also recorded. STATISTICAL ANALYSIS: Association between ADRs and PIM use was assessed using Chi Square test. Bivariate analysis and subsequently multivariate logistic regression was used to identify predictors of PIM use. RESULTS: PIM use was observed in 191 of 814 enrolled patients. At least one PIM at admission and during hospital stay was received by 2.4% (20) and 22.1% (180) patients respectively. High-severity PIM use showed a higher prevalence compared to low severity [26.8% (218) vs. 5.5% (45)]. Amongst the patients who received polypharmacy (> or = 5 concurrent medications), 1.4% (5/362) and 22.1% (163/736) patients received PIMs at admission and during hospital stay respectively. Use of aspirin/clopidogrel/diclofenac in the presence of blood clotting disorder or anticoagulant therapy (8.3%) was the most commonly encountered PIM use. Medications not listed in BC were associated with increased occurrence of ADRs compared to medications listed in BC (349 vs. 11) (chi2 =98.4, P<0.001). Increased number of concurrent medications' use (> or = 9) during the stay in medicine wards was identified as an influential predictor of PIM use [Odds ratio: 1.9, 95% Confidence Interval: 1.34-2.69, P<0.001) in the hospitalized elderly. CONCLUSION: PIM use was common (23.5%) among the elderly patients during their stay in medicine wards in two tertiary care hospitals. Measures targeted only at BC medications may do little to change the risk of ADRs in elderly. PMID- 20739764 TI - Maternal indicators and obstetric outcome in the north Indian population: a hospital-based study. AB - BACKGROUND: Understanding the effect of maternal parameters on obstetric outcome has public health importance because these indicators are associated with infant health and survival and influence development and health in later life. AIM: To determine the effects of various maternal indicators on pregnancy outcome in north-Indian women. SETTINGS AND DESIGN: A prospective study of all consecutive women with singleton pregnancy, who were registered in the first two months of pregnancy and delivered in the hospital. MATERIALS AND METHODS: Maternal indicators such as age, height, prepregnancy weight, body mass index (BMI), hemoglobin and parity were correlated with pregnancy outcome. The women with a medical disorder or complication that developed during the course of pregnancy were excluded. RESULTS: A total of 2027 women were analyzed. Maternal height, weight, BMI and parity had a positive significant correlation with birth weight of the newborn (r=0.081, P value < 0.001, r=0.148, P value <0.001, r = 0.121, P value < 0.001 and r = 0.099, P value < 0.001, respectively). Maternal height, weight and period of gestation were significant indicators for low birth weight on multivariate logistic regression. The rate of preterm delivery was significantly higher in women with hemoglobin < 7 g% and women with parity >3. The chances of caesarian section increased significantly with increase in maternal height, weight and BMI. CONCLUSIONS: A prepregnancy weight of more than 40 kg, BMI of more than 19.8 and hemoglobin of at least 7 g% or more favor good obstetric outcome. PMID- 20739765 TI - Statins: cost analysis in Indian scenario from eight major clinical trials. AB - BACKGROUND AND AIMS: Coronary heart disease (CHD) is the leading cause of death in India resulting in loss of young Indians. Statins have proved to reduce the CHD mortality in various clinical trials. The aim of the study is to find the cost-effectiveness ratio (CER) for each major coronary event averted and a coronary death avoided by use of statins in different clinical settings based on the data from the major clinical trials on statins. MATERIALS AND METHODS: Using electronic database and as per our inclusion and exclusion criteria we selected the West of Scotland Coronary Prevention Study (WOSCOPS), the Air Force Coronary Atherosclerosis Prevention Study (AFCAPS) and the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA) study for primary prevention; the Cholesterol and Recurrent Events Trial (CARE), the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study and the Scandinavian Simvastatin Survival Study (4S) for secondary prevention and two studies, the Heart Protection Study (HPS) and the Pravastatin in elderly individuals at risk of vascular disease (PROSPER) study for high-risk patients. The results of these studies were used for cost-effectiveness analysis of statins in different patient groups. STATISTICAL ANALYSIS: Absolute risk reduction, Number Needed to Benefit (NNTB), NNTB/year for total sample and in subgroups of males, females and age >65 was derived. CER for branded and generic versions was calculated by using the prices of statins listed in Indian Drug Review Triple i. RESULTS: Cost effectiveness ratio (CER) in primary prevention studies i.e., the WOSCOPS, the AFCAPS and the ASCOT-LLA was Rs. 25.8 lacs, Rs. 23.8 lacs and Rs. 7.9 lacs per major coronary event averted respectively. CER in secondary prevention studies i.e., the CARE and the LIPID was approximately Rs. 20 lacs per major coronary event averted while it was Rs. 52.4 lacs and Rs. 37 lacs per coronary heart disease (CHD) death avoided. CER from the 4S was Rs. 6.9 lacs per major coronary event and Rs. 16.9 lacs per CHD death averted. CER in the HPS and the PROSPER study was Rs. 17.9 lacs and Rs. 27.1 lacs per major coronary event avoided in high-risk patients. CONCLUSION: Cost associated with the use of statins is higher in primary prevention as compared to secondary prevention. More studies are needed to confirm the cost-effectiveness of statins to make any decision for health policy. PMID- 20739766 TI - A t (11; 22) (p13; q12) EWS-WT 1 positive desmoplastic small round cell tumor of the maxilla: an unusual case indicating the role of molecular diagnosis in round cell sarcomas. AB - A desmoplastic small round cell tumor (DSRCT) is an uncommon tumor characterized by polyphenotypic expression and a specific reciprocal translocation t (11; 22) (p13; q12). It has been rarely identified in the head and neck region. Herein, we describe a DSRCT in the maxilla of a young man, who was initially diagnosed with a primitive neuroectodermal tumor (PNET), based on histopathological appearance of a round cell tumor, with MIC2 and -FLI-1 positivity, on immunohistochemistry (IHC). Diagnosis of a DSRCT was confirmed on molecular analysis with positive -RT PCR and sequencing results for EWS-WT1 transcript and negativity for EWS-FL1. The case is presented to highlight the value of molecular diagnosis in round cell sarcomas at uncommon sites, especially when similar IHC markers can be expressed in a PNET and a DSRCT. An exact diagnosis of a round cell sarcoma has a therapeutic relevance. PMID- 20739767 TI - Paradoxical embolism causing stroke and migraine. AB - This case report describes a lady who underwent investigations as a part of a clinical study. A 32-year-old woman with a history of episodes of severe migraine with aura, deep vein thrombosis and recurrent epistaxis, presented with two episodes of stroke with no particular cause evident on routine investigations. A contrast echocardiogram demonstrated a patent foramen ovale (PFO). She was found to be positive for the Factor V Leiden mutation. The PFO was closed percutaneously. However, a substantial right to left shunt of 14% persisted. Pulmonary angiography revealed multiple arterio-venous malformations (AVMs) and she was diagnosed with hereditary hemorrhagic telangiectasia. The AVMs were embolized and she has had no further cerebral events. Interestingly, her episodes of 'migraine' have also improved dramatically following the closure of the PFO and the embolization of the AVMs. This case demonstrates the complex relationship between right to left shunts, cryptogenic stroke and migraine. PMID- 20739768 TI - Takotsubo cardiomyopathy presenting as postoperative atrial fibrillation. AB - Takotsubo cardiomyopathy (TC) is a condition which was first acknowledged in Japan and is characterized by a reversible systolic dysfunction of the apical or mid segments of the left ventricle. Typically affecting women in the post menopausal population, it is triggered by intense emotional, physical or medical stress. Also known as apical ballooning syndrome or stress cardiomyopathy, TC derives its name from the left ventricular angiographic appearance of a 'Takotsubo', literally translated as an 'octopus fishing trap' in Japanese. Patients often describe chest pain, have ischemic electrocardiogram (ECG) changes and positive cardiac enzymes mimicking an acute coronary syndrome. Obstructive coronary artery disease is excluded with prompt cardiac catheterization. We present the case of a 78-year-old lady, post gynecological surgery, presenting with palpitations and ECG confirming fast atrial fibrillation. Despite spontaneous cardioversion, she went on to develop ECG changes and cardiac enzyme elevations suggestive of an acute myocardial infarction. Cardiac catheterization was performed and confirmed the diagnosis of TC. It highlights an atypical presentation of TC, which can present initially as an arrhythmia in the postoperative phase as a consequence of the supraphysiological effects of elevated circulating plasma catecholamines. It reiterates the importance of prompt diagnosis and treatment to prevent cardiac decompensation in a condition poorly understood. PMID- 20739769 TI - Normal pressure hydrocephalus after gamma knife radiosurgery for vestibular schwannoma. AB - Vestibular schwannomas are not uncommon, and gamma knife radiosurgery is one of the treatment options for symptomatic tumors. Hydrocephalus is a complication of gamma knife treatment of vestibular schwannoma, though the mechanism of the development of hydrocephalus remains controversial. We present an unusual case of normal pressure hydrocephalus (NPH) after gamma knife radiosurgery of a vestibular schwannoma in which the timeline of events strongly suggests that gamma knife played a contributory role in the development of the hydrocephalus. This is probably the first case of NPH post radiosurgery with normal cerebrospinal fluid protein. Communicating hydrocephalus should be treated with placement of shunt while non-communicating hydrocephalus can be treated with third ventriculostomy. Frequent monitoring and early intervention post radiosurgery is highly recommended to prevent irreversible cerebral damage. PMID- 20739770 TI - Renal hemosiderosis: a case of black kidneys causing renal failure. PMID- 20739771 TI - Atypical ANCA pattern with simultaneous presence of MPO and PR3-ANCA in systemic lupus erythematosus. PMID- 20739772 TI - Glomus tumor occuring in male breast - an unusual site of presentation. PMID- 20739773 TI - FDG-PET/CT in diagnosis and early response evaluation of extra-pulmonary tuberculosis in a patient with aplastic anemia. PMID- 20739774 TI - Is b3a2 a better prognostic variant in childhood chronic myeloid leukemia? PMID- 20739775 TI - Ascaris lumbricoides: a stranger in the urinary bladder causing urinary retention. PMID- 20739776 TI - CD4 + /NKa + /CD8(dim+) T-cell large granular lymphocytic leukemia: a rare entity. PMID- 20739777 TI - Clinically effective CK-MB reporting: how to do it? AB - The clinical utility of measuring the Muscle Brain (MB) isoenzyme of creatine kinase (CK) in the diagnosis of myocardial injury is well established. CK/CK-MB measurement in combination or CK-MB alone is widely used and reporting the results of CK-MB in absolute unit is the common current practice. CK-MB is widely measured by "Immunoinhibition" in India, which gives falsely elevated CK-MB results in the following circumstances: Central nervous system damage, childbirth, macro CK-immunoglobulin complex, in patients with carcinoma of various organs, such as prostate carcinoma and other adenocarcinomas. But, reporting %CK-MB rather than the absolute CK-MB results assists in detection of macroCK (or CK variants), associated proliferative and autoimmune pathologies and their prognosis. PMID- 20739778 TI - Esomeprazole-induced photoallergic dermatitis. AB - There are no published case reports of esomeprazole-induced photoallergic dermatitis. We report here a 58-year-old lady with prior history of propylthiouracil and carbimazole-induced photoallergy, who presented with heartburn and dysphagia. She was diagnosed to have erosive esophagitis and was treated with esomeprazole, following which she developed photoallergic dermatitis. It improved on cessation of the drug and did not recur on subsequent treatment with ranitidine. Naranjo score for this adverse drug event was 8, thereby making it a probable adverse drug reaction. This reaction may be due to sulphur moiety, which is common to all these drugs. Physicians must be aware of this possible side-effect, especially in patients with prior history of photoallergy to other drugs. PMID- 20739779 TI - Lymphatic filariasis in India: epidemiology and control measures. AB - Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is an important public health problem in India. Both parasites produce essentially similar clinical presentations in man, related mainly to the pathology of the lymphatic system. Filariasis is endemic in 17 States and six Union Territories, with about 553 million people at risk of infection. The Government of India has accorded a high priority for elimination of this infection through mass chemotherapy programme (annual, single dose of Diethylcarbamazine citrate, i.e. DEC - 6 mg/kg of bodyweight, plus Albendazole repeated four to six times). This campaign has become a part of the National Vector-Borne Disease Control Programme in 2003 under the National Health Policy 2002 and aims to eliminate filariasis by 2015. We discuss here the epidemiology and current control strategy for filariasis; highlighting key issues, challenges and options in the implementation of the programme, and suggesting measures for mid-course corrections in the elimination strategy. PMID- 20739780 TI - PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility. AB - Systemic lupus erythematosus (SLE) is a prototype autoimmune disease. SLE is a result of one or more immune mechanisms, like autoantibody production, complement activation, multiple inflammation and immune complex deposition leading to organ tissue damage. SLE affected patients are susceptible to common and opportunistic infections. There are several reports suggesting that Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Genetic factors and environmental factors also play an important role in the overall susceptibility to SLE pathophysiology. Recently, protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene, has been found to be associated with several autoimmune diseases like SLE, Grave's disease and Hashimoto thyroiditis. The missense R620W polymorphism, rs 2476601, in PTPN22 gene at the nucleotide 1858 in codon 620 (620Arg > Trp) has been associated with autoimmune diseases. The PTPN22 locus is also found to be responsible for development of pulmonary tuberculosis in certain populations. The PTPN22 1858C/T gene locus will be ideal to look for SLE susceptibility to tuberculosis in the Indian population. In this review, we focus on human PTPN22 gene structure and function as well as the association of PTPN22 gene polymorphisms with SLE susceptibility. PMID- 20739781 TI - Systemic lupus erythematosus and tuberculosis: a review of complex interactions of complicated diseases. AB - Infections, renal failure and cardiovascular disease account for the majority of mortality in systemic lupus erythematosus (SLE). Although most infections are caused by Gram-positive or Gram-negative bacteria, there is an increase in the incidence of Mycobacterium tuberculosis and other opportunistic infections that also account for increased mortality. The higher prevalence of tuberculous infections in SLE is attributed to multiple immune abnormalities seen in these patients. SLE and tuberculosis (TB) interact in complicated ways - they may have similar presentation and may mimic each other. In an individual patient, it becomes important to differentiate one from the other. In this review, we have highlighted the complex interactions of these diseases, the impact of one on the other and the various modalities available for the evaluation and management and their shortcomings. Considering the high prevalence of TB in India, it becomes all the more important for us to be aware of this interaction in our population. PMID- 20739782 TI - Solitary cysticercus granuloma-treatment with albendazole: what is the optimal duration? PMID- 20739783 TI - Limb-girdle muscular dystrophy type 2A. PMID- 20739784 TI - Sporadic hemiplegic migraine in children. PMID- 20739785 TI - Progressive myoclonic epilepsy. AB - Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects. PMID- 20739786 TI - Abnormal expression of dopamine and serotonin transporters associated with the pathophysiologic mechanism of Tourette syndrome. AB - BACKGROUND: Tourette syndrome (TS) is a neurobehavioral and neuropsychiatric disorder and its pathophysiology is not well understood. However, recent studies provide evidence implicating metabolic abnormalities of dopamine (DA) and serotonin (5-HT) of the basal ganglia both in TS patients and TS animal models. It is also well known that dopamine and serotonin transporters (DAT and SERT) are monoamine neurotransmitter transporters, which participate in the metabolism of DA and 5-HT, respectively. OBJECTIVE: To evaluate whether expression of DAT and SERT in the striatum could lead to pathophysiological change in TS rat model. MATERIALS AND METHODS: Twenty-four Wistar male rats were randomly allocated to: TS model group (n=12) and control group (n=12). The stereotypy counts were recorded during the 2-week period of inducing TS rat models. The levels of DA and 5-HT in striatum homogenate were measured by ELISA. The protein and mRNA expression of DAT and SERT in the striatum were tested respectively by Immunofluorescence, Western blot and quantitative real-time PCR. Results : ANOVA analysis indicated that the stereotypy scores were much higher in the TS model group than in the control group at different time points (P<0.01). By ELISA analysis, the DA concentration in striatum homogenate was higher in the TS model group (130.92 +/- 25.60 ng/mL) than in the control group (101.00 +/- 20.14 ng/mL) (P<0.01), but 5-HT concentration in striatum was found to be lower in the TS model group (59.79 +/- 14.73 ng/mL) compared to the control group (77.01 +/- 14.05 ng/mL) (P<0.05). Analysis of protein and mRNA levels revealed a lower expression of DAT, concomitant with a higher expression of SERT in striatum of the TS model group than in the control group. CONCLUSIONS: Lower expression in DAT, concomitant with higher expression in SERT could participate in the pathophysiology of TS. PMID- 20739787 TI - Protective effects of the calcium-channel blocker flunarizine on crush injury of sciatic nerves in a rat model. AB - BACKGROUND: Neural damage can be mitigated by calcium-channel blockers (CCBs). However, the mechanism of action of CCBs is not yet fully understood. Objective : To investigate the mechanism of action and efficacy of CCB, flunarizine in restoring neural function after crush injury to the nerves. MATERIALS AND METHODS: The sciatic nerves of rats were crushed using pincers to establish the model for crush injury. Two hundred and eighty-eight Sprague-Dawley (SD) rats were randomly divided into sham-operated, saline, and low-dose flunarizine and high-dose flunarizine (FI and FII) groups. The expression of the protein c-fos in the dorsal root ganglia (DRG) after crush injury to the sciatic nerves was investigated by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The effect of flunarizine on c-fos expression and its efficacy in restoring neural function was evaluated. RESULTS: The c-fos messenger ribonucleic acid (mRNA) and protein expression in FI and FII groups was significantly lower than in the saline group and was the least in the FII group. Nerve-conduction velocity was increased in the order of: saline < FI< FII< sham operated. There was no significant difference in the nerve-conduction velocity in the sham-operated and FII groups (P>.05). CONCLUSIONS: When administered after crush injury to peripheral nerves, flunarizine may protect neurons with lesions from further damage and improve neural function by downregulating c-fos expression. PMID- 20739788 TI - Are somatosensory evoked potentials of the tibial nerve the most sensitive test in diagnosing multiple sclerosis? AB - BACKGROUND: Multiple sclerosis (MS) is mostly diagnosed clinically, but the diagnosis has significantly improved through the use of brain magnetic resonance imaging (MRI), testing of cerebrospinal fluid, and multimodal evoked potentials (MEPs). Even though MRI is the superior method in diagnosing this illness, MEPs remain important because they can detect clinically silent lesions in the sensory and motor pathways of the central nervous system (CNS). AIM: The aim of the study is to test the diagnostic sensitivity of MEPs and MRI and the ratio of their sensitivity in patients with MS. MATERIALS AND METHODS: The study subjects included 293 patients with MS with disease duration of two to six years: 249 patients with relapsing-remitting (RR) MS and 44 with primary-progressive (PP) MS. All patients were subjected to an MRI brain scan, visual evoked potentials (VEPs), median somatosensory evoked potentials (SEPs), tibial somatosensory evoked potentials (SEPs), and auditory evoked potentials (AEPs). Abnormal Findings Included : changed wave morphology, interside difference in wave amplitude, absolute and interwave latency increased by 2.5 SD as compared with the control group. The control group comprised of 35 healthy subjects. Results : In this study the most abnormal findings were tibial SEPs, median SEPs, and VEPs. Our results suggest different sensitivity of MEPs in patients suffering from different forms of MS. In RR-MS the sensitivity of tibial SEPs was statically significant (Fischer's exact probability test) as compared to other evoked potential modalities. Similarly VEPs were more sensitive as compared to AEPs. In the PP-MS, median SEPs have been found to be more sensitive than VEPs, while tibial SEPs have been found to be more sensitive than AEPs. There was no significant difference in the sensitivity of MRI and MEPs both the forms of MS. CONCLUSION: Tibial SEPs produce the most abnormal results and the highest sensitivity in the RR-MS. We propose that this test as useful criterion for the diagnosis of MS. PMID- 20739789 TI - Sural nerve biopsy in chronic inflammatory demyelinating polyneuropathy: are supportive pathologic criteria useful in diagnosis? AB - BACKGROUND: According to American Academy of Neurology (AAN) criteria, demonstration of demyelination in the sural nerve by teased fiber or ultrastructure is considered mandatory for diagnosis of chronic inflammatory demyelinating polyneuropathies (CIDP). In resource-restricted settings where these techniques are not freely available, it is useful to determine the utility of 'supportive' pathologic criteria (subperineurial edema, inflammation, onion bulb formation, and demyelination) proposed by AAN for diagnosis of CIDP. SETTINGS AND DESIGN: Tertiary care hospital, retrospective study. PATIENTS AND METHODS: Forty-six patients with idiopathic CIDP (32 with progressive course and 14 with relapsing-remitting course) satisfying AAN clinical and electrophysiologic criteria evaluated between January 1991 and August 2004 were reviewed. Frequency of specific pathological alterations such as demyelination, inflammation, onion bulb formation, and axonal changes in sural nerve biopsies was evaluated. Statistical Analysis : SPSS statistical package was used to calculate mean, range, and standard deviation. Student's t test, chi-square test, and ANOVA were used for determining statistical significance. RESULTS AND CONCLUSION: Reduction in myelinated fiber density was most frequent (93.5%), followed by demyelination (82.8%), inflammation (58.7%), and onion bulb formation (28.3%). Endoneurial inflammation was frequent in the relapsing-remitting form and epineurial inflammation and axonal changes in those with progressive course. Greater disability at presentation, poor response to immunomodulation, and lower CSF protein levels was seen in those with axonal pathology. Pathological abnormalities were demonstrable in all (100%), whereas electrophysiological abnormalities were detected in 90.8%, suggesting that supportive histologic AAN criteria are helpful in diagnosis of CIDP. PMID- 20739790 TI - Limb girdle muscular dystrophy type 2A in India: a study based on semi quantitative protein analysis, with clinical and histopathological correlation. AB - BACKGROUND: Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutation in the gene encoding for calpain-3 resulting in total or partial loss of protein. Diagnosis of LGMD2A, the most prevalent form of LGMD, is established by analyzing calpain-3 protein deficiency or CAPN3 gene mutation. Since there is no data from India regarding the incidence of LGMD2A, this study was undertaken. AIMS: To study the frequency of LGMD2A in Indian population on the basis of protein analysis by immunoblotting and to correlate pathological and clinical features with protein analysis. SETTINGS AND DESIGN: One hundred and seventy-one muscle biopsies of clinically suspected LGMD, unclassified muscular dystrophy or myopathy were analyzed in a tertiary national referral centre for neurosciences. Materials and Methods : Histopathological, immunohistochemical and enzyme histochemical analysis of muscle biopsies was performed followed by protein analysis for calpain-3 and dysferlin by immunoblotting. RESULTS: Immunoblot identified 75 patients (43.8%) with calpain-3 deficiency, of which 36 (45%) had complete loss and 39 (55%) had partial loss of calpain-3 protein. In patients with LGMD phenotype alone, the incidence of LGMD2A was 47%. The biopsies of these patients displayed variety of morphological changes ranging from dystrophic pattern with presence of active fibre necrosis, regeneration and lobulated fibres to end stage muscle disease. The mean age of presentation and disease onset was 24 and 18 years respectively. CONCLUSIONS: This series of 75 patients is probably the first confirmed cases of LGMD2A (calpainopathy) from India. Our study suggests that LGMD2A is the most frequent form of LGMD in India, similar to the Western data, thus, highlighting the importance of immunoblotting for an accurate diagnosis. PMID- 20739791 TI - Underlying prothrombotic states in pregnancy associated cerebral venous thrombosis. AB - BACKGROUND: The exact pathogenesis of pregnancy associated cerebral venous thrombois is still unsettled. Aims : To identify possible inherited and acquired prothrombotic risk factors and also identify the factors associated with mortality in pregnancy associated CVT. SETTINGS AND DESIGN: Prospective cohort study to identify prothrombotic risk factors and case control study of influence of local traditional practice of puerperal water restriction on postpartum CVT. MATERIALS AND METHODS: Consecutive patients with pregnancy associated CVT seen over a period of three years. Thrombotic workup included genetic markers, protein assays, and other factors. STATISTICAL ANALYSIS: Univariate and chi-square analysis. RESULTS: Of the 41 patients studied during the study period, 71% of patient had a single and 34% had multiple prothrombotic risk factors. Methylene tetrahydro-folate reductase (MTHFR) heterozygosity (19.5%) and factor V Leiden heterozygous (7.3%) were the commonest genetic markers. Hyperhomocysteinemia (34%) and elevated factor VIII levels (14.6%) were the other important risk factors. In this cohort the mortality was 17%. Mortality increased by odds of 1.3 for every additional prothrombotic marker. The factors associated with increased mortality included: status epileptics (P = 0.05, OR 13.2, 95% CI 1.002 - 173), deep venous system involvement (P = 0.016, OR 9.64, 95% CI 1.53 - 60.6), presence of midline shift (P = 0.012, OR 24.7, 95% CI 2.05 - 29.8) and diffuse cerebral edema (P = 0.006, OR 14.5, 95% CI 2.18- 96.4). The traditional practice of decrease intake of water during puerperium was significant in woman with pregnancy associated CVT when compared to control subjects (P < 0.02). CONCLUSION: In patients with pregnancy associated CVT, prothrombotic markers can be multiple and are associated with increased odds of mortality. Deep venous system involvement, presence of midline shift and diffuse cerebral edema increased mortality. Peuperial water restriction may be a modifiable risk factor. PMID- 20739792 TI - Comparison of 1 week versus 4 weeks of albendazole therapy in single small enhancing computed tomography lesion. AB - BACKGROUND: The appropriate duration of albendazole therapy in neurocysticercosis is uncertain. The observation in small uncontrolled randomized trials in children that short-course therapy (1 week) is as effective as the conventional regimen (4weeks) must be tested. OBJECTIVE: To compare the efficacy of 1 and 4 weeks of albendazole therapy in children with single small enhancing computed tomographic lesion (SSECTL). STUDY DESIGN: An open-labeled, randomized, clinical trial. MATERIALS AND METHODS: One hundred twenty children with SSECTLs presenting with seizure. INTERVENTION: The subjects were assigned to two groups using random tables: group A (n=58) received albendazole for 1 week and group B (n=62) for 4 weeks. All the subjects were followed up for 6 months. RESULTS: The proportions of subjects with complete resolution of lesion in the two groups were similar (group A 63.8% versus group B 51.6%). The proportion of subjects in the two groups in whom the lesion calcified on follow up (group A 19% versus group B 24.2%) also did not differ significantly. The incidence of seizure recurrence during the 6-month follow-up period was also similar in both the groups (group A 9.6% versus group B 3.4%, P > 0.05). CONCLUSION: One week of albendazole therapy is as effective as 4 weeks of therapy in children with SSECTLs. PMID- 20739793 TI - Depressive symptoms in patients with epilepsy: analysis of self-rating and physician's assessment. AB - BACKGROUND: Depression has significant negative impact on the quality of life in patients with epilepsy (PWE). AIM: This study assessed the prevalence of depression in PWE and the impact of seizure variables on the depression scores. SETTINGS AND DESIGN: A case-control study of randomly selected PWE attending a tertiary hospital in a metropolitan, Nigeria. MATERIALS AND METHODS: A total of 152 randomly selected subjects the Beck Depression Inventory (BDI) for quantitative assessment of depression, while the Hamilton Rating Scale for Depression (HRSD) was used by the investigators. STATISTICAL ANALYSIS: The Student t test assessed statistical significance of differences in the BDI and HRSD scores, whereas the scores were correlated with Pearson's correlation coefficient. Logistic regression analysis and Chi-square test for trend assessed the impact of seizure variables on the scores. The level of significance was taken as P < 0.05. RESULTS: The prevalence of depressive symptoms was 42% and 45% using the HRSD and BDI, respectively, with significant differences in the scores of the patients and controls on the both scales (P < 0.001). The PWE scores on both scales yielded a correlation coefficient of 0.8 indicating their utility in detecting depressive symptoms. Seizure control was the most potent predictor of depression (HRSD: P = 0.004; BDI: P = 0.001). CONCLUSIONS: Depressive symptoms are common in epilepsy. Early detection and prompt management are recommended. Good seizure control with an appropriate antiepileptic drug, among other interventional measures, may contribute to the prevention of depression in epilepsy. PMID- 20739794 TI - Intraoperative angiography in aneurysm surgery: an initial experience. AB - BACKGROUND: Intraoperative angiography (IOA) assumes an important role in the prevention of complications such as aneurysmal neck remnant or compromise of adjacent cerebral vasculature during surgery for cerebral aneurysms. Aims : To determine the feasibility, efficacy and safety of IOA in aneurysmal surgery. SETTINGS AND DESIGN: Prospective study of IOA in patients undergoing aneurysmal surgery. MATERIALS AND METHODS: IOA was performed using digital subtraction angiography (DSA) compatible C-arm, radiolucent operating table and appropriate femoral sheath, guiding catheters and guide wires in 20 consecutive patients after surgical clipping of the cerebral aneurysm. The post-clipping IOA was compared with preoperative angiogram. RESULTS: Complete aneurysmal obliteration was confirmed in all the patients. In two patients compromization of adjacent vessels was noted, which could be rectified by repositioning of the clip. Some degree of vasospasm was noted in all the patients. Intra-arterial nimodipine was administered in four patients with severe vasospasm. There was improvement in two patients. Time taken for performing IOA varied from 30 to 45 min. No complications attributable to IOA were encountered in this study. CONCLUSION: IOA is a safe and effective adjunctive tool for aneurysm clipping. Routine use of IOA in all cases of aneurysmal surgery is recommended. PMID- 20739795 TI - Endovascular embolization of very small cerebral aneurysms. AB - BACKGROUND: Very small cerebral aneurysms are considered to be one of the challenges for endovascular treatment, with difficulty for catheterization and high risk for intraoperative rupture. We report the treatment of very small (< 3 mm) cerebral aneurysms by coil embolization. MATERIALS AND METHODS: We performed a retrospective analysis of 11 consecutive patients with very small aneurysms treated by coil embolization in our institute between February 2007 and February 2009. RESULTS: Three-dimensional rotational angiography (3DRA) was most accurate in the detection of these aneurysms; 3DRA revealed the aneurysms in two patients in whom conventional angiography failed to demonstrate the aneurysms. The Hunt Hess (HH) grade was grade 0 (unruptured aneurysm) in one patient and grade I in ten patients. Coil embolization was successfully performed in 11 patients. Complete (n = 8) or near complete (n = 3) immediate occlusion was obtained. One or three soft coils were used in all the patients with the shortest available length. Balloon assistance was used in one patient and stent assistance was used in seven patients. Although coil migration into the MCA was seen in one patient and intraoperative aneurismal rupture occurred in one patient, no untoward clinical complication was seen. Follow-up DSA in 11 patients demonstrated persistent occlusion (n = 9) or progressive thrombosis (n = 2) of the aneurysms. All the patients with available follow-up had a modified Rankin Score (mRS) of 0. CONCLUSION: HH grade 0 and I very small cerebral aneurysms can be treated by endovascular coil embolization. Use of short, soft coils and balloon/stent assistance is useful. PMID- 20739796 TI - Neurological complication of dengue infection. AB - Dengue infection is endemic in more than 100 countries, mostly in the developing world. Recent observations indicate that the clinical profile of dengue is changing, and that neurological manifestations are being reported more frequently. The exact incidence of various neurological complications is uncertain. The pathogenesis of neurological manifestations is multiple and includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. In countries endemic to dengue, it will be prudent to investigate for dengue infection in patients with fever and acute neurological manifestations. There is need for understanding of the pathogenesis of various neurological manifestations. PMID- 20739797 TI - Encephalitis in the clinical spectrum of dengue infection. AB - Dengue viral infections are common worldwide. Clinical manifestations form a broad spectrum, and include uncomplicated dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Encephalopathy has been well reported and has classically been thought to result from the multisystem derangement that occurs in severe dengue infection; with liver failure, shock, and coagulopathy causing cerebral insult. However, there is increasing evidence for dengue viral neurotropism, suggesting that, in a proportion of cases, there may be an element of direct viral encephalitis. Understanding the pathophysiology of dengue encephalopathy is crucial toward developing a more effective management strategy. This review provides an overview of the clinical spectrum of dengue infection, and examines evidence supporting the existence of dengue encephalitis. PMID- 20739798 TI - Dengue infection causing acute hypokalemic quadriparesis. AB - Dengue infection is endemic to India and an important public health problem. We report three confirmed cases of dengue infection with acute, pure motor, reversible quadriparesis due to hypokalemia. Clinicians should be aware of such an association and consider the clinical possibility in the differential diagnosis while evaluating acute quadriparesis in patients with dengue fever, especially in endemic areas. PMID- 20739799 TI - Acute disseminating encephalomyelitis with hemorrhage following dengue. PMID- 20739800 TI - Unilateral diaphragmatic paralysis following dengue infection. PMID- 20739801 TI - Dengue myositis and myocarditis. PMID- 20739802 TI - Acute disseminated encephalomyelitis following dengue hemorrhagic fever. PMID- 20739803 TI - Clinical utility of susceptibility-weighted imaging in vascular diseases of the brain. AB - Susceptibility-weighted imaging (SWI) is a rapidly evolving technique that utilizes both the magnitude and phase information to obtain valuable information about susceptibility changes between tissues. SWI is very sensitive to the paramagnetic effects of deoxyhemoglobin. SWI plays an important role in the diagnostic evaluation and management of acute stroke. In addition, it also plays an important role in the imaging of patients with chronic arterial occlusion and in understanding the effects of chronic infarction, like incomplete infarction and cortical laminar necrosis. The hemodynamic status and oxygen extraction fraction can also be evaluated. SWI is useful in evaluating cerebral venous sinus thrombosis by demonstrating the hemorrhagic venous infarction and thrombus in the sinus and the cortical veins, as well as secondary phenomena like venous stasis in the form of engorged cortical and transmedullary veins and collateral slow flow. Low-flow vascular malformations that are not visualized well on conventional sequences are depicted in exquisite detail along with the venous components on SWI. SWI is used for evaluating cavernomas, developmental venous anomalies, telangiactasias, dural arteriovenous fistulas and the various components of arteriovenous malformations. It has also evolved as a noninvasive technique for evaluating various anomalies of the venous system without administering contrast. Vasculopathies and vasculitis are associated with cerebral microbleeds which are detected on SWI. On the basis of the additional information provided by SWI, it can be included in the routine brain imaging protocol. PMID- 20739804 TI - Susceptibility-weighted imaging in the evaluation of brain arteriovenous malformations. AB - BACKGROUND: Digital subtraction angiography (DSA) remains the gold standard in the evaluation of arteriovenous malformations (AVMs). Susceptibility-weighted imaging (SWI), a relatively new magnetic resonance imaging (MRI) technique, exploits the magnetic susceptibility differences of various tissues, such as blood, iron and calcification. Earlier studies have shown that the magnitude and phase information of SWI offers improved sensitivity, revealing low-flow vascular malformations that are invisible on conventional gradient-echo (GRE) sequences. AIM: To evaluate the imaging appearance of AVMs on SWI. MATERIALS AND METHODS: In this retrospective study, the appearance of the various components (feeding artery, nidus, and draining veins) of AVMs on the phase, magnitude, and minimal intensity projection (minIP) images of SWI were analyzed in 14 patients with AVM and compared with conventional sequences. RESULTS: Detection and delineation of various components of AVMs was best achieved in the magnitude images. Although minIP was most effective in detecting hemorrhage and calcification, it was the magnitude image that could separate the hemorrhagic and calcified component in the nidus from the remaining nidus. The minIP was less effective in detecting the AVM components, especially nidus and draining vein, whereas conspicuity was poor with the phase images. CONCLUSION: The magnitude images of the SWI help in differentiating the different components of AVM and also helps in differentiating nidus from hemorrhage and calcification. PMID- 20739805 TI - Susceptibility-weighted imaging in differentiating bilateral medial thalamic venous and arterial infarcts. AB - Bilateral medial thalamic infarcts may be due to thrombosis of internal cerebral veins or occlusion of artery of Percheron. Conventional MR imaging is often not helpful in differentiating the two. We discuss two cases in whom susceptibility weighted imaging, including phase images contributed in demonstrating the thrombosed or patent internal cerebral veins. PMID- 20739806 TI - Susceptibility-weighted imaging in capillary telangiectasia. PMID- 20739807 TI - Middle cerebral artery susceptibility sign and venous prominence in acute ischemic stroke. PMID- 20739808 TI - Clinical and genetic study of a Chinese family with spinocerebellar ataxia type 7. AB - Spinocerebellar ataxia 7 (SCA7) is a rare disease, and only few SCA7 families have been reported, especially from East Asia. Clinical features of a genetically confirmed SCA7 Chinese family were evaluated. The onset of the disease varied from 4 years to 48 years, and the initial presenting feature was cerebellar ataxia or visual impairment, or both. There were abnormal findings on fundus photography, electroretinogram, flash visual evoked potential and oscillatory potentials. Abnormal mitochondria were also found in skeletal muscle or liver biopsies. The number of cytosine adenine guanine (CAG) repeats ranged from 50 to 97, and the length of CAG repeat was inversely correlated with the age of onset (r=-0.867, P=0.025). CONCLUSION: The clinical manifestations and SCA7 gene of SCA7 patients were homogeneous in this study. Larger CAG repeats had not only resulted in earlier onset, but also related to the rapid progression and severity of the disease. Abnormal mitochondria may be a common finding in biopsy studies of various organs in SCA7 patients. PMID- 20739809 TI - R778L, H1069Q, and I1102T mutation study in neurologic Wilson disease. AB - There is paucity of the studies on mutations in neurologic Wilson disease (WD) in India. We studied H1069Q, R778L, I1102T mutations in 26 patients with neurologic WD from 25 families in north India. The basis of diagnosis of neurologic WD was clinical, Kayser-Fleischer (KF) ring, and ceruloplasmin. Data collected included: family history, clinical characteristics, laboratory data, ultrasound findings, magnetic resonance imaging (MRI) findings, and severity of the disease. DNA was isolated from venous blood and subjected to H1069Q, R778L, and I1102T mutation study. The age range was 5-41 years. Family history was present in 8 patients. The H1069Q, R778L, and I1102T mutations were absent in all the patients and in 16 parents and siblings. Severity of the illness was related to the extent of MRI changes but not with age of onset and hepatic involvement. H1069Q, R778L, and I1102T mutations were absent in our patients, which may be due to genetic and ethnic heterogeneity and further studies are required. PMID- 20739810 TI - Migraine, epileptic seizures and psychogenic non-epileptic seizures: observations in Indian patients in a clinic-based study. AB - The present study focuses on the incidence of epileptic seizures in 1000 patients (200 children and 800 adults) with migraine. Very few patients with migraine had history of epileptic seizures. No patient had migraine-induced seizures and none had seizure-induced migraine like headaches. Occurrence of psychogenic non epileptic attacks during migraine headaches had not been highlighted in the past. In the present study, about a quarter of patients with migraine, especially adolescent and adult females, had history of psychogenic non-epileptic seizures during attacks of acute migraine. This appears to be the first report on these features in Indian subjects with migraine. PMID- 20739811 TI - Bony reconstruction by reposition of bony chips in suboccipital craniectomy. AB - In suboccipital craniectomy where the bone is not repositioned, there may be a significant cosmetic defect due to lack of skull bone in the suboccipital region. It may accompanied by sensory symptoms, including pain. To prevent any cosmetic defect and sensory symptoms we repositioned the bone chips at the craniectomy site in 42 suboccipital craniectomies before the closure of the scalp. At a mean follow-up of 22 months (range: 5-44 months), two patients complained of mild discomfort in the healed wound or of occasional local pain. One patient complained of mild itching at the site. In two patients, bone chips were accumulated at the lower part of the suboccipital craniectomy and failed to form a uniform bone cover at the operated site. In one patient, all bone chips were reabsorbed and there was no bone at the operated site. There was pseudomeningocele formation in one patient. In the rest of the cases there was satisfactory bone coverage at the operated site, both clinically and radiologically. The wound sites were aesthetically acceptable in 40 cases. Our study suggests that in the majority of cases where suboccipital craniotomy is not possible or not done, repositioning of the bone chips at the craniectomy site is associated with satisfactory aesthetic and functional outcome and formation of bone coverage at the operated site. PMID- 20739812 TI - Concomitant occurrence of subfrontal extradural hematoma and orbital subperiosteal hematoma: a rare entity. AB - Subfrontal extradural hematomas are uncommon, similar are orbital subperiosteal hematomas. Co-occurrence of both following head trauma is very rare. We describe co-occurrence of sub frontal extradural and orbital subperiosteal hematomas in four patients. The presenting symptoms were proptosis and visual complaints. Diagnosis was confirmed on computed tomography in three patients and magnetic resonance imaging in one patient. Frontal craniotomy and superior orbitotomy with evacuation of hematoma resulted in complete resolution of proptosis and visual symptoms. We emphasize on the early diagnosis of this rare condition and also emergency treatment to prevent permanent visual loss. PMID- 20739813 TI - Hyper insulinemia in an hemicrania continua patient with sexual headache: Hypothesizing the basis for this unusual association. AB - The coexistence of hemicrania continua with another primary headache disorder is a very rare event. We report a male patient with both hemicrania continua of 16- year duration and pre-orgasmic headache of three-year duration. Both headache disorders responded to indomethacin. The patient had also in addition persistent elevation of fasting serum insulin. PMID- 20739814 TI - Cervical rib with stroke as the initial presentation. AB - Cervical ribs rarely become symptomatic. Cerebral ischemia or infarct due to cervical rib is extremely rare and, invariably, these patients have a history of upper limb symptoms before presenting with stroke. We report a young boy with cervical rib who presented with stroke. A right sided cervical rib was noted during angiogram, causing mild stenosis and post stenotic dilatation of right subclavian artery distal to the rib. An abduction angiogram showed complete occlusion of the right subclavian artery and visualization of collaterals. Right carotid angiogram also showed evidence of thromboembolic episodes in the right middle cerebral artery territory. PMID- 20739815 TI - Sporadic hemiplegic migraine in children: a report of two new cases. AB - Two cases of sporadic hemiplegic migraine, which fulfilled the diagnostic criteria as laid down in International Classification of Headache Disorders (ICHD)-2, are reported in children. In the first case, two unusual features were noted, namely, the occurrence of dysphsia in association with a left hemiparesis and the spread of sensory symptoms to the contralateral side during attacks. The second case is perhaps the youngest patient reported with this disorder. PMID- 20739816 TI - Cerebellar glioblastoma multiforme with non-contiguous grade 2 astrocytoma of the temporal lobe in the same individual. AB - Multicentric Gliomas, both supratentorial and infratentorial, with varying histopathological picture is extremely rare. We report a unique occurrence of such a combination in a 50-year-old man who presented with features of elevated intracranial pressure, ataxia and vertigo. Magnetic resonance imaging showed a diffuse non-enhancing lesion in the temporal lobe and insula and another non contigous well defined enhancing lesion in the cerebellum. Both the lesions had mass effect. The lesions were decompressed; first the temporal lesion and then the cerebellar lesion. Histopathology revealed grade II astrocytoma in the temporal lobe and glioblastoma multiforme in the cerebellum. He recieved whole brain radiotherapy with which he showed symptomatic improvement and survived for 1.5 years. PMID- 20739817 TI - Acute spontaneous subdural hematoma of arterial origin: a report of four cases and review of literature. AB - Acute spontaneous subdural hematoma of arterial origin, a neurosurgical emergency resulting from rupture of the perisylvian cortical artery, is a rare occurrence. We report four such patients who presented with progressive neurological deterioration. All the patients were operated and perisylvian cortical artery was identified as the source of bleeding in all the patients. Three of the patients had associated hypertension. We reviewed the clinical characteristics, etiology, and outcome of the reported cases in the literature. A high index of suspicion is necessary even in young patients in view of the phenomenon of re-rupture mimicking stroke. Early diagnosis and a wide craniotomy over the sylvian fissure to obtain hemostasis of bleeding points results in good outcome. PMID- 20739818 TI - Contrasting behavior of glio-ependymal cysts: a report of two cases and literature review. AB - Cystic lesions of the brain may present with seizures or headache due to raised intracranial pressure. These cysts when associated with developmental brain anomalies may turn out to be pathologic surprises. In the present communication, two patients with glio-ependymal cysts were described with contrasting symptomatologies and surgical management. Non-enhancing cystic lesions of the brain, without mural nodule, may turn out to be glio-ependymal cysts, requiring total surgical excision or marsupilization. PMID- 20739819 TI - Unusual cause for ventriculoperitoneal shunt failure: carcinoma breast compressing distal catheter. AB - Insertion of a ventriculoperitoneal (VP) shunt is one of the most common surgical procedures in any neurosurgery unit worldwide. Distal catheter obstruction outside the peritoneum is a rare cause of shunt failure. We report the first case of distal obstruction in a 70-year old female by carcinoma breast engulfing the catheter and causing kinking. Intraoperatively, the catheter was intratumoral with no flow of cerebrospinal fluid distally. She underwent relocation of a new catheter to the opposite side of the abdomen and modified mastectomy with resolution of the hydrocephalus. The postoperative course has been uneventful. PMID- 20739820 TI - Bethlem myopathy: a study of two families. PMID- 20739821 TI - Occipital condyle syndrome as a rare metastatic presentation of small cell lung carcinoma. PMID- 20739822 TI - Coexistent of muscle specific tyrosine kinase and acetylcholine receptor antibodies in a myasthenia gravis patient. PMID- 20739823 TI - Heparin-induced thrombocytopenia and cerebral venous thrombosis after low molecular weight heparin. PMID- 20739824 TI - Xp21.2 contiguous gene syndrome due to deletion involving glycerol kinase and Duchenne muscular dystrophy loci. PMID- 20739825 TI - Idiopathic anti-NMDA-receptor encephalitis in a young Indian girl. PMID- 20739826 TI - Gradual onset of dyskinesia induced by mirtazapine. PMID- 20739827 TI - Neurosarcoidosis: an uncommon presentation. PMID- 20739828 TI - Hematomyelia due to anterior spinal artery aneurysm in a patient with coarctation of aorta. PMID- 20739829 TI - Cerebellopontine angle endodermal cyst: a rare occurrence. PMID- 20739830 TI - Ruptured spinal dermoid with central canal and intraventricular extension. PMID- 20739831 TI - "Split thalamus": internal medullary involvement in Wilson's disease. PMID- 20739832 TI - Meningeal presentation of an atypical teratoid/rhabdoid tumor. PMID- 20739833 TI - Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression. AB - Synthetic oligodeoxynucleotides (ODN) with a CpG-motif are recognized by Toll like receptor 9 (TLR9) and pleiotropic immune responses are elicited. Stimulation of macrophages with TLR9 agonist prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). CpG ODN mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway. Inhibition of TLR9 by small interfering (si) RNA or an inhibitor suppressed CpG ODN-mediated anti-apoptosis. Analysis of signaling pathways revealed that the anti-apoptotic effect of CpG ODN required phosphorylation of FoxO3a and its translocation from the nucleus to the cytosol. Overexpression of FoxO3a increased apoptosis induced by serum deprivation and CpG ODN blocked these effects through FLIP expression. In contrast, siRNA knock-down of FoxO3a decreased apoptosis by serum deprivation. In addition, Akt activation was involved in CpG ODN-induced phosphorylation of FoxO3a, expression of FLIP, and anti-apoptosis. Taken together, these results demonstrate the involvement of Akt-FoxO3a in TLR9 mediated anti-apoptosis and indicate that FoxO3a is a distinct regulator for FLIP expression. PMID- 20739834 TI - World health and population. PMID- 20739835 TI - The determinants of early cessation of breastfeeding in Bangladesh. AB - Early cessation of breastfeeding is a cause of significant concern in many developing countries. Premature discontinuation of breastfeeding is known to be associated with avoidable childhood morbidity and mortality as well as high levels of parity and avoidable pregnancies. Using a publicly available demographic dataset from Bangladesh, we applied a life table and Cox's proportional hazard model to investigate the duration and predictors of breastfeeding. The observed mean duration of breastfeeding was 27.5 months regardless of the level of parity. The results showed that age, age at the time of marriage, religion, the level of education of the mother, the geographic region of residence, employment status, parity and the use of contraceptives are important predictors of early cessation of breastfeeding. PMID- 20739836 TI - A participatory approach to assessing refugee perceptions of health services. AB - OBJECTIVE: The necessity and value of beneficiary input is widely recognized by the humanitarian community. Nevertheless, limited beneficiary involvement occurs due to various barriers. This study explores the effectiveness of an innovative, participatory approach to assessing beneficiary perceptions in resource-limited settings. METHODS: A unique hybrid of qualitative and quantitative methodologies assessed perceptions of health programs within five refugee camps in Kenya and Tanzania. A database of perceptions and opinions was established through key informant interviews, focus group discussions and free-response questionnaires among refugees, community leaders and healthcare providers. Each participant subsequently force-ranked the collected views into quasi-normal distribution according to level of agreement. Responses were analyzed using by-person factor analysis software. FINDINGS: Eighty-one individuals (96%) successfully completed the participatory exercise. The methodologies identified detailed levels of consensus, rank-ordered priorities and unique sub-population opinions. CONCLUSION: The authors illustrate benefits and feasibility of qualitative quantitative participatory methodology in assessing beneficiary perceptions of refugee services. PMID- 20739837 TI - Use of health services by women with gynecological symptoms in rural China. AB - BACKGROUND: To examine the relation between demographic factors and symptom type in the use of gynecological health services in rural China. METHODS: Married women aged 19 to 45 years from three rural communities in Anhui province, central China, were invited to participate in a structured interview in the summer of 2006. They provided information on gynecological symptoms, healthcare-seeking behaviour and socio-demographic characteristics. Risk factors were analyzed using logistic regression. RESULTS: 860/1221(70.4%) reported at least one gynecological symptom during the previous year, with 485 (39.7%) reporting three or more. Of the women with symptoms, 36.7% sought treatment during the previous year. Younger women and those with multiple symptoms were more likely than others to seek treatment. Women with abnormal vaginal bleeding or discharge were more likely to delay seeking treatment. Years of education were strongly related to seeking treatment. More highly educated women and women with a higher household income were more likely than others to seek treatment at the highest level (county or city hospital) of the tertiary healthcare system rather than at a village clinic or township hospital. Women who did not seek treatment were more likely to report that they saw no need than to say that they could not afford care. CONCLUSION: There may be a misperception of the need for, and utility of, treatment for gynecological symptoms, particularly in more disadvantaged women. Interventions should both address women's negative perceptions and reinforce the capacity of the local health facilities to ensure effective care. PMID- 20739838 TI - HIV/AIDS awareness and knowledge among secondary school students in China. AB - With a goal of helping design appropriate HIV/AIDS education and prevention programs for adolescents in China, we analyzed data from 995 secondary school students in Nanjing. Our analysis examined the students' sources of HIV/AIDS information and assessed the overall level, and possible gender and grade (middle school vs. high school) differences, in their HIV/AIDS awareness and knowledge. Data in the current study indicated an overall low and inconsistent level of AIDS knowledge among secondary school students in China. Most of the students could identify models of HIV transmission, but a large proportion held misconceptions regarding symptoms, activities that did not transmit the virus, treatment and preventive measures. The level of using school, family and peers for obtaining information about HIV/AIDS was generally low. There was a discrepancy between the level of utilization and trust of mass media as the main source of HIV/AIDS knowledge. Findings are discussed in terms of implications for HIV/AIDS prevention and education among adolescents in China. PMID- 20739839 TI - Exploring the meaning of childhood disability: perceptions of disability among mothers of children with disabilities (CWD) in Kuwait. AB - The purpose of this exploratory research was to examine perceptions of mothers with children with disabilities (CWD) in Kuwait in order to understand the meaning of disability from their perspective and to explore the extent to which such perceptions influence rehabilitative services that their children receive. Ten semi-structured interviews were conducted with mothers of CWD receiving services at a large pediatric facility in Kuwait. Four themes emerged from the interviews: (1) mother's perceptions of disability, (2) mother's extended caregiver role, (3) religious beliefs as a coping strategy, and (4) perception of rehabilitation services. Our findings suggest that despite a traditional acceptance of disability as divine intervention or a challenge sent to them by God, mothers were motivated to maximize rehabilitation services in order to improve the functional capacity of their children. Kuwaiti mothers may hold both the fatalistic view of disability, and the belief that the course of disability can be altered through a rehabilitative intervention, in tension. An appreciation of this phenomenon might move toward a rehabilitation delivery model that integrates and harmonizes such beliefs. PMID- 20739840 TI - Peripheral T-cell lymphoma with progression to a clonally related, Epstein Barr virus+, cytotoxic aggressive T-cell lymphoma: evidence for secondary EBV infection of an established malignant T-cell clone. AB - We report a case of primary Epstein Barr virus (EBV) negative peripheral T-cell lymphoma (PTCL) NOS in a 56-year-old female who-after an initially indolent course - simultaneously developed an aggressive, EBV+ cytotoxic large T-cell lymphoma, clonally related to the primary PTCL, and an EBV+, clonal large B-cell lymphoproliferation. The initial, EBV-negative PTCL had shown some features of angioimmunoblastic T-cell lymphoma and had responded well to steroid therapy. Two years later, rapidly fatal, progressive disease with multivisceral involvement developed. Histologically, extensive infiltrates of EBV+, CD8+ large cells were present, in addition to areas of the initial PTCL. Extensive comparative phenotypic and molecular analyses confirmed the presence of an identical CD8+ T cell clone in the initial EBV-negative PTCL and the EBV+, CD8+ large cell lymphoma at the time of aggressive transformation. These results also justified the retrospective classification of PTCL, NOS for the initial lymphoma. This case shows that secondary EBV infection of an established malignant T-cell clone can occur and may contribute to aggressive transformation of PTCL. PMID- 20739841 TI - Health care reform: what went wrong. PMID- 20739842 TI - Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. AB - BACKGROUND AND OBJECTIVE: Sentinel lymph node dissection (SLND) has eliminated the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND for patients with tumor-involved SNs remains the standard to achieve locoregional control. Few studies have examined the outcome of patients who do not undergo ALND for positive SNs. We now report local and regional recurrence information from the American College of Surgeons Oncology Group Z0011 trial. METHODS: American College of Surgeons Oncology Group Z0011 was a prospective trial examining survival of patients with SN metastases detected by standard H and E, who were randomized to undergo ALND after SLND versus SLND alone without specific axillary treatment. Locoregional recurrence was evaluated. RESULTS: There were 446 patients randomized to SLND alone and 445 to SLND + ALND. Patients in the 2 groups were similar with respect to age, Bloom Richardson score, estrogen receptor status, use of adjuvant systemic therapy, tumor type, T stage, and tumor size. Patients randomized to SLND + ALND had a median of 17 axillary nodes removed compared with a median of only 2 SN removed with SLND alone (P < 0.001). ALND also removed more positive lymph nodes (P < 0.001). At a median follow-up time of 6.3 years, there were no statistically significant differences in local recurrence (P = 0.11) or regional recurrence (P = 0.45) between the 2 groups. CONCLUSIONS: Despite the potential for residual axillary disease after SLND, SLND without ALND can offer excellent regional control and may be reasonable management for selected patients with early-stage breast cancer treated with breast-conserving therapy and adjuvant systemic therapy. PMID- 20739843 TI - Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. AB - BACKGROUND: The existence of primary fibrinolysis (PF) and a defined mechanistic link to the "Acute Coagulopathy of Trauma" is controversial. Rapid thrombelastography (r-TEG) offers point of care comprehensive assessment of the coagulation system. We hypothesized that postinjury PF occurs early in severe shock, leading to postinjury coagulopathy, and ultimately hemorrhage-related death. METHODS: Consecutive patients over 14 months at risk for postinjury coagulopathy were stratified by transfusion requirements into massive (MT) >10 units/6 hours (n = 32), moderate (Mod) 5 to 9 units/6 hours (n = 15), and minimal (Min) <5 units/6 hours (n = 14). r-TEG was performed by adding tissue factor to uncitrated whole blood. r-TEG estimated percent lysis was categorized as PF when >15% estimated percent lysis was detected. Coagulopathy was defined as r-TEG clot strength = G < 5.3 dynes/cm. Logistic regression was used to define independent predictors of PF. RESULTS: A total of 34% of injured patients requiring MT had PF, which was associated with lower emergency department systolic blood pressure, core temperature, and greater metabolic acidosis (analysis of variance, P < 0.0001). The risk of death correlated significantly with PF (P = 0.026). PF occurred early (median, 58 minutes; interquartile range, 1.2-95.9 minutes); every 1 unit drop in G increased the risk of PF by 30%, and death by over 10%. CONCLUSIONS: Our results confirm the existence of PF in severely injured patients. It occurs early (<1 hour), and is associated with MT requirements, coagulopathy, and hemorrhage-related death. These data warrant renewed emphasis on the early diagnosis and treatment of fibrinolysis in this cohort. PMID- 20739844 TI - Early tracking would improve the operative experience of general surgery residents. AB - OBJECTIVE(S): High surgical complexity and individual career goals has led most general surgery (GS) residents to pursue fellowship training, resulting in a shortage of surgeons who practice broad-based general surgery. We hypothesize that early tracking of residents would improve operative experience of residents planning to be general surgeons, and could foster greater interest and confidence in this career path. METHODS: Surgical Operative Log data from GS and fellowship bound residents (FB) applying for the 2008 American Board of Surgery Qualifying Examination (QE) were used to construct a hypothetical training model with 6 months of early specialization (ESP) for FB residents in 4 specialties (cardiac, vascular, colorectal, pediatric); and presumed these cases would be available to GS residents within the same program. RESULTS: A total of 142 training programs had both FB residents (n = 237) and GS residents (n = 402), and represented 70% of all 2008 QE applicants. The mean numbers of operations by FB and GS residents were 1131 and 1091, respectively. There were a mean of 252 cases by FB residents in the chief year, theoretically making 126 cases available for each GS resident. In 9 defined categories, the hypothetical model would result in an increase in the 5-year operative experience of GS residents (mastectomy 6.5%; colectomy 22.8%; gastrectomy 23.4%; antireflux procedures 23.4%; pancreatic resection 37.4%; liver resection 29.3%; endocrine procedures 19.6%; trauma operations 13.3%; GI endoscopy 6.5%). CONCLUSIONS: The ESP model improves operative experience of GS residents, particularly for complex gastrointestinal procedures. The expansion of subspecialty ESP should be considered. PMID- 20739845 TI - Is risk-adjusted mortality an indicator of quality of care in general surgery?: a comparison of risk adjustment to peer review. AB - OBJECTIVE(S): Profiling of hospitals using risk-adjusted mortality rates as a measure of quality is becoming increasingly frequent. We sought to determine the validity of this approach by comparing the risk-adjusted predicted mortality to the findings of concurrent peer review and retrospective chart review of deaths that occur on a general surgery service. METHODS: Consecutive patients admitted to a busy general surgery service from January 2000 to January 2006 were prospectively entered into the Surgical Activity Tracking System. Rigorous, systematic peer review was performed concurrently by service members on all deaths. Adjudication was later validated by an independent senior surgeon. Three methodologies of risk adjustment (University Health Consortium, Physiological and Operative Severity Score for the enUmeration of Mortality, and the Charlson index) were used and compared the "excess mortality" predicted by each to the number of potentially preventable deaths determined by peer review. RESULTS: A total of 9623 patients were admitted and 75 died (0.7%). University Health Consortium and Physiological and Operative Severity Score predicted an excess mortality of 62 and 65 deaths, respectively; Charlson predicted that 73% of the cohort would be dead in 1 year. Concurrent and retrospective peer review found that death was potentially preventable in only 22 and 21 patients, respectively. CONCLUSIONS: Peer adjudication and extensive clinical review adds much to the analysis of an adverse outcome, similar to the "black box" in an airplane crash. Although methods of risk adjustment may be helpful in identifying patients for peer review, they should be used for internal process improvement and not published as metrics of hospital or provider performance. PMID- 20739846 TI - Ulceration as a predictive marker for response to adjuvant interferon therapy in melanoma. AB - OBJECTIVE: This analysis was performed to investigate the hypothesis that ulceration predicts improved response to adjuvant interferon (IFN) therapy. SUMMARY BACKGROUND DATA: Several studies have demonstrated that adjuvant therapy for high-risk melanoma patients with IFN alfa-2b improves disease-free survival (DFS), although the impact on overall survival (OS) is controversial. Recent data have suggested that IFN therapy may preferentially benefit patients with ulcerated primary melanomas. METHODS: Post hoc analysis was performed by a prospective multi-institutional randomized study of observation versus adjuvant IFN therapy for melanoma. All patients underwent sentinel lymph node biopsy; completion lymphadenectomy was performed for patients with sentinel lymph node metastasis. Patients were stratified by Breslow thickness, ulceration, and nodal status. Kaplan-Meier analysis of DFS and OS was performed and included univariate and multivariate analyses. RESULTS: A total of 1769 patients were analyzed (1311 without ulceration, 458 with ulceration) with a median follow-up of 71 months. Ulceration was associated with significantly worse DFS and OS in both node negative and node-positive patients. Kaplan-Meier analysis of node-negative and node-positive patients by ulceration status revealed that the only significant impact of interferon was improved DFS in the ulcerated node-positive patients (P = 0.0169). IFN therapy had no significant impact on OS regardless of ulceration status, however. On multivariate analysis, IFN treatment was a significant independent predictor of DFS among ulcerated patients (odds ratio, 0.51; 95% confidence interval, 0.30-0.83; P = 0.0053), but not among patients without ulceration. CONCLUSIONS: These data support the conclusion that ulceration is a predictive marker for response to adjuvant IFN therapy. Future studies to evaluate specifically the differential effect of IFN on patients with ulcerated melanomas may allow us to focus this therapy on patients most likely to benefit from it. PMID- 20739847 TI - Surgical quality and nodal ultrastaging is associated with long-term disease-free survival in early colorectal cancer: an analysis of 2 international multicenter prospective trials. AB - BACKGROUND: The National Quality Forum has endorsed a minimum of 12 lymph node (LN) as a surrogate measure of quality in colorectal cancer (CRC). The prognostic value of ultrastaging hematoxylin and eosin (H&E) negative LNs (N0) using pan cytokeratin immunohistochemistry (pan-CK-IHC) is unknown. PURPOSE: To assess the effect on survival of surgical quality and focused pathologic analysis. PATIENTS AND METHODS: Between 2001 and 2007, 253 evaluable patients with resectable CRC were enrolled. Multiple sectioning and pan-CK-IHC were performed on N0 LNs (American Joint Commission on Cancer Stage II). Follow-up was performed at 6 month intervals with a 4-year disease-free survival (DFS) primary end-point. RESULTS: There were 253 patients, 177 N0 and 76 N1/N2 patients, staged conventionally. Thirty-six (20%) N0 patients were upstaged using ultrastaging (N0 ->N0i+ [n = 27] and N0-->N1mi [n = 9]). At a mean follow-up of 3.4 +/- 1.6 years, 38 (15%) have recurred. Only 3% (3/108) of patients with > or =12 LNs, negative by H&E and pan-CK-IHC (N0i-), compared with 18% (6/33) with <12 LNs/N0i- (6/33; P = 0.0015) have recurred. Four-year DFS differed significantly according to surgical quality (<12 vs. > or =12 LNs) among Stage II patients only (DFS, <12 vs. > or =12 LNs: Stage I, 90.5% vs. 97.7%, P = 0.22; Stage II, 67.5% vs. 94.7%, P = 0.0036; Stage III, 61% vs. 61%, P = 0.61). CONCLUSION: This represents the first prospective report demonstrating that both surgical quality and nodal ultrastaging impacts survival in Stage II CRC. Patients with Stage II CRC having > or =12 LNs negative for micrometastases (N0i-) are likely cured by surgery alone. Both surgical and pathologic quality measures are imperative in early CRC to improve patient selection for adjuvant chemotherapy. PMID- 20739848 TI - The efficacy of medical team training: improved team performance and decreased operating room delays: a detailed analysis of 4863 cases. AB - OBJECTIVES: Medical team training (MTT) has been touted as a way to improve teamwork and patient safety in the operating room (OR). METHODS: OR personal completed a 1-day intensive MTT training. A standardized briefing/debriefing/perioperative routine was developed, including documentation of OR miscues, delays, and a case score (1-5) assigned by the OR team. A multidisciplinary MTT committee reviewed and rectified any systems problems identified. Debriefing items were analyzed comparing baseline data with 12 and 24 month follow-up. A safety attitudes questionnaire was administered at baseline and 1 year. RESULTS: A total of 4863 MTT debriefings were analyzed. One year following MTT, case delays decreased (23% to 10%, P < 0.0001), mean case score increased (4.07-4.87, P < 0.0005), and both changes were sustained at 24 months. One-year and 24-month follow-up data demonstrated decreased frequency of preoperative delays (16%-7%, P = 0.004), hand-off issues (5.4%-0.3%, P < 0.0001), equipment issues/delays (24%-7%, P < 0.0001), cases with low (<3) case scores (23%-3%, P < 0.0005), and adherence to timing guidelines for prophylactic antibiotic administration improved (85%-97%, P < 0.0001). Surveys documented perception of improved teamwork and patient safety. A major systems issue regarding perioperative medication orders was identified and corrected. CONCLUSIONS: MTT produced sustained improvement in OR team function, including decreased delays and improved case scores. When combined with a high-level debriefing/problem-solving process, MTT can be a foundation for improving OR performance. This is the largest case analysis of MTT and one of the few to document an impact of MTT on objective measures of operating room function and patient safety. PMID- 20739849 TI - A validated value-based model to improve hospital-wide perioperative outcomes: adaptability to combined medical/surgical inpatient cohorts. AB - OBJECTIVES: Authors hypothesized that building safe hospital systems to improve value-based surgical outcomes is predicated on workflow redesign for dynamic risk stratification, coupled with "real-time" mitigation of risk. We developed a comanagement model for hospitalized surgical cohort, and determined whether this iterative process redesign for surgery will be adaptable to disparate hospital systems and will be beneficial for combined medical/surgical adult inpatients. CONTEXT: Concerns about preventable harm in hospitalized patients have generated a plethora of both, process-driven and outcome-based strategies in US Healthcare. Although comparison between hospitals is a common mechanism to drive quality, other innovative approaches are needed for real-time risk mitigation to improve outcomes. METHODS: Prospective implementation of Surgical Continuum of Care (SCoC) model in hospitals initially for surgery patients; subsequently Continuum of Care (CoC) for medical/surgical population. Redesign of hospital care delivery model: patient cohorting, floor-based team building, and intensivist/hospitalist staffing of progressive care unit (PCU). Work flow redesign for clinical effectiveness: multidisciplinary team rounds, acuity stratified care rounding based on dynamic risk assessment into a novel HAWK (high risk)/DOVE (low risk) patient grouping, intensivist/hospitalist comanagement of surgical patients, and targeted response. STUDY: Pre- and postintervention with concurrent cohort control design. SETTING: Academic medical centers for SCoC and integrated health system hospital for CoC. PATIENT GROUPS: SCoC Pilot Study-Campus A: Preintervention control group 1998-2000, Intervention Group 2001-2004; Campus B: Comparator Control Group 1998-2004. SCoC Validation Study-Campus C: Preintervention Group 2001-2005; Intervention Group 2006-2008. CoC Study-Campus D: Hospital-wide Group 2009. METRICS: Mortality, length of stay (LOS): overall, surgical intensive care unit and PCU, readmission rates, and cost. Case mix index for risk adjustment. RESULTS: Total >100,000 admissions. There was a significant reduction in overall surgical mortality in both, pilot (P < 0.002) and validation (P < 0.02) SCoC studies and overall hospital mortality in the medical/surgical CoC study (risk-adjusted mortality index progressively declined in CoC study from 1.16 pre-CoC to 0.77 six months post-CoC implementation; significant at 75% confidence level). Case mix index was unchanged during study period in each campus. Nested study in validation cohort of hospital-wide versus surgery alone (observed/expected mortality index) demonstrated significant benefit to SCoC in intervention group. The mortality benefit was primarily derived from risk stratified rounding and actively managing risk prone population in the PCU. Surgical intensive care unit, PCU, and total hospital patient-days significantly decreased in SCoC pilot study (P < 0.05), reflecting enhanced throughput. LOS reduction benefit persisted in SCoC validation and CoC studies. In addition to decreased LOS, cost savings were in PCU (range, $851,511-2,007,388) and top diagnosis-related groups, for example, $452 K/yr for diagnosis-related group 148. CONCLUSIONS: SCoC is patient-centered, outcomes-driven, value-based approach for hospital-wide surgical patient safety. The principles of this value paradigm are adaptable to other hospitals as demonstrated in our longitudinal study in 3 hospital systems, and the initial experience of CoC suggests that this model will have benefit beyond surgical hospital cohort. PMID- 20739850 TI - HuR status is a powerful marker for prognosis and response to gemcitabine-based chemotherapy for resected pancreatic ductal adenocarcinoma patients. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a devastating disease that killed nearly 38,000 people in the United States this past year. OBJECTIVE: Treatment of PDA typically includes surgery and/or chemotherapy with gemcitabine. No reliable biomarker exists for prognosis or response to chemotherapy. Two previously proposed prognostic markers, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), are regulated by Hu protein antigen R (HuR), an mRNA binding protein that we have previously demonstrated to be a promising predictive marker of gemcitabine response. This study was designed to evaluate the clinical utility of HuR, COX-2, and VEGF as potential prognostic and predictive biomarkers for PDA. METHODS: A tissue microarray of 53 PDA specimens from patients who underwent potentially curative pancreatic resection was analyzed. HuR, COX-2, and VEGF status were correlated with clinicopathologic and survival data. We also performed ribonucleoprotein immunoprecipitation assays using an HuR antibody to assess VEGF and COX-2 mRNA binding to HuR in pancreatic cancer cells. RESULTS: Roughly 50% (27/53) of patients had high cytoplasmic HuR expression. These patients had worse pathologic features as assessed by T staging (P = 0.005). Only cytoplasmic HuR status correlated with tumor T staging, whereas VEGF (P = 1.0) and COX-2 (P = 0.39) expression did not correlate with T staging. Additionally, HuR status was an unprecedented positive predictive marker for overall survival in patients treated with gemcitabine, pushing median survival over 45 months in the high cytoplasmic HuR expressing patient population compared with less than 23 months in the low cytoplasmic HuR expressing patient group (P = 0.033 for log-rank test and P = 0.04 in a Cox regression model) for the low versus high cytoplasmic HuR expressing group. We also validated that mRNA transcripts for both VEGF and the gemcitabine metabolizing enzyme, deoxycytidine kinase, are specifically bound by HuR in pancreatic cancer cells. CONCLUSIONS: HuR is a useful prognostic biomarker for PDA patients as indicated by its association with higher tumor T stage. Additionally, HuR status is a robust predictor of outcome for patients with resected PDA in the setting of adjuvant gemcitabine therapy. Finally, HuR binds to VEGF mRNA implying that HuR, in part, regulates VEGF expression in PDA. This study supports the notion that HuR status should be used by clinicians for the individualized treatment of PDA in the future. PMID- 20739851 TI - Risk of colorectal adenoma and carcinoma after colectomy for colorectal cancer in patients meeting Amsterdam criteria. AB - OBJECTIVE: To report the risk of metachronous colorectal neoplasia after colectomy for cancer in Hereditary Nonpolyposis Colorectal Cancer (HNPCC) syndrome. SUMMARY BACKGROUND DATA: Patients meeting Amsterdam criteria for diagnosis of HNPCC have a lifetime colorectal cancer risk approaching 80%, and a metachronous cancer rate of approximately 25%. Therefore, when colon cancer is diagnosed, total rather than segmental colectomy is advocated. However, information about adenoma and carcinoma risk after index surgery is still underreported. METHODS: A hereditary colorectal cancer database was reviewed for patients meeting Amsterdam criteria who underwent colectomy for cancer. Patient demographics, surgical management, and results of follow-up were recorded. Metachronous colorectal adenoma and carcinoma development were the primary end points. RESULTS: A total of 296 patients (253 with segmental colectomy and 43 with total colectomy/ileorectal anastomosis) were analyzed. Of the 253 segmental colectomy patients, 221 (88%) had postoperative endoscopic surveillance with median follow-up of 104 months. In 74 patients (33%), 256 adenomas were detected, including 140 high-risk adenomas in 48 patients (22%). Fifty-five patients (25%) developed a second colorectal cancer at a median of 69 months after index surgery. Stages of the metachronous cancers were I-16, II-18, III-12, and IV-2. By comparison, 4 of 38 patients (11%) who underwent total colectomy developed subsequent high-risk adenomas and 3 (8%) developed metachronous cancer. CONCLUSIONS: Amsterdam patients undergoing partial colectomy have a high rate of metachronous high-risk adenomas and carcinomas. Total colectomy for the index cancer is the procedure of choice. For either surgical option, yearly endoscopic surveillance is essential to remove premalignant adenomas. PMID- 20739852 TI - A statewide assessment of surgical site infection following colectomy: the role of oral antibiotics. AB - OBJECTIVE: To determine the utility of adding oral nonabsorbable antibiotics to the bowel prep prior to elective colon surgery. SUMMARY BACKGROUND DATA: Bowel preparation prior to colectomy remains controversial. We hypothesized that mechanical bowel preparation with oral antibiotics (compared with without) was associated with lower rates of surgical site infection (SSI). METHODS: Twenty four Michigan hospitals participated in the Michigan Surgical Quality Collaborative-Colectomy Best Practices Project. Standard perioperative data, bowel preparation process measures, and Clostridium difficile colitis outcomes were prospectively collected. Among patients receiving mechanical bowel preparation, a logistic regression model generated a propensity score that allowed us to match cases differing only in whether or not they had received oral antibiotics. RESULTS: Overall, 2011 elective colectomies were performed over 16 months. Mechanical bowel prep without oral antibiotics was administered to 49.6% of patients, whereas 36.4% received a mechanical prep and oral antibiotics. Propensity analysis created 370 paired cases (differing only in receiving oral antibiotics). Patients receiving oral antibiotics were less likely to have any SSI (4.5% vs. 11.8%, P = 0.0001), to have an organ space infection (1.8% vs. 4.2%, P = 0.044) and to have a superficial SSI (2.6% vs. 7.6%, P = 0.001). Patients receiving bowel prep with oral antibiotics were also less likely to have a prolonged ileus (3.9% vs. 8.6%, P = 0.011) and had similar rates of C. difficile colitis (1.3% vs. 1.8%, P = 0.58). CONCLUSIONS: Most patients in Michigan receive mechanical bowel preparation prior to elective colectomy. Oral antibiotics may reduce the incidence of SSI. PMID- 20739854 TI - A national study of attrition in general surgery training: which residents leave and where do they go? AB - OBJECTIVE(S): Implementation of the 80-hour mandate was expected to reduce attrition from general surgery (GS) residency. This is the first quantitative report from a national prospective study of resident/program characteristics associated with attrition. METHODS: Analysis included all categorical GS residents entered on American Board of Surgery residency rosters in 2007 to 2008. Cases of attrition were identified by program report, individually confirmed, and linked to demographic data from the National Study of Expectations and Attitudes of Residents in Surgery administered January 2008. RESULTS: All surgical categorical GS residents active on the 2007-2008 resident rosters (N = 6,303) were analyzed for attrition. Complete National Study of Expectations and Attitudes of Residents in Surgery demographic information was available for 3959; the total and survey groups were similar with regard to important characteristics. About 3% of US categorical residents resigned in 2007 to 2008, and 0.4% had contracts terminated. Across all years (including research), there was a 19.5% cumulative risk of resignation. Attrition was highest in PGY-1 (5.9%), PGY-2 (4.3%), and research year(s) (3.9%). Women were no more likely to leave programs than men (2.1% vs. 1.9%). Of several program/resident variables examined, postgraduate year-level was the only independent predictor of attrition in multivariate analysis. Residents who left GS whose plans were known most often pursued nonsurgical residencies (62%), particularly anesthesiology (21%) and radiology (11%). Only 13% left for surgical specialties. CONCLUSIONS: Attrition rates are high despite mandated work hour reductions; 1 in 5 GS categorical residents resigns, and most pursue nonsurgical careers. Demographic factors, aside from postgraduate year do not appear predictive. Residents are at risk for attrition early in training and during research, and this could afford educators a target for intervention. PMID- 20739855 TI - Prevention of surgical resident attrition by a novel selection strategy. AB - OBJECTIVE(S): We modified the resident selection strategy in an attempt to reduce resident attrition (RA). SUMMARY BACKGROUND DATA: Despite implementation of the Accreditation Council for Graduate Medical Education work rules, lifestyle and generational priorities have fostered a persistent and relatively high attrition rate for surgical trainees. METHODS: An independent external review of residents who left the training program and a detailed analysis of the resident selection strategy were performed by an organizational management expert. Modifications implemented in 2005 (the intervention) included standardization of the screening and interview format. Applicants were required to submit a 500 words essay related to stress management, organizational skills, future aspirations, and prioritization abilities. Their responses formed the basis of an extended, personalized, and structured interview script. Candidate characteristics and RA were compared for the 5 years before and after the intervention, using Fisher exact test or chi2. RESULTS: Age, sex, birthplace, medical school ranking, step 1 score, and American Board of Surgey In-Training Examination performance were not significantly different between the selection strategy groups. Risk factors for RA included ABSITE performance and gender. Resident performance and subsequent RA were significantly affected by the resident selection strategy. CONCLUSIONS: RA was dramatically reduced following the intervention. A custom designed process to identify candidates most likely to succeed substantially improved resident retention in a demanding academic training program. PMID- 20739853 TI - Glucose control in severely thermally injured pediatric patients: what glucose range should be the target? AB - OBJECTIVE: To determine which glucose levels are associated with improved morbidity and mortality in thermally injured patients. SUMMARY BACKGROUND DATA: Tight euglycemic control was rapidly implemented in intensive care units around the world, but there is increasing evidence that tight euglycemic control is associated with detrimental outcomes. Currently, no study exists that indicates which glucose range should be targeted. METHODS: Two-hundred and eight severely burned pediatric patients with burns over 30% of their total body surface area were included in this trial. Several statistical models were used to determine the daily average and 6 AM glucose target that were associated with improved morbidity and mortality. Patients were then divided into good glucose controlled and poor glucose controlled patients and demographics, clinical outcomes, infection, sepsis, inflammatory, and hypermetabolic responses were determined. RESULTS: Statistical modeling showed that hyperglycemia is a strong predictor of adverse hospital outcome and that daily 6 am glucose level of 130 mg/dL and daily average glucose levels of 140 mg/dL are associated with improved morbidity and mortality postburn. When patients were divided into good glucose control and poor glucose control, we found that patients with glucose levels of 130 mg/dL exert attenuated hypermetabolic and inflammatory responses, as well as significantly lower incidence of infections, sepsis, and mortality compared with patients with poor glucose control, P < 0.05. CONCLUSIONS: Given the controversy over glucose range, glucose target, and risks and detrimental outcomes associated with hypoglycemia we suggest that in severely burned patient's blood glucose of 130 mg/dL should be targeted. PMID- 20739856 TI - Patient socioeconomic status is an independent predictor of operative mortality. AB - OBJECTIVE: To evaluate the impact of patient socioeconomic status (SES) on operative mortality within the context of associated factors. SUMMARY OF BACKGROUND DATA: Outcomes disparities among surgical patients are a significant concern. Previous studies have suggested that the correlation between SES and outcomes is attributable to other patient- or hospital-level explanatory factors such as race or hospital wealth. These studies have typically focused on a single explanation for the existence of these inequalities. METHODS: Analyzing more than 1 million records of the Nationwide Inpatient Sample, we used multimodel inference to evaluate the effects of socioeconomic predictors on surgical mortality. RESULTS: Using univariate and multivariate logistic regression, we find that patient's SES is a strong predictor of operative mortality. Multivariate regressions incorporated many additional hospital- and patient-level covariates. A single-level increase in patient SES results in a mean decrease in operative mortality risk of 7.1%. CONCLUSIONS: SES at the level of the individual patient has a statistically significant effect on operative mortality. Mortality is greatest among patients in the lowest socioeconomic strata. The effect of patient SES on mortality is not mitigated by other explanatory hospital- or patient-level factors. PMID- 20739857 TI - Early postoperative outcomes of metabolic surgery to treat diabetes from sites participating in the ASMBS bariatric surgery center of excellence program as reported in the Bariatric Outcomes Longitudinal Database. AB - OBJECTIVE: Small case series suggest bariatric surgery may be an effective treatment for type 2 diabetes mellitus in patients who do not meet body weight criteria for morbid obesity (body mass index [BMI], <35 kg/m), but large multi institutional series, which allow better assessment of the safety and efficacy of treatment, have not been reported. METHODS: Data from 66,264 research-consented patients with a primary bariatric surgery encounter in the Bariatric Outcomes Longitudinal Database from June 2007 to June 2009 were queried to identify patients with a BMI > or =30 but <35 kg/m2 (1.2%, n = 794) and diabetes requiring any medication (29%). RESULTS: A total of 235 patients met inclusion criteria. The 2 most common procedures, adjustable gastric banding (n = 109) and gastric bypass (n = 109), were compared. Laparoscopic access was used in 92% of procedures. Gender (76.6% female), race (80.4% White), and age (mean 52.6 +/- 10.4 years) did not differ between procedure groups. Gastric bypass provided superior weight loss and diabetes remission but demonstrated more frequent complications (90-day complications: 18% vs. 3%, P < 0.05). No mortalities were reported, and most complications were minor. CONCLUSIONS: The data suggest early effectiveness of surgical treatment of diabetes in patients who do not meet criteria for morbid obesity. Gastric bypass provides more effective treatment for diabetes than adjustable gastric banding within 6 to 12 months. PMID- 20739859 TI - Surgical complications need to be considered beyond their treatment and outcome. PMID- 20739861 TI - Standardizing lymphadenectomy for rectal cancer. PMID- 20739862 TI - Reducing biliary morbidity in full graft deceased donor liver transplantation: is it really a matter of T-tube? PMID- 20739865 TI - Improving the preoperative diagnostic yield of gallbladder cancers. PMID- 20739866 TI - Impact of motorcycle helmets and state laws on society's burden: a national study. PMID- 20739867 TI - The influence of mechanical bowel preparation in elective lower colorectal surgery. PMID- 20739870 TI - A 21st-century approach to cystic fibrosis: optimizing outcomes across the disease spectrum. PMID- 20739871 TI - Concomitant lymphoma and cryptococcosis in a patient with acquired immune deficiency syndrome. PMID- 20739872 TI - Recurrent carbon monoxide poisoning from cigarette smoking. AB - Carbon monoxide intoxication remains a major cause of morbidity and mortality in the United States with an estimate of 50,000 cases annually in emergency departments nationwide (Weaver, N Engl J Med. 2009;360:1217-25). Sources of carbon monoxide most often include car exhaust, malfunctioning heating systems and inhaled smoke. It has been well established that there is a dose-dependent increase in carboxyhemoglobin (COHb) concentration with tobacco use. It is generally accepted that heavy smokers have COHb levels <10% to 15% (Ernst and Zibrak, N Engl J Med. 1998;339:1603-8). The authors report a 48-year-old woman with significant tobacco abuse who presented with COHb levels as high as 24.2% in the face of tobacco use. PMID- 20739873 TI - Aspirin desensitization/challenge in 3 patients with unstable angina. AB - Aspirin sensitivity is relatively frequent and can be a major problem in patients who need percutaneous coronary intervention and stenting with subsequent dual antiplatelet therapy. Desensitization is often the therapy in these patients, but this can prolong the time to revascularization significantly. Rapid oral aspirin desensitization protocols have been described since 2000. However, data are lacking on the optimal strategy for aspirin desensitization and determining which patients are mostly benefited from this desensitization. The authors describe the use of a Wong-modified protocol in 3 patients who had known aspirin sensitivity and who had unstable angina and an indication for percutaneous coronary intervention. PMID- 20739874 TI - Therapeutic effects of marine collagen peptides on Chinese patients with type 2 diabetes mellitus and primary hypertension. AB - INTRODUCTION: Marine collagen peptides (MCPs) from deep sea fish are shown to ameliorate hyperlipidemia in animal models. The study aimed at examining the effects of MCPs on glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus (T2DM) and primary hypertension. METHODS: One hundred patients with T2DM and primary hypertension and 50 healthy subjects (normal controls) were recruited for a randomized double blind study. The patients were randomized into MCPs treatment or patient control groups (n = 50 per group). Both patient controls and normal controls were given carboxymethylcellulose twice daily whereas the MCPs treatment group was given MCPs twice daily for 3 months. Blood pressure, glucose and lipid metabolism, serum high-sensitivity C-reactive protein, cytochrome P450, nitric oxide, bradykinin, prostacyclin, creatinine, uric acid and adipokines were measured at baseline, 1.5 and 3 months after treatment. All patients received regular medicines for control of hyperglycemia and hypertension. RESULTS: Compared with patient controls, significantly reduced levels of fasting blood glucose, HbA1c, diastolic blood pressure, mean arterial pressure and creatinine but increased levels of Insulin Sensitivity Index and Insulin Secretion Index were observed in patients receiving MCPs treatment. Furthermore, significantly reduced levels of serum triglycerides, total cholesterol, low-density lipoprotein, free fatty acids, cytochrome P450, nitric oxide and prostacyclin but increased levels of high-density lipoprotein, bradykinin and adiponectin were detected in patients taking MCPs. CONCLUSIONS: MCPs supplement may benefit glucose and lipid metabolism, insulin sensitivity, renal function and hypertension management in Chinese patients with T2DM and hypertension. PMID- 20739875 TI - Coincidence of multiple endocrine neoplasia type 2A with acromegaly. AB - Medullary thyroid carcinoma (MTC) occurs as a part of multiple endocrine neoplasia (MEN) type 2. Acromegaly, a pituitary adenoma, occurs as a part of MEN1. Rarely, MEN2 and MEN1 coexist in a single patient simultaneously. A 40-year old man with a history of pituitary adenomectomy for acromegaly had a surgical resection of thyroid carcinoma clinically diagnosed as MTC. His mother, who had MTC and pheochromocytoma, had a germline mutation in the RET gene that could cause the subtype, MEN2A. Identification of gene mutations in RET and MEN1 were examined in the subject. The resected tumor was pathologically diagnosed as MTC. Genomic examinations revealed the RET mutation C634F, which was identical to the mutation of his mother, but no MEN1 gene mutation was found. Although the simultaneous occurrence of both MEN2A and sporadic acromegaly may be accidental, there is evidence to suggest a genetic interaction between MEN2 and acromegaly. PMID- 20739876 TI - Clot formation in canine whole blood as measured by rotational thromboelastometry is influenced by sample handling and coagulation activator. AB - The objective of the present study was to systematically evaluate the impact of methodology on thromboelastometry with canine whole blood. Thromboelastometry was performed on citrated blood using a variety of combinations of clotting activators [ex-tem (tissue factor or TF), in-tem (ellagic acid), diluted TF from Innovin, or Ca (recalcification only)] and storage times. Thromboelastometry was also performed using diluted TF from Innovin on blood collected into a contact inhibitor. Ex-vivo contact activation was compared between canine and human blood. Clotting activator had a marked impact on coagulation time, a minor impact on alpha angle, and no impact on clot formation time or maximum clot firmness. When ex-tem or in-tem was the clotting activator, sample storage up to 30 min did not affect results. With diluted TF from Innovin or Ca, sample storage was associated with the development of increased coagulability (as indicated by shorter coagulation time and clot formation time and higher alpha angle) due to ex-vivo contact activation. Canine blood underwent markedly more ex-vivo contact activation than did human blood. Canine blood undergoes significant ex-vivo contact activation during and after collection, which influences thromboelastometry results when a weak clotting activator (such as low TF or recalcification) is used. Thromboelastometry with a strong activator (such as ex tem or in-tem) is less influenced by ex-vivo changes, and, therefore, likely to be more reflective of in-vivo hemostatic capabilities and to provide consistently interpretable and comparable results. PMID- 20739877 TI - Platelet glycoprotein IIIa (platelet antigen 1/platelet antigen 2) polymorphism and 1-year outcome in patients with stable coronary artery disease. AB - Platelet glycoprotein IIb/IIIa is a membrane receptor which plays a key role in coronary artery disease and thrombotic events. However, there is a considerable controversy regarding the clinical impact of glycoprotein IIIa platelet antigen 1 (PlA1)/platelet antigen 2 (PlA2) polymorphism as a risk factor for myocardial infarction. To evaluate the association between glycoprotein IIIa PlA1/PlA2 polymorphism and 1-year cardiovascular events occurrence in aspirin-treated patients with stable coronary artery disease. We prospectively included 188 postacute coronary syndrome patients (183 men) aged 59 +/- 10 years and receiving aspirin (250 mg/day). The clinical outcome at 1 year was the composite end point of nonfatal myocardial infarction, stroke, recurrent unstable angina or cardiac death. Genotyping for PlA1/PlA2 polymorphism was conducted using PCR and restriction fragment length polymorphism analysis. The genotype distribution of glycoprotein IIIa PlA1/PlA2 polymorphism was PlA1/PlA1, 55.3%; PlA1/PlA2, 39.3% and PlA2/PlA2, 4%. Incidence of composite end point in homozygous PlA1/PlA1 carriers was significantly higher than in PlA2/PlA2 and PlA1/PlA2 patients [14.4 vs. 3.6% odds ratio 4.5 (1.2-16.6, 95% confidence interval); P = 0.012]. Multivariate analysis identified three strong predictive factors of cardiac death: age more than 65 years [odds ratio = 6.8, (1.4-34, 95% confidence interval); P = 0.018], ventricular ejection fraction less than 50% [odds ratio = 8.6, (1.7-42.6, 95% confidence interval); P = 0.008] and homozygous PlA1/PlA1 genotype [odds ratio = 8.8, (1.0-78.6, 95% confidence interval); P = 0.014]. Our results demonstrated that glycoprotein IIIa PlA1/PlA1 genotype carriers have a significantly increased risks of acute vascular ischemic events associated with a poor prognosis at 1 year. These postacute coronary syndrome patients might require an optimized secondary antithrombotic prophylaxis strategy. PMID- 20739878 TI - Blood groups and susceptibility to virus infection: new developments. AB - PURPOSE OF REVIEW: Histo-blood group antigens belonging to the P1PK and GLOB blood group systems are involved in bacterial infections, but a substantial body of evidence is emerging that some of these glycosphingolipids play a role in HIV infection. These recent findings have raised additional questions regarding the possible role of the P/Gb3 histo-blood group antigen in HIV-1 infection. RECENT FINDINGS: Early studies implicated a number of glycosphingolipids able to interact with HIV envelope glycoprotein 120. It has been recently reported that cellular or soluble P/Gb3 histo-blood group antigen provides protection from HIV 1 infection. This resistance mechanism appears to be mediated through inhibition of fusion of the HIV-1 envelope to the cell target membrane. Protection has been shown to be provided to both HIV-1 X4 and R5 tropic strains. Indeed, an inverse correlation has been documented between the expression of P/Gb3 on the cellular membrane and susceptibility to HIV infection. Moreover, soluble P/Gb3 analogues have been shown to inhibit HIV infection. SUMMARY: The P/Gb3 histo-blood group antigen is the first described cell surface expressed natural resistance factor for prevention of HIV infection. Increased expression of P/Gb3 correlates to decreased HIV infection, whereas decreased or absent P/Gb3 increases HIV susceptibility. Soluble P/Gb3 analogues can inhibit HIV by two mechanisms: direct inhibition of the free virus and inhibition of viral entry. Future development of soluble P/Gb3 analogues, pharmacologic means of increasing cell surface expression of P/Gb3 on HIV susceptible target cells or both may result in novel therapeutic modalities for the prevention and eradication of HIV/AIDS. PMID- 20739879 TI - Recent progress in understanding the pathogenesis of immune thrombocytopenia. AB - PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is a bleeding disorder in which both antibody and cell-mediated autoimmune responses are directed against an individual's own platelets and/or megakaryocytes, leading to either enhanced platelet destruction and/or reduced platelet production, respectively. The cause of this platelet-specific autoimmunity remains unknown, but there has been a constant stream of recent publications that suggest ITP is the result of T-cell dysregulation. RECENT FINDINGS: In the last 18 months, a rich tapestry of studies has emerged that seems to clarify some immunopathologic issues in ITP while raising new questions related to ITP pathogenesis. The current view on the immunopathogenic mechanisms associated with ITP appears to particularly concentrate on how incompetent CD4+ T-regulatory cells (Tregs) allow autoimmune effector mechanisms to proceed and cause thrombocytopenia. There is a parallel body of recent literature focusing on molecular mimicry mechanisms, B-cell abnormalities, abnormal cytokine patterns and genetic studies in ITP. Of interest, one can recognize inter-relationships between these immune dysregulations. SUMMARY: This article will discuss the literature from the past 18 months pertaining to these observations and will show that whereas many of the T-cell defects have been clarified, new questions have also come to light and more immunopathological research is warranted. PMID- 20739881 TI - Cord blood transplants: one, two or more units? AB - PURPOSE OF REVIEW: This review summarizes the current status of double-unit cord blood transplantation (CBT) to improve engraftment, reduce transplant-related mortality, and improve disease-free survival. RECENT FINDINGS: Transplantation of cord blood provides a potentially curative therapy for many patients without a suitably human leukocyte antigen-matched related or unrelated donor. Single-unit CBT outcomes have been compromised, however, in adults and larger children by limited cell dose. The introduction of double-unit CBT has improved engraftment and transplant-related mortality in adult patients transplanted for hematologic malignancies, with recent data also suggesting a protection against relapse. These improved outcomes are seen despite only a single unit being responsible for sustained donor hematopoiesis in nearly all patients. The study of double-unit CBT provides unique insights into transplant biology, with emerging data suggesting unit dominance is related to unit viability and unit-versus-unit immune interactions. Multiple unit CBT further serves as a platform to test novel graft manipulations. SUMMARY: The development of double-unit CBT now allows the majority of patients, regardless of size or racial/ethnic background, access to transplant therapy. Ongoing investigation will serve to further improve outcomes and expand the role of CBT in the future. PMID- 20739880 TI - Clinical relevance of microparticles from platelets and megakaryocytes. AB - PURPOSE OF REVIEW: Platelet microparticles were identified more than 40 years ago and are the most abundant circulating microparticle subtype. Yet fundamental questions about their formation and role in human disease are just beginning to be understood at the cellular and molecular level. This review will address mechanisms of platelet microparticle generation and evaluate our current understanding of their clinical relevance. RECENT FINDINGS: New evidence indicates that the majority of CD41 microparticles circulating in healthy individuals derive directly from megakaryocytes. CD41 microparticles also form from activated platelets upon loss of cytoskeleton-membrane adhesion, which occurs in a multitude of disease states characterized by elevated platelet microparticle levels. More recent studies have demonstrated that platelet microparticles function as a transport and delivery system for bioactive molecules, participating in hemostasis and thrombosis, inflammation, malignancy infection transfer, angiogenesis, and immunity. The mechanism of platelet microparticle participation in specific disease entities such as rheumatoid arthritis has been elucidated. SUMMARY: Continued research into how platelet microparticles are generated and function as a transcellular delivery system will advance our basic understanding of microparticle physiology and may enable new strategies for treatment of select disease entities. PMID- 20739882 TI - Phospholipase A2 inhibition and atherosclerotic vascular disease: prospects for targeting secretory and lipoprotein-associated phospholipase A2 enzymes. AB - PURPOSE OF REVIEW: Selective inhibitors of secretory phospholipase A2 and lipoprotein-associated phospholipase A2 are potential candidates for reducing recurrent cardiovascular events in patients with established coronary heart disease (CHD). With the active enrollment of CHD patients into phase III clinical trials with both classes of inhibitors, this article reviews the available experimental animal and human trial evidence that provides the rationale for the development of the phospholipase A2 inhibitors varespladib methyl and darapladib as preventive therapy. RECENT FINDINGS: Recently completed experimental animal studies, human biomarker data, and vascular imaging studies provide support for proceeding with clinical outcome trials secretory phospholipase A2 and lipoprotein-associated phospholipase A2 inhibition. SUMMARY: Both secretory phospholipase A2 and lipoprotein-associated phospholipase A2 inhibitors hold promise for the reduction of recurrent cardiovascular events in patients treated with current standards of care. The completion of the ongoing clinical event trials has the potential to provide a new dimension to secondary preventive therapy. PMID- 20739883 TI - Novel drugs in familial combined hyperlipidemia: lessons from type 2 diabetes mellitus. AB - PURPOSE OF REVIEW: Familial combined hyperlipidemia (FCHL) and type 2 diabetes mellitus (T2DM) are prevalent entities that share many features of the metabolic syndrome. Recent findings suggest that FCHL and T2DM are less distinct than initially anticipated, which could offer new insights for their therapeutic approach. RECENT FINDINGS: Genetic association studies have provided evidence for a common genetic background (upstream transcription factor 1, activating transcription factor 6, transcription factor 7-like 2 and hepatocyte nuclear factor 4 alpha) between FCHL and T2DM. The metabolic overlap can be illustrated by the presence of ectopic fat accumulation and insulin resistance (muscle, adipose tissue and liver). We have shown that FCHL patients are at increased risk to develop T2DM. This indicates that both entities are not static, but instead the former is able to migrate to the latter as insulin resistance progresses. Given these new findings, it can be anticipated that FCHL patients could also benefit from insulin-sensitizing therapy such as pioglitazone and metformin. Indeed, pilot studies have demonstrated that pioglitazone might be advantageous in FCHL patients. SUMMARY: Recent studies suggest that FCHL patients have an increased risk to develop T2DM, which has important clinical implications. Further studies are necessary to evaluate whether FCHL patients can be protected from new-onset T2DM and premature cardiovascular events with insulin-sensitizing therapy. PMID- 20739884 TI - Myofascial pain in the adolescent. AB - PURPOSE OF REVIEW: Whereas in the recent past pain in the child and adolescent was directed to cancer management, there is increasing interest in pain in children and adolescents in relation to nonmalignant conditions. Additionally, there is an emerging literature related to disorders of myofascial function as a cause of pain. RECENT FINDINGS: Pain associated with myofascial dysfunction is common in the adolescent female. Pain in this group of women has been shown to extend into adulthood. Although there has been attention directed to the management of endometriosis through laparoscopic surgical approaches, these are seen as limiting. Myofascial dysfunction is now regarded as an important factor in the evaluation of adolescent pain. One of the most important approaches to the reduction of severe pain in the adolescent is the complete menstrual suppression through use of continuous oral contraceptives or contraceptive rings. Operative laparoscopy has been heavily utilized but there are increasing concerns about the overutilization of this procedure SUMMARY: Alternative approaches to myofascial pain include multidisciplinary care with a rehabilitative perspective. PMID- 20739885 TI - Risk of pelvic organ fistula in patients undergoing hysterectomy. AB - PURPOSE OF REVIEW: To summarize and describe present knowledge regarding the incidence, cause and risk factors of pelvic organ fistula related to hysterectomy. RECENT FINDINGS: The reported incidence of pelvic organ fistula after hysterectomy ranges from 0.1 to 4% in different studies, and a higher incidence is generally reported after radical hysterectomy compared with hysterectomy on benign indications. Iatrogenic injury to the urinary tract or bowels during surgery, and postoperative infections, are probably the main etiologic factors involved in the pathogenesis of fistula formation subsequent to hysterectomy. Evidence from observational studies suggests that hysterectomy increases the risk for pelvic organ fistula disease compared with women with an intact uterus and that risk factors include laparoscopic and total abdominal hysterectomy, increasing age, smoking, diverticulitis and pelvic adhesions. SUMMARY: In industrialized countries, where pelvic organ fistula is rare owing to advances in modern obstetric care, hysterectomy is an important cause of fistula disease. This review demonstrates that hysterectomy is associated with pelvic organ fistula and describes a number of predisposing factors. Although rarely encountered in a general population, pelvic organ fistula disease may have a devastating effect on all aspects of quality of life and should be considered in the surgical decision at the time of hysterectomy. PMID- 20739887 TI - Epidermal growth factor receptor inhibitors in oncology. AB - PURPOSE OF REVIEW: Inhibition of the epidermal growth factor receptor (EGFR) by small molecules or antibodies has been pursued as a paradigm to treat human cancers for over two decades. It is now clear that these agents can induce tumor regressions in a variety of human cancers, proving the critical role of EGFR signals for tumor maintenance in subsets of patients with these cancers. Clinically meaningful responses, however, are only transient and further refinement of EGFR-targeted therapies is urgently needed. RECENT FINDINGS: Several studies provide new insights into the molecular basis of EGFR kinase inhibitor resistance, including co-activation of the MET growth factor receptor, loss of the phosphatase and tensin homolog (PTEN) tumor suppressor, and KRAS mutation. Potential strategies are emerging to overcome acquired EGFR kinase inhibitor resistance associated with the T790 M EGFR mutation, including a new compound identified in a chemical library screen and a combination regimen of an anti-EGFR antibody plus a small molecule EGFR kinase inhibitor. Lastly, pulsatile dosing schedules are being pursued to accomplish more complete target inhibition. SUMMARY: Current data point toward a strong association between EGFR genotype and EGFR kinase inhibitor response, similar to the findings with other oncogenic kinases (BCR-ABL, HER2, KIT, PDGFRA, BRAF). This relationship is less obvious for antibodies targeting EGFR. More complete inhibition of EGFR in tumor cells and more focused clinical drug development remain important goals toward further success with this class of anticancer agents. PMID- 20739886 TI - Poly ADP-ribose polymerase inhibitors: science and current clinical development. AB - PURPOSE OF REVIEW: Poly ADP-ribose polymerase inhibitors are a promising new area in cancer therapeutics. This review summarizes the current understanding of their mechanism of action, their state of clinical development, and possible mechanisms of resistance. RECENT FINDINGS: Poly ADP-ribose polymerase inhibitors were predicted to cause lethality in cells with lesions in homologous recombination, as well as to be synergistic with cytotoxic chemotherapy. Recent clinical trial results have validated both of these hypotheses. In addition, studies have begun to examine possible mechanisms of resistance. SUMMARY: Poly ADP-ribose polymerase inhibitors were developed with the idea of synthetic lethality in mind, a concept from classical genetics that may be a general approach to finding new targets for cancer therapy. They show activity as monotherapy in cancers with defective homologous recombination, and they may potentiate the action of conventional cytotoxic chemotherapy. PMID- 20739888 TI - Steroid receptor and microRNA regulation in cancer. AB - PURPOSE OF REVIEW: Steroid hormone receptors (SHR) are crucial regulators of disease and the basis for clinical intervention in cancers. Recent evidence confirms that microRNAs (miRNAs) impact the pathobiology of hormone-regulated malignancies. Therefore, elucidating miRNA regulation of SHR expression and modulation of miRNAs by SHRs may provide diagnostic biomarkers or therapeutic targets. RECENT FINDINGS: Estrogen receptor status has been established as a key factor in breast cancer prognosis and treatment. Recent studies detail the interactions between estrogen receptor and miRNAs in cancers. New evidence indicates involvement of miRNAs in the regulation of androgen receptor, progesterone receptor, glucocorticoid receptor in hormone responsive cancers. Several miRNAs regulate the expression of the SHRs, while other miRNAs are themselves regulated by SHR signaling in cancer. SUMMARY: Cancers have distinct miRNA expression profiles that contribute to the pathobiology of the disease. In hormone-responsive cancers, the regulatory interactions between the SHR and miRNA may contribute to disease progression. The miRNA regulation of estrogen receptor in cancer has been established in estrogen-dependent cancers. The role of miRNAs in regulating progesterone receptor, androgen receptor and glucocorticoid receptor is under investigation with new insights emerging. These interactions can provide prognostic utility as well as the potential for therapeutic intervention in the future. PMID- 20739889 TI - T-cell immunotherapy for malignant glioma: toward a combined approach. AB - PURPOSE OF REVIEW: Immunotherapies using T lymphocytes are now considered as promising approaches for treating malignant glioma patients. This review discusses how basic understanding of antitumor T-cell responses in the brain are now leading to the rational planning of such novel therapeutic modalities. RECENT FINDINGS: Clinical trials show that therapeutic vaccination with defined glioma antigens or dendritic cells pulsed with glioma lysates is feasible and generally well tolerated, but clinical efficacy has yet to be demonstrated in randomized trials. Preclinical data have established that effector T cells can be engineered to more efficiently recognize tumor cells via high-affinity T-cell receptors or chimeric antibody-like receptors. Animal studies have demonstrated that glioma immunotherapy is enhanced if immunosuppressive molecules (including transforming growth factor-beta) and glioma infiltrating regulatory T cells are inactivated. Clinical trials are under way assessing transforming growth factor-beta2 antisense oligonucleotides and regulatory T cell depletion. Combination of any of the above approaches with chemotherapy or radiotherapy is strongly supported by animal and clinical observations. SUMMARY: Future T-cell immunotherapies will combine different strategies to deliver potent T cells to the glioma bed. The synergy of immunotherapies with radiotherapy and chemotherapy requires optimization, but it is now clear that these modalities are partners and not enemies. PMID- 20739890 TI - Hypothalamic versus neocortical control of sleep. AB - PURPOSE OF REVIEW: Regions of the neocortex most strongly activated during waking exhibit increased sleep intensity during subsequent sleep. The novel concept that aspects of sleep homeostasis are determined locally in the cortex contrasts with the established views that global changes in neocortical activity during sleep are achieved through inhibition of ascending arousal systems that originate in the brainstem and hypothalamus. RECENT FINDINGS: Experiments in animals and humans document asymmetries in neocortical electroencephalogram (EEG) slow-wave activity (SWA), a marker of homeostatic sleep need, as a result of functional activity during waking. In addition to local, use-dependent augmentation of EEG SWA and evoked potentials, expression of plasticity-related genes and of sleep regulatory cytokines and neuromodulators have been shown to be elevated in a use dependent manner in neocortex. The functional consequences of local sleep are hypothesized to involve regulation of synaptic plasticity, synaptic homeostasis and energy balance. SUMMARY: The evidence for use-dependent modulation of neocortical activity during sleep is compelling and provides novel insights into sleep function. However, local changes in neocortex are generally expressed on a background of global sleep. It remains to be determined if events initiated in the cortex have global sleep-promoting effects and how neocortical and hypothalamic mechanisms of sleep control interact. PMID- 20739891 TI - Impact of cystic fibrosis on bone health. AB - PURPOSE OF REVIEW: This review summarizes recently published data on the epidemiology, pathophysiology and treatment of cystic fibrosis (CF)-related low bone mineral density (BMD). RECENT FINDINGS: A systematic literature review reports that the pooled prevalence of osteoporosis in adults with CF is 23.5% [95% confidence interval (CI) 16.6-31.0] and the pooled prevalences of radiologically confirmed vertebral and nonvertebral fractures are 14% (95% CI 7.8 21.7) and 19.7% (95% CI 6.0-38.8), respectively. Recent data suggest that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in bone cells and that CFTR dysfunction affects bone cell activity. The secondary effects of CFTR dysfunction also influence bone metabolism. For example, bone resorption increases during CF pulmonary exacerbations due to the stimulatory effects of proinflammatory cytokines on osteoclast activity. Bisphosphonates inhibit osteoclastic bone resorption and recent data show that both oral and intravenous bisphosphonates improve BMD in patients with CF. SUMMARY: CF-related low BMD is a common but treatable complication of CF. PMID- 20739892 TI - Effects of age on F0 discrimination and intonation perception in simulated electric and electroacoustic hearing. AB - OBJECTIVES: Recent research suggests that older listeners may have difficulty processing information related to the fundamental frequency (F0) of voiced speech. In this study, the focus was on the mechanisms that may underlie this reduced ability. We examined whether increased age resulted in decreased ability to perceive F0 using fine-structure cues provided by the harmonic structure of voiced speech sounds or cues provided by high-rate envelope fluctuations (periodicity). DESIGN: Younger listeners with normal hearing and older listeners with normal to near-normal hearing completed two tasks of F0 perception. In the first task (steady state F0), the fundamental frequency difference limen (F0DL) was measured adaptively for synthetic vowel stimuli. In the second task (time varying F0), listeners relied on variations in F0 to judge intonation of synthetic diphthongs. For both tasks, three processing conditions were created: eight-channel vocoding that preserved periodicity cues to F0; a simulated electroacoustic stimulation condition, which consisted of high-frequency vocoder processing combined with a low-pass-filtered portion, and offered both periodicity and fine-structure cues to F0; and an unprocessed condition. RESULTS: F0 difference limens for steady state vowel sounds and the ability to discern rising and falling intonations were significantly worse in the older subjects compared with the younger subjects. For both older and younger listeners, scores were lowest for the vocoded condition, and there was no difference in scores between the unprocessed and electroacoustic simulation conditions. CONCLUSIONS: Older listeners had difficulty using periodicity cues to obtain information related to talker fundamental frequency. However, performance was improved by combining periodicity cues with (low frequency) acoustic information, and that strategy should be considered in individuals who are appropriate candidates for such processing. For cochlear implant candidates, this effect might be achieved by partial electrode insertion providing acoustic stimulation in the low frequencies or by the combination of a traditional implant in one ear and a hearing aid in the opposite ear. PMID- 20739893 TI - Reinforced laryngeal mask airway compared with endotracheal tube for adenotonsillectomies. AB - BACKGROUND: The endotracheal tube (ETT) has traditionally been considered the best airway device during adenotonsillectomy because a well protected and secured airway is provided. This has been challenged by the introduction of the reinforced laryngeal mask airway (RLMA). It does not kink, is less traumatic during insertion and better tolerated during emergence. The purpose of this study was to compare the use of the RLMA with ETT with regards to postoperative pain, nausea, vomiting and perioperative efficacy in a series of children due for adenotonsillectomy. METHODS: One hundred and thirty-four children, aged 3-16 years and scheduled for ambulatory adenotonsillectomies, were randomly assigned to two groups where the airways were secured with either the ETT (n = 62) or the RLMA (n = 69). We registered the incidence of peroperative and postoperative anaesthesiological complications and time consume, in addition to postoperative pain, nausea and overall satisfaction. RESULTS: The Group RLMA scored significantly lower for maximal pain during the first 4 h postoperatively (P = 0.015). There were no significant differences in pain scores at 24 h or rescue pain medication postoperatively. The Group RLMA spent mean 4.2 min less in the operating room after surgery (P = 0.001). There were no significant differences in postoperative nausea. In those patients finally treated with ETT, including five conversions from RLMA, significantly more patients (10 vs. 2) had airway irritations (P < 0.02). CONCLUSION: The RLMA, when feasible, is a well tolerated and effective alternative to the ETT for use during adenotonsillectomies in children, with beneficial effects on airway irritations, operating room efficiency and early postoperative pain. PMID- 20739894 TI - Efficacy of perphenazine to prevent postoperative nausea and vomiting: a quantitative systematic review. AB - BACKGROUND AND OBJECTIVE: despite the introduction of newer antiemetics in the prevention of postoperative nausea and vomiting (PONV), perphenazine is recommended in current guidelines, as the concept of multimodal management of PONV in high-risk patients requires more than two drugs to be combined. The aim of this quantitative systematic review was to assess the efficacy and safety of perphenazine in the prophylaxis of PONV in adults and children. METHODS: randomised controlled trials investigating the efficacy of perphenazine in the prevention of PONV in comparison with any other drug or placebo were systematically searched in MEDLINE, EMBASE, CINAHL and the Cochrane Library. Dichotomous data on the efficacy and adverse effects were combined and relative risks (RRs) as well as corresponding 95% confidence intervals (CIs) were calculated. RESULTS: eleven trials published between 1965 and 1999 including a total of 2081 participants fulfilled the inclusion criteria and were further analysed. In children, perphenazine 0.07 mg kg was effective in preventing vomiting (RR, 0.31; 95% CI, 0.18-0.54), whereas in adults, a dose of about 5 mg was effective for the prevention of PONV (RR, 0.50; 95% CI, 0.37-0.67). When compared with established newer drugs, for example, ondansetron, dexamethasone or droperidol, no significant differences were observed in the pooled analysis with limited data. Reporting of adverse events was poor. Transient sedation was reported in three eligible trials (RR, 0.9; 95% CI, 0.40-2.05). CONCLUSION: there is evidence that perphenazine is effective in the prevention of PONV in children and adults without serious adverse effects compared with placebo. PMID- 20739895 TI - Intestinal flora imbalance results in altered bacterial translocation and liver function in rats with experimental cirrhosis. AB - BACKGROUND/PURPOSE: The intestinal microflora plays a major role in human health. Intestinal flora imbalances are seen in clinical settings, such as cirrhosis, in which bacterial translocation (BT) results in migration of bacteria or bacterial products from the intestinal lumen to extraintestinal sites. In this study, we explored the effect of alterations in gut flora on BT and liver function in cirrhotic rats. METHODS: In this study, we used a carbon tetrachloride-induced cirrhotic rat model to compare the abundance of major aerobic and anaerobic bacterial species in healthy and cirrhotic rats. We used antibiotic (norfloxacin) and different probiotic treatments to change the status of gut flora in the cirrhotic rats and evaluated BT, liver function, and endotoxemia in the different models. RESULTS: We found higher levels of Enterobacteriaceae in cirrhotic rats when compared with healthy rats. Bifidobacteria treatment resulted in lower levels of Enterobacteriaceae along with increased levels of Lactobacillus when compared with the normal saline group. Both Bifidobacteria and Enterococcus treatments resulted in lower endotoxin levels than in the normal saline group. CONCLUSION: Gut flora imbalances in cirrhotic rats result in significant changes in BT and liver function in cirrhotic rats. PMID- 20739896 TI - Infliximab dependency is related to decreased surgical rates in adult Crohn's disease patients. AB - BACKGROUND: Infliximab dependency in children with Crohn's disease (CD) has recently been described and found to be associated with a decreased surgery rate. AIM: To assess infliximab dependency of adult CD patients, evaluate the impact on surgery, and search for possible clinical and genetic predictors. METHODS: Two hundred and forty-five CD patients treated with infliximab were included from Danish and Czech Crohn Colitis Database (1999-2006). Infliximab response was assessed as immediate outcome, 1 month after infliximab start: complete, partial, and no response. Three months outcome, after last intended infusion: prolonged response (maintenance of complete/partial response), infliximab dependency (relapse requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response). RESULTS: Forty-seven percent obtained prolonged response, 29% were infliximab dependent and 24% nonresponders. The cumulative probability of surgery 40 months after infliximab start was 20% in prolonged responders, 23% in infliximab-dependent patients and 76% in nonresponders (P<0.001). The cumulative probability of surgery at 40 months in patients on maintenance versus on demand regime was 33 and 31%, respectively (P=0.63). No relevant clinical or genetic predictors were identified. CONCLUSION: The infliximab dependency response seems to be equivalent to the prolonged response in adult CD patients when comparing surgery rates. PMID- 20739897 TI - Preventing mother to child transmission of HIV with highly active antiretroviral treatment in Tanzania--a prospective cost-effectiveness study. AB - Recent guidelines recommend that all HIV-infected women should receive highly active antiretroviral therapy throughout pregnancy and lactation, irrespective of whether or not they need it for their own health. This strategy for prevention of mother to child transmission (PMTCT) of HIV is more effective than the well established use of single-dose nevirapine, but it is also a more costly alternative. In this economic evaluation, we use a decision model to combine the best available clinical evidence with cost, epidemiological and behavioral data from Northern Tanzania. We find that a highly active antiretroviral therapy-based PMTCT Plus regimen is more cost effective than the current Tanzanian standard of care with single-dose nevirapine. Although PMTCT Plus is roughly 40% more expensive per pregnant woman than single-dose nevirapine, the expected health benefits are 5.2 times greater. The incremental cost effectiveness ratio of the PMTCT Plus intervention is calculated to be 4062 USD per child infection averted and 162 USD per disability adjusted life year. PMID- 20739899 TI - Intermittent pericardial bleeding from cardiac trauma: computed tomography findings. PMID- 20739898 TI - Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens. AB - BACKGROUND: To investigate genotypic resistance profiles to emtricitabine + tenofovir (FTC + TDF) in-vivo and in-vitro, and compare them with lamivudine + tenofovir (3TC + TDF). METHODS: Three hundred fifty-two HIV-1 B-subtype pol sequences from 42 FTC + TDF-treated patients, 40 3TC + TDF-treated patients, and 270 patients treated with 3TC plus another nucleoside reverse transcriptase inhibitor (but not TDF). All patients never received FTC, 3TC, and TDF in their previous therapeutic regimen. 3TC/FTC +/- TDF resistance was investigated using in vitro selection experiments and docking simulations. RESULTS: The M184V mutation is less prevalent in FTC + TDF-treated patients than in 3TC + TDF treated, and 3TC-treated/TDF-naive patients (14.3% versus 40.0%, P = 0.01 and 55.6%, P < 0.001). Multivariable analysis shows that factors correlated with a lower probability of M184V emergence at failure were the use of FTC compared with 3TC [odds ratio (OR): 0.32 (95% confidence interval (CI): 0.10 to 0.99), P = 0.04], the use of boosted protease inhibitor, and the use of TDF [OR: 0.20 (95% CI: 0.11 to 0.37), P < 0.001, and OR: 0.47 (95%CI: 0.22 to 1.01), P = 0.05, respectively]. In vitro selection experiments and docking analysis show that other reverse transcriptase (RT) mutations, even localized in RT connection domain, can be selected by 3TC + TDF or FTC + TDF in M184V absence and can affect RT affinity for 3TC/FTC and/or TDF. CONCLUSIONS: Our study shows lower rates of M184V development in FTC + TDF regimens versus 3TC + TDF and suggests a potential role of boosted protease inhibitors and TDF in delaying the M184V emergence. Novel RT mutational patterns, more complex than currently known, can contribute to 3TC, FTC, and TDF resistance. PMID- 20739900 TI - Naproxen-induced ST-elevation myocardial infarction in a 33-year-old man. PMID- 20739901 TI - Takotsubo cardiomyopathy in patient with situs viscerum inversus. PMID- 20739902 TI - A comparative study of surgical treatment of small aortic root with or without aortic root enlargement using a single prosthesis type. AB - BACKGROUND: The ideal management of aortic stenosis in patients with a small aortic root remains controversial. Reports of adverse effects of patient prosthesis mismatch (PPM) from a small-sized valve have to be weighed against the increased morbidity and mortality of aortic root enlargement procedures. METHODS: The present study retrospectively reviewed and compared clinical data of patients with predominant aortic stenosis with small aortic root (n = 209) who underwent isolated aortic valve replacement without (AVR group, n = 162) or with aortic root enlargement (AVR + ARE group, n = 47) using a single prosthesis type between January 2002 and June 2008 to assess their effect on perioperative outcomes. RESULTS: The in-hospital mortality (4.28% in AVR + ARE vs. 3.08% in AVR group) and other perioperative outcomes were similar in both the groups. Although patients of the AVR + ARE group had a greater degree of left-ventricular (LV) mass regression (-41.3 +/- 32.1 vs. -21.5 +/- 37.4) in the follow-up period at 12 months, there was no significant difference in functional outcome. Patients with severe postoperative PPM (indexed effective orifice area <=0.65 cm2/m2 body surface area) showed increased perioperative mortality (9.52 vs. 1.85%) and less regression of LV mass (-13.2.8 +/- 27.1 vs. -27.6 +/- 31.9), higher transvalvular gradient and were more symptomatic at 12-month follow-up (New York Heart Association class 1.44 +/- 0.41 vs. 1.22 +/- 0.28) compared to those who were having only mild to moderate PPM (indexed effective orifice area > 0.65). CONCLUSION: ARE procedures are invaluable techniques in surgical management of small aortic root patients and can be used without significantly increasing early morbidity and mortality, particularly in those cases in which AVR with a small prosthesis will lead to severe PPM. PMID- 20739903 TI - Use of calcium channel blockers is associated with better cognitive performance in older hypertensive patients with subjective memory complaints. AB - BACKGROUND: Hypertension is strongly associated with cognitive decline and a promising target for dementia prevention. Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints. PATIENTS AND METHODS: Three hundred and seventy-eight elderly hypertensive patients more than 60 years (mean age 70.4 +/- 6.3 years) treated with at least one antihypertensive agent and presenting with subjective memory complaints but without dementia were prospectively recruited and underwent a combination of neuropsychological tests, brain magnetic resonance imaging with semiquantification of white matter hyperintensities, carotid echotracking, brachial endothelial function, and ambulatory blood pressure assessments. RESULTS: None of the three composite scores (memory score, verbal fluency, and visual memory capacity) was found associated with blood pressure levels. On the other hand, age-adjusted and sex-adjusted analyses showed a significant and positive association between memory score and use of calcium channel blockers (CCBs) (users: +0.14 +/- 0.09 versus nonusers: -0.12 +/- 0.06; P = 0.016). Multivariate analyses also revealed that CCB use was significantly associated with a better memory score, independently of age, male sex, white matter hyperintensities, and carotid wall cross-sectional area, all of which were associated with worse memory scores. CONCLUSION: In elderly hypertensive treated patients with subjective memory complaints, CCB use was associated with better memory performance independently of blood pressure level and macrovascular and microvascular alterations, suggesting a specific neuroprotective effect of this pharmacological class. Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline. PMID- 20739904 TI - Limb lengthening combined with deformity correction in children with the Taylor Spatial Frame. AB - It is difficult to replicate the regular rate and rhythm described by Ilizarov while lengthening with the Taylor Spatial Frame. The purpose of the study was to examine whether this breach of Ilizarov's principles has any deleterious effect on the ability of children to make healthy regenerate bone. A retrospective case control study was performed comparing pediatric patients undergoing primarily lengthening with Taylor Spatial Frame rings and struts, and patients undergoing lengthening with Taylor Spatial Frame rings and Ilizarov clickers. Fifteen patients had primarily lengthening with Taylor Spatial Frame rings and struts, and six patients had lengthening with Taylor Spatial Frame rings and Ilizarov clickers. Statistically, there was no significant difference between the two groups in terms of age, latency, pre-operative bone length percentage, and average length gained. The lengthening index for the strut group (1.79 months/cm) was significantly different from the clicker group (1.33 months/cm) with P=0.012. For a pediatric patient with lower extremity long bone deformities in multiple planes, the Taylor Spatial Frame is an excellent option. However, the surgeon should anticipate a slightly longer duration of treatment with the Taylor Spatial Frame compared to Ilizarov frames and plan his/her fixation accordingly. For the straightforward lengthening of pediatric long bones without significant concomitant deformity, our results indicate that the Ilizarov method appears to be superior to the Taylor Spatial Frame struts and should still be considered the gold standard. PMID- 20739905 TI - The utility of the nonattenuation corrected 18F-FDG PET images in the characterization of solitary pulmonary lesions. AB - OBJECTIVE: To determine the accuracy of nonattenuation corrected (NAC) F fluorodeoxyglucose positron emission tomography (F-FDG PET) images in the evaluation of solitary pulmonary lesion as compared with more established methods. METHODS: Fifty-six patients received F-FDG PET/CT for diagnosing solitary pulmonary nodules or mass lesions based on histopathology (n=39) and clinical follow-up (n=17). Visual pulmonary lesion FDG uptake was graded by consensus of two nuclear medicine physicians on both attenuation corrected (AC) [absent, less than mediastinal blood pool (MBP), equal to MBP, greater than MBP] and NAC (absent, less than skin, equal to skin, greater than skin) images. Standardized uptake values (SUV) were also measured from AC images. SUV, visual AC, and visual NAC methods' diagnostic performances were compared, distinguishing benign from malignant pulmonary nodules. RESULTS: There were 34 malignant and 22 benign lesions. Lesion diameter varied from 5 to 100 mm (mean +/- SD, 24.0 +/- 17.9 mm). The NAC, AC, and SUV method sensitivities and specificities were 100/64%, 91/59%, and 79/77%, respectively. For lesions less than 3 cm, NAC, AC, and SUV methods yielded accuracies of 85%, 78%, and 73%, respectively. The NAC method was the most sensitive and accurate especially for small nodules. CONCLUSION: Visual assessment of NAC F-FDG PET images alone may provide a more accurate characterization of solitary pulmonary lesions. PMID- 20739906 TI - Cerivastatin in vitro metabolism by CYP2C8 variants found in patients experiencing rhabdomyolysis. AB - OBJECTIVES: Cerivastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor withdrawn from the market because of serious adverse effects, is metabolized primarily by CYP2C8. The occurrence of associated myotoxicity and rhabdomyolysis were attributed to altered cerivastatin pharmacokinetics on account of gemfibrozil-inhibition or genetic variations in CYP2C8 and drug transporters involved in cerivastatin clearance. However, the effect of CYP2C8 genetic variation on cerivastatin metabolism has not been fully elucidated. METHODS: In this study, patients (n=126) with confirmed cases of rhabdomyolysis after cerivastatin administration had their CYP2C8 gene resequenced and the metabolism of cerivastatin by the discovered CYP2C8 variants was assessed in proteins expressed in Escherichia coli. RESULTS: In this unique patient population, 12 novel single nucleotide polymorphisms were discovered of which six were exclusively found in patients not using gemfibrozil. Three rare exonic variants resulted in amino acid substitutions and a frame shift deletion (V472fsL494 generating a defective mostly heme-free CYP2C8 protein). A particular promoter located deletion (-635_-634delTA) was tightly linked to CYP2C8*3. Heterologously expressed CYP2C8.3 and CYP2C8.4 displayed an increase in cerivastatin metabolic clearance of up to six-fold compared with the wild-type enzyme. Similarly, an independent sample of microsomes from human livers carrying the CYP2C8*3 and CYP2C8*4 alleles exhibited a 2-fold to 14-fold increase in normalized cerivastatin intrinsic clearance, compared with microsomes from livers carrying only the wild type allele. CONCLUSION: Gain or loss of catalytic function found in the CYP2C8 gene could certainly alter cerivastatin pharmacokinetics and may influence, at least in part, susceptibility to the development of myotoxicity. PMID- 20739907 TI - A single nucleotide polymorphism tags variation in the arylamine N acetyltransferase 2 phenotype in populations of European background. AB - The arylamine N-acetyltransferase 2 (NAT2) slow acetylation phenotype is an established risk factor for urinary bladder cancer. We reported earlier on this risk association using NAT2 phenotypic categories inferred from NAT2 haplotypes based on seven single nucleotide polymorphisms (SNPs) in a study in Spain. In a subsequent genome-wide scan, we have identified a single common tag SNP (rs1495741) located in the 3' end of NAT2 that is also associated with bladder cancer risk. The aim of this report is to evaluate the agreement between the common tag SNP and the 7-SNP NAT2 inferred phenotype. The agreement between the 7 SNP NAT2 inferred phenotype and the tag SNP, rs1495741, was initially assessed in 2174 individuals from the Spanish Bladder Cancer Study (SBCS), and confirmed in a subset of individuals from the Main and Vermont component the New England Bladder Cancer Study (NEBCS). We also investigated the association of rs1495741 genotypes with NAT2 catalytic activity in cryopreserved hepatocytes from 154 individuals of European background. We observed very strong agreement between rs1495741 and the 7-SNP inferred NAT2 phenotype: sensitivity and specificity for the NAT2 slow phenotype was 99 and 95%, respectively. Our findings were replicated in an independent population from the NEBCS. Estimates for the association between NAT2 slow phenotype and bladder cancer risk in the SBCS and its interaction with cigarette smoking were comparable for the 7-SNP inferred NAT2 phenotype and rs1495741. In addition, rs1495741 genotypes were strongly related to NAT2 activity measured in hepatocytes (P<0.0001). A novel NAT2 tag SNP (rs1495741) predicts with high accuracy the 7-SNP inferred NAT2 phenotype, and thus can be used as a sole marker in pharmacogenetic or epidemiological studies of populations of European background. These findings illustrate the utility of tag SNPs, often used in genome-wide association studies (GWAS), to identify novel phenotypic markers. Further studies are required to determine the functional implications of rs1495741 and the structure and evolution of the haplotype on which it resides. PMID- 20739908 TI - PharmGKB summary: cytochrome P450, family 2, subfamily J, polypeptide 2: CYP2J2. PMID- 20739909 TI - Low incidence of bacterial vaginosis in cohort of young Australian women. AB - Cohort study of incident bacterial vaginosis (BV) in Australian students. BV only occurred in vaginally sexually active women (BV incidence = 2.2 [95% confidence interval, 0.8-4.9]/100 woman-years), and no incident BV occurred in women who did not engage in vaginal sex during the cohort period (0 [95% confidence interval, 0 3.2]/100 woman-years), P = 0.10. In university students, incident BV was uncommon and absent in sexually abstinent women. PMID- 20739910 TI - Longitudinal examination of alcohol use: a predictor of risky sexual behavior and Trichomonas vaginalis among African-American female adolescents. AB - BACKGROUND: Alcohol use has been linked to risky sexual practices among adolescents. However, limited research on alcohol use and risky sexual behavior has been conducted on African-American female adolescents. This study examined high quantity of alcohol as a longitudinal predictor of risky sexual behavior and sexually transmitted diseases (STDs) among African-American female adolescents, a high-risk population for STDs. METHODS: Three hundred ninety-three adolescent females, 15 to 21 years, were assessed on sociodemographics, alcohol use, and risky sexual behaviors. Participants also provided 2 swab specimens that were assayed for STDs. High quantity of alcohol use was defined as >= 3 drinks in 1 sitting. RESULTS: Binary generalized estimating equation models were conducted assessing the impact of alcohol use at baseline on risky sexual behavior and STDs over a 12-month period. Age, intervention group, and baseline outcome measures were entered as covariates. The results indicated that high quantity of alcohol use predicted positive TV test results, inconsistent condom use, high sexual sensation seeking, multiple sexual partners, sex while high on alcohol or drugs, and having anal sex over a 12-month follow-up period. CONCLUSIONS: These findings suggest that HIV/STD-related behavioral interventions for African-American adolescents should discuss the link between alcohol and HIV/STD-risk behavior. A deeper understanding is paramount to the development of efficacious prevention programs at individual and community levels. PMID- 20739911 TI - Serologic testing for syphilis in the United States: a cost-effectiveness analysis of two screening algorithms. AB - BACKGROUND: The introduction of automated treponemal enzyme immunoassays and chemiluminescence assays (EIA/CA) tests has led some laboratories in the United States to use new syphilis screening algorithms that start with a treponemal test. We compared the economic and health outcomes of this new algorithm with the standard algorithm from the perspective of the United States health system. METHODS: We used a cohort decision analysis to estimate the expected costs and effects (including follow-ups and overtreatment) of the 2 algorithms from a health-care system perspective. In the standard algorithm, rapid plasma reagin (RPR) is followed (if reactive) by EIA/CA (Nontreponemal-First). In the new algorithm, EIA/CA is followed (if reactive) by RPR. If the RPR is negative, Treponema pallidum passive particle agglutination assay (TP-PA) test is used (Treponemal-First). RESULTS: For a cohort of 200,000 individuals (1000 current infections and 10,000 previous infections), the net costs were $1.6 m (Treponemal First) and $1.4 m (Nontreponemal-First). The Treponemal-First option treated 118 more cases (986 vs. 868) but resulted in a substantially higher number of follow ups (11,450 vs. 3756) and overtreatment (964 vs. 38). Treating the additional 118 cases might prevent 1 case of tertiary syphilis. The estimated cost-effectiveness ratios were $1671 (Treponemal-First) and $1621 (Nontreponemal-First) per case treated. The overtreatment was a function of the specificity of the EIA/CA and the lack of independence of EIA/CA and TP-PA. CONCLUSION: The Treponemal-First option costs slightly more and results in more unnecessary treatment. PMID- 20739912 TI - Reinfections during the Florida syphilis epidemic, 2000-2008. AB - BACKGROUND: The last 3 syphilis epidemics in the United States peaked after 5 to 6 years, but rates have now increased for 8 years. We questioned whether persons with multiple syphilis diagnoses (repeaters) are fueling the epidemic. METHODS: The Florida Department of Health database of all syphilis cases reported between 2000 and 2008 was used to examine demographics and disease presentation of repeaters and nonrepeaters using bivariate and multivariate analyses. RESULTS: Of 26,070 persons diagnosed with syphilis, 643 (2.5%) were repeaters (range, 2-5 diagnoses): 82 women, 444 men who have sex with men (MSM), and 117 men identified as either heterosexual (n = 43) or unknown sexual orientation (n = 74). The mean time between first and second diagnosis was approximately 3 years. Median titer increase among those with a second diagnosis of early latent was 32-fold. In multivariate analysis, compared with nonrepeaters, repeaters were more likely to be MSM (odds ratio [OR], 5.3), human immunodeficiency virus (HIV)-infected (OR, 2.0), white (OR, 1.5), ages 35 to 39 (OR, 1.8), and to live in Miami-Dade or Broward Counties (OR, 1.7). Overall, the stage at diagnosis was similar for repeaters, whether it was their initial or subsequent diagnosis. However, HIV infected MSM were more likely to be diagnosed with early latent at second diagnosis compared with initial diagnosis (P <= 0.01). CONCLUSIONS: Most syphilis diagnosed in the current Florida epidemic is among persons infected for the first time. Repeaters are mainly MSM who present with symptoms or large increases in titers. HIV-infected MSM may have higher rates of early asymptomatic disease because of more frequent screening. These are likely to be true new infections. PMID- 20739914 TI - Laminectomy in patients with achondroplasia: the impact of time to surgery on long-term function. AB - STUDY DESIGN: Retrospective analysis, survey. OBJECTIVE: To describe a cohort of individuals with achondroplasia undergoing thoracolumbar laminectomy and to examine if shorter time to surgery was related to improvement in long-term functional outcome. SUMMARY OF BACKGROUND DATA: Data on the long-term benefits of laminectomy are mixed for such patients. Earlier intervention may be associated with greater likelihood of long-term benefit, but quantified data are lacking. METHODS: We retrospectively studied 49 patients with achondroplasia who underwent primary laminectomy for spinal stenosis. Patients completed a questionnaire to assess symptoms, walking distance, and independence (per Modified Rankin Scale), before surgery and currently. Responses were analyzed for the likelihood of improved walking distance or Rankin level. RESULTS: Our patients had the following mean values: age, 37.7 +/- 10.6 years; body mass index, 31.8 +/- 5.5; symptom duration, 74.0 +/- 100.1 months; preoperative symptom severity score, 2.7 +/- 1.0 points; mean changes in blocks walked, +0.39 +/- 2.0; and Rankin level, +0.08 +/- 1.47. Patients with a time-to-surgery interval of <6 months were 7.13 times (95% confidence interval [CI], 1.39-36.66) more likely to experience improvement in walking distance and 4.00 times (95% CI, 1.05-15.21) more likely to experience Rankin level improvement than patients whose interval was >6 months. Intervals of up to 12 and 24 months were associated with increased likelihoods of 4.95 (95% CI, 1.41-17.41) and 3.43 (95% CI, 1.05-11.22), respectively, of improved walking distance compared with those with longer time to surgery intervals, but those Rankin level improvements were not statistically significant. CONCLUSION: Time from symptom onset to surgery in patients with achondroplasia is an important predictor of long-term functional outcome. For sustained long-term postsurgical improvement, the window of opportunity might be relatively narrow. Patients with achondroplasia should seek medical advice for spinal stenotic symptoms as soon as possible. PMID- 20739913 TI - Dissolution of primary intimate relationships during incarceration and associations with post-release STI/HIV risk behavior in a Southeastern city. AB - BACKGROUND: Incarceration is associated with sexually transmitted infections (STIs) including human immunodeficiency virus (HIV). It may contribute to STI/HIV by disrupting primary intimate relationships that protect against high-risk partnerships. METHODS: In an urban sample of men (N = 229) and women (N = 144) in North Carolina, we assessed how often respondents experienced the dissolution of a primary intimate relationship at the time of their own (among men) or their partner's (among women) incarceration. We then measured the association between dissolution of relationships during incarceration and STI/HIV-related risk behaviors. RESULTS: Among men who had ever been incarcerated for 1 month or longer (N = 72), 43% (N = 31) had a marital or nonmarital primary partner at the time of the longest prior sentence. Among women, 22% (N = 31) had ever had a primary partner who had been incarcerated for 1 month or longer. Of men and women who were in a relationship at the time of a prior incarceration of 1 month or longer (N = 62), more than 40% of men and 30% of women reported that the relationship ended during the incarceration. In analyses adjusting for sociodemographic characteristics and crack/cocaine use, loss of a partner during incarceration was associated with nearly 3 times the prevalence of having 2 or more new partners in the 4 weeks before the survey (prevalence ratio: 2.80, 95% confidence interval: 1.13-6.96). CONCLUSIONS: In this sample, incarceration disrupted substantial proportions of primary relationships and dissolution of those relationships was associated with subsequent STI/HIV risk. The results highlight the need for further research to investigate the effects of incarceration on relationships and health. PMID- 20739915 TI - Thermomechanical effects of spine surgery rods composed of different metals and alloys. AB - STUDY DESIGN: A basic science study monitoring changes in the curvature of hand contoured commercially pure titanium (CPTi), titanium-aluminum-vanadium alloy (Ti 6Al-4V), and stainless steel (SS) rods maintained at different temperature conditions. OBJECTIVE: To quantify changes in rod-shape at temperatures representative of those used in clinical practice. SUMMARY OF BACKGROUND DATA: The shape of implanted rods can be displaced due to thermo-mechanical properties of the materials. Warmer temperatures likely initiate this effect. A study of shape loss characteristics of various rod implants may help eliminate undesirable outcomes caused by shape displacement. METHODS: Three different types of rods (CPTi, SS, and Ti-6Al-4V) were hand contoured and then maintained in one of following temperature conditions for 35 days: (1) room temperature (20 degrees C 25 degrees C) without autoclaving before contouring; (2) preliminary autoclaving (1, 5, 10, 20 cycles) at 135.0 degrees C +/- 2 degrees C before contouring followed by body temperature (37.2 degrees C +/- 2 degrees C). Each rod was 5 mm in diameter and 200 mm long. The rods were mounted over graph paper in fixed positions and photographed to measure displacement of the tip as a function of the curvature. RESULTS.: Statistically significant shape loss of the rods manufactured from all the tested materials was found. The hand contoured CPTi rods displayed considerably higher loss of curvature over time than Ti-6Al-4V and SS rods at all tested temperature conditions. Preliminary autoclaving at 135 degrees C before contouring tended to amplify this effect, in particular 1 cycle of autoclaving. If the number of preliminary autoclaving cycles was higher (5 10), a tendency of decrease of shape loss effect was observed in Ti-6Al-4V and CPTi rods. CONCLUSION: The shape of the hand contoured CPTi rods was the least stable of the rods across all applied temperature conditions. The SS and Ti-6Al 4V rods were more stable than CPTi rods. Autoclaving before handcontouring tended to increase rods' shape loss. PMID- 20739916 TI - Morbidity and mortality in the surgical treatment of six hundred five pediatric patients with isthmic or dysplastic spondylolisthesis. AB - STUDY DESIGN: Retrospective analysis of prospectively collected database. OBJECTIVE: To analyze the rate of complications, including neurologic deficits, associated with operative treatment of pediatric isthmic and dysplastic spondylolisthesis. SUMMARY OF BACKGROUND DATA: Pediatric isthmic and dysplastic spondylolisthesis are relatively uncommon dis-orders. Several prior studies have suggested a high rate of complication associated with operative intervention. How ever, most of these studies were performed with sufficiently small sample sizes such that the presence of one complication could significantly affect the overall rate. The Scoliosis Research Society (SRS) prospectively collects morbidity and mortality (M&M) data from its members. This multicentered, multisurgeon database permits analysis of the surgical treatment of this relatively rare condition on an aggregate scale and provides surgeons with useful information for preoperative counseling. METHODS: Patients who underwent surgical treatment for isthmic or dysplastic spondylolisthesis from 2004 to 2007 were identified from the SRS M&M database. Inclusion criteria for analysis included age <= 21 and a primary diagnosis of isthmic or dysplastic spondylolisthesis. RESULTS: Of 25,432 pediatric cases reported, there were a total of 605 (2.4%) cases of pediatric dysplastic (n ? 62, 10%) and isthmic (n ? 543, 90%) spondylolisthesis, with a mean age of 15 years (range, 4-21). Approximately 50% presented with neural element compression, and less than 1% of cases were revisions. Surgical procedures included fusions in 92%, osteotomies in 39%, and reductions in 38%. The overall complication rate was 10.4%. The most common complications included postoperative neurologic deficit (n ? 31, 5%), dural tear (n ? 8, 1.3%), and wound infection (n ? 12, 2%). Perioperative deep venous thrombosis and pulmonary embolus were reported in 2 (0.3%) and 1 (0.2%) patients, respectively. There were no deaths in this series. CONCLUSION: Pediatric isthmic and dysplastic spondylolisthesis are relatively uncommon disorders, representing only 2.4% of pediatric spine procedures in the present study. Even among experienced spine surgeons, surgical treatment of these spinal conditions is associated with a relatively high morbidity. PMID- 20739917 TI - Health-related quality of life improvements in patients undergoing lumbar spinal fusion as a revision surgery. AB - STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: To investigate health related quality of life improvements in patients undergoing lumbar fusion to revise a previous lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Spinal fusion is often used as a surgical intervention in patients who have previously undergone lumbar surgery. Prior studies suggest results that are inferiorto primary fusions. However, most of these studies are based on subjective surgeon evaluations, lack patient-reported outcomes, and include various diagnoses such as prior discectomy, adjacent level degeneration, and nonunion. METHODS: From a single-center database, we identified 171 patients who underwent lumbar fusion to revise a previous lumbar spine surgery. All had prospectively collected outcome measures at a minimum 2-year follow-up. The study group included 91 patients who had previous discectomy or laminectomy, 42 patients undergoing revision for adjacent segment degeneration (ASD) and 38 patients undergoing revision for nonunion. All patients completed the Oswestry Disability Index (ODI), MOS Short Form 36 (SF-36), and back and leg pain numerical rating scores before surgery and at 1 and 2 years after surgery. We compared mean changes in outcome measures and percentage of patients reaching the minimum clinically important difference (MCID) threshold in the 3 groups. Logistic regression analysis was performed to identify preoperative factors which could predict significant improvement. RESULTS: Statistically significant improvements were noted in back pain, leg pain, and ODI in all 3 groups. Postdecompression and ASD patients demonstrated significant improvements in SF-36 PCS at 2 years, while nonunion patients did not. A total of 49% of postdecompression patients, 38% of ASD patients, and 29% of nonunion patients reached the MCID for ODI. About 46% of postdecompression patients, 40% of ASD patients, and 24% of nonunion patients reached the MCID for SF-36 PCS. Significant improvement from index surgery was the only factor which able to predict reaching the MCID for ODI, while worker's compensation and narcotic use predicted failure to reach the MCID for SF-36 PCS. CONCLUSION: The current study demonstrates that patients undergoing lumbar fusion as a revision of a prior lumbar surgery can expect only modest improvements in health-related quality of life. Postdecompression patients achieved moderate improvements in clinical outcome measures, whereas ASD and nonunion patients showed only modest improvements. Further investigation is needed to identify preoperative predictors that will assist the selection of patients who will benefit from revision lumbar fusion. PMID- 20739918 TI - Potential of magnetic resonance imaging findings to refine case definition for mechanical low back pain in epidemiological studies: a systematic review. AB - STUDY DESIGN: systematic review and meta-analysis. OBJECTIVE: to assess how confidently low back pain (LBP) can be attributed to abnormalities on magnetic resonance imaging (MRI), and thereby explore the potential value of MRI abnormalities in refining case definition for mechanical LBP in epidemiological research. SUMMARY OF BACKGROUND DATA: most epidemiological studies of mechanical LBP have defined cases only by reported symptoms, but it is possible that the potency of causes differs depending on whether there is demonstrable underlying spinal pathology. METHODS: we reviewed the published data on MRI abnormalities, looking for data on the repeatability of their assessment, their prevalence in people free from LBP, and their association with LBP. Where data were sufficient, we calculated a summary estimate of prevalence in people without LBP and a meta estimate of the odds ratio for the association with LBP. A formula was then applied to estimate the corresponding prevalence rate ratio, assuming 3 possible prevalence rates for LBP in the general population. RESULTS: data were most extensive for disc protrusion, nerve root displacement or compression, disc degeneration, and high intensity zone, all of which could be assessed repeatedly. All were associated with LBP, meta-estimates of odds ratios ranging from 2.3 (nerve root displacement or compression) to 3.6 (disc protrusion). However, even for disc protrusion, estimates of the corresponding prevalence rate ratios were mostly less than 2. CONCLUSION: MRI findings of disc protrusion, nerve root displacement or compression, disc degeneration, and high intensity zone are all associated with LBP, but individually, none of these abnormalities provides a strong indication that LBP is attributable to underlying pathology. This limits their value in refining epidemiological case definitions for LBP. PMID- 20739919 TI - Accurate prediction of dose-dependent CYP3A4 inhibition by itraconazole and its metabolites from in vitro inhibition data. AB - Inhibitory drug metabolites may contribute to drug-drug interactions (DDIs). The aim of this study was to determine the importance of inhibitory metabolites of itraconazole (ITZ) in in vivo cytochrome P450 (CYP) 3A4 inhibition. The pharmacokinetics of ITZ and midazolam (MDZ) were determined in six healthy volunteers in four sessions after administration of MDZ with and without oral ITZ. After doses of 50, 200, and 400 mg of ITZ, the clearance of orally administered MDZ decreased by 27, 74, and 83%, respectively. The in vivo half maximal inhibitory concentration (IC(50)) for ITZ ranged from 5 to 132 nmol/l in the six subjects. The metabolites of ITZ were estimated to account for ~50% of the total CYP3A4 inhibition, with the relative contribution increasing with time after ITZ dosing. Of the total of 18 interactions observed, 15 (84%) could be predicted within a twofold error margin, with improved accuracy observed when ITZ metabolites were included in the predictions. This study shows that the metabolites of ITZ contribute to CYP3A4 inhibition and need to be accounted for in quantitative rationalization of ITZ-mediated DDIs. PMID- 20739920 TI - Communicating pharmacogenetic research results to breastfeeding mothers taking codeine: a pilot study of perceptions and benefits. AB - Sixty-two codeine-prescribed breastfeeding mothers from a pharmacogenetic study were interviewed regarding the communication of individual CYP2D6 genotype results and overall research findings. All participants wanted to receive the results of their individual genetic tests; however, individuals placed different values on the usefulness of this information toward future medical decisions. Receiving one's pharmacogenetic test results was not associated with a negative psychosocial impact. Thirty-three percent of the participants wished to withhold these results from their physicians. Participants' expectations seem to dictate the extent of transparency of pharmacogenetic research results. PMID- 20739921 TI - Clinical development and review times for new drugs in Japan: associated factors. AB - The length of clinical development and review procedures related to new drugs approved in Japan in 2000-2009 were analyzed. The length of time taken for clinical development varied depending on diversification of strategies, and the review times showed a decline during this period. Regression analyses suggested that clinical development times were significantly shorter for non-new molecular entities (non-NMEs), priority reviews, conditional approvals, and drugs utilizing foreign clinical data. The review times were shorter for new drug applications (NDAs) submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) and for priority reviews. The effects of pre-NDA consultations were mixed; the review time was shorter, but the clinical development period was prolonged. PMID- 20739922 TI - Dementia and the TAR DNA binding protein 43. PMID- 20739923 TI - Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line. AB - Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady-state protein concentrations in multi-cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two-thirds of protein abundance variation. mRNA sequence lengths, amino-acid properties, upstream open reading frames and secondary structures in the 5' untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3'UTR explained a larger proportion of protein abundance variation than characteristics of the 5'UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post-transcriptional regulation. PMID- 20739924 TI - microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. AB - Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)-gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122 controlled genes and impairment of mitochondrial metabolism. In conclusion, miR 122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients. PMID- 20739925 TI - Structured digital tables on the Semantic Web: toward a structured digital literature. AB - In parallel to the growth in bioscience databases, biomedical publications have increased exponentially in the past decade. However, the extraction of high quality information from the corpus of scientific literature has been hampered by the lack of machine-interpretable content, despite text-mining advances. To address this, we propose creating a structured digital table as part of an overall effort in developing machine-readable, structured digital literature. In particular, we envision transforming publication tables into standardized triples using Semantic Web approaches. We identify three canonical types of tables (conveying information about properties, networks, and concept hierarchies) and show how more complex tables can be built from these basic types. We envision that authors would create tables initially using the structured triples for canonical types and then have them visually rendered for publication, and we present examples for converting representative tables into triples. Finally, we discuss how 'stub' versions of structured digital tables could be a useful bridge for connecting together the literature with databases, allowing the former to more precisely document the later. PMID- 20739926 TI - Modeling genome-wide replication kinetics reveals a mechanism for regulation of replication timing. AB - Microarrays are powerful tools to probe genome-wide replication kinetics. The rich data sets that result contain more information than has been extracted by current methods of analysis. In this paper, we present an analytical model that incorporates probabilistic initiation of origins and passive replication. Using the model, we performed least-squares fits to a set of recently published time course microarray data on Saccharomyces cerevisiae. We extracted the distribution of firing times for each origin and found that the later an origin fires on average, the greater the variation in firing times. To explain this trend, we propose a model where earlier-firing origins have more initiator complexes loaded and a more accessible chromatin environment. The model demonstrates how initiation can be stochastic and yet occur at defined times during S phase, without an explicit timing program. Furthermore, we hypothesize that the initiators in this model correspond to loaded minichromosome maintenance complexes. This model is the first to suggest a detailed, testable, biochemically plausible mechanism for the regulation of replication timing in eukaryotes. PMID- 20739928 TI - Transcriptional regulation is only half the story. PMID- 20739927 TI - A model of yeast cell-cycle regulation based on multisite phosphorylation. AB - In order for the cell's genome to be passed intact from one generation to the next, the events of the cell cycle (DNA replication, mitosis, cell division) must be executed in the correct order, despite the considerable molecular noise inherent in any protein-based regulatory system residing in the small confines of a eukaryotic cell. To assess the effects of molecular fluctuations on cell-cycle progression in budding yeast cells, we have constructed a new model of the regulation of Cln- and Clb-dependent kinases, based on multisite phosphorylation of their target proteins and on positive and negative feedback loops involving the kinases themselves. To account for the significant role of noise in the transcription and translation steps of gene expression, the model includes mRNAs as well as proteins. The model equations are simulated deterministically and stochastically to reveal the bistable switching behavior on which proper cell cycle progression depends and to show that this behavior is robust to the level of molecular noise expected in yeast-sized cells (approximately 50 fL volume). The model gives a quantitatively accurate account of the variability observed in the G1-S transition in budding yeast, which is governed by an underlying sizer+timer control system. PMID- 20739929 TI - Parkinson's disease. PMID- 20739930 TI - Biomarkers: casting the net wide. PMID- 20739931 TI - Slowing the decline. PMID- 20739932 TI - Treatment frontiers. PMID- 20739933 TI - Secrets of the shaking palsy. PMID- 20739934 TI - Levodopa: the story so far. PMID- 20739935 TI - Parkinson's disease: a model dilemma. PMID- 20739936 TI - Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation. AB - Successful partition of replicated genomes at cell division requires chromosome attachment to opposite poles of mitotic spindle (bi-orientation). Any defects in this regulation bring about chromosomal instability, which may accelerate tumour progression in humans. To achieve chromosome bi-orientation at prometaphase, the chromosomal passenger complex (CPC), composed of catalytic kinase Aurora B and regulatory components (INCENP, Survivin and Borealin), must be localized to centromeres to phosphorylate kinetochore substrates. Although the CPC dynamically changes the subcellular localization, the regulation of centromere targeting is largely unknown. Here we isolated a fission yeast cyclin B mutant defective specifically in chromosome bi-orientation. Accordingly, we identified Cdk1 (also known as Cdc2)-cyclin-B-dependent phosphorylation of Survivin. Preventing Survivin phosphorylation impairs centromere CPC targeting as well as chromosome bi-orientation, whereas phosphomimetic Survivin suppresses the bi-orientation defect in the cyclin B mutant. Survivin phosphorylation promotes direct binding with shugoshin, which we now define as a conserved centromeric adaptor of the CPC. In human cells, the phosphorylation of Borealin has a comparable role. Thus, our study resolves the conserved mechanisms of CPC targeting to centromeres, highlighting a key role of Cdk1-cyclin B in chromosome bi-orientation. PMID- 20739939 TI - A46G and C79G polymorphisms in the beta2-adrenergic receptor gene (ADRB2) and essential hypertension risk: a meta-analysis. AB - No consensus has been reached on the association between the beta2-adrenergic receptor polymorphisms A46G and C79G and essential hypertension risk. We performed a meta-analysis to confirm the possible association. After reviewing 303 reports in PubMed and 359 reports in Embase, we included in our meta-analysis 18 articles (20 studies) that met our inclusion criteria. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. There was no statistical association between A46G and hypertension risk in all subjects, Asians or Caucasians. However, an association was observed in the dominant genetic model (AA vs. (AG+GG)) (P=0.04, odds ratio (OR)=1.38, 95% confidence interval (CI) 1.01-1.87, P(heterogeneity)=0.98, fixed-effects model) in the subgroup of mixed Africans. No overall statistical association could be found between C79G and hypertension risk or any ethnic subgroup. In the research conducted on severe hypertension (systolic blood pressure >=160 mm Hg and/or diastolic blood pressure >=95 mm Hg hypertensive population), significant association was found in the dominant genetic model (CC vs. (CG+GG)) (P=0.04, OR=1.38, 95% CI 1.02-1.86, P(heterogeneity)=0.03, random-effects model), and there was also a borderline significance between the C79 allele and severe hypertension (P=0.05, OR=1.26, 95% CI 1.00-1.57, P(heterogeneity)=0.04, random-effects model). No association could be found in this study between the two polymorphisms and stage 2 hypertension. More studies stratified for different ethnicities and different stages of hypertension should be performed in the future. PMID- 20739937 TI - The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. AB - Centromeres are specified epigenetically, and the histone H3 variant CENP-A is assembled into the chromatin of all active centromeres. Divergence from H3 raises the possibility that CENP-A generates unique chromatin features to mark physically centromere location. Here we report the crystal structure of a subnucleosomal heterotetramer, human (CENP-A-H4)(2), that reveals three distinguishing properties encoded by the residues that comprise the CENP-A targeting domain (CATD; ref. 2): (1) a CENP-A-CENP-A interface that is substantially rotated relative to the H3-H3 interface; (2) a protruding loop L1 of the opposite charge as that on H3; and (3) strong hydrophobic contacts that rigidify the CENP-A-H4 interface. Residues involved in the CENP-A-CENP-A rotation are required for efficient incorporation into centromeric chromatin, indicating specificity for an unconventional nucleosome shape. DNA topological analysis indicates that CENP-A-containing nucleosomes are octameric with conventional left handed DNA wrapping, in contrast to other recent proposals. Our results indicate that CENP-A marks centromere location by restructuring the nucleosome from within its folded histone core. PMID- 20739938 TI - Structure of RCC1 chromatin factor bound to the nucleosome core particle. AB - The small GTPase Ran enzyme regulates critical eukaryotic cellular functions including nuclear transport and mitosis through the creation of a RanGTP gradient around the chromosomes. This concentration gradient is created by the chromatin bound RCC1 (regulator of chromosome condensation) protein, which recruits Ran to nucleosomes and activates Ran's nucleotide exchange activity. Although RCC1 has been shown to bind directly with the nucleosome, the molecular details of this interaction were not known. Here we determine the crystal structure of a complex of Drosophila RCC1 and the nucleosome core particle at 2.9 A resolution, providing an atomic view of how a chromatin protein interacts with the histone and DNA components of the nucleosome. Our structure also suggests that the Widom 601 DNA positioning sequence present in the nucleosomes forms a 145-base-pair nucleosome core particle, not the expected canonical 147-base-pair particle. PMID- 20739940 TI - Compound heterozygous PMP22 deletion mutations causing severe Charcot-Marie-Tooth disease type 1. AB - We present a 31/3-year-old girl with severe Charcot-Marie-Tooth disease type 1 (Dejerine-Sottas disease), who was a compound heterozygote carrying a deletion of the whole peripheral myelin protein 22 (PMP22) and a deletion of exon 5 in the other PMP22 allele. Haplotype analyses and sequence determination revealed a 11.2 kb deletion spanning from intron 4 to 3'-region of PMP22, which was likely generated by nonhomologous end joining. Severely affected patients carrying a PMP22 deletion must be analyzed for the mutations of the other copy of PMP22. PMID- 20739941 TI - GATA transcription factors in congenital heart defects: a commentary on a novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. PMID- 20739942 TI - Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations. AB - Hearing loss (HL) is the most prevalent sensory defect affecting 1 in 500 neonates. Genetic factors are involved in half of the cases. The extreme heterogeneity of HL makes it difficult to analyze and determine the accurate genetic causes of the impairment. Up to now, 10 genes, namely, GJB2, GJB6, SLC26A4, TECTA, PJVK, Col11A2, Myo15A, TMC1, RDX and microRNA (miR-183), have been studied in an Iranian population. The prevalence of HL in Iran was estimated to be 2-3 times higher than that in other parts of the world. Here, the most common bases of congenital nonsyndromic hearing loss (NSHL) are discussed. We reviewed GJB2, GJB6 (large deletion), TECTA, SLC26A4 and PEJVK mutations, and studied their frequencies and distributions in different ethnic groups in 1934, 500, 121, 80 and 34 unrelated families throughout Iran, respectively. GJB2 mutation was the most common factor causing NSHL, with a mean frequency of 18.17% in the Iranian population. The importance of Iran's geographical location in the migration pathway from west to east through the silk route was also highlighted. SLC26A4 and TECTA mutations were the second and third main reasons of HL and accounted for up to 10 and 4% of prelingual HL in Iran, respectively. Mutations in GJB2, SLC26, TECTA and PJVK genes have an important role in HL in Iran and a screening test should be generated for better intervention and diagnosis programs. PMID- 20739943 TI - Genetics of Moyamoya disease. AB - Moyamoya disease (MMD) is a disease pattern consisting of bilateral stenosis of the intracranial internal carotid arteries (ICA) accompanied by a network of abnormal collateral vessels that bypass the stenosis. Once symptomatic, insufficient cerebral blood flow or rupture of the fragile collaterals may cause stroke or hemorrhage, resulting in severe neurological dysfunction or death. The etiology of MMD is still unknown, although few associations with other diseases and environmental factors have been described. Strong regional differences in epidemiological data, as well as known familial cases, turned the focus to genetics for the insight into the disease's pathogenesis. Thus far, several reports have suggested specific genetic loci and individual genes as predisposing to MMD, but none have demonstrated reproducible results in independent cohorts. Small sample sizes, as well as a likely multifactorial origin, seem to be the most challenging tasks in identifying the disease-causing mechanisms. Once identified, susceptibility genes may allow preventive screening and a possible development of novel therapeutic options. PMID- 20739944 TI - Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia. AB - Hearing impairment is one of the most common disorders of sensorineural function and the incidence of profound prelingual deafness is about 1 per 1000 at birth. GJB2 gene mutations make the largest contribution to hereditary hearing impairment. The spectrum and prevalence of some GJB2 mutations are known to be dependent on the ethnic origin of the population. This study presents data on the carrier frequencies of major GJB2 mutations, c.35delG, c.167delT and c.235delC, among 2308 healthy persons from 18 various populations of Eurasia: Russians, Bashkirs, Tatars, Chuvashes, Udmurts, Komi-Permyaks and Mordvins (Volga-Ural region of Russia); Belarusians and Ukrainians (East Europe); Abkhazians, Avars, Cherkessians and Ingushes (Caucasus); Kazakhs, Uighurs and Uzbeks (Central Asia); and Yakuts and Altaians (Siberia). The data on c.35delG and c.235delC mutation prevalence in the studied ethnic groups can be used to investigate the prospective founder effect in the origin and prevalence of these mutations in Eurasia and consequently in populations around the world. PMID- 20739945 TI - No evidence that human papillomavirus is responsible for the aggressive nature of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma. PMID- 20739946 TI - Localization, age- and site-dependent expression, and regulation of 11beta hydroxysteroid dehydrogenase type 1 in skin. AB - Glucocorticoids (GCs) are highly detrimental to skin integrity and function both when applied topically for anti-inflammatory treatments and during conditions of circulating excess, e.g., Cushing's syndrome. Within target tissues, GC availability is regulated at a prereceptor level, independently of systemic levels, by isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) that interconvert active cortisol and inactive cortisone. Many of the adverse effects of GCs on skin are also reminiscent of the natural aging process. 11beta-HSD1 (which activates cortisol), but not 11beta-HSD2 (which inactivates cortisol), was expressed in epidermal keratinocytes and dermal fibroblasts in human skin and also in outer hair follicle root sheath cells in murine skin. 11beta-HSD1 activity was present ex vivo in both species and increased with age in human skin tissue explants. In primary human dermal fibroblasts (HDF) from both photoprotected and photoexposed sites, 11beta-HSD1 also increased with donor age. Additionally, photoexposed HDF displayed higher 11beta-HSD1 mRNA expression than donor-matched photoprotected HDF. GC treatment of HDF caused upregulation of 11beta-HSD1 mRNA levels independent of donor age or site. The age- and site associated increase in dermal 11beta-HSD1, and the ensuing increased local GC activation, may contribute to the adverse changes in skin morphology and function associated with chronological aging and photoaging. PMID- 20739947 TI - UV exposure boosts transcutaneous immunization and improves tumor immunity: cytotoxic T-cell priming through the skin. AB - Immunologic approaches to combat cancer aim at the induction of tumor-reactive immune responses to achieve long-term protection. In this context, we recently developed a transcutaneous immunization (TCI) method using the Toll-like receptor (TLR) 7 agonist imiquimod and a peptide epitope. Application onto intact skin induces potent cytotoxic T lymphocyte (CTL) responses and protection against transplanted tumors. The purpose of this study was to explore the effects of UV irradiation on imiquimod-based TCI. Here we show that skin exposure to low-dose UV light before TCI with imiquimod strongly boosts specific CTL responses leading to memory formation and enhanced tumor protection. Toward the mechanisms, we show that the activation of bone-marrow-derived dermal dendritic cells (DCs), but not Langerin-expressing DCs, is responsible for enhanced CTL activation. We describe an optimized TCI method that mediates enhanced CTL and antitumor responses by a DC- and TLR-dependent mechanism. These data may provide the basis for the future development of advanced vaccination protocols against tumors and persistent virus infections. PMID- 20739948 TI - Spontaneous regression of highly immunogenic Molluscum contagiosum virus (MCV) induced skin lesions is associated with plasmacytoid dendritic cells and IFN-DC infiltration. AB - Molluscum contagiosum virus (MCV) infection induces self-limiting cutaneous lesions in an immunocompetent host that can undergo spontaneous regression preceded by local inflammation. On histology, a large majority of MCV-induced lesions are characterized by islands of hyperplastic epithelium containing infected keratinocytes and surrounded by scarce inflammatory infiltrate. However, spontaneous regression has been associated with the occurrence of a dense inflammatory reaction. By histology and immunohistochemistry, we identified MCV induced lesions showing a dense inflammatory infiltrate associated with cell death in keratinocytes (inflammatory Molluscum contagiosum (I-MC)). In I-MC, hyperplastic keratinocytes were highly immunogenic as demonstrated by the expression of major histocompatibility complex class I and II molecules. Immune cell infiltration consisted of numerous cytotoxic T cells admixed with natural killer cells and plasmacytoid dendritic cells (PDCs). Accordingly, a type I IFN signature associated with PDC infiltration was demonstrated in both keratinocytes and inflammatory cells. Among the latter, a cell population resembling IFN-DC (CD123(+)CD11c(+)CD16(+)CD14(+)MxA(+)) was identified in proximity to islands of apoptotic keratinocytes. In vitro-generated IFN-DCs expressed a strong cytotoxic signature, as demonstrated by high levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL). This study establishes a previously unreported model to underpin the role of innate immune cells in viral immune surveillance. PMID- 20739949 TI - The beneficial effect of blocking Kv1.3 in the psoriasiform SCID mouse model. AB - The Kv1.3 channel is important in the activation and function of effector memory T cells. Recently, specific blockers of the Kv1.3 channel have been developed as a potential therapeutic option for diverse autoimmune diseases. In psoriatic lesions, most lymphocytes are memory effector T cells. The aim of the present study was to detect the expression of Kv1.3 channels in these cells in psoriatic lesions as well as in human psoriasiform skin grafts using the severe combined immunodeficient (SCID) mouse model. Histological and immunohistochemical staining for Kv1.3 expression and various inflammatory markers was performed in sections obtained from six psoriatic patients and 18 beige-SCID mice with psoriasiform human skin grafts. Six grafted mice were treated with Stichodactyla helianthus neurotoxin (ShK), a known Kv1.3 blocker. The results showed an increased number of Kv1.3+ cells in the psoriatic skin as well as in the psoriasiform skin grafts as compared with normal skin and normal skin grafts. Injections of ShK showed a marked therapeutic effect in three of six psoriasiform skin grafts. A significantly decreased number of Kv1.3+ cells was observed in the responders compared with the control grafts. This pilot study, although performed in a small number of mice, reveals the possible beneficial effect of Kv1.3 blockers in psoriasis patients. PMID- 20739950 TI - Selection of tumorigenic melanoma cells using ALDH. AB - Despite increasing knowledge regarding melanoma-initiating cells (MICs), questions persist regarding the number and phenotypic nature of cells with tumor generating capability. Evidence for a phenotypically distinct human MIC has been found in NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice. However, a phenotypically distinct human MIC was not found in the NOD/SCIDIl2rg( )/(-) (NSG) mouse model. The demonstration of a distinct population of human melanoma cells responsible for tumorigenesis and tumor cell self-renewal would provide an important target for new melanoma therapies. In this study, we show a 100-fold range in MIC frequency in human melanoma (1 in 18,000 to 1 in 1,851,000 cells) in the NOD/SCID mouse. In this model, human melanoma cells with high aldehyde dehydrogenase (ALDH) activity were enriched 16.8-fold in tumorigenic cells over unfractionated (UNF) cells, such that 1 in 21,000 cells was a MIC. In the NSG mouse, the ALDH expressing cell population was enriched 100-fold in tumorigenic cells over UNF cells, such that one in four cells was a MIC. Xenograft melanomas that developed from ALDH(+) cells displayed robust self renewal, whereas those from ALDH(-) cells showed minimal self-renewal in vitro. Thus, ALDH(+) melanoma cells have enhanced tumorigenicity over ALDH(-) cells and superior self-renewal ability. PMID- 20739951 TI - Eczema prevalence in the United States: data from the 2003 National Survey of Children's Health. AB - Using the 2003 National Survey of Children's Health sponsored by the federal Maternal and Child Health Bureau, we calculated prevalence estimates of eczema nationally and for each state among a nationally representative sample of 102,353 children 17 years of age and under. Our objective was to determine the national prevalence of eczema/atopic dermatitis in the US pediatric population and to further examine geographic and demographic associations previously reported in other countries. Overall, 10.7% of children were reported to have a diagnosis of eczema in the past 12 months. Prevalence ranged from 8.7 to 18.1% between states and districts, with the highest prevalence reported in many of the East Coast states, as well as in Nevada, Utah, and Idaho. After adjusting for confounders, metropolitan living was found to be a significant factor in predicting a higher disease prevalence with an odds ratio of 1.67 (95% confidence interval of 1.19 2.35, P=0.008). Black race (odds ratio 1.70, P=0.005) and education level in the household greater than high school (odds ratio 1.61, P=0.004) were also significantly associated with a higher prevalence of eczema. The wide range of prevalence suggests that social or environmental factors may influence disease expression. PMID- 20739952 TI - Genomic profiling of high-risk acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia (ALL) is a heterogeneous disease comprising multiple subtypes with different genetic alterations and responses to therapy. Recent genome-wide profiling studies of ALL have identified a number of novel genetic alterations that target key cellular pathways in lymphoid growth and differentiation and are associated with treatment outcome. Notably, genetic alteration of the lymphoid transcription factor gene IKZF1 is a hallmark of multiple subtypes of ALL with poor prognosis, including BCR-ABL1-positive lymphoid leukemia and a subset of 'BCR-ABL1-like' ALL cases that, in addition to IKZF1 alteration, harbor genetic mutations resulting in aberrant lymphoid cytokine receptor signaling, including activating mutations of Janus kinases and rearrangement of cytokine receptor-like factor 2 (CRLF2). Recent insights from genome-wide profiling studies of B-progenitor ALL and the potential for new therapeutic approaches in high-risk disease are discussed. PMID- 20739954 TI - Identification of disease- and therapy-associated proteome changes in the sera of patients with myelodysplastic syndromes and del(5q). AB - Using ProteinChip array technology, which is based on the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed proteomic analyses on sera from myelodysplastic syndromes (MDSs) patients with an interstitial deletion of the long arm of chromosome 5 (del(5q)) and those from control individuals. One analysis with 80 samples from 29 patients and 51 control subjects resulted in the detection of 61 peak differences. Another analysis with 36 paired-samples from 18 patients collected before and after the treatment with lenalidomide (Revlimid) identified 19 differential peak features. We also observed differential profiles between the pre-treatment samples from the responders and those from the non-responders reflected by eight peak differences. On the basis of these data we developed two classification models that could distinguish between the diseased and the control subjects or between the responders and the non-responders. Efforts were made to purify and identify a range of differential peak proteins. We conclude that inter-alpha trypsin inhibitor, heavy chain H4 (fragments), serum transferrin, transthyretin (variants), haemoglobin and a protein peak at m/z 2791 could be potential disease associated markers for del(5q) MDS. Platelet factor 4 (PF-4) and a peak at m/z 8559 may serve as therapy-associated markers and be potentially useful for monitoring and predicting the response to therapy. PMID- 20739953 TI - High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias. AB - In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg Prkdc(scid)IL2rg(tmlWjl)/SzJ (NOD-severe combined immune deficient (scid) IL2rg( /-)) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1-7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg(-/-) mice. In this highly sensitive NOD-scid IL2Rg(-/-)-based assay, 1-100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL. PMID- 20739955 TI - Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. AB - We prospectively studied the impact of several cytogenetic abnormalities (CAs) in patients with relapsed/refractory myeloma who received lenalidomide and dexamethasone (RD) with or without the addition of bortezomib (V). On the basis of the presence of previous neuropathy, 50 patients were treated with RD and 49, without preexisting neuropathy, with VRD. The overall response rate was 63%, similar for RD and VRD. Poor risk cytogenetics were associated with lower response rates in RD (P=0.01), but not in VRD (P=0.219). The median progression free survival (PFS) was similar for RD (9 months) and VRD (7 months). The median overall survival (OS) for all patients was 16 months, with no differences between RD or VRD regimens. Poor risk cytogenetics, especially del17p, resistance to previous thalidomide, elevated lactate dehydrogenase (LDH) and presence of extramedullary disease were associated with inferior response to therapy and shorter PFS and OS. The impact of other CAs on OS was more pronounced in RD. In conclusion, the presence of CAs is an important adverse prognostic factor for patients with relapsed/refractory myeloma, but resistance to previous thalidomide, elevated LDH and presence of extramedullary disease remain of major prognostic importance. The outcome of patients with del17p remains extremely poor even with VRD combination. PMID- 20739956 TI - Analysis of BCR-ABL1 tyrosine kinase domain mutational spectra in primitive chronic myeloid leukemia cells suggests a unique mutator phenotype. PMID- 20739957 TI - Meis1 disrupts the genomic imprint of Dlk1 in a NUP98-HOXD13 leukemia model. PMID- 20739958 TI - Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1. AB - Recent developments in the field of oncolytic or tumor-selective viruses have meant that the clinical applications of these agents are now being considered in more detail. Like most cancer therapies it is likely that they will be used primarily in combination with other therapeutics. Although several reports have shown that oncolytic viruses can synergize with chemotherapies within an infected cancer cell, it would be particularly important to determine whether factors released from infected cells could enhance the action of chemotherapies at a distance. Here, we demonstrate in vitro synergy between oncolytic vaccinia and taxanes. However, we also show, for the first time, that this synergy is at least partly due to the release of factors from the infected cells that are capable of sensitizing surrounding cells to chemotherapy. Several cellular factors were identified as being mediators of this bystander effect, including type I interferon released soon after infection and high-mobility group protein B1 (HMGB1) released after cell death. This represents the first description of these mechanisms for beneficial interactions between viral and traditional tumor therapies. These data may provide a direct basis for the design of clinical trials with agents currently in the clinic, as well as providing insight into the development of next generation viral vectors. PMID- 20739959 TI - Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage. AB - The ideal gene therapy vector should enable persistent expression without the limitations of safety and reproducibility. We previously reported that a prototype plasmid vector, containing a scaffold matrix attachment region (S/MAR) domain and the luciferase reporter gene, showed transgene expression for at least 6 months following a single administration to MF1 mice. Following partial hepatectomy of the animals, however, we found no detectable vector replication and subsequent propagation in vivo. To overcome this drawback, we have now developed an in vivo liver selection strategy by which liver cells transfected with an S/MAR plasmid are provided with a survival advantage over non-transfected cells. This allows an enrichment of vectors that are capable of replicating and establishing themselves as extra-chromosomal entities in the liver. Accordingly, a novel S/MAR plasmid encoding the Bcl-2 gene was constructed; Bcl-2 expression confers resistance against apoptosis-mediated challenges by the Fas-activating antibody Jo2. Following hydrodynamic delivery to the livers of mice and frequent Jo2 administrations, we demonstrate that this Bcl-luciferase S/MAR plasmid is indeed capable of providing sustained luciferase reporter gene expression for over 3 months and that this plasmid replicates as an episomal entity in vivo. These results provide proof-of-principle that S/MAR vectors are capable of preventing transgene silencing, are resistant to integration and are able to confer mitotic stability in vivo when provided with a selective advantage. PMID- 20739962 TI - Australia's mixed climate. PMID- 20739960 TI - Evidence for male allocation in pipefish? AB - Sexual differences in the extent and type of parental care lie at the heart of sexual selection theory, and evolution resulting from parental conflict has produced some striking behavioural and morphological adaptations. In a study of male pregnancy in Gulf pipefish, Paczolt and Jones showed that more eggs were transferred to the male's brood pouch and more offspring survived following mating with large females (preferred by males) than with small (less preferred) females. Although the authors conclude that the lower survival of embryos from small females is most consistent with males actively removing resources from these offspring, no data are presented to directly support this hypothesis (ref. 2, and Supplementary Information therein) and the data do not refute the alternative explanation that differential egg survival is caused by female effects mediated by variation in fecundity and egg size or quality. We argue that only by experimentally manipulating female attractiveness separately from the quality of eggs deposited in the brood pouch can the extent of sexual conflict in this role-reversed system be assessed. PMID- 20739963 TI - Collateral damage. PMID- 20739970 TI - Journal club. A physicist and biogeochemist gets a kick out of the problem of Brownian motion and diffusion. PMID- 20739976 TI - Big science feels the pinch in Europe. PMID- 20739977 TI - Sugar synthesis speeds up. PMID- 20739978 TI - G-whizzes disagree over gravity. PMID- 20739979 TI - Key Alzheimer's findings questioned. PMID- 20739980 TI - Battle to degas deadly lakes continues. PMID- 20739981 TI - Nuclear theory nudged. PMID- 20739982 TI - Genetics: Pet project. PMID- 20739983 TI - Proposals for surface-temperature databank now open for scrutiny. PMID- 20739984 TI - Clarifying knowledge ownership in Europe's medicines initiative. PMID- 20739985 TI - Misconduct: don't penalize the honest majority of scientists. PMID- 20739986 TI - Misconduct: don't assume science is self-correcting. PMID- 20739987 TI - Consumers have a right to affordable genetic testing. PMID- 20739988 TI - Mosquitoes: just how much biodiversity does humanity need? PMID- 20739989 TI - Mosquitoes: retain an ex situ population for ecological insurance. PMID- 20739990 TI - Mosquitoes: first evaluate impacts of eradicating them. PMID- 20739991 TI - Mosquitoes: schemes to render them extinct are impracticable. PMID- 20739992 TI - Disasters widen the rich-poor gap. PMID- 20739993 TI - Save your census. PMID- 20739997 TI - Condensed-matter physics: The dance of electrons and holes. PMID- 20739998 TI - Structural biology: Conservation in vesicle coats. PMID- 20739999 TI - Astrophysics: Making black holes from scratch. PMID- 20740001 TI - Cell cycle: Retinoblastoma, a trip organizer. PMID- 20740002 TI - Neurodegeneration: An expansion in ALS genetics. PMID- 20740003 TI - Quantum mechanics: The usefulness of uselessness. PMID- 20740004 TI - Cancer: Viruses' backup plan. PMID- 20740005 TI - The evolution of eusociality. AB - Eusociality, in which some individuals reduce their own lifetime reproductive potential to raise the offspring of others, underlies the most advanced forms of social organization and the ecologically dominant role of social insects and humans. For the past four decades kin selection theory, based on the concept of inclusive fitness, has been the major theoretical attempt to explain the evolution of eusociality. Here we show the limitations of this approach. We argue that standard natural selection theory in the context of precise models of population structure represents a simpler and superior approach, allows the evaluation of multiple competing hypotheses, and provides an exact framework for interpreting empirical observations. PMID- 20740006 TI - Lithospheric layering in the North American craton. AB - How cratons-extremely stable continental areas of the Earth's crust-formed and remained largely unchanged for more than 2,500 million years is much debated. Recent studies of seismic-wave receiver function data have detected a structural boundary under continental cratons at depths too shallow to be consistent with the lithosphere-asthenosphere boundary, as inferred from seismic tomography and other geophysical studies. Here we show that changes in the direction of azimuthal anisotropy with depth reveal the presence of two distinct lithospheric layers throughout the stable part of the North American continent. The top layer is thick ( approximately 150 km) under the Archaean core and tapers out on the surrounding Palaeozoic borders. Its thickness variations follow those of a highly depleted layer inferred from thermo-barometric analysis of xenoliths. The lithosphere-asthenosphere boundary is relatively flat (ranging from 180 to 240 km in depth), in agreement with the presence of a thermal conductive root that subsequently formed around the depleted chemical layer. Our findings tie together seismological, geochemical and geodynamical studies of the cratonic lithosphere in North America. They also suggest that the horizon detected in receiver function studies probably corresponds to the sharp mid-lithospheric boundary rather than to the more gradual lithosphere-asthenosphere boundary. PMID- 20740009 TI - Direct formation of supermassive black holes via multi-scale gas inflows in galaxy mergers. AB - Observations of distant quasars indicate that supermassive black holes of billions of solar masses already existed less than a billion years after the Big Bang. Models in which the 'seeds' of such black holes form by the collapse of primordial metal-free stars cannot explain the rapid appearance of these supermassive black holes because gas accretion is not sufficiently efficient. Alternatively, these black holes may form by direct collapse of gas within isolated protogalaxies, but current models require idealized conditions, such as metal-free gas, to prevent cooling and star formation from consuming the gas reservoir. Here we report simulations showing that mergers between massive protogalaxies naturally produce the conditions for direct collapse into a supermassive black hole with no need to suppress cooling and star formation. Merger-driven gas inflows give rise to an unstable, massive nuclear gas disk of a few billion solar masses, which funnels more than 10(8) solar masses of gas to a sub-parsec-scale gas cloud in only 100,000 years. The cloud undergoes gravitational collapse, which eventually leads to the formation of a massive black hole. The black hole can subsequently grow to a billion solar masses on timescales of about 10(8) years by accreting gas from the surrounding disk. PMID- 20740007 TI - Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. AB - The causes of amyotrophic lateral sclerosis (ALS), a devastating human neurodegenerative disease, are poorly understood, although the protein TDP-43 has been suggested to have a critical role in disease pathogenesis. Here we show that ataxin 2 (ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models. ATXN2 and TDP-43 associate in a complex that depends on RNA. In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. To assess the involvement of ATXN2 in ALS, we analysed the length of the polyQ repeat in the ATXN2 gene in 915 ALS patients. We found that intermediate-length polyQ expansions (27-33 glutamines) in ATXN2 were significantly associated with ALS. These data establish ATXN2 as a relatively common ALS susceptibility gene. Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies. PMID- 20740008 TI - Heterochromatin silencing of p53 target genes by a small viral protein. AB - The transcription factor p53 (also known as TP53) guards against tumour and virus replication and is inactivated in almost all cancers. p53-activated transcription of target genes is thought to be synonymous with the stabilization of p53 in response to oncogenes and DNA damage. During adenovirus replication, the degradation of p53 by E1B-55k is considered essential for p53 inactivation, and is the basis for p53-selective viral cancer therapies. Here we reveal a dominant epigenetic mechanism that silences p53-activated transcription, irrespective of p53 phosphorylation and stabilization. We show that another adenoviral protein, E4-ORF3, inactivates p53 independently of E1B-55k by forming a nuclear structure that induces de novo H3K9me3 heterochromatin formation at p53 target promoters, preventing p53-DNA binding. This suppressive nuclear web is highly selective in silencing p53 promoters and operates in the backdrop of global transcriptional changes that drive oncogenic replication. These findings are important for understanding how high levels of wild-type p53 might also be inactivated in cancer as well as the mechanisms that induce aberrant epigenetic silencing of tumour-suppressor loci. Our study changes the longstanding definition of how p53 is inactivated in adenovirus infection and provides key insights that could enable the development of true p53-selective oncolytic viral therapies. PMID- 20740010 TI - Formation of asteroid pairs by rotational fission. AB - Pairs of asteroids sharing similar heliocentric orbits, but not bound together, were found recently. Backward integrations of their orbits indicated that they separated gently with low relative velocities, but did not provide additional insight into their formation mechanism. A previously hypothesized rotational fission process may explain their formation-critical predictions are that the mass ratios are less than about 0.2 and, as the mass ratio approaches this upper limit, the spin period of the larger body becomes long. Here we report photometric observations of a sample of asteroid pairs, revealing that the primaries of pairs with mass ratios much less than 0.2 rotate rapidly, near their critical fission frequency. As the mass ratio approaches 0.2, the primary period grows long. This occurs as the total energy of the system approaches zero, requiring the asteroid pair to extract an increasing fraction of energy from the primary's spin in order to escape. We do not find asteroid pairs with mass ratios larger than 0.2. Rotationally fissioned systems beyond this limit have insufficient energy to disrupt. We conclude that asteroid pairs are formed by the rotational fission of a parent asteroid into a proto-binary system, which subsequently disrupts under its own internal system dynamics soon after formation. PMID- 20740011 TI - Coherent measurements of high-order electronic correlations in quantum wells. AB - Strong, long-range Coulomb interactions can lead to correlated motions of multiple charged particles, which can induce important many-body effects in semiconductors. The exciton states formed from correlated electron-hole pairs have been studied extensively, but basic properties of multiple-exciton correlations-such as coherence times, population lifetimes, binding energies and the number of particles that can be correlated-are largely unknown because they are not spectroscopically accessible from the ground state. Here we present direct observations of high-order coherences in gallium arsenide quantum wells, achieved using two-dimensional multiple-quantum spectroscopy methods in which up to seven successive light fields were used. The measurements were made possible by the combination of a reconfigurable spatial beam-shaper that formed multiple beams in specified geometries and a spatiotemporal pulse-shaper that controlled the relative optical phases and temporal delays among pulses in all the beams. The results reveal triexciton coherences (correlations of three excitons or six particles), whose existence was not obvious because the third exciton spin is unpaired, and the values of their coherence times and binding energies. Rephasing of biexcitons, triexcitons and unbound two-exciton coherences was demonstrated. We also determined that there are no significant unbound correlations of three excitons and no bound or unbound four-exciton (eight-particle) correlations. Thus, the limits, as well as the properties, of many-body correlations in this system were revealed. The measurement methods open a new window into high-order many-body interactions in materials and molecules, and the present results should guide ongoing work on first-principles calculations of electronic interactions in semiconductor nanostructures. PMID- 20740012 TI - Upper-ocean-to-atmosphere radiocarbon offsets imply fast deglacial carbon dioxide release. AB - Radiocarbon in the atmosphere is regulated largely by ocean circulation, which controls the sequestration of carbon dioxide (CO(2)) in the deep sea through atmosphere-ocean carbon exchange. During the last glaciation, lower atmospheric CO(2) levels were accompanied by increased atmospheric radiocarbon concentrations that have been attributed to greater storage of CO(2) in a poorly ventilated abyssal ocean. The end of the ice age was marked by a rapid increase in atmospheric CO(2) concentrations that coincided with reduced (14)C/(12)C ratios (Delta(14)C) in the atmosphere, suggesting the release of very 'old' ((14)C depleted) CO(2) from the deep ocean to the atmosphere. Here we present radiocarbon records of surface and intermediate-depth waters from two sediment cores in the southwest Pacific and Southern oceans. We find a steady 170 per mil decrease in Delta(14)C that precedes and roughly equals in magnitude the decrease in the atmospheric radiocarbon signal during the early stages of the glacial interglacial climatic transition. The atmospheric decrease in the radiocarbon signal coincides with regionally intensified upwelling and marine biological productivity, suggesting that CO(2) released by means of deep water upwelling in the Southern Ocean lost most of its original depleted-(14)C imprint as a result of exchange and isotopic equilibration with the atmosphere. Our data imply that the deglacial (14)C depletion previously identified in the eastern tropical North Pacific must have involved contributions from sources other than the previously suggested carbon release by way of a deep Southern Ocean pathway, and may reflect the expanded influence of the (14)C-depleted North Pacific carbon reservoir across this interval. Accordingly, shallow water masses advecting north across the South Pacific in the early deglaciation had little or no residual (14)C depleted signals owing to degassing of CO(2) and biological uptake in the Southern Ocean. PMID- 20740018 TI - Cellular imaging: Taking a long, hard look. PMID- 20740019 TI - Cellular imaging: A long-term live-cell commitment. PMID- 20740013 TI - IkappaBbeta acts to inhibit and activate gene expression during the inflammatory response. AB - The activation of pro-inflammatory gene programs by nuclear factor-kappaB (NF kappaB) is primarily regulated through cytoplasmic sequestration of NF-kappaB by the inhibitor of kappaB (IkappaB) family of proteins. IkappaBbeta, a major isoform of IkappaB, can sequester NF-kappaB in the cytoplasm, although its biological role remains unclear. Although cells lacking IkappaBbeta have been reported, in vivo studies have been limited and suggested redundancy between IkappaBalpha and IkappaBbeta. Like IkappaBalpha, IkappaBbeta is also inducibly degraded; however, upon stimulation by lipopolysaccharide (LPS), it is degraded slowly and re-synthesized as a hypophosphorylated form that can be detected in the nucleus. The crystal structure of IkappaBbeta bound to p65 suggested this complex might bind DNA. In vitro, hypophosphorylated IkappaBbeta can bind DNA with p65 and c-Rel, and the DNA-bound NF-kappaB:IkappaBbeta complexes are resistant to IkappaBalpha, suggesting hypophosphorylated, nuclear IkappaBbeta may prolong the expression of certain genes. Here we report that in vivo IkappaBbeta serves both to inhibit and facilitate the inflammatory response. IkappaBbeta degradation releases NF-kappaB dimers which upregulate pro-inflammatory target genes such as tumour necrosis factor-alpha (TNF-alpha). Surprisingly, absence of IkappaBbeta results in a dramatic reduction of TNF-alpha in response to LPS even though activation of NF-kappaB is normal. The inhibition of TNF-alpha messenger RNA (mRNA) expression correlates with the absence of nuclear, hypophosphorylated IkappaBbeta bound to p65:c-Rel heterodimers at a specific kappaB site on the TNF alpha promoter. Therefore IkappaBbeta acts through p65:c-Rel dimers to maintain prolonged expression of TNF-alpha. As a result, IkappaBbeta(-/-) mice are resistant to LPS-induced septic shock and collagen-induced arthritis. Blocking IkappaBbeta might be a promising new strategy for selectively inhibiting the chronic phase of TNF-alpha production during the inflammatory response. PMID- 20740020 TI - Cellular imaging: A software spot. PMID- 20740025 TI - Transmission dynamics of an emerging infectious disease in wildlife through host reproductive cycles. AB - Emerging infectious diseases are major threats to wildlife populations. To enhance our understanding of the dynamics of these diseases, we investigated how host reproductive behavior and seasonal temperature variation drive transmission of infections among wild hosts, using the model system of cyprinid herpesvirus 3 (CyHV-3) disease in common carp. Our main findings were as follows: (1) a seroprevalence survey showed that CyHV-3 infection occurred mostly in adult hosts, (2) a quantitative assay for CyHV-3 in a host population demonstrated that CyHV-3 was most abundant in the spring when host reproduction occurred and water temperature increased simultaneously and (3) an analysis of the dynamics of CyHV 3 in water revealed that CyHV-3 concentration increased markedly in breeding habitats during host group mating. These results indicate that breeding habitats can become hot spots for transmission of infectious diseases if hosts aggregate for mating and the activation of pathogens occurs during the host breeding season. PMID- 20740024 TI - In situ dynamics of O2, pH and cyanobacterial transcripts associated with CCM, photosynthesis and detoxification of ROS. AB - The relative abundance of transcripts encoding proteins involved in inorganic carbon concentrating mechanisms (CCM), detoxification of reactive oxygen species (ROS) and photosynthesis in the thermophilic cyanobacterium Synechococcus OS-B' was measured in hot spring microbial mats over two diel cycles, and was coupled with in situ determinations of incoming irradiance and microenvironmental dynamics of O(2) and pH. Fluctuations in pH and O(2) in the mats were largely driven by the diel cycle of solar irradiance, with a pH variation from ~7.0 to ~9.5, and O(2) levels ranging from anoxia to supersaturation during night and day, respectively. Levels of various transcripts from mat cyanobacteria revealed several patterns that correlated with incident irradiance, O(2) and pH within the mat matrix. Transcript abundances for most genes increased during the morning dark-light transition. Some transcripts remained at a near constant level throughout the light period, whereas others showed an additional increase in abundance as the mat underwent transition from low-to-high light (potentially reflecting changes in O(2) concentration and pH), followed by either a decreased abundance in the early afternoon, or a gradual decline during the early afternoon and into the evening. One specific transcipt, psbA1, was the lowest during mid day under high irradiance and increased when the light levels declined. We discuss these complex in situ transcriptional patterns with respect to environmental and endogenous cues that might impact and regulate transcription over the diel cycle. PMID- 20740026 TI - Unveiling an abundant core microbiota in the human adult colon by a phylogroup independent searching approach. AB - The potential presence of widespread and stable bacterial core phylogroups in the human colon has promoted considerable attention. Despite major efforts, no such phylogroups have yet been identified. Therefore, using a novel phylogroup- and tree-independent approach, we present a reanalysis of 1,114,722 V2 region and 71,550 near full-length 16S rRNA sequences from a total of 210 human beings, with widespread geographic origin, ethnic background and diet, in addition to a wide range of other mammals. We found two highly prevalent core phylogroups (cores 1 and 2), belonging to the clostridial family Lachnospiraceae. These core phylogroups showed a log-normal distribution among human individuals, while non core phylogroups showed more skewed distributions towards individuals with low levels compared with the log-normal distribution. Molecular clock analyses suggest that core 2 co-evolved with the radiation of vertebrates, while core 1 co evolved with the mammals. Taken together, the stability, prevalence and potential functionality support the fact that the identified core phylogroups are pivotal in maintaining gut homeostasis and health. PMID- 20740028 TI - Good blogosphere practices. A recent brouhaha over corporate-sponsored scientific blogs sharing the same platform as those that are editorially independent highlights the need for clearly disclosing any potential conflicts of interest in the blogosphere. PMID- 20740027 TI - The earthworm Aporrectodea caliginosa stimulates abundance and activity of phenoxyalkanoic acid herbicide degraders. AB - 2-Methyl-4-chlorophenoxyacetic acid (MCPA) is a widely used phenoxyalkanoic acid (PAA) herbicide. Earthworms represent the dominant macrofauna and enhance microbial activities in many soils. Thus, the effect of the model earthworm Aporrectodea caliginosa (Oligochaeta, Lumbricidae) on microbial MCPA degradation was assessed in soil columns with agricultural soil. MCPA degradation was quicker in soil with earthworms than without earthworms. Quantitative PCR was inhibition corrected per nucleic acid extract and indicated that copy numbers of tfdA-like and cadA genes (both encoding oxygenases initiating aerobic PAA degradation) in soil with earthworms were up to three and four times higher than without earthworms, respectively. tfdA-like and 16S rRNA gene transcript copy numbers in soil with earthworms were two and six times higher than without earthworms, respectively. Most probable numbers (MPNs) of MCPA degraders approximated 4 * 10(5) g(dw)(-1) in soil before incubation and in soil treated without earthworms, whereas MPNs of earthworm-treated soils were approximately 150 * higher. The aerobic capacity of soil to degrade MCPA was higher in earthworm-treated soils than in earthworm-untreated soils. Burrow walls and 0-5 cm depth bulk soil displayed higher capacities to degrade MCPA than did soil from 5-10 cm depth bulk soil, expression of tfdA-like genes in burrow walls was five times higher than in bulk soil and MCPA degraders were abundant in burrow walls (MPNs of 5 * 10(7) g(dw)(-1)). The collective data indicate that earthworms stimulate abundance and activity of MCPA degraders endogenous to soil by their burrowing activities and might thus be advantageous for enhancing PAA degradation in soil. PMID- 20740030 TI - MeCP2 and drug addiction. AB - Two studies in this issue show that the protein MeCP2, which is implicated in Rett syndrome, also critically regulates behavioral responses to psychostimulants. Although the two studies highlight different mechanisms of MeCP2 in regulating these behaviors, both underscore the importance of epigenetic mechanisms in establishing drug addiction. PMID- 20740031 TI - Dnmt3a: addiction's molecular forget-me-not? AB - A new study examines the contribution of DNA methylation to long-term behavioral and morphological changes produced by cocaine exposure or chronic social defeat stress. PMID- 20740032 TI - Handling accumulated internal Cl- at inhibitory synapses. AB - A study in this issue finds that under conditions of intense activity at specific inhibitory synapses, the voltage gated Cl- channel CIC-2 is vital for allowing efflux of accumulated internal Cl-. PMID- 20740033 TI - Zooming in on mouse vision. AB - An examination of the micro-organization of visual cortex using two-photon calcium imaging provides a new level of insight into retinotopic maps, finding that retinotopy is scrambled on fine scales in mouse primary visual cortex. PMID- 20740034 TI - Building the preBotzinger complex. PMID- 20740035 TI - Part 1: The overall contribution. PMID- 20740036 TI - Part 2: The contributions of individual departments. PMID- 20740037 TI - Self-evaluation and self-audit in general practice. PMID- 20740039 TI - The practice activity analysis method. PMID- 20740040 TI - Experience and lessons from practice activity analysis. PMID- 20740042 TI - Discussion topics for practice audit. PMID- 20740041 TI - Results. PMID- 20740043 TI - Conclusions. PMID- 20740044 TI - Conjunctival Inflammatory Nodule in a Patient with Pityriasis Lichenoides et Varioliformis Acuta. AB - AIM: To report a case of a patient with pityriasis lichenoides et varioliformis acuta (PLEVA) who developed a conjunctival inflammatory nodule. CASE REPORT: a 13 year-old boy with a diffuse papulovesicular rash diagnosed as PLEVA presented to our clinic complaining of irritation in his right eye. Slitlamp examination revealed a conjunctival inflammatory nodule. His symptoms resolved under topical steroid treatment. DISCUSSION: Pityriasis lichenoides (PL) is a rare condition, diagnosed by a combination of a typical clinical presentation and histopathology. Mucous membrane involvement has been described in severe cases. Ocular involvement in PL has seldom been reported. We suggest that conjunctival inflammatory nodules may be part of the clinical spectrum of this condition and should be looked for and treated in these patients. PMID- 20740045 TI - Knowledge, attitudes, cultural, social and spiritual beliefs on healthseeking behaviors of Gambian adults with HIV/AIDS. AB - HIV/AIDS continues to grow exponentially in sub-Saharan Africa. Early HIV/AIDS care is essential for early interventions to increase quality of life and reduce mortality. The objectives of the study were: (1) to determine the relationship among attitudes, spiritual beliefs, cultural beliefs, social beliefs and knowledge on health-seeking behaviors (HSB) of Gambian adults living with HIV/AIDS; and (2) to provide preliminary data on psychometric characteristics of the newly developed HIV/AIDS Knowledge, Attitudes and Beliefs Patient Questionnaire. The descriptive design included 93 adults aged 21 to 65 years. Correlation and hierarchical regression analyses were used. Bivariate analyses demonstrated significant relationships between all five variables and HSB at p 50 mmHg) was observed more frequently in group Y (40%) than in group O (0%; P < 0.05). The difference between the E(T)CO(2) and PaCO(2) was 10.4 +/- 8.9 mmHg in group Y and 4.6 +/- 3.9 mmHg in group O (P < 0.05). Hypercarbia and acidosis occurred more frequently in patients with CO(2) insufflation than those without insufflation in group Y. CONCLUSIONS: Although the anesthesia for VATS in pediatric patients was successfully accomplished, the infants and younger children presented with more intra operative problems when compared with older children. The anesthetic management for VATS in infants and younger children requires careful and vigilant monitoring. PMID- 20740215 TI - Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta. AB - BACKGROUND: Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in the endothelium. We tested the antioxidant effect of lidocaine and procaine on ROS-induced endothelial damage in the rabbit aorta. METHODS: Aortic rings isolated from rabbits were suspended in an organ bath filled with Krebs Henseleit (K-H) solution bubbled with 5% CO(2) and 95% O(2) at 37.5. After precontraction with phenylephrine (PE, 10(-6) M), changes in tension were recorded following a cumulative administration of acetylcholine (ACh 3 x 10(-8) to 10(-6) M). Differences were measured as percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS as generated by electrolysis of the K-H solution. The aortic rings were pretreated with lidocaine or procaine (10(-5) M to 3 x 10(-3) M) to compare their effects, as well as ROS scavengers, catalase, mannitol, sodium salicylate, and deferoxamine, and a catalase inhibitor, 3-amino-1,2,4-triazole (3AT). RESULTS: Lidocaine and procaine dose dependently maintained endothelium-dependent relaxation induced by ACh despite ROS activity (P < 0.05 vs control value). The 3AT pretreated procaine (3 x 10(-3) M) group decreased more significantly than the un-pretreated procaine group (P < 0.05). CONCLUSIONS: These findings suggest that lidocaine and procaine dose dependently preserve endothelium-dependent vasorelaxation against ROS attack, potentially via hydrogen peroxide scavenging. PMID- 20740216 TI - Spreading pattern of contrast medium in the high thoracic epidural space in rabbits: the effect of neck flexion and extension. AB - BACKGROUND: Neck flexion has been shown to increase cranial spread of contrast agent when a small fixed volume was injected into the high thoracic epidural space. The purpose of this study was to evaluate the effect of volume of contrast medium on its distribution through the high thoracic epidural space during neck extension and flexion using the rabbit model. METHODS: An epidural catheter was introduced into the epidural space of New Zealand white rabbits with the tip located at the T3-4 intervertebral level. The neck was extended or flexed (n = 8 for each group), and the contrast medium was injected with the volume increasing by increments of 0.1 ml/kg, up to 0.3 ml/kg. The spread of contrast medium was determined by counting the number of vertebral body units using lateral epidurographic images. RESULTS: In both groups, the total spread of contrast medium was similar, increasing continuously with injected volume. The cranial spread was greater in the flexion group than the extension group. However, the caudal spread was greater in the extension than in the flexion group. In the extension group, the contrast medium spread caudally about twice as far as it spread cranially, but there was no statistically significant difference between cranial and caudal spread in the flexion group. CONCLUSIONS: In the high thoracic epidural space of rabbit, the contrast medium of varying doses showed limited cranial spread. The flexion of the neck increased cranial spread and extension of the neck increased caudal spread. PMID- 20740217 TI - Severe bradycardia during suspension laryngoscopy performed after tracheal intubation using a direct laryngoscope with a curved blade -A case report-. AB - There are a few reports about bradycardia or asystole caused by direct laryngoscopy. However, we encountered severe bradycardia in response to suspension laryngoscopy for laryngeal polypectomy after safely completing tracheal intubation using a direct laryngoscope with a curved blade. The tip of the curved blade of the direct laryngoscope is positioned at the vallecula (between the base of the tongue and the pharyngeal surface of the epiglottis) during tracheal intubation, while the blade tip of the suspension laryngoscope lifts the laryngeal surface of the epiglottis or supraglottic area during surgery. Therefore, suspension laryngoscopy can be said more vagotonic than curved-blade direct laryngoscopy. Because of the possibility of bradycardia induced by suspension laryngoscopy, clinicians must be careful about severe bradycardia even after safely completing intubation using direct laryngoscopy. PMID- 20740218 TI - Spinal epidural hematoma after epidural anesthesia in a patient receiving enoxaparin -A case report-. AB - Spinal epidural hematoma is a rare but serious neurological complication of neuraxial anesthesia. Enoxaparin sodium is a low molecular weight heparin (LMWH) for use in preventing deep venous thrombosis in patients undergoing total hip arthroplasty and total knee arthroplasty. Hemorrhage is an uncommon but documented adverse reaction when using LMWH. We report a case of epidural hematoma after lumbar epidural anesthesia in a patient who administered enoxaparin in perioperative period. PMID- 20740219 TI - Cardiac arrest induced by tension pneumothorax during ventilating bronchoscopy -A case report-. AB - Tension pneumothorax during ventilating bronchoscopy for foreign body removal is a rare but life-threatening complication. The authors present a case of cardiac arrest caused by tension pneumothorax in a 9-month-old girl who underwent ventilating bronchoscopy for foreign body (peanut) removal. Tension pneumothorax was due to tracheobronchial lacerations caused by a bronchoscope. The patient was successfully resuscitated by cardiopulmonary resuscitation and chest tube insertion. The airway injury was effectively repaired by thoracotomy under extracorporeal membrane oxygenation. PMID- 20740220 TI - Resolution of peripheral artery catheter-induced ischemic injury in infants -Two case reports-. AB - The occurrence of catheter-induced vasospasm of small caliber arteries is a well known complication of arterial catheterization in neonates. However, there is rare publication about these complications in infants. We report infants with peripheral ischemia caused by arterial catheterization of the femoral artery. PMID- 20740221 TI - An anesthetic experience with cesarean section in a patient with vasovagal syncope -A case report-. AB - Epidural anesthesia was performed for a cesarean section in a patient with vasovagal syncope. A 26-year-old woman at 41 weeks of gestation and with a known history of vasovagal syncope was scheduled to undergo an emergency cesarean section. She received epidural anesthesia for the cesarean delivery and showed signs and symptoms of vasovagal syncope, which were treated successfully with fluids and the administration of a vasoconstrictor. This case highlights the need for anesthesiologists to understand vasovagal syncope precisely because severe hypotension in a patient under anesthesia for a cesarean section is dangerous to both the mother and baby. PMID- 20740222 TI - Novel synthesis of bismuth tungstate hollow nanospheres in water-ethanol mixed solvent. AB - Bi(2)WO(6) hollow nanospheres were prepared in a sacrificial templates approach by converting the reaction medium from aqueous solution to a mixed solvent of water and ethanol. PMID- 20740223 TI - Synthetically accessible, tunable, low-molecular-weight oligopeptide organogelators. AB - We report a synthetically simple approach to effective and tunable low molecular weight gelators based on amine-initiated oligomerisation of an amino acid N carboxyanhydride. PMID- 20740224 TI - Molten matrix sputtering synthesis of water-soluble luminescent Au nanoparticles with a large Stokes shift. AB - Water-soluble luminescent AuNPs of 1.3 +/- 0.3 nm in diameter with a large Stokes shift were facilely synthesized by a new molten matrix sputtering (MMS) method. PMID- 20740225 TI - Ionic nature of Ge(II)-centered dications: a germanium K-edge X-ray absorption near edge structures study. AB - Measurement of the ionic nature of [Ge(cryptand[2.2.2])](2+) by XANES has provided direct experimental evidence that the germanium center is best described as a nearly-naked dication encased within an electron rich cryptand cage. PMID- 20740226 TI - A comparison of five bioconjugatable ferrocenes for labeling of biomolecules. AB - Five electroactive ferrocene tags for labelling of biomolecules are contrasted with regard to conjugation reactivity with amine and thiol moieties, stability to loss of electrochemical activity, and impact of molecular structure on the redox potential of the free and DNA-conjugated forms. PMID- 20740227 TI - Porous protein frameworks with unsaturated metal centers in sterically encumbered coordination sites. AB - Described is an engineered metal-binding protein, MBPPhen2, which forms porous crystalline frameworks that feature coordinatively unsaturated Zn- and Ni centers. PMID- 20740229 TI - Inorganic nanocrystals self ordered in 2D superlattices: how versatile are the physical and chemical properties? AB - Here we point out some parameters, such as substrate roughness, deposition modes, alkyl chain length of the coating agents and solvent used to disperse the nanocrystals, that play a role in the control of nanocrystal ordering in 2D superlattices. The interparticle distances do not follow the rules which imply that they are controlled by the length of the alkyl chain used as coating agent. The solvent in which the nanocrystals are dispersed is a key parameter. From DDA simulations it is observed that collective optical properties of 5 nm noble nanoparticles self-organized in a 2D hexagonal planar array markedly differ with the nanomaterial used (Au and Ag). There is no splitting of the surface plasmon resonance observed for Au nanoparticles, whereas for Ag nanoparticles, with a similar geometry, a splitting is observed when decreasing the interparticle spacing d/(2R) to around one nanoparticle radius due to the strengthening of the dipolar interactions between the nanoparticles. Here it is shown by using AMB-1 magnetostatic bacteria that the change in the hysteresis loop when the nanoparticles are aligned is preferentially due to induced dipolar interactions rather than to the orientation of the easy axes. Intrinsic collective chemical properties due to the nanocrystals ordering are presented. PMID- 20740228 TI - A fluopol-ABPP HTS assay to identify PAD inhibitors. AB - Protein Arginine Deiminase (PAD) activity is dysregulated in numerous diseases, e.g., Rheumatoid Arthritis. Herein we describe the development of a fluorescence polarization-Activity Based Protein Profiling (fluopol-ABPP) based high throughput screening assay that can be used to identify PAD-selective inhibitors. Using this assay, streptonigrin was identified as a potent, selective, and irreversible PAD4 inactivator. PMID- 20740235 TI - Anion-tuned supramolecular gels: a natural evolution from urea supramolecular chemistry. AB - This tutorial review looks at the formation of low molecular weight gels from molecular principles using the well-explored supramolecular chemistry of ureas as an example. Synthesising lessons learned from classical urea inclusion chemistry, ureas in crystal engineering, ureas in self-assembly, urea functional groups in anion binding and sensing, and ureas as organocatalysts lead to the development and understanding of a new class of anion-tunable, urea-based soft materials. This review concludes with a look at emerging application areas for tunable gel phase materials as controlled crystal growth media, both in templating metallic nanoparticles and in the growth and isolation of high quality crystals of molecular organic compounds, including polymorphic pharmaceuticals. PMID- 20740236 TI - Optically addressable single-use microfluidic valves by laser printer lithography. AB - We report the design, fabrication, and characterization of practical microfluidic valves fabricated using laser printer lithography. These optofluidic valves are opened by directing optical energy from a solid-state laser, with similar power characteristics to those used in CD/DVD drives, to a spot of printed toner where localized heating melts an orifice in the polymer layer in as little as 500 ms, connecting previously isolated fluidic components or compartments. Valve functionality, response time, and laser input energy dependence of orifice size are reported for cyclo-olefin polymer (COP) and polyethylene terephthalate (PET) films. Implementation of these optofluidic valves is demonstrated on pressure driven and centrifugal microfluidic platforms. In addition, these "one-shot" valves comprise a continuous polymer film that hermetically isolates on-chip fluid volumes within fluidic devices using low-vapor-permeability materials; we confirmed this for a period of one month. The fabrication and integration of optofluidic valves are compatible with a range of polymer microfabrication technologies and should facilitate the development of fully integrated, reconfigurable, and automated lab-on-a-chip systems, particularly when reagents must be stored on chip for extended periods, e.g. for medical diagnostic devices, lab-on-a-chip synthetic systems, or hazardous biochemical analysis platforms. PMID- 20740237 TI - Synthesis of eta(2)-cyclooctene iridium and rhodium complexes supported by a novel P,N-chelate ligand and their reactivity toward hydrosilanes: facile Cl migration from metal to silicon via silylene complex intermediates and formation of a base-stabilised silylene complex. AB - eta2-Cyclooctene iridium and rhodium complexes bearing a P,N-chelate ligand C6H3Me-3-PCy2-4-NMe2 (abbreviated as PcyN), (PcyN-P,N)MCl(eta2-coe) (1: M = Ir, 2: M = Rh), were synthesised and reactions toward several sterically hindered hydrosilanes were investigated to clarify their reactivity. The reaction of 1 with H2SiMes2 (Mes = mesityl = 2,4,6-trimethylphenyl) proceeded at 40 degrees C to give a di-iridium complex bridged by a chlorosilylene ligand (PcyN P,N)2Ir2H2(MU-Cl)(MU-H)(MU-SiClMes) (5). The reaction of 1 with HSiMe2SiMes2Me occurred at room temperature to afford HSiMesMe2 and a silyl complex 6 formed by metallation of an ortho-methyl group of Mes, which slowly dimerised to give a dinuclear complex containing a chlorosilyl ligand (PcyN-P,N)2Ir2H(MU-Cl)(MU-H)[MU SiMeCl(C6H3-2,4-Me2-6-CH)-Si,C,C] (7). The formation of complexes 5, 6 and 7 suggests that facile migration of Cl from Ir to Si occurs probably via silylene iridium intermediates. Treatment of 1 with HSiMe2SiMe2OMe at room temperature yielded a methoxy-bridged bis(silylene) complex (PcyN P,N)IrHCl[SiMe2..O(Me)..SiMe2-Si,Si] (8) quantitatively, whose X-ray crystal structure was determined as the first iridium complex of this type. The reactions of 1 and 2 with a bulky trihydrosilane H3SiC(SiMe3)3 underwent an intramolecular gamma-Si-Me activation to afford (PcyN-P,N)MHn[SiMe2C(SiMe3)2SiClMe-Si,Si] (9: M = Ir, n = 3; 10: M = Rh, n = 1). Complex 1 even reacted with an extremely sterically hindered terphenylhydrosilane H3SiDmp (Dmp = 2,6-dimesitylphenyl) in the presence of PMe3 to give a chlorosilyl complex (PcyN-P,N)IrH2(PMe3)(SiHClDmp) (11) without intramolecular bond activation. Complex 1 also reacted with H3SiTrip (Trip = 2,4,6-triisopropylphenyl) in the presence of excess 4 (dimethylamino)pyridine (DMAP) at room temperature to give a chlorido(dihydrosilyl) complex (PcyN-P,N)IrHCl(DMAP)(SiH2Trip) (12) instantaneously. Treatment of complex 12 with LiB(C6F5)4.2.5Et2O provided a cationic DMAP-stabilised silylene complex [(PcyN-P,N))IrH2(DMAP)(SiHTrip <- DMAP)][B(C6F5)4] (13). PMID- 20740238 TI - Development of next-generation photolabile copper cages with improved copper binding properties. AB - Seven new nitrogen-donor ligands that contain a photoactive nitrophenyl group within the ligand backbone have been prepared and evaluated for their binding affinity for copper(ii) and zinc(ii). Among this series, the ligand 3Gcage (pyridine-2-carboxylic acid {1-(2-nitro-phenyl)-3-[(pyridin-2-ylmethyl)-amino] propyl}-amide) has the best affinity for copper(ii), with an apparent dissociation constant at pH 7.4 of 0.18 fM. Exposure of buffered aqueous solutions of 3Gcage or Cu(ii)-bound 3Gcage to UV light induces bond cleavage in the ligand backbone, which reduces the denticity of the ligands. The quantum yields of photolysis for 3Gcage in the absence and presence of Cu(ii) are 0.66 and 0.43, respectively. Prior to photolysis, the 3Gcage ligand inhibits copper from generating hydroxyl radicals in the presence of hydrogen peroxide and ascorbic acid; however, hydroxyl radical formation increases by more than 300% following light activation, showing that the reactivity of the copper center can be triggered by light. PMID- 20740239 TI - Development of a multi-layer microfluidic array chip to culture and replate uniform-sized embryoid bodies without manual cell retrieval. AB - We have developed a multi-layer, microfluidic array platform containing concave microwells and flat cell culture chambers to culture embryonic stem (ES) cells and regulate uniform-sized embryoid body (EB) formation. The main advantage of this platform was that EBs cultured within the concave microwells of a bottom layer were automatically replated into flat cell culture chambers of a top layer, following inversion of the multi-layer microfluidic array platform. This allowed EB formation and EB replating to be controlled simultaneously inside a single microfluidic device without pipette-based manual cell retrieval, a drawback of previous EB culture methods. PMID- 20740240 TI - Trifluoromethylated cyclic-ADP-ribose mimic: synthesis of 8-trifluoromethyl-N(1) [(5''-O-phosphorylethoxy)methyl]-5'-O-phosphorylinosine-5',5''-cyclic pyrophosphate (8-CF(3)-cIDPRE) and its calcium release activity in T cells. AB - A convenient trifluoromethylation method was firstly applied to the synthesis of 8- CF(3)-purine nucleosides. On the basis of this method, new protection and deprotection strategies were developed for the successful synthesis of the trifluoromethylated cyclic-ADP-ribose mimic, 8-CF(3)-cIDPRE 1. Using intact, fura 2-loaded Jurkat T cells compound 1 and 2',3'-O-isopropylidene 8-CF(3)-cIDPRE 14 were characterized as membrane-permeant cADPR agonists. Contrary to the 8 substituted cADPR analogues that mainly act as antagonists of cADPR in cells, 8 substituted cIDPRE derivatives were shown to be Ca(2+) mobilizing agonists. Here we report that even compound 1, the 8-substituted cIDPRE with the strong electron withdrawing CF(3) group, behaves as an agonist in T cells. Interestingly, also the partially protected 2',3'-O-isopropylidene 8-CF(3)-cIDPRE activated Ca(2+) signaling indicating only a minor role for the hydroxyl groups of the southern ribose of cADPR for its biological activity. To our knowledge 8-CF(3)-cIDPRE 1 is the first reported fluoro substituted cADPR mimic and 8-CF(3)-cIDPRE 1 and compound 14 are promising molecular probes for elucidating the mode of action of cADPR. PMID- 20740241 TI - AAZTA-based bifunctional chelating agents for the synthesis of multimeric/dendrimeric MRI contrast agents. AB - Monomeric and dimeric bifunctional chelates based on the AAZTA (6-amino-6 methylperhydro-1,4-diazepinetetraacetic acid) platform bearing arylamino and isothiocyanate groups for conjugation to biomolecules were synthesised. Both systems were used for the preparation of high relaxivity dendrimeric (PAMAM G1) and multimeric octa-Gd(III) complexes. These systems show enhanced relaxometric properties attributed to the presence of two coordinated, fast exchanging, water molecules (q = 2) on each metal ion and to a rather rigid and compact molecular structure. PMID- 20740242 TI - Direct synthesis of alpha-bromoketones from alkylarenes by aerobic visible light photooxidation. AB - The direct synthesis of alpha-bromoketones from alkylarenes by aerobic photooxidation with hydrobromic acid is reported. The key success for this direct oxidative reaction is due to control of bromination with acetic acid and ethanol, which are generated in situ by solvolysis of ethyl acetate in the course of the reaction. PMID- 20740243 TI - A simple method for the preparation of propargylamines using molecular sieve modified with copper(II). AB - A new, heterogeneous, 4 A molecular sieve-supported copper(ii) catalyst was developed and was used successfully in the A(3) coupling of alkynes, aldehydes and amines under simple reaction conditions. PMID- 20740244 TI - Synthesis and application of 4-[(18)F]fluorobenzylamine: A versatile building block for the preparation of PET radiotracers. AB - A novel synthesis of 4-[(18)F]fluorobenzylamine ([(18)F]FBA) by means of transition metal-assisted sodium borohydride reduction of 4 [(18)F]fluorobenzonitrile ([(18)F]FBN) is described. This approach could successfully be extended to borohydride exchange resin (BER) enabling a viable option for use in automated syntheses. [(18)F]FBA was used for the synthesis of 4 [(18)F]fluorobenzylamine-based thiol group-reactive prosthetic groups 4 [(18)F]fluorobenzyl-2-bromoacetamide ([(18)F]FBBA) and 4 [(18)F]fluorobenzylamidopropionyl maleimide ([(18)F]FBAPM). [(18)F]FBBA and [(18)F]FBAPM were obtained in radiochemical yields of 75% and 55%, respectively. Feasibility of using [(18)F]FBAPM as novel prosthetic group for peptide and protein labelling was demonstrated with cysteine-containing tripeptide glutathione (GSH). [(18)F]FBBA was used for labelling of a fully phosphorothioated 20mer oligodesoxynucleotide (ODN). PMID- 20740245 TI - Synthesis of 1,2-annulated and 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5 ones (cycl[3.3.2]azin-5-ones) via [3+2] cycloadditions of 1-oxoquinolizinium ylides with cyclic alkenes. AB - 1,2-Annulated pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) 6a-6k, 8a-8b and 9 have been synthesized by one pot tandem reactions of 2-acetyl-N phenacylpyridinium bromides (1a-1d) with electron-deficient cyclic alkenes (N alkyl(aryl)maleimides, benzoquinones and naphthoquinone) in the presence of sodium carbonate as a base and tetrakispyridinecobalt(II) dichromate (TPCD) as an oxidant. These products are formed by 1.3-dipolar cycloaddition of the 1 oxoquinolizinium ylides generated in situ from 1a-1d with the alkene followed by dehydrogenation of the primary cycloadduct under the action of TPCD. Similar reactions of the ylides generated in situ from 1a-1f with maleic anhydride gave the 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones 7a-7f via oxidative bisdecarboxylation and dehydrogenation of the primary cycloadducts under the action of TPCD. PMID- 20740246 TI - Diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysenes: solution-phase synthesis and the bowl-to-bowl inversion barrier. AB - Diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysenes 2 were straightforwardly prepared in around 20% yield from 9,10-diarylphenanthrenes 3 by palladium catalyzed intramolecular arylations. The bowl-to-bowl inversion barrier for buckybowl 2-iPr is predicted to be approximately 7 kcal mol(-1) based on density functional theory calculations and this value is consistent with the results of a variable-temperature (1)H-NMR study. PMID- 20740247 TI - Highly conducting two-dimensional copper(I) 4-hydroxythiophenolate network. AB - An unprecedented 2-D Cu-S network is constructed by self-assembly coordination between Cu(I) and 4-hydroxythiophenol and its structure was determined by using powder X-ray diffraction data. The self-assembled coordination network displays ionic behavior with a bulk electrical conductivity value of 120 S cm(-1). PMID- 20740248 TI - Quantitative synthesis and full characterization of the first isolated and stable pincer palladium(IV) complexes. Quantitative and regioselective synthesis of the C-X (X = Cl, Br) reductive elimination products. AB - The pincer complexes [Pd(O(1),N(1),C(1)-L)X], where X = Cl, Br and L is the monoanionic ligand resulting from deprotonation of the acetyl methyl group of the monoketal of 2,6-diacetylpyridine (dap), react with excess of Cl(2) or Br(2) affording, quantitatively, the Pd(IV) complexes [Pd(O(1),N(1),C(1)-L)X(3)], which have been characterized by X-ray diffraction, and their decomposition that quantitatively affords the reductive elimination products L-X has been studied. PMID- 20740249 TI - Understanding the mechanism of stereoselective synthesis of cyclopentenes via N heterocyclic carbene catalyzed reactions of enals with enones. AB - The N-heterocyclic carbene (NHC) catalyzed addition of enals to enones to yield trans-cyclopentenes has been investigated using DFT methods at B3LYP/6-31G** computational level. This NHC catalyzed reaction comprises several steps. The first one is the formation of a Breslow intermediate, which nucleophilically attacks to the conjugated position of the enone to yield an enol-enolate. This second step is responsible for the trans relationship at the final cyclopentene. An intramolecular aldolic condensation allows for the formation of the alkoxy cyclopentane intermediate, that by intramolecular nucleophilic attack on the carbonyl group yields a bicyclic ether. The extrusion of the NHC catalyst affords a bicyclic lactone, yielding by CO(2) elimination, the final trans-cyclopentene. PMID- 20740250 TI - Regiospecific synthesis of functionalised 1,3-diarylisobenzofurans via palladium- and rhodium-catalysed reaction of boronic acids with o-acylbenzaldehydes under thermal or microwave activation. AB - Variously substituted 1,3-diarylisobenzofurans have been regiospecifically prepared via palladium- and rhodium-catalysed reaction of functionalised boronic acids onto o-acylbenzaldehydes. Rhodium catalysis has furthermore been improved using microwave activation. Thus, isobenzofurans containing aryl groups substituted by halogens, unprotected amine, alcohol and even aldehyde groups, have been obtained directly in good to satisfactory yields. Divergent results have been observed when palladium-, rhodium- and MW-activated rhodium-catalysis was applied to the reaction of phenylboronic acid with an iodinated o acylbenzaldehyde, leading principally to Suzuki coupling product and/or to iodinated isobenzofuran. PMID- 20740251 TI - Visible light induced wetting of nanostructured N-F co-doped titania films. AB - Nitrogen and fluorine co-doped TiO(2) films have been prepared by dip coating of a modified titania sol-gel based on a nitrogen precursor and a nonionic fluorosurfactant as pore template and fluorine source. The modified NF-TiO(2) films absorb in the visible spectral range, between 400-510 nm and undergo reversible hydrophilic conversion under visible light to a final contact angle of 8 degrees , in contrast to the UV limited optical response of their undoped anatase TiO(2) analogues. The phenomenon takes place at a rate slower than the corresponding one observed for the UV stimulated superhydrophilic effect. The wetting response of the N-F doped TiO(2) films correlates well with the variation of their optical properties and surface morphological characteristics and most importantly with their photocatalytic activity, rendering these materials very promising for self-cleaning applications under visible light. PMID- 20740252 TI - Evolutionary analysis reveals low coverage as the major challenge for protein interaction network alignment. AB - Local alignments of protein interaction networks have found little conservation among several species. While this could be a consequence of the incompleteness of interaction data-sets and presence of error, an intriguing prospect is that the process of network evolution is sufficient to erase any evidence of conservation. Here, we aim to test this hypothesis using models of network evolution and also investigate the role of error in the results of network alignment. We devised a distance metric based on summary statistics to assess the fit between experimental and simulated network alignments. Our results indicate that network evolution alone is unlikely to account for the poor quality alignments given by real data. Alignments of simulated networks undergoing evolution are considerably (4 to 5 times) larger than real alignments. We compare several error models in their ability to explain this discrepancy. Our estimates of false negative rates vary from 20 to 60% dependent on whether incomplete proteome sampling is taken into account or not. We also find that false positives appear to affect network alignments little compared to false negatives indicating that incompleteness, not spurious links, is the major challenge for interactome-level comparisons. PMID- 20740253 TI - Osteosarcoma masked by osteomyelitis and cellulitis in a dog. AB - CASE DESCRIPTION: This clinical report describes a 10-year-old female spayed German Shepherd dog cross that was presented with cellulitis of the left proximal forelimb and osteomyelitis of the left proximal humerus, and was ultimately diagnosed with metastatic osteosarcoma. CLINICAL FINDINGS: The diagnosis of cellulitis and osteomyelitis was made using ultrasound, radiography, cytology and histopathology, all of which were consistent with cellulitis and osteomyelitis. Cultures were negative. TREATMENT: The patient was treated using two surgical debridements and long-term broad-spectrum antibiotic drugs. Despite surgical and medical treatment, the dog's condition progressed. A lytic lesion of the left proximal humerus was identified radiographically. OUTCOME: One hundred forty-one days after initial presentation, the dog was presented with a non-weight bearing lameness of the left forelimb. An amputation was scheduled. Preoperative computed tomography scan of the thorax revealed gross metastatic disease to the lungs. The patient was euthanatized and a post-mortem examination revealed osteosarcoma of the left proximal humerus with widespread metastasis. CLINICAL RELEVANCE: To our knowledge, this case is the first reported case of osteomyelitis masking osteosarcoma in a dog. It serves as a reminder to maintain a high index of suspicion when managing cases with a signalment, history and radiographic lesion that are consistent with a primary bone tumour. PMID- 20740254 TI - Cartilage thickness and split-line pattern at the canine humeral trochlea. AB - OBJECTIVE: To characterise the humeral trochlea in middle to large breed dogs in respect to split-line pattern and cartilage thickness. METHODS: In 15 paired cadaveric elbow joints of mature dogs (>20 kg body weight) collagen network orientation of the hyaline cartilage of the humeral trochlea was visualised using a traditional split-line technique in which a dissecting needle dipped in India ink was inserted into the cartilage (n = 10). Cartilage thickness was measured radiographically on osteochondral plugs harvested at four representative locations within the joint surface of the humeral trochlea (n = 15). RESULTS: The joint surface of the humeral trochlea showed a distinct pattern of centripetally oriented split-lines with less pronounced or even absent split-lines caudo- proximally towards the olecranon fossa. Median cartilage thickness at the canine humeral trochlea was 0.51 mm (interquartile range: 0.42 - 0.61 mm). Centrally, at the region where osteochondrosis lesions commonly occur in middle to large breed dogs, the median cartilage thickness was 0.55 mm (interquartile range: 0.48 - 0.62 mm). CLINICAL SIGNIFICANCE: When focusing on anatomical joint resurfacing while performing osteochondral transplantation at the canine humeral trochlea, transplants should be implanted such that their split-lines are oriented centripetally. Hyaline cartilage thickness of transferred grafts should be in the range of half a millimetre to optimally match the situation at the canine humeral trochlea. PMID- 20740255 TI - Computer-assisted surgical correction of an antebrachial deformity in a dog. AB - OBJECTIVE: To report the use of three dimensional (3D) computed tomographic (CT) imaging, computer simulation and rapid prototype modelling to aid surgical correction of a complex antebrachial deformity in a dog. METHODS: A six-year-old, 13 kg spayed female Chihuahua crossbreed dog was presented for worsening forelimb gait and exercise intolerance. Both forelimbs had gross angular limb deformity with carpal hyper-flexion, valgus and radial procurvatum. Surgical planning from radiographs was problematic therefore CT data were used to generate 3D reconstructions of the antebrachium. Using imaging software we then quantified the nature of the deformity using a previously unreported method based on the centre of rotation of angulation as a 3D model. Computer simulated closing of the virtual wedge osteotomy was then performed as proof of concept. A stereolithographic model complete with osteotomy axes, was then created in plastic using a rapid prototyping machine. Oscillating saw guides were fabricated in polymethylmethacrylate and cold sterilised. A closing wedge osteotomy with de rotation was performed and stabilised with a pre-contoured dynamic compression plate. At the three- and six-month follow-up examinations there was improved weight-bearing and cosmetic appearance. CONCLUSIONS: Computer assistance was valuable for locating and quantifying this antebrachial deformity and conceptualising the corrective surgery. The results of our study suggest that rapid prototyping can be used to create models and saw guides to simplify one stage corrective osteotomies and more accurately treat angular limb deformity. PMID- 20740256 TI - Demineralised bone matrix in veterinary orthopaedics: a review. AB - Demineralised bone matrix (DBM) is commonly used in human orthopaedics as an allograft prepared from cortical bone. As such, there is a background of literature on the basic science, experimental animal studies and clinical human use of DBM. Because canine DBM is now increasingly available and used in veterinary orthopaedics, this review aims to update the veterinary orthopaedic specialist with the properties and activities of this bone allograft product. PMID- 20740257 TI - Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part II: two year clinical results. AB - OBJECTIVES: To determine the clinical effects of juvenile pubic symphysiodesis (JPS) treatment in hip dysplasia-prone puppies with comparison to similar untreated control puppies. DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies, of which six were part of the control group, with a positive Ortolani or hip distraction index (DI)>=0.40. PROCEDURES: The following eight clinical tests were evaluated preoperatively, and at one and two years postoperatively: Ortolani, hip reduction angle (HRA), gait evaluation, osteoarthritis, hip pain, and three Norberg angles (angle-extended mode [N-OFA], angle-compression mode [N-COM], and angle-distracted mode [N-DIS]). Juvenile pubic fusion (JPS) was performed by unipolar electro-cautery at 12 to 24 weeks of age; the control puppies received a sham operation. RESULTS: For the JPS puppies, the mean osteoarthritis level did not significantly increase (11%). There was a 74% reversal of preoperative positive Ortolani signs. Hip reduction angle, DI and N-DIS also improved significantly. Only N-DIS fully detected Norberg angle laxity. Within the control group, osteoarthritis increased significantly (55%) with no improvement in Ortolani incidence, N-OFA or N-COM angles. A decrease in HRA and DI was associated with increased osteoarthritis levels. Signs of hip pain increased by 33%, which was not significant. Dogs with initial severe hip laxity (DI>=0.70) experienced progressive osteoarthritis. CONCLUSIONS AND CLINICAL RELEVANCE: In JPS dogs with preoperative mild to moderate hip laxity (DI = 0.40 0.69), insignificant osteoarthritis occurred at two years. Juvenile pubic symphysiodesis surgery also improved other clinical criteria (Ortolani, HRA, hip pain, N-DIS). Osteoarthritis was generally not prevented by JPS in dogs with initial severely lax hips (DI>=0.70). Juvenile pubic symphysiodesis surgery at 12 to 24 weeks of age was an effective and safe pre-emptive bilateral treatment for mild to moderate hip dysplasia. PMID- 20740258 TI - Canine hip dysplasia treated by juvenile pubic symphysiodesis. Part I: two year results of computed tomography and distraction index. AB - OBJECTIVES: To measure one and two year effects of juvenile pubic symphysiodesis (JPS) in puppies defined as 'at-risk' for canine hip dysplasia (CHD) using the following objective hip conformation criteria: Acetabular angle (AA), dorsal acetabular rim angle (DARA) and hip laxity (PennHIP(c) distraction index (DI). DESIGN: Controlled clinical case study. ANIMALS: Thirty-nine dysplastic puppies (six controls). PROCEDURES: The dogs were anaesthetised and acetabular angle, DARA, and DI values were obtained by computed tomography and radiography preoperatively. Electro-cautery fusion of the pubic symphysis was performed between 12 - 24 weeks of age. The imaging was repeated at one and two years of age. RESULTS: Significant hip improvements were seen at the two-year follow-up appointments for: AA (JPS dogs 31% increase, control 3%), DARA (JPS 38% decrease, control 15%) and DI (JPS 41% decrease in laxity, controls 20%) for all postoperative versus preoperative values. Pubic fusion occurred with minor morbidity. CONCLUSION: Juvenile pubic symphysiodesis resulted in significant improvements in hip conformation (AA and DARA), especially in mild to moderately lax hips (DI = 0.40-0.69). Most dogs with DI>=0.70 increased in osteoarthritis grade by two years of age. CLINICAL RELEVANCE: Juvenile pubic symphysiodesis surgery at 12-24 weeks of age significantly improved hip conformation and decreased laxity in at-risk CHD dogs. Early-age (12 to 16 week) recognition of hip laxity offered greater JPS benefits than surgery performed at 19- to 24-weeks old. Dogs with severe laxity (DI>=0.70) continued to increase in osteoarthritis. An early (12-16 weeks) positive laxity test (Ortolani) should alert one to obtain objective laxity determinations (PennHIP(c) DI). PMID- 20740259 TI - Morphometric assessment of the canine hip joint using the acetabular angle of retrotorsion. AB - Morphometric assessment of the canine hip joint using acetabular angle of retrotorsion was used in this study. The aim of our study was to compare the acetabular angle of retrotorsion (AAR) with values of the Norberg angle (NA) and the hip score (HS) in the Leonberger dog breed and to determine the cut-off point of AAR that distinguish between normal and dysplastic hip status on the basis of Federation Cynologique Internationale (FCI) hip evaluation. Retrospective analysis of NA and AAR was measured from standard ventrodorsal pelvic radiographs with extended femurs in 387 Leonberger dogs (141 males and 246 females) from 18 to 63 months of age, which were then divided into five age-groups. Through analysis of these radiographs, it was determined that the cut-off point for NA was 105 degrees , AAR was 15 degrees , and the acetabular angle of retrotorsion was positively correlated with Norberg angle and negatively correlated with hip score. The results of our study indicate that the acetabular angle of retrotorsion may represent a reliable morphometric assessment tool in evaluating acetabular cup conformation, and values of AAR may help to assess the FCI grade of canine hip dysplasia. PMID- 20740260 TI - Treatment of tarsal joint deformities with hinged transarticular external fixators in three young birds. AB - Pelvic limb deformities are common in many avian species. Three young birds, including a six-week-old Cockatoo and two three-month-old goslings, were presented with tarsal joint deformities. They were treated with an experimental prototype of a hinged linear external fixator, placed in a transarticular fashion, in order to maintain joint function during treatment. All birds had close to normal leg function at six to ten weeks postoperatively. These results suggest that the hinged external fixator may be a viable treatment option for tarsal joint deformities in young birds. PMID- 20740261 TI - Short- and long-term outcomes of primary Achilles tendon repair in cats: 21 cases. AB - OBJECTIVES: To evaluate the short- and long-term outcomes of surgically repaired Achilles tendons in cats. METHODS: Twenty-one cats that underwent surgical repair of Achilles tendon injuries were retrospectively examined. Signalment, type of injury, time from injury to surgery, the surgical repair, complications, and long term outcomes were recorded. Statistical comparisons were made between traumatic and atraumatic injuries using Student's paired t-tests. RESULTS: Both traumatic and atraumatic causes of disruption were equally represented and female cats were significantly over-represented. Type I and Type IIc injuries were found in cats, but the type did not affect short- or long-term outcome. A complication rate of 33% was identified and was always attributable to the method of external coaptation. None of the cats that were augmented with a splint developed complications, however complications did occur in those with transarticular external skeletal fixators. Long-term clinical outcome found an 84% overall success rate and a 79% success rate for cats with Type IIc injuries. A significantly shorter time from injury to surgery was identified for traumatic injuries, but not for age, weight, or long-term outcome. CLINICAL SIGNIFICANCE: Surgical correction resulted in excellent functional outcome in all cases but one, and should be considered in both complete and partial disruption of the Achilles mechanism in cats. A direct comparison between surgical and conservative management of Type IIc injuries in cats should be considered to determine which method is most appropriate to manage these injuries. PMID- 20740262 TI - Are bi-axial proximal sesamoid bone fractures in the British Thoroughbred racehorse a bone fatigue related fracture? A histological study. AB - OBJECTIVES: To investigate whether microfractures and alterations in the trabecular bone area are associated with catastrophic bi-axial proximal sesamoid bone fractures (PSBF). METHODS: Proximal sesamoid bones (PSB) from 10 racehorses with PSBF and from 10 control racehorses without musculoskeletal injury were examined using the bulk basic fuchsin method. Bone histomorphometric and microfracture analysis was performed, and cases and controls compared using two sample t-test, paired t-test, and Mann-Whitney U test. RESULTS: There was no significant difference in the microfracture density and the trabecular bone area between bones from case and control horses, and between fractured and non fractured bones in case horses. CLINICAL RELEVANCE: Microfracture density was low in the areas of the PSB examined. Microfracture density was not significantly different between groups, indicating that propagation of micro-cracks is an unlikely predisposing pathologic alteration in PSBF in British racehorses. There was no significant difference in the bone surface area between groups, which one would expect if modelling, adaptation and an increase in bone density were associated with PSBF fracture in the case horses. Therefore, PSBF in the British racehorse does not appear to be associated with microfractures of the trabecular bone of the PSB. The PSB fractures might represent an acute monotonic fracture; however, the aetiology of the fractures remains unknown with additional research required. PMID- 20740263 TI - Randomised controlled clinical trial for the use of deracoxib during intense rehabilitation exercises after tibial plateau levelling osteotomy. AB - During intense physical exercise, the cyclo-oxygenase-2 (COX-2) pathway is upregulated which contributes to soreness. The aim of this study was to determine if there was a clinical affect of deracoxib (COX-2 selective antagonist) on dogs engaged in intense rehabilitation following tibial plateau levelling osteotomy for cranial cruciate ligament rupture. Our hypothesis was that dogs receiving deracoxib would demonstrate less lameness, better range-of-motion (ROM), and faster muscle mass recovery than the control dogs. Thirty dogs were randomised to the treatment (deracoxib at 1-2 mg/kg once daily by mouth) or control (no treatment) group. Outcomes including gait analysis, thigh circumference, and goniometry, were measured by one investigator, who was masked to group preoperatively, and at the end of each intense rehabilitation week (3, 5, and 7 weeks postoperatively). The only difference between groups for any outcome measure at any time point was a greater preoperative stifle ROM in the group receiving deracoxib (p = 0.04). This study showed that treatment with deracoxib did not provide better outcomes when dogs were subjected to intense rehabilitation after tibial plateau levelling osteotomy. Each patient should be evaluated individually to determine if administration of deracoxib is appropriate. PMID- 20740264 TI - Canine meningioma: a case report of a rare subtype and novel atlanto basioccipital surgical approach. AB - OBJECTIVE: To describe a novel histological subtype of skull base and cranial cervical meningioma operated upon through an uncommon atlanto basioccipital approach. STUDY DESIGN: Clinical case report. ANIMAL: A seven-year-old neutered female Boxer. METHODS: The dog was presented due to lethargic behavior, signs of head and neck pain, and ongoing tetraparesis. Neurological examination and magnetic resonance imaging led to diagnosis of a ventral spinal canal mass causing severe cord and brainstem compression and which required surgical management. RESULTS: The mass was approached through a ventral craniectomy extending cranially on the basioccipital bone. Extemporaneous cytological examination of the mass led to confirmation of neoplastic nature of the abnormal tissue. Cytoreduction of the mass was performed using multiple cycles of curettage, lavage and suction. Histopathological examination of the tumour was consistent with a papillary variant of meningioma. Adjuvant therapy was declined by the owners. The dog improved considerably in the postoperative period, however three months after surgery signs of recurrence led to euthanasia. CONCLUSIONS: Basioccipital craniectomy allowed a limited but sufficient approach for cytoreduction of a compressive meningioma of the brainstem and cranial cervical spinal cord. Papillary meningiomas are locally infiltrative and postoperative recurrence is common. CLINICAL RELEVANCE: Basioccipital approach combined with cranial atlanto corpectomy can be performed to relieve compression of the caudal brainstem and cranial cervical cord. PMID- 20740265 TI - Searching for high-quality articles about intervention studies in occupational health--what is really missed when using only the Medline database? AB - OBJECTIVE: Most occupational health physicians access electronic databases to obtain reliable medical information. Although it has been demonstrated that the use of Medline alone does not ensure comprehensiveness, many experts rely solely on this database. Our study aimed to discover to what extent the physician who limits his/her search to Medline misses studies of high quality. METHODS: We constructed a "gold standard" database of high-quality intervention studies gathering all the references included in the systematic reviews of the Cochrane Library and indexed under the topic "occupational health field". We then searched all these references, one by one, in Medline. RESULTS: Overall, 88.8% [95% confidence interval (95% CI) 86.1-91.5] of the high quality studies included in our gold standard database were indexed in Medline. References included in reviews on psychiatric or psychological topics were significantly less often indexed in Medline [81.7% (95% CI 75.9-88.5)] than references included in reviews on other topics [92.2% (95% CI 89.5-95.0)] (P=0.001). CONCLUSION: The recall ratio of Medline for high-quality intervention studies is close to 90%. For occupational health practitioners who aim to find reliable answers to their daily practice questions, searching Medline only is more cost-effective than previously thought. PMID- 20740266 TI - Self-reported symptoms and neuropsychological function among tunnel workers previously exposed to acrylamide and N-methylolacrylamide. AB - OBJECTIVE: The aim of this study was to examine possible exposure-related symptoms and neuropsychological changes among tunnel workers previously exposed to grout containing acrylamide and N-methylolacrylamide. METHODS: In a cross sectional study, 44 male tunnel workers previously exposed to acrylamide and N methylolacrylamide during grouting operations were exam-in-ed with neuropsychological tests, 2-10 years after last exposure. The control group consisted of 49 male tunnel workers with no history of acrylamide exposure. Questionnaires were used to assess retrospectively recalled symptoms during work and current symptoms at the time of the examination. RESULTS: The prevalence of paresthesia in hands and legs, and leg cramps during work peri-ods were higher in the exposed than control group. Self-reported prevalence of skin irritation, peeling of skin on the hands, white-finger attacks, headache, and breathlessness was also higher among the exposed workers. The Q-16 questionnaire on current symptoms indicated higher symptom prevalence among the exposed of impaired memory and concentration, emotional change, sleep disturbances, tiredness, headache, and sensory or motor changes. In contrast, no association was found between neuropsychological test results and acrylamide exposure, adjusting for relevant confounders. However, selected motor symptoms were associated with the corresponding results on tests for motor function. CONCLUSIONS: Despite higher prevalences of self-reported current symptoms among the acrylamide-exposed compared to the control group, we did not find an association between occupational acrylamide exposure and health out-comes as measured by the chosen neuropsychological tests. Observed associations between chemical exposure and self-reported symptoms should be interpreted with great caution. PMID- 20740267 TI - [Vena cava filters in trauma patients]. AB - BACKGROUND: The introduction of removable inferior vena cava filters (IVCF) has created new options for the prevention of pulmonary embolisms in surgical trauma patients. We have observed increasing use in trauma patients. PATIENTS AND METHODS: A retrospective analysis was carried out of 49 trauma patients out of 85 who received IVCFs at our level 1 trauma centre in 2008. RESULTS: The indications for IVCF placement were multiple trauma in 33 patients, severe head injury in 13 and spinal injury in 3 patients. Of the patients 34 underwent successful removal, 11 (22%) patients had had no retrieval attempt by December 2009 and attempts at removal were unsuccessful in 3 patients. The mean age of the patients was 33.3 years. CONCLUSION: In 2008 the vast majority of IVCFs were inserted for prophylaxis in trauma patients. To increase the number of retrieved IVCFs, responsibility for the removal should be clarified in every hospital. The indications, advantages, safety and also the design of IVCFs are still under debate. A randomized controlled trial is needed to determine the appropriate use and indications for this potentially useful device in trauma patients. PMID- 20740268 TI - [Surgical treatment of Achilles tendon rupture]. AB - The open tendon suture is the most commonly used method of treatment for Achilles tendon rupture in Germany. Over the last decade the therapeutic spectrum of operative methods has been further enlarged by the development of new minimally invasive surgical techniques. Important criteria for planning treatment are the location and age of the rupture and comorbidities. For recent Achilles tendon ruptures minimally invasive suturing is indicated but for older ruptures a reconstruction often has to be carried out. The decisive disadvantage of an open tendon suture is the relatively high risk of infection. Using minimally invasive surgical techniques the frequency of postoperative infection could be significantly reduced. The suture methods without opening the ruptured region can be collectively grouped under the term percutaneous suture techniques and the minimally invasive methods with opening of the rupture region as combined open percutaneous techniques. Documented problems with the Ma-Griffith technique, such as injury of the sural nerve, low stability of the suture and insufficient adaption of the tendon stumps have been minimized by new minimally invasive operation techniques. Achilles tendon ruptures which nearly always arise without any external influence or accidents can have substantial psychological consequences regarding the integrity of one's own body especially for people actively engaged in sport. This aspect should be considered and accepted in particular during postoperative treatment. PMID- 20740269 TI - [Acute bleeding from the innominate artery after removal of percutaneous tracheotomy]. AB - Percutaneous tracheotomy is a standard procedure in intensive care units. Even though complications associated with this intervention have been described, acute massive bleeding from the innominate artery is rare and necessitates immediate intervention. We report a case with acute bleeding after removal of a percutaneous tracheotomy cannula. PMID- 20740270 TI - [Ligament healing results after type C pelvic ring fractures. Results of triangular vertebropelvic support]. AB - BACKGROUND: Posterior pelvic ring fractures are often associated with injuries of lumbopelvic soft tissue structures. The aim of this prospective MR study was to examine whether ruptured iliolumbal ligaments could be diagnosed in types B and C pelvic ring fractures. The influence of triangular lumbopelvic stabilization (TLPS) was also investigated with respect to stiffening of the lumbopelvic region. MATERIAL AND METHODS: Using a 1.5 Tesla MRI, 20 patients with types B and C fractures were examined to identify ruptured iliolumbal ligaments. In a retrospective study of 30 patients previously stabilized with a TLPS, pain scores, clinical instability testing and measuring of the segmental dislocation in extension, flexion and lateral flexion based on x-rays were also investigated. RESULTS: Of the patients 3 (1 type B, 2 type C fractures) had incompletely ruptured iliolumbal ligaments. In five patients pain intensity and localization could be significantly correlated with clinical instability of the lumbopelvic region, segmental hypermobility and instability. CONCLUSION: Pelvic ring fractures types B and C can be associated with ruptured iliolumbal ligaments. Lumbopelvic instability can be correlated with early implant loosening of TLPS. PMID- 20740271 TI - Health behaviours, socioeconomic status and diabetes incidence: the Australian Diabetes Obesity and Lifestyle Study (AusDiab). AB - AIMS/HYPOTHESIS: To identify the impact of socioeconomic status on incident impaired glucose metabolism and type 2 diabetes and to investigate the mediating role of health behaviours on this relationship using national, population-based data. METHODS: The Australian Diabetes Obesity and Lifestyle (AusDiab) Study is a national, population-based, longitudinal study of adults aged 25 years and above. A total sample of 4,405 people provided complete baseline (1999-2000) and 5 year follow-up (2004-2005) data relevant for these analyses. Fasting plasma glucose and 2 h plasma glucose were obtained from an OGTT, and demographic, socioeconomic and behavioural data were collected by interview and questionnaire. Multinomial logistic regression examined the role of socioeconomic position in the development of diabetes and mediation analyses tested the contribution of health behaviours in this relationship. RESULTS: Highest level of education was a stronger predictor of incident impaired glucose tolerance and type 2 diabetes (p = 0.002), compared with household income (p = 0.103), and occupational grade (p = 0.202). Education remained a significant independent predictor of diabetes in fully adjusted models. However, the relationship was attenuated by the health behaviours (smoking and physical activity). Mediation analyses indicated that these behaviours were partial mediators (explaining 27%) of the socioeconomic status-diabetes relationship. CONCLUSION/INTERPRETATION: Smoking and physical activity partly mediate the relationship between low education and type 2 diabetes. Identification of these modifiable behavioural mediators should facilitate the development of effective health promotion campaigns to target those at high risk of developing type 2 diabetes. PMID- 20740273 TI - Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. AB - PURPOSE: Platelet-rich plasma (PRP) therapy is a simple, low-cost and minimally invasive method that provides a natural concentrate of autologous blood growth factors (GFs) that can be used to enhance tissue regeneration. In a previous analysis of a 12-month follow-up study, promising results were obtained when treating patients affected by knee degeneration with PRP intra-articular injections. The main purpose of this study was to investigate the persistence of the beneficial effects observed. METHODS: Of the 91 patients evaluated in the previous 12-month follow-up study, 90 were available for the 2-year follow-up (24 patients presented a bilateral lesion, in a total of 114 knees treated). All of the patients presented a chronic knee degenerative condition and were treated with three intra-articular PRP injections. IKDC and EQ-VAS scores were used for clinical evaluation. Complications, adverse events and patient satisfaction were also recorded. RESULTS: All of the evaluated parameters worsened at the 24-month follow-up: these parameters were at significantly lower levels with respect to the 12-month evaluation (the IKDC objective evaluation fell from 67 to 59% of normal and nearly normal knees; the IKDC subjective score fell from 60 to 51), even if they remained higher than the basal level. Further analysis showed better results in younger patients (P = 0.0001) and lower degrees of cartilage degeneration (P < 0.0005). The median duration of the clinical improvement was 9 months. CONCLUSIONS: These findings indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy. Further studies are needed to confirm these results and understand the mechanism of action, and to find other application modalities, with different platelet and GF concentrations and injection timing, which provide better and more durable results. PMID- 20740275 TI - Non-enzymatic roles for the URE2 glutathione S-transferase in the response of Saccharomyces cerevisiae to arsenic. AB - The response of Saccharomyces cerevisiae to arsenic involves a large ensemble of genes, many of which are associated with glutathione-related metabolism. The role of the glutathione S-transferase (GST) product of the URE2 gene involved in resistance of S. cerevisiae to a broad range of heavy metals was investigated. Glutathione peroxidase activity, previously reported for the Ure2p protein, was unaffected in cell-free extracts of an ure2Delta mutant of S. cerevisiae. Glutathione levels in the ure2Delta mutant were lowered about threefold compared to the isogenic wild-type strain but, as in the wild-type strain, increased 2-2.5 fold upon addition of either arsenate (As(V)) or arsenite (As(III)). However, lack of URE2 specifically caused sensitivity to arsenite but not to arsenate. The protective role of URE2 against arsenite depended solely on the GST-encoding 3' end portion of the gene. The nitrogen source used for growth was suggested to be an important determinant of arsenite toxicity, in keeping with non-enzymatic roles of the URE2 gene product in GATA-type regulation. PMID- 20740274 TI - Proprioception following partial meniscectomy in stable knees. AB - PURPOSE: to investigate the proprioceptive function of patients with isolated meniscal tears of the knee before and after arthroscopic partial meniscectomy. METHODS: one hundred subjects (50 patients who underwent a knee arthroscopy and 50 normal controls) were evaluated using single-leg dynamic postural stabilometry. All participants were assessed clinically and radiologically. Knee outcome scores were obtained for all subjects. RESULTS: of the 50 patients arthroscoped, 34 were found to have meniscal tears. Twenty-nine of these patients were reassessed 3 months post-operatively. There was a significant proprioceptive deficit in subjects with meniscal tears when compared to their normal contra lateral knee (P < 0.001) and the control group (P < 0.001). Partial meniscectomy resulted in a significant improvement in knee outcome scores but not proprioception measurements (n.s.). CONCLUSION: patients with isolated meniscal tears were found to have a significant proprioceptive deficit which persisted following arthroscopic partial meniscectomy despite an otherwise successful clinical outcome. PMID- 20740277 TI - Infrared spectroscopic study of molecular interaction of tacticity-controlled poly(N-isopropylacrylamide) in a cast film deposited on a solid substrate. AB - Analytical results of a series of poly(N-isopropylacrylamide) (PNiPA) with different tacticities using infrared spectroscopy are presented for studying the influence of the solvation and molecular interactions between the polymeric chains. Infrared spectra of solid matter samples of the compounds exhibit a systematic band intensity change for three band components at 1,680, 1,659, and 1,628 cm(-1) involved in the amide I band. The three components correspond to the free, half, and full hydrogen bondings of the secondary amide group, which reflect the molecular configuration depending on the tacticity. When cast films of the compounds prepared on a solid surface are analyzed by infrared transmission spectrometry, another factor of the solvent used for the film preparation is found to be another factor which plays an important role in determining the molecular architecture in the films. This molecular imprint mechanism after the solvation is confirmed by measuring infrared multiple-angle incidence resolution spectra of annealed films. The molecular interactions in the polymeric samples have been revealed by the use of infrared spectroscopy and the tacticity-controlled samples. PMID- 20740276 TI - Serotonin 5-HT4 receptors in the nucleus accumbens are specifically involved in the appetite suppressant and not locomotor stimulant effects of MDMA ('ecstasy'). AB - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) abuse is a substantial problem in young adults. Due to a high focus on body image in this population, two main factors that may encourage MDMA use are the appetite suppressant and locomotor stimulant effects of this drug. The nucleus accumbens (NAc) is a brain region associated with the regulation of motivated and locomotor behaviours, and recent evidence suggests that NAc 5-HT4 receptors are likely to be involved in the appetite suppressant effect of MDMA. It has not yet been shown whether 5-HT4 receptors of the NAc are involved in the locomotor stimulant effects of MDMA, which may also contribute to a reduction in food intake. OBJECTIVES: This study aimed to investigate the effect of local antagonism of serotonin 5-HT4 receptors in the NAc in the appetite suppressant and locomotor stimulant effects of MDMA. METHODS: Male hooded Wistar rats underwent surgery for the implantation of bilateral NAc microinjection cannulae under isofluorane anesthesia. Following 5-7 days of recovery, the rats received bilateral microinjections of the 5-HT4 antagonist RS39604 into the NAc immediately prior to either saline or MDMA administration. Food intake, water intake, body weight and locomotor activity were measured. RESULTS: RS39604 significantly increased food intake and increased weight loss in MDMA-treated but not saline-treated rats. Measures of MDMA-induced water intake or locomotor activity were not altered by antagonist administration. CONCLUSIONS: These results demonstrate that 5-HT4 receptors in the NAc specifically regulate the appetite suppressant effects of MDMA but not MDMA induced water intake or locomotor activity. PMID- 20740278 TI - Direct detection of Delta9-tetrahydrocannabinol in aqueous samples using a homogeneous increasing fluorescence immunoassay (HiFi). AB - The detection of the major active component of cannabis, Delta9 tetrahydrocannabinol (THC), becomes increasingly relevant due to its widespread abuse. For control purposes, some easy-to-use, sensitive and inexpensive test methods are needed. We have developed a fluorescence immunoassay utilising THC fluorescein conjugate as tracer. Fluorescence spectroscopy of the conjugate revealed an unusual property: The relatively weak fluorescence of a dilute tracer solution was increased by a factor of up to 5 after binding of a THC-specific antibody. Fluorescence lifetime measurements in aqueous solutions suggested two different tracer conformations both associated with quenching of fluorescein fluorescence by the intramolecular THC moiety. After antibody binding, the tracer enters a third conformation in which fluorescence quenching of fluorescein is completely suppressed. Utilising this property, we established a homogeneous competitive immunoassay (homogeneous increasing fluorescence immunoassay) with low detection limits. The test requires only two reagents, the new tracer molecule and an anti-THC antibody. A single test takes only 8 min. The dynamic detection range for THC is 0.5 to 20 ng/mL in buffer, with a limit of detection (LOD) of 0.5 ng/mL. The test also works in diluted saliva samples (1:10 dilution with buffer) with an LOD of 2 ng/mL and a dynamic range of 2-50 ng/mL. PMID- 20740279 TI - Perfluorinated compounds (PFCs) in groundwater and aqueous soil extracts: using inline SPE-LC-MS/MS for screening and sorption characterisation of perfluorooctane sulphonate and related compounds. AB - Perfluorinated compounds (PFCs) have been recognised as emerging pollutants of global relevance. A fully automated method with inline solid-phase extraction coupled to electrospray ionisation liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) is presented and used for characterisation of soil adsorption and desorption for six PFCs: perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorobutane sulphonate (PFBS), and perfluorooctane sulphonate (PFOS). The method reduces sample turnaround time and solvent consumption and is suitable for low volume sampling. The only sample preparation necessary for water samples was sedimentation by centrifugation. The method has a total runtime of 21 min including inline sample cleanup (2 min for injection and SPE, 14 min for the chromatographic separation, 5 min for reconditioning). Negative AP-ESI with selective reaction monitoring (SRM) was used and the method was documented for quantification of the six environmentally important PFCs in subsoil matrix and related aqueous matrixes (groundwater and drainage water). Linearity was demonstrated in the range 5 to 2,500 ng/l and the LOD was between 2 and 8 ng/l in groundwater. Adsorption was characterised by linear Freundlich isotherms for all six compounds in two agricultural top soils (A horizon, sandy and clayey soil).Variability in sorption characteristics for soil types as well as compound properties were found, and correlation between the organic carbon normalised sorption coefficient (K (OC)) and PFC molecular weight was demonstrated. The K (d) values were in the range 0.1 to 33 (l/kg), and 0.3 to 65 (l/kg) for sorption and desorption respectively. PMID- 20740280 TI - Classification of nucleotide sequences using support vector machines. AB - Species identification is one of the most important issues in biological studies. Due to recent increases in the amount of genomic information available and the development of DNA sequencing technologies, the applicability of using DNA sequences to identify species (commonly referred to as "DNA barcoding") is being tested in many areas. Several methods have been suggested to identify species using DNA sequences, including similarity scores, analysis of phylogenetic and population genetic information, and detection of species-specific sequence patterns. Although these methods have demonstrated good performance under a range of circumstances, they also have limitations, as they are subject to loss of information, require intensive computation and are sensitive to model mis specification, and can be difficult to evaluate in terms of the significance of identification. Here, we suggest a new DNA barcoding method in which support vector machine (SVM) procedures are adopted. Our new method is nonparametric and thus is expected to be robust for a wide range of evolutionary scenarios as well as multilocus analyses. Furthermore, we describe bootstrap procedures that can be used to test the significances of species identifications. We implemented a novel conversion technique for transforming sequence data to real-valued vectors, and therefore, bootstrap procedures can be easily combined with our SVM approach. In this study, we present the results of simulation studies and empirical data analyses to demonstrate the performance of our method and discuss its properties. PMID- 20740281 TI - Recombination within and between species of the alpha proteobacterium Bartonella infecting rodents. AB - Bartonella infections from wild mice and voles (Apodemus flavicollis, Mi. oeconomus, Microtus arvalis and Myodes glareolus) were sampled from a forest and old-field habitats of eastern Poland; a complex network of Bartonella isolates, referrable to B. taylorii, B. grahamii, B. birtlesii and B. doshiae, was identified by the sequencing of a gltA fragment, comparable to previous studies of Bartonella diversity in rodents. Nested clade analysis showed that isolates could be assigned to zero- and one-step clades which correlated with host identity and were probably the result of clonal expansion; however, sequencing of other housekeeping genes (rpoB, ribC, ftsZ, groEl) and the 16S RNA gene revealed a more complex situation with clear evidence of numerous recombinant events in which one or both Bartonella parents could be identified. Recombination within gltA was found to have generated two distinct variant clades, one a hybrid between B. taylorii and B. doshiae, the other between B. taylorii and B. grahamii. These recombinant events characterised the differences between the two step and higher clades within the total nested cladogram, involved all four species of Bartonella identified in this work and appear to have played a dominant role in the evolution of Bartonella diversity. It is clear, therefore, that housekeeping gene phylogenies are not robust indicators of Bartonella diversity, especially when only a single gene (gltA or 16S RNA) is used. Bartonella clades infecting Microtus were most frequently involved in recombination and were most frequently tip clades within the cladogram. The role of Microtus in influencing the frequency of Bartonella recombination remains unknown. PMID- 20740283 TI - Hand-assisted versus straight laparoscopic sigmoid colectomy on a training simulator: what is the difference? A stepwise comparison of hand-assisted versus straight laparoscopic sigmoid colectomy performance on an augmented reality simulator. AB - BACKGROUND: We hypothesized that simulator-generated metrics and intraoperative errors may be able to differentiate the technical differences between hand assisted laparoscopic (HAL) and straight laparoscopic (SL) approaches. METHODS: Thirty-eight trainees performed two laparoscopic sigmoid colectomies on an augmented reality simulator, randomly starting by a SL (n = 19) or HAL (n = 19) approach. Both approaches were compared according to simulator-generated metrics, and intraoperative errors were collected by faculty. RESULTS: Sixty-four percent of surgeons were experienced (>50 procedures) with open colon surgery. Fifty-five percent and 69% of surgeons were inexperienced (<10 procedures) with SL and HAL colon surgery, respectively. Time (P < 0.001), path length (P < 0.001), and smoothness (P < 0.001) were lower with the HAL approach. Operative times for sigmoid and splenic flexure mobilization and for the colorectal anastomosis were significantly shorter with the HAL approach. Time to control the vascular pedicle was similar between both approaches. Error rates were similar between both approaches. Operative time, path length, and smoothness correlated directly with the error rate for the HAL approach. In contrast, error rate inversely correlated with the operative time for the SL approach. CONCLUSIONS: A HAL approach for sigmoid colectomy accelerated colonic mobilization and anastomosis. The difference in correlation between both laparoscopic approaches and error rates suggests the need for different skills to perform the HAL and the SL sigmoid colectomy. These findings may explain the preference of some surgeons for a HAL approach early in the learning of laparoscopic colorectal surgery. PMID- 20740282 TI - Molecular detection of anaerobic ammonium-oxidizing (anammox) bacteria in high temperature petroleum reservoirs. AB - Anaerobic ammonium-oxidizing (anammox) process plays an important role in the nitrogen cycle of the worldwide anoxic and mesophilic habitats. Recently, the existence and activity of anammox bacteria have been detected in some thermophilic environments, but their existence in the geothermal subterranean oil reservoirs is still not reported. This study investigated the abundance, distribution and functional diversity of anammox bacteria in nine out of 17 high temperature oil reservoirs by molecular ecology analysis. High concentration (5.31-39.2 mg l(-1)) of ammonium was detected in the production water from these oilfields with temperatures between 55 degrees C and 75 degrees C. Both 16S rRNA and hzo molecular biomarkers indicated the occurrence of anammox bacteria in nine out of 17 samples. Most of 16S rRNA gene phylotypes are closely related to the known anammox bacterial genera Candidatus Brocadia, Candidatus Kuenenia, Candidatus Scalindua, and Candidatus Jettenia, while hzo gene phylotypes are closely related to the genera Candidatus Anammoxoglobus, Candidatus Kuenenia, Candidatus Scalindua, and Candidatus Jettenia. The total bacterial and anammox bacterial densities were 6.4 +/- 0.5 * 10(3) to 2.0 +/- 0.18 * 10(6) cells ml(-1) and 6.6 +/- 0.51 * 10(2) to 4.9 +/- 0.36 * 10(4) cell ml(-1), respectively. The cluster I of 16S rRNA gene sequences showed distant identity (<92%) to the known Candidatus Scalindua species, inferring this cluster of anammox bacteria to be a new species, and a tentative name Candidatus "Scalindua sinooilfield" was proposed. The results extended the existence of anammox bacteria to the high temperature oil reservoirs. PMID- 20740285 TI - [HER2 ASCO guidelines. The answer to everything?]. AB - The HER2 gene is amplified and overexpressed in about 15%-20% of breast cancers. For every newly diagnosed breast cancer HER2 testing is a standard routine procedure. This article focuses on a number of issues raised in the context of current HER2 testing in breast cancer. It particularly points out issues arising in the recently published ASCO-CAP (American Society of Clinical Oncology/College of American Pathologists) guideline recommendations for clinical testing of HER2. Despite the significant correlation between HER2 status determination by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), standard considerations of laboratory testing, such as test accuracy, reproducibility and precision as well as current data, favor FISH methods over IHC assay methods for the determination of HER2 status. Biological and technical considerations of HER2 testing are also important in clinical practice. For example, HER2 gene amplification is directly linked to the protein expression level in breast cancer; however, the HER2 protein is not consistently analyzed on formalin fixed tissues due to variability in fixation methods/times and the impact of this fixation on HER2 protein antigenicity. FISH is significantly less dependent on tissue fixation artifacts. Hence, FISH is more reproducible between both central and peripheral laboratories than IHC and is more accurate for HER2 measurement, as well as being more strongly correlated with responsiveness to trastuzumab and lapatinib treatment. Until other methods are able to ensure similar test accuracy, reproducibility, precision and predictive value, FISH is recommended as the primary HER2 testing modality for women with breast cancer who are candidates for HER2-targeted therapies. PMID- 20740284 TI - Autophagosome formation in mammalian cells. AB - Autophagy is a fundamental intracellular trafficking pathway conserved from yeast to mammals. It is generally thought to play a pro-survival role, and it can be up regulated in response to both external and intracellular factors, including amino acid starvation, growth factor withdrawal, low cellular energy levels, endoplasmic reticulum (ER) stress, hypoxia, oxidative stress, pathogen infection, and organelle damage. During autophagy initiation a portion of the cytosol is surrounded by a flat membrane sheet known as the isolation membrane or phagophore. The isolation membrane then elongates and seals itself to form an autophagosome. The autophagosome fuses with normal endocytic traffic to mature into a late autophagosome, before fusing with lysosomes. The molecular machinery that enables formation of an autophagosome in response to the various autophagy stimuli is almost completely identified in yeast and-thanks to the observed conservation-is also being rapidly elucidated in higher eukaryotes including mammals. What are less clear and currently under intense investigation are the mechanism by which these various autophagy components co-ordinate in order to generate autophagosomes. In this review, we will discuss briefly the fundamental importance of autophagy in various pathophysiological states and we will then review in detail the various players in early autophagy. Our main thesis will be that a conserved group of heteromeric protein complexes and a relatively simple signalling lipid are responsible for the formation of autophagosomes in mammalian cells. PMID- 20740286 TI - Mitochondrial abnormalities in the putamen in Parkinson's disease dyskinesia. AB - Prolonged treatment of Parkinson's disease (PD) with levodopa leads to disabling side effects collectively referred to as 'dyskinesias'. We hypothesized that bioenergetic function in the putamen might play a crucial role in the development of dyskinesias. To test this hypothesis, we used post mortem samples of the human putamen and applied real time-PCR approaches and gene expression microarrays. We found that mitochondrial DNA (mtDNA) levels are decreased in patients who have developed dyskinesias, and mtDNA damage is concomitantly increased. These pathologies were not observed in PD subjects without signs of dyskinesias. The group of nuclear mRNA transcripts coding for the proteins of the mitochondrial electron transfer chain was decreased in patients with dyskinesias to a larger extent than in patients who had not developed dyskinesias. To examine whether dopamine fluctuations affect mtDNA levels in dopaminoceptive neurons, rat striatal neurons in culture were repeatedly exposed to levodopa, dopamine or their metabolites. MtDNA levels were reduced after treatment with dopamine, but not after treatment with dopamine metabolites. Levodopa led to an increase in mtDNA levels. We conclude that mitochondrial susceptibility in the putamen plays a role in the development of dyskinesias. PMID- 20740287 TI - Treatment of pathological humerus shaft fractures with intramedullary nails with or without cement fixation. AB - INTRODUCTION: Bone metastasis is a severe complication for patients with cancer. Not only does it cause intractable pain and other clinical problems such as fracture after trivial injury, it also signifies that the malignant process is incurable. Since life expectancy of metastasised cancer patients has improved due to advanced oncological treatment but is still limited, appropriate surgical intervention has increased. METHOD: This is a retrospective control study of 21 patients who underwent cemented intramedullary nailing for pathological fractures in the humeral shaft between 2005 and 2009 as compared to a historical control group of 19 patients that underwent locked intramedullary nailing for pathological fractures in the humeral shaft between 1999 and 2004. Four major outcomes were assessed, namely, pain relief, use of analgesics, recovery of function and rate of complication. RESULTS: Patients treated with cemented intramedullary nailing had better pain relief, less use of analgesics and better functional restoration immediately after surgical procedure when compared to the patients without cement fixing. The rate of complication did not differ between these two groups. CONCLUSION: Since surgery for metastases does not prolong life but improves the quality of life, the aim towards a short postoperative rehabilitation time is recommended. Cement fixation gives immediate stabilisation to the fracture site and thus allows less pain but full range of motion from the first postoperative day. PMID- 20740288 TI - Sonographic basal ganglia alterations are related to non-motor symptoms in multiple sclerosis. AB - The anatomical basis of cognitive dysfunction and other non-motor symptoms in multiple sclerosis (MS) is poorly understood. In MS patients, transcranial sonography (TCS) shows neurodegenerative disease-like lesions of the substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation. The present study deals with the question of whether sonographic changes of SN, brainstem raphe, lenticular nucleus (LN) or caudate nucleus are related to non-motor symptoms of MS. We used TCS to investigate 54 MS patients and 54 age- and sex matched healthy subjects. Degree of cognitive (executive) dysfunction, fatigue, depression, and urinary urge incontinence in MS patients was assessed using the Paced Auditory Serial Addition Test, the Faces Symbol Test, the Modified Fatigue Impact Scale, the Beck Depression Inventory, and the Urinary Distress Inventory. Abnormal TCS findings of SN, brainstem raphe, LN, and caudate nucleus were found in 13, 7, 11, and 6% of the healthy subjects, but in 54, 43, 62, and 41% (each, p < 0.001) of the MS patients, with similar frequency in relapsing-remitting and primary or secondary progressive MS patients. Sonographic alteration of the LN correlated with cognitive dysfunction. Combined alteration of both, LN and SN, was clearly associated with cognitive dysfunction and cognitive fatigue. The combined sonographic alteration of SN and brainstem raphe indicated severe urinary urge incontinence irrespective of the presence of spinal MS lesions. No relation was found between depression and any of the TCS findings. These findings suggest that neurodegenerative processes affecting deep brain structures contribute to cognitive and autonomic dysfunction in MS. PMID- 20740290 TI - Abundance-occupancy relationships in metapopulations: examples of rock pool Daphnia. AB - Intraspecific positive relationships between abundance and occupancy are observed for many species, suggesting that the same processes drive local and regional species dynamics. Two main groups of mechanisms explain this relationship: spatiotemporal variation in local population growth rates due to variation in habitat quality, or dispersal effects that increase occupancy of a species when locally abundant. Several studies show that spatiotemporal variation in population growth rates causes positive abundance-occupancy relationships, but few have shown dispersal effects. It is believed that such effects should be more evident for species whose dispersal is limited, e.g. metapopulations, but those studies are limited. This study investigates abundance-occupancy relationships in three Daphnia metapopulations in rock pools and the degree to which dispersal or habitat quality affect their local abundances and occurrence. Daphnia longispina and Daphnia magna showed positive abundance-occupancy relationships, but not Daphnia pulex. No single ecological factor could explain the abundance-occupancy relationships of any given species. Instead, dispersal processes and rock pool quality (mainly salinity and depth) seem to act together to shape the abundance occupancy relationships. Such a conclusion is also supported by an immigration experiment in natural rock pools. This study suggests that although positive abundance-occupancy relationships may be commonly found for metapopulations, both dispersal processes and variation in habitat quality can be factors determining the abundance-occupancy relationship of metapopulations experiencing habitat heterogeneity. PMID- 20740289 TI - Levels of plasma homocysteine in pseudoexfoliation glaucoma. AB - BACKGROUND: To examine levels of serum homocysteine (Hcy), vitamin B12 and folic acid in patients with pseudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and healthy control subjects. METHODS: This study included 36 patients with PEXG, 40 with POAG, and 40 age-matched healthy subjects. Fasting plasma Hcy concentrations and levels of serum vitamin B12 and folic acid were measured using competitive chemiluminescent enzyme immunoassay; values exceeding 14 MUm/l were considered elevated. RESULTS: Mean plasma Hcy was significantly higher in PEXG (16.55 +/- 7.23 MUm/l) compared with POAG (13.91 +/- 3.61 MUm/l) and controls (13.12 +/- 5.13 MUm/l) (p = 0.03 and p = 0.0007 respectively). There were no statistical differences in serum vitamin B12 and folic acid levels among PEXG, POAG and control subjects (p > 0.05). A moderate, although statistically significant, relationship between Hcy and folic acid levels was found in the PEXG group (R(2) = 0.23, p = 0.003). Hcy levels were found not to be related with folic acid or vitamin B12 in either POAG or control subjects. CONCLUSIONS: In this study, plasma Hcy is significantly higher in PEXG group than the POAG and control groups. Hyper-Hcy might play a role in the pathogenesis of PEXG. Hyper Hcy may be an independent factor stressing vasculopathy in addition to pseudoexfoliation, so might be a modifiable risk factor for PEXG. PMID- 20740291 TI - Effects of climate and snow depth on Bromus tectorum population dynamics at high elevation. AB - Invasive plants are thought to be especially capable of range shifts or expansion in response to climate change due to high dispersal and colonization abilities. Although highly invasive throughout the Intermountain West, the presence and impact of the grass Bromus tectorum has been limited at higher elevations in the eastern Sierra Nevada, potentially due to extreme wintertime conditions. However, climate models project an upward elevational shift of climate regimes in the Sierra Nevada that could favor B. tectorum expansion. This research specifically examined the effects of experimental snow depth manipulations and interannual climate variability over 5 years on B. tectorum populations at high elevation (2,175 m). Experimentally-increased snow depth had an effect on phenology and biomass, but no effect on individual fecundity. Instead an experimentally increased snowpack inhibited population growth in 1 year by reducing seedling emergence and early survival. A similar negative effect of increased snow was observed 2 years later. However, a strong negative effect on B. tectorum was also associated with a naturally low-snow winter, when seedling emergence was reduced by 86%. Across 5 years, winters with greater snow cover and a slower accumulation of degree-days coincided with higher B. tectorum seedling density and population growth. Thus, we observed negative effects associated with both experimentally increased and naturally-decreased snowpacks. It is likely that the effect of snow at high elevation is nonlinear and differs from lower elevations where wintertime germination can be favorable. Additionally, we observed a doubling of population size in 1 year, which is alarming at this elevation. PMID- 20740292 TI - Anthropogenic disturbance and the risk of flea-borne disease transmission. AB - Anthropogenic disturbance may lead to the spread of vector-borne diseases through effects on pathogens, vectors, and hosts. Identifying the type and extent of vector response to habitat change will enable better and more accurate management strategies for anthropogenic disease spread. We compiled and analyzed data from published empirical studies to test for patterns among flea and small mammal diversity, abundance, several measures of flea infestation, and host specificity in 70 small mammal communities of five biomes and three levels of human disturbance: remote/wild areas, agricultural areas, and urban areas. Ten of 12 mammal and flea characteristics showed a significant effect of disturbance category (six), biome (four), or both (two). Six variables had a significant interaction effect. For mammal-flea communities in forest habitats (39 of the 70 communities), disturbance affected all 12 characteristics. Overall, flea and mammal richness were higher in remote versus urban sites. Most measures of flea infestation, including percent of infested mammals and fleas/mammal and fleas/mammal species increased with increasing disturbance or peaked at intermediate levels of disturbance. In addition, host use increased, and the number of specialist fleas decreased, as human disturbance increased. Of the three most common biomes (forest, grassland/savanna, desert), deserts were most sensitive to disturbance. Finally, sites of intermediate disturbance were most diverse and exhibited characteristics associated with increased disease spread. Anthropogenic disturbance was associated with conditions conducive to increased transmission of flea-borne diseases. PMID- 20740293 TI - Genetic TPH2 variants and the susceptibility for migraine: association of a TPH2 haplotype with migraine without aura. AB - The serotonergic system plays a major role in the etiology of migraine. The rate limiting enzyme in serotonin homeostasis and availability is tryptophan hydroxylase (TPH). The TPH2 isoform is responsible for the cerebral serotonin biosynthesis. To investigate the role of genetic variation in TPH2 in the pathogenesis of migraine eight haplotype tagging SNPs covering the whole TPH2 gene where chosen using Haploview and genotyped in 503 migraineurs and 515 healthy controls. Association analysis was performed on a single SNP and haplotype basis using chi2 and logistic regression analysis. Single SNP analysis revealed a weak association with migraine, which did not remain after correction for multiple testing. Haplotype analyses revealed association of a haplotype with migraine without aura. Stratification by aura and triptan response did not reveal a positive association with the investigated polymorphisms. These results suggest a possible influence of genetic variation in TPH2 in the pathogenesis of migraine. PMID- 20740294 TI - Chlorophyll fluorescence images demonstrate variable pathways in the effects of plasma membrane excitation on electron flow in chloroplasts of Chara cells. AB - Chlorophyll fluorescence Imaging and Microscopy PAM fluorometry were applied to study spatial dynamics of photosystem II quantum yield (DeltaF/F'(m)) and non photochemical quenching (NPQ) in resting and electrically stimulated Chara corallina cells in the absence and presence of the hydrophilic electron acceptor methyl viologen (MV) in the external medium. Electrical excitation of the plasma membrane temporarily enhanced the heterogeneity of photosynthetic patterns under physiological conditions (in the absence of MV), but irreversibly eliminated these patterns in the presence of MV. These findings suggest that the action potential (AP) of the excitable plant cell affects the spatial patterns of photosynthesis and chlorophyll fluorescence through different pathways operated in the absence and presence of MV. Based on the extent of NPQ as an indicator of MV-dependent electron flow, it is supposed that MV cannot permeate into the chloroplasts of photosynthetically active "acid cell regions" but gains an immediate access to the stroma of these chloroplasts after triggering of an AP. The AP-triggered MV-dependent non-photochemical quenching in the chloroplasts of acidic cell regions was routinely observed at 0.1 mM Ca(2+) in the medium but not at elevated (2 mM) external Ca(2+) concentration. The results are interpreted in terms of competition between two permeant divalent ion species, Ca(2+) and MV(2+), for their passage through the voltage-gated calcium channels of the plasma membrane. It is proposed that the herbicidal activity of MV in characean cells, here serving as model object, can be manipulated by triggering AP and varying Ca(2+) concentration in the environmental medium. PMID- 20740295 TI - Towards a custom chelator for mercury: evaluation of coordination environments by molecular modeling. AB - A chelator is a molecule which binds a metal or metalloid ion by two or more functional groups to form a stable ring complex known as a chelate. Despite the widespread clinical use of so-called chelation therapy to remove mercury, none of the drugs currently in use have been shown to chelate mercury. Mercury can adopt three common coordination environments: linear diagonal, trigonal planar, and tetrahedral. We have previously discussed some of the structural criteria for optimal binding of mercury in linear-diagonal coordination with thiolate donors (George et al. in Chem. Res. Toxicol. 17:999-1006, 2004). Here we employed density functional theory and X-ray absorption spectroscopy to evaluate the ideal chain length for simple alkane dithiolate chelators of Hg(2+). We have also extended our previous calculations of the optimum coordination geometries to the three-coordinate [Hg(SR)(3)](-) case. Finally, we propose a new chelator "tripod" molecule, benzene-1,3,5-triamidopropanethiolate, or "Trithiopod," which is expected to bind Hg(2+) in three-coordinate geometry with very high affinity. PMID- 20740296 TI - Identification of ligand binding site on RXRgamma using molecular docking and dynamics methods. AB - Retinoid X receptors (RXRalpha, beta and gamma) are recently known to be cancer chemotherapies targets. The ligand binding domains of RXRs have been crystallized, but the information of RXRgamma ligand binding site is not yet available due to the lack of liganded complex. A thorough understanding of the ligand binding sites is essential to study RXRs and may result in cancer therapeutic breakthrough. Thus we aimed to study the RXRgamma ligand binding site and find out the differences between the three subtypes. Alignment and molecular simulation were carried out for identifying the RXRgamma ligand binding site, characterizing the RXRgamma ligand binding mode and comparing the three RXRs. The result has indicated that the RXRgamma ligand binding site is defined by helices H5, H10, beta-sheet s1 and the end loop. Besides hydrophobic interactions, the ligand 9-cis retinoic acid interacts with RXRgamma through a hydrogen bond with Ala106, a salt bridge with Arg95 and the pi-pi interactions with Phe217 and Phe218. The binding modes exhibit some similarities among RXRs, such as the interactions with Arg95 and Ala106. Nonetheless, owing to the absence of Ile47, Cys48, Ala50, Ala51 and residues 225~237 in the active site, the binding pocket in RXRgamma is two times larger than those of RXRalpha and RXRbeta. Meanwhile, spatial effects of Trp84, Arg95, Ala106, Phe217 and Phe218 help to create a differently shaped binding pocket as compared to those of RXRalpha and RXRbeta. Consequently, the ligand in RXRgamma undergoes a "standing" posing which is distinct from the other two RXRs. PMID- 20740297 TI - An incarcerated appendix: report of three cases and a review of the literature. AB - We came across three rare cases of incarcerated hernia, with different presentations. The first case was an elderly female, who presented with an incarcerated incisional hernia on the right lower iliac region diagnosed on contrast enhanced computed tomography (CT); the contents were the small bowel and the perforated tip of the appendix. In the second case of inguinal incarcerated hernia, ultrasonography showed the inflammed appendix in the subcutaneous plane of the hernial sac, which is very rarely diagnosed pre-operatively and was confirmed during surgery. Inflammed appendix with gangrenous tip was found in the inguinal hernial sac. In yet another case of incarcerated inguinal hernia, the contents were a gangrenous part of the ascending colon and transverse colon, with the tip of the inflamed appendix--also only rarely observed. The colon extended to the scrotum in this case. We could find no description within the existing medical literature on either transverse or ascending colon as contents in inguinal hernia although transverse colon alone has been reported in four cases. The surgical options for dealing with the appendix in an Amyand's hernia depend on the mode of presentation. The presence of a normal appendix does not require an appendicectomy to be performed, but its removal is necessary if inflamed. PMID- 20740298 TI - Perception of the Ecuadorian population living in Barcelona regarding access to health services. AB - OBJECTIVES: To analyse the factors that influence access to health services from the point of view of the Ecuadorian population living in Barcelona. METHODS: A qualitative, descriptive and phenomenological study was carried out by semi structured individual interviews on a sample of Ecuadorians (18) with maximum variation in age, sex, time since arrival and administrative status. The analysis was conducted according to Colaizzi's method. The study area was Barcelona. RESULTS: Access was considered to be easy for personal health-care card (PHC) holders. However, interviewees identified few factors that facilitated access related to the Ecuadorian population (PHC holder, language, social networks) and the health system (free care, opening hours). In contrast, a number of hindering factors related to both the Ecuadorian population (insufficient knowledge of the system, problems with the documentation in obtaining the PHC, working conditions) and to the system itself (information availability, resources, organisation, attitude of staff) were also identified. CONCLUSIONS: Although access was perceived as easy, the Ecuadorian population has to overcome a number of barriers to obtain care. These obstacles may have consequences on immigrants' health and on the efficiency of the system. PMID- 20740299 TI - In vitro testing for anti-inflammatory properties of compounds employing peripheral blood mononuclear cells freshly isolated from healthy donors. AB - INTRODUCTION: Inflammation is crucially involved in a variety of diseases like autoimmune syndromes, cardiovascular and neurodegenerative disorders, cancer, sepsis and allograft rejection. METHODS: Freshly isolated human peripheral blood mononuclear cells (PBMCs) are used as a screening assay for anti-inflammatory properties of compounds. Determinations of neopterin production by ELISA and of tryptophan degradation by HPLC are used as read-outs. Results are compared with further markers of immune response and oxidative stress. RESULTS: Phytohaemagglutinin induced significant tryptophan degradation and neopterin formation in PBMC, which correlated with IFN-gamma, TNF-alpha, soluble cytokine receptors and isoprostane-8. Addition of vitamin C and E suppressed the responses dose-dependently. DISCUSSION: The determination of tryptophan degradation and neopterin production in PBMC reflects various pro- and anti-inflammatory cascades that are of relevance also in patients. It constitutes a robust and reliable approach to screen anti-inflammatory or immunosuppressive drugs and may improve throughput, speed and cost-effectiveness in drug discovery. PMID- 20740300 TI - Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers. AB - OBJECTIVE: Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, is metabolized primarily by cytochrome P450 (CYP) 3A with minor contributions from CYP1A2, CYP2C19, and glucuronidation. Co-administration with CYP inhibitors may increase systemic exposure to axitinib and alter its safety profile. This study evaluated changes in axitinib plasma pharmacokinetic parameters and assessed safety and tolerability in healthy subjects, following axitinib co-administration with the potent CYP3A inhibitor ketoconazole. METHODS: In this randomized, single-blind, two-way crossover study, 32 healthy volunteers received placebo, followed by a single 5-mg oral dose of axitinib, administered either alone or on the fourth day of dosing with oral ketoconazole (400 mg/day for 7 days). RESULTS: Axitinib exposure was significantly increased in the presence of ketoconazole, with a geometric mean ratio for area under the plasma concentration-time curve from time zero to infinity of 2.06 (90% confidence interval [CI]: 1.84-2.30) and a geometric mean ratio for maximum plasma concentration (C(max)) of 1.50 (90% CI: 1.33-1.70). For axitinib alone or with ketoconazole, C(max) occurred 1.5 and 2.0 h after dosing, respectively. Adverse events were predominantly mild; the most commonly reported treatment-related adverse events were headache and nausea. CONCLUSIONS: Axitinib plasma exposures and peak concentrations were increased following concurrent administration of axitinib and ketoconazole in healthy volunteers. Axitinib alone and in combination with ketoconazole was well tolerated. These findings provide an upper exposure for expected axitinib plasma concentrations in the presence of potent metabolic inhibition. PMID- 20740301 TI - Branch retinal artery occlusion with visual field and multifocal erg in Susac syndrome: a case report. AB - A 19-year-old woman presented with subacute encephalopathy and subsequently developed hearing loss and occlusions of branches of the central retinal artery. The triad of microangiopathy of the brain, retina and cochlea is typical for Susac syndrome. The etiology of this syndrome is still unknown, but the prognosis is good in most cases. Spontaneous resolution usually occurs, but early treatment minimizes the risk of sequelae. Multifocal ERG may be useful to assess subclinical retinal dysfunction after recovery of subjective symptoms of BRAO in Susac syndrome. PMID- 20740302 TI - Effect of vascular endothelial growth factor on remodeling of C6 glioma tissue in vivo. AB - Pathological characteristics and biological behaviors of tumor are considered to result from pathological tissue remodeling regulated by the interaction of factors in the tumor microecosystem (TMES). Vascular endothelial growth factor (VEGF) is one of the factors that probably play an important role in the process of tissue remodeling. This study was a comprehensive investigation of the effects of VEGF on remodeling of glioma tissue in vivo. C6 cells with expression vectors containing sense (C6/VEGF+) or antisense (C6/VEGF-) VEGF(164) complementary DNA (cDNA) or an empty vector (C6/vec) were implanted into athymic mice, which served as an in vivo model with different levels of VEGF expression. VEGF expression, water content, and morphological characteristics of these tumor tissues were assayed. Expression of VEGF and water content in C6/VEGF- glioma (C6/VEGF-G) tissues were lower than in C6, C6/VEGF+, and C6/vec glioma (C6G, C6/VEGF+G, C6/vecG) (P < 0.01, P < 0.05); water content correlated with VEGF expression (r = 0.791, P = 0.000). In C6/VEGF-G, tumor cells were not tightly adhered to vascular walls, and the basal lamina surrounded by collagen fibers was monolayer and not continuous. However, in C6G, C6/VEGF+G, and C6/vecG, tumor cells were very close to the vascular walls, with some extending their processes to the wall. Generally, loose basal laminae surrounded by small amounts of collagen fibers were multilayer, integrated, and continuous. Vesicular vacuolar organelle (VVO) structures were observed in plasma of vascular endothelial cells (VECs), and significant correlation was found between VEGF expression level and VVO density (Spearman's r = 0.642, P = 0.007). No correlation was found between VEGF expression and fenestrae formation in VECs (Pearson's correlation r = -0.053, P = 0.846), and fenestrae in neither VECs nor intercellular clefts correlated with water content of tumor tissue (Pearson's correlation r = 0.018, P = 0.947). These results demonstrate that VEGF can aggravate edema in tumor tissues by increasing VVOs and plays critical roles in the stickiness of tumor cells to vessel wall and in the integrity and continuity of the basal lamina of vessels. Our data indicate a possible mechanism of remodeling of glioma tissue and suggest that blocking VEGF might contribute to a therapeutic strategy for glioma. PMID- 20740303 TI - Intracranial meningiomas of atypical (WHO grade II) histology. AB - Atypical (WHO grade II) meningiomas occupy an intermediate risk group between benign (WHO grade I) and anaplastic (WHO grade III) meningiomas. Although grade II meningiomas have traditionally been recognized in only about 5% of cases, after changes in diagnostic criteria with the current 2007 WHO standards, they now comprise approximately 20-35% of all meningiomas. Given the magnitude of this change, much work is now needed to solidify the adoption of these standards, to render inter-observer and inter-institutional comparisons more uniform, and to more carefully define the incidence of grade II histology. However, it is clear that they carry a several-fold increased risk of recurrence, as well as an increased rate of mortality. We will discuss the definition, diagnosis, and treatment of patients with atypical meningioma; review the current phase II cooperative trials; and draw attention to some questions timely for pre-clinical and clinical research. PMID- 20740304 TI - Papillary endothelial hyperplasia presenting as recurrent malignant glioma. AB - The initial management of patients with malignant gliomas depends on accurate histologic diagnosis which, in turn, directs appropriate treatment planning. However, the diagnosis of recurrent disease is often based solely on radiological data which can occasionally be misinterpreted as showing recurrent tumor. Lack of awareness of conditions that mimic recurrent tumor and potentially confound radiological diagnosis can lead to inappropriate therapeutic decisions. We report the case of a patient whose imaging studies suggested recurrence of malignant glioma; however, surgical resection of the lesion guided by MRI scans resulted in the correct diagnosis of papillary endothelial hyperplasia and led to appropriate management of this condition that mimicked tumor recurrence. In this report, we provide a comprehensive review of this rare entity and emphasize the importance of adequately pursuing appropriate diagnostic considerations prior to making definitive treatment decisions. PMID- 20740305 TI - Anti-hyperlipidemic and insulin sensitizing activities of fenofibrate reduces aortic lipid deposition in hyperlipidemic Golden Syrian hamster. AB - Cholesterol ester transfer protein (CETP) and apolipoprotein (apo) E are important in peroxisome proliferation activated receptor-alpha (PPAR-alpha) mediated regulation of lipoprotein metabolism. Therefore, popularly used apolipoprotein E knockout mice are not suitable to evaluate PPAR-alpha agonists. In this study, we aimed to: a) evaluate hamster as a model for insulin resistance, hyperlipidemia and atherosclerosis; and b) investigate the effect of a PPAR-alpha activator, fenofibrate, in this model. A high fat high cholesterol (HFHC) diet increased serum cholesterol and triglycerides, but inclusion of fenofibrate in the diet decreased cholesterol and proatherogenic lipoproteins, VLDL and LDL, in a time-dependent manner. Concomitantly, serum levels of triglycerides also decreased. These reductions were attributed, in part, to the down-regulation of lipogenic genes and upregulation of lipoprotein lipase. The HFHC diet caused body weight gain and mild insulin resistance, both of which were prevented following the treatments with fenofibrate. Insulin resistance was further investigated in high fructose-fed hamsters. Fenofibrate prevented both hyperinsulinemia and hypertriglyceridemia. The insulin sensitizing activity of fenofibrate appeared to occur via reductions in protein tyrosine phophatase-1B. To determine whether lowering of lipids by fenofibrate treatment contributed to the reduced risks of developing atherosclerosis in hyperlipidemic hamsters, we measured lipid deposition in the aorta. Our results showed that fenofibrate treatment reduced aortic lipid deposition by 70%. These findings suggest that hamster may be an adequate animal model to evaluate the efficacy of lipid lowering, insulin sensitizing and antiatherosclerotic agents. We also show that fenofibrate is an effective antiatherosclerotic agent in hyperlipidemic hamster model. PMID- 20740306 TI - Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration. AB - The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(epsilon-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation on random scaffolds was significantly higher compared to the oriented ones. Delivery of BMP-2 alone suppressed MSC proliferation and increased the ALP activity to a higher level than that with BMP 7 delivery. Proliferation rate was suppressed the most by the sequential delivery of the two growth factors from the random scaffold on which the ALP activity was the highest. Results indicated the distinct effect of scaffold architecture and the mode of growth factor delivery on the proliferation and osteogenic differentiation of MSCs, enabling us to design multifunctional scaffolds capable of controlling bone healing. PMID- 20740307 TI - Low temperature fabrication of magnesium phosphate cement scaffolds by 3D powder printing. AB - Synthetic bone replacement materials are of great interest because they offer certain advantages compared with organic bone grafts. Biodegradability and preoperative manufacturing of patient specific implants are further desirable features in various clinical situations. Both can be realised by 3D powder printing. In this study, we introduce powder-printed magnesium ammonium phosphate (struvite) structures, accompanied by a neutral setting reaction by printing farringtonite (Mg(3)(PO(4))(2)) powder with ammonium phosphate solution as binder. Suitable powders were obtained after sintering at 1100 degrees C for 5 h following 20-40 min dry grinding in a ball mill. Depending on the post-treatment of the samples, compressive strengths were found to be in the range 2-7 MPa. Cytocompatibility was demonstrated in vitro using the human osteoblastic cell line MG63. PMID- 20740308 TI - Patterns of aggressive behavior and peer victimization from childhood to early adolescence: a latent class analysis. AB - The developmental period characterized by the transition from childhood and elementary school to early adolescence and middle school has been associated with increases in aggressive behavior and peer victimization. Few longitudinal studies, however, have examined the stability of aggression and victimization during this critical transition. This study uses latent class analysis (LCA) to examine patterns of aggressive behavior and victimization during the transition to middle school among urban, public school students (N = 458; Girls = 53%; Latino/a = 53%; M age at t1 = 10.2 years). Independent LCA models were conducted using self-reported data assessing subjects' involvement in aggressive conduct and victimization during the spring semesters of grades four, five, and six. Elementary school students in the fourth grade initially belonged to one of four groups identified as aggressor, victim, aggressor-victim, and uninvolved latent classes. Contrary to prior research, membership in these classes changed significantly by the time students completed their first year of middle school with most youth participating in episodes of aggression and victimization during the transition. Six common paths that describe patterns of aggressive behavior and victimization from the last two years of elementary school to the first year of middle school were found. Findings are discussed in the context of social dominance theory and prior research that has found greater stability in aggression and victimization among early adolescents. PMID- 20740309 TI - Racial and ethnic variations in temporal changes in fetal deaths and first day infant deaths. AB - The purpose was to examine changes in overall and gestational age-specific proportions and rates of fetal death, first day death (<24 h), and combined fetal first day death from 1990-1991 to 2001-2002. Changes were considered by race/ethnicity. Deliveries to U.S. white, black, and Hispanic mothers were selected from the NCHS linked live birth-infant death cohort and fetal deaths files (1990-1991 and 2001-2002). There was an overall improvement in mortality, but improvements were not uniform across all racial/ethnic groups or by gestational age. The fetal mortality rate among whites and Hispanics declined 4.32 and 12.82 percent, respectively. For blacks, the fetal mortality rate increased 4.06 percent between 1990-1991 and 2001-2002. Despite overall reductions in perinatal and <24 h mortality, black rates in all outcomes maintained a twofold disparity. The overall black: white fetal mortality rate ratio increased from 2.17 to 2.36 over time. The gestational age-specific black: white combined fetal-first day mortality rate ratios were greater than 1 at later gestational ages. In some cases, the ratio increased over time, indicating that despite reductions, fetal mortality did not decline uniformly among whites and blacks at term and post-term. Despite overall improvements in fetal, first day, and combined fetal-first day mortality, racial disparities persisted and in some cases widened. This study identifies lack of improvements in fetal death in the black population compared to the white or Hispanic population at later gestational ages. PMID- 20740310 TI - Complete nucleotide sequence and genome organization of a Chinese isolate of Tobacco vein distorting virus. AB - Tobacco bushy top disease is caused by tobacco bushy top virus (TBTV, a member of the genus Umbravirus) which is dependent on tobacco vein-distorting virus (TVDV) to act as a helper virus encapsidating TBTV and enabling its transmission by aphids. Isometric virions from diseased tobacco plants were purified and disease symptoms were reproduced after experimental aphid transmission. The complete genome of TVDV was determined from cloned RT-PCR products derived from viral RNA. It was 5,920 nucleotides (nts) long and had the six major open reading frames (ORFs) typical of a member of the genus Polerovirus. Sequence comparisons showed that it differed significantly from any of the other species in the genus and this was confirmed by phylogenetic analyses of the RdRp and coat protein. SDS PAGE analysis of purified virions gave two protein bands of about 26 and 59 kDa both of which reacted strongly in Western blots with antiserum produced to prokaryotically expressed TVDV CP showing that the two forms of the TVDV CP were the only protein components of the capsid. PMID- 20740311 TI - Human papillomavirus infection and sporadic breast carcinoma risk: a meta analysis. AB - Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between HPV infection and risk of breast carcinoma, the studies remain inconclusive. Here, a meta-analysis was conducted to estimate the prevalence of HPV in breast carcinoma and test the association. Studies on HPV DNA detection in sporadic breast carcinoma in female using polymerase chain reaction were included. Information on overall and type specific (HPV 6, 11, 16, 18, 31, 33, 35, 45 and 51) HPV prevalence were required, plus detailed descriptions of study populations, HPV DNA source, publication calendar period and PCR primers used for HPV DNA detection and typing. We revealed that 24.49% of the breast carcinoma cases were associated with HPV, 32.42% occurred in Asia and 12.91% in Europe. The four most commonly identified HPV types, in the order of decreased prevalence, were HPV33, 18, 16, and 35. The detection of HPV was mostly influenced by publication calendar period and PCR primers used. In addition, the analysis of ten case-control studies containing 447 breast carcinoma cases and 275 controls showed a significant increase in breast carcinoma risk with HPV positivity (OR = 3.63, 95% CI = 1.42-9.27). These results suggest that it's difficult to rule out the possibility of the association of HPV and breast carcinoma at present according to available publication proofs. PMID- 20740312 TI - The management of ductal intraepithelial neoplasia (DIN): open controversies and guidelines of the Istituto Europeo di Oncologia (IEO), Milan, Italy. AB - The management of ductal intraepithelial neoplasia (DIN) has substantially changed over the past 30 years, as its incidence has increased (from 2-3% to more than 20%), mainly due to the widespread use of mammography screening. This article describes not only the more widespread theoretical concepts on DIN but also the differences in the practical applications of the theory between different countries, different oncology specialists, and different cancer centers. Papers related to the international multicentre-randomized trials and retrospective studies were analyzed. We include articles and papers published between 1993 and 2010 related to patients with DIN, and abstracts and reports from MEDLINE and other sources were indentified. The standard of care for DIN consists of (a) breast conservative surgery (mastectomy is still indicated in large lesions--masses or microcalcifications--in about 30% of cases); (b) radiotherapy (RT) after conservative surgery, and (c) medical treatment in estrogen receptors-positive patients. However, most studies have shown significant differences between theory and practical application. Moreover, there are differences regarding (a) the indications of sentinel lymph node biopsy, (b) the definition and identification of low-risk DIN subgroups that can avoid RT and tamoxifen, and (c) the research into new alternative drugs in adjuvant medical therapy. A general agreement on the best management of DIN does not exist as yet. New large trials are needed in order to define the best management of DIN patients which is (in most respects) still complex and controversial. PMID- 20740313 TI - One-pot microwave-assisted protocol for the synthesis of substituted 2-amino-1H imidazoles. AB - An efficient microwave-assisted one-pot two-step protocol was developed for the construction of disubstituted 2-amino-1H-imidazoles. This process involves the sequential formation of 2,3-dihydro-2-hydroxyimidazo[1,2-a]pyrimidinium salts from readily available 2-aminopyrimidines and alpha-bromoketones, followed by cleavage of the pyrimidine ring with hydrazine. PMID- 20740314 TI - Integration-mediated prediction enrichment of quantitative model for Hsp90 inhibitors as anti-cancer agents: 3D-QSAR study. AB - The present study describes a systematic 3D-QSAR study consisting of pharmacophore modeling, docking, and integration of ligand-based and structure based drug design approaches, applied on a dataset of 72 Hsp90 inhibitors as anti cancer agents. The best pharmacophore model, with one H-bond donor (HBD), one H bond acceptor (HBA), one hydrophobic_aromatic (Hy_Ar), and two hydrophobic_aliphatic (Hy_Al) features, was developed using the Catalyst/HypoGen algorithm on a training set of 35 compounds. The model was further validated using test set, external set, Fisher's randomization method, and ability of the pharmacophoric features to complement the active site amino acids. Docking analysis was performed using Hsp90 chaperone (PDB-Id: 1uyf) along with water molecules reported to be crucial for binding and catalysis (Sgobba et al. ChemMedChem 4:1399-1409, 2009). Furthermore, an integration of the ligand-based as well as structure-based drug design approaches was done leading to the integrated model, which was found to be superior over the best pharmacophore model in terms of its predictive ability on internal [integrated model 2: R ((train)) = 0.954, R ((test)) = 0.888; Hypo-01: R ((train)) = 0.912 and R ((test)) = 0.819] as well as on external data set [integrated model 2: R ((ext.set)) = 0.801; Hypo-01: R ((ext.set)) = 0.604]. PMID- 20740315 TI - Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR, FB QSSR, multi objective (MO-QSPR) and MIF studies. AB - The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors. PMID- 20740317 TI - MGMT immunoexpression in aggressive pituitary adenoma and carcinoma. AB - Recent case reports have documented the efficacy of temozolomide therapy in some aggressive pituitary adenomas and pituitary carcinomas resistant to multimodality therapy. Evidence suggests that low O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression correlates with response to temozolomide chemotherapy. Herein, we aimed to study MGMT immunoexpression in a spectrum of pituitary tumors, indolent, aggressive and malignant. A literature review of the use of temozolomide in pituitary tumors was also performed. Immunohistochemistry for MGMT was performed on 60 pituitary tumors identified in the Mayo Clinic Tissue Registry and the consultation files of one of us (BWS). The group included 30 pituitary carcinomas (15 ACTH, 10 PRL, 1 FSH/LH, 1 TSH, 1 silent subtype 3 and 2 null cell). Tissue from recurrences was available in 17 cases. In addition, 30 functionally different pituitary adenomas were studied, including 15 invasive and 15 non-invasive adenomas. Overall, 32 cases of pituitary tumors (54%) demonstrated low MGMT immunoexpression. This included 17 of 30 (57%) carcinomas, 9 of 15 (60%) invasive adenomas, and 6 of 15 cases (40%) of non-invasive pituitary adenomas. There was no significant change in MGMT immunoexpression between primary and recurrent tumors. Prolactin-producing carcinomas had the highest proportion of tumors (80%) with low expression. A significant proportion of pituitary adenomas and carcinomas demonstrate low MGMT immunoexpression. In an effort to anticipate the likelihood of a temozolomide response, all cases of aggressive pituitary tumors should be assessed for MGMT expression. PMID- 20740318 TI - Should indications for skin-reducing mastectomy be expanded? PMID- 20740316 TI - Current quality of life and its determinants among opiate-dependent individuals five years after starting methadone treatment. AB - PURPOSE: This study explores the current QoL of opiate-dependent individuals who started outpatient methadone treatment at least 5 years ago and assesses the influence of demographic, psychosocial, drug and health-related variables on individuals' QoL. METHODS: Participants (n = 159) were interviewed about their current QoL, psychological distress and severity of drug-related problems, using the Lancashire Quality of Life Profile, the Brief Symptom Inventory and the Addiction Severity Index. Potential determinants of QoL were assessed in a multiple linear regression analysis. RESULTS: Five years after the start of methadone treatment, opiate-dependent individuals report low QoL scores on various domains. No association was found between drug-related variables and QoL, but a significant negative impact of psychological distress was identified. Severity of psychological distress, taking medication for psychological problems and the inability to change one's living situation were associated with lower QoL. Having at least one good friend and a structured daily activity had a significant, positive impact on QoL. CONCLUSIONS: Opiate-dependent individuals' QoL is mainly determined by their psychological well-being and a number of psychosocial variables. These findings highlight the importance of a holistic approach to treatment and support in methadone maintenance treatment, which goes beyond fixing the negative physical consequences of opiate dependence. PMID- 20740319 TI - Hepatic intra-arterial injection of drug-eluting bead, irinotecan (DEBIRI) in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study. AB - INTRODUCTION: Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy. METHODS: This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival. RESULTS: Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1 5), median treatment dose was 100 mg (range 100-200 mg), with total hepatic treatment of 200 mg (range 200-650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1-3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months. CONCLUSIONS: Hepatic arterial drug eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver. PMID- 20740320 TI - Incidental thyroid carcinoma by FDG-PET/CT: a study of clinicopathological characteristics. AB - BACKGROUND: The rising incidence of incidental thyroid carcinoma (ITC) detected during fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scanning poses a challenge to clinicians. The present study aims to critically evaluate the clinicopathological characteristics of ITC detected by FDG-PET/CT. METHODS: Among the 557 patients managed at our institution, 40 (7.2%) patients were identified as having ITC. Of these, 22 patients had their tumor detected by FDG-PET/CT (PET group) and 11 by ultrasonography (USG group). Additional bedside ultrasonography +/- fine-needle aspiration (FNA) was done in all patients at their clinic visit. The clinicopathological characteristics were compared between the PET and USG groups. RESULTS: The PET group had significantly more patients with history of nonthyroidal malignancy (P < 0.001). Papillary carcinoma was the most common histological type in both groups. Despite having similar histological and prognostic features including tumor size, tumor multifocality, capsular invasion, extrathyroidal extension, and lymph node metastases, tumor bilaterality (or presence of contralateral tumor focus) was significantly more frequent in the PET than the USG group (P = 0.04). The tumors were also more advanced by the tumor node-metastasis (TNM) staging system in the PET group (P = 0.021). None of the contralateral tumor foci were evident preoperatively. One patient in the USG group developed metastatic thyroid carcinoma in neck lymph nodes 28 months after thyroid resection. CONCLUSION: ITC by FDG-PET/CT had higher incidence of tumor bilaterality than those detected by ultrasonography. Total thyroidectomy should be considered for ITC detected by FDG-PET/CT even for tumor size <10 mm. PMID- 20740321 TI - Long-term surgical cure of severe obstructive sleep apnea in an adult patient with craniofacial dysostosis (Crouzon's syndrome): a case report and literature review. PMID- 20740322 TI - Update in perioperative medicine. PMID- 20740323 TI - Presenteeism: are we hurting the patients we are trying to help? PMID- 20740325 TI - Selenomethionine: an effective selenium source for sow to improve Se distribution, antioxidant status, and growth performance of pig offspring. AB - The present study was to investigate the efficiency of maternal selenomethionine intake on growth performance, Se distribution, and antioxidant status of pig offspring by comparing with sodium selenite. A total of 12 sows (Landrace * Yorkshire) with same pregnancy were randomly divided into two groups; each group was replicated six times. These two groups received the same basal gestation and lactation diets containing 0.04 mg Se/kg, supplemented with 0.3 mg Se/kg sodium selenite and selenomethionine (i.e., seneno-DL: -methylseleno), respectively. The feeding trial lasted for 60 days, with 32 and 28 days for gestation and lactation period, respectively. Compared with sodium selenite, maternal selenomethionine intake significantly (p < 0.05) increased the daily weight gain of piglet from birth to weaning. The Se concentration in the colostrum and milk and tissue Se content of piglets were significantly higher (p < 0.05) in the selenomethionine treated group. The antioxidant status was greatly improved in piglets of selenomethionine-treated group and was illuminated by the increased total antioxidant capability, glutathione peroxidase, superoxide dismutase, and glutathione, and decreased the malondialdehyde level in the organs of piglets. The increased (p < 0.05) triiodothyronine (T(3)) and decreased (p < 0.05) thyroxine (T(4)) concentration indicated the improved protein synthesis and energy production in the selenomethionine-treated group. The increased (p < 0.05) pancreatic digestive enzymes of protease, amylase, and lipase activities indicated that maternal selenomethionine intake may have a positive effect on the degradation and absorption of nutrients in its piglets. In summary, we concluded that maternal selenomethionine intake increased Se deposition, antioxidant status, and nutrient use efficiency, thus providing an effective way to improve the growth performance of piglets from birth to weaning. PMID- 20740324 TI - Medical professionalism: conflicting values for tomorrow's doctors. AB - BACKGROUND: New values and practices associated with medical professionalism have created an increased interest in the concept. In the United Kingdom, it is a current concern in medical education and in the development of doctor appraisal and revalidation. OBJECTIVE: To investigate how final year medical students experience and interpret new values of professionalism as they emerge in relation to confronting dying patients and as they potentially conflict with older values that emerge through hidden dimensions of the curriculum. METHODS: Qualitative study using interpretative discourse analysis of anonymized student reflective portfolios. One hundred twenty-three final year undergraduate medical students (64 male and 59 female) from the University of Cambridge School of Clinical Medicine supplied 116 portfolios from general practice and 118 from hospital settings about patients receiving palliative or end of life care. RESULTS: Professional values were prevalent in all the portfolios. Students emphasised patient-centered, holistic care, synonymous with a more contemporary idea of professionalism, in conjunction with values associated with the 'old' model of professionalism that had not be directly taught to them. Integrating 'new' professional values was at times problematic. Three main areas of potential conflict were identified: ethical considerations, doctor-patient interaction and subjective boundaries. Students explicitly and implicitly discussed several tensions and described strategies to resolve them. CONCLUSIONS: The conflicts outlined arise from the mix of values associated with different models of professionalism. Analysis indicates that 'new' models are not simply replacing existing elements. Whilst this analysis is of accounts from students within one UK medical school, the experience of conflict between different notions of professionalism and the three broad domains in which this conflict arises are relevant in other areas of medicine and in different national contexts. PMID- 20740326 TI - Adhesion pattern and prognosis studies of T4N0M0 colorectal cancer following en bloc multivisceral resection: evaluation of T4 subclassification. AB - In current TNM stage system, T4 lesions represent a complex group and should be considered to further optimize the classification. This study evaluates the significance of adhesion pattern in T4 subclassification based on prognostic analysis of T4N0M0 colorectal cancer following en bloc multivisceral resection (MVR). Prospectively collected data (1992-2004) were analyzed for 278 patients with stage T4N0M0 lesions following MVR for colorectal cancer. Patients were divided into inflammatory adhesion (IA) and malignant invasion (MI) groups based on adhesion to adjacent organs. Survival was evaluated by Kaplan-Meier and Cox proportional hazards regression analyses. MI was detected in 249 of 460 (54.1%) resected organs and in 159 of 287 (55.40%) patients undergoing MVR. Compared with IA group, patients in MI group showed no significant difference in clinicopathological data except tumor differentiation (P = 0.0376). Cox proportional hazards regression showed that MI was independently associated with overall survival among both colon (HR = 2.028; P = 0.0001) and rectal (HR = 0.451; P = 0.0002) cancer patients. Kaplan-Meier analysis showed that MI patients had a significantly higher MVR compared with IA patients (colon cancer: P = 0.0018; rectal cancer: P = 0.0116). In conclusion, MI was validated as an adverse prognostic factor for stage T4N0M0 colorectal cancer following MVR suggesting that it may be classified as a T4-subgroup in order to reinforce practice guidelines. PMID- 20740327 TI - Locally-administered intrathecal thrombolytics following aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. AB - BACKGROUND: The volume and clearance rate of blood in the basal cisterns and ventricles are important predictors of complications following aneurysmal subarachnoid hemorrhage (SAH). Thus, there is a strong rationale for interventions aimed at accelerating the clearance of blood. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane databases, references of review articles and gray literature sources to identify randomized controlled trials (RCTs) assessing the efficacy of locally-administered, intrathecal thrombolytics in patients with SAH. Primary outcomes included the occurrence of poor neurologic recovery and delayed neurologic deficits (DNDs). Secondary outcomes included angiographic vasospasm, chronic hydrocephalus and treatment-related complications. Data were extracted and appraised independently and in duplicate, using standardized forms. Fixed or random effects models, as appropriate based on the degree of study heterogeneity were applied to calculate summary measures. RESULTS: Five RCTs, enrolling 465 patients, met eligibility criteria. The methodology, results and risk of bias varied considerably across individual studies. Overall, use of intrathecal thrombolytics was associated with significant reductions in the development of poor outcomes (OR 0.52, 0.34-0.78, P < 0.01), DNDs (OR 0.54, 0.34-0.87, P = 0.01), angiographic vasospasm (OR 0.32, 0.15-0.70, P < 0.01) and chronic hydrocephalus (OR 0.33, 0.15-0.74, P < 0.01), without any increment in hemorrhagic or infectious complications. These findings were dampened by the exclusion of a study which concomitantly administered intrathecal vasodilators and thrombolytics. CONCLUSIONS: Current data suggests that intrathecal thrombolytics improve outcomes following SAH. However, there are important limitations to existing RCTs, with considerable risk of bias. Further standardization of techniques and evaluation in larger, more rigorous RCTs is required. PMID- 20740328 TI - An unusual presentation of subfrontal meningioma: a case report and literature review for Foster Kennedy syndrome. PMID- 20740329 TI - Pharmacomodulation of high-density lipoprotein metabolism as a therapeutic intervention for atherosclerotic disease. AB - The high-density lipoproteins (HDLs) are produced by the liver and small intestine as well as on the surface of lipid-enriched macrophages in the subendothelial space of arterial walls. Unlike the apo B100-containing lipoproteins, the HDLs are uniquely antiatherogenic. Based on prospective observational studies performed throughout the world, there is a consistent inverse relationship between serum levels of HDLs and risk for cardiovascular events: low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with increased risk, whereas high levels are usually associated with reduced risk for myocardial infarction, ischemic stroke, and cardiovascular mortality. Post hoc analyses of a number of studies using statins and fibrates have shown that raising serum HDL-C correlates with a reduction in risk for cardiovascular morbidity and mortality. Given these observations, enormous resources are being committed to the development of novel means by which to pharmacologically increase rates of HDL biosynthesis, modulate the functionality of HDL, and to promote reverse cholesterol transport with intravenous infusions of HDL particles. PMID- 20740330 TI - The management of pyothorax-associated lymphoma using 18F-FDG PET/CT. AB - OBJECTIVE: Pyothorax-associated lymphoma (PAL) is a rare form of lymphoma and its management on (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined computed tomography (CT) has not been well reported. The purpose of this study was to evaluate the usefulness of FDG PET/CT in patients with PAL. MATERIALS AND METHODS: Twenty-four PET/CT images in seven patients (5 men and 2 women) with PAL were studied retrospectively. Five of the 24 PET/CT scans were done for diagnosis and staging, 6 for restaging, 3 for follow-up, and 10 to evaluate the treatment response. PET/CT scan interpretations were performed visually and using the maximum standardized uptake values (SUVmax). Additionally, the efficacy of the enhanced CT findings in pre- and post-treatments was described. RESULTS: Six of the 7 patients with PAL received radiotherapy, and the efficacy of treatment was observed in their lesions. The percentage decrease of SUVmax in PAL was useful in providing complementary information. Enhanced CT findings showed decreasing enhancement of PAL after treatment; however, in five cases, residual masses were confirmed after treatment. CONCLUSION: FDG PET/CT may be an ideal modality for reducing the false-positive interpretation of residual masses occurring after treatment for PAL. The SUVmax provides complementary information for the management of PAL. PMID- 20740331 TI - Production of monoclonal antibodies to P-glycoprotein: its application in detection of soluble and surface P-glycoprotein of leukemia patients. AB - Multidrug resistance (MDR) in leukemia is commonly associated with the expression of a transmembrane protein, P-glycoprotein (P-gp). In this study, two monoclonal antibodies (mAbs) specific for the extracellular domain of P-gp were generated. By employing the generated mAbs, a two-color lysed whole blood flow cytometric method for surface P-gp and an efficient sandwich ELISA for soluble P-gp determinations were established. By using the established methods, surface and soluble P-gp were detected in several leukemia patients. The presence of soluble P-gp could be used to identify the P-gp surface expression patients. Detection of soluble P-gp reported provides a new basis that may lead to a better understanding of the MDR mechanism in leukemia. PMID- 20740332 TI - Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium. AB - Levothyroxine is a narrow therapeutic index, and to avoid adverse effect associated with under or excessive dosage, the dose response is carefully titrated. The tablets are marketed with a score providing an option to split. However, there are no systematic studies evaluating the effect of splitting on dose accuracy, and current study was undertaken to evaluate effects of splitting and potential causes for uniformity failures by measuring assay and content uniformity in whole and split tablets. Stability was evaluated by assaying drug for a period of 8 weeks. Effect of formulation factors on splittability was evaluated by a systematic investigation of formulation factors by preparing levothyroxine tablets in house by varying the type of excipients (binder, diluent, disintegrant, glidant) or by varying the processing factors (granulating liquid, mixing type, compression pressure). The tablets were analyzed using novel analytical tool such as near infrared chemical imaging to visualize the distribution of levothyroxine. Assay was not significantly different for whole versus split tablets irrespective of method of splitting (hand or splitter), and splitting also had no measurable impact on the stability. Split tablets either by hand or splitter showed higher rate of content uniformity failures as compared to whole tablets. Tablet splitter produced more fragmentation and, hence, more content uniformity and friability failures. Chemical imaging data revealed that the distribution of levothyroxine was heterogeneous and was dependent on type of binder and the process used in the manufacture of tablets. Splitting such tablets could prove detrimental if sub- or super-potency becomes an issue. PMID- 20740333 TI - Preparation and in vitro evaluation of ethosomal total alkaloids of Sophora alopecuroides loaded by a transmembrane pH-gradient method. AB - A novel transmembrane pH gradient active loading method to prepare alkaloids binary ethosomes was developed in this work. Using this novel method, binary ethosomes containing total alkaloids extracted from Sophora alopecuroides (TASA) were prepared successfully at the temperature below the phase transition temperature (Tc) of the phosphatidyl choline (PC). Several factors affecting this method were investigated. The qualities of the TASA binary ethosomes were characterized by the shape, particle size, and encapsulation efficiency (EE). The percutaneous absorption study of TASA binary ethosomes was performed using confocal laser scanning microscopy and Franz diffusion cells. The results showed that more than 90% sophoridine, 47% matrine, 35% sophocarpine, and 32% lemannine in TASA were entrapped within 1 h at 40 degrees C, with an efficiency improvement of 8.87, 8.10, 7.63, and 7.78-fold than those observed in passive loading method. Transdermal experiments showed that the penetration depth and fluorescence intensity of Rhodamine B from binary ethosome prepared by pH gradient active loading method were much greater than that from binary ethosome prepared by passive loading method or hydroalcoholic solution. These results suggested transmembrane pH gradient active loading method may be an effective method to prepare alkaloids ethosomal systems at the temperatures below the Tc of PC. PMID- 20740334 TI - Factors affecting the chemical durability of glass used in the pharmaceutical industry. AB - Delamination, or the generation of glass flakes in vials used to contain parenteral drug products, continues to be a persistent problem in the pharmaceutical industry. To understand all of the factors that might contribute to delamination, a statistical design of experiments was implemented to describe this loss of chemical integrity for glass vials. Phase I of this study focused on the effects of thermal exposure (prior to product filling) on the surface chemistry of glass vials. Even though such temperatures are below the glass transition temperature for the glass, and parenteral compounds are injected directly into the body, data must be collected to show that the glass was not phase separating. Phase II of these studies examined the combined effects of thermal exposure, glass chemistry, and exposure to pharmaceutically relevant molecules on glass delamination. A variety of tools was used to examine the glass and the solution contained in the vial including: scanning electron microscopy and dynamic secondary ion mass spectroscopy for the glass; and visual examination, pH measurements, laser particle counting, and inductively coupled plasma-optical emission spectrometry for the analysis of the solution. The combined results of phase I and II showed depyrogenation does not play a significant role in delamination. Terminal sterilization, glass chemistry, and solution chemistry are the key factors in the generation of glass flakes. Dissolution of silica may be an effective indicator that delamination will occur with a given liquid stored in glass. Finally, delamination should not be defined by the appearance of visible glass particulates. There is a mechanical component in the delamination process whereby the flakes must break away from the interior vial surface. Delamination should be defined by the observation of flakes on the interior surface of the vial, which can be detected by several other analytical techniques. PMID- 20740335 TI - Patellar fractures. PMID- 20740337 TI - Solid-state SPECT technology: fast and furious. PMID- 20740338 TI - Synchronous liver metastasis in colorectal cancer in Sri Lanka. AB - OBJECTIVE: To assess the incidence of synchronous colorectal liver metastasis in patients referred to a tertiary referral center in Sri Lanka and to evaluate the differences in the clinicopathological features of patients with and without synchronous metastasis. METHODS: Records of 438 patients were retrospectively analyzed. Patients were classified into metastatic group (n = 34, 8%) and non metastastatic group (n = 404, 92%). In the two groups macroscopic features compared were: tumor size (2 cm, 2-5 cm, and >5 cm), site of primary tumor and side of liver involved. Carcinoembryonic antigen (CEA) levels were recorded. At microscopy, tumor differentiation, invasion and nodal status were evaluated. RESULTS: The rectum was the primary site of the tumor in a majority (60%) of patients. There was no difference in the distribution of the primary site and size of the tumor, pathological stage, lymphatic infiltration and the degree of tumor differentiation in two groups (p > 0.05). Patients with metastasis had higher levels of CEA, higher frequency of vascular infiltration and N3 nodes involved (p < 0.05). CONCLUSION: The incidence of synchronous colorectal liver metastasis seems to be lower in our patients. Association of higher CEA level, advanced nodal stage and presence of vascular invasion needs to be further assessed with risk of developing metachronous liver metastasis. PMID- 20740339 TI - Does the handling time of unrefrigerated human fecal specimens impact the detection of Clostridium difficile toxins in a hospital setting? AB - BACKGROUND: The stability of Clostridium difficile toxins is an important factor in determining the accuracy of the enzyme immunoassay (EIA). The Centers for Disease Control has stated that C. difficile toxins may become undetectable in unrefrigerated stool specimens within 2 h after collection. PURPOSE: The purpose of our study was to determine how the unrefrigerated handling time of human fecal specimens affects the results of C. difficile infection (CDI) testing. METHODS: A retrospective review of CDI testing with PremierTM Toxins A and B kit was conducted in northern New Jersey, USA. Stool collection times and receiving times were recorded for each specimen. The unrefrigerated handling time was calculated for each. RESULTS: A total of 1126 fecal specimens were submitted. We excluded 72 fecal specimens due to incomplete documentation. We included 1054 fecal specimens collected from 636 hospitalized patients. A total of 132 out of 1054 specimens (12.5%) tested positive for C. difficile toxins. Nine hundred and fifty-four specimens were unrefrigerated for 13 h or less, of which 127 (13.3%) tested positive. Five (5%) of the 100 specimens that were unrefrigerated for more than 13 h tested positive (p = 0.02). CONCLUSION: C. difficile toxins can still be detected up to 13 h after collection in unrefrigerated human fecal specimens. However, fecal specimens should be processed according to the current recommendations to ensure the reliability of EIA testing until the results of our study are confirmed with prospective studies. PMID- 20740340 TI - Quality of life assessment of patients with chronic liver disease in eastern India using a Bengali translation chronic liver disease questionnaire. AB - AIMS: The aim of this study was to translate and validate chronic liver disease questionnaire (CLDQ) into Bengali using a standard protocol and use it to assess the impact of socioeconomic factors, etiology, disease severity and complications on the quality of life of patients. METHODS: Formal translation of CLDQ to Bengali was done. Cronbach's alpha and test-retest was performed for reliability analysis. Patients with clinically stable chronic liver disease (CLD) without significant associated co-morbid states were administered Bengali CLDQ in the Liver Clinic. The clinical, biochemical and disease parameters were recorded for analysis. RESULTS: Bengali CLDQ was administered to 100 patients with CLD. Cronbach's alpha of overall scores was 0.90 and test-retest correlation coefficient of average CLDQ was 0.86 (P<0.001). Patients with history of decompensation (96.51 vs. 109.61; P=0.039) and Child's C status (92.24 vs. 105.71; P=0.028) had significantly lower CLDQ scores. CLDQ scores showed a moderate inverse correlation with Child's status (r= -0.35) and a poor correlation with MELD score (r= -0.09). CONCLUSION: Bengali translation of CLDQ was found to be reliable. History of decompensation, Child's C status was associated with worse CLDQ scores. Child's status may have some role in predicting quality of life of patients with CLD. MELD score had poor predictability of quality of life. PMID- 20740341 TI - Immunosuppression following surgical and traumatic injury. AB - Severe sepsis and organ failure are still the major causes of postoperative morbidity and mortality after major hepatobiliary pancreatic surgery. Despite recent progress in understanding the immune conditions of abdominal sepsis, the postoperative incidence of septic complications after major visceral surgery remains high. This review focuses on the clinical and immunological parameters that determine the risk of the development and lethal outcome of postoperative septic complication following major surgery and trauma. A review of the literature indicates that surgical and traumatic injury profoundly affects the innate and adaptive immune responses, and that a marked suppression in cell mediated immunity following an excessive inflammatory response appears to be responsible for the increased susceptibility to subsequent sepsis. The innate and adaptive immune responses are initiated and modulated by pathogen-associated molecular-pattern molecules and by damage-associated molecular-pattern molecules through the pattern-recognition receptors. Suppression of cell-mediated immunity may be caused by multifaceted cytokine/inhibitor profiles in the circulation and other compartments of the host, excessive activation and dysregulated recruitment of polymorphonuclear neutrophils, induction of alternatively activated or regulatory macrophages that have anti-inflammatory properties, a shift in the T helper (Th)1/Th2 balance toward Th2, appearance of regulatory T cells, which are potent suppressors of the innate and adaptive immune system, and lymphocyte apoptosis in patients with sepsis. Recent basic and clinical studies have elucidated the functional effects of surgical and traumatic injury on the immune system. The research studies of interest may in future aid in the selection of appropriate therapeutic protocols. PMID- 20740342 TI - Recent advances in histone deacetylase targeted cancer therapy. AB - Epigenetic regulators such as histone acetyltransferases (HATs) and histone deacetylases (HDACs) are known to play an important role in gene expression. Of these enzymes, HDACs have been shown to be commonly associated with many types of cancers and to affect cancer development. Consequently, HDACs have been considered as promising targets for cancer therapy. In addition, the inhibition of HDACs by histone deacetylase inhibitors (HDACIs) shifts the balance between the deacetylating activity of HDACs and the acetylating activity of HATs in the regulation of gene expression. Therefore, HDACIs are an exciting new addition in cancer therapies. Numerous HDACIs have been identified and some have recently been used in clinical trials for cancer treatment, although the mechanisms underlying the anticancer effects of HDACIs remain unclear. In this review, we examine the most recent developments in HDACIs and various aspects of HDAC targeted cancer treatment. PMID- 20740343 TI - Malignant potential of intraductal papillary mucinous neoplasms of the pancreas. AB - An intraductal papillary mucinous neoplasm (IPMN) is now a well-recognized disease entity. In general, the prognosis of IPMN is much more favorable than that of pancreatic ductal adenocarcinoma (PDAC). However, IPMN has a broad biological spectrum and it sometimes progresses, slowly showing neoplastic transformations. International consensus guidelines have been recently proposed for the management of IPMN. While they significantly contribute to appropriate management of IPMN, various issues including the natural history and malignant potential of IPMN are not fully elucidated. This review focuses on the malignant potential, including the postoperative recurrence of IPMN, coincidence of IPMN with PDAC, and extrapancreatic malignancy that may affect the long-term survival of the patients rather than IPMN itself. PMID- 20740344 TI - Radio-guided parathyroidectomy in patients with primary hyperparathyroidism and concomitant multinodular goiter. AB - PURPOSE: We investigated possible instances where the standard bilateral neck exploration for parathyroid adenoma may be omitted in primary hyperparathyroidism (pHPT) if preoperative diagnostics for the location have been performed. METHODS: Ten patients underwent surgical treatment for pHPT and multinodular goiter between October 2006 and October 2008. Identification of the parathyroid adenomas' location with cervical ultrasound and (99m)technetium-sestamibi nuclear scanning ((99m)Tc-MIBI) was not possible in any of these patients. An extirpation of the parathyroid adenomas was performed with intraoperative use of the (99m)Tc MIBI-guided probe technique. The median follow-up time was 17.5 months (range 2 30). RESULTS: Ten patients underwent an elective operation for solitary (n = 9) or dual (n = 1) parathyroid adenomas and concomitant thyroid disease. Definitive proof of the parathyroid adenomas was achieved in all of the patients without further neck exploration. The adenomas were 1.3 cm (range 1-2) in diameter. Calcium and parathyroid hormonal levels were reduced on the first postoperative day (P = 0.003). There were no postoperative complications. All patients were free from recurrence. CONCLUSION: The intraoperative probe technique is feasible in patients with pHPT and limited diagnostics for the location of parathyroid adenomas with concomitant goiter. This diagnostic technique identified the parathyroid adenoma in all cases, and thus rendered a bilateral neck exploration obsolete. PMID- 20740346 TI - Perforation of peptic ulcer following abrupt cessation of long-term opiate use. AB - PURPOSE: Unaided and abrupt cessation of opiate use without drug substitution and step-down, referred to as "cold turkey," is a common and difficult process for substance users, and is associated with several withdrawal symptoms and complications. This report presents a preliminary series of patients treated at an urban public hospital with acute perforation of peptic ulcers following abrupt cessation of long-term opiate use, a phenomenon that has not been previously described in the literature. METHODS: Thirty-five patients with acute gastroduodenal perforation and a history of opiate addiction with a recent and abrupt cessation of opiate use were admitted between February 2004 and October 2008. This study evaluated the demographics, antecedent drug use, substance use characteristics, previous medical or surgical treatment of peptic ulcer disease, and surgical findings. RESULTS: The mean age was 32.3 years (range, 21-41 years) and the patients were overwhelmingly male (94%). The most frequent agent in single opiate users was opium (62.9%) followed by heroin (22.9%). The time interval between opiate cessation and perforation onset was 2-65 days (mean, 6.1 days). All patients underwent an immediate exploratory laparotomy, and the majority of perforations were found to be in the postpyloric area (94%) with mean size of 4.3 x 5.1 mm. Two patients (6%) had perforations in the lesser curvature of the stomach. CONCLUSION: All of the perforations occurred following sudden self-cessation without step-down or classic maintenance therapy, and this may prove the importance of supervised medical detoxification with special attention to gastroprotective agents such as antacid drugs. PMID- 20740347 TI - Hand-assisted laparoscopic restorative proctocolectomy for ulcerative colitis: the optimization of instrumentation toward standardization. AB - PURPOSE: Hand-assisted laparoscopic surgery (HALS) is increasingly used for complex and extensive colorectal diseases, such as a restorative proctocolectomy (RP) for ulcerative colitis (UC). However, the optimal instrumentation for this procedure has yet to be determined. This study reviewed the optimization of the instrumentation employed for HALS-RP and evaluated their impact in standardizing HALS-RP for UC. METHODS: Sixty-six cases with HALS-RP for UC were reviewed. Cases were divided into subgroups according to (1) hand-access devices and (2) vascular control devices, and their intraoperative/postoperative outcomes were compared. RESULTS: All groups had comparable backgrounds. (1) The hand-access devices employed were first LapDisc (n = 14), then HandPort (n = 25), and recently GelPort (n = 27). The surgical time was shortest in GelPort group in comparison to the other two groups. (2) Laparosonic coagulating shears (LCS) with clips were used for vascular control in the first 29 patients, and the bipolar vessel sealing system (LigaSure) was employed in the 37 subsequent patients. The surgical time was shorter and blood loss was less in the LigaSure group. No differences were seen in postoperative outcomes, including the complication rate and length of hospital stay. CONCLUSION: The new instrumentation contributed to improved outcome of HALS-RP. HALS-RP can become a more comfortable and standardized procedure for UC with the adoption of evolving technologies. PMID- 20740345 TI - Prognostic importance of neuroendocrine differentiation in Japanese breast cancer patients. AB - PURPOSE: To evaluate the frequency and prognostic importance of neuroendocrine differentiation (NED) in Japanese breast cancer patients. METHODS: We used standard immunohistochemical techniques to examine 50 patients who underwent resection of breast cancer between 1988 and 1993 at the Department of Surgery II, Nagoya University Hospital, for NED, defined as positive reactivity for four markers: neuron-specific enolase (NSE), synaptophysin, CD57, and chromogranin A (CGA). Neuroendocrine differentiation was defined by the presence of at least one marker including CGA, CD57, and synaptophysin, or at least two markers when one was positive for NSE. RESULTS: Neuroendocrine differentiation was found in 13 (26%) of the 50 patients examined. There were no significant differences in the distribution of patients with positive or negative NED in terms of age, menopausal status, tumor size, lymph node metastasis, histological grade, ER, PgR, and HER2. We calculated the cumulative survival rates of patient groups according to NED status, and found no significant difference in overall or disease-free survival between patients with and those without NED. CONCLUSION: Neuroendocrine differentiation was identified in a subset (26%) of Japanese breast cancer patients, but this appeared to have no relationship with established prognostic factors or patient outcome. PMID- 20740348 TI - Mucin-producing intrahepatic biliary papillomatosis. AB - PURPOSE: Mucin-producing intrahepatic biliary papillomatosis (MPIBP) is an uncommon tumor. The purpose of this study was to evaluate the clinical, radiological, and histopathological characteristics of MPIBP, and its prognosis. METHODS: A retrospective analysis was conducted of 11 patients who underwent surgery for MPIBP. The clinical features and radiological, pathological, and operative findings were reviewed, and the survival rates were determined. RESULTS: Repeated episodes of fever and epigastric pain with or without jaundice were the common clinical manifestations. Radiologically, all patients showed diffuse bile duct dilatation with cystic change in intrahepatic bile duct. All patients underwent a hepatic resection with or without an extrahepatic bile duct resection. No in-hospital mortality occurred. All patients survived without any signs of recurrence (median 12 +/- 7 months); three patients, including two patients who underwent a palliative resection, had an attack of cholangitis, which was effectively treated with antibiotics. CONCLUSIONS: A diagnosis of MPIBP is usually made in patients with biliary dilatation following a radiologic study. Magnetic resonance cholangiopancreatography is more valuable than other modalities in diagnosis. Mucin-producing intrahepatic biliary papillomatosis is a premalignant disease with high malignant potential. The prognosis of MPIBP is excellent if an aggressive resection is performed. A combination of cholangioscopy and frozen sections during the operation is beneficial for a radical successful surgical resection. PMID- 20740349 TI - Suppressive effect of bevacizumab on peritoneal dissemination from gastric cancer in a peritoneal metastasis model. AB - PURPOSE: Vascular endothelial growth factor (VEGF) has been reported to enhance vascular permeability and angiogenesis in the abdominal wall, thereby contributing to peritoneal dissemination with malignant ascites. We conducted this experimental study to find out if bevacizumab, a humanized monoclonal antibody against VEGF, had a suppressive effect on peritoneal dissemination from gastric cancer, in an experimental nude mouse model of peritoneal metastasis. METHODS: Each mouse was treated with a single intraperitoneal (i.p.) injection of bevacizumab. Five mice were killed, and we measured their body weight, the mean number of tumor nodules, and the volume of ascites. We also extracted retroperitoneal tissues for histological examination, to count the frequency of mitosis, and to calculate the mitotic index. Another five mice were monitored until death, and their mean survival duration was calculated. RESULTS: The volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group (P = 0.042 and P < 0.01, respectively). The survival curve of the therapy group was significantly higher than that of the nontherapy group (P = 0.005). CONCLUSION: Bevacizumab may suppress peritoneal dissemination from gastric cancer. PMID- 20740350 TI - Protective effect of carnosol on lung injury induced by intestinal ischemia/reperfusion. AB - PURPOSE: Carnosol is a phenolic diterpene that has potent antioxidant and anti inflammatory activities. The purpose of this study was to investigate the preconditioning effects of carnosol on lung injury induced by intestinal ischemia/reperfusion (II/R). METHODS: Rats were divided into control, II/R, and carnosol groups. The II/R model was established by clamping the superior mesenteric artery for 1 h and reperfusion at 2, 4, and 6 h after ischemia. The carnosol group received 3 mg/kg carnosol intraperitoneally 1 h before the operation. The rats were then euthanized, and blood and lung specimens were obtained for analysis. RESULTS: The II/R induced lung injury, characterized by histological changes and significant increasing of bronchoalveolar lavage fluid protein. The activity of lung tissue superoxide was weakened, the tissue myeloperoxidase activity and serum interleukin-6 level increased significantly in II/R groups. A strong positive expression of lung intercellular adhesion molecule 1 (ICAM-1) and nuclear factor kappa B (NF-kappaB) were observed. Pretreatment with carnosol markedly reduced lung injury by increasing the tissue superoxide activity and decreasing the myeloperoxidase activity and interleukin-6 level, which was parallel to the decreased expression of ICAM-1 and NF-kappaB. CONCLUSION: Carnosol was able to ablate lung injury induced by II/R, partly attributed to the inhibition of NF-kappaB activation. PMID- 20740351 TI - Thrombosed abdominal aortic aneurysm associated with an extensively "shaggy" aorta repaired anatomically via a thoracoabdominal approach with supraceliac aortic clamping: report of a case. AB - A 76-year-old man with a history of multiple laparotomies and severe coronary artery disease was referred to our hospital after the sudden development of pain and numbness in the lower extremities. Computed tomography showed a thrombosed abdominal aortic aneurysm and diffuse aortic atherosclerosis; compatible with a "shaggy aorta." A good response to thrombolytic therapy permitted elective scheduling of abdominal aortic surgery after coronary artery bypass grafting. We operated via an extended left retroperitoneal approach through a thoracoabdominal incision. Epiaortic ultrasonography revealed that only the supraceliac aorta was free of mobile thrombi and had minimal plaque; we therefore placed a proximal aortic cross-clamp there. Anatomic aortic reconstruction was then performed successfully using an aorto-biiliac graft to restore adequate distal blood flow. There were no vital-organ ischemic complications, and the postoperative course was satisfactory. PMID- 20740352 TI - Cardiac lipoma originating from the left ventricular apex diagnosed using the magnetic resonance imaging fat suppression technique: report of a case. AB - A 70-year-old male patient had a tumor in the left ventricular apex that was detected by transthoracic echocardiography. He had no clinical manifestations. A diagnosis of benign lipoma was made using the noninvasive fat suppression technique of cardiac magnetic resonance imaging (MRI). Video-assisted surgery was performed to resect the tumor, and the histopathological examination confirmed the diagnosis of lipoma. A small part of the tumor was not resected. The postoperative course was uneventful. No signs of recurrence were detected on transthoracic echocardiography or MRI during a 22-month post surgical follow-up period. PMID- 20740353 TI - Gangrenous intrathoracic appendicitis, a rare cause of right-sided chest pain: report of a case. AB - Diaphragmatic hernias are becoming increasingly common due to radiofrequency ablation of malignant liver tumors. Most patients eventually present with symptoms caused by bowel obstruction. A 54-year-old woman with pleuritic pain and fever had a right-sided enterothorax probably caused by hemihepatectomy several years before. The patient was diagnosed with perforated gangrenous intrathoracic appendicitis during an emergency laparotomy for suspected incarceration of her diaphragmatic hernia. She was treated with an appendectomy and suturing of her right hemidiaphragm. An acquired diaphragmatic hernia should therefore be surgically repaired as soon as it is diagnosed in order to avoid complications. PMID- 20740354 TI - Successful left hemihepatectomy and perioperative management of a patient with biliary cystadenocarcinoma, complicated with MELAS syndrome: report of a case. AB - Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS) is a rare, fetal disease caused by a mutation in mitochondrial DNA that leads to impaired oxidative metabolism in skeletal muscle, the central nervous system, and liver function. This report presents the case of a 50-year-old woman with biliary cystadenocarcinoma complicated by MELAS who underwent a successful left hemihepatectomy. In this case, the diagnostic key for the malignant tumor was an (18)F-fluorodeoxyglucose positron emission tomography study, which was useful even in a patient with MELAS, which causes abnormal glucose metabolism. The perioperative management of such patients includes special precautions to prevent lactic acidosis and deterioration of the reserved liver function after a hepatectomy, since the mitochondrial function in MELAS patients is abnormal. The patient in this report has remained free of liver dysfunctions and cancer recurrence for 2 years following the hepatectomy. This is the first report of a successful major hepatectomy for a patient with MELAS. PMID- 20740355 TI - Solitary hepatic lymphangioma: report of a case. AB - A 52-year-old woman presented with upper abdominal pain. Abdominal ultrasonography showed a 4-cm well-defined mass containing solid and cystic components in segment IV of the liver, and contrast-enhanced T1-weighted magnetic resonance imaging revealed heterogeneous enhancement within the tumor, indicating a solid or fibrous component. There were no cystic lesions in any other organs. A partial hepatectomy was performed, based on a preoperative diagnosis of sclerosing hemangioma and biliary cystadenoma or cystadenocarcinoma. Pathologically, the tumor appeared to be a multilocular and cystic lesion lined by attenuated endothelial- like cells with no atypia. Immunohistochemistry demonstrated the endothelial-like cells to be positive for the lymphatic-specific markers D2-40, LYVE-1, and Prox-1, which proved helpful for confirming the diagnosis as solitary hepatic lymphangioma. This case is presented with details of the pathologic and radiologic findings, because solitary hepatic lymphangioma is an extremely rare tumor and no previous reports have provided details of the immunohistochemical characteristics. PMID- 20740356 TI - Modification of the surgical procedure to enable the complete resection of lung cancer with carcinomatous pleuritis. AB - Carcinomatous pleuritis, accompanied by pleural dissemination or malignant pleural effusion, is listed as one of the factors limiting adequate surgical treatment. It is relatively easy to peel the parietal pleura of the chest wall and mediastinum during a pleuropneumonectomy, but it is quite difficult to peel the parietal pleura of the diaphragm. A pleuropneumonectomy was conducted with the combined resection of the pericardium and all layers of the diaphragm without opening of the peritoneum through a posterolateral subcostal approach. This approach thus made it possible to perform a complete resection of the diaphragm relatively easily in a reliable manner, and also contributed to a more thorough resection of pleural dissemination without a second thoracotomy. PMID- 20740357 TI - Midline uterosacral plication anterior colporrhaphy combo (MUSPACC): preliminary surgical report. AB - INTRODUCTION AND HYPOTHESIS: the objective of this study is to examine the surgical safety and early efficacy of the midline uterosacral (ligament) plication anterior colporrhaphy (MUSPACC) procedure. METHODS: a retrospective review of the perioperative data of 41 women who had undergone an MUSPACC procedure without any other vaginal vault supportive procedure was performed. RESULTS: the MUSPACC procedure can be performed comfortably through a single midline anterior vaginal wall incision, providing concomitant levels 1 and 2 support at anterior colporrhaphy. The procedure is safe and relatively quick (median 23 min) with consistent access to the intermediate section of the uterosacral ligament. Blood loss is generally minimal to small. Dissection is relatively limited. The ureters (2 cm or more lateral) are not deemed to be at risk. Short-term anatomical results are promising. There was no significant change in vaginal length. CONCLUSIONS: the MUSPACC procedure is safe, relatively quick, and free of significant bleeding. It provides concomitant levels 1 and 2 vaginal support. PMID- 20740358 TI - Laparoscopic sacrocolpopexy: an observational study of functional and anatomical outcomes. AB - INTRODUCTION AND HYPOTHESIS: the aim of the study was to evaluate the clinical and functional outcomes of laparoscopic sacrocolpopexy, in particular its effect on female sexual function. METHODS: a retrospective observational study of women undergoing laparoscopic sacrocolpopexy between February 2005 and March 2009 was undertaken. Pelvic organ support was assessed objectively using the pelvic organ prolapse quantification scale (POP-Q). Functional outcomes were assessed using the International Consultation on Incontinence questionnaire for vaginal symptoms (ICIQ-VS), both preoperatively and at 6-36 months postoperatively. RESULTS: eighty-four women with a mean age of 65 years (range, 49-78 years) were studied. At follow-up in clinic, all women had good vault support (mean point C, -8.9; range, 10 to -8). Subjective improvements in prolapse symptoms and sexual well being were observed with significant reductions in the respective questionnaire scores. CONCLUSIONS: our results confirm previous findings that laparoscopic sacrocolpopexy is a safe and efficacious surgical treatment for post-hysterectomy vaginal vault prolapse. It provides excellent apical support and good functional outcome with overall improvement in sexual function. PMID- 20740359 TI - Laparoscopic sacrospinous ligament fixation for uterovaginal prolapse: experience with 93 cases. AB - INTRODUCTION AND HYPOTHESIS: the aim of this study was to investigate the technique, efficacy, and safety of laparoscopic sacrospinous ligament fixation (LSSLF) for patients with uterovaginal prolapse. METHODS: from May 2004 to December 2006, 93 patients underwent LSSLF at Southwest Hospital, Chongqing, China. All patients had either grade 3 or 4 uterovaginal prolapse. The surgical results and complications were evaluated. RESULTS: all patients had their surgery completed by LSSLF. The average time for LSSLF was 65 min. The average blood loss was 105 ml. Bladder was injured in four cases (4.3%). The mean follow-up was 18 onths. Of the 93 patients, 87 (93.5%) had been cured of their vault or uterovaginal prolapse. Minor postoperative complications were observed. CONCLUSIONS: LSSLF can be successfully completed in patients with uterovaginal prolapse. It is a safe and effective treatment method for patients with uterovaginal prolapse. A long-term follow-up is necessary to detect therapeutic effect and late complication. PMID- 20740360 TI - Stimulation of ENaC activity by rosiglitazone is PPARgamma-dependent and correlates with SGK1 expression increase. AB - Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARgamma) agonists used to treat type 2 diabetes. TZD treatment induces side effects such as peripheral fluid retention, often leading to discontinuation of therapy. Previous studies have shown that PPARgamma activation by TZD enhances the expression or function of the epithelial sodium channel (ENaC) through different mechanisms. However, the effect of TZDs on ENaC activity is not clearly understood. Here, we show that treating Xenopus laevis oocytes expressing ENaC and PPARgamma with the TZD rosiglitazone (RGZ) produced a twofold increase of amiloride-sensitive sodium current (Iam), as measured by two-electrode voltage clamp. RGZ-induced ENaC activation was PPARgamma-dependent since the PPARgamma antagonist GW9662 blocked the activation. The RGZ-induced Iam increase was not mediated through direct serum- and glucocorticoid-regulated kinase (SGK1) dependent phosphorylation of serine residue 594 on the human ENaC alpha-subunit but by the diminution of ENaC ubiquitination through the SGK1/Nedd4-2 pathway. In accordance, RGZ increased the activity of ENaC by enhancing its cell surface expression, most probably indirectly mediated through the increase of SGK1 expression. PMID- 20740361 TI - Sample size for prospective studies of hip joint space width narrowing in osteoarthritis by the use of radiographs. AB - OBJECTIVE: To determine the number of participants required in controlled clinical trials investigating the progression of osteoarthritis (OA) of the hip as evaluated by the joint space width (JSW) on radiographs and to evaluate the reproducibility of the JSW measurement methods. MATERIALS AND METHODS: Anteroposterior radiographs of hip were taken from 13 healthy volunteers and from 18 subjects with radiographic hip OA. The reproducibility of the JSW was determined from four segments using digital caliper measurements performed on film radiographs and using semiautomatic computerized image analysis of digitized images. Pearson correlation coefficient, coefficient of variability [CV (%)], and sample size values were calculated. RESULTS: It was found that 20 was a typical number of patients for a sufficiently powered study. The highest sample size was found in subjects with OA in the lateral segment. The reproducibility of the semiautomatic computerized method was not significantly better than the digital caliper method. CONCLUSION: The number of study subjects required to detect a significant joint space narrowing in follow-up studies is influenced by the baseline hip joint OA severity. The JSW measurements with computerized image analysis did not improve the reproducibility and thus performing JSW measurements with a digital caliper is acceptable. PMID- 20740363 TI - Neural coding of echo-envelope disparities in echolocating bats. AB - The effective use of echolocation requires not only measuring the delay between the emitted call and returning echo to estimate the distance of an ensonified object. To locate an object in azimuth and elevation, the bat's auditory system must analyze the returning echoes in terms of their binaural properties, i.e., the echoes' interaural intensity and time differences (IIDs and ITDs). The effectiveness of IIDs for echolocation is undisputed, but when bats ensonify complex objects, the temporal structure of echoes may facilitate the analysis of the echo envelope in terms of envelope ITDs. Using extracellular recordings from the auditory midbrain of the bat, Phyllostomus discolor, we found a population of neurons that are sensitive to envelope ITDs of echoes of their sonar calls. Moreover, the envelope-ITD sensitivity improved with increasing temporal fluctuations in the echo envelopes, a sonar parameter related to the spatial statistics of complex natural reflectors like vegetation. The data show that in bats envelope ITDs may be used not only to locate external, prey-generated rustling sounds but also in the context of echolocation. Specifically, the temporal fluctuations in the echo envelope, which are created when the sonar emission is reflected from a complex natural target, support ITD-mediated echolocation. PMID- 20740364 TI - Human papilloma virus persistence and neopterin, folate and homocysteine levels in cervical dysplasias. AB - OBJECTIVE: To investigate the relationship between human papilloma virus (HPV) infection persistence and serum folate, vitamin B12, homocysteine, neopterin levels in cervical dysplasia. STUDY DESIGN: Through the years 2007-2008, 122 women who have admitted to Gynecology Clinic were evaluated for cervical cytology, demographical characteristics, HPV infection, serum folate, vitamin B12, homocysteine, albumin, and neopterin levels. RESULTS: Considering all the cases, the highest percentage of the HPV-infected patients was in high-grade squamous intraepithelial lesion (HSIL) group (83%, n = 25). The serum folate levels in all patient groups [HSIL 10.0 +/- 0.4 ng/ml, low-grade squamous intraepithelial lesion (LSIL) 10.6 +/- 0.5 ng/ml, atypical squamous cells undetermined significance (ASCUS) 11.1 +/- 0.8 ng/ml] were lower than control group (11.9 +/- 0.5 ng/ml; p < 0.05). The vitamin B12 levels were not significantly altered in any of the patient groups. The serum homocysteine levels in all patient groups (HSIL 10.4 +/- 0.5 Umol/l, LSIL 10.1 +/- 0.5 Umol/l, ASCUS 10.5 +/- 0.7 Umol/l) were higher than the control group (7.9 +/- 0.5 Umol/l; p < 0.05). The neopterin levels of HSIL group (1.0 +/- 0.2 ng/ml) were lower than the control group (1.5 +/- 0.2 ng/ml; p < 0.05). The serum neopterin concentrations of HSIL with HPV group (0.6 +/- 0.1 ng/ml) were significantly lower than HSIL without HPV (2.4 +/- 0.9 ng/ml) and other study groups (p < 0.05). The serum homocysteine levels of HSIL HPV(+) group and LSIL HPV(+) were higher than control group (p < 0.05). The serum albumin levels of HSIL with HPV group are lower than control and other groups (p < 0.05). In all cervical dysplasia groups, folate levels in patients infected with HPV are lower than in HPV(-) patients (p < 0.05). CONCLUSIONS: Folic acid deficiency could be caused by insufficient cellular immunity. In case of folate deficiency, the predisposition of HPV infection persistency and progression of cervical dysplasia increase. The fact that neopterin is a strong cellular immunity marker and it was detected in patients with HPV persistence and cervical dysplasia in lower levels shows that these patients may have relatively insufficient immune system. In order for dysplasia progression to be prevented, folate fortification on diets may be advised to HPV-infected women. PMID- 20740365 TI - Quality of life and toxicity in breast cancer patients using adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), in comparison with FAC (doxorubicin, cyclophosphamide, 5-fluorouracil). AB - OBJECTIVES: The aim of this study was to compare two regimens of chemotherapy in patients with breast cancer, including FAC (doxorubicin, cyclophosphamide, and 5 fluorouracil) and TAC (docetaxel, doxorubicin and cyclophosphamide); and analyze the toxicity of these treatments and observe patient's health-related quality of life. METHODS: Health-related quality of life was assessed for up to 4 months (from the beginning to the end of chemotherapy cycles), using European organization and cancer treatment quality of life questionnaire (EORTC) QLQ-C30. A group of 100 patients, with node-positive breast cancer were studied in order to compare the toxicity of adjuvant therapy TAC with FAC and the subsequent effects on the patient's quality of life. RESULTS: After a 4-month follow-up of patients, our findings showed that despite having the same mean score of QOL at the start of adjuvant chemotherapy, the QOL in TAC arm was decreased more as a result of the higher range of toxicity in TAC regimen. CONCLUSION: In spite of increase in disease-free patients who received TAC regimen and increase their survival rate, there is significant toxicity and decrease in QOL in TAC protocol compare to FAC protocol. Using prophylactic granulocyte colony stimulating factor (G-CSF) along with increased education aimed at improving patient's knowledge and also the provision of a supportive group involving psychiatrics and patients that have successfully experienced the same treatment may be helpful. PMID- 20740366 TI - Clinical characteristics of inflammatory bowel disease associated with primary sclerosing cholangitis. AB - PURPOSE: Only a few studies have documented the characteristics of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC). We aimed to clarify the clinical and histopathological characteristics of IBD associated with PSC (PSC-IBD). METHODS: Twenty-nine patients with PSC and 60 patients with ulcerative colitis (UC) but without complicating PSC were enrolled in this study. First, the age and sex distribution, affected area, clinical course, number of recurrent attacks, and severity of UC were investigated. Then, mucosal specimens obtained from the right side (cecum and ascending colon), transverse colon, and the left side (descending colon, sigmoid colon, and rectum) during colonoscopy were studied for inflammatory cell infiltration, the presence of crypt abscesses, the degree of goblet cell disappearance, and edema. RESULTS: (1) The incidence of IBD in PSC patients was 68.9% (20/29). There were two peaks in the age distribution of PSC. Male PSC patients demonstrated a first peak and female patients a second peak. Male PSC-IBD patients were in their teens and 20s making the first peak. Female PSC-IBD patients were in their 50s and 60s making the second peak. The PSC-IBD patents were significantly younger than the patients without IBD (33.6 vs. 58.9 years, p < 0.001). (2) PSC-IBD showed a right-sided predominance colonoscopically. (3) None of the patients had a severe clinical course, and a half of them were asymptomatic. (4) Histopathological examination demonstrated severe inflammatory cell infiltration in the cecum and ascending colon, whereas the degree was mild in the rectum/descending colon. CONCLUSIONS: PSC-IBD shows characteristic clinical, colonoscopic, and histopathological findings. PMID- 20740368 TI - Intracranial spontaneous hypotension associated with CSF cervical leakage successfully treated by lumbar epidural blood patch. PMID- 20740367 TI - Protease-activated receptor-2 regulates cyclooxygenase-2 expression in human bile duct cancer via the pathways of mitogen-activated protein kinases and nuclear factor kappa B. AB - BACKGROUND/PURPOSE: Recent studies have suggested that protease-activated receptor-2 (PAR-2) activity correlates with cell proliferation and tumor growth, and its activation induces expression of cyclooxygenase-2 (COX-2). However, no previous reports have investigated PAR-2 signaling pathways in bile duct cancer. The aim of this study was to determine whether PAR-2 activation can regulate COX 2 expression via mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) in human bile duct cancer cells. METHODS: We immunohistochemically examined PAR-2 and COX-2 expression in 104 resected human specimens of extrahepatic bile duct cancer. We then determined how inhibitors of MAPKs and NF-kappaB signaling pathways influence COX-2 expression under PAR-2 activation in HuCCT1 and TKKK, human bile duct cancer cell lines. RESULTS: PAR-2 and COX-2 proteins were immunohistochemically recognized in 63 and 57% of specimens and were significantly correlated. PAR-2 agonist peptide activated mRNA and protein expression of COX-2 in HuCCT1 and TKKK. Pharmacologic blockade of p44/42 or p38 MAPK significantly inhibited PAR-2-activated mRNA and protein expression of COX-2 in both cells. COX-2 protein expression was also inhibited by the blocker of NF-kappaB pathway in both cells. CONCLUSIONS: PAR-2 may regulate COX-2 expression in human bile duct cancer via the MAPKs and NF-kappaB pathways. PMID- 20740369 TI - Non-ionic contrast media neurotoxicity mimicking intracerebral hematoma. PMID- 20740370 TI - Radial oxygen gradients over rat cortex arterioles. AB - PURPOSE: We present the results of the visualisation of radial oxygen gradients in rats' cortices and their potential use in neurocritical management. METHODS: PO2 maps of the cortex of ten sedated, intubated and controlled ventilated Wistar rats were obtained with a camera (SensiMOD, PCO, Kelheim, Germany). Those pictures were analysed and edited by a custom-made software. A virtual matrix, designed to evaluate the cortical O2 partial pressure, was placed vertically to the artery under investigation, and afterwards multiple regions of interest were measured (width 10 pixels, length 15-50 pixels). The results showed a map of the cerebral oxygenation, which allowed us to calculate radial oxygen gradients over arterioles. Three groups were defined according to the level of the arterial pO2: PaO2 < 80, PaO2 80-120 and PaO2 > 120. Gradients were analysed from the middle of the vessel to its border (1), from the border into the parenchyma next to the vessel (2) and a combination of both (3). RESULTS: Gradient 1 showed significantly different cortical pO2 values between the three different groups. The mean pO2 values were 2.62, 5.29 and 5.82 mmHg/mm. Gradient 2 measured 0.56, 0.90 and 1.02 mmHg/mm respectively. Gradient 3 showed significant results between the groups with values of 3.18, 6.19 and 6.84 mmHg/mm. CONCLUSION: Using these gradients, it is possible to describe and compare the distribution of oxygen to the brain parenchyma. With the presented technique, it is possible to detect pO2 changes in the oxygen supply of the brain cortex. PMID- 20740371 TI - Accurate prediction of the burial status of transmembrane residues of alpha-helix membrane protein by incorporating the structural and physicochemical features. AB - Predicting the burial status (the residue exposure to the lipid bilayer or buried within the protein core) of transmembrane (TM) residues of alpha-helix membrane protein (alphaHMP) is of great importance for genome-wide annotation and for experimental researchers to elucidate diverse physiological processes. In this work, we developed a new computational model that can be used for predicting the burial status of TM residues of alphaHMP. By incorporating physicochemical scales and conservation index, an efficient prediction model using least squares support vector machine (LS-SVM) was developed. The model was developed from 43 protein chains and its prediction ability was evaluated by an independent test set of other non-redundant ten protein chains. The prediction accuracy of our method was much better than the results of the reported works. Our results demonstrate that the LS-SVM prediction model incorporating structural and physicochemical features derived from sequence information could greatly improve the prediction accuracy. PMID- 20740372 TI - Study of device malfunctions in patients with implantable ventricular assist devices living at home. AB - Clinical introduction of implantable ventricular assist devices (VADs) is expected to encourage VAD therapy for severe heart failure patients in Japan. Since even minor device malfunctions can lead to serious outcomes in these patients, it is very important to collect and analyze data on device malfunctions occurring during their use at home. This study was undertaken to collect and analyze such data from 9 patients with implanted VADs (EVAHEARTTM, 4 patients; Jarvik2000, 3 patients; DuraheartTM, 2 patients) living at home, within the framework of a clinical trial carried out at our hospital. During the home stay period of 449 +/- 253 days (range 12-801 days, total 4044 days), the total number of device malfunctions was 31 (0.31 events/patient/year). Those with EVAHEARTTM were Cool-seal system-related (9 events) and battery-related (6 events) malfunctions. Those with Jarvik2000 were battery-related (7 events), alarm (1 event) and uncertain cause (1 event) malfunctions. Those with DuraheartTM were battery-related (3 events), alarm (3 events) and other component (1 event) malfunctions. Although the incidence was not very high and none of these device malfunctions led to cessation of blood pump operation in this study, it is necessary to establish a communication system for properly obtaining detailed information in the event of serious device malfunctions. Furthermore, establishment of a home-living-patient support system covering extensive areas is urgently needed, since this can facilitate rapid action to deal with serious device malfunctions. PMID- 20740373 TI - Fermentation of cellulosic hydrolysates obtained by enzymatic saccharification of sugarcane bagasse pretreated by hydrothermal processing. AB - This work aims to evaluate the fermentability of cellulosic hydrolysates obtained by enzymatic saccharification of sugarcane bagasse pretreated by hydrothermal processing using Candida guilliermondii FTI 20037 yeast. The inoculum was obtained from yeast culture in a medium containing glucose as a carbon source supplemented with rice bran extract, CaCl(2).2H(2)O and (NH(4))(2)SO(4) in 50 mL Erlenmeyer flasks, containing 20 mL of medium, initial 5.5 pH under agitation of an orbital shaker (200 rpm) at 30 degrees C for 24 h. The cellulosic hydrolysates, prior to being used as a fermentation medium, were autoclaved for 15 min at 0.5 atm and supplemented with the same nutrients employed for the inoculum, except the glucose, using the same conditions for the inoculum, but with a period of 48 h. Preliminary results showed the highest consumption of glucose (97%) for all the hydrolysates, at 28 h of fermentation. The highest concentration of ethanol (20.5 g/L) was found in the procedure of sugarcane bagasse pretreated by hydrothermal processing (195 degrees C/10 min in 20 L reactor) and delignificated with NaOH 1.0% (w/v), 100 degrees C, 1 h in 500 mL stainless steel ampoules immersed in an oil bath. PMID- 20740374 TI - Characterization of a legumain/vacuolar processing enzyme and YVADase activity in Papaver pollen. AB - Legumains, also known as Vacuolar Processing Enzymes (VPEs) have received considerable attention recently, as they share structural properties with mammalian caspase-1 and exhibit YVADase/caspase-1-like cleavage activity. Although many legumains have been cloned, knowledge about their detailed characteristics and intracellular localization is relatively limited. We previously identified several caspase-like activities activated by self incompatibility (SI) in pollen; a DEVDase was required for programmed cell death (PCD), but YVADase was not (Bosch and Franklin-Tong in Proc Natl Acad Sci USA 104:18327-18332, 2007; Thomas and Franklin-Tong in Nature 429:305-309, 2004). Here we report identification of a legumain/VPE from Papaver rhoeas pollen (PrVPE1) that binds to the DEVD tetrapeptide, a signature substrate for caspase 3. A detailed characterization of the recombinant PrVPE1 cleavage activity revealed that, like other VPEs, it has YVADase activity and requires an acidic pH for activity. Unlike other legumain/VPEs, it also exhibits DEVDase and IETDase activities and apparently does not require processing for activity. The pollen expressed PrVPE1 localizes to a reticulate compartment resembling the vacuole. Examination of YVADase activity using live-cell imaging of pollen tubes revealed YVADase activity in mitochondria of growing pollen tubes. The unexpected features of PrVPE1, together with evidence for YVADase activity in plant mitochondria, indicate that VPEs, YVADases, their localization and functions in plant cells merit further investigation. PMID- 20740375 TI - Health assessment of the Arab American community in southwest Brooklyn. AB - Data on Arab American health is lacking nationwide. This survey of the Arab American community in southwest Brooklyn assessed perceptions of health status, needs, behaviors, and access to services. Bilingual interviewers administered a structured survey to community members in public gathering places. Of 353 surveyed, 43% were men and 57% women, most spoke Arabic and were Muslim, and most had moved to the U.S. after 1990. One quarter were unemployed. Over 50% reported household incomes below federal poverty level. Nearly 30% had no health insurance. 58% reported choosing their health care venue based on language considerations. 43% reported problems in getting health care, including ability to pay, language barriers, and immigration. 42% of men, and 8% of women reported current smoking. Almost half of respondents never exercised. Rates of poverty, lack of health insurance, and smoking in men are cause for concern and were high even for immigrant groups. PMID- 20740376 TI - Unprotected sexual behavior and HIV risk in the context of primary partnerships for transgender women. AB - Previous research has reported that transgender women are likely to be exposed to HIV through unprotected sex with a male primary partner. We examined prevalence and correlates of unprotected sex with a primary male partner in a sample of n = 174 transgender women. Participants completed surveys on demographic characteristics, relationship dynamics with their male primary partner, sexual behavior, substance use, and psychosocial factors. Overall, 41% reported HIV positive status, 13% had another sexually transmitted infection during the past year, and 34% had unprotected sex with a male primary partner during the past 3 months. Factors associated with unprotected sex with a primary partner included living with the partner, drug use, alcohol use, education level, low self efficacy to use condoms, and perceived discrimination. Notably, 35% of transgender women in HIV-discordant primary partnerships had unprotected sex with their male primary partner during the past 3 months, and 18% of transgender women in HIV-positive concordant primary partnerships had unprotected sex with an outside partner during the past 3 months. HIV prevention interventions for transgender women must address risk behavior in the context of primary partnerships as well as sex with concurrent partners outside the relationship. Couples-focused interventions involving transgender women and their male primary partners can be particularly promising. PMID- 20740377 TI - Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design. AB - Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant. PMID- 20740378 TI - Coding and traceability: cells and tissues in North America. AB - Cell and tissue banking professionals in North America have long understood the value of labeling their allografts with descriptive names that make them easily recognized. They have also understood that advantages exist in possessing the capability to track them internally and externally to better understand tissue handling from donation through distribution. An added insight that can assist with strategic planning is to know who uses them, how many, and for what purpose or application. Uniquely coding allografts naturally aids tracking in event of recall or the rare need to link them if implicated in an adverse outcome report. These values relate to an ability or inability to sufficiently track specific cell/tissue types throughout the allograft's lifetime. These concepts easily fit into the functions of a Quality Program and promote recipient safety. It is management oversight that drives the direction taken and either optimizes this knowledge or limits it. How concepts related to coding and tracing human cells and tissues for transplantation have evolved in North America, and where they may be headed, are described in this manuscript. Many protocols are in place but they exist in numerous operational silos. Quality Management System concepts should drive decision-making and include considerations for future planning beyond our own professional lifetimes. PMID- 20740379 TI - Time-course changes in bone turnover markers and fat-soluble vitamins after obesity surgery. AB - BACKGROUND: The available evidence indicates a progressive increase in the incidence and severity of the deficiency of certain vitamins and related clinical conditions (i.e., metabolic bone disease). Because of the potential role of fat soluble vitamins and carotenoids in bone metabolism, our aim was to assess the time-course changes of fat-soluble vitamins and serum markers of bone metabolism in candidates for obesity surgery and following two bariatric procedures. METHODS: Sixty-five candidates for bariatric surgery and 150 serum samples after obesity surgery (i.e., Roux-en-Y gastric bypass, n = 85; biliopancreatic diversion, n = 65) were consecutively analyzed over a period of more than 2 years. Retinol, alpha- and gamma-tocopherol, 25-OH-vitamin D3, beta cryptoxanthin, and beta-carotene were analyzed by high-performance liquid chromatography. Calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), osteocalcin, beta-crosslaps, and N-terminal peptide of procollagen I (P1NP) were determined using commercial kits. RESULTS: Retinol, beta-cryptoxanthin, beta-carotene, and alpha- and gamma-tocopherol levels were significantly lower in post-surgery samples while osteocalcin, b-crosslaps, and P1NP were significantly increased. Along the time and regardless of the surgical procedure, P1NP, b-crosslaps, and osteocalcin increased during the first 12-24 months but declined afterward. 25-OH-vitamin D increased during the first 12 months and tended to decrease afterward while iPTH remained constant or decreased but increased after 1 year in both groups. Vitamin A remained constant but alpha- and gamma-tocopherol, beta-cryptoxanthin, and beta-carotene decreased in both groups. CONCLUSIONS: In addition to the nutritional assessment, regular monitoring of bone markers seems necessary in these patients and the early introduction of preventive strategies (i.e., the use of antiresorptive agents) should be evaluated. PMID- 20740380 TI - Adaptive evolution of Escherichia coli inactivated in the phosphotransferase system operon improves co-utilization of xylose and glucose under anaerobic conditions. AB - Modification of the phosphoenolpyruvate/sugar phosphotransferase system (PTS) has shown improvement in sugar coassimilation in Escherichia coli production strains. However, in preliminary experiments under anaerobic conditions, E. coli strains with an inactive PTS and carrying pLOI1594, which encodes pyruvate decarboxylase and alcohol dehydrogenase from Zymomonas mobilis, were unable to grow. These PTS- strains were previously evolved under aerobic conditions to grow rapidly in glucose (PTS- Glucose+ phenotype). Thus, in this work, applying a continuous culture strategy under anaerobic conditions, we generate a new set of evolved PTS Glucose+ mutants, VH30N1 to VH30N6. Contrary to aerobically evolved mutants, strains VH30N2 and VH30N4 carrying pLOI1594 grew in anaerobiosis; also, their growth capacity was restored in a 100%, showing specific growth rates (MU ~ 0.12 h-1) similar to the PTS+ parental strain (MU = 0.11 h-1). In cultures of VH30N2/pLOI1594 and VH30N4/pLOI1594 using a glucose-xylose mixture, xylose was totally consumed and consumption of sugars occurred in a simultaneous manner indicating that catabolic repression is alleviated in these strains. Also, the efficient sugar coassimilation by the evolved strains caused an increment in the ethanol yields. PMID- 20740382 TI - Tracheal bronchus (pig bronchus). PMID- 20740383 TI - Short stature, shots and shortcomings. PMID- 20740384 TI - Dry lung syndrome: a distinct clinical entity. AB - Infants with preterm prolonged rupture of membranes can present with immediate onset of pulmonary insufficiency and need aggressive ventilatory support. Dry lung syndrome remains an under-recognised clinical entity and very few cases are reported in the literature, though a working definition has been previously proposed. The proposed underlying etiopathogenesis for this is functional hypoplasia of the lung where higher than usual ventilatory pressure for initial 1 2 days can improve oxygenation. This study presents two cases which had similar antenatal and immediate postnatal course, but had diametrically opposite outcomes. Strategies to optimise outcomes in the setting of early premature rupture of the membranes should include antenatal assessment of mothers with monitoring of the liquor volume as well as the strength of foetal breathing movements, in-utero transfer with delivery in perinatal centres and attendance by neonatal staff of appropriate experience. PMID- 20740385 TI - Organophosphate poisoning presenting as acute respiratory distress. PMID- 20740386 TI - Patent ductus arteriosus ligation and post-operative hemodynamic instability: case report and framework for enhanced neonatal care. AB - Ligation of a patent ductus arteriosus can lead to severe cardiorespiratory compromise in preterm infants. This report reviews the postoperative course of a patient with significant cardiorespiratory instability following surgical ligation of the patent ductus arteriosus and presents a framework for enhanced cardiovascular care in this population. A preterm infant, born at 24 wk gestation underwent ligation of a large haemodynamically significant ductus arteriosus after failure of 2 courses of indomethacin. He developed systemic hypotension, which was aggressively treated with high doses of multiple cardiotropic agents. After 10 hr of refractory hypotension, the addition of hydrocortisone normalized blood pressure. This article outlines preprocedural categorization of infants according to ductal illness severity which facilitates the risk assignment for postoperative deterioration, development of clinical guidelines specific to the likely haemodynamic changes, enhanced role of functional echocardiography for guiding therapy, and interprofessional education. PMID- 20740387 TI - Laboratory tests in pediatric rheumatology. AB - Laboratory tests in rheumatology are important tools that help to support the diagnosis of autoimmune diseases, evaluate the disease activity, monitor the side effects of therapy, and also assist the physician to exclude rheumatologic mimics. Few relevant tests should be ordered after a detailed clinical review of the patient has been carried out and a provisional clinical diagnosis has been reached. There is no test that can rule in or rule out any rheumatologic disease and therefore, there is no role of a detailed "Rheumatology panel" of investigations. In this review, routine blood investigations, acute phase reactants, auto antibodies, HLA B27 and complements have been discussed. PMID- 20740388 TI - Defibrillation and resuscitation in a piglet model of pediatric ventricular fibrillation following AHA 2005 guidelines. AB - OBJECTIVE: To evaluate the efficacy and safety of defibrillation on children according to AHA 2005 recommendations METHODS: Pig resembles human in the chest configuration, anatomy and physiology of the cardiovascular and pulmonary systems. Piglets weighing 7.0 Kg +/- 1.4kg, 14.0kg +/- 2.8kg, 25.0kg +/- 5.0kg respectively, which represented children 1 to 8 yr old were induced ventricular fibrillation (VF). An adult biphasic AED was used in conjunction with pediatric attenuating electrodes which could deliver 50-J shock for 2 min and two min of cardiopulmonary resuscitation (CPR) immediately followed it. If VF did not reverse, 70-J shock combined with CPR was used, and the protocol was repeated five times. If an organized cardiac rhythm with mean aortic pressure more than 60 mmHg persisted for an interval of 5 minutes, the animal was regarded as successfully resuscitated. If the AED recognized a "non-shockable" rhythm, CPR was also performed immediately for 2 min. The same resuscitation program was exercised on piglets of manual defibrillator group. Neurologic alertness score, hemodynamic and myocardial functions were evaluated, autopsy was routinely performed to document possible injuries. RESULTS: In the AED group, 14 out of 15 animals, were successfully resuscitated, among them 11 piglets were resuscitated by 50-J defibrillation combined with cardiopulmonary resuscitation, and other three recovered to normal by 1 or 2 times of 70-J shocks and CPR. All animals in manual defibrillator group were successfully resuscitated by 50-J shocks and CPR. Left ventricular ejection fraction and fractional area change were reduced significantly during 3-4 hr post-resuscitation (P<0.05) and returned to baseline ranges at the end of 72 hr. There was no evidence of myocardial and pulmonary damage during autopsy, and neurologic recovery was also normal. Data of blood gas analysis, blood electrolytes and myocardial enzymes does not show any statistically significant difference (P> 0.05) in the groups. 50 J biphasic dose defibrillation combined with effective CPR, successfully terminated VF without adverse effects on myocardial function and survival in a piglet defibrillation model for young children 1 to 8 yr of age. CONCLUSIONS: The new guidelines recommendation that one shock immediately followed by CPR is reasonable. Adults AED combined with pediatric electrodes is feasible to the diagnosis and treatment of pediatric VF model. But the user should not rely too much on AED's "automatic" function, but should accumulate and integrate his experience with AED technology. PMID- 20740389 TI - Otitis media in children with congenital immunodeficiencies. AB - Otitis media represents one of the most common infections in childhood. Within the first 3 years of life, up to 80% of children experience at least one episode of otitis media. It is often resolved with supportive therapies and consequently not considered a worrisome problem. However, it may be an early manifestation of a severe underlying disease. Primary immunodeficiencies are rare congenital defects of the immune system that often remain unrecognized, or diagnosis can be delayed, sometimes resulting in fatal consequences for the child. Patients suffer from recurrent, prolonged, and/or unusual infections leading to local sequelae, failure to thrive, developmental delays, and systemic infections with severe courses. This review provides a brief insight into primary immunodeficiencies and an overview of leading findings that should result in further evaluation of the immune system in cases of otitis media. A stepwise diagnostic approach is proposed to facilitate early and accurate diagnosis and, consequently, effective and timely therapy to improve the patient's outcome and quality of life. PMID- 20740390 TI - Disaggregating the relationship between posttraumatic stress disorder symptom clusters and chronic orofacial pain: implications for the prediction of health outcomes with PTSD symptom clusters. AB - BACKGROUND: Research has established a significant relationship between posttraumatic stress disorder (PTSD) symptoms and pain; however, very little research has examined the differential role of PTSD symptom clusters on pain outcomes. PURPOSE: (a) To confirm the most appropriate PTSD symptom factor structure for an orofacial pain population and (b) to test a model of prediction of pain outcomes with PTSD symptom clusters. METHODS: The study was a cross sectional, retrospective case series of 411 female patients with orofacial pain (mean 41.0 years, SD 13.1). A series of structural equation modeling analyses were conducted to examine five competing models of PTSD symptom clusters. RESULTS: Two four-factor models of PTSD symptom clusters fit the data reasonably well, and differing PTSD symptom clusters predicted different components of pain. CONCLUSIONS: To increase predictive utility for pain and for a wide range of health disorders, researchers should examine the unique predictive power of PTSD symptom clusters rather than examining a one-factor model of PTSD symptoms. PMID- 20740391 TI - Television viewing time and risk of chronic kidney disease in adults: the AusDiab Study. AB - BACKGROUND: Television viewing time independent of physical activity is associated with a number of chronic diseases and related risk factors; however, its relationship with chronic kidney disease is unknown. PURPOSE: The purpose of this study is to examine the cross-sectional and prospective relationships of television viewing time with biomarkers of chronic kidney disease. METHODS: Participants of the Australian Diabetes, Obesity and Lifestyle Study attended the baseline (n = 10,847) and 5-year follow-up (n = 6,293) examination. RESULTS: Television viewing was significantly associated with increased odds of prevalent albuminuria and low estimated glomerular filtration rate. In the gender stratified analyses this pattern was seen for men, but not for women. In the longitudinal analyses, odds of de novo albuminuria and low estimated glomerular filtration rate were increased only in unadjusted models. CONCLUSIONS: Television viewing time may be directly related to markers of chronic kidney disease and through intertwined associated risk factors such as diabetes, hypertension, and obesity. PMID- 20740392 TI - Risk of coronary artery stenosis in Iranian type 2 diabetics: is there a role for matrix metalloproteinase-3 gene (-1612 5A/6A) polymorphism? AB - To investigate the association of matrix metalloproteinase-3 (MMP-3) polymorphism with susceptibility to coronary artery stenosis (CAS) and the number of diseased vessels in patients with type 2 diabetes mellitus (T2DM). The study population comprised 618 unrelated Iranian individual subjects, including 305 angiographically documented CAS patients with T2DM and 313 control subjects with T2DM. MMP3 genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Significant differences between cases and controls were observed for MMP3 genotype frequencies (p<0.01). The 6A allele was high frequently seen in the disease group, compared with the control group (64.75 vs. 56.24%, 6A/6A + 5A/6A vs. 5A/5A, p<0.05). The association of this polymorphism with the severity of stenosis were also evaluated which according to results distribution of MMP3 genotypes were not significantly different as compared with the severity of stenosis (p>0.05). Frequency of the 6A allele of the human MMP3 gene is an independent risk factor for CAS in the Iranian T2DM studied. PMID- 20740393 TI - [Evaluation of ADC mapping as an early predictor for tumor response to chemotherapy in recurrent glioma treated with bevacizumab/irinotecan: proof of principle]. AB - PURPOSE: The assessment of the radiological response of recurrent glioma is based on the Macdonald or RECIST criteria 8 to 10 weeks from the start of treatment. Magnetic resonance imaging using an apparent diffusion coefficient map may provide an earlier measure for predicting the response to therapy of recurrent glioma. MATERIALS AND METHODS: Twelve patients with recurrent high-grade glioma were enrolled in a feasibility study of pretreatment MRI on day 1, intra treatment MRI in week 3, and post-treatment MRI in week 12. Prognostically relevant ADC values (ADCprog) of each recurrent glioma at 3 weeks were calculated as a function of their pre- and intra-therapy ADC values (ADCpre - ADCintra = ADCprog). Because we hypothesized that smaller ADC values correlate with less Brownian motion of water molecules in the extracellular space and that a higher cell density may restrain this water diffusion, we set smaller ADC values at a second time point as "progressive disease" (PD) and higher ADC values as "partial response" (PR). A change in ADCprog of less than 10 * 10-6mm2 /sec was set as "stable disease" (SD). The ADCprog values were always calculated before the final scan after 3 months was performed. The readers were blinded to the future development of the tumor. RESULTS: In 10 of the 12 patients we could correctly predict the tumor response to chemotherapy. One patient died before the three month control, and one recurrent glioma did not develop as predicted. ADC mapping is found to predict patient response at 3 weeks from the start of treatment, revealing that early changes in tumor diffusion values could be used as a prognostic indicator also for chemotherapeutically treated recurrences of high grade glioma. PMID- 20740394 TI - [Sellink MRI in graft versus host reaction of the intestine]. PMID- 20740395 TI - [Micronutrients and their relevance for the eye--function of lutein, zeaxanthin and omega-3 fatty acids]. AB - Micronutrients play an important role in function and health maintenance for the eye. Especially lutein, zeaxanthin and omega-3 fatty acids perform remarkable functions: lutein together with zeaxanthin forms the macular pigment, these carotenoids filter out the damaging blue light component from the sunlight as well as the ultraviolet light which leads to improved contrast sensitivity and less problems with screen glare. Furthermore, the macular pigment has antioxidant and anti-inflammatory effects. The omega-3 fatty acids also possess anti inflammatory effects and, when converted into neuroprotectin, they protect against oxidative induced apoptosis in the retina. They are also responsible for the fluidity and supply to the photoreceptor membrane. These properties are important for the prevention and treatment of degenerative eye diseases like age related macular degeneration. However, older people are often not sufficiently supplied of micronutrients in their diet. Because the supply of nutrients can hardly be achieved by dietary change, the additional intake in the form of food supplements is useful in this age group. Scientific studies have shown the positive effects of supplementation with micronutrients such as lutein/zeaxanthin, vitamin C, vitamin E, zinc and omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid (DHA and EPA). Currently available nutritional products are based in part on the ingredients of the ARED study (Age Related Eye Disease Study). According to more recent studies formulations containing lutein and omega-3 fatty acids in physiologically meaningful doses without additional beta-carotene should be preferred. 10 to 20 mg of lutein and zeaxanthin represent a safe daily dose Regarding to the context above, beta carotene in high doses plays a minor role to the eye and is especially critical for the health of smokers. This paper summarises the functions of the presented micronutrients in the eye and can assist ophthalmologists in advising their patients. PMID- 20740396 TI - [No increase of incidence of retinopathy of prematurity and improvement of its outcome in a university perinatal centre level III - a prospective observational study from 1978 to 2007]. AB - BACKGROUND: There is a controversy over whether the improved survival rate of extremely low birth weight (ELBW; birth weight < 1000 g) and of extremely low gestational age (ELGA; gestational age < 28 weeks) infants has resulted in a higher incidence of severe retinopathy of prematurity (ROP) and induced blindness. We studied the incidence, treatment and the structural outcome of ROP in a Perinatal Centre Level III over a 30-year period in infants < 1500 g birth weight (VLBW = very low birth weight). PATIENTS AND METHODS: 1473 VLBW infants, who survived the first 28 days, had ocular examinations from 1978 to 2007. Neonatal and ROP data were collected prospectively. Proliferative ROP, threshold disease and high-risk prethreshold ROP indicated treatment for peripheral retinal ablation in respect to the CRYO-ROP and ETROP studies. Incidence, treatment and structural outcome of ROP were analysed for the periods 1978 - 1992 (P1) and 1993 - 2007 (P2) and for children with BW < 1000 g and > 1000 g. RESULTS: In P 1 43.1 % (n = 87) ELBW infants survived and 82.3 % (n = 372) in P 2, whereas the survival rates of the infants with a BW of 1000 - 1499 g were 74.6 % (n = 453) and 95.1 % (561), respectively. The ROP incidence was decreased from 27.6 % (n = 149) in P 1 to 15.1 % (n = 141) in P 2 significantly (p < 0.003) as well the mean BW 1136.6 +/- 211.3 g to a mean BW 822.3 +/- 215.3 g and the mean gestational age (GA) 29.3 +/- 2.2 weeks and to a mean GA 26.4 +/- 2 weeks, respectively (both differences p < 0.001). Also the coagulation rate was significantly decreased from 13 % (n = 70) in P 1 to 6.8 % (n = 63) in P 2 (p = 0.043). The blindness rates (structurally unfavourable outcome of both eyes) of 1.5 % in P 1 and 1.0 % in P 2 were not significantly reduced (p = 0.543). Among the ELBW the number of ROP infants was increased from 39 in P 1 to 117 in P 2 while the ROP incidence decreased from 44.8 % to 31.5 % (p = 0.053) and the ROP-OP rate from 19.5 % to 14.8 % (p = 0.029). Also among the ELGA the number ROP infants was increased from 66 in P 1 to 121 in P 2 but the ROP incidence was reduced from 70.2 % to 27.6 % and the ROP-OP rate from 30.9 % to 13.2 % (both p < 0.001). CONCLUSIONS: Inspite of an increase of the number of ELBW/ELGA infants and their survival rate in 1978 - 2007 there is no increase in the incidence of ROP, operations and blindness among the VLBW and VLGA infants. PMID- 20740397 TI - [Retinotopic mapping of the human visual cortex with functional magnetic resonance imaging - basic principles, current developments and ophthalmological perspectives]. AB - Since its initial introduction in the mid-1990 s, retinotopic mapping of the human visual cortex, based on functional magnetic resonance imaging (fMRI), has contributed greatly to our understanding of the human visual system. Multiple cortical visual field representations have been demonstrated and thus numerous visual areas identified. The organisation of specific areas has been detailed and the impact of pathophysiologies of the visual system on the cortical organisation uncovered. These results are based on investigations at a magnetic field strength of 3 Tesla or less. In a field-strength comparison between 3 and 7 Tesla, it was demonstrated that retinotopic mapping benefits from a magnetic field strength of 7 Tesla. Specifically, the visual areas can be mapped with high spatial resolution for a detailed analysis of the visual field maps. Applications of fMRI based retinotopic mapping in ophthalmological research hold promise to further our understanding of plasticity in the human visual cortex. This is highlighted by pioneering studies in patients with macular dysfunction or misrouted optic nerves. PMID- 20740398 TI - [Sorafenib in relapsed and refractory FLT3-ITD positive acute myeloid leukemia: a novel treatment option]. AB - BACKGROUND: The therapeutic options for relapsed or refractory FLT3-ITD positive AML are limited, particularly in case of a prior allogenic stem cell transplantation (SCT) or poor performance status. The clinical value of a targeted intervention using the FLT3-ITD-specific inhibitor sorafenib in this situation is largely unknown. PATIENTS AND METHODS: Between 2007 and 2010 eight patients (4 men, 4 women; age 40-75 years) with relapsed or refractory FLT3-ITD positive acute myeloid leukemia (AML) before (n=4) and after allogenic SCT (n=5) were treated off-label with sorafenib. RESULTS: All patients showed rapid hematological responses. There were three complete molecular remissions when sorafenib was given after allogenic SCT. Two of them are ongoing for 12 and 15 months, respectively. Long-term remissions after prior allogenic SCT were associated with the re-establishment of a chronic graft versus host reaction. Side effects could be controlled by dose reduction. CONCLUSION: Sorafenib is apparently an effective treatment alternative for patients with relapsed or refractory FLT3-ITD positive AML. In the context of a prior allogenic SCT it may have curative potential via inducing a synergism between targeted inhibition of FLT3-ITD and anti-leukemic immunity. PMID- 20740399 TI - Unclear focal liver lesions in contrast-enhanced ultrasonography--lessons to be learned from the DEGUM multicenter study for the characterization of liver tumors. AB - PURPOSE: To discuss the difficulties of contrast-enhanced ultrasound (CEUS) in a large multi-center trial. MATERIALS AND METHODS: CEUS was performed on 1349 liver lesions with an unclear diagnosis after native ultrasound using a standardized protocol (phase inversion; low MI < 0.4; Sonovue Bolus 1.2 - 4.8 ml). The early arterial, arterial, portal venous and late phase > 2 min. were documented. The diagnosis based on CEUS results was compared to the final diagnosis (histology: n = 1006; MRI: n = 269; CT: n = 269 - multiple examinations possible). RESULTS: Of the 1349 enclosed liver lesions, 20 could not be definitively diagnosed even using all diagnostic steps including histology (the others were proven to be benign n = 573 or malignant n = 756). Of the 1349 unclear liver lesions, 1257 could be differentiated with an accuracy of 90.3% using CEUS. The sensitivity, specificity, and positive and negative predictive value for malignant liver lesions was 95.8%, 83.1%, 88.2% and 93.7% respectively. 92 liver lesions (6.8%) could not be definitively diagnosed using CEUS. Most of them were benign (n = 67) on final diagnosis. The CEUS diagnosis was wrong for 39 lesions. However, only 8 lesions classified as benign by CEUS turned out to be malignant. In 3 cases HCC proven by histology was incorrectly diagnosed by CEUS as adenoma and 2 lesions incorrectly diagnosed by CEUS as FNH turned out to be an HCC and a metastasis. Two lesions diagnosed by CEUS as hemangiomas turned out to be an HCC and a metastasis. One lesion classified as benign by CEUS was ultimately diagnosed as a lymphoma. CONCLUSION: Even in this multi-center trial, CEUS proved to be an excellent method for clarifying liver lesions remaining unclear after native ultrasound. The CEUS diagnosis of benign was only incorrect in a few cases. PMID- 20740400 TI - [Cerebral Neurocytoma. Pictorial essay]. PMID- 20740410 TI - [Impact factor RoFo higher than 2.0 for the first time]. PMID- 20740414 TI - [Conditions of reimbursement group A 3 are mandatory for classification as senior physician in accordance with TV doctors]. PMID- 20740416 TI - Influence of surface modification on the adhesion between Nitinol wire and fluoropolymer films. AB - PURPOSE: One of the current challenges for the medical device industry is how to manufacture and assemble biomedical implants consisting of a metallic wire component and a fluorocarbon film without the use of an adhesive. In an attempt to answer this question, samples of Nitinol wire and fluorinated ethylene propylene (FEP) film were surface modified by various treatments before being thermally bonded into a composite pull-out strength test specimen and mechanically tested to determine their adhesion strength. METHODS: The two surface treatments for Nitinol wire included mechanical roughening with sandpaper, and adding a fluorocarbon coating followed by polymerization and curing by a helium plasma treatment. The two surface treatments for FEP film included helium plasma and helium-oxygen plasma under atmospheric conditions. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurements were also taken to characterize the appearance and chemistry of the surfaces before and after modification. A unique pull-out strength test method was developed to assess the level of adhesion between these various candidates. RESULTS: The pull-out force for untreated Nitinol bonded to untreated FEP film was 30.5 +/- 2.4 N. Significant improvements of up to 14% in this level of adhesion were obtained with the mechanically roughened Nitinol wire bonded to the helium plasma treated films. However, coating the wire with a liquid fluorocarbon monomer mixture (TG-10) was not successful and after thermal bonding to FEP film the level of adhesion decreased by over 80%. CONCLUSIONS: Thus, the bonding strength between the wire and the film can be significantly improved by mechanically roughening the Nitinol wire and treating the FEP film with helium plasma prior to thermal bonding. PMID- 20740415 TI - Nanotoxicology of metal wear particles in total joint arthroplasty: a review of current concepts. AB - Metal-on-metal (M-M) joint replacement has raised concerns about the long-term effects of metal wear debris and corrosion products. This review summarizes the current concepts in biological reactivity to metal wear particles, ions, and corrosion products. Attention is focused on Co-Cr-Mo alloy since it is the most diffused and discussed material in arthroplasty. PMID- 20740417 TI - Sol-gel silicon alkoxides-polyethylene glycol derived hybrids for drug delivery systems. AB - PURPOSE: The potential application of hybrid systems based on silicon alkoxides and polyethylene glycol 400 as drug delivery systems was studied. METHODS: They were synthesized using the sol-gel technique, using ketoprofen as a model drug. The preparation of the materials and their characterization by X-ray diffraction, infrared spectroscopy, thermogravimetric analysis are reported. Drug loading was performed during the gelation of the sols. Drug release studies were performed at pH 1.2 and 7.5 mimicking gastrointestinal environments. RESULTS: Drug release was affected by the presence of polyethylene glycol in the formulation: a faster release was observed for polyethylene glycol hybrids. CONCLUSIONS: The results suggest that these devices should guarantee long durability after implantation and could be suitable for sustained release: after a first period of release by diffusion, complete release will be reached by bioerosion of the matrix. PMID- 20740418 TI - Mechanical characterization of actomyosin complex by molecular mechanics simulations. AB - PURPOSE: Knowledge of the mechanical behavior of myosin and actin monomer is critical for understanding the molecular mechanism of actomyosin-based muscle and non-muscle motility. Different experimental studies concerning actomyosin interaction have been performed in vitro, but studies at the single molecule level have just begun. The aim of this study was to provide a mechanical characterization of myosin II and actin monomer using a numerical approach. METHODS: The elastic properties of the two proteins involved in muscle contraction were assessed by performing stretching simulations up to 10% protein elongation using the restraining method. Interaction properties of the actomyosin complex were evaluated at eight intermolecular distances during which the entire system was left free to move. RESULTS: According to our results, the values of the elastic modulus of the myosin motor domain and actin are 0.30 GPa, and 0.08 GPa, respectively. As for the actomyosin complex, the interaction force has a maximum value of 541.15 pN. CONCLUSIONS: Mechanical properties of molecular motors are currently being debated. Our results match a number of experimental data, therefore, supporting the idea that molecular mechanics may be a powerful tool to find a way in this complex subject. PMID- 20740419 TI - Perspectives of the Si3N4-TiN ceramic composite as a biomaterial and manufacturing of complex-shaped implantable devices by electrical discharge machining (EDM). AB - PURPOSE: In this work we investigated the suitability of electroconductive silicon nitride/titanium nitride composite for biomedical implantable devices with particular attention on the processing route that allows the net-shaping of complex components by electrical discharge machining (EDM). METHODS: The composite, constituted mainly of a beta-Si3N4, dispersed TiN grains and a glassy grain boundary phase, exhibited a low density and high hardness, strength and toughness. Bulk, surface characteristics and properties of the Si3N4-TiN composite were analyzed. After the EDM process, the microstructure of the machined surface was examined. RESULTS AND CONCLUSIONS: The obtained results showed that the Si3N4-TiN ceramic composite together with the EDM manufacturing process might potentially play a key role in implantable load-bearing prosthesis applications. PMID- 20740420 TI - The effect of immersion times on the solubility and bonding stress of hydroxyapatite coated Ti6al4v pedicle screws. AB - PURPOSE: Main aim of the present study was to test and show the dissolution of coatings onto Ti6Al4V pedicle screws by both in vitro and in vivo analysis. METHODS: Hydroxyapatite (HA) was coated on Ti6Al4V by electrophoretic deposition (EPD). The dissolution of the coatings was tested in vitro. The coating was characterized before and after implantation via pull-out tests, X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The coating materials were immersed in a simulated body fluid (SBF) from 1 day to 6 weeks, in vitro, and the elemental analysis were undertaken in a calf spine, in vivo. Fourteen coated (7) and uncoated (7) Ti6Al4V pedicle screws were implanted in a calf spine for 12 weeks and the elemental concentration was analyzed using the wavelength dispersive X-ray fluorescence (WDXRF) technique. RESULTS: The analysis of elemental concentrations by WDXRF are presented and 97% of the dissolved elements were determined as Ca, P, Ti, O and 3% of K, Na, Fe, Ni, Zn, Mg, S in total. The solubility of the coating materials increased with increasing immersion time and, interestingly, it increased substantially for reasonably longer times, for example, 6 weeks. CONCLUSIONS: Through the in vivo experiments, on the HA coated and uncoated pedicle screws implanted on a calf vertebra, the elemental concentrations by WDXRF analysis showed the Ca(%) around the pedicle screws increased by 30% after re-implantation process. The results may lead us to reconsider such ceramic coatings to test in vitro and/or in vivo for longer periods before clinical applications. PMID- 20740421 TI - Novel sol-gel organic-inorganic hybrid materials for drug delivery. AB - PURPOSE: The aim of the present study was to synthetize and characterize novel sol-gel organic-inorganic hybrid materials to be used for controlled drug delivery application. MATERIALS AND METHODS: Organic-inorganic hybrid class I materials based on poly(epsilon-caprolactone) (PCL 6, 12, 24 and 50 wt%) and zirconia-yttria (ZrO2-5%Y2O3) were synthesized by a sol-gel method, from a multicomponent solution containing zirconium propoxide [Zr(OC2H7)4], yttrium chloride (YCl3), PCL, water and chloroform (CHCl3). The structure of the hybrids was obtained by means of hydrogen bonds between the Zr-OH group (H-donor) in the sol-gel intermediate species and the carboxylic group (H-acceptor) in the repeating units of the polymer. RESULTS: The presence of hydrogen bonds between organic-inorganic components of the hybrid materials was suggested by Fourier transform infrared (FTIR) analysis, and strongly supported by solid-state NMR. A single-step, sol-gel process was then used to precipitate microspheres containing ketoprofen or indomethacin for controlled drug delivery applications. Release kinetics in a simulated body fluid (SBF) were subsequently investigated. The amount of drug released was detected by UV-VIS spectroscopy. Pure anti inflammatory agents exhibited linear release with time, in contrast drugs entrapped in the organic-inorganic hybrids were released with a logarithmic time dependence, starting with an initial burst effect followed by a gradual decrease. CONCLUSIONS: The synthesis of amorphous materials containing drugs, obtained by sol-gel methods, helps to devise new strategies for controlled drug delivery system design. PMID- 20740423 TI - 3D fiber deposition technique to make multifunctional and tailor-made scaffolds for tissue engineering applications. AB - Tissue engineering represents an interesting approach which aims to create tissues and organs de novo. In designing scaffolds for tissue engineering applications, the principal goal is to mimic the function of the natural extracellular matrix, providing a temporary template for the growth of target tissues. For this reason, scaffolds should possess suitable mechanical properties and architecture to play their specific role. In this paper, limitations of conventional scaffold fabrication methods will be briefly introduced, and rapid prototyping techniques will be described as advanced processing methods to realize customized scaffolds with controlled internal microarchitecture. Among the rapid prototyping techniques, the potential and challenges of 3D fiber deposition to create multifunctional and tailor-made scaffolds will be reviewed. PMID- 20740422 TI - Microbial contamination and inhibitory effect against Streptococcus mutans from fifth-generation bonding systems. AB - PURPOSE: The aim of this study was to evaluate microbial contamination and inhibitory effect against Streptococcus mutans (SM) of Prime & Bond (PB), Single Bond (SB) and Excite (EX) bonding systems before use, and after 10 and 20 applications. METHODS: The bonding material was collected by applying a drop of the material directly on broth brain-heart infusion. The samples were homogenized, diluted and seeded on blood agar plates. To evaluate the inhibitory effect on SM, a drop of each bonding material was dispensed on filter discs and placed on blood agar plates. The Cochran statistical analysis was used to evaluate the total amount of viable bacteria among the different bonding systems. Comparisons between the inhibitory effects on SM were made using the Kruskal Wallis test. RESULTS: Adhesives SB and EX presented microbial contamination (p<0.05) and inhibitory effect (p<0.05) over SM strains with statistically significant differences concerning PB. SB and EX inhibitory capacity remained after 20 applications. CONCLUSIONS: The monomer's variation in chemical composition, solvent and application technique of the bonding systems had an influence on contamination by the total number of bacteria and on the inhibitory effect on SM. PMID- 20740424 TI - Anodic Spark Deposition treatments to increase reliability of Ti6Al4V modular prostheses. AB - PURPOSE: The aim of this study was to evaluate whether an Anodic Spark Deposition treatment, which assures increased resistance of titanium alloys to fretting corrosion, improves the structural reliability of Ti6Al4V modular hip prostheses, thus preventing the recently noticed in vivo mechanical failures of these components due to fatigue events. METHODS: Three commercial treatments were tested in this work. Microhardness, roughness and fatigue resistance measurements were carried out to investigate the treatment performances. RESULTS: The experimental tests showed that the implant responded differently based on the treatment. The treatment that assured the best performances induced an increase in fatigue resistance with respect to the initial properties of the non-treated Ti6Al4V alloy. CONCLUSIONS: Since in previous research the same surface treatment was shown to prevent fretting corrosion phenomena, the study tests confirmed that the Anodic Spark Deposition treatment can significantly increase the structural reliability of Ti6Al4V multi-component prostheses. PMID- 20740425 TI - Biomimetic calcium-silicate cements aged in simulated body solutions. Osteoblast response and analyses of apatite coating. AB - PURPOSE: Calcium-silicate cements have been recently proposed for application in dentistry as root-end filling and root-perforation repair materials. The aim of this study was to investigate the effect of ageing of experimental calcium silicate cements on the chemistry, morphology and in vitro bioactivity of the surface, as well as on osteoblast viability and proliferation. METHODS: Two experimental cements (wTC-Bi, containing bismuth oxide and wTC), mainly based on dicalcium-silicate and tricalcium-silicate, were prepared and tested for their bioactivity after soaking in Dulbecco's phosphate buffered saline (DPBS), used as simulated body fluid. Human marrow stromal cells (HMSC) were seeded on the cements maintained in DPBS for 5 hr (non-aged group), 14 and 28 days (aged group). Cell viability was assessed by the Alamar blueTM test and morphology by scanning electron microscopy (SEM) at different time endpoints. The surface of the soaked cements was analyzed by environmental scanning electron microscopy or SEM coupled with energy dispersive X-ray microanalysis (ESEM/EDX or SEM/EDX respectively) and the micro-Raman technique. RESULTS: The ESEM/EDX results showed a uniform surface composed of CSH hydrogel (mainly derived from the hydration of belite and alite) on both non-aged cements. Micro-Raman spectroscopy revealed the presence of calcium carbonate, anhydrite, ettringite, alite and belite. The SEM/EDX data showed an irregular calcium-phosphate multi-layered biocoating with many sharp and protruding crystals on both the aged cements. Micro-Raman spectroscopy revealed crystalline apatite and calcite. The osteoblast response results showed that both the experimental cements exerted no acute toxicity in the cell assay systems. The non-aged samples promoted greater cell growth. SEM showed cells well spread and adherent to the non-aged materials. A reduced number of attached cells was noticed on the aged cements. Bismuth oxide-containing cement allowed a reduced cell viability suggesting some cytotoxic effects. However, the thick biocoating formed on the 28-day aged samples lowered the deleterious effect of bismuth oxide on cell growth. Actually, micro-Raman spectroscopy revealed progressive bismuth oxide depletion on the wTC-Bi surface, due to the increased thickness of the apatite deposit. CONCLUSIONS: The study demonstrated that (1) these materials support osteogenic cells growth and may induce early bone formation, (2) the ageing in DPBS reduced the growth of HMSC, but eliminated the deleterious effect of the bismuth oxide on cell growth. In conclusion, the experimental cements have adequate biological properties to be used as root-end/root repair filling materials or pulp capping materials. PMID- 20740426 TI - Crystallochemical comparison between Portland cements and mineral trioxide aggregate (MTA). AB - PURPOSE: The aims of this study were to compare the crystal chemical properties of some commercial mineral trioxide aggregate (MTA) and Portland cements (PC) and to propose a new white MTA product. METHODS: The samples (four MTA and two PC types) were analyzed by 1) optical microscopy; 2) laser granulometry; 3) X-ray diffraction and fluorescence; 4) scanning electron microscopy (SEM) and electron probe microanalysis (EPM) (wavelength-dispersive). RESULTS: MTA and PC specimens yielded similar characteristics in their clinker component. The MTA-Angelus specimens displayed a composition overlapping the classical clinker composition (wt%) i.e. 25 silica, nine alumina and 66 lime. However, the bismite, present in large amounts (~15-19 wt%) in all MTA products, contained considerable and diffused heavy (toxic) metals as Pb and Mo, other than Bi. In the MTA clinkers the formation of Portlandite, at water-clinker interface, is favored by the smaller grain size of the MTA particles. However, this may also favor the diffusion of the toxic elements linked to Bi. SIGNIFICANCE: In terms of bulk physico-chemical properties, the MTA products can be easily substituted by a fine grained Portland clinker by adding a non-toxic radio-opaque component, for example, Ba-carbonate. PMID- 20740427 TI - In vitro evaluation of bacterial leakage through different perforation repair materials of teeth. AB - PURPOSE: This study was conducted to evaluate micro-leakage through different furcation repair dental materials which are used to repair iatrogenic perforations in teeth. Six commercially available dental materials high copper amalgam, glass ionomer cements (GIC) Fuji II and Fuji IX, intermediate restorative material (IRM), mineral trioxide aggregate (MTA) and fully injectable calcium phosphate cement (Chitra-CPC) were evaluated. METHODS: Eighty extracted human molar teeth were prepared chemo-mechanically and allocated to six experimental and two control groups, each comprising of 10 teeth. Microleakage was evaluated using the Enterococcus fecalis bacterial penetration test and confirmed with a confirmatory broth. On a daily basis broth was evaluated for visual turbidity for 45 days and leakage was confirmed using Mac Conkey's medium. RESULTS: Statistical analysis using the Chi-Square test has revealed a significant difference among the materials tested, with MTA and Chitra-CPC showing minimal leakage when compared to the other repair materials within this period. CONCLUSIONS: MTA and Chitra-CPC showed a similar micro leakage patterns and had a better sealing ability when compared to other materials in this study. PMID- 20740428 TI - The effect of spin finishes on hydrolysis rates of medical grade polyester. AB - PURPOSE: The rate of alkaline hydrolysis of medical grade poly(ethylene terephthalate) of grey, scoured, and solvent extracted samples have been studied to understand their degradation behavior during surface modification which is used to produce antithrombus grafts. METHODS: The changes in properties were examined using weight loss, mechanical properties loss and infrared spectrum. RESULTS: It was found that the rate of hydrolysis of grey sample was always slower than the scoured, and solvent extracted samples. The slower rate of degradation of the grey polyester is attributed to the presence of spin finishes in the polyester biomaterials. Further, different scouring methods also gave samples with varying rates of hydrolysis. This is due to the different spin finish removal efficiency of different scouring procedures. The weight loss (%) of the solvent extracted samples were the largest which demonstrated that the solvent extraction technique is perhaps the best to remove spin finish from the polyester. CONCLUSIONS: Thus, these results serve as foundation for polyester biomaterials which are hydrolyzed before implantation in order to improve the protein binding capabilities to minimize thrombosis. PMID- 20740429 TI - Fabrication of chemically cross-linked porous gelatin matrices. AB - PURPOSE: The aim of this study was to chemically cross-link gelatin, by reacting its free amino groups with an aliphatic diisocyanate. METHODS: To produce hydrogels with controllable properties, the number of reacting amino groups was carefully determined. Porosity was introduced into the gelatin-based hydrogels through the lyophilization process. Porous and non-porous matrices were characterized with respect to their chemical structure, morphology, water uptake and mechanical properties. RESULTS: The physical, chemical and mechanical properties of the porous matrices are related to the extent of their cross linking, showing that they can be controlled by varying the reaction parameters. Water uptake values (24 hours) vary between 160% and 200% as the degree of cross linking increases. The flexibility of the samples also decreases by changing the extent of cross-linking. Young's modulus shows values between 0.188 KPa, for the highest degree, and 0.142 KPa for the lowest degree. CONCLUSIONS: The matrices are potential candidates for use as tissue-engineering scaffolds by modulating their physical chemical properties according to the specific application. PMID- 20740430 TI - Physicochemical properties of collagen sheet from bovine femur. AB - PURPOSE: In the present study collagen sheets were prepared from the spongy part of the bovine femur and characterized from the physicochemical point of view. METHODS: The physicochemical properties of the collagen sheets were studied using scanning electronic microscopy (SEM) and thermogravimetrical analysis (TGA). RESULTS: The SEM studies showed that the collagen sheets are porous and exhibit a fibrous nature. The TGA study revealed that the collagen sheets are a two-phase system containing a protein and a mineral phase. In order to determine the collagen type present in the sample, the sheets were dissolved and studied by circular dichroism (CD) and electrophoresis techniques. The results obtained showed that the nature of the collagen is type I. CONCLUSIONS: The type I collagen sheets from bovine femur isolated in this study are proposed as a biomaterial for medical applications, for example, as an osteoinductive material or they could be used as a bone substitute. PMID- 20740431 TI - Authors Index vol 7 2009. PMID- 20740432 TI - Subjects Index vol 7 2009. PMID- 20740433 TI - Nano-approaches in cartilage repair. AB - Technological improvements in biology, medicine, chemistry, engineering and material science have allowed deeper insights into the architectural and molecular organization levels of tissues and materials, providing innovative approaches and tools for medical treatments. One of the therapeutic targets that may benefit from these new issues is damaged human articular cartilage, a tissue unable to self-heal. In this review, we have not taken into consideration the pathological degenerations that may cause cartilage damage, but we have concentrated on the means of repair, providing a brief overview of the consolidated cellbased approaches for cartilage resurfacing. However, we have also focused on the tight relationships between chondrocytes and their surrounding extracellular matrix. The aim was to evidence the requirements of the cell components of the tissue, the un-fulfillment of which may cause unsatisfactory therapeutic outcomes in present therapies. A deeper analysis of the structural microand nano-characteristics of the articular cartilage matrix is presented to motivate the most recent "nano-approaches" that have been developed and published in the literature. Nanofiber technology, material surface topography and bioactivation, and recent advances in nanoparticle modifications are thus considered for their interesting contributions aimed at improving tissue engineering-based cartilage repair. PMID- 20740434 TI - The observation of nano-crystalline calcium phosphate precipitate in a simple supersaturated inorganic blood serum model - composition and morphology. AB - Aim. Calcium phosphate deposition in blood vessels is correlated to increased mortality risk. In this study, the formation of solid calcium phosphate in an in vitro solution mimicking the inorganic part of blood serum was studied. Methods. The precipitates formed were analyzed using several experimental techniques, including infrared spectroscopy, Raman spectroscopy, X-ray energy dispersive spectroscopy, chemical analysis of combustion gases, thermogravimetric analysis, as well as transmission electron microscopy and scanning electron microscopy. Results. The results indicate a microscopically amorphous but nano-crystalline material with an overall apatite structure. A plausible stoichiometry was determined to Ca5(PO4)3(HCO3).4H2O with an estimated solubility constant of 6.10 39 (mol/L)9. Bicarbonate in the water solution was shown to be essential for the precipitation, giving implications for in vitro studies. Conclusions. The calcium phosphate formed in this study shows many similarities to pathological calcium phosphates regarding composition, morphology and crystallinity. PMID- 20740435 TI - Mechanical characterization of an innovative dental implant system. AB - PURPOSE: The research presented is aimed at the characterization of the mechanical resistance of an innovative system of an abutment-fixture connection in dental implants. This innovative connection system is composed of a triangular prismatic connection designed to improve the anti-rotational properties of the implant, and to seal any gap between the abutment and the fixture. METHODS: The mechanical performances of the dental implant system were investigated by means of static mechanical strength tests, which allowed the identification of the bending, torque and compression resistance of the system, and fatigue testing, according to the practice standard - ISO 14801. Surface finishing was also analyzed by scanning electron microscopy (SEM) observations and laser profilometry tests. RESULTS: The analyzed implant exhibited good mechanical characteristics, both in static and in fatigue tests. Moreover, the gap between the fixture and the abutment detected by SEM analyses was restricted, both before and after fatigue tests, being approximately 4 mum in the worst case observed: this is representative of optimal sealing against fluid infiltration. CONCLUSIONS: The modification of traditional dental implants with the introduction of a triangular prismatic connection system not only allowed the implant rotational stability and sealing performances to increase, but also conferred optimal mechanical resistance to the implant. PMID- 20740436 TI - Effect of exogenous nitric oxide on the proliferation of a human osteoblast (HOS) cell line induced by hydroxyapatite. AB - AIM: The aim of this study was to test the hypothesis that the proliferation of hydroxyapatite (HA)-induced human osteoblast cell line (HOS cells) may be up regulated by exogenous nitric oxide (NO). METHODS: HOS cells were cultured on the surface of HA with or without the presence of a NO donor, S-nitroso acetyl penicillamine (SNAP) or nitroso acetyl penicillamine (NAP). 2-(4-carboxyphenyl) 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) known as carboxy PTIO, a NO scavenger, was added in the cell cultures with or without the presence of SNAP. The cells were also pre-treated with L-N5-(1-iminoethyl)orthinine hydrochloride (L-NIO), an endothelial nitric oxide synthase (eNOS) inhibitor, or anti-integrin alphaV antibody before culturing on HA surfaces with or without the presence of SNAP. Medium, cells alone or cells pretreated with these inhibitors or antibodies was used as the controls. Cell proliferation was assessed by colorimetric assay. RESULTS: The results showed that SNAP, but not NAP, augmented HA-induced HOS cell proliferation. This modulatory effect of SNAP on HA-induced HOS cell proliferation was abolished by carboxy PTIO or anti-integrin alphaV antibody, but only partially reduced by L-NIO. CONCLUSION: Therefore, the results of this study suggest that exogenous NO alone may up-regulate the proliferation of HOS cells attached on HA surfaces via integrin alphaV molecules. PMID- 20740437 TI - Evaluation of the mechanical behavior of a direct compression molded porous tantalum-UHMWPE construct: a microstructural model. AB - Monoblock constructs, for example, porous tantalum and ultra high molecular weight polyethylene (UHMWPE), offer an opportunity to combine the fixation properties of metal-backing and the wear properties of UHMWPE for total joint replacement in one component. AIM: The objective of this research was to develop a two-dimensional microstructural finite element (FE) model to represent a monoblock-construct's structure and to investigate the influence of various design parameters on the construct's structural response. METHOD: A parametric study to evaluate the mechanical behavior of a direct compression molded porous tantalum - UHMWPE construct was performed through a microstructural FE modeling approach. RESULTS: Using a factorial analysis of the overall stiffness, it was found that the most significant design parameters were the Trabecular MetalTM porosity and UHMWPE thickness. It was shown that under normal implant operating conditions (linearly elastic stress and small strain epsilon <0.002), increasing the porosity level and polyethylene layer thickness decreased the structure's stiffness. CONCLUSIONS: Based on different values for apparent elastic modulus from the literature and the parametric analysis, a preliminary UHMWPE thickness could be determined for a proposed design. This approach could help to develop designs in which implant stiffness is sought to be similar to the original stiffness of the biological structure and to better understand the interaction between the main parameters. PMID- 20740438 TI - Normalized specimen thickness requirements of a compact sandwich test for measuring fracture toughness of bone. AB - AIM: Fracture toughness is one of the properties that assesses bone quality. Compact sandwich (CS) test gives a better choice of bone sample size and therefore suits a wide variety of fracture toughness testing needs and constraints. This study addresses one of the important standardization aspects of CS test for fracture toughness testing of bone. The aim of this study is to establish normalized specimen thickness requirements of CS test. METHODS: This study used finite element (FE) simulation of CS test in order to establish the requirements, and experimental fracture toughness tests to verify the same. Statistical analysis validated the FE and experimental results. RESULTS: Validation of FE model was performed using post-hoc analysis of existing experimental data. The experimental CS tests gave statistically valid stress intensity factor and energy release rate of bone. CONCLUSIONS: Reliable normalized specimen thickness requirements of CS test are established. This serves as a guideline to carry out CS test. CS test helps in meeting the fracture toughness testing requirements at macroscopic and sub-millimetre scales. PMID- 20740439 TI - Selected short papers from SIB Societa Italiana Biomateriali Italian National Congress, 17-19 September 2008, Follonica - Italy. PMID- 20740440 TI - Engineering injured spinal cord with bone marrow-derived stem cells and hydrogel based matrices: a glance at the state of the art. AB - Concerning the broad topic of neural tissue engineering, we present a review relating to the state of the art in spinal cord injury repair strategies. Particular attention is given to spinal cord damage causes and effects, in neural and mesenchymal stem cell therapeutic approaches, in the use of hydrogels as cell carriers and in the mathematical modeling of involved phenomena. High importance is given to multidisciplinary strategies applied to spinal cord repair, since new research frontiers are believed to be now on 3D gel/cells and neuroprotective agent constructs for neural reconstruction purposes. PMID- 20740441 TI - Mechanical loading modulates intracellular calcium signaling in human mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) are a promising cell source for tissue-engineered connective tissue repair strategies. Additionally, increasing evidence confirms the role of the mechanical environment in maintaining tissue homeostasis, with calcium signaling implicated as a mediator in mechanotransduction pathways. Spontaneous intracellular calcium signaling was observed in a subset of MSCs embedded within 4% alginate hydrogel constructs, measured by a Ca2+ indicator fluo-4 in conjunction with confocal laser-scanning microscopy. By the use of pair wise analysis, it was shown that distinct populations of MSCs up-regulated and down-regulated the frequency of calcium transients with the application of a 20% static uniaxial compressive strain of 20 min duration, delivered after a 20 min unstrained period. Calcium transients in control specimens were monitored throughout two unstrained 20 min periods. These values were statistically significant (p<0.05) by chi 2 test of independence. This dual-response indicator highlights the heterogeneous nature of MSC populations, which may have important implications for their successful use in cell therapies. PMID- 20740442 TI - Antimicrobial potential of bioactive bone cements. AB - Poly(methyl methacrylate) (PMMA) based bone cement is widely used to anchor artificial joints. In recent years, antibiotics have been incorporated in bone cements and administered systemically to either prevent or reduce the severity of infections. Certain antibiotics, such as tobramycin or vancomycin antibiotics have been incorporated at high concentrations into PMMA bone cements when dealing with infected hip joints, however, the inclusion of some antibiotics adversely affect the mechanical properties of the cement. Furthermore, studies have indicated that the incorporation of gentamicin in PMMA cements does not have a statistically significant effect on the biofilm formation of species such as Staphylococcus aureus (S. aureus). Bioactive glasses have been shown to have numerous applications in the biomedical field because of their properties in bonding to both hard and soft tissues. Bioglass(R) undergoes surface dissolution in a physiological environment forming a hydroxycarbonate apatite layer and, in addition, exhibits the anti-inflammatory properties. Recent studies have shown that two paste bioactive bone cement systems that use Bioglass(R) as filler exhibit physical and mechanical properties comparable to PMMA cements with low polymerization exotherm and better mechanical properties with improved adhesion to bone and implant surfaces. In this study, Bioglass(R) containing two paste bone cements were investigated for their potential bacteriostatic properties and compared with PMMA cements with and without antibiotics. The results of this study indicated that the PMMA cement containing the antibiotic, gentamycin and the Bioglass(R) containing cements both pre- and post-immersion in simulated body fluid (SBF) for brief periods showed the inhibition zones were not statistically significantly different in their average size for any of the three bacterial species, namely Pseudomonas aeruginosa, S. aureus and Staphylococcus epidermidis. However, the PMMA cement without any antibiotic, namely gentamycin (CMW1) did not show any inhibition zones around the specimens for any of the three bacterial species. It was also noted that both Bioglass(R) filled bioactive cements immersed in SBF showed statistically significant increases in inhibition zones for all three specimens compared to specimens that were not immersed (p<0.001). PMID- 20740443 TI - Detection of the insertion end point of cementless hip prostheses using the comparison between successive frequency response functions. AB - Vibration analysis is a non-destructive testing technique, which has a potential to assess the mechanical properties of the stem/femur system in total hip replacement (THR). Different methods based on vibration analysis have already been successfully used to determine bone mechanical properties, to monitor fracture healing, and to quantify the fixation of dental implants. This paper describes an in vitro study of the change in the frequency response function (FRF) of the hip stem/femur structure during implant insertion. At successive insertion stages, the FRF of the system was measured by impulse excitation on the prosthesis neck, in the range 0-5000 Hz. To quantify the difference between two successive FRF spectra, the Pearson's correlation coefficient and the cross correlation function were used. The stiffness of the implant/bone system varies during insertion, which results in a change in FRF, especially in the range of higher frequencies. If the FRF spectrum shifts to the right, then the stiffness of the implant/bone connection increases and, consequently, the stability of the implant increases as well. If the FRF does not change between two successive insertion stages, then the mechanical properties of the prosthesis-femur structure does not change; therefore, the stem-bone connection is stable and the insertion should stop to avoid intra-operative fractures. Based on the obtained results, a per-operative protocol based on FRF analysis can be designed to assess the stability of a cementless hip prosthesis, and to detect the insertion end point. PMID- 20740444 TI - Examination of failed polyurethane gastrostomy devices and comparison with samples incubated in vitro. AB - Percutaneous endoscopic gastrostomy (PEG) devices provide a route for nourishment and medication to those unable to swallow. The disintegration and discoloration of a type of polyurethane PEG device was evaluated. Five ex vivo samples were obtained and they showed discoloration, pitting and environmental stress cracking (ESC). A group of unused PEG devices were exposed to a gastric acid and pepsinogen formulation at 37 degrees C for up to 6 weeks. An additional cohort was investigated for fungal colonization by incubating with a Candida culture preparation at 37 degrees C for up to 6 weeks. Candida was shown to grow on all PEG samples exposed to it. The samples incubated in Candida hardened and discoloured and showed pitting but no ESC. In contrast, the samples incubated in the gastric acid formulation tended to soften and showed ESC but no discoloration. PMID- 20740445 TI - A computational modeling approach for the characterization of mechanical properties of 3D alginate tissue scaffolds. AB - Scaffold guided tissue engineering is an innovative approach wherein cells are seeded onto biocompatible and biodegradable materials to form 3-dimensional (3D) constructs that, when implanted in the body facilitate the regeneration of tissue. Tissue scaffolds act as artificial extracellular matrix providing the environment conducive for tissue growth. Characterization of scaffold properties is necessary to understand better the underlying processes involved in controlling cell behavior and formation of functional tissue. We report a computational modeling approach to characterize mechanical properties of 3D gellike biomaterial, specifically, 3D alginate scaffold encapsulated with cells. Alginate inherent nonlinearity and variations arising from minute changes in its concentration and viscosity make experimental evaluation of its mechanical properties a challenging and time consuming task. We developed an in silico model to determine the stress-strain relationship of alginate based scaffolds from experimental data. In particular, we compared the Ogden hyperelastic model to other hyperelastic material models and determined that this model was the most suitable to characterize the nonlinear behavior of alginate. We further propose a mathematical model that represents the alginate material constants in Ogden model as a function of concentrations and viscosity. This study demonstrates the model capability to predict mechanical properties of 3D alginate scaffolds. PMID- 20740446 TI - Evaluation of genotoxicity of recycled Ni-Cr dental casting alloys: an in vitro study. AB - This study was conducted to evaluate the genotoxicity of nickel-chromium (Ni-Cr) base metal alloys in their reused state at different time intervals. Two commercially available Ni-Cr alloys (Wiron 99, remanium Cse) were evaluated. Three groups of alloy specimens (disks 3 mm x 5 mm) were fabricated from each of these alloys. The first groups were made with 100% new alloy, the second groups with 50 wt% of new alloy and 50 wt% of once used alloy and the third groups with 100% once used alloy. Distilled water conditioned with the alloy specimens for four time intervals of 1, 2, 4 and 8 weeks was used for testing the genotoxicity on Chinese hamster V79-HG04 fibroblasts using the micronucleus assay. Cells were examined for the number of micronuclei in the cytoplasm. More numbers of micronuclei the more the DNA damage. Statistical analysis was carried out using one-way ANOVA to determine whether the group means differed from one another significantly. Post hoc analysis was done using Bonferroni 't' test to compare the differences in mean values between groups. The highest genotoxicity was noticed at 4 weeks. It did not alter significantly when the length of conditioning was increased to 8 weeks. The lowest genotoxicity was observed for the first groups, intermediate results for the second groups and the greatest genotoxicity for the third groups when compared to controls. There were no significant differences between Wiron 99 and remanium CSe. Considering the elevated genotoxicity of Ni-Cr alloys in their reused state, the practice of reusing the alloy just for economic reasons should be discouraged. PMID- 20740447 TI - Influence of the suture in the propagation of tears in calf pericardium employed in the construction of cardiac bioprostheses. AB - The tearing of the fibers of biomaterials employed in implants or bioprostheses leads to early the failure of these devices. The purpose of this study was to determine the force necessary to propagate a tear in a biological tissue, calf pericardium, when sutured. We analyzed the outcome of 230 trials. There was a loss of resistance to tearing in samples sutured edge-to-edge as compared to unsutured control samples. This loss was not observed when the suture was preceded by an intact or protective zone. The values corresponding to the tearing force for an overlapping suture, especially when sewn with Gore-Tex(R), were higher than those obtained in controls. This study confirms the deleterious effect of the edge-to-edge suture, which can be minimized by protecting the suture, and the excellent behavior of the overlapping suture. PMID- 20740448 TI - Modeling and mechanobiology of cerebral aneurysms. AB - The purpose of this work is to review the computational models of the adaptive behavior of the cerebral vascular wall aimed at simulating aneurysm formation and enlargement. Cerebral aneurysms are localized abnormal enlargements of the intracranial arterial vessels. The origin of this pathology is still unclear: however, aneurysm formation is thought to be the result of interplay between biomechanical properties of the vessel wall and their possible changes, such as adaptive response to mechanical stimuli. Recently, different computational approaches were suggested in the literature aiming to describe the mechanobiology of the cerebral vascular wall. Most of the computational adaptive models showed a common approach for the geometrically non-linear kinematic description of the phenomenon, whilst the constitutive laws defining the rates of growth variables may differ considerably according to the specific phenomenon considered. These studies allowed the reproduction of some peculiar aspects of aneurysm mechanobiology; however, continued interdisciplinary research is mandatory for a better understanding of the mechanisms involved in the evolution of cerebral aneurysms. PMID- 20740449 TI - Simulation of extreme loads on the proximal femur for implant fixation assessment. AB - Total joint replacement patients today are younger, heavier, and more active than total joint replacement patients 40 yrs ago. Consequently, patient expectations and prosthesis requirements have increased and there is a need to re-evaluate preclinical testing methods. We present the design rationale for a novel load simulator for the proximal femur, capable of applying a more aggressive load profile than previous simulators. This simulator was used to measure three dimensional micromotion of a cemented total hip replacement femoral stem under simulated physiological loading. We assessed the influence of a separate abductor muscle force, a higher joint reaction force, and a more accurate implant stability measurement system included in the new simulator and compared the results to the lower, single joint reaction force included in a previously published simulator. Per-cycle motion at both cement interfaces and stem and cement mantle migration obtained from both simulators using the same femoral stem design, are compared. Although the new simulator applied higher loads, per-cycle motions were lower than previously reported. In both studies, regardless of the presence or lack of a separate muscle force, the greatest motions were in the medial-lateral direction (new: 27 +/- 4 mum, old: 67 +/- 21 mum). The findings indicate that magnitude and direction of peak joint reaction force and inclusion of a separate muscle force have a significant effect on femoral stem stability measurements. We recommend that future femoral stem stability studies consider using load simulation techniques and a direct motion measurement system comparable to the one presented in this study. PMID- 20740450 TI - The effects of cell culture parameters on cell release kinetics from thermoresponsive surfaces. AB - The thermoresponsive properties of poly(N-isopropyl acrylamide) (pNIPAM) have led to its wide use in bioengineering applications, including the reversible adhesion of mammalian cells. The groups performing this research have used different solutions to initiate cell release and have varied the temperature of the solution during detachment. To our knowledge, there has been no direct correlation between the solution identity or temperature on the efficiency of cell release from pNIPAM films. In this work, we present a study of the effect of the solution type and temperature used to initiate detachment on the time required to achieve 100% detachment of bovine aortic endothelial cells (BAECs) from pNIPAM. The pNIPAM films used in this work were obtained using a novel technique using a spin-coated solution containing pNIPAM (spNIPAM). We found that the fastest, most reliable release of cells occurred below the LCST of the polymer at 4 degrees C in serum free media (SFM). As it is sometimes desirable to stop cell metabolism at the time of detachment (e.g., to "freeze" protein expression prior to subsequent analysis), the use of extremely cold SFM would be ideal in such cases. PMID- 20740451 TI - The effect of cross-linking time on a porous freeze-dried collagen scaffold using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a cross-linker. AB - Collagen is a widely studied natural polymer for use as a scaffold material for various tissue engineering applications. Untreated collagen, however, has a fast biodegradation rate and low mechanical strength. Additionally, collagen cross linking has been studied extensively and different cross-linking agents and methods have been explored. Although glutaraldehyde (GA) is the most convenient and traditional chemical agent currently used for this purpose, it nevertheless poses potential cytotoxicity. Therefore, 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDC) is widely being studied as well, due to its characteristic of being a zero-length cross-linker that does not remain in the collagen's structure. Nevertheless, cross-linking with EDC can be implemented in several ways. In this study, two methods of cross-linking with EDC, prior to and post freeze-drying, were examined for freezedried collagen scaffolds. Four different collagen concentrations between 0.3 and 2.0 w% were inspected and different cross-linking methods were examined by a differential scanning calorimeter (DSC) to determine the collagen's denaturation temperature (Td). Furthermore, the water uptake abilities of the scaffolds were tested in phosphate buffered saline (PBS) and the scaffolds' pore structure was examined with a scanning electron microscope (SEM). As assumed, the DSC measurements demonstrated that collagen Td values increased with increasing collagen concentration. With lower collagen concentrations, the cross-linking post freeze-drying enhanced the Td values, but with higher collagen concentrations, the Td values were increased only with cross-linking prior to freeze-drying. The water uptake measurement showed increased water uptake ability when cross-linking post freezedrying. The pore sizes of the different collagen scaffolds were between 50 and 120 mum. PMID- 20740452 TI - Parametric FE mesh generation: application to the cervical spine. AB - A voxel-based reconstruction algorithm, targeted at the generation of finite element (FE) meshes of structures with schematic geometry, is presented. The algorithm is able to generate three dimensional fully hexahedral FE meshes of structures composed of volumes with a schematic geometry. In order to be meshed, each volume must be described in terms of a set of surfaces which enclose the volume. Due to its schematic nature, the method allows the generation of fully parameterized FE models, thus it facilitates the investigation of the mechanical relevance of geometrical parameters by speeding up the mesh generation process. The algorithm was employed in the automatic construction of an FE model of the C3 C7 spinal segment with schematic geometry, made up exclusively of hexahedral elements. Non-linear simulations were carried out in different loading conditions: flexion- extension, lateral bending and axial rotation. The results were compared to data retrieved from the literature in order to ensure the validity of the model. Moment-rotation curves for each loading condition were determined. The range of motion was obtained for each spinal unit and loading condition. Both principal and coupled rotations were determined in lateral bending and axial rotation, for each spinal unit. The intradiscal pressure was also computed in the nucleus pulposus, for all the intervertebral levels. Geometrical parameterization of the models offers potential for the biomechanical investigation of pathologic conditions and surgical procedures, such as spinal fusion and disc arthroplasty, even on a patient-specific basis. PMID- 20740453 TI - Green chemical synthesis of calcium phosphate bioceramics. AB - A standard preparation technique of the graft relevant calcium phosphates (which includes the dissolution of watersoluble compounds containing calcium cations and phosphate anions, the slow addition of one solution into another under alkaline pH, followed by aging, suspension separation, washing off, drying and sintering at elevated temperatures) has been reconsidered from an environmental point of view. The entire process has been simplified to a single stage, and a number of intermediate stages have been excluded without influencing the quality of the final products. In this report, we launch a new environmentally friendly preparation technique of calcium phosphate bioceramics for potential use as bone grafts. PMID- 20740454 TI - Mechanical strength of dental implants. AB - A series of mechanical strength tests have been carried out in order to characterize some dental implants. Most specimens tested were of the tapered joint kind, but for comparison further tests have been carried out on screw joined implants. The loads applied were similar to those existing in the typical working conditions of the component; however, in order to conform to the ISO standard 14801, loads higher than those achieved in working conditions were applied. The static characterization tests determined the strength of the system, with large deformations preceding rupture. The fatigue tests led to the determination of the fatigue limit of the dental implant, defined conventionally in these cases as the maximum value under which the system has a life of at least 2.106 cycles. The fatigue limit is higher than the stress that the teeth endure during the normal process of mastication, and it confirms the suitable structural design of the device. Failure analysis has shown that the fatigue crack leading to rupture commonly occurs in the section in which the hexagonal insert in the tapered joint begins. PMID- 20740455 TI - Performances of an accelerometric device for detecting fall and loss of consciousness. AB - Falls and loss of consciousness (FLoC) is the leading cause of serious health problems, above all in the elderly population, since the subjects involved are not able to ask for help and may lie in critical conditions for a long time, thus deteriorating into severe conditions which can even lead to death. Therefore, developing a device capable of automatically detecting a FLoC and activating an alarm call seems to be of utmost importance. This study intended to develop such a device using an accelerometer sensor. Four hundred and sixty simulated falls were performed by 20 subjects: 10 young subjects and 10 elderly subjects. The young subjects were asked to perform 200 FLoCs as well as 60 non common activities (NCAs), whereas the elderly subjects were asked to carry out only 200 activities of daily living (ADL). The signal used to detect the fall event was acquired by a single accelerometer placed on the subjects' belts. The test set was divided into two groups of the same size: Training Set (TS) and Verification Set (VS). The first set was meant to determine the related algorithm, whereas the second set was intended to check its reliability. The proposed algorithm was devised to detect the effects of the three phases of a FLoC (impact of the body on the ground, lying position and immobility) into the acceleration and jerk signals along the cranio-caudal axis (CCA). The correct detection of all FLoC cases and the absence of false positives among ADL corroborate the usefulness of the device proposed. PMID- 20740456 TI - Biomaterials, tissue engineering, gene therapy. PMID- 20740457 TI - Cells response to topographic and chemical micropatterns. AB - It is well known that surface features, such as topographical or chemical cues, can affect cell behavior from initial attachment and migration to differentiation and production of new tissues; this phenomenon is called contact guidance. A great improvement in studies concerning this phenomenon comes from progress in microfabrication techniques such as photolithography or soft lithography. Due to these techniques, a wide variety of micro-patterned surfaces can be realized to control cell size, shape, spatial organization and proliferation. These studies promoted the development of cellular bioassays that provide entirely new insights into the factors that control cell adhesion, proliferation and differentiation onto material surfaces and molecular signaling pathways. The ability to control shape and spreading is also important to direct stem cells to different specific lineages, but it is also of great importance for the design of cell culture substrates for tissue engineering. In this work, the possibility of patterning surfaces is investigated, with particular focus on the micrometric scale. The response of different types of cells is also investigated. PMID- 20740458 TI - Biomechanical effects of autonomous augmentation on the adjacent unaugmented vertebral bodies: influence of the number of functional spinal units in a finite element model. AB - PURPOSE: The results of finite element analysis (FEA) studies on the effect of augmentation of one vertebral body (VB), using vertebroplasty (VP) or balloon kyphoplasty (BKP), on the biomechanics of the adjacent and nonadjacent VBs are contradictory. One reason for this record is that different levels of the spine, numbers of structures, and numbers of functional spinal units (FSUs) (X) were included in the models used in different studies. The purpose of the present study was to clarify this effect as far as X is concerned. METHODS: A validated three-dimensional solid model of the lumbar spine was constructed from computed tomography scans and prophylactic augmentation of L2 was simulated. In the FEA, the model was subjected to a uniformly distributed compressive load (total load = 1300 N) on the superior endplate of L1. The extent to which a change in X affects the values of the mean von Mises stress (sigmaVM) and the mean elastic strain energy density (ESED) in all structures adjacent to L2 was determined. (These changes were with respect to the case where all the VBs in the model are intact.) RESULTS: As X increased (from 1 to 2, from 2 to 3, and from 3 to 4), there were clear variations in the number of stable changes in both sigmaVM and ESED in each structure. The largest number of these changes occurred when X changed from 2 to 3. CONCLUSION: The results suggest that three is the number of FSUs that should be included in models of the lumbar spine to be used in FEA studies of VP and BKP. PMID- 20740459 TI - A comparison between internal and surface temperature measurement techniques during phacoemulsification cataract surgery: thermocamera versus thermocouple. AB - PURPOSE: Corneal and scleral burns, one of the main complications that can occur during a cataract operation, are produced by overheating due to the use of the phacoemulsifier. The temperature of the anterior chamber of the eye can be measured both invasively using thermocouples and non-invasively, but only superficially, using a thermocamera. METHODS: To compare the measures obtained from both techniques an in vitro experimental analysis was conducted on pigs' eyes. During a simulated phacoemulsification cataract operation both the surface temperature with a thermocamera and the temperature inside the anterior chamber with a thermocouple were recorded. For each procedure, the maximum temperature values measured by each technique were compared. RESULTS: The results of this research show that the difference between the maximum values measured with the two techniques is on average 0.5 degrees C. CONCLUSIONS: It is possible to employ a thermocamera technique instead of a thermocouple technique to provide an indication of the temperature inside the anterior chamber. PMID- 20740460 TI - Spontaneous gait recovery after sciatic nerve transection impairs the non invasive evaluation of artificial nerve guides in rats. AB - PURPOSE: The study of the in-vivo regeneration of a nerve, made by purely histological methods, requires a high number of animals: this poses serious problems of technique, ethics and funding. A cheaper analysis, performed on the same animal along the duration of a study, is seeked with favour and Authors wanted to evaluate gait recovery after sciatic nerve transection as a non invasive method to evaluate the performance of an artificial nerve-guide in rats. METHODS: Male Wistar rats (n=16) were divided into three groups: in group A (n=5) the experimental gap produced was bridged by a custom-made guide; in group B (n=7) animals were "sham-operated"; in group C (n=4) a PMMA cap sealed the proximal nerve stump. RESULTS: In group A a regenerated nerve was retrieved after 8 weeks, in all animals. In group B it was possible to retrieve mostly bulbous neuromatous stumps. In group C all the animals presented a voluminous neuroma. Signs of auto-mutilation had the following distribution: 1/5 in group A; 4/7 in group B; 3/4 in group C. A clear difference in gait recovery exists only between group C (no recovery) and the two other groups (early recovery in both). CONCLUSIONS: The present study highlights that in the male Wistar rat sciatic model a spontaneous recovery in gait pattern occurs very early (within the first or second week); with this animal model, a recovery in gait is likely to ensue irrespective of the kind of device eventually tested since it may happen even without a device. PMID- 20740461 TI - Biomechanical behavior of a novel composite intervertebral body fusion device. AB - PURPOSE: Low back pain related to intervertebral disc (IVD) degeneration represents a socio-economic problem which affects quality of life. In order to solve this problem the current gold standard techniques such as spinal arthroplasty and arthrodesis (or fusion) are considered. As for spinal arthroplasty, over the past 40 yrs, IVD prostheses have been designed to maintain the correct IVD spacing and to allow for motion, while providing stability. However, there are many difficulties in incorporating important features such as viscoelastic and shock absorber behavior of natural IVDs in a prosthetic disc design. Moreover, in some cases, the use of IVD prostheses does not represent the ideal solution. Consequently, the aim of this study was to improve the design of alternative devices for spinal fusion, which overcome the problems related to metal ones currently available on the market, such as stress shielding, stress concentration effects and eventual bone corrosive or inflammatory reaction. METHODS: Accordingly, a novel polyetherimide (PEI)-based cage reinforced with carbon fibers through filament winding and compression molding technologies was realized. RESULTS: The characterization through a porcine model has produced very interesting results. The small values obtained from local compression tests have suggested that a reduction in mobility occurred, whereas distributed compression tests on IVDs prosthesized by employing the PEI-based cage reinforced with carbon fibers have highlighted a compressive stiffness of 100 MPa. This stiffness is lower than that of the IVD prosthesized through the titanium cage (146 MPa), and closer to the stiffness of natural porcine IVDs (90 MPa). CONCLUSIONS: Through a suitable composite cage design it is possible to control stress-strain distributions and the mechanical signals to bone, thus avoiding the stress shielding phenomena, but also corrosion and metal ions release which are typical of the metallic implants. PMID- 20740462 TI - Electrochemical surface modification of titanium for implant abutments can affect oral bacteria contamination. AB - PURPOSE: This research concerns the characterization of an electrochemical surface treatment applied to titanium, focused especially on the treatment of the transmucosal area of dental implants and abutments. The treatment is applied to improve soft tissue adhesion, to control and limit bacteria adhesion and proliferation, and to improve the aesthetic performance through a proper colorization of the metal surface. METHODS: The electrochemical treatment considered, obtained on titanium by Anodic Spark Deposition technique (ASD), was performed in a calcium phosphate enriched solution. The bacteria behaviour was assessed by in vitro and in vivo tests. RESULTS: The investigated ASD treatment showed some antibacterial effect. No negative cytocompatibility effects were found on MG63 - human osteosarcoma cell lines and L929 - murine fibroblasts. CONCLUSIONS: The ASD modified treatment was found capable of modifying the titanium oxide layer providing a prevalent anatase crystalline structure and a microporous morphology, which can play an important role in the tissue integration process. The treatment was found capable of enriching the surface with calcium, providing improved biocompatibility and a light gray colorization. This last point is important for the aesthetic improvement of dental implant systems in the transgingival area. PMID- 20740463 TI - Kinematics of trunk movements: protocol design and application in obese females. AB - PURPOSE: Whether kinematic analysis of the trunk can provide useful clinical insight into the relationship between function and various spinal conditions is still under debate. The aim of this study was to develop a clinical protocol and an associated biomechanical model to characterize quantitatively the trunk movements in obese subjects. METHODS: Twenty (10 obese, 10 control) female subjects were evaluated with an optoelectronic system and passive markers attached to the spine during forward flexion, lateral bending, and rotation of the trunk. RESULTS: We found a systematic error due to skin artifacts of less than 5 degrees in both groups. Intra- and inter-subject standard deviation was less than 6 degrees . Obese subjects demonstrated a significantly reduced motion in the thoracic spine associated with an increased pelvic tilt angle as compared to controls. CONCLUSIONS: Our protocol was able to characterize trunk mobility in obese and normal subjects suggesting that kinematics could represent, even in an obese population, a promising method to investigate subclinical spinal disorders and to assess the effectiveness of rehabilitation programs. PMID- 20740465 TI - Authors Index vol 6 2008. PMID- 20740464 TI - Porous biodegradable microtubes-based scaffolds for tissue engineering, part I: production and preliminary in vitro evaluation. AB - PURPOSE: we aimed at investigating spinning as a potential technology to produce porous microtubes for constructing scaffolds. Spinning is indeed a well known technique for producing polymeric fibres, also used in the biomedical field, but its applications for tissue engineering purposes has never been deeply investigated. METHOD: the behaviour of a multi-phase poly-lactide-caprolactone copolymer based solution was here studied for the production under spinning condition of porous microtubes for patterning planar and three dimensional bioactive systems to be used for tissue regeneration. Obtained non-woven fabrics were tested investigating cells response with fibroblast, osteoblasts and chondrocytes. RESULTS: once achieved optimal process parameters, microtubes were produced with a controlled and well diffused porosity which were then used to build two and three dimensional scaffolds. Cytocompatibility tests performed on these scaffolds showed good results on all tested cell models, both qualitatively (SEM imaging) and quantitatively. Particularly, cell proliferation assays by Alamar Blue staining indicated increasing trends with time and comparable values with controls. CONCLUSIONS: results hereby described represent a proof of concept of the process developed and its applicability for obtaining microtubes with controlled porosity. Moreover, two and three dimensional scaffolds built from such fibres showed to be very promising substrates for cell adhesion and growth. Finally, the process developed can be taken into GMP qualification and thus scaffolds can be upgraded to medical devices and used for regenerative medicine into human applications. PMID- 20740466 TI - Subjects Index vol 6 2008. PMID- 20740467 TI - Polymer-based composite scaffolds for tissue engineering. AB - Tissue engineering may be defined as the application of biological, chemical and engineering principles toward the repair, restoration or regeneration of living tissue using biomaterials, cells and biologically active molecules alone or in combinations. The rapid restoration of tissue biomechanical function represents a great challenge, highlighting the need to mimic tissue structure and mechanical behavior through scaffold designs. For this reason, several biodegradable and bioresorbable materials, as well as technologies and scaffold designs, have been widely investigated from an experimental and/or clinical point of view. Accordingly, this review aims at stressing the importance of polymer-based composite materials to make multifunctional scaffolds for tissue engineering, with a special focus on bone, ligaments, meniscus and cartilage. Moreover, polymer-based nanocomposites will also be briefly introduced as an interesting strategy to improve the biological and mechanical performances of polymer scaffolds, especially for bone tissue engineering. PMID- 20740468 TI - Cyclic mechanical stimulation favors myosin heavy chain accumulation in engineered skeletal muscle constructs. AB - PURPOSE: Since stretching plays a key role in skeletal muscle tissue development in vivo, by making use of an innovative bioreactor and a biodegradable microfibrous scaffold (DegraPol(R)) previously developed by our group, we aimed to investigate the effect of mechanical conditioning on the development of skeletal muscle engineered constructs, obtained by seeding and culturing murine skeletal muscle cells on electrospun membranes. METHODS: Following 5 days of static culture, skeletal muscle constructs were transferred into the bioreactor and further cultured for 13 days, while experiencing a stretching pattern adapted from the literature to resemble mouse development and growth. Sample withdrawal occurred at the onset of cyclic stretching and after 7 and 10 days. Myosin heavy chain (MHC) accumulation in stretched constructs (D) was evaluated by Western blot analysis and immunofluorescence staining, using statically cultured samples (S) as controls. RESULTS: Western blot analysis of MHC on dynamically (D) and statically (S) cultured constructs at different time points showed that, at day 10, the applied stretching pattern led to an eight-fold increase in myosin accumulation in cyclically stretched constructs (D) with respect to the corresponding static controls (S). These results were confirmed by immunofluorescence staining of total sarcomeric MHC. CONCLUSIONS: Since previous attempts to reproduce skeletal myogenesis in vitro mainly suffered from the difficulty of driving myoblast development into an architecturally organized array of myosin expressing myotubes, the chance of inducing MHC accumulation via mechanical conditioning represents a significant step towards the generation of a functional muscle construct for skeletal muscle tissue engineering applications. PMID- 20740469 TI - Stress distribution in retentive arms of combination clasps used on premolars. AB - INTRODUCTION: Stresses resulting from cast clasp arms during insertion and the removal of removable partial dentures are the main causes of deformations or fractures. Therefore, achieving clasp designs producing less stress is very important. OBJECTIVE: Retentive clasp arms used for premolars were investigated through the reverse engineering approach. The aim was to determine stress distribution in oval and half-oval clasps cross-sections in order to analyse biomechanical behavior. MATERIAL AND METHODS: Purposely designed experimental three-dimensional (3D) models of the clasp arms were constructed on the buccal surface of an upper first premolar, to be used for structural simulations. 3D teeth models obtained after laser scanning were used as a support for retentive clasp arms modeling. Parameters of the clasp arms like length, thickness and cross-section were considered for the simulation of stainless steel wires. A concentrated load of 5 N was applied at the inner tip of the clasp arm. RESULTS: A precise model of the coronal buccal surface of an upper first premolar was generated. This model was a useful tool in designing stainless steel clasp arms of different thickness and cross-section. In all cases, high stress values were located on the inner surface of the clasp arm, in the part located above the height of the contour. A similar bending stiffness was observed between the half round cross-section design with a diameter of 1 mm and the round cross-section design with a diameter between 0.6 and 0.7 mm. CONCLUSIONS: This in vitro study demonstrated that the reverse engineering approach and structural analyses provide a powerful tool for designing clasps and visualizing fracture risk areas and for choosing the adequate cross-section for each case. Within the limitations of this study, it was suggested that, on premolars, the biomechanical performance of half-round cross-sections for the retentive arms may be higher than round sections of clasp arms showing similar mechanical stiffness. PMID- 20740470 TI - Thermal stabilization of highly crosslinked UHMWPE: a comparative study between annealed and remelted resins. AB - PURPOSE: An important issue related to the use of highly crosslinked ultra-high molecular weight polyethylene (HXLPE) in arthroplasty concerns the long-term oxidation of the polymer and related degradation of its end-user properties. Although in very recent years several procedures have been introduced into the manufacturing of prosthetic components to overcome this problem, the risk of long term oxidation has not been completely eliminated. The aim of this study is to compare the effects on the physical and mechanical properties of HXLPE from two different thermal treatments used to promote oxidative stabilization. It also gives a description of the effects of oxidative degradation on the mechanical performance of HXLPE. MATERIALS AND METHODS: Virgin medical grade UHMWPE GUR 1020 was irradiated at 100 kGy and submitted to heat treatments at either 110 degrees C (annealing) or 150 degrees C (remelting). Oxidation analysis, Wear tests, Tensile tests and Charpy impact tests were carried out. RESULTS: The temperature of the thermal treatment affects both oxidation resistance and impact strength of HXLPE, whereas wear resistance is not affected. CONCLUSION: The study provides a confirmation that oxidative degradation is a serious issue for the long-term performance of HXLPE prostheses. PMID- 20740471 TI - Biological evaluation of solid freeformed, hard tissue scaffolds for orthopedic applications. AB - PURPOSE: Hydroxyapatite (HA) lattices were made by extrusion freeforming, a rapid prototyping process, and sintered to produce hard tissue scaffolds for bone regeneration. These highly reticulated lattice structures can be built directly from a computer design file which decides and controls their macroscopic shape, pore structure and size distribution. They are therefore defect-specific and show potential in tissue engineering for non-load bearing sites. METHODS: Using a commercial human osteoblast-like cell line (HOS TE 85), biocompatibility was evaluated in an in vitro study. A high level of cell adhesion was evident by scanning electron microscopy on both convex and concave surfaces and the cell attachment was revealed at different depths into the scaffold. An AlamarBlue(R) assay was carried out to assess cell proliferation, which was further confirmed by quantifying total DNA concentration and total protein content. RESULTS: The cell proliferation was significant and the pattern was comparable to that of the tissue culture control, ThermanoxTM. ALP activity and osteocalcin were quantified to evaluate the extent of cell differentiation, which confirmed the retention of the phenotype for the period studied. Mineralization of the matrix was determined via formation of nodules. CONCLUSIONS: HA scaffolds are non-toxic, able to maintain cell viability and support cell growth, proliferation, differentiation, and nodule formation. PMID- 20740472 TI - Lumbar total disc replacement: a numerical study. AB - AIM: The aim of this study was to evaluate the biomechanical effects of the Maverick(R) disc prosthesis at the implanted and adjacent level by the finite element (FE) method. MATERIALS AND METHODS: A 3D FE model of the L3-L5 segment was built. To simulate the different physiological movements (flexion, extension, lateral bending, axial rotation) pure moments of 10 Nm were applied. To evaluate the effect of the prosthesis, a 3D model of the device was built and inserted in the L3-L5 model. The ROMs obtained with the intact model were imposed as maximal rotations to the instrumented model, therefore implementing the Panjabi hybrid protocol. RESULTS: Increased ROMs at the implanted level and reduced ROMs at the adjacent level were predicted. A similar moment-rotation behavior was calculated after simulation of prosthesis insertion. No significant effect was predicted in terms of von Mises stress at the adjacent level after implantation of the prosthesis. CONCLUSIONS: Within the limitations of the models, the numerical results of this study predicted a preserved kinematics and stress at the adjacent segment, after insertion of the prosthesis. PMID- 20740475 TI - Effects of oral dosage form and storage period on the antioxidant properties of four species used in traditional herbal medicine. AB - Herbal infusions and decoctions in water are some of the most commonly consumed beverages in the world. Although water is not a good solvent for many of the active components in herbs, liquid preparations are rich in several bioactive compounds. Most of them have powerful antioxidant activity and have been related to medicinal herbs' properties. Herein, decoctions and infusions in water of lemon-verbena (Aloysia citrodora) aerial parts and leaves, fennel (Foeniculum vulgare), pennyroyal (Mentha pulegium) and spearmint (Mentha spicata) aerial parts with different periods of storage (0, 30, 60 and 120 days), were prepared. The effects of the method of preparation and storage period on their antioxidant properties were analysed. For all the analysed species, infusions gave better results than the corresponding decoctions. Spearmint infusions showed the highest antioxidant properties, at all the storage periods, probably due to the highest levels and synergy between phenolics, flavonoids and ascorbic acid found in this sample. Linear discriminant analysis confirmed that the length of storage period has a significant influence on the antioxidant activity and antioxidant content. Flavonoids and reducing sugars proved to be the parameters that most highly contributed to cluster individual groups according to different periods of storage. PMID- 20740476 TI - Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells. AB - Aggregated beta-amyloid (Abeta) and elevated plasma levels of homocysteine have been implicated as critical factors in the pathogenesis of Alzheimer's disease. The neuroprotective effects and possible mechanism of four structurally similar dibenzocyclooctadiene lignans (namely schisandrin, schisantherin A, schisandrin B and schisandrin C) isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) against Abeta25-35 and homocysteine toxicity in PC12 cells was studied. Exposure of PC12 cells to 0.5 um Abeta25-35 caused significant cell death, increased the number of apoptotic cells, elevated reactive oxygen species, increased the levels of the pro-apoptotic protein Bax and caspase-3 activation. All these effects induced by Abeta25-35 were markedly reversed by schisandrin B and schisandrin C pretreatment, while schisandrin and schisantherin A had no obvious effects. Meanwhile, schisandrin B and schisandrin C reversed homocysteine-induced cytotoxicity. The results indicated that schisandrin B and schisandrin C protected PC12 cells against Abeta toxicity by attenuating ROS production and modulating the apoptotic signal pathway through Bax and caspase-3. Further structure-activity analysis of Schisandra lignans and evaluations of their neuroprotective effects using AD animal models are warranted. PMID- 20740477 TI - HandTutorTM enhanced hand rehabilitation after stroke--a pilot study. AB - BACKGROUND AND PURPOSE: This study assessed the potential therapeutic benefi t of using HandTutorTM in combination with traditional rehabilitation in a post-stroke sub-acute population. The study compares an experimental group receiving traditional therapy combined with HandTutorTM treatment, against a control group receiving only traditional therapy. METHOD: An assessor-blinded, randomized controlled pilot trial, was conducted in the Reuth rehabilitation unit in Israel. Thirty-one stroke patients in the sub-acute phase, were randomly assigned to one of the two groups (experimental or control) in sets of three. The experimental group (n = 16) underwent a hand rehabilitation programme using the HandTutorTM combined with traditional therapy. The control group (n = 15) received only traditional therapy. The treatment schedules for both groups were of similar duration and frequency. Improvements were evaluated using three indicators: 1) The Brunnstrom-Fugl-Meyer (FM) test, 2) the Box and Blocks (B&B) test and 3) improvement parameters as determined by the HandTutorTM software. RESULTS: Following 15 consecutive treatment sessions, a signifi cant improvement was observed within the experimental group (95% confi dence intervals) compared with the control group: B&B p = 0.015; FM p = 0.041, HandTutorTM performance accuracy on x axis and performance accuracy on y axis p < 0.0003. CONCLUSION: The results from this pilot study support further investigation of the use of the HandTutorTM in combination with traditional occupational therapy and physiotherapy during post stroke hand function rehabilitation. PMID- 20740478 TI - Young serious and vulnerable offenders in the Netherlands: a cohort follow-up study after completion of a PIJ (detention) order. AB - BACKGROUND: About 150-200 'Placement in an Institution for Juveniles Orders' (PIJ orders) are imposed each year in the Netherlands. Many of the young people under these orders have mental disorders or 'threatened psychological development' and are thought to be at high risk of recidivism. There are no previous studies of the range of judicial, correctional or psychiatric contacts after the PIJ order, but this could extend understanding of any links between post-treatment psychological development of these young offenders and their reoffending or desistence from it. AIMS: To examine reoffending and judicial, correctional or psychiatric contacts of juveniles after a PIJ order, any relationship between seriousness of the index offence and first reoffence, and to test the hypothesis that 'threatened psychological development' is associated with higher recidivism rates. METHODS: A records-based follow-up study of a 9-year (1995-2003) national release cohort of 781 Dutch juvenile offenders finishing a PIJ order under the Juvenile Entrustment Act. Descriptive statistics were used to show patterns of reoffending and the reoffending and non-reoffending groups compared. RESULTS: The mean length of the PIJ order was 2.5 years, and mean time subsequently at risk for offending was 83.5 months (range 51-135 months). After treatment under a PIJ order, serious criminal offending was reduced by 50%, and there was a trend towards less serious property offences. Contrary to prediction, 'threatened psychological development' was not associated with worse outcomes. CONCLUSIONS: The data offer support for the value of the PIJ order. The recidivism rate remains high, and although the trend to less serious offending is encouraging, the findings raise questions about whether criminogenic needs are sufficiently met. By contrast, the apparently low rates of adult mental disorder, even among those regarded as having had 'threatened psychological development', suggest that PIJ institutions are doing a good job with respect to mental health. PMID- 20740479 TI - Inhibition of TNF-alpha-mediated endothelial cell-monocyte cell adhesion and adhesion molecules expression by the resveratrol derivative, trans-3,5,4' trimethoxystilbene. AB - Resveratrol (RSV) has been shown to have anti-inflammatory activity and to have a protective role against atherosclerosis. Here it is shown, for the first time, that its derivative trans-3,5,4'-trimethoxystilbene (TMS) may be a more potent anti-inflammatory agent than resveratrol. A comparative analysis of the inhibitory activities of related stilbenes, resveratrol, TMS and polydatin (PD), on monocyte adhesion to TNF-alpha-activated endothelial cells showed TMS to be the most effective, with PD being the least effective. RSV and its analogues inhibited, albeit differentially, the protein and mRNA expression levels of inducible cell adhesion molecules, ICAM-1 and VCAM-1, in cultured endothelial cells. The mechanism of the inhibitory effects of these stilbenes on endothelial cell-monocyte cell adhesion can be attributed mainly to inhibition of NF-kappaB pathway activation. The results demonstrate that all three investigated stilbene compounds, especially TMS, exhibit a potent inhibitory effect on inflammation induced cell-cell adhesion, expression of adhesion molecules and activation of the NF-kappaB pathway. PMID- 20740480 TI - The performance of 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid as mobile phase additive in HPLC-based lipophilicity assessment. AB - Ionic liquids have been widely used as green alternative mobile phase additives to shield the residuals silanols groups and modify the stationary/mobile phase HPLC systems. The present study aimed to evaluate the performance of the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) in producing extrapolated logk(w) indices suitable to substitute for octanol-water logP or logD values. The effect of [EMIM][BF4] was investigated for a set of basic and neutral drugs using two different columns, BDS and ABZ(+) . [EMIM][BF4] was added simply alone or in combination with n-octanol and was compared with the conventional masking agent n-decylamine. [EMIM][BF4] reduced the retention by suppressing silanophilic interactions, althoug to a lower extent than n decylamine. Addition of n-octanol further decreased the retention by shielding silanol sites on BDS and/or interacting with polar groups through hydrogen bonding on ABZ(+) . Logk(w) /logD(7.4) relationships proved moderate compared with those derived upon addition of n-decylamine. They were considerably improved upon the introduction of protonated fraction F(+) in the correlation, reflecting ion pair formation between the chaotropic anion [BF4](-) and the protonated basic compounds. In this aspect, the ionic liquid [EMIM][BF4], although efficient as a masking agent, cannot be recommended as mobile phase additive to reproduce octanol-water partitioning. PMID- 20740482 TI - Inference for meta-analysis with a suspected temporal trend. AB - There is sometimes a clear evidence of a strong secular trend in the treatment effect of studies included in a meta-analysis. In such cases, estimating the present-day treatment effect by meta-regression is both reasonable and straightforward. We however consider the more common situation where a secular trend is suspected, but is not strongly statistically significant. Typically, this lack of significance is due to the small number of studies included in the analysis, so that a meta-regression could give wild point estimates. We introduce an empirical Bayes meta-analysis methodology, which shrinks the secular trend toward zero. This has the effect that treatment effects are adjusted for trend, but where the evidence from data is weak, wild results are not obtained. We explore several frequentist approaches and a fully Bayesian method is also implemented. A measure of trend analogous to I(2) is described, and exact significance tests for trend are given. Our preferred method is one based on penalized or h-likelihood, which is computationally simple, and allows invariance of predictions to the (arbitrary) choice of time origin. We suggest that a trendless standard random effects meta-analysis should routinely be supplemented with an h-likelihood analysis as a sensitivity analysis. PMID- 20740484 TI - Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA membrane and molecular dynamics simulations. AB - The hERG1 gene (Kv11.1) encodes a voltage-gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template-driven de-novo design with ROSETTA-membrane modeling using side-chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2-Kv2.1 chimera channels, the missing parts are modeled de-novo. The impact of several alignments on the structure of the S4 helix in the voltage-sensing domain was also tested. Herein, final models are evaluated for consistency to the reported structural elements discovered mainly on the basis of mutagenesis and electrophysiology. These structural elements include salt bridges and close contacts in the voltage sensor domain; and the topology of the extracellular S5-pore linker compared with that established by toxin foot-printing and nuclear magnetic resonance studies. Implications of the refined hERG1 model to binding of blockers and channels activators (potent new ligands for channel activations) are discussed. PMID- 20740485 TI - The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: a randomized, double-blind, placebo-controlled study. AB - Based on several open-label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real rTMS (90% of resting motor threshold, 5 Hz, 600 pulses-a-day for 10 days) over the left DLPFC, and another group receiving sham-rTMS. An investigator blinded to the treatment performed three video-taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long-term effect). Mini-Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn-Yahr, Epworth Sleepiness, Visual Analog and Montgomery-Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points (31.9%, P = 0.06). In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. PMID- 20740486 TI - Repetitive transcranial magnetic stimulation as treatment for depression in Parkinson's disease. PMID- 20740487 TI - Response to: ATP13A2 mutations (PARK9) cause neurodegeneration with brain iron accumulation. PMID- 20740488 TI - Drug-induced cranial myoclonus. PMID- 20740489 TI - Template-tethered collagen mimetic peptides for studying heterotrimeric triple helical interactions. AB - Collagen mimetic peptides (CMPs) have been used to elucidate the structure and stability of the triple helical conformation of collagen molecules. Although CMP homotrimers have been widely studied, very little work has been reported regarding CMP heterotrimers because of synthetic difficulties. Here, we present the synthesis and characterization of homotrimers and ABB type heterotrimers comprising natural and synthetic CMP sequences that are covalently tethered to a template, a tris(2-aminoethyl) amine (TREN) succinic acid derivative. Various tethered heterotrimers comprising synthetic CMPs [(ProHypGly)6, (ProProGly)6] and CMPs representing specific domains of type I collagen were synthesized and characterized in terms of triple helical structure, thermal melting behavior, and refolding kinetics. The results indicated that CMPs derived from natural type I collagen sequence can form stable heterotrimeric helical complexes with artificial CMPs and that the thermal stability and the folding rate increase with the increasing number of helical stabilizing amino acids (e.g. Hyp) in the peptide chains. Covalent tethering enhanced the thermal stability and refolding kinetics of all CMPs; however, their relative values were not affected suggesting that the tethered system can be used for comparative study of heterotrimeric CMP's folding behavior in regards to chain composition and for characterization of thermally unstable CMPs. PMID- 20740491 TI - Differences in hippocampal protein levels between C57Bl/6J, PWD/PhJ, and Apodemus sylvaticus are paralleled by differences in spatial memory. AB - There is a significant strain-dependent performance in the Morris water maze (MWM), a paradigm for the evaluation of spatial memory. In contrast, information on molecular differences that may be responsible for differences in spatial memory performance is limited. The aim of the study was therefore to investigate differences in hippocampal protein levels in three groups with different performance in the MWM. C57BL/6J (inbred laboratory strain), PWD/PhJ (inbred strain derived from wild animals of Mus musculus), and Apodemus sylvaticus (AS, genus Apodemus) mice were used for the experiments. Proteins from hippocampi, obtained from a behavioral study on these animals, were extracted and run on two dimensional gel electrophoresis. Proteins spots were quantified, and spots with significantly different levels were identified by mass spectrometry using an ion trap. A series of 49 proteins from different pathways and cascades (signaling, neuronal network, protein synthesis, secretion and degradation, and antioxidant system; intermediary, fat, and carbohydrate metabolism) were significantly different among hippocampi at the stringent statistical level of P <= 0.001. These findings are paralleled by differences in the spatial navigation abilities between the strains within the species Mus musculus (C57BL/6 vs. PWD/PhJ) and between the genera Mus and Apodemus. As shown previously, AS learned the task in the MWM and showed good memory retention when tested at the probe trial (day 12), whereas C57BL/6J learned the task, but failed at the probe trial at day 12 as well as PWD/PhJ that failed to learn the task and failed at the probe trial at day 12. A list of above-mentioned proteins were different between PWD/PhJ with bad and AS with good memory retention and may therefore be related to performance in the MWM and thus to spatial memory formation. The experimental approach, however, does not allow discriminating between differences in protein levels a priori and different protein levels induced by the MWM testing. (c) 2010 Wiley Liss, Inc. PMID- 20740490 TI - Collagen oligomers modulate physical and biological properties of three dimensional self-assembled matrices. AB - Elucidation of mechanisms underlying collagen fibril assembly and matrix-induced guidance of cell fate will contribute to the design and expanded use of this biopolymer for research and clinical applications. Here, we define how Type I collagen oligomers affect in-vitro polymerization kinetics as well as fibril microstructure and mechanical properties of formed matrices. Monomers and oligomers were fractionated from acid-solubilized pig skin collagen and used to generate formulations varying in monomer/oligomer content or average polymer molecular weight (AMW). Polymerization half-times decreased with increasing collagen AMW and closely paralleled lag times, indicating that oligomers effectively served as nucleation sites. Furthermore, increasing AMW yielded matrices with increased interfibril branching and had no correlative effect on fibril density or diameter. These microstructure changes increased the stiffness of matrices as evidenced by increases in both shear storage and compressive moduli. Finally, the biological relevance of modulating collagen AMW was evidenced by the ability of cultured endothelial colony forming cells to sense associated changes in matrix physical properties and alter vacuole and capillary like network formation. This work documents the importance of oligomers as another physiologically-relevant design parameter for development and standardization of polymerizable collagen formulations to be used for cell culture, regenerative medicine, and engineered tissue applications. PMID- 20740492 TI - Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task. AB - Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging, functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high functioning autism and 13 controls (age-, IQ-, and gender-matched) were scanned while performing an Embedded Figures Task. Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in the left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher-order working memory/executive areas and visuospatial regions (between frontal and parietal occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal-posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist. PMID- 20740493 TI - Flexibility and inhibitor binding in cdc25 phosphatases. AB - Cdc25 phosphatases involved in cell cycle checkpoints are now active targets for the development of anti-cancer therapies. Rational drug design would certainly benefit from detailed structural information for Cdc25s. However, only apo- or sulfate-bound crystal structures of the Cdc25 catalytic domain have been described so far. Together with previously available crystalographic data, results from molecular dynamics simulations, bioinformatic analysis, and computer generated conformational ensembles shown here indicate that the last 30-40 residues in the C-terminus of Cdc25B are partially unfolded or disordered in solution. The effect of C-terminal flexibility upon binding of two potent small molecule inhibitors to Cdc25B is then analyzed by using three structural models with variable levels of flexibility, including an equilibrium distributed ensemble of Cdc25B backbone conformations. The three Cdc25B structural models are used in combination with flexible docking, clustering, and calculation of binding free energies by the linear interaction energy approximation to construct and validate Cdc25B-inhibitor complexes. Two binding sites are identified on top and beside the Cdc25B active site. The diversity of interaction modes found increases with receptor flexibility. Backbone flexibility allows the formation of transient cavities or compact hydrophobic units on the surface of the stable, folded protein core that are unexposed or unavailable for ligand binding in rigid and densely packed crystal structures. The present results may help to speculate on the mechanisms of small molecule complexation to partially unfolded or locally disordered proteins. PMID- 20740495 TI - Evidence that polymorphic deletion of the glutathione S-transferase gene, GSTM1, is associated with esophageal atresia. AB - BACKGROUND: Esophageal atresia (EA) is a life-threatening congenital condition whose etiology and pathogenesis are still poorly understood. An increasing trend of this pathology in some Italian regions suggests a possible interaction between xenobiotics and genes involved in detoxification processes during early embryonic development. For the first time polymorphisms of GSTM1, GSTT1, and GSTP1 genes were analyzed in association with EA. METHODS: The study population consisted of 25 EA children, 50 unrelated healthy children, 20 of the EA children's mothers, and 40 unrelated mothers. GSTM1 and GSTT1 null genotypes were identified by PCR amplification, and GSTP1 polymorphism was detected by RFLP analysis. RESULTS: An association was found between homozygosity for the GSTM1 null genotype and EA in affected children (p = 0.0022) and their mothers (p = 0.022). No association was found between GSTT1 and GSTP1 polymorphisms and EA children or their mothers. CONCLUSIONS: Results suggest that the GSTM1(-/-) null genotype may play an important role in the development of EA during early embryogenesis as a consequence of altered detoxification processes both in children and in the mothers. We hypothesize that GSTM1 allelic loss could be responsible for reduced or null catalytic activity in tissues exposed to amniotic fluid, and inefficient detoxification could be a trigger altering proliferation/apoptotic pattern of gut trachea separation. PMID- 20740496 TI - In silico models of bone remodeling from macro to nano--from organ to cell. AB - Computational modeling is a tool through which researchers can achieve a greater understanding of the mechanisms governing biological systems. In the field of bone biology, a plethora of models exist which attempt to replicate and investigate bone's dynamic behavior at different scales. At organ level, models are continuum based and describe the variation of bone's apparent density as a function of both biological and external mechanical stimuli. At tissue level, models include bone microarchitecture and more descriptive parameters such as trabecular thickness, osteoclast resorption depth, and activation frequency. Finally, at cell level, models employ partial differential equations to describe complex cellular interactions in the temporal domain. Although informative, these models exist in isolation. Consequently, their interpretation is limited. In this review, we present an overview of the organ-, tissue-, and cell-level models and assess their ability to reflect bone's metabolic processes reliably. Existing interscale synergies are then presented along with a computational framework which could be exploited to achieve a fully integrated, multiscale modeling approach. PMID- 20740494 TI - Extending the PRIME model for protein aggregation to all 20 amino acids. AB - We extend PRIME, an intermediate-resolution protein model previously used in simulations of the aggregation of polyalanine and polyglutamine, to the description of the geometry and energetics of peptides containing all 20 amino acid residues. The 20 amino acid side chains are classified into 14 groups according to their hydrophobicity, polarity, size, charge, and potential for side chain hydrogen bonding. The parameters for extended PRIME, called PRIME 20, include hydrogen-bonding energies, side chain interaction range and energy, and excluded volume. The parameters are obtained by applying a perceptron-learning algorithm and a modified stochastic learning algorithm that optimizes the energy gap between 711 known native states from the PDB and decoy structures generated by gapless threading. The number of independent pair interaction parameters is chosen to be small enough to be physically meaningful yet large enough to give reasonably accurate results in discriminating decoys from native structures. The most physically meaningful results are obtained with 19 energy parameters. PMID- 20740497 TI - Species co-occurrence patterns and dietary resource competition in primates. AB - Diamond (Assembly of species communities. In: Cody ML, Diamond JM, editors. Ecology and evolution of communities. Cambridge: Belknap. p 342-444 (1975)) argued that interspecific competition between species occupying similar niches results in a nonrandom pattern of species distributions. In particular, some species pairs may never be found in the same community due to competitive exclusion. Rigorous analytical methods have been developed to investigate the possible role that interspecific competition has on the evolution of communities. Many studies that have implemented these methods have shown support for Diamond's assembly rules, yet there are numerous exceptions. We build on this previous research by examining the co-occurrence patterns of primate species in 109 communities from across the world. We used EcoSim to calculate a checkerboard (C) score for each region. The C score provides a measure of the proportion of species pairs that do not co-occur in a set of communities. High C scores indicate that species are nonrandomly distributed throughout a region, and interspecific competition may be driving patterns of competitive exclusion. We conducted two sets of analyses. One included all primate species per region, and the second analysis assigned each species to one of four dietary guilds: frugivores, folivores, insectivores, and frugivore-insectivores. Using all species per region, we found significantly high C scores in 9 of 10 regions examined. For frugivores, we found significantly high-C scores in more than 50% of regions. In contrast, only 23% of regions exhibited significantly high-C scores for folivores. Our results suggest that communities are nonrandomly structured and may be the result of greater levels of interspecific competition between frugivores compared to folivores. PMID- 20740498 TI - Intentional cutmarks on an early mesolithic human calvaria from Margaux Cave (Dinant, Belgium). AB - Margaux Cave (Belgium) yielded a Pre-Boreal Early Mesolithic burial covered by what resembled a burial mound. The hundreds of human bones excavated belonged to 7 to 10 adult females. Among these bones, the CR3 cranium presents numerous cutmarks on both zygomatic processes, on the frontal squama and along the two coronal sutures, as well as on the left part of the posterior cranium. The cutmarks on the zygomatic processes correspond to the removal of the mandible while those on the top of the forehead and the occipital may result from the removal of the scalp. Therefore, these cutmarks may be interpreted as part of a mortuary ritual. PMID- 20740499 TI - Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons. AB - Excess administration of glutamate is known to induce Ca(2+) overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg(2+) in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg(2+) in the excitotoxicity, we simultaneously measured intracellular Ca(2+) and Mg(2+), using fluorescent dyes, Fura red, a fluorescent Ca(2+) probe, and KMG-104, a highly selective fluorescent Mg(2+) probe developed by our group, respectively. Administration of 100 MUM glutamate supplemented with 10 MUM glycine to rat hippocampal neurons induced an increase in intracellular Mg(2+) concentration ([Mg(2+)](i)). Extracellular Mg(2+) was not required for this glutamate-induced increase in [Mg(2+)](i), and no increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) or [Mg(2+)](i) was observed in neurons in nominally Ca(2+)-free medium. Application of 5 MUM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca(2+)](i) and [Mg(2+)](i). Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg(2+)](i) but did induce an additive increase in [Ca(2+)](i). Moreover, the glutamate-induced increase in [Mg(2+)](i) was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg(2+) efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca(2+) uniporter, prevented this [Mg(2+)](i) increase. These results indicate that glutamate-induced increases in [Mg(2+)](i) result from the Mg(2+) release from mitochondria and that Ca(2+) accumulation in the mitochondria is required for this Mg(2+) release. PMID- 20740502 TI - A pilot study of balloon dilation in an animal model resulting in cricoid cartilage fracture: implications for the stenotic pediatric airway. AB - OBJECTIVE: Endoscopic balloon dilation is increasingly popular as primary therapy for infants with subglottic stenosis. We aim to determine the maximum balloon diameter and pressure where no fracture of the cricoid would occur, minimum balloon size and pressures where a gross fracture of the cricoid occurs, and location of these fractures. We tested these objectives by performing balloon dilation in laryngotracheal complexes of eight euthanized adult male New Zealand white rabbits, with airway characteristics similar to a 3- to 9-month-old infant. METHODS: Subglottic airway diameter of each specimen was determined using endotracheal tubes (Cotton-Myer grading system). Preexistent subglottic disease was excluded by rigid endoscopy. Serial dilation with balloon catheters was performed, employing incremental balloon sizes and pressures, to determine balloon size and pressure, which resulted in a cricoid fracture. Locations of gross fractures were validated by two independent observers. RESULTS: Airway diameter of all specimens was 5.4 mm (size 4.0 endotracheal tube). Four of the seven cricoid cartilages exhibited gross fractures. Dilation with balloon diameters less than 6.0 mm failed to induce a fracture despite maximal inflation to 16.0 atmospheres. The minimum balloon size required to create a fracture was 7.0 mm, at a pressure of 6.0 atmospheres. All fractures occurred at the anterior lamina of cricoid ring. CONCLUSIONS: No fractures occurred when balloon dilation was performed with a balloon 0.6 mm or smaller than the measured subglottic diameter. Fractures of the cricoid occurred when balloon dilation was performed with a balloon 1.6 mm or larger than the subglottic diameter. PMID- 20740500 TI - Biologic and immunologic effects of preoperative trastuzumab for ductal carcinoma in situ of the breast. AB - BACKGROUND: Through this study, the authors sought to investigate the biologic and immunologic effects of preoperative trastuzumab in patients with ductal carcinoma in situ (DCIS) of the breast. METHODS: Patients with DCIS were enrolled in this open-label phase 2 trial and tested for HER2. Trastuzumab was given by intravenous infusion (8 mg/kg). The patients then had surgery 14 to 28 days after treatment. Tissue and peripheral blood samples were obtained before therapy and at the time of surgery to examine residual disease and immunologic response. RESULTS: Median age of the 69 enrolled patients was 53 years, mean mammographic size of the DCIS lesions was 5.2 +/- 1.2 cm, and 24 patients (35%) were found to have HER2 overexpression/amplification (12 received trastuzumab and 12 untreated patients provided tissue for blinded, controlled biomarker analyses). No overt histologic evidence of response was noted. No significant change in mean pretherapy staining for Ki-67 (44.3 +/- 3.4%) and cleaved caspase-3 (2.6 +/- 0.8%) was noted when surgical specimens from drug-treated patient samples were compared with those not treated. Trastuzumab significantly augmented antibody dependent cell mediated cytotoxicity (ADCC) in 100% of patients; this was demonstrated to be mediated through CD56+ degranulating natural killer cells (P < .01). One patient developed a significant anti-HER2 humoral CD4 T-cell response. CONCLUSIONS: Single-dose monotherapy with trastuzumab for patients with HER2 positive DCIS does not result in significant, clinically overt, histologic, antiproliferative, or apoptotic changes, but does result in the ability to mount ADCC mediated through natural killer cells and may also induce T-cell dependent humoral immunity. Further studies of trastuzumab for DCIS appear warranted. Cancer 2011. (c) 2010 American Cancer Society. PMID- 20740503 TI - Cytology of endobronchial ultrasound-guided transbronchial needle aspiration versus conventional transbronchial needle aspiration. AB - BACKGROUND: Conventional endoscopic transbronchial needle aspiration (TBNA) is a common procedure used to obtain samples for diagnosing and staging lung lesions. Recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) has been developed and increasingly used by clinicians. Clinical data suggest that EBUS-TBNA has higher sensitivity and specificity than conventional TBNA in staging lung cancers. In this study, the authors have investigated the cytological features and compared the diagnostic yield of these procedures in lung cancer patients. METHODS: A computer search of the cytopathology archives at The Johns Hopkins Hospital revealed 188 EBUS-TBNA cases (308 lymph nodes; 47 lung lesions) and 74 TBNA cases (106 lymph nodes; 44 lung lesions) over a 28-month period. All cytological material was correlated with available corresponding surgical material. RESULTS: The most frequently sampled lymph nodes were stations 4R and 7 in both TBNA and EBUS-TBNA; in addition, the EBUS-TBNA showed a wide range of lymph node sampling. EBUS-TBNA had a significantly lower nondiagnostic rate (8.7%) compared with TBNA (28.3%, P < .05) in staging lung cancers. In lymph node sampling, the sensitivity and specificity were 54.5% and 100% in the TBNA group and 85.2% and 100% in the EBUS-TBNA group. In lung specimens, the nondiagnostic rates of TBNA and EBUS-TBNA were 6.8% and 4.3%, respectively (P > .05), and the sensitivity and specificity were 78.9% and 100% in the TBNA group; and 89.5% and 100% in the EBUS-TBNA group. CONCLUSIONS: Findings indicated that EBUS-FNA cytology is an optimal modality for diagnosing and staging in lung cancer patients, in comparison to conventional TBNA. PMID- 20740504 TI - Distress levels in patients undergoing chemotherapy in Brazil. AB - OBJECTIVE: The objective of this study was to measure distress at three points during the course of chemotherapy: beginning, middle, and the last day of therapy in a private cancer center in Brazil. METHODS: One hundred patients were assessed at three points during chemotherapy using the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). The data were analyzed with the support of SPSS 15.0 software. RESULTS: At the beginning of chemotherapy, patients mean scores were distress (82%), anxiety (78%) and depression (55%). In the middle of treatment, the percentages of distress, anxiety and depression decreased to 36.4, 25 and 25.3%, respectively. On the last day, the levels were 18.2% for distress and 14.3% for both anxiety and depression. CONCLUSION: Distress is highest in these patients at the beginning of chemotherapy, suggesting that evaluation of patients for psychosocial needs is important. Screening with a simple rapid instrument such as the DT is feasible and useful. PMID- 20740505 TI - Allowance for antibody bivalence in the characterization of interactions by ELISA. AB - The objective of this review is to remove empiricism from the characterization of immunospecific interactions by enzyme-linked immunosorbent assay (ELISA). In place of the original presumption that the absorbance generated by the enzyme linked assay could be regarded as a measure of free antibody concentration, the stance is taken that the parameter being monitored is the concentration of antibody complexed with immobilized antigen on the microtiter plate. After the presentation of general binding theory that takes ligand multivalence into account, that theory is adapted to incorporate the simplifying circumstances that prevail in an ELISA study. Validity of the original expressions for characterizing antigen-antibody interactions by competitive ELISA is confirmed, thereby refuting reported concerns about the need for amendment of the theoretical expressions to take into account bivalence of the antibody. PMID- 20740506 TI - Defense attorneys' concerns about the competence of adolescent defendants. AB - Research indicates that a sizable proportion of adolescent defendants have difficulty understanding and participating in legal proceedings against them, and may be incompetent to stand trial. To examine attorneys' experience in defending adolescents with competence-related difficulties, 214 juvenile attorneys were surveyed. Findings indicated that attorneys have doubts about the competence of approximately 10% of adolescent defendants, and that they find these cases particularly challenging to defend. Most attorneys appear to recognize that developmental factors may contribute to adolescents' competence-related difficulties, and believe that the law should accept developmental immaturity as a basis for incompetence findings. In approximately half of the cases in which attorneys had doubts about competence, attorneys did not request a competence evaluation but instead made other efforts to address competence issues, such as by teaching adolescents about legal proceedings and further involving their parents. The implications of these findings are discussed. PMID- 20740507 TI - Strategic synthesis of hierarchical TiO2 microspheres with enhanced photocatalytic activity. PMID- 20740508 TI - Oxidative coupling of aromatic substrates with alkynes and alkenes under rhodium catalysis. AB - Aromatic substrates with oxygen- and nitrogen-containing substituents undergo oxidative coupling with alkynes and alkenes under rhodium catalysis through regioselective C-H bond cleavage. Coordination of the substituents to the rhodium center is the key to activate the C-H bonds effectively. Various fused-ring systems can be constructed through these reactions. PMID- 20740509 TI - An oxidative Prins-pinacol tandem process and its application to the synthesis of (-)-platensimycin. PMID- 20740510 TI - A biologically inspired organometallic fuel cell (OMFC) that converts renewable alcohols into energy and chemicals. PMID- 20740511 TI - Circularly polarized luminescent CdS quantum dots prepared in a protein nanocage. PMID- 20740512 TI - Fluorescent quantum dots as artificial antennas for enhanced light harvesting and energy transfer to photosynthetic reaction centers. PMID- 20740513 TI - Well-defined cationic methallyl alpha-keto-beta-diimine complexes of nickel. PMID- 20740514 TI - Hybrid uranium-oxalate fullerene topology cage clusters. PMID- 20740516 TI - High-density energetic mono- or bis(oxy)-5-nitroiminotetrazoles. PMID- 20740515 TI - Ligand-clustered "patchy" nanoparticles for modulated cellular uptake and in vivo tumor targeting. PMID- 20740517 TI - Palladium-catalyzed carbonylative C-H activation of heteroarenes. PMID- 20740519 TI - Intermolecular addition of glycosyl halides to alkenes mediated by visible light. PMID- 20740518 TI - The third hydrogenase: a ferracyclic carbamoyl with close structural analogy to the active site of Hmd. PMID- 20740520 TI - Analysis of light scattering from human breast tissue using a custom dual-optical scanning near-field optical microscope. AB - In this paper we introduce a custom scanning near-field optical microscope (SNOM) that simultaneously collects reflection and transmission near-field images along with topography. This dual-optical SNOM uses a bent probe, which allows for axial reflection imaging, accurate surface scanning, and easy identification of topographic artifacts. Using this novel dual-optical SNOM, we image desiccated and non-desiccated human breast epithelial tissue. By comparing the simultaneous SNOM images, we isolate the effects of tissue morphology and variations in refractive indices on the forward- and back-scattering of light from the tissue. We find that the reduction in back-scattering from tissue, relative to the glass slide, is caused by dense packing of the scattering sites in the cytoplasm (morphology) in the desiccated tissue and a thin-film of water adhering to the glass slide (refractive index) in the non-desiccated tissue sample. Our work demonstrates the potential of our customized dual-optical SNOM system for label free tissue diagnostics. PMID- 20740521 TI - Determination of distinctive carbohydrate signatures obtained from the Aeromonas hydrophila (chemotype II) core oligosaccharide pinpointing the presence of the 4 O-phosphorylated 5-O-linked Kdo reducing end group using electrospray ionization quadrupole orthogonal time-of-flight mass spectrometry and tandem mass spectrometry. AB - The electrospray quadrupole orthogonal time-of-flight mass spectrometric (ESI QqTOF-MS) structural elucidation of the core oligosaccharide of Aeromonas hydrophila (chemotype II) lipopolysaccharide has been investigated and it was demonstrated that it contained an 4-O-phosphorylated Kdo reducing end group, which was glycosylated by the remaining outer core oligosaccharide through its O 5 position. After releasing the core oligosaccharide from the native LPS with acid, the phosphorylated Kdo residue eliminated phosphoric acid, to produce a core oligosaccharide containing a mixture of diastereomeric 4,8- and 4,7-anhydro alpha-keto acids and an open-chain olefinic Kdo residue. The characteristic glycone sequence was elucidated by collision-induced dissociation tandem mass spectrometry (CID-MS/MS) of the protonated molecule of the native core oligosaccharide. In addition, the analysis of the Hakomori permethylated core oligosaccharide was carried out by electrospray ionization quadrupole orthogonal time-of-flight mass spectrometry (ESI-QqTOF-MS) and matrix-assisted laser desorption/ionization (MALDI)-QqTOF-MS analyses. The presence of more than nine isobaric isomers of this core was detected. The CID-MS/MS analysis of the various protonated permethylated core oligosaccharide molecules showed a similar and diagnostic fragmentation pattern. The over-methylation of the permethylated core oligosaccharide containing either the 4,7- or the 4,8-anhydro-alpha-keto acid unit and the open-chain olefinic Kdo unit was reported. It was realized that the extra minor satellite signals obtained in the ESI-QqTOF-MS and MALDI-TOF-MS analyses were dimethyl sulfoxide (DMSO) stable covalent addition products, which have occurred by a Michael addition on the 4,8-Kdo exocyclic double bond. The occurrence of this series of covalent addition products during the MS analysis of a permethylated core oligosaccharide should be considered as 'carbohydrate distinctive signatures' establishing and confirming the presence of a 4-O phosphorylated-5-O-linked Kdo reducing end group. PMID- 20740522 TI - Comparison of secondary ion mass spectrometry and micromilling/continuous flow isotope ratio mass spectrometry techniques used to acquire intra-otolith delta18O values of wild Atlantic salmon (Salmo salar). AB - The chemical signals in the sequential layers of fish otoliths have the potential to provide fisheries biologists with temporal and spatial details of migration which are difficult to obtain without expensive tracking methods. Signal resolution depends, however, on the extraction technique used. We compared the use of mechanical micromilling and continuous flow isotope ratio mass spectrometry (CF-IRMS) methods with secondary ion mass spectrometry (SIMS) to obtain delta(18)O profiles from otoliths of wild Atlantic salmon (Salmo salar) and used these to corroborate the time of freshwater emigration of the juvenile with macroscopic patterns within the otolith. Both techniques showed the transition occurring at the same visible feature on the otolith, allowing future analyses to easily identify the juvenile (freshwater) versus adult (marine) life stages. However, SIMS showed a rapid and abrupt transition whereas micromilling provided a less distinct signal. The number of samples that could be obtained per unit area sampled using SIMS was 2 to 3 times greater than that when using micromilling/CF-IRMS although the delta(18)O values and analytical precisions (approximately 0.2 per thousand) of the two methods were comparable. In addition, SIMS delta(18)O results were used to compare otolith aragonite values with predicted values calculated using various isotope fractionation equations. PMID- 20740523 TI - Delta15N of soil N and plants in a N-saturated, subtropical forest of southern China. AB - We investigated the delta(15)N profile of N (extractable NH(4)(+), NO(3)(-), and organic N (EON)) in the soil of a N-saturated subtropical forest. The order of delta(15)N in the soil was EON > NH(4)(+) > NO(3)(-). Although the delta(15)N of EON had been expected to be similar to that of bulk soil N, it was higher than that of bulk soil N by 5 per thousand. The difference in delta(15)N between bulk soil N and EON (Delta(15)N(bulk-EON)) was correlated significantly with the soil C/N ratio. This correlation implies that carbon availability, which determines the balance between N assimilation and dissimilation of soil microbes, is responsible for the high delta(15)N of EON, as in the case of soil microbial biomass delta(15)N. A thorough delta(15)N survey of available N (NH(4)(+), NO(3)( ), and EON) in the soil profiles from the organic layer to 100 cm depth revealed that the delta(15)N of the available N forms did not fully overlap with the delta(15)N of plants. This mismatch in delta(15)N between that of available N and that of plants reflects apparent isotopic fractionation during N uptake by plants, emphasizing the high N availability in this N-saturated forest. PMID- 20740524 TI - Limitations of mass spectrometric methods for the characterization of polydisperse materials. AB - This paper is a review of work on the characterization of coal liquids and petroleum residues and asphaltenes over several decades in which various mass spectrometric methods have been investigated. The limitations of mass spectrometric methods require exploration in order to understand what the different analytical methods can reveal about environmental pollution by these kinds of samples and, perhaps more importantly, what they cannot reveal. The application of mass spectrometry to environmental problems generally requires the detection and determination of the concentration of specific pollutants released into the environment by accident or design. The release of crude petroleum or coal liquids into the environment can be detected and tracked during biodegradation processes through specific chemicals such as alkanes or polyaromatic hydrocarbons (PAHs). However, petroleum asphaltenes are polydisperse materials of unknown mass range and chemical structures and, therefore, there are no individual chemicals to detect. It is necessary to determine methods of detection and the ranges of mass of such materials. This can only be achieved through fractionation to reduce the polydispersity of the initial sample. Comparison of mass spectrometric results with results from an independent analytical method such as size-exclusion chromatography with a suitable eluent is advisable to confirm that all the sample has been detected and mass discrimination effects avoided. PMID- 20740525 TI - Fragmentation study of iridoid glycosides including epimers by liquid chromatography-diode array detection/electrospray ionization mass spectrometry and its application in metabolic fingerprint analysis of Gardenia jasminoides Ellis. AB - A high-performance liquid chromatography-diode array detection/electrospray ionization mass spectrometry (HPLC-DAD/ESI-MS) method was applied to the characterization of ten iridoid glycosides in Gardenia jasminoides Ellis, a traditional Chinese medicine. During the process of structural elucidation, two groups of isomers including two epimers were structurally characterized and differentiated according to their distinctive fragmentation patterns which were closely related to their isomeric differentiations. Subsequently, the major compounds were purified by multi-dimensional chromatography and semi-preparative HPLC and the structure identification was confirmed with NMR techniques. The major fragmentation pathways of iridoid glycosides in Gardenia jasminoides Ellis obtained through the MS data were schemed systematically, which provided the best sensitivity and specificity for characterization of the iridoid glycosides especially the isomers so far. Based on the fragmentation patterns of iridoid glycosides concluded, seven major iridoid glycosides were characterized in rat plasma after intravenous administration of Gardenia jasminoides Ellis. PMID- 20740526 TI - Unique para-effect in electron ionization mass spectra of bis(perfluoroacyl) derivatives of bifunctional aminobenzenes. AB - A new kind of 'para-effect' under electron ionization (EI) conditions has been discovered for a series of bis(perfluoroacyl) derivatives of o-, m- and p phenylenediamines, -hydroxybenzeneamines and -mercaptobenzeneamines of a common structure RCOX-C(6)H(4)-NHCOR (X = NH, S, O; R = CF(3), C(2)F(5), C(3)F(7)). Only the para-isomers showed successive loss of a radical RCO* and a molecule RCN, leading to very intense peaks in the EI spectra. The composition and the origin of the [M-COR-NCR](+) ions were confirmed by exact mass measurements and linked scan experiments. The proposed mechanism of their formation takes into account likely para-quinoid structures of the precursor ions. A similar rearrangement has not been observed for para-isomers in the series of bis(perfluoroacyl) derivatives of benzenediols, mercaptophenols and dimercaptobenzenes. PMID- 20740527 TI - Rapid screening and identification of caffeic acid and its esters in Erigeron breviscapus by ultra-performance liquid chromatography/tandem mass spectrometry. AB - Caffeic acid and its esters (CAEs) are widely distributed in the plant kingdom and have been reported to elicit a wide range of exceptional biological activities. Present methods for screening and characterization of CAEs normally need the use of liquid chromatography diode-array detection/multistage mass spectrometry (LC-DAD/MS(n)). In this report, a rapid and efficient method coupling ultra-performance liquid chromatography (UPLC) with fragment-targeted multi-reaction monitoring (MRM) has been developed for screening CAEs in a crude extract of Erigeron breviscapus, while a UPLC/quasi-MS(n) method has been applied in the structural identification of these compounds. Furthermore, a simple quasi UPLC/MS/MS method based on in-source collision-induced dissociation (CID) has been proposed for rapid identification of the CAEs. As a result, a total of more than 34 CAEs were detected and their structures characterized. Nine of them were reported from E. breviscapus for the first time. Applications of these strategies in the chemical investigation of an injection of E. breviscapus resulted in the identifications of 16 CAEs. These strategies, if appropriate modifications are made, will be very useful in screening and characterization not only of CAEs, but of other structural types of compounds in various complex matrices. PMID- 20740528 TI - Minimization of sample requirement for delta18O in benzoic acid. AB - The measurement of the oxygen stable isotope content in organic compounds has applications in many fields, ranging from paleoclimate reconstruction to forensics. Conventional High-Temperature Conversion (HTC) techniques require >20 microg of O for a single delta(18)O measurement. Here we describe a system that converts the CO produced by HTC into CO(2) via reduction within a Ni-furnace. This CO(2) is then concentrated cryogenically, and 'focused' into the isotope ratio mass spectrometry (IRMS) source using a low-flow He carrier gas (6-8 mL/min). We report analyses of benzoic acid (C(7)H(6)O(2)) reference materials that yielded precise delta(18)O measurement down to 1.3 microg of O, suggesting that our system could be used to decrease sample requirement for delta(18)O by more than an order of magnitude. PMID- 20740529 TI - Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling. AB - Isobaric product ions cannot be differentiated by exact mass determinations, although in some cases deuterium labeling can provide useful structural information for identifying isobaric ions. Proposed fragmentation pathways of fentanyl were investigated by electrospray ionization ion trap mass spectrometry coupled with deuterium labeling experiments and spectra of regiospecific deuterium labeled analogs. The major product ion of fentanyl under tandem mass spectrometry (MS/MS) conditions (m/z 188) was accounted for by a neutral loss of N-phenylpropanamide. 1-(2-Phenylethyl)-1,2,3,6-tetrahydropyridine (1) was proposed as the structure of the product ion. However, further fragmentation (MS(3)) of the fentanyl m/z 188 ion gave product ions that were different from the product ion in the MS/MS fragmentation of synthesized 1, suggesting that the m/z 188 product ion from fentanyl includes an isobaric structure different from the structure of 1. MS/MS fragmentation of fentanyl in deuterium oxide moved one of the isobars to 1 Da higher mass, and left the other isobar unchanged in mass. Multistage mass spectral data from deuterium-labeled proposed isobaric structures provided support for two fragmentation pathways. The results illustrate the utility of multistage mass spectrometry and deuterium labeling in structural assignment of isobaric product ions. PMID- 20740530 TI - Simplified capillary electrophoresis nanospray sheath-flow interface for high efficiency and sensitive peptide analysis. AB - We report a simple nanospray sheath-flow interface for capillary electrophoresis. This interface relies on electrokinetic flow to drive both the separation and the electrospray; no mechanical pump is used for the sheath flow. This system was interfaced with an LCQ mass spectrometer. The best results were observed with a 2 microm diameter emitter tip and a 1-mm spacing between the separation capillary tip and the emitter tip. Under these conditions, mass detection limits (3sigma) of 100 amol were obtained for insulin receptor fragment 1142-1153. The separation efficiency exceeded 200,000 plates for this compound. The relative standard deviation generated during continual infusion of a 50 microM solution of angiotensin II was 2% for the total ion count and 3% for the extracted ion count over a 40-min period. Finally, the interface was also demonstrated for negative ion mode. PMID- 20740531 TI - Electrospray ionization mass spectrometry from discrete nanoliter-sized sample volumes. AB - We describe a method for nanoelectrospray ionization mass spectrometry (nESI-MS) of very small sample volumes. Nanoliter-sized sample droplets were taken up by suction into a nanoelectrospray needle from a silicon microchip prior to ESI. To avoid a rapid evaporation of the small sample volumes, all manipulation steps were performed under a cover of fluorocarbon liquid. Sample volumes down to 1.5 nL were successfully analyzed, and an absolute limit of detection of 105 attomole of insulin (chain B, oxidized) was obtained. The open access to the sample droplets on the silicon chip provides the possibility to add reagents to the sample droplets and perform chemical reactions under an extended period of time. This was demonstrated in an example where we performed a tryptic digestion of cytochrome C in a nanoliter-sized sample volume for 2.5 h, followed by monitoring the outcome of the reaction with nESI-MS. The technology was also utilized for tandem mass spectrometry (MS/MS) sequencing analysis of a 2 nL solution of angiotensin I. PMID- 20740532 TI - Ultrasound ionization of biomolecules. AB - To date, mass spectrometric analysis of biomolecules has been primarily performed with either matrix-assisted laser desorption/ionization (MALDI) or electrospray ionization (ESI). In this work, ultrasound produced by a simple piezoelectric device is shown as an alternative method for soft ionization of biomolecules. Precursor ions of proteins, saccharides and fatty acids showed little fragmentation. Cavitation is considered as a primary mechanism for the ionization of biomolecules. PMID- 20740533 TI - Liquid chromatography/tandem mass spectrometry sensitivity enhancement via online sample dilution and trapping: applications in microdosing and dried blood spot (DBS) bioanalysis. AB - A simple online sample dilution, enrichment, and cleanup technique was developed for sensitive microdosing and dried blood spot (DBS) liquid chromatography/tandem mass spectrometric (LC/MS/MS) bioanalysis. Samples are diluted online with water and enriched in a trap column which is subsequently switched inline with the analytical column. Excellent lansoprazole (in acetonitrile) peak shape is maintained even with an 80-microL injection. In comparison, similar chromatographic peaks were observed only when a small volume of the same solution, i.e., 1 microL, was injected on a regular high-performance liquid chromatography (HPLC) system, where an injection of 5 microL resulted in severe peak fronting. A substantial enhancement in sensitivity is realized in the trapping mode using large injection volumes. The trap column is washed at the beginning and at the end of each injection with aqueous and organic solvent respectively to remove matrix components. This ultimately leads to reduction of matrix effects and mass spectrometer noise, thus facilitating the utilization of protein precipitation as the sample preparation for plasma samples. A lower limit of quantitation (LLOQ) of 0.5 pg/mL was demonstrated for lansoprazole in human plasma with a signal-to-noise (S/N) ratio of 13 using a 100 microL injection. Excellent intra-day precision and accuracy were established for lansoprazole in human plasma with good linearity (R(2) > 0.999) from 0.5 to 500 pg/mL. This level of LLOQ makes LC/MS/MS a practical alternative for microdosing bioanalysis, where the dose is typically 100 times lower than the therapeutic dose. The same technique was applied to quantitate lansoprazole in human whole blood employing DBS technology. With a single 3-mm punch, i.e. approximately 2 microL of whole blood or approximately 1 microL plasma, a LLOQ of 0.1 ng/mL showed sufficient S/N ratio (40) for lansoprazole when 75 microL of extract was injected. In all, the online sample dilution, cleanup, and enrichment technique demonstrated the practical utility of LC/MS/MS in microdosing and DBS bioanalysis. PMID- 20740534 TI - Ionspray microchip. AB - An ionspray microchip is introduced. The chip is based on the earlier presented nebulizer microchip that consists of glass and silicon plates bonded together. A liquid inlet channel, nebulizer gas inlet, and nozzle are etched on the silicon plate and a platinum heater is integrated on the glass plate. The nebulizer microchip has been previously used in atmospheric pressure chemical ionization, atmospheric pressure photoionization, sonic spray ionization, and thermospray ionization modes. In this work we show that the microchip can be operated also in ionspray mode by introducing high voltage to the silicon plate of the microchip. The effects of operation parameters (voltage, nebulizer gas pressure, sample solution flow rate, solvent composition, and analyte concentration) on the performance of the ion spray microchip were studied. Under optimized conditions the microchip provides efficient ionization of small and large compounds and good quantitative performance. The feasibility of the ion spray microchip in liquid chromatography/mass spectrometry (LC/MS) was demonstrated by the analysis of tryptic peptides of bovine serum albumin. PMID- 20740535 TI - Role of 2-oxo and 2-thioxo modifications on the proton affinity of histidine and fragmentation reactions of protonated histidine. AB - A combination of electrospray ionisation (ESI), multistage and high-resolution mass spectrometry experiments was used to compare the gas-phase chemistry of the amino acids histidine (1), 2-oxo-histidine (2), and 2-thioxo-histidine (3). Collision-induced dissociation (CID) of all three different proton-bound heterodimers of these amino acids led to the relative gas-phase proton affinity order of: histidine >2-thioxo-histidine >2-oxo-histidine. Density functional theory (DFT) calculations confirm this order, with the lower proton affinities of the oxidised histidine derivatives arising from their ability to adopt the more stable keto/thioketo tautomeric forms. All protonated amino acids predominately fragment via the combined loss of H(2)O and CO to yield a(1) ions. Protonated 2 and 3 also undergo other small molecule losses including NH(3) and the imine HN=CHCO(2)H. The observed differences in the fragmentation pathways are rationalised through DFT calculations, which reveal that while modification of histidine via the introduction of the oxygen atom in 2 or the sulfur atom in 3 does not affect the barriers against the loss of H(2)O+CO, barriers against the losses of NH(3) and HN=CHCO(2)H are lowered relative to protonated histidine. PMID- 20740536 TI - Direct analysis of trace level bisphenol A, octylphenols and nonylphenol in bottled water and leached from bottles by ultra-high-performance liquid chromatography/tandem mass spectrometry. AB - A high-throughput method was developed for the direct analysis of trace level bisphenol A (BPA), 4-n-octylphenol (4-n-OP), 4-tert-octylphenol (4-t-OP) and 4-n nonylphenol (4-n-NP) in water samples by ultra-high-performance liquid chromatography/tandem mass spectrometry (uHPLC/MS/MS) using an isotope-labeled internal standard. Aliquots of water samples were spiked with the internal standard and analyzed without sample cleanup or enrichment. All target analytes were chromatographically separated within 3 min and detected using the highly selective multiple reaction monitoring (MRM) detection mode. The method detection limits were statistically calculated and ranged from 0.040 ppb (BPA) to 0.057 ppb (4-n-NP). Excellent correlation of determination was achieved for each analyte with r greater than 0.995. Precision was achieved within 8% relative standard deviation (RSD) for all analytes, and recoveries from spiked samples ranged from 97% to 106.2% except for 4-n-OP which may be corrected by using an isotope labeled analog as internal standard. This method was used for analyzing eight randomly selected bottled water samples and found no detectable target analytes. This method was also used to analyze target analytes leached from bottles (6 low cost bottles and 6 brand-name baby-feeding bottles). Low levels of BPA were found in three bottles after they had been heated in a microwave oven, and a trace amount of 4-n-NP was also found in three bottles. 4-t-OP, which has not been reported as a leachable chemical, was found in two brand name baby-feeding bottles from the same manufacturer, and was confirmed with bottles from different batches. PMID- 20740537 TI - Mass spectrometric characterization of metal triflates and triflimides (Lewis superacid catalysts) by electrospray ionization and tandem mass spectrometry. AB - Trifluoromethylsulfonate (triflate) and bis(trifluoromethylsulfonyl)imide (triflimide) salts, well-known Lewis acid catalysts, present some difficulty in their characterization. By using nitromethane as the solvent, useful electrospray mass spectra in positive and negative ion mode were obtained for salts of metals in oxidation states +2 and +3. In positive mode, addition of a strong Lewis base (triphenylphosphine oxide, TPPO), capable of displacing a triflate (TfO(-)) or a triflimide (Tf(2)N(-)) anion, is necessary for obtaining useful spectra. Under these conditions of solvent and added ligand, the most abundant ions were [M(2+)(A(-))(TPPO)(2)](+) or [M(3+)(A(-))(2)(TPPO)(2)](+) with A(-) = TfO(-) or Tf(2)N(-). The MS/MS spectra of these diagnostic ions provide additional analytical information. The breakdown curves, in the form of % dissociated as a function of the ion activation energy, offer a mean for investigating the bonding in these ions. PMID- 20740539 TI - Design and performance of an evolved gas analysis ion attachment mass spectrometer. AB - We designed a simple evolved gas analysis (EGA) system to act as a sampler between solid samples at atmospheric pressure and the high vacuum inside a mass spectrometer. The newly designed stainless steel system is simple, small and rugged and fulfills all the basic requirements for EGA. The temperature is programmable with 60 degrees C/min as the maximum heating rate and the temperature range is up to 600 degrees C. With this system coupled with lithium ion attachment mass spectrometry (IAMS), it is possible to study the temperature programmed decomposition of a number of solid materials by detecting any chemical species on a real-time basis. For illustrative purposes, EGA-IAMS experiments of polyethylene polymers have been conducted. PMID- 20740538 TI - Mass spectrometric characterization of gelsolin isoforms. AB - Gelsolin is the most widely expressed member of the actin capping and severing family of proteins. There are two isoforms of gelsolin: isoform 1, a secretory (plasma) protein that is 51 amino acids longer than isoform 2, a cytosolic protein, at the N-terminus; the first 27 amino acids is a signal sequence. Both isoforms are coded by a single gene and differ as a result of alternative initiation site/splicing. The level of gelsolin in the blood and cerebrospinal fluid (CSF) is altered in many diseases including amyloidoses and other neurodegenerative disorders. Although quantitative analysis of gelsolin has been reported, lack of suitable antibodies makes it impossible to differentiate these two isoforms by immunodetection techniques and no other technique is available. Therefore, ambiguity exists whether gelsolin present in circulation is isoform 1 or also isoform 2 released from lysed cells. We report in this communication a mass spectrometric approach to identify isoform 1 of gelsolin immunopurified from human plasma and CSF. Recombinant isoform 1 was used as reference. PMID- 20740540 TI - Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) and UPLC/MS(E) analysis of RNA oligonucleotides. AB - Fast and efficient ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) analysis of short interfering RNA oligonucleotides was used for identity confirmation of the target sequence-related impurities. Multiple truncated oligonucleotides and metabolites were identified based on the accurate mass, and their presumed sequence was confirmed by MS/MS and MS(E) (alternating low and elevated collision energy scanning modes) methods. Based on the resulting fragmentation of native and chemically modified oligonucleotides, it was found that the MS(E) technique is as efficient as the traditional MS/MS method, yet MS(E) is more general, faster, and capable of producing higher signal intensities of fragment ions. Fragmentation patterns of modified oligonucleotides were investigated using RNA 2'-ribose substitutions, phosphorothioate RNA, and LNA modifications. The developed sequence confirmation method that uses the MS(E) approach was applied to the analysis of in vitro hydrolyzed RNA oligonucleotide. The target RNA and metabolites, including the structural isomers, were resolved by UPLC, and their identity was confirmed by MS(E). Simultaneous RNA truncations from both termini were observed. The UPLC quadrupole time-of-flight (QTOF) MS/MS and MS(E) methods were shown to be an effective tool for the analysis and sequence confirmation of complex oligonucleotide mixtures. PMID- 20740541 TI - Electron ionisation mass spectrometry of the pentafluoropropionate esters of trichothecene analogues and culmorin compounds from Fusarium species. AB - This paper reports the mass spectra, obtained after electron ionisation (EI) at 70 eV, of 34 trichothecenes and five culmorin compounds after acylation with pentafluoropropionic anhydride. The derivatised fungal metabolites were separated by gas chromatography, and the mass spectra were obtained by scanning of a single quadrupole mass filter in the scan range m/z 200-900. The fragmentation pathways of three trichothecenes (triacetyl-deoxynivalenol, 4,15-diacetoxy-scirpenol, T-2 toxin) have been studied in more detail by linked scan-high-resolution mass spectrometry. The most common trichothecenes are today more often routinely analysed using LC/MS-based methodologies. However, EI-MS may give complementary structural information, and the data that are summarised in this article may help to identify analogues of one of the largest class of mycotoxins, the tricothecenes, as well as culmorin compounds that are commonly co-produced by Fusarium culmorum and F. graminearum in cultures or naturally contaminated samples. PMID- 20740542 TI - Quantitation of a de-fluorinated analogue of casopitant mesylate by normal-phase liquid chromatography/mass spectrometry. AB - The introduction of Quality by Design (QbD) in Drug Development has resulted in a greater emphasis on chemical process understanding, in particular on the origin and fate of impurities. Therefore, the identification and quantitation of low level impurities in new Active Pharmaceutical Ingredients (APIs) play a crucial role in project progression and this has created a greater need for sensitive and selective analytical methodology. Consequently, scientists are constantly challenged to look for new applications of traditional analytical techniques. In this context a normal-phase liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) method was developed to determine the amount of a de fluorinated analogue impurity in Casopitant Mesylate, a new API under development in GlaxoSmithKline, Verona. Normal-phase LC provided the selectivity needed between our target analyte and Casopitant, while a single quadrupole mass spectrometer was used to ensure the sensitivity needed to detect the impurity at <0.05%w/w. Standard solutions and samples were prepared in heptane/ethanol (50:50, v/v) containing 1% of 2 M NH(3) in ethanol; the mobile phase consisted of heptane/ethanol (95:5, v/v) with isocratic elution (flow rate: 1.0 mL/min, total run time: 23 min). To allow the formation of ions in solutions under normal-phase (apolar) conditions, a post-column infusion of a solution of 0.1% v/v of formic acid in methanol was applied (flow rate: 200 microL/min). The analysis was carried out in positive ion mode, monitoring the impurity by single ion monitoring (SIM). The method was fully validated and its applicability was demonstrated by the analysis of real-life samples. This work is an example of the need for selective and accurate methodology during the development of a new chemical entity in order to develop an appropriate control strategy for impurities to ultimately ensure patient safety. PMID- 20740543 TI - A high-performance, safer and semi-automated approach for the delta18O analysis of diatom silica and new methods for removing exchangeable oxygen. AB - The determination of the oxygen isotope composition of diatom silica in sediment cores is important for paleoclimate reconstruction, especially in non-carbonate sediments, where no other bioindicators such as ostracods and foraminifera are available. Since most currently available analytical techniques are time consuming and labour-intensive, we have developed a new, safer, faster and semi automated online approach for measuring oxygen isotopes in biogenic silica. Improvements include software that controls the measurement procedures and a video camera that remotely records the reaction of the samples under BrF(5) with a CO(2) laser. Maximum safety is guaranteed as the laser-fluorination unit is arranged under a fume hood in a separate room from the operator. A new routine has been developed for removing the exchangeable hydrous components within biogenic silica using ramp degassing. The sample plate is heated up to 1100 degrees C and cooled down to 400 degrees C in approximately 7 h under a flow of He gas (the inert Gas Flow Dehydration method--iGFD) before isotope analysis. Two quartz and two biogenic silica samples (approximately 1.5 mg) of known isotope composition were tested. The isotopic compositions were reproducible within an acceptable error; quartz samples gave a mean standard deviation of <0.15 per thousand (1sigma) and for biogenic silica <0.25 per thousand (1sigma) for samples down to approximately 0.3 mg. The semi-automated fluorination line is the fastest method available at present and enables a throughput of 74 samples/week. PMID- 20740544 TI - Gas-phase synthesis of hydrodiphenylcyclopropenylium via nonclassical Favorskii rearrangement from alkali-cationized alpha,alpha'-dibromodibenzyl ketone. AB - The gas-phase synthesis of hydrodiphenylcyclopropenylium from alkali-cationized alpha,alpha'-dibromodibenzyl ketone (1) via nonclassical Lewis-acid-induced Favorskii rearrangement has been studied by electrospray ionization/tandem mass spectrometry (ESI-MS/MS) and theoretical methods, showing that cations [1-Br](+) by debromination from 1 and 1.M(+)(M = Li or Na) by alkali-metal cationization of 1 could convert into the protonated diphenylcyclopropenone 2.H(+) by collision induced dissociation in the gas phase. A concerted mechanism for the Lewis-acid induced Favorskii rearrangement from alkali-metal-cationized alpha,alpha' dibromodibenzyl ketone was proposed and studied, based on mass spectrometric results and theoretical methods. PMID- 20740545 TI - Measurement of the delta34S value in methionine by double spike multi-collector thermal ionization mass spectrometry using Carius tube digestion. AB - Methionine is an essential amino acid and is the primary source of sulfur for humans. Using the double spike ((33)S-(36)S) multi-collector thermal ionization mass spectrometry (MC-TIMS) technique, three sample bottles of a methionine material obtained from the Institute for Reference Materials and Measurements have been measured for delta(34)S and sulfur concentration. The mean delta(34)S value, relative to Vienna Canyon Diablo Troilite (VCDT), determined was 10.34 +/- 0.11 per thousand (n = 9) with the uncertainty reported as expanded uncertainties (U). These delta(34)S measurements include a correction for blank which has been previously ignored in studies of sulfur isotopic composition. The sulfur concentrations for the three bottles range from 56 to 88 microg/g. The isotope composition and concentration results demonstrate the high accuracy and precision of the DS-MC-TIMS technique for measuring sulfur in methionine. PMID- 20740546 TI - Analysis of catalpol derivatives by characteristic neutral losses using liquid chromatography combined with electrospray ionization multistage and time-of flight mass spectrometry. PMID- 20740547 TI - Comments on "Discrepancies between isotope ratio infrared spectroscopy and isotope ratio mass spectrometry for the stable isotope analysis of plant and soil waters". PMID- 20740548 TI - Efficient platinum-free counter electrodes for dye-sensitized solar cell applications. AB - Nanoporous layers of poly(3,4-propylenedioxythiophene) (PProDOT) were fabricated by electrical-field-assisted growth using hydrophobic ionic liquids as the growing medium. A series of PProDoT layers was prepared with three different ionic liquids to control the microstructure and electrochemical properties of the resulting dye-sensitized solar cells, which were highly efficient and showed a power conversion efficiency of >9% under different sunlight intensities. The current-voltage characteristics of the counter electrodes varied depending on the ionic liquids used in the synthesis of PProDOT. The most hydrophobic ionic liquids exhibited high catalytic properties, thus resulting in high power conversion efficiency and allowing the fabrication of platinum-free, stable, flexible, and cost-effective dye-sensitized solar cells. PMID- 20740549 TI - Meta-analyses of effects of phytochemicals on digestibility and rumen fermentation characteristics associated with methanogenesis. AB - BACKGROUND: A meta-analysis study was conducted to investigate the changes in rumen fermentation characteristics when methane inhibition by phytochemicals is employed. The whole database containing 185 treatment means from 36 published studies was divided into four subsets according to the major phytochemicals used in the studies, i.e. saponins, tannins, essential oils (EO) and organosulfur compounds (OS). RESULTS: Changes in protozoal numbers showed linear relationships with changes in methane production by saponins (R(2) = 0.48), tannins (R(2) = 0.30) and EO (R(2) = 0.20) but not OS. Concentrations of total volatile fatty acids (VFA) and acetate did not show any relationship (P > 0.1) with changes in methane due to saponins. However, propionate production increased linearly with increasing inhibition of methane (R(2) = 0.31), which resulted in a linear (R(2) = 0.26) decrease in acetate/propionate ratio (A/P) with decreasing methane production. Concentrations of total VFA, acetate and propionate did not change with changes in methane production by tannins. However, A/P showed a significant linear relationship (R(2) = 0.27) with decreasing methane formation. Concentrations of total VFA (R(2) = 0.44) and propionate (R(2) = 0.15) changed linearly and positively with changes in methane production by EO. However, acetate production (R(2) = 0.22) and A/P (R(2) = 0.17) increased linearly with increasing inhibition of methane by EO. Changes in concentrations of total VFA (R(2) = 0.60) and acetate (R(2) = 0.35) decreased linearly while those of propionate increased linearly (R(2) = 0.23) with increasing inhibition of methane by OS. Consequently, A/P decreased linearly (R(2) = 0.30) with decreasing methane production by OS. Digestibilities of organic matter (OM) and neutral detergent fibre were not affected by inhibition of methane production by saponins, EO and OS, but digestibility of OM decreased with decreasing methane production by tannins. CONCLUSION: The inhibition of methane production by phytochemicals results in changes in rumen fermentation that differ depending on the types of phytochemicals. PMID- 20740550 TI - Biogenic amine formation in Turkish dry fermented sausage (sucuk) as affected by nisin and nitrite. AB - BACKGROUND: The effects of nitrite (0, 100, and 200 mg kg(-1)) and nisin (0, 250, and 500 mg kg(-1)) on biogenic amine formation in sucuk were investigated by utilising a central composite design of response surface methodology. RESULTS: The addition of nitrite led to decreased levels of tryptamine, 2 phenylethylamine, putrescine, cadaverine, tyramine, and histamine, whereas nisin decreased the tryptamine level and counts of lactic acid bacteria. However, nisin increased putrescine, cadaverine, and spermidine levels. Their interactive effect was also found to be significant (P < 0.05) for putrescine values. CONCLUSION: The additional nitrite levels can be decreased by the addition of nisin, which will hinder biogenic amine formation. PMID- 20740551 TI - Physiological optimality, allocation trade-offs and antioxidant protection linked to better leaf yield performance in drought exposed mulberry. AB - BACKGROUND: Mulberry (Morus spp. L.), usually linked to silkworm rearing, is now considered as a potential forage for livestock feeding and has great potential in world agriculture. Trait-based investigations for leaf yield stability in mulberry under water stress have not been studied extensively. The present study aims to identify candidate traits conferring leaf yield stability in mulberry under drought. RESULTS: Four popular, indigenous mulberry cultivars (Morus indica L. cvs AR-12, K-2, M. Local and V-1) were investigated. Low leaf temperature (T(l)), higher internal/ambient CO(2) ratios (C(i)/C(a)), greater stomatal conductance to CO(2) (g(s)) and stability in photosystem II efficiency were associated with better net photosynthetic rates (P(n)) in V-1, generating maximum leaf yield when compared to other drought-exposed cultivars. Increased accumulation of foliar alpha-tocopherol and ascorbic acid-glutathione pool, associated with higher carotenoids, proline and glycine betaine, facilitated lower lipid peroxidation and better leaf yield in V-1 under drought. CONCLUSION: Minimal plasticity in photosynthetic gas exchange traits and better quantitative growth characteristics were attributed to leaf yield stability under drought. Lower photoinhibition, stabilized photochemistry, effective osmoregulation and enhanced activity of foliar antioxidants extensively contributed to drought tolerance and higher leaf yield in mulberry. PMID- 20740552 TI - Consonant closed likelihood ratio test procedures with application to dose response study. AB - Coherence and Consonance are two important concepts in multiple testing procedures (MTP). Closed test is a well-known coherent hypothesis testing procedure, which is not necessarily consonant. In this paper, we propose two consonant closed likelihood ratio tests which are compared with the step-down Dunnett test (SD) and Dunnett-Tamhane step-up test (SU) in several aspects. Simulation and dose-response study examples show that the new procedures have certain advantages over the SD and SU test. For example, the rejection region of our new procedures is larger than that of the SD test particularly when most of the null hypotheses are false. The new procedures control the family-wise error rate (FWER) strongly without the equal correlation assumption, which is a necessary condition for the SU test. In terms of computing effort, the new procedures require similar moderate computation for critical constants as the SU test and they follow the same steps as any closed test procedures. We also provide guideline in applying consonance adjustment in multivariate analysis with mixed model and repeated measurements. PMID- 20740553 TI - SKATE: a docking program that decouples systematic sampling from scoring. AB - SKATE is a docking prototype that decouples systematic sampling from scoring. This novel approach removes any interdependence between sampling and scoring functions to achieve better sampling and, thus, improves docking accuracy. SKATE systematically samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. Efficient systematic sampling is achieved by pruning the combinatorial tree using aggregate assembly, discriminant analysis, adaptive sampling, radial sampling, and clustering. Because systematic sampling is decoupled from scoring, the poses generated by SKATE can be ranked by any published, or in-house, scoring function. To test the performance of SKATE, ligands from the Asetex/CDCC set, the Surflex set, and the Vertex set, a total of 266 complexes, were redocked to their respective receptors. The results show that SKATE was able to sample poses within 2 A RMSD of the native structure for 98, 95, and 98% of the cases in the Astex/CDCC, Surflex, and Vertex sets, respectively. Cross-docking accuracy of SKATE was also assessed by docking 10 ligands to thymidine kinase and 73 ligands to cyclin-dependent kinase. PMID- 20740554 TI - Ab initio and quantum chemical topology studies on the isomerization of HONO to HNO2. Effect of the basis set in QCT. AB - The article focus on the isomerization of nitrous acid HONO to hydrogen nitryl HNO(2). Density functional (B3LYP) and MP2 methods, and a wide variety of basis sets, have been chosen to investigate the mechanism of this reaction. The results clearly show that there are two possible paths: 1) Uncatalysed isomerisation, trans-HONO --> HNO(2), involving 1,2-hydrogen shift and characterized by a large energetic barrier 49.7 divided by 58.9 kcal/mol, 2) Catalysed double hydrogen transfer process, trans-HONO + cis-HONO --> HNO(2) + cis-HONO, which displays a significantly lower energetic barrier in a range of 11.6 divided by 18.9 kcal/mol. Topological analysis of the Electron Localization Function (ELF) shows that the hydrogen transfer for both studied reactions takes place through the formation of a 'dressed' proton along the reaction path. Use of a wide variety of basis sets demonstrates a clear basis set dependence on the ELF topology of HNO(2). Less saturated basis sets yield two lone pair basins, V(1)(N), V(2)(N), whereas more saturated ones (for example aug-cc-pVTZ and aug-cc-pVQZ) do not indicate a lone pair on the nitrogen atom. Topological analysis of the Electron Localizability Indication (ELI-D) at the CASSCF (12,10) confirms these findings, showing the existence of the lone pair basins but with decreasing populations as the basis set becomes more saturated (0.35e for the cc-pVDZ basis set to 0.06e for the aug-cc-pVTZ). This confirms that the choice of basis set not only can influence the value of the electron population at the particular atom, but can also lead to different ELF topology. PMID- 20740555 TI - Modeling environmental effects on charge density distributions in polar organometallics: validation of embedded cluster models for the methyl lithium crystal. AB - The charge density and its Laplacian at the Li-C and C-H bond critical points and other features of the electron density distribution of the methyl lithium crystal have been compared by density functional methods for (i) the isolated (LiCH(3))(4) tetramer or larger clusters, (ii) for quantum mechanically treated clusters in polarizable continuum model (PCM) surroundings, (iii) for clusters augmented by the periodic electrostatic embedded cluster model (PEECM), and for (iv) the periodic crystal. Comparisons with identical functional and basis sets indicate that both PCM and PEECM embedding of only a tetramer did not fully account for the environmental effect. In contrast, embedding of a full unit cell gave results that were essentially converged to the periodic crystal data. Effects of basis set and exchange correlation functional on the QTAIM bond descriptors are of a comparable order of magnitude as the crystal environmental effects. In this context, embedded cluster computations provide distinct advantages over explicit solid-state calculations with respect to their freedom of the choice of computational and theoretical level. This is demonstrated by embedded MP2 calculations. PMID- 20740556 TI - Counting the cyclocized polyphenacenes. AB - In general the cyclocized polyphenacenes have a geometric nonplanar structure. This article gives an explicit expression of the counting formula for the two types of cyclocized polyphenacenes, viz., the belt-type and Mobius type, respectively. The result implies that almost all the belt-type cyclocized polyphenacenes, roughly speaking, are chiral if they are sufficiently large. The numerical results for these two types with the number of phenyl rings from 3 up to 18 are listed, as an example. PMID- 20740557 TI - Accurate prediction of enthalpies of formation for a large set of organic compounds. AB - This article describes a multiparameter calibration model, which improves the accuracy of density functional theory (DFT) for the prediction of standard enthalpies of formation for a large set of organic compounds. The model applies atom based, bond based, electronic, and radical environmental correction terms to calibrate the calculated enthalpies of formation at B3LYP/6-31G(d,p) level by a least-square method. A diverse data set of 771 closed-shell compounds and radicals is used to train the model. The leave-one-out cross validation squared correlation coefficient q(2) of 0.84 and squared correlation coefficient r(2) of 0.86 for the final model are obtained. The mean absolute error in enthalpies of formation for the dataset is reduced from 4.9 kcal/mol before calibration to 2.1 kcal/mol after calibration. Five-fold cross validation is also used to estimate the performance of the calibration model and similar results are obtained. PMID- 20740558 TI - A high-performance parallel-generalized Born implementation enabled by tabulated interaction rescaling. AB - Implicit solvent representations, in general, and generalized Born models, in particular, provide an attractive way to reduce the number of interactions and degrees of freedom in a system. The instantaneous relaxation of the dielectric shielding provided by an implicit solvent model can be extremely efficient for high-throughput and Monte Carlo studies, and a reduced system size can also remove a lot of statistical noise. Despite these advantages, it has been difficult for generalized Born implementations to significantly outperform optimized explicit-water simulations due to more complex functional forms and the two extra interaction stages necessary to calculate Born radii and the derivative chain rule terms contributing to the force. Here, we present a method that uses a rescaling transformation to make the standard generalized Born expression a function of a single variable, which enables an efficient tabulated implementation on any modern CPU hardware. The total performance is within a factor 2 of simulations in vacuo. The algorithm has been implemented in Gromacs, including single-instruction multiple-data acceleration, for three different Born radius models and corresponding chain rule terms. We have also adapted the model to work with the virtual interaction sites commonly used for hydrogens to enable long-time steps, which makes it possible to achieve a simulation performance of 0.86 micros/day for BBA5 with 1-nm cutoff on a single quad-core desktop processor. Finally, we have also implemented a set of streaming kernels without neighborlists to accelerate the non-cutoff setup occasionally used for implicit solvent simulations of small systems. PMID- 20740559 TI - DNA-backbone radio resistivity induced by spin blockade effect. AB - Coherent control of OH-free radicals interacting with the spin-triplet state of a DNA molecule is investigated. A model Hamiltonian for molecular spin singlet triplet resonance is developed. We illustrate that the spin-triplet state in DNA molecules can be efficiently populated, as the spin-injection rate can be tuned to be orders of magnitudes greater than the decay rate due to small spin-orbit coupling in organic molecules. Owing to the nano-second life-time of OH free radicals, a non-equilibrium free energy barrier induced by the injected spin triplet state that lasts approximately longer than one-micro second in room temperature can efficiently block the initial Hydrogen abstraction and DNA damage. For a direct demonstration of the spin-blockade effect, a molecular simulation based on an ab-initio Car-Parrinello molecular dynamics is deployed. PMID- 20740560 TI - Time-dependent quantum study of H(2S) + FO(2Pi) --> OH(2Pi) + F(2P) reaction on the 1(3)A' and 1(3)A'' states. AB - The dynamics of the H((2)S) + FO((2)Pi) --> OH((2)Pi) + F((2)P) reaction on the adiabatic potential energy surface of the 1(3)A' and 1(3)A'' states is investigated. The initial state selected reaction probabilities for total angular momentum J = 0 have been calculated by using the quantum mechanical real wave packet method. The integral cross sections and initial state selected reaction rate constants have been obtained from the corresponding J = 0 reaction probabilities by means of the simple J-Shifting technique. The initial state selected reaction probabilities and reaction cross section do not manifest any sharp oscillations and the initial state selected reaction rate constants are sensitive to the temperature. PMID- 20740561 TI - Chemical reactivity predictions: use of data mining techniques for analyzing regioselective azidolysis of epoxides. AB - Azidolysis of epoxides followed by reduction of the intermediate azido alcohols constitutes a valuable synthetic tool for the construction of beta-amino alcohols, an important chemical functionality occurring in many biologically active compounds of natural origin. However, depending on conditions under which the azidolysis is carried out, two regioisomeric products can be formed, as a consequence of the nucleophilic attack on both the oxirane carbon atoms. In this work, predictive models for quantitative structure-reactivity relationships were developed by means of multiple linear regression, k-nearest neighbor, locally weighted regression, and Gaussian Process regression algorithms. The specific nature of the problem at hand required the creation of appropriate new descriptors, able to properly reflect the most relevant features of molecular moieties directly involved in the opening process. The models so obtained are able to predict the regioselectivity of the azidolysis of epoxides promoted by sodium azide, in the presence of lithium perchlorate, on the basis of steric hindrance, and charge distribution of the substituents directly attached to the oxirane ring. PMID- 20740562 TI - A density-functional study of the phase diagram of cementite-type (Fe,Mn)3C at absolute zero temperature. AB - The phase diagram of (Fe(1-x) Mn(x))(3)C has been investigated by means of density-functional theory (DFT) calculations at absolute zero temperature. The atomic distributions of the metal atoms are not random-like as previously proposed but we find three different, ordered regions within the phase range. The key role is played by the 8d metal site which forms, as a function of the composition, differing magnetic layers, and these dominate the physical properties. We calculated the magnetic moments, the volumes, the enthalpies of mixing and formation of 13 different compositions and explain the changes of the macroscopic properties with changes in the electronic and magnetic structures by means of bonding analyses using the Crystal Orbital Hamilton Population (COHP) technique. PMID- 20740563 TI - An optimum strategy for solution chemistry using semiempirical molecular orbital method. II. Primary importance of reproducing electrostatic interaction in the QM/MM framework. AB - For the purpose of executing direct dynamic and statistical calculation of chemical reactions in solution, we proposed an optimum strategy using semiempirical molecular orbital (MO) method with neglect of diatomic differential overlap (NDDO) approximation with specific solution reaction parameters (SSRPs), that is, the NDDO-SSRP method. It has been further extended to develop the NDDO MAIS-SSRP method, which is the NDDO-SSRP method reinforced with the method adopted for intermolecular studies (MAIS), to correct the description of the intermolecular core-core repulsion interaction energy. In this strategy, the empirical parameters of the semiempirical MO method are optimized individually for a target chemically reacting molecular system by reference to the ab initio MO calculation data for a lot of instantaneous geometries on the potential energy surface near the reaction path. For demonstration, the NDDO-MAIS-SSRP method was applied, within the QM/MM framework, to a molecular cluster, that is, a couple of a QM solute NH(3)-H(2)O molecule pair and a MM solvent H(2)O molecule. The NDDO MAIS-SSRP method can reproduce the electrostatic energy in the region R > 4.0 A, though the electrostatic energy shows large difference with those of MP2 level calculations in the region R < 4.0 A in some cases. Both the NDDO-SSRP and the NDDO-MAIS-SSRP methods could promise in the dynamical application to chemical reaction in solution (Takenaka et al., Chem Phys Lett 2010, 485, 119; Koyano et al., Bull Chem Soc Jpn, in press). PMID- 20740564 TI - The role of water in the proton transfer reaction mechanism in tryptophan. AB - The role of water in the proton transfer mechanism between the carboxylic and the amino group in tryptophan was studied through the direct, intramolecular reaction in presence of a continuum and the single water molecule mediated, intermolecular reaction in vacuum and in presence of a continuum. The introduction of the continuum reduced the activation barriers for the proton transfer from the neutral form and stabilized the zwitterion in both cases. The reaction force and the reaction electronic flux along the intrinsic reaction coordinate allowed in combination with a Natural Bond Order Analysis a more detailed description of the influence of water on the reaction mechanism. Represented as a continuum model, water reduced the energy required for bond reorganization and did not alter the first part of the intermolecular reaction, characterized through the approximation of the water molecule to the functional groups of the amino acid and a polarization of the system. The absence of a water molecule in the intramolecular proton transfer with continuum changed the reaction coordinate to a reduction of the angle between the functional groups of the amino acid leaving the energy required for bond formation unaffected. Thus, the smaller activation barrier obtained in the direct intramolecular proton transfer with continuum model in comparison to the water mediated reaction, originates from the energetically more favorable angle reduction in comparison the approximation of a water molecule. PMID- 20740565 TI - Electronic structures and nonlinear optical properties of highly deformed halofullerenes C(3v) C60F18 and D(3d) C60Cl30. AB - Electronic structures and nonlinear optical properties of two highly deformed halofullerenes C(3v) C(60)F(18) and D(3d) C(60)Cl(30) have been systematically studied by means of density functional theory. The large energy gaps (3.62 and 2.61 eV) between the highest occupied and lowest unoccupied molecular orbitals (HOMOs and LUMOs) and the strong aromatic character (with nucleus-independent chemical shifts varying from -15.08 to -23.71 ppm) of C(60)F(18) and C(60)Cl(30) indicate their high stabilities. Further investigations of electronic property show that C(60)F(18) and C(60)Cl(30) could be excellent electron acceptors for potential photonic/photovoltaic applications in consequence of their large vertical electron affinities. The density of states and frontier molecular orbitals are also calculated, which present that HOMOs and LUMOs are mainly distributed in the tortoise shell subunit of C(60)F(18) and the aromatic [18] trannulene ring of C(60)Cl(30), and the influence from halogen atoms is secondary. In addition, the static linear polarizability and second-order hyperpolarizability of C(60)F(18) and C(60)Cl(30) are calculated using finite-field approach. The values of and for C(60)F(18) and C(60)Cl(30) molecules are significantly larger than those of C(60) because of their lower symmetric structures and high delocalization of pi electrons. PMID- 20740566 TI - Simulaid: a simulation facilitator and analysis program. AB - Simulaid performs a large number of simulation-related tasks: interconversion and modification of structure and trajectory files, optimization of orientation, and a large variety of analysis functions. The program can handle structures in PDB (Berman et al., Nucleic Acids Res 2000, 28, 235), Charmm (Brooks et al., J Comput Chem 4, 187) CRD, Amber (Case et al.), Macromodel (Mohamadi et al., J Comput Chem 1990, 11, 440), Gromos/Gromacs (Hess et al.), InsightII (InsightII. Accelrys Inc.: San Diego, 2005), Grasp (Nicholls et al., Proteins: Struct Funct Genet 1991, 11, 281) .crg, Tripos (Tripos International, S. H. R., St. Louis, MO) .mol2 (input only), and in the MMC (Mezei, M.; MMC: Monte Carlo program for molecular assemblies. Available at: http://inka.mssm.edu/~mezei/mmc) formats; and trajectories in the formats of Charmm, Amber, Macromodel, and MMC. Analysis features include (but are not limited to): (1) simple distance calculations and hydrogen-bond analysis, (2) calculation of 2-D RMSD maps (produced both as text file with the data and as a color-coded matrix) and cross RMSD maps between trajectories, (3) clustering based on RMSD maps, (4) analysis of torsion angles, Ramachandran (Ramachandran and Sasiskharan, Adv Protein Chem 1968, 23, 283) angles, proline kink (Visiers et al., Protein Eng 2000, 13, 603) angles, pseudorotational (Altona and Sundaralingam, J Am Chem Soc 1972, 94, 8205; Cremer and Pople, J Am Chem Soc 1975, 97, 1354) angles, and (5) analysis based on circular variance (Mezei, J Mol Graphics Model 2003, 21, 463). Torsion angle evolutions are presented in dial plots (Ravishanker et al., J Biomol Struct Dyn 1989, 6, 669). Several of these features are unique to Simulaid. PMID- 20740567 TI - Incorporation of deMon2k as a new parallel quantum mechanical code for the PUPIL system. AB - The PUPIL system is a combination of software and protocols for the systematic linkage and interoperation of molecular dynamics and quantum mechanics codes to perform QM/MD (sometimes called QM/MM) calculations. The Gaussian03 and Amber packages were added to the PUPIL suite recently. However, efficient parallel QM codes are critical because calculation of the QM forces is the overwhelming majority of the computational load. Here we report details of incorporation of the deMon2k density functional suite as a new parallel QM code. An additional motivation is to add a highly optimized, purely DFT code. We illustrate with a demonstration study of the influence of perchlorate as a dopant ion of the poly(3,4-ethylenedioxythiophene) conducting polymer in explicit acetonitrile solvent using Amber and deMon2k. We discuss unanticipated requirements for use of a scheme for semi-empirical correction of Kohn-Sham eigenvalues to give physically meaningful one-electron gap energies. We provide comparison of both geometric parameters and electronic properties for nondoped and doped systems. We also present results comparing deMon2k and Gaussian03 calculation of forces for a short sequence of steps. We discuss briefly some difficult problems of quantum zone SCF convergence for the anionically doped system. The difficulties seem to be caused by well-know deficiencies in simple approximate exchange-correlation functionals. PMID- 20740568 TI - Linear mixed models for skew-normal/independent bivariate responses with an application to periodontal disease. AB - Bivariate clustered (correlated) data often encountered in epidemiological and clinical research are routinely analyzed under a linear mixed model (LMM) framework with underlying normality assumptions of the random effects and within subject errors. However, such normality assumptions might be questionable if the data set particularly exhibits skewness and heavy tails. Using a Bayesian paradigm, we use the skew-normal/independent (SNI) distribution as a tool for modeling clustered data with bivariate non-normal responses in an LMM framework. The SNI distribution is an attractive class of asymmetric thick-tailed parametric structure which includes the skew-normal distribution as a special case. We assume that the random effects follow multivariate SNI distributions and the random errors follow SNI distributions which provides substantial robustness over the symmetric normal process in an LMM framework. Specific distributions obtained as special cases, viz. the skew-t, the skew-slash and the skew-contaminated normal distributions are compared, along with the default skew-normal density. The methodology is illustrated through an application to a real data which records the periodontal health status of an interesting population using periodontal pocket depth (PPD) and clinical attachment level (CAL). PMID- 20740569 TI - Prenatal and early life factors and risk of Parkinson's disease. AB - Few studies have investigated the relation between early life factors and risk of Parkinson's disease (PD), although a potential role of exposures during pregnancy and childhood has been hypothesized. The study population comprised participants in two prospective cohorts: the Nurses' Health Study (121,701 female nurses followed up from 1976-2002) and the Health Professionals Follow-up Study (51,529 male health professionals followed up from 1986-2002). PD risk was examined in relation to season of birth, birthweight, parental age at birth, preterm birth, multiple birth, ever having been breast-fed, and handedness. We identified 659 incident PD cases. No significant relation with PD was observed for birthweight, paternal age, preterm birth, multiple birth, and having been breast-fed. A modest nonsignificant association was suggested for season of birth (30% higher risk of PD associated with spring versus winter birth) and for older maternal age at birth (75% increased risk among those with mothers aged 30 years and older versus younger than 20 years). Left-handedness was associated with a 62% increased risk of PD in women but not in men. Further investigation of the relation between prenatal, perinatal, or neonatal factors and PD in other study populations is suggested. PMID- 20740570 TI - Subacute axonal neuropathy in Parkinson's disease with cobalamin and vitamin B6 deficiency under duodopa therapy. AB - We describe two patients who developed subacute axonal peripheral neuropathy under duodopa treatment. Comprehensive diagnostic workup including muscle and sural nerve biopsy revealed that the most probable cause of subacute axonal peripheral neuropathy was cobalamin and vitamin B6 deficiency in both the patients. PMID- 20740573 TI - Ki-67 proliferation index and gastric cancer: answers or more questions. PMID- 20740574 TI - Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancer. AB - BACKGROUND AND OBJECTIVES: We designed this study to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. METHODS: Gastric cancer tissue from 245 patients were immunostained for Ki-67. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. In addition, we have previously evaluated the expressions of nine epithelial mesenchymal transition (EMT)-related proteins. The relationship between Ki-67 PI and clinicopathologic parameters, patient survival, and EMT data were sought. RESULTS: Low Ki-67 PI was correlated with poorly differentiated histology (P = 0.034), an advanced T stage (P < 0.001), and lymph node metastasis (P = 0.011). Also, the low PI group was found to have a significantly worse prognosis than the high PI group (P = 0.003, log-rank test). Multivariate analysis revealed that Ki 67 PI remained as an independent prognostic factor (hazard ratio (95% CI) = 0.670 (0.450-0.999)). Furthermore, greater expressional changes of EMT-related proteins were found to be significantly associated with low Ki-67 PI (P = 0.025). CONCLUSIONS: These findings suggest that Ki-67 PI is an effective tool for predicting survival in gastric cancer. In addition, we found that an invasive property presented as EMT-related protein expressional changes was inversely correlated with a proliferative activity in gastric cancer. PMID- 20740575 TI - SBRT for unresectable HCC: a familiar tune? PMID- 20740577 TI - Outcome of selected breast cancer patients with micrometastasis or isolated tumor cells in sentinel node biopsy and no completion axillary lymph node dissection. AB - BACKGROUND AND OBJECTIVES: Axillary lymph node dissection (ALND) is the standard of care in patients with tumor-positive sentinel nodes (SN). However, approximately half of these patients do not have additional metastases in their axilla and therefore do not benefit from completion ALND. Our aim was to examine the outcome of highly selected breast cancer patients with tumor-positive SN without completion ALND. METHODS: Altogether 48 patients with tumor-positive SN without ALND were included in this study. Twenty-two patients had micrometastasis and 26 had isolated tumor cells (ITC) in their sentinel node biopsy. The median follow-up time was 37 months (range 9-78). RESULTS: No axillary recurrences occurred during the follow-up. One patient had a local recurrence. Distant metastases as the first event were observed in two patients. One of them died in breast cancer. Nine patients died from intercurrent causes. CONCLUSIONS: Omitting ALND seems safe in selected breast cancer patients with SN micrometastasis or ITC. PMID- 20740576 TI - Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. AB - BACKGROUND AND OBJECTIVES: To evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of localized hepatocellular carcinoma (HCC) in the absence of another standard treatment option. METHODS: The authors reviewed the details of 38 patients with inoperable HCC (diameter <10 cm) treated by SBRT in a prospectively registered database at their institution. All patients had been treated by transcatheter arterial chemoembolization before SBRT, which had been finally deemed ineffective. SBRT dosages (33-57 Gy in three or four fractions) were administered according to tumor volumes, which ranged from 11 to 464 ml (median, 40.5 ml). RESULTS: Two-year overall survival and local progression-free survival rates were 61.4% and 66.4%, respectively. The local response rate was 63% at 3 months after SBRT. A high radiation dose was found to be independently related to survival. A decline in liver function was observed in six patients (16%) and Grade 3 musculoskeletal toxicity in one patient (2.7%). CONCLUSIONS: This study showed that SBRT can be safely administered to select HCC patients, and these results suggest that this technique should be considered a salvage treatment. A further well-controlled large-scale study and longer follow up are needed to determine optimal dose-fraction schedules and characterize late complications. PMID- 20740578 TI - A nomogram to predict for malignant diagnosis of BI-RADS Category 4 breast lesions. AB - BACKGROUND AND OBJECTIVE: BI-RADS Category classification is the most powerful predictor of breast cancer (BC). However, BI-RADS Category 4 lesions are associated with a highly variable rate of BC. The purpose of this study was to develop and validate a nomogram for the prediction of individual probability of BC in patients with BI-RADS Category 4 lesions. METHODS: The study included all patients with BI-RADS Category 4 lesions at screening mammogram, who underwent diagnostic cytology or biopsy and, as needed, surgery or follow-up. Univariate and multivariate logistic regression analyses were used to develop the model and build the nomogram. This nomogram was evaluated on a training set of 170 patients treated at IGR Cancer Center, Paris, France. Nomogram performance was evaluated on an external independent dataset of 188 patients from MDA Cancer Center, Houston, Texas. RESULTS: A total of 51 (28.5%) patients in the training set and 73 (42.4%) patients in the validation set were diagnosed with BC. The final, most informative, nomogram included information on patient age (P = 0.04), palpable tumor (P = 0.002), menopausal status (P = 0.32), lesion size (P = 0.81), HRT (P = 0.09), and Gail risk (P = 0.58). The predictive accuracy of the nomogram was 0.716, respectively. The concordance index of the model was 0.66 in the validation set. CONCLUSION: The nomogram based on clinical and radiological findings may help inform the patients before surgical explorations, to decrease the number of missed cancer cases but currently cannot replace FNA or biopsy. PMID- 20740579 TI - The prediction of lymph node metastasis in ductal carcinoma in situ with microinvasion by assessing lymphangiogenesis. AB - BACKGROUND AND OBJECTIVES: Lymph node (LN) metastasis of ductal carcinoma in situ with microinvasion (DCISM) is variable (0-14%). To ascertain the role of lymphangiogenesis in LN metastasis in DCISM, we compared the lymphatic vessel density with the presence of LN metastasis in a group of patients that underwent axillary dissection with breast surgery due to DCISM. METHODS: We identified 46 patients with a diagnosis of DCISM who underwent breast surgery with axillary dissection to evaluate LN status from June 1996 to March 2008. Microvessel density (MVD) and lymphatic vessel density (LVD) was measured by immunohistochemical staining with two markers, CD34 and D2-40. RESULTS: LVD of the patients with LN metastasis was significantly higher than that of the patients without LN metastasis (P = 0.04). Correlation in the total score of progesterone receptor and LN metastasis was also noted (P = 0.017). There was no statistically significant relation between LVD and clinicopathologic parameters such as size and type of underlying DCIS, nuclear grade, presence of lymphovascular invasion, hormone receptor, and HER-2 status. CONCLUSIONS: Lymphangiogenesis may be significantly associated with LN metastasis in DCISM. This is the first attempt to predict axillary LN metastasis in DCISM by quantifying the LVD. PMID- 20740580 TI - Severe tumor budding is a risk factor for lateral lymph node metastasis in early rectal cancers. AB - BACKGROUND: Lateral lymph node (LLN) metastasis sometimes occurs in patients with early rectal cancer that has invaded the submucosa (SM) and muscularis propria (MP). This study aims to identify the risk factor(s) for LLN metastasis in such patients. METHOD: We retrospectively analyzed 65 patients with pathological SM or MP lower rectal adenocarcinoma, for whom radical resection had been performed at a single institution. RESULTS: We performed LLN dissection in 52 (80%) patients. The LLN dissection rates in the case of pathological SM and MP tumors were 65.6% and 94.4%, respectively, and the corresponding LLN metastasis rates were 6.9% and 11.1%. Severe tumor budding was found to be a risk factor for LLN metastasis (P = 0.002). Further, of six patients with LLN metastasis, four did not have coincident mesenteric lymph node metastasis. CONCLUSION: In rectal cancer that has pathologically invaded SM and MP, LLN metastasis is not negligible. LLN dissection could lower the local recurrence rate of SM and MP rectal cancer. In case LLN dissection is not performed, patients with a high tumor budding grade should be administered adjuvant therapy. PMID- 20740581 TI - Tumour budding, uPA and PAI-1 are associated with aggressive behaviour in colon cancer. AB - AIMS: The proteases PAI-1 and uPA play a major role in extracellular matrix degradation, which facilitates tumour progression. Tumour budding is a histomorphological expression of enhanced tumour cell migration. MATERIALS AND METHODS: To investigate their prognostic value for and correlation with colon cancer, a prospective study was performed. We analysed tissue levels of uPA and PAI-1 of 55 colon cancer tumours employing a commercially available enzyme-linked immunosorbent assay (ELISA). Tumour budding was analysed on cytokeratin-stained slides. RESULTS: There was a strong correlation between uPA and tumour budding (R = 0.440; P < 0.001). uPA levels were increased in high grade tumours, whereas PAI 1 was elevated in cases with venous invasion (P = 0.004 and P = 0.028). PAI-1 values and tumour budding are associated significantly with the occurrence of distant metastases (P < 0.001 and P = 0.034, respectively). Tumour budding was significantly associated with lymph node metastases (P = 0.034). Multivariate analysis revealed PAI-1 and lymph node metastases to be independently predictive of distant metastases (P = 0.007 and P = 0.004, respectively). CONCLUSIONS: The results of our study show that tumour budding and the plasmin/plasminogen system are related. PAI-1 was independently predictive for the occurrence of distant metastasis. PMID- 20740582 TI - Intratumoral macrophage counts correlate with tumor progression in colorectal cancer. AB - BACKGROUND: The role of intratumoral tumor-associated macrophages (TAMs) in colorectal cancer (CRC) is not clear. We aim to examine the relationships of TAMs and the clinicopathologic features of CRC and the expression of matrix metalloproteinases (MMP)-2 and MMP-9. METHODS: Immunohistochemical staining of CD68, MMP-2, and MMP-9 was determined in tissue samples from CRC patients. To test the biological effect of macrophages on tumor cells, cancer cells were cocultured with macrophages and function change of cancer cells were examined. RESULTS: Intratumoral TAM count correlated with depth of invasion (P = 0.048), lymph node metastasis (P < 0.0001), and staging (P < 0.0001) of CRC. MMP-2 and MMP-9 expression was significantly associated with lymph node metastasis and staging. A significant association between intratumoral TAM counts and MMP-2 (P < 0.0001) and MMP-9 (P < 0.0001) expression was noted. When cocultured with macrophages, cancer cells increased their invasiveness and migration and elevated MMP-2 and MMP-9 secretion. CONCLUSIONS: Intratumoral TAMs cause cancer cells to have a more aggressive behavior, and this may be due to an upregulation of tumor cell-derived MMP-2 and MMP-9. Examination of intratumoral TAMs can serve as a progressive marker for CRC patients. PMID- 20740583 TI - Clinicopathologic features and prognostic factors in alpha-fetoprotein-producing gastric cancers: analysis of 104 cases. AB - BACKGROUND AND OBJECTIVES: There were no comprehensive studies on the clinicopathologic features and prognosis of alpha-protein-producing gastric cancer. The aim of this study was to elucidate the clinicopathologic characteristics and prognostic factors of alpha-fetoprotein (AFP)-producing gastric cancer. METHODS: Among 4,426 gastric cancer patients receiving surgery in the Cancer Hospital of Fudan University from 1996 to 2007, there were 111 patients with elevated serum level of AFP preoperatively after excluding chronic hepatitis, hepatocirrhosis, and hepatocellular carcinoma. Primary lesions of 104 patients were stained positively for AFP. The clinicopathologic characteristics and prognostic factors of AFP-producing gastric cancer were analyzed. Additionally, 208 stage-matched AFP-negative gastric cancer patients were selected as control. RESULTS: There was a significantly higher incidence of vascular invasion, lymph node metastasis, and liver metastasis in AFP-positive group than in the negative group. The overall 5-year survival rates of AFP positive and negative groups were 28% and 38%, respectively. The AFP-positive group had a significantly poorer survival in comparison to the stage-matched negative group. The independent prognostic factors of AFP-positive group included liver metastasis and pathological stage. CONCLUSIONS: AFP-positive gastric cancer had more aggressive behavior than that of AFP-negative gastric cancer. In addition to surgery, multimodal therapy should be considered. PMID- 20740584 TI - Safety and efficacy of curative intent surgery for peri-ampullary liver metastasis. AB - INTRODUCTION: The management of patients with peri-ampullary liver metastasis remains controversial. We sought to assess the safety and efficacy of curative intent surgery for peri-ampullary liver metastasis. METHODS: Between 1993 and 2009, 40 patients underwent curative intent surgery (resection and/or radiofrequency ablation (RFA)) for peri-ampullary liver metastasis. Clinicopathologic and outcome data were collected and analyzed. RESULTS: Location of the primary tumor was pancreas head (n = 20), ampulla of Vater (n = 10), distal bile duct (n = 5), or duodenum (n = 5). Most patients (n = 27) presented with synchronous disease, while 13 patients presented with metachronous disease following a median disease-free interval of 22 months. Most patients (n = 25) presented with hepatic metastasis from pancreaticobiliary origin (pancreatic or distal common bile duct) compared with 15 patients who had metastasis from an intestinal-type primary (ampullary or duodenal). There were no differences in metastatic tumor number or size between these groups (P > 0.05). Post-operative morbidity and mortality was 30% and 5% respectively. Overall 1- and 3-year survival was 55% and 18%. Patients who underwent resection of liver metastasis from intestinal-type tumors experienced a longer survival compared with patients who had pancreaticobiliary lesions (median: 13 months vs. 23 months; P = 0.05). CONCLUSION: Curative intent surgery for peri-ampullary liver metastasis was associated with post-operative morbidity and a 5% mortality rate. Although the overall survival benefit was modest, patients with liver metastasis from intestinal-type tumors experienced improved survival following resection of liver metastasis compared with pancreaticobiliary lesions. PMID- 20740585 TI - Genetic polymorphism of CCR2-64I increased the susceptibility of hepatocellular carcinoma. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate genetic impact of monocyte chemoattractant protein-1 (MCP-1) and its receptor chemokine receptor-2 (CCR2) gene polymorphisms on the susceptibility and clinicopathological characteristics of hepatocellular carcinoma (HCC). METHODS: A total of 446 subjects, including 344 healthy controls and 102 patients with HCC, were recruited in this study and subjected to PCR-RFLP to estimate the impact of these two polymorphic variants on HCC. RESULTS: No relationship between MCP-1 2518G/A gene polymorphism and HCC risk was found among our recruited HCC patients and healthy controls. However, there was a significantly increased risk (AOR = 1.91; 95% CI = 1.11-3.29) of having HCC among subjects with GA heterozygotes of CCR2 V64I after adjusting for other confoundings. There was no synergistic effect between gene polymorphism and environmental risk factors, including tobacco and alcohol consumptions, as well as clinicopathological parameters of HCC for MCP-1 2518G/A and CCR2 V64I genes, respectively. CONCLUSIONS: CCR2-64I gene polymorphism is an important factor for the susceptibility of HCC but it might not influence the clinical pathological progression of HCC, and the contribution of CCR2-64I gene polymorphism on the susceptibility of HCC could be not through the affection of liver injury-related clinical pathological characteristics. PMID- 20740586 TI - Clinical outcomes of minimally invasive surgery using acridine orange for musculoskeletal sarcomas around the forearm, compared with conventional limb salvage surgery after wide resection. AB - BACKGROUND AND OBJECTIVES: We recently developed and established a new surgical therapy combining photodynamic surgery and radiodynamic therapy using acridine orange (AO) therapy after marginal or intralesional tumor resection, providing excellent limb function to sarcoma patients. The present study evaluated local recurrence rate and limb function using Disability of Arm, Shoulder, and Hand (DASH) score of patients with primary musculoskeletal sarcoma around the forearm treated with AO therapy, compared to that of patients treated with conventional wide resection. METHODS: Subjects were 18 patients with primary musculoskeletal sarcoma around the forearm and treated with AO therapy (AO: n = 8) after marginal or intralesional resection, or conventional wide resection followed by limb reconstruction surgery (WR: n = 10). RESULTS: Mean age of the 18 patients was 45 years, and mean durations of follow-up for Groups AO and WR were 67 and 74.1 months. Local recurrence rates for AO and WR were 12.5% and 20% (P = 0.63), DASH disability scores were 3.9 and 21 (P = 0.04), and 5-year survival rates were 100% and 90% (P = 0.40), respectively. CONCLUSIONS: AO therapy offers maintenance of excellent upper limb function and inhibition of local tumor recurrence, representing a useful modality for limb salvage surgery in patients with sarcoma around the forearm. PMID- 20740587 TI - Aspirin and compression devices versus low-molecular-weight heparin and PCD for VTE prophylaxis in orthopedic oncology patients. AB - BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are possible sources of morbidity and mortality in patients with musculoskeletal neoplasms (MSN). OBJECTIVE: To compare the efficacy of aspirin (ASA) and pneumatic compression devices (PCD) to low-molecular-weight heparin (LMWH) and PCD in patients undergoing orthopedic procedures for MSN of the pelvis or lower extremity. METHODS: Of 348 patients who met the study criteria, 195 were treated with ASA/PCD and 153 with LMWH/PCD. There were 18 DVT including 8 in ASA/PCD group and 10 in LMWH/PCD group. There were four PEs, all in the LMWH/PCD group. RESULTS: We found no significant difference in DVT rate between ASA/PCD and LMWH/PCD when used for prophylaxis against thromboembolic complications. Our analysis shows that procedures of the thigh, soft tissue resections, and malignant disease were more often managed with ASA/PCD while joint arthroplasty, procedures of the hip/pelvis, and metastatic disease were more often managed with LMWH/PCD. CONCLUSION: DVT prophylaxis in orthopedic oncology remains a complex topic in which physicians must balance the risks of thromboembolic disease against the risks of post-operative complications. PMID- 20740588 TI - Ten years later: a single hospital experience with malignancy in HIV/AIDS. AB - BACKGROUND AND OBJECTIVE: We present our experience in the era of HAART with 5,112 patients having HIV infection or AIDS, treated between 2002 and 2006 in our hospital, 182 of whom had malignancies (3.56%). We compared our findings to those from a similar cohort of patients studied 10 years earlier. METHODS: The charts were reviewed and data was electronically collected as in our 1993-1998 study. Similar statistical analyses were performed in both studies and the results were compared. RESULTS: For the current study the average patient age increased by 9 years. A decrease in AIDS-defining cancers (ADC), from 63.6% to 37.3% and a higher incidence of non-AIDS-defining cancers (NADC), 62.7 as opposed to 37.9% was found. No decrease in the incidence of non-Hodgkin's B cell lymphoma (NHL) was noted. There was an increase in the number of opportunistic infections notably hepatitis C virus (HCV) and hepatitis B virus (HBV). CONCLUSIONS: HIV/AIDS patients on HAART are older, have lower rates of AIDS related Kaposi's sarcoma and a higher incidence of NADCs than did patients in the early HAART era. No decrease in the proportion of NHL was observed. PMID- 20740589 TI - An evolution of clinical application of inferior pedicle based rectus abdominis myocutaneous flap for repair of perineal defects after radical surgery for cancer. AB - The inferior epigastric artery based rectus abdominis myocutaneous flap (RAMF) is one of the most versatile flaps used to bridge gaps in the perineum and groin, in the reconstruction of vagina after radical resections for cancer and in selected patients with benign and non-healing perineal lesions. Its use for reconstruction after Abdomino-perineal resection was first described in 1984. This review attempts to summarize the anatomic-technical aspects of inferiorly based RAMF and its applications. PMID- 20740590 TI - An urgent need to develop novel markers for prognosis in colon cancer. PMID- 20740592 TI - Routine biopsy of Cloquet's node is of limited value in sentinel node positive melanoma patients. AB - BACKGROUND AND OBJECTIVES: Biopsy of Cloquet's node (CN) during groin dissection has been used to indicate need for pelvic dissection. With earlier detection of microscopic regional disease in the era of sentinel node biopsy (SNB), frequency of positive CN may be so low that routine biopsy is unwarranted. METHODS: Patients with positive groin SNB from 2000 to 2008 were identified from two centers. Cases where CN was identified at completion node dissection were selected. Lymphoscintigraphic, surgical, pathologic, and recurrence data were reviewed. RESULTS: CN was identified in 53 cases. Median age was 44.5 years (range 7-77); median Breslow depth, 1.98 mm (range 0.5-25.0); % Clark's level IV/V, 90%; and % ulceration, 41.5%. Fifty (94.3%) underwent groin dissection alone; three others underwent concomitant pelvic dissection. Two (3.8%) patients had positive CN; both had additional indications for pelvic dissection. Delayed pelvic recurrence rate was 2/53 (3.8%); both patients had negative CN. In the three patients treated with concurrent groin and pelvic dissection, CN reflected pelvic nodal status in two cases; the third had pelvic metastases despite negative CN. CONCLUSIONS: After positive SNB, disease involvement of CN is rare. Patients with positive biopsies of CN in the SNB era appear likely to have additional indications for pelvic dissection, minimizing utility of CN biopsy. Routine intraoperative sampling of CN may not be warranted during groin dissection for positive SNB. PMID- 20740593 TI - An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. AB - The number of mouse mutants and strains with neural tube defects (NTDs) now exceeds 240, including 205 representing specific genes, 30 for unidentified genes, and 9 multifactorial strains. These mutants identify genes needed for embryonic neural tube closure. Reports of 50 new NTD mutants since our 2007 review (Harris and Juriloff, 2007) were considered in relation to the previously reviewed mutants to obtain new insights into mechanisms of NTD etiology. In addition to null mutations, some are hypomorphs or conditional mutants. Some mutations do not cause NTDs on their own, but do so in digenic, trigenic, and oligogenic combinations, an etiology that likely parallels the nature of genetic etiology of human NTDs. Mutants that have only exencephaly are fourfold more frequent than those that have spina bifida aperta with or without exencephaly. Many diverse cellular functions and biochemical pathways are involved; the NTD mutants draw new attention to chromatin modification (epigenetics), the protease activated receptor cascade, and the ciliopathies. Few mutants directly involve folate metabolism. Prevention of NTDs by maternal folate supplementation has been tested in 13 mutants and reduces NTD frequency in six diverse mutants. Inositol reduces spina bifida aperta frequency in the curly tail mutant, and three new mutants involve inositol metabolism. The many NTD mutants are the foundation for a future complete genetic understanding of the processes of neural fold elevation and fusion along mechanistically distinct cranial-caudal segments of the neural tube, and they point to several candidate processes for study in human NTD etiology. PMID- 20740595 TI - Polytomous logistic regression as a tool for exploring heterogeneity across birth defect subtypes: an example using anencephaly and spina bifida. AB - BACKGROUND: In birth defect epidemiology, phenotypic subgroups are often combined into a composite phenotype in an effort to increase statistical power. Although the validity of using composite phenotypes has been questioned, formal evaluations of the underlying assumption of effect homogeneity across component phenotypes have not been conducted. METHODS: Polytomous logistic regression was used to assess effect heterogeneity of several generally accepted neural tube defect (NTD) risk factors across the component phenotypes of anencephaly and spina bifida. Data for these analyses were obtained from the National Birth Defects Prevention Study. RESULTS: The use of a composite phenotype has the potential to mask associations specific to a component phenotype and in some cases the effect of a variable may be misattributed to the composite phenotype. For example, an association between infant sex and anencephaly (adjusted odds ratio [AOR], 1.5; 95% CI, 1.1-1.9) was masked when data from all NTDs were analyzed (AOR, 1.1; 95% CI, 0.9-1.3), whereas an association with maternal body mass index that was specific to spina bifida (AOR, 1.9; 95% CI, 1.6-2.4) was attributed to all NTDs (AOR, 1.6; 95% CI, 1.4-2.0). Furthermore, conclusions regarding effect heterogeneity based on ad hoc comparisons, rather than some formal assessment, may be vulnerable to considerable subjectivity, as was the case for the association of maternal Hispanic ethnicity with spina bifida (AOR, 1.4; 95% CI, 1.2-1.8) and anencephaly (AOR, 2.0; 95% CI, 1.5-2.8). CONCLUSIONS: Polytomous logistic regression provides a useful tool for evaluating putative risk factors for which there is no a priori basis for assuming effect homogeneity across component phenotypes. PMID- 20740594 TI - Periconceptional nutrient intakes and risks of neural tube defects in California. AB - BACKGROUND: This study investigated the association of neural tube defects (NTDs) with maternal periconceptional intake of folic acid-containing supplements and dietary nutrients, including folate, among deliveries that occurred after folic acid fortification in selected California counties. METHODS: The population-based case-control study included fetuses and live born infants with spina bifida (189) or anencephaly (141) and 625 nonmalformed, live born controls delivered from 1999 to 2003. Mothers reported supplement use during telephone interviews, which included a 107-item food frequency questionnaire. For dietary nutrients, intakes <25th, 25th to <75th (reference), and > or =75th percentile were compared, based on control distributions. RESULTS: After adjustment for potential confounders, any versus no supplement intake resulted in ORs of 0.8 (95% CI, 0.5-1.3) for anencephaly and 0.8 (95% CI, 0.6-1.2) for spina bifida. After stratification by maternal intake of vitamin supplements, most factors in the glycemic pathway were not associated with either NTD, with the exception of low levels of fructose and glucose that were significantly associated with anencephaly. Some nutrients that contribute to one-carbon metabolism showed lowered risks (folate, riboflavin, vitamins B(6) and B(12)); others did not (choline, methionine, zinc). Antioxidant nutrients tended to be associated with lowered risks (vitamins C, E, A, beta carotene, lutein). CONCLUSIONS: Mothers' intake of vitamin supplements was modestly if at all associated with a lowered risk of NTDs. Dietary intake of several nutrients contributing to one-carbon metabolism and oxidative stress were associated with reduced NTD risk. PMID- 20740596 TI - Proliferation and mineralization of bone marrow cells cultured on macroporous hydroxyapatite scaffolds functionalized with collagen type I for bone tissue regeneration. AB - This study concerns the preparation and in vitro characterization of functionalized hydroxyapatite (HA) porous scaffolds, which are intended to be used as drug-delivery systems and bone-regeneration matrices. Hydroxyapatite scaffolds were prepared using the polymer replication method, and, after being submitted to a specific sintering cycle, collagen Type I was incorporated on the surface. After the coating procedure, collagen was crosslinked using the N-(3 dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N hydroxysuccinimide (NHS) conjugation method. In this study, hydroxyapatite scaffolds with uncrosslinked and crosslinked Type I collagen were evaluated. Cell morphology and deposition of extracellular matrix were assessed by scanning electron microscopy, whereas cell distribution was visualized by means of methylene blue staining. MTS and total DNA quantification assays were used to evaluate the viability and proliferation of human bone marrow cells cultured on all the materials for 28 days. Results showed that the cells were able to adhere, proliferate, and form a mineralized matrix on the surface of all the materials. Furthermore, the cells were able to spread from one pore to another and form cell clusters. The results show that these scaffolds are good candidates to serve as drug delivery vehicles and for tissue engineering purposes. PMID- 20740597 TI - Diffusion of interleukin-2 from cells overlaid with cytocompatible enzyme crosslinked gelatin hydrogels. AB - In designing an implantable cell encapsulation construct to continuously deliver therapeutic proteins to a patient, it is critical that the biomaterial be compatible with the encapsulated cells, as well as conducive to the diffusion of desired molecules. As a continuation of our previous work, which demonstrated the cytocompatibility of gelatin hydrogels enzymatically crosslinked by microbial transglutaminase (mTG-gels), this work seeks to elucidate the diffusion properties that are needed for sustained release of therapeutic proteins produced by the engineered cells. HEK293 cells genetically engineered to secrete an anticancer drug, interleukin-2 (hIL2), through 4% mTG-gels used as a 1D diffusion model. Under steady-state conditions, cells secrete hIL2 at a therapeutic rate of 5.0-5.7 ng/cm(2)/h/10(6) cells. The diffusion coefficient of hIL2 through the hydrogels is D(m) = 4.0 x 10(-7) cm(2)/s. This value is comparable with similarly sized proteins through hydrogels and is further verified by modeling nonsteady state diffusion through various thicknesses of the hydrogels, as well as by acellular diffusion chamber experiments. These findings demonstrate that the enzymatically crosslinked hydrogels are not only cytocompatible but also have suitable transport properties that will facilitate the design of sustained drug release devices. PMID- 20740598 TI - Tissue-response to calcium-bonded titanium surface. AB - Our previous study demonstrated that calcium-bonded titanium surface (Ca-Ti) can be obtained by hydrothermal reaction between titanium (Ti) and CaCl(2) and that bone-apatite like formation was observed after immersion in simulated body fluid. The purpose of the study was to determine the in vivo response to Ca-Ti surface using a rodent tibia model. Cylinders of commercially pure Ti were divided into three groups: (1) untreated group; (2) NaOH+hTi group: soaked in 5 mol/L NaOH solution at 60 degrees C then heated at 400 degrees C for 1 h; and (3) Ca-Ti group: hydrothermally treated in the presence of 10 mmol/L CaCl(2) at 200 degrees C for 24 h. The cylinders implanted in surgically created defects in tibias of 8 week old male Wistar rats were retrieved after 1, 2, and 4 weeks. Histomorphometric evaluations were made on stained decalcified thin sections. Results showed that at 1, 2, and 4 week after implantation, respectively, bone contact was 55.2 +/- 16.4%, 88.1 +/- 9.9%, and 96.1 +/- 4.8% for Ca-Ti implants, 5.7 +/- 5.3%, 19.9 +/- 1.2%, 57.4 +/- 4.8% for untreated; and 27.2 +/- 0.7%, 70.9 +/- 7.7%, and 96.0 +/- 5.1% for NaOH+hTi implants. These results suggest that hydrothermal treatment with CaCl(2) provides a bioactive Ca-Ti bonded surface that allows bone formation greater than that obtained with NaOH+heat treated Ti surfaces. PMID- 20740599 TI - Protein adsorption on biodegradable polyanhydride microparticles. AB - The in vitro adsorption of plasma proteins on polyanhydride microparticles based on sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis(p carboxyphenoxy)-3,6-dioxaoctane (CPTEG) was studied. Three model proteins from bovine serum (albumin (BSA), immunoglobulin G (IgG), and fibrinogen (Fg)) were used. The adsorption was studied using X-Ray Photoelectron Spectroscopy and gel electrophoresis. 2D electrophoresis was used to study the adsorption of plasma proteins from bovine serum. Differences in the amount of protein adsorbed were detected as a function of the following: (i) copolymer composition and (ii) specific protein studied. A direct correlation between polymer hydrophobicity and protein adsorbed was observed and higher quantities of Fg and IgG were absorbed. In vitro release studies were performed with ovalbumin-encapsulated microparticles that were incubated with Fg; these studies showed a reduction in the amount of ovalbumin released from the microparticles when Fg is adsorbed on the surface. An understanding of protein adsorption patterns on parenteral delivery devices is valuable in optimizing their in vivo performance. PMID- 20740600 TI - Electrospun nanofibrous matrix improves the regeneration of dense cortical bone. AB - Numerous in vitro studies have indicated the potential of using electrospun nanofibrous scaffolds for tissue regeneration. However, few reports have demonstrated their utility in real tissue repair models. The present investigation tested the hypothesis that electrospun poly-L-lactic acid (PLLA) nanofibrous membrane leads to dense cortical bone regeneration and improves the efficacy of currently-used collagenous guided bone regeneration (GBR) membrane. In vitro, the function of bone marrow-derived mesenchymal stem cells (BMSCs) on nanofibrous scaffolds was evaluated. In an in vivo experiment, large bony defects were created in rabbit tibia and treated with a nanofiber-reinforced bilayer membrane, nanofibrous membrane, or collagenous membrane alone. Three and six weeks after operation, bone defect healing was assessed radiologically and histologically. In vitro differentiation studies showed that BMSCs had much higher expression of Runx2 and collagen type I, alpha 1 mRNAs, when cultured on nanofibrous scaffolds. The radiographic and histological data both showed that the group treated with bilayer membrane had more bony tissue formation at 3 weeks. Moreover, at 6 weeks, only the bilayer membrane-treated bone defects displayed better regeneration of cortical bone tissue, whereas in the other groups the defects were filled with spongy bone-like tissue. The results demonstrated that electrospun nanofibrous membrane improves the regeneration of cortical bone, suggesting that this type of membrane can be combined with current collagenous GBR membrane to improve guided bone regeneration technology. PMID- 20740601 TI - A new amido phosphonate derivative of carboxymethylcellulose with an osteogenic activity and which is capable of interacting with any Ti surface. AB - A new phosphonate derivative of carboxymethylcellulose (CMC) was recently synthesized (CMCAPh). The phosphonate polysaccharide was obtained by using a carbodiimide-like activating agent for carboxylic groups and 2-aminoethyl phosphonic acid to create an amide bond between the amine of the phosphonate agent and the carboxylic acids of CMC. The polymer was characterized by (31)P NMR, FT-IR, and potentiometric titration. CMCAPh showed different properties from CMC and its amidated derivative polymer CMCA. The behavior in solution of CMCAPh polymer towards normal human osteoblasts (NHOst) was studied in vitro, monitoring the cell proliferation, cell differentiation, and osteogenic activity and was then compared with the amidic derivative of carboxymethylcellulose (CMCA). Furthermore, CMCAPh was used to coat titania disks with the aim of increasing the osteogenic activity of implant surfaces. The polymer film on the titania surface was characterized by AFM and TOF-SIMS analysis. An ATR FT-IR study was carried out to evaluate the polymer bonding mode onto the titanium surface. Osteoblast morphology was evaluated by SEM. Adhesion analysis of NHOst demonstrated a better adhesion on the titanium surface coated with CMCAPh than on the bare titanium surface. PMID- 20740602 TI - Distinct immunohistomorphologic changes in periprosthetic hip tissues from historical and highly crosslinked UHMWPE implant retrievals. AB - Assessment of immune response to implant wear debris in periprosthetic tissue following total hip arthroplasty suggests that multiple factors are involved in the loss implant function. The current study investigated wear debris and the associated immunohistomorphologic changes in tissues from nine patients with historical (gamma air-sterilized) and nine highly crosslinked UHMWPE implant components. Paraffin embedded tissue sections were evaluated for the presence of histiocytes, giant cells, fibrocartilage/bone, and necrosis. To determine the incidence, degree and co-localization of immunohistomorphologic changes and wear, overlapping full-field tissue arrays were collected in brightfield and polarized light. The historical cohort tissues predominantly showed histiocytes associated with significant accumulations of small wear (0.5-2 microm), and giant cells associated with large wear (> or =2 microm). Frequently, focal regions of necrosis were observed in association with wear debris. For the highly crosslinked cohort, inflammation and associated wear debris were limited, but in tissues from patients revised after implantation times of >2 years a response was observed. Whereas significant amounts of fibrocartilage/bone were observed in patients at earlier implantation times. In both cohorts, tissue responses were more extensive in the retroacetabular or proximal femoral regions. The current findings suggest that wear debris-induced inflammation may be a major contributor to the loss of implant function for both the historical and highly crosslinked cohorts, but it is not the primary cause of early implant loosening. This study highlights the importance of using a more quantitative and standardized assessment of immunohistomorphologic responses in periprosthetic tissues, and emphasizes differences in specific anatomical regions of individual patient tissues. PMID- 20740603 TI - Biocompatibility of poly(ethylene glycol)-based hydrogels in the brain: an analysis of the glial response across space and time. AB - Poly(ethylene glycol) or PEG-based hydrogels provide a useful methodology for tissue engineering and the controlled-release of drugs within the central nervous system (CNS). To be successful, the local neuroinflammatory response to an implant must be well understood. Toward this end, the focus was to examine the localized recruitment and activation of microglia and astrocytes following implantation of PEG-based hydrogels in the brain. Because they are of clinical relevance and may impact brain tissue differently, hydrogels with different mass loss profiles were examined. At all time points, a needle penetration in sham animals evoked a greater astrocytic response than hydrogel conditions. The astrocyte response that ensued varied with degradation rate. An attenuated response was present in more slowly degrading and nondegrading conditions. Relative to sham, hydrogel conditions attenuated the acute microglial response during the week after implant. By 56 days, microglial levels in shams decreased below the observed response in slowly degrading and nondegradable gels, which remained constant overtime. Although the inflammatory response to PEG-based hydrogels was complex depending on degradation rates, the magnitude of the acute microglia response and the long-term astrocyte response were attenuated suggesting the use of these materials for drug and cell delivery to the CNS. PMID- 20740604 TI - Effect of TBCD and its regulatory interactor Arl2 on tubulin and microtubule integrity. AB - Assembly of the alpha/beta tubulin heterodimer requires the participation of a series of chaperone proteins (TBCA-E) that function downstream of the cytosolic chaperonin (CCT) as a heterodimer assembly machine. TBCD and TBCE are also capable of acting in a reverse reaction in which they disrupt native heterodimers. Homologs of TBCA-E exist in all eukaryotes, and the amino acid sequences of alpha- and beta-tubulin isotypes are rigidly conserved among vertebrates. However, the efficiency with which TBCD effects tubulin disruption in vivo depends on its origin: bovine (but not human) TBCD efficiently destroys tubulin and microtubules upon overexpression in cultured cells. Here we show that recombinant bovine TBCD is produced in HeLa cells as a stoichiometric cocomplex with beta-tubulin, consistent with its behavior in vitro and in vivo. In contrast, expression of human TBCD using the same host/vector system results in the generation of TBCD that is not complexed with beta-tubulin. We show that recombinant human TBCD functions indistinguishably from its nonrecombinant bovine counterpart in in vitro CCT-driven folding reactions, in tubulin disruption reactions, and in tubulin GTPase activating protein assays in which TBCD and TBCC stimulate GTP hydrolysis by beta-tubulin at a heterodimer concentration far below that required for polymerization into microtubules. We conclude that bovine and human TBCD have functionally identical roles in de novo tubulin heterodimer assembly, and show that the inability of human TBCD to disrupt microtubule integrity upon overexpression in vivo can be overcome by siRNA-mediated suppression of expression of the TBCD regulator Arl2 (ADP ribosylation factor like protein). PMID- 20740605 TI - Cardiomyopathy in ankylosing spondylitis. PMID- 20740606 TI - Cost-effectiveness of biologic response modifiers compared to disease-modifying antirheumatic drugs for rheumatoid arthritis: a systematic review. PMID- 20740607 TI - Cost-effectiveness of biologics in polyarticular-course juvenile idiopathic arthritis patients unresponsive to disease-modifying antirheumatic drugs. AB - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease and can have long-term effects leading to disability in adulthood. Biologics are a new class of drugs increasingly used to treat JIA. The primary study objective was to determine the incremental costs of biologics per additional responder compared to conventional treatment (methotrexate). METHODS: A separate decision model was created for etanercept, infliximab, adalimumab, and abatacept. The study population consisted of polyarticular-course JIA patients with a prior inadequate response or intolerance to disease-modifying antirheumatic drugs (DMARDs). The effectiveness measure was the proportion of patients who had a treatment response at 1 year according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) improvement criteria. Direct and indirect costs were calculated in 2008 Canadian dollars. Incremental cost effectiveness ratios and 95% confidence intervals (95% CIs) were calculated for each biologic agent using probabilistic sensitivity analyses. RESULTS: The additional costs per additional ACR Pedi 30 responder at 1 year were $26,061 (95% CI $17,070, $41,834), $46,711 (95% CI $30,042, $75,787), $16,204 (95% CI $11,393, $22,608), and $31,209 (95% CI $16,659, $66,220) for etanercept, adalimumab, abatacept, and infliximab, respectively. CONCLUSION: Biologics are more effective than methotrexate in achieving a short-term response in JIA patients with prior inadequate responses to DMARDs; however, this comes at a high annual cost. Adequate long-term data with respect to both safety and effectiveness are not currently available, nor are utility estimates. Such data will be important to estimate value for money for treating JIA with biologic drugs over the long term. PMID- 20740608 TI - Associations with digital ulcers in a large cohort of systemic sclerosis: results from the Canadian Scleroderma Research Group registry. AB - OBJECTIVE: Digital ulcers are a common complication of systemic sclerosis (SSc; scleroderma). Approximately half of SSc patients have had a digital ulcer, but information is lacking on whether digital ulcers are associated with patient demographics and clinical outcomes. We wanted to determine the associations between digital ulcers and other SSc vascular complications and organ involvement. METHODS: Data from the Canadian Scleroderma Research Group are collected annually on SSc patients, including presence, location, and number of digital ulcers; complications from digital ulcers; internal organ involvement; skin score; and laboratory results. Correlation coefficients, chi-square test, and logistic regression modeling were done to determine the associations of digital ulcers with other factors, including internal organ complications. RESULTS: A total of 938 patients were included; 86% were women, the mean age was 55 years, the mean disease duration was 13.6 years, and 50% had limited cutaneous SSc. Eight percent had a digital ulcer currently and 44% had a digital ulcer ever; 53.1% had digital pitting scars. Digital ulcers were associated with increased modified Rodnan skin score (P = 0.0001), hand and finger skin score (P = 0.0001), Health Assessment Questionnaire score (P = 0.0001) and disease duration (P = 0.001), younger age of SSc onset (P = 0.0001), interstitial lung disease (ILD; P = 0.0001), and topoisomerase I (Scl-70) antibodies (P = 0.0001) in limited and diffuse cutaneous SSc subsets. Digital ulcers were not associated with sex (P = 0.95), smoking (P = 0.9), pulmonary arterial hypertension (PAH; P = 0.35), and scleroderma renal crisis (SRC; P = 0.569). Digital ulcers were further associated with reduced diffusing capacity for carbon monoxide (DLCO; P = 0.0001) and esophageal involvement (P = 0.0001) in diffuse cutaneous SSc only. CONCLUSION: Digital ulcers are associated with worse disease, including skin and lung involvement, but are not associated with PAH and SRC. However, the low DLCO that is associated with SRC could represent ILD or microvasculopathy. PMID- 20740609 TI - Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study. AB - OBJECTIVE: Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown. METHODS: We analyzed data from the Women's Health Initiative Observational Study (n=76,861 postmenopausal women, ages 50-79 years). Incident cases (n=213: 178 for RA, 27 for SLE, and 8 for both) were identified based on self-report and use of disease-modifying antirheumatic drugs at year 3 of followup. We examined self-reported residential or work place insecticide use (personally mixing/applying by self and application by others) in relation to RA/SLE risk, overall and in relation to farm history. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were adjusted for age, race, region, education, occupation, smoking, reproductive factors, asthma, other autoimmune diseases, and comorbidities. RESULTS: Compared with never used, personal use of insecticides was associated with increased RA/SLE risk, with significant trends for greater frequency (HR 2.04, 95% CI 1.17-3.56 for >=6 times/year) and duration (HR 1.97, 95% CI 1.20-3.23 for >=20 years). Risk was also associated with long term insecticide application by others (HR 1.85, 95% CI 1.07-3.20 for >=20 years) and frequent application by others among women with a farm history (HR 2.73, 95% CI 1.10-6.78 for >=6 times/year). CONCLUSION: These results suggest residential and work place insecticide exposure is associated with the risk of autoimmune rheumatic diseases in postmenopausal women. Although these findings require replication in other populations, they support a role for environmental pesticide exposure in the development of autoimmune rheumatic diseases. PMID- 20740610 TI - Tumor necrosis factor antagonist-associated neutropenia: comment on the article by Hastings et al. PMID- 20740611 TI - Inflammatory and autoimmune mechanisms in the induction of atherosclerotic damage in systemic rheumatic diseases: two faces of the same coin. PMID- 20740612 TI - Serum IgA rheumatoid factor and pyridinoline in very early arthritis as predictors of erosion(s) at two years: a simple model of prediction from a conservatively treated community-based inception cohort. AB - OBJECTIVE: To identify, in conservatively treated, very early arthritis patients, predictors of >=1 erosion(s) at 2 years, and to construct a prediction model. METHODS: Community-based adults (n=310) who had never taken disease-modifying antirheumatic drugs (DMARDs) or steroids with swelling of >=2 joints persisting for >4 weeks and lasting <6 months were recruited. Erosion status was assessed at 0, 6, 12, and 24 months; evaluations were comprised of clinical criteria (Disease Activity Score, Health Assessment Questionnaire), C-reactive protein level, erythrocyte sedimentation rate, autoantibodies, bone and cartilage markers, hand densitometry, and HLA class II shared epitopes. Patients meeting American College of Rheumatology rheumatoid arthritis (RA) criteria or with undifferentiated arthritis (UA) were followed and treated conservatively: one-third of RA patients and three-fourths of UA patients received no DMARDs during 2 years; a biologic agent was given to 1.8% of the patients during the first year. The main judgment criterion was >=1 erosion(s) at 2 years. RESULTS: At 2 years, 219 patients were assessed; 31.3% with RA and 10.6% with UA had >=1 erosion(s). Logistic regression analysis at that time showed erosion(s) strongly associated with serum IgA rheumatoid factor (IgA-RF) and pyridinoline levels for the 190 patients with no baseline erosions, with the corresponding receiver operating characteristic curve having an area under the curve of 0.77 (95% confidence interval 0.64-0.86). A prediction model was constructed with IgA-RF thresholds of 5 and 25 IU/ml and a pyridinoline threshold of 10 nM/liter; odds ratios ranged from 1 for IgA-RF<5 IU/ml and pyridinoline <10 nM/liter to 50.75 for the association of IgA-RF>=5 IU/ml and pyridinoline>=10 nM/liter. CONCLUSION: This model, using serum IgA-RF and pyridinoline concentrations, was able to predict>=1 erosion(s) at 2 years in very early arthritis patients. PMID- 20740613 TI - Chronic monarthritis of the ankle in a young man. PMID- 20740615 TI - Course of dermal ulcers and musculoskeletal involvement in systemic sclerosis patients in the scleroderma lung study. AB - OBJECTIVE: To evaluate changes in vascular and musculoskeletal involvement in subjects in the Scleroderma Lung Study, a multicenter, double-blind, randomized, controlled trial comparing placebo treatment with oral cyclophosphamide (CYC) for 1 year in systemic sclerosis patients with interstitial lung disease. Subjects were then followed off the study agent for an additional 12 months. METHODS: The following parameters were noted at baseline and every 6 months for each patient: digital tip ulcers, other dermal ulcers, joint swelling, joint tenderness, large joint contractures, muscle tenderness, muscle weakness, oral aperture, hand extension, and fist closure. RESULTS: A total of 158 patients were enrolled from 13 centers in the US; 79 were randomized to the CYC group and 79 to the placebo group. There were no differences in dermal ulcer and musculoskeletal measures between the CYC and placebo groups at baseline and 12 and 24 months. Improvement in percent predicted forced vital capacity was associated with improvement in the Rodnan skin thickness score (P<0.05) at 12 and 24 months, and with increased mean oral aperture at 24 months (P=0.005). CONCLUSION: These data document the frequency and course of these vascular and musculoskeletal features over time, therefore providing essential information for sample size calculations and magnitude of effect in future clinical trials. There was no treatment effect of CYC on the vascular and musculoskeletal features described. PMID- 20740616 TI - Tocilizumab in refractory adult Still's disease. AB - OBJECTIVE: There is an unmet need for the treatment of adult Still's disease (ASD), the pathogenesis of which may involve interleukin-6 (IL-6). We report the first series of patients with ASD treated with tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody. METHODS: All ASD patients treated with TCZ in France between July 2006 and July 2009 after failure to all available therapies were included in this cohort study. The main outcome measures were the European League Against Rheumatism (EULAR) improvement criteria and resolution of systemic symptoms at the 3- and 6-month followup periods. RESULTS: Fourteen patients with refractory ASD were included. At the start of TCZ treatment, despite a mean prednisone dosage of 23.3 mg/day, based on a 28-joint count, mean tender joints were 10.5, mean swollen joints were 7.9, and the mean Disease Activity Score in 28 joints was 5.61. Recurrent systemic involvement, including fever and rash, was present in 7 patients. TCZ was administered at 5-8 mg/kg every 2 or 4 weeks (8 mg/kg/month, n = 9). Eleven patients successfully completed the 6-month study; 1 withdrew due to necrotizing angiodermatitis, another due to chest pain at each TCZ infusion, and a third due to systemic flare. A good EULAR response was observed in 64% of patients (9 of 14) at 3 months and EULAR remission was observed in 57% (8 of 14) at 6 months. Systemic symptoms were resolved in 86% of patients (6 of 7). Moreover, corticosteroid dose was reduced by 56%. No other severe adverse effects occurred. CONCLUSION: TCZ is a promising new treatment for ASD. PMID- 20740617 TI - Safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis: data from the French Autoimmunity and Rituximab registry. AB - OBJECTIVE: Management of nonviral cryoglobulinemia vasculitis has yet to be defined. Rituximab has emerged as a novel and promising therapeutic alternative, but data are scarce. Our objective was to evaluate the safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis in off-trial real-life patients. METHODS: Prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with rituximab in off-label conditions, were analyzed. RESULTS: Twenty-three patients received treatment with rituximab for cryoglobulinemia vasculitis. Tolerance was marked by the occurrence of side effects in almost half of the patients, including severe infections in 6 (26%) of 23, with a rate of 14.1 per 100 patient-years. These infections occurred in a particular subset of patients ages>70 years, with essential type II mixed cryoglobulinemia and renal failure with a glomerular filtration rate of <60 ml/minute, and receiving high-dose corticosteroids. Three of these patients died. In contrast, clinical and immunologic efficacy was noted in all evaluable patients. Clinical relapses occurred in half of the patients after a median time of 13.5 months following rituximab administration, and were more frequent in patients refractory to previous immunosuppressive therapy than in previously untreated patients. CONCLUSION: Data from the AIR registry show a dramatic efficacy and a steroid sparing effect of rituximab, but also show the occurrence of severe infections in elderly patients with renal failure and high-dose steroids. The role of rituximab in nonviral cryoglobulinemia vasculitis remains to be defined in well-designed randomized controlled trials. PMID- 20740618 TI - Safety and effectiveness of black tattoo clearance in a pig model after a single treatment with a novel 758 nm 500 picosecond laser: a pilot study. AB - BACKGROUND: Optimal selective photothermolysis of a pigment particle requires pulse durations equal to or less than the particle's thermal relaxation time (t(1/2)). Since tattoo particles in skin range in diameter from 40 to 300 nm, picosecond pulses would approximate t(1/2) more closely and, therefore, might be more effective at tattoo particle fragmentation. MATERIALS AND METHODS: India Ink (carbon) or iron oxide tattoos were placed on the back of a Yorkshire pig. Six weeks later, each tattoo was treated with either a 758 nm 500 picosecond laser (Cynosure), a 755 nm 30-50 nanoseconds laser, or left untreated. After 4 weeks, clinical responses were evaluated by three dermatologists based on pre- and post treatment photographs; histopathologic findings were evaluated by a dermatopathologist; and electron microscopic findings were analyzed for treated and non-treated carbon tattoos. RESULTS: After a single treatment, picosecond domain pulses at 758 nm produced a significantly greater degree of carbon tattoo clearance compared to nanosecond-domain pulses at 755 nm. For iron oxide tattoos, both modalities produced minimal-to-poor clearance that was generally comparable. Neither modality resulted in scarring, textural changes, or hypopigmentation, and there was no histopathologic evidence of scarring. Electron micrographs revealed the presence of amorphous material (treated pigment) in picosecond and nanosecond laser-treated tattoos, consistent with effective targeting of India Ink pigment. CONCLUSIONS: The 758 nm 500 picosecond laser is more effective at carbon tattoo clearance after one session in a porcine model than the 30-50 nanosecond laser emitting at a similar wavelength. Both lasers cleared carbon tattoos more effectively than iron oxide tattoos. Both lasers have a comparable safety profile, and neither produced clinical or histopathologic scarring. Further studies in humans are necessary to evaluate whether repeated treatments with picosecond versus nanosecond domain modalities might yield superior tattoo pigment clearance with a comparable safety profile. PMID- 20740619 TI - Experimental validation of the effects of microvasculature pigment packaging on in vivo diffuse reflectance spectroscopy. AB - BACKGROUND: Diffuse reflectance spectroscopy (DRS) uses the steady-state diffuse reflectance measured from the tissue surface to determine absorption and scattering properties of sampled tissue. Many inverse models used to determine absorber properties have assumed a homogeneous distribution of blood. However, blood in tissue is confined to blood vessels that occupy a small fraction of the overall volume. This simplified assumption can lead to large errors when measuring optical properties. The objective of this study was to examine the effect of confining absorbers to small volumes, such as the microvasculature, on in vivo DRS. STUDY DESIGN: We fabricated multi-layer microfluidic devices to mimic blood vessels with a size similar to skin microvasculature. We studied the effect of varying channel size (diameter = 22 and 44 microm) and absorber concentration (10-80% food color dye in water) on diffuse reflectance measurements. We also examined the in vivo reflectance from normal skin and non melanoma skin cancer on 14 patients. RESULTS: Our results demonstrate that both absorption coefficient and vessel diameter affect the diffuse reflectance spectra. An empirically calculated packaging correction factor based on our experiments shows good agreement with previous theoretical derivations of the same factor. In vivo measurements on normal skin and basal cell carcinoma show that incorporating a correction factor greatly improves the fit of the inverse model to the spectra. In addition, there were statistically significant differences in measured mean vessel diameter and blood volume fraction between normal skin and basal cell carcinoma. CONCLUSION: We have demonstrated experimentally the effect of pigment packaging in blood vessels over a physiologically relevant range of blood vessel size and absorption. The correction factors implemented to account for the packaging effect could potentially be used as diagnostic parameters for diagnosing skin cancers. PMID- 20740620 TI - Increasing the efficiency of photodynamic therapy by improved light delivery and oxygen supply using an anticoagulant in a solid tumor model. AB - BACKGROUND AND OBJECTIVE: The main factors in photodynamic therapy (PDT) are: photosensitizer retention, photon absorption, and oxygen supply. Each factor has its unique set of problems that poses limitation to the treatment. Both light delivery and oxygen supply are significant bottlenecks in PDT. Vascular closure during PDT reduces oxygen supply to the targeted tissue. On the other hand, with the changes in blood perfusion, the tissue optical properties change, and result in variation in irradiation light transmission. For these reasons, it becomes very important to avoid blood coagulation and vascular closure during PDT. STUDY DESIGN/MATERIALS AND METHODS: The efficiency of PDT combined with the anticoagulant heparin was studied in a BALB/c mouse model with subcutaneous EMT6 mammary carcinomas. Mice were randomized into three groups: control, PDT-only, and PDT with heparin. The photosensitizer Photofrin was used in our experiments. Light transmission, blood perfusion, and local production of reactive oxygen species (ROS) were monitored during the treatment. The corresponding histological examinations were performed to determine the thrombosis immediately after irradiation and to evaluate tumor necrosis 48 hours after the treatment. RESULTS: The results clearly demonstrated that PDT combined with pre-administered heparin can significantly reduce thrombosis during light irradiation. The blood perfusion, oxygen supply, and light delivery are all improved. Improved tumor responses in the combined therapy, as shown with the histological examination and tumor growth assay, are clearly demonstrated and related to an increased local ROS production. CONCLUSION: Transitory anticoagulation treatment significantly enhances the antitumor effect of PDT. It is mainly due to the improvement of the light delivery and oxygen supply in tumor, and ultimately the amount of ROS produced during PDT. PMID- 20740621 TI - In vitro investigation of the biological effects associated with human dermal fibroblasts exposed to 2.52 THz radiation. AB - BACKGROUND: Terahertz (THz) radiation sources are increasingly being used in military, defense, and medical applications. However, the biological effects associated with this type of radiation are not well characterized. In this study, we evaluated the cellular and molecular response of human dermal fibroblasts exposed to THz radiation. METHODS: In vitro exposures were performed in a temperature-controlled chamber using a molecular gas THz laser (2.52 THz, 84.8 mW cm(-2), durations: 5, 10, 20, 40, or 80 minutes). Both computational and empirical dosimetric techniques were conducted using finite-difference time domain (FDTD) modeling approaches, infrared cameras, and thermocouples. Cellular viability was assessed using conventional MTT assays. In addition, the transcriptional activation of protein and DNA sensing genes were evaluated using qPCR. Comparable analyses were also conducted for hyperthermic and genotoxic positive controls. RESULTS: We found that cellular temperatures increased by 3 degrees C during all THz exposures. We also found that for each exposure duration tested, the THz and hyperthermic exposure groups exhibited equivalent levels of cell survival (>=90%) and heat shock protein expression (~3.5-fold increases). In addition, the expression of DNA sensing and repair genes was unchanged in both groups; however, appreciable increases were observed in the genotoxic controls. CONCLUSIONS: Human dermal fibroblasts exhibit comparable cellular and molecular effects when exposed to THz radiation and hyperthermic stress. These findings suggest that radiation at 2.52 THz generates primarily thermal effects in mammalian cells. Therefore, we conclude that THz-induced bioeffects may be accurately predicted with conventional thermal damage models. PMID- 20740622 TI - Innovative activities for teaching anatomy of speech production. AB - Courses in anatomy have traditionally relied on lectures and cadaver dissection laboratories. In speech and hearing sciences, there tends to be less access to cadavers than in medical schools and other allied health professions. It is more typical to use anatomical models, diagrams and lecture slides. Regardless of the resources available, anatomy is a subject that lends itself to hands-on learning. This article briefly reviews teaching methods and describes a variety of innovative activities to enhance learning of anatomical concepts and clinical relevance of anatomy for speech production. Teaching strategies and activities were developed to capitalize on students' multimodal learning preferences as revealed by responses to a survey administered to 49 undergraduates in the beginning of an anatomy of speech production course. At the end of the semester, students completed a second survey. A five-point Likert scale was used to assess the usefulness of each activity as a learning tool or level of clinical relevance and the level of enjoyability. The responses were overwhelmingly positive with level of usefulness and level of clinical relevance rated higher on average than the level of enjoyment. PMID- 20740624 TI - Anthroposophic medicine in paediatric oncology in Germany: results of a population-based retrospective parental survey. AB - BACKGROUND: Anthroposophic medicine (AM) is frequently utilised in German speaking countries as a complementary and alternative medicine (CAM) treatment approach. PROCEDURE: This study presents results of a retrospective parental questionnaire comparing responses of AM-users and users of other CAM in paediatric oncology in Germany. The differences between these two groups are investigated with respect to usage, associated demographic characteristics and previous experience with CAM. RESULTS: Ninety-eight patients (27%) of the 367 CAM users were exposed to anthroposophic treatments or therapies. Treatment duration amounted to a median 619 days for AM and 225 days for other CAM treatments. Most parents with previous experience of AM also used AM for treatment of their child's cancer disease. AM-users had a higher social status. Physicians played a relevant role for users of AM both in procuring information (24% vs. 11%; P < 0.001) and in prescribing medicines and therapies (73.0% vs. 34.9%; P < 0.001) compared to users of other CAM. AM-users communicate more frequently with their physicians about the use of CAM treatments (89.8% vs. 63.9%) and recommend CAM more often than other CAM-users (95.9% vs. 87%). CONCLUSIONS: AM plays a major role in paediatric oncology in Germany. Patients using AM sustain treatment and therapies considerably longer than patients using other CAM treatments. Furthermore, most families who had used AM before their child was diagnosed with cancer also used AM for the treatment of their child's cancer. Compared to other CAM treatments, patient satisfaction with AM appears to be very high. PMID- 20740623 TI - Initial testing (stage 1) of the Akt inhibitor GSK690693 by the pediatric preclinical testing program. AB - BACKGROUND: GSK690693 is a small molecule ATP-competitive inhibitor of the pro survival kinase Akt. Since Akt regulates multiple downstream targets including transcription factors, glycogen synthase 3, the pro-apoptotic protein Bad, as well as MDM2 and mTORC1, it was tested against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP). PROCEDURES: GSK690693 was tested in vitro at concentrations from 1 nM to 10 uM, and against the in vivo panel of xenografts at a dose of 30 mg/kg daily * 5 for 6 consecutive weeks. Three measures of in vivo antitumor activity were used: (1) an objective response measure modeled after the clinical setting; (2) a treated to control (T/C) tumor volume measure; and (3) a time to event measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. RESULTS: GSK690693 inhibited cell growth in vitro with IC(50) values between 6.5 nM and >10 uM. In vivo, GSK690693 significantly increased EFS in 11 of 34 (32%) solid tumor xenografts, most notably in all 6 osteosarcoma models, but not in any of the 8 ALL xenografts tested. No objective responses were observed and only one solid tumor met EFS T/C criteria for intermediate activity. CONCLUSIONS: GSK690693 demonstrated broad activity in vitro, however our results against both the solid tumor and ALL PPTP in vivo panels demonstrate that, as single agent at the dose and schedule used, GSK690693 has only modest antitumor activity. PMID- 20740625 TI - Antigenotoxic effects of p53 on spontaneous and ultraviolet light B--induced deletions in the epidermis of gpt delta transgenic mice. AB - Tumor development in the skin may be a multistep process where multiple genetic alterations occur successively. The p53 gene is involved in genome stability and thus is referred to as "the guardian of the genome." To better understand the antigenotoxic effects of p53 in ultraviolet light B (UVB)-induced mutagenesis, mutations were measured in the epidermis of UVB-irradiated p53(+/+) and p53(-/-) gpt delta mice. In the mouse model, point mutations and deletions are separately identified by the gpt and Spi(-) assays, respectively. The mice were exposed to UVB at single doses of 0.5, 1.0, or 2.0 kJ/m(2) . The mutant frequencies (MFs) were determined 4 weeks after the irradiation. All doses of UVB irradiation enhanced gpt MFs by about 10 times than that of unirradiated mice. There were no significant differences in gpt MFs and the mutation spectra between p53(+/+) and p53(-/-) mice. The predominant mutations induced by UVB irradiation were G:C to A:T transitions at dipyrimidines. In contrast, in unirradiated p53(-/-) mice, the frequencies of Spi(-) large deletions of more than 1 kb and complex-type deletions with rearrangements were significantly higher than those of the Spi(-) large deletions in p53(+/+) counterparts. The specific Spi(-) mutation frequency of more than 1 kb deletions and complex types increased in a dose-dependent manner in the p53(+/+) mice. However, no increase of such large deletions was observed in irradiated p53(-/-) mice. These results suggest that the antigenotoxic effects of p53 may be specific to deletions and complex-type mutations induced by double-strand breaks in DNA. PMID- 20740626 TI - Effect of shoulder angle on the activation pattern of the elbow extensors during a submaximal isometric fatiguing contraction. AB - The aim of this study was to examine the effect of shoulder angle on the electromyographic (EMG) activation pattern of the elbow extensors during a fatiguing contraction. Ten young men (23.5 +/- 1.7) were tested on two occasions with the elbow angle at 90 degrees and the shoulder at either 0 degrees or 90 degrees of flexion. EMG was recorded by fine wire electrodes inserted into the lateral, medial, and long heads of the triceps brachii and the anconeus. An EMG torque relationship was determined prior to a sustained isometric contraction at 20% of maximum voluntary contraction (MVC) until target failure. Endurance time was shorter, and postfatigue MVC torque was lower at 90 degrees (40.4 +/- 12.7 Nm) versus 0 degrees (47.9 +/- 14.7 Nm) of flexion. EMG activity of the long head during the final 10% of the fatiguing contraction was significantly greater at 90 degrees versus 0 degrees with no effect of shoulder angle on any other muscle portions. The findings suggest that measures from one muscle portion of the elbow extensors are not representative of the whole group, and the relative activation of the two-joint long head was changed depending on shoulder angle during a fatigue task. PMID- 20740628 TI - Probabilistic muscle characterization using quantitative electromyography: application to facioscapulohumeral muscular dystrophy. AB - Based on quantitative electromyography, a muscle can be categorized as normal or affected by a neuromuscular disorder. The objective of this work was to compare the utility of probabilistic to conventional means and outlier methods of categorization of myopathic and normal muscles. Various sets of motor unit potential (MUP) features detected in biceps brachii muscles of control subjects and patients with facioscapulohumeral muscular dystrophy were used to categorize them as normal or myopathic based on conventional means and outlier categorization (CMC) as well as a new probabilistic muscle categorization (PMC). The sensitivity, specificity, and accuracy provided by each categorization method were compared. The categorizations made using PMC were significantly more accurate (by at least 10%) compared with CMC (P < 10(-10)) for muscles evaluated in this study. Area, duration, and thickness were highly discriminative MUP features. PMID- 20740627 TI - Permissive environment for B-cell maturation in myositis muscle in the absence of B-cell follicles. AB - Myositis muscle contains antigen-matured B-cells and plasma cells. Myositis muscle biopsy specimens were examined for nodular collections of T-cells, B cells, myeloid dendritic cells, plasma cells, and follicular dendritic cells. Immunoglobulin and B-cell-activating factor (BAFF) transcripts were quantitated. Laser-capture microdissection was used to isolate single plasma cells, and their immunoglobulin transcripts were sequenced. Dense inflammatory infiltrates contained histological elements of ectopic lymphoid tissue but not B-cell follicles. Immunoglobulin transcript sequence analysis demonstrated spatially distributed, clonally related B-cells and plasma cells, suggesting local maturation of B-cells into plasma cells in myositis muscle. Regions of dense cellular infiltrates in myositis muscle are sometimes areas of B-cell maturation into antibody-producing plasma cells. An atypical lymphoid histology, lacking concentrated collections of germinal-center-like B-cell follicles, is capable of antigen-stimulated clonal maturation of antibody-producing plasma cells. PMID- 20740630 TI - Germ cell mutagens: risk assessment challenges in the 21st century. AB - Heritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human germline mutagens, and large data gaps that often impede risk assessment. Moreover, most regulatory assessments are based on the assumption that somatic cell mutation assays also protect the germline by default, which has not been adequately confirmed. The field is also faced with new challenges aimed at dramatically reducing animal testing, and attempts to rapidly classify thousands of chemicals using high throughput in vitro assays. These approaches may not adequately capture effects that may be particular to gametes, since many aspects of the germline are unique. In light of these challenges, an urgent need exists to develop new approaches to evaluate the potential of toxicants to cause germline mutation. The application of new technologies will greatly enhance our understanding of mutation in humans exposed to environmental mutagens. However, we must be poised to collect and interpret these data, and facilitate risk translation to regulators and the public. Genetic toxicologists must also become actively involved in the development of high-throughput tools to study germline mutation. Appropriate attention to these areas will result in the development of policies that prioritize the protection of the germline and future generations from DNA sequence mutations. PMID- 20740631 TI - A novel SOD1 mutation in a young amyotrophic lateral sclerosis patient with a very slowly progressive clinical course. AB - Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial, and the Cu/Zn superoxide dismutase (SOD1) gene mutation accounts for 20% of them. More than 100 SOD1 mutations have been described, some with peculiar phenotypes. Moreover, mutations in the SOD1 gene have been described in apparently sporadic ALS cases. We report a new mutation (D11Y) in the Cu/Zn superoxide dismutase gene in a patient with ALS and an unusually slow disease progression. PMID- 20740632 TI - Reference data for commonly used sensory and motor nerve conduction studies. PMID- 20740633 TI - Strategies for the follow-up of positive results in the in vitro genotoxicity assays--an international collaborative initiative. PMID- 20740634 TI - Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. AB - Industrial application of titanium dioxide nanoparticles (TiO(2) -NPs) as an additive in pharmaceutical and cosmetic products is increasing. However, the knowledge about the toxicity of this material is still incomplete and data concerning health and environmental safety and results of recent studies on TiO(2) nanotoxicology are inconsistent. The in vitro geno- and cytotoxicity of TiO(2) -NPs in the anatase crystal phase was evaluated in human peripheral blood lymphocytes from 10 male donors. Initially, transmission electron microscopy (TEM) was performed to describe particle morphology and size, the degree of particle aggregation, and the intracellular distribution. Cells were exposed to nanoparticles in increasing concentrations of 20, 50, 100, and 200 MUg/ml for 24 hr. Cytotoxic effects were analyzed by trypan blue exclusion test and the single cell microgel electrophoresis (comet) assay was applied to detect DNA double strand breakage. TiO(2) -NPs were sphere shaped with a diameter of 15-30 nm. Despite dispersive pretreatment, a strong tendency to form aggregates was observed. Particles were detected in the cytoplasm of lymphocytes, but also a transfer into the nucleus was seen. The trypan blue exclusion test did not show any decrease in lymphocyte viability, and there was no evidence of genotoxicity in the comet assay for any of the tested concentrations. In conclusion, TiO(2) NPs reached the cytoplasm as well as the nucleus and did not induce cyto- or genotoxic effects in human peripheral blood lymphocytes. Complement investigations on different human cell systems will be performed to estimate the biocompatibility of TiO(2) -NPs. Environ. Mol. Mutagen. PMID- 20740635 TI - New and emerging technologies for genetic toxicity testing. AB - The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow-up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. PMID- 20740637 TI - Oncomutations as biomarkers of cancer risk. AB - Cancer risk assessment impacts a range of societal needs, from the regulation of chemicals to achieving the best possible human health outcomes. Because oncogene and tumor suppressor gene mutations are necessary for the development of cancer, such mutations are ideal biomarkers to use in cancer risk assessment. Consequently, DNA-based methods to quantify particular tumor-associated hotspot point mutations (i.e., oncomutations) have been developed, including allele specific competitive blocker-PCR (ACB-PCR). Several studies using ACB-PCR and model mutagens have demonstrated that significant induction of tumor-associated oncomutations are measureable at earlier time points than are used to score tumors in a bioassay. In the particular case of benzo[a]pyrene induction of K-Ras codon 12 TGT mutation in the A/J mouse lung, measurement of tumor-associated oncomutation was shown to be an earlier and more sensitive endpoint than tumor response. The measurement of oncomutation by ACB-PCR led to two unexpected findings. First, oncomutations are present in various tissues of control rodents and "normal" human colonic mucosa samples at relatively high frequencies. Approximately 60% of such samples (88/146) have mutant fractions (MFs) >10(-5), and some have MFs as high as 10(-3) or 10(-4). Second, preliminary data indicate that oncomutations are present frequently as subpopulations in tumors. These findings are integrated into a hypothesis that the predominant preexisting mutations in particular tissues may be useful as generic reporters of carcinogenesis. Future research opportunities using oncomutation as an endpoint are described, including rodent to human extrapolation, dose-response assessment, and personalized medicine. PMID- 20740636 TI - Superoxide dismutase protects cells from DNA damage induced by trivalent methylated arsenicals. AB - Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide. Heterozygous mice of strain B6;129S7-Sod1(tm1Leb)/J were obtained from Jackson Laboratories and bred to produce offspring that were heterozygous (+/Sod1(tm1Leb)), homozygous wild-type (+/+), and homozygous knockout (Sod1(tm1Leb) /Sod1(tm1Leb)) for the Cu/Zn superoxide dismutase (Sod1) gene. Splenocytes from these mice were exposed to several concentrations of either sodium arsenite (As3 [0-200 MUM]), monomethylarsonous acid (MMA3 [0-10 MUM]), or dimethylarsinous acid (DMA3 [0-10 MUM]) for 2 hr. Cells were then examined for DNA damage using the alkaline single cell gel electrophoresis assay. Methyl methanesulfonate (MMS) was used as a positive control. Splenocytes from each of the three genotypes for Sod1 were equally sensitive to MMS and As3. However, at equimolar concentrations, DMA3 and MMA3 produced significantly more DNA damage in the homozygous knockout mouse splenocytes than in the splenocytes from the wild type or heterozygous mice. These findings suggest that superoxide is involved either directly or indirectly in producing DNA damage in cells exposed to trivalent methylated arsenicals. These arsenicals may generate reactive oxygen species that damage DNA. This DNA damage may be a key factor in initiating cancer in vivo. PMID- 20740638 TI - Growing up with DNA repair and joining the EMS. AB - I recount some personal history, as I rode the crest of the wave of discovery and excitement in the DNA repair field from the early 1960s and eventually came to appreciate that the Environmental Mutagen Society is the appropriate professional "home" for researchers in this field: it places them in the context of the broader genetic, societal, and regulatory issues raised from their studies. In return, the wisdom provided from basic research on cellular processing of damaged DNA is essential to mechanism-based decisions in the domain of genetic toxicology. PMID- 20740641 TI - Expression of DNA repair and apoptosis genes in mitochondrial mutant and normal cells following exposure to ionizing radiation. AB - In double-strand DNA damage repair, nonhomologous end joining (NHEJ) is more error-prone than homologous recombination repair (HRR), indicating that the relative prevalence of NHEJ may lead to more incorrect repair and thus to increases in chromosome damage. If DNA damage is extensive and cells are unable to repair that damage they typically undergo apoptosis. The mechanism(s) by which cells decide to switch from DNA repair to apoptosis is unknown. Since DNA repair and apoptosis are both energy-demanding processes, the answer may involve ATP utilization. We used human mitochondrial mutant cell lines obtained from people with phenotypic manifestations of compromised ATP generation. We hypothesized that these cells may not have adequate capacity for dealing with the additional demands for ATP required for repairing DNA damage after genotoxic exposure, perhaps making the cells more prone to undergo apoptosis instead of initiating repair. This study describes changes in the expression of genes involved in NHEJ or HRR, as well as genes involved in apoptosis, in one normal and two mitochondrial mutant human cell lines following ionizing radiation exposure. Compared to normal cells, both mutant cell lines showed reduced expression of genes involved in NHEJ and HRR. Analysis of expression changes in genes involved in apoptosis revealed marked increases in expression in the mutants compared to normal cells. These results indicate that following ionizing radiation exposure, mitochondrial mutant cells have decreased levels of mRNA expression of DNA repair genes and increased expression levels of genes involved in apoptosis compared to normal cells. This study provides information that might be useful in characterizing energy dependent processes following exposure to stress or genotoxic agents. PMID- 20740640 TI - Proposal of an in vivo comet assay using haemocytes of Drosophila melanogaster. AB - This study presents the first application of an in vivo alkaline comet assay using haemocytes of Drosophila melanogaster larvae. These cells, which play a role similar to that of mammalian blood, can be easily obtained and represent an overall exposure of the treated larvae. To validate the assay, we evaluated the response of these cells to three well-known mutagenic agents: ethyl methanesulfonate (EMS), potassium dichromate (PD), and gamma radiation (gamma irradiation). Third-instar Drosophila larvae were exposed to different concentrations of EMS (1, 2, and 4 mM) and PD (0.5, 1, and 2.5 mM) and to different doses of gamma-irradiation (2, 4, and 8 Ggamma). Subsequently, haemolymph was extracted from the larvae, and haemocytes were isolated by centrifugation and used in the comet assay. Haemocytes exhibited a significant dose-related increase in DNA damage, indicating that these cells are clearly sensitive to the treatments. These results suggest that the proposed in vivo comet test, using larvae haemocytes of D. melanogaster, may be a useful in vivo assay for genotoxicity assessment. PMID- 20740639 TI - Genetics and women's health issues--the commitment of EMS to women scientists and gender-associated disease topics. AB - This manuscript presents an overview of a symposium held at the 2009 annual meeting of the Environmental Mutagen Society (EMS) in St. Louis, MO. The symposium was sponsored by the Women in the Environmental Mutagen Society (WEMS) special interest group, and it covered current molecular genetics technologies and their impact on diagnosis and treatment of diseases that primarily or differentially affect women. Four speakers presented groundbreaking new information from such areas as cancer genetics, gene-environment interactions, epigenetics, DNA repair, and molecular epidemiology. Although cancer was a primary focus of the symposium, other health issues such as obesity and cardiovascular disease were addressed. The rapid evolution in genomic technologies discussed in this symposium should provide new tools to explore some of the critical questions raised by the research projects described in this article. This symposium demonstrates that EMS provides a forum for the presentation, discussion, and extension of the data generated by the investigators featured in this article and other researchers engaged in the study of the molecular mechanisms and gene-environment interactions that impact women's health. PMID- 20740642 TI - Differential methylation of CpG sites in two isoforms of myosin binding protein C, an important hypertrophic cardiomyopathy gene. AB - Hypertrophic cardiomyopathy (HCM) is a common form of cardiac disease. Over 400 causative mutations have been identified in 20 sarcomere and myofilament related genes. The high density of mutations found in genes associated with HCM may suggest that mechanisms promoting increased mutability play a role in disease prevalence. The objective of this study was to evaluate the CpG methylation level of the exonic regions of the cardiac myosin binding protein C gene (MYBPC3), a common causal gene for HCM. To determine if the methylation level is gene specific and possibly involved with gene mutability, we also evaluated the methylation of the CpGs within the exonic regions of the skeletal muscle isoform of the myosin binding protein C gene (MYBPC2); there are no known mutations that lead to the development of familial human disease within this gene. We determined that although the mean number of CG sites was identical within the coding region of each gene, the mean methylation level of CpGs was significantly higher in MYBPC3 than MYBPC2 (P < 0.0001). The results of this study suggest that there are unique aspects of this cardiac gene or its epigenetic environment which may result in increased genetic mutability. Evaluation of the methylation levels of additional causal cardiomyopathic genes is warranted. PMID- 20740643 TI - Cognitive impairment in multiple sclerosis is associated to different patterns of gray matter atrophy according to clinical phenotype. AB - OBJECTIVE: To investigate whether cognitive impairment in multiple sclerosis (MS) patients is associated to different patterns of gray matter (GM) atrophy and T2 visible lesion distribution according to the clinical phenotype. EXPERIMENTAL DESIGN: Twenty-two relapsing remitting (RR), 29 secondary progressive (SP), and 22 primary progressive (PP) MS patients, and 39 healthy controls underwent high field structural magnetic resonance imaging and an extensive neuropsychological battery. Voxel-wise distribution of GM damage and T2-lesions was compared between cognitively impaired (CI) and cognitively preserved (CP) patients according to their clinical phenotype. PRINCIPAL OBSERVATIONS: Thirty-nine MS patients were CI. In all MS groups, regional GM loss was correlated with cognitive impairment. Different patterns of regional distribution of GM atrophy and T2-visible lesions were found between CI vs. CP MS patients, according to their clinical phenotype. No areas were significantly more atrophied in CI SPMS vs. CI RRMS patients. Conversely, compared with CI PPMS, CI SPMS patients had a significant GM loss in several regions of the fronto-temporal lobes, the left hypothalamus and thalami. While in RRMS and SPMS patients there was a correspondence between presence of T2 visible lesions and GM atrophy in several areas, this was not the case in PPMS patients. CONCLUSION: Distinct patterns of regional distribution of GM damage and T2-visible lesions are associated with cognitive impairment in MS patients with different clinical phenotypes. The correspondence between lesion formation and GM atrophy distribution varies in the different forms of MS. PMID- 20740644 TI - Regional gray matter density associated with emotional intelligence: evidence from voxel-based morphometry. AB - Emotional Intelligence (EI) is the ability to monitor one's own and others' emotions and the ability to use the gathered information to guide one's thinking and action. EI is thought to be important for social life making it a popular subject of research. However, despite the existence of previous functional imaging studies on EI, the relationship between regional gray matter morphology and EI has never been investigated. We used voxel-based morphometry (VBM) and a questionnaire (Emotional Intelligence Scale) to measure EI to identify the gray matter correlates of each factor of individual EI (Intrapersonal factor, Interpersonal factor, Situation Management factor). We found significant negative relationships between the Intrapersonal factor and regional gray matter density (rGMD) (1-a) in an anatomical cluster that included the right anterior insula, (1 b) in the right cerebellum, (1-c) in an anatomical cluster that extends from the cuneus to the precuneus, (1-d) and in an anatomical cluster that extends from the medial prefrontal cortex to the left lateral fronto-polar cortex. We also found significant positive correlations between the Interpersonal factor and rGMD in the right superior temporal sulcus, and significant negative correlations between the Situation Management factor and rGMD in the ventromedial prefrontal cortex. These findings suggest that each factor of EI in healthy young people is related to the specific brain regions known to be involved in the networks of social cognition and self-related recognition, and in the somatic marker circuitry. PMID- 20740645 TI - Historical perspective on the development of the genetic toxicity test battery in the United States. AB - The currently used genetic toxicity testing battery (the Ames Salmonella test, the in vitro mammalian cell mouse lymphoma assay and/or the in vitro mammalian cell chromosome assay, and the rodent bone marrow chromosome aberration or micronucleus assay) had its origins in the early-to-mid 1970s. By the late 1970s, a large number of genetic tests had been proposed or recommended by the US-EPA for identifying germ cell mutagens and carcinogens. After a number of modifications that were primarily directed toward minimizing the number of tests used, the test battery reached its current state in the mid-1980s. This test battery, with some minor modifications in the timing or ordering of the tests is mandated by regulatory authorities worldwide. Although it would be intellectually satisfying to presume that this compendium of tests was developed and selected for regulatory screening based solely on scientific grounds, it was actually based on a combination of scientific data, theoretical considerations, chance, and advocacy, and not always in equal proportions. The evolution of the current genetic toxicity test battery, and some of the activities and considerations that directed this evolution are described. PMID- 20740646 TI - Assessment of genotoxicity of waterpipe and cigarette smoking in lymphocytes using the sister-chromatid exchange assay: a comparative study. AB - Tobacco smoking is a major world health problem. Recently, waterpipe smoking has become more popular in many countries. Although the genotoxicity associated with cigarette smoking has been extensively investigated, studies evaluating such toxicity in waterpipe users are still lacking. In this study, we examined the genotoxicity of waterpipe smoking in lymphocytes compared with the genotoxicity of cigarette smoking. Genotoxicity was evaluated using the sister chromatid exchanges (SCEs) assay. Fifty waterpipe smokers and 18 healthy nonsmokers participated in this study. Additionally, 18 heavy cigarette smokers (CS) were recruited for comparison. The results show that waterpipe smoking and cigarette smoking significantly increase the frequencies of SCEs (P < 0.01) compared with those of nonsmokers, indicating the genotoxic effect of tobacco smoking. In addition, frequencies of SCEs were significantly higher among waterpipe smokers compared with CS (P < 0.01), indicating that waterpipe smoking is more genotoxic than cigarette smoking. Moreover, the frequency of SCEs increased with the extent of waterpipe use. In conclusion, waterpipe smoking is genotoxic to lymphocytes and the magnitude of its genotoxicity is higher than that induced by regular cigarette smoking. PMID- 20740647 TI - Dietary influences on mutagenesis--where is this field going? AB - Early studies on dietary mutagenesis were mostly observational, with large numbers of potential dietary mutagens being identified from every conceivable dietary source. These included known dietary carcinogens such as aflatoxin B1 and benzo[a]pyrene, and hitherto unrecognized dietary mutagens, such as the pyrolysis products formed during the heating of proteinaceous materials (heterocyclic amines). The 1993 evaluation of 2-amino-3-methyl-3H-imidazo(4,5-j)quinoline as a probable human carcinogen by the International Agency for Research on Cancer was a landmark, as this was done in the absence of specific human carcinogenicity data, and strongly influenced by mutagenicity test data. In the 21st century, the field has moved from the identification of more and more mutagens, to molecular epidemiologic approaches that not only show a mutagenic effect but also seek to link it to a dietary (or environmental) cause. Effects of diet in stimulating chronic inflammation may lead to reactive species and thereby mutation as a secondary consequence, while dietary deficiencies and nutrient imbalances may be strong sources of mutagenesis. Recognition of the roles of nutrients in cell signaling processes and control of microRNAs suggest major influences on gene expression, in the absence of permanent DNA changes. Genome-wide association studies have highlighted new pathways such as JAK/STAT signaling that profoundly influence genomic instability and responses to dietary mutagens. With improved methodologies for DNA sequencing and epigenetic changes, it is time to apply more sophisticated approaches to recognizing and proving the role of diet as a primary modulator of mutagenesis in humans. PMID- 20740648 TI - Amygdala and hippocampus volumetry and diffusivity in relation to dreaming. AB - Microstructural analyses by MRI brain scans and by DTI analysis of MR images were used to investigate the possible relationship between deep gray matter structures (amygdala and hippocampus) and dreaming in healthy subjects. Thirty-four subjects ranging in age 20s to 70s underwent to a MRI protocol for the assessment of volume and mean diffusivity (MD) in the amygdala and hippocampus and were asked to fill out a dream diary via audiotape recording upon morning awakening for two weeks. Multiple regression analyses evaluated the relationships between anatomical measures and quantitative and qualitative measures of the reported dreams. The main result points to a dissociation between some quantitative and qualitative aspects of dream reports. While the mean number of dreams recalled per day did not show any significant relationship with the neuroanatomical measures, significant associations with some qualitative features of the recalled dreams (emotional load, bizarreness, and vividness) and, to some extent, with the length of dream reports were observed. Particularly, a higher MD of the left amygdala, reflecting a decreased microstructural integrity, was associated with shorter dream reports and lower scores on emotional load. Bizarreness of dream reports was negatively correlated with the left amygdala volume and positively correlated with the right amygdala MD. Some specific, although weaker, relationships were also found between bizarreness and hippocampal measures. These findings indicate some direct relationships between volumetric and ultrastructural measures of the hippocampus-amygdala complex and specific qualitative features of dreaming. PMID- 20740649 TI - Functional connectivity of cortical motor areas in the resting state in Parkinson's disease. AB - Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self-initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre-SMA) and bilateral primary motor cortex (M1) as "seed" regions, because the pre-SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre-SMA or the M1 was changed in PD. Connectivity with the pre-SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. PMID- 20740650 TI - Accelerated cardiac magnetic resonance imaging in the mouse using an eight channel array at 9.4 Tesla. AB - MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. Two- and three-dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function, T(1)-relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine-data allowed for the first time in mice measurement of left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration. PMID- 20740651 TI - Caffeine treatment of ovine cytoplasts regulates gene expression and foetal development of embryos produced by somatic cell nuclear transfer. AB - Treatment of ovine oocytes during the latter stages of maturation in vitro with caffeine, a phosphodiesterase inhibitor, can increase the activities of maturation promoting factor and mitogen-activated protein kinases at metaphase II. When used as cytoplast recipients for somatic cell nuclear transfer (NT), caffeine-treated oocytes produced blastocysts with increased cell numbers. The objectives of these studies were to determine the effects of caffeine treatment on the expression profile of genes involved in early embryonic development and whether induction or maintenance of pregnancy was subsequently altered. No differences in overall expression patterns were observed between fertilised, caffeine-treated fertilised and parthenogenetic embryos. In control NT embryos, altered levels of gene expression were found for OCT4, five genes regulated by OCT4 (H2AF.Z, NANOG, SOX2, FGF4 and INFT) and the heat-shock response genes (HSP27 and HSP70.1). Levels of OCT4, H2AF.Z, NANOG, HSP 27 and FGF4 decreased, while those of INFT, HSP70.1 and SOX2 increased. In contrast, expression levels of these genes in caffeine-treated NT embryos were similar to those in fertilised controls. Following transfer to surrogate recipients no differences were observed in the frequency of pregnancy; however, ewes receiving caffeine-treated embryos maintained pregnancies for longer periods and delivered a live lamb. Taken together, these results suggest that treatment of ovine oocytes with caffeine can affect gene expression and improve developmental competence. Further studies on the mechanisms behind this alteration of gene expression are required and will aid in understanding the molecular mechanisms involved in nuclear reprogramming. PMID- 20740652 TI - Novel spherical phantoms for Q-ball imaging under in vivo conditions. AB - For the validation of complex diffusion imaging techniques like q-ball imaging that aim to resolve multiple fiber directions, appropriate phantoms are highly desirable. However, previous q-ball imaging phantoms had diffusion anisotropies well below those of in vivo white matter. In this work, fiber phantoms of well defined geometry are presented. The fibers are wound on a spherical spindle yielding high packing densities and consequently high diffusion anisotropies (fractional anisotropy 0.93 +/- 0.02 at b = 500 s/mm(2)). Phantoms with 90 degrees and 45 degrees crossing angle were constructed both with two crossing types. In the "stacked" crossing, two fiber strings were wound consecutively to simulate two touching fibers, in the "interleaved" crossing, fibers were wound alternately. The stacked crossing allows the alteration of partial volumes, whereas the interleaved crossing provides constant partial volumes, allowing e.g. the easy alteration of the SNR by varying the slice thickness. Exemplary q-ball imaging validation measurements using different b-values and slice thicknesses are presented. PMID- 20740653 TI - Protein polymer MRI contrast agents: Longitudinal analysis of biomaterials in vivo. AB - Despite recent advances in tissue engineering to regenerate biological function by combining cells with material supports, development is hindered by inadequate techniques for characterizing biomaterials in vivo. Magnetic resonance imaging is a tomographic technique with high temporal and spatial resolution and represents an excellent imaging modality for longitudinal noninvasive assessment of biomaterials in vivo. To distinguish biomaterials from surrounding tissues for magnetic resonance imaging, protein polymer contrast agents were developed and incorporated into hydrogels. In vitro and in vivo images of protein polymer hydrogels, with and without covalently incorporated protein polymer contrast agents, were acquired by magnetic resonance imaging. T(1) values of the labeled gels were consistently lower when protein polymer contrast agents were included. As a result, the protein polymer contrast agent hydrogels facilitated fate tracking, quantification of degradation, and detection of immune response in vivo. For the duration of the in vivo study, the protein polymer contrast agent containing hydrogels could be distinguished from adjacent tissues and from the foreign body response surrounding the gels. The hydrogels containing protein polymer contrast agent have a contrast-to-noise ratio 2-fold greater than hydrogels without protein polymer contrast agent. In the absence of the protein polymer contrast agent, hydrogels cannot be distinguished by the end of the gel lifetime. PMID- 20740654 TI - Reference-based linear curve fitting for bolus arrival time estimation in 4D MRA and MR perfusion-weighted image sequences. AB - The bolus arrival time (BAT) based on an indicator dilution curve is an important hemodynamic parameter. As the direct estimation of this parameter is generally problematic, various parametric models have been proposed that describe typical physiological shapes of indicator dilution curves, but it remains unclear which model describes the real physiological background. This article presents a method that indirectly incorporates physiological information derived from the data available. For this, a patient-specific hemodynamic reference curve is extracted, and the corresponding reference BAT is determined. To estimate a BAT for a given signal curve, the reference curve is fitted linearly to the signal curve. The parameters of the fitting process are then used to transfer the reference BAT to the signal curve. The validation of the method proposed based on Monte Carlo simulations showed that the approach presented is capable of improving the BAT estimation precision compared with standard BAT estimation methods by up to 59% while at the same time reduces the computation time. A major benefit of the method proposed is that no assumption about the underlying distribution of indicator dilution has to be made, as it is implicitly modeled in the reference curve. PMID- 20740655 TI - Determination of spin compartment in arterial spin labeling MRI. AB - A major difference between arterial-spin-labeling MRI and gold-standard radiotracer blood flow methods is that the compartment localization of the labeled spins in the arterial-spin-labeling image is often ambiguous, which may affect the quantification of cerebral blood flow. In this study, we aim to probe whether the spins are located in the vascular system or tissue by using T2 of the arterial-spin-labeling signal as a marker. We combined two recently developed techniques, pseudo-continuous arterial spin labeling and T2-Relaxation-Under-Spin Tagging, to determine the T2 of the labeled spins at multiple postlabeling delay times. Our data suggest that the labeled spins first showed the T2 of arterial blood followed by gradually approaching and stabilizing at the tissue T2. The T2 values did not decrease further toward the venous T2. By fitting the experimental data to a two-compartment model, we estimated gray matter cerebral blood flow, arterial transit time, and tissue transit time to be 74.0 +/- 10.7 mL/100g/min (mean +/- SD, N = 10), 938 +/- 156 msec, and 1901 +/- 181 msec, respectively. The arterial blood volume was calculated to be 1.18 +/- 0.21 mL/100 g. A postlabeling delay time of 2 s is sufficient to allow the spins to completely enter the tissue space for gray matter but not for white matter. PMID- 20740656 TI - Highly localized positive contrast of small paramagnetic objects using 3D center out radial sampling with off-resonance reception. AB - In this article, we present a 3D imaging technique, applying center-out RAdial Sampling with Off-Resonance reception, to accurately depict and localize small paramagnetic objects with high positive contrast while suppressing long T(2) (*) components. The center-out RAdial Sampling with Off-Resonance reception imaging technique is a fully frequency-encoded 3D ultrashort echo time acquisition method, which uses a large excitation bandwidth and off-resonance reception. By manually introducing an offset, Deltaf(0), to the central reception frequency (f(0)), the typical radial signal pileup observed in 3D center-out sampling caused by a dipolar magnetic field disturbance can be shifted toward the source of the field disturbance, resulting in a hyperintense signal at the magnetic center of the small paramagnetic object. This was demonstrated both theoretically and using 1D time domain simulations. Experimental verification was done in a gel phantom and in inhomogeneous porcine tissue containing various objects with very different geometry and susceptibility, namely, subvoxel stainless steel spheres, a puncture needle, and paramagnetic brachytherapy seeds. In all cases, center-out RAdial Sampling with Off-Resonance reception was shown to generate high positive contrast exactly at the location of the paramagnetic object, as was confirmed by X-ray computed tomography. PMID- 20740658 TI - Human deciduous mandibular molar incremental enamel development. AB - Quantitative studies of incremental markings retained within human enamel have reconstructed the duration and rate (crown and cusp formation times, initiation and completion, daily enamel secretion rates) of permanent tooth development. This approach has provided one way of estimating human age-at-death, and facilitated comparative dental studies of primate evolution. Similar applications from deciduous enamel are inhibited because developmental reconstructions from incremental markings for these teeth are less frequently reported in the literature. This study quantified the duration and rate of enamel development for mesial (protoconid, metaconid) and distal cusps (hypoconid, entoconid) for first (dm1) and second (dm2) deciduous mandibular molars from an archaeological sample of modern human juveniles. Crown formation time can be calculated from the dm1 protoconid because growth initiates and completes in this cusp, and from the dm2 protoconid combined with the final period of hypoconid growth. The dm1 postnatal crown formation time included the time taken for the tubercle of Zuckerkandl to develop, and differed slightly compared to radiographic methods. The majority of dm1 protoconid cuspal (occlusal region) enamel formed before birth. The dm2 entoconid enamel formed mainly after birth. Birth reduced daily enamel secretion rates, changed the visibility of incremental markings, and disrupted enamel growth for 3 to 8 days. Findings presented here can contribute to age-at-death estimates for human infants aged 13-postnatal months or less, and should facilitate comparisons of primate deciduous incremental enamel development in an evolutionary context. Regression equations are included so that cuspal formation time can be estimated from enamel thickness. PMID- 20740657 TI - Performance of external and internal coil configurations for prostate investigations at 7 T. AB - Three different coil configurations were evaluated through simulation and experimentally to determine safe operating limits and evaluate subject size dependent performance for prostate imaging at 7 T. The coils included a transceiver endorectal coil (trERC), a 16-channel transceiver external surface array (trESA) and a trESA combined with a receive-only ERC (trESA+roERC). Although the transmit B(1) (B 1+) homogeneity was far superior for the trESA, the maximum achievable B 1+ is subject size dependent and limited by transmit chain losses and amplifier performance. For the trERC, limitations in transmit homogeneity greatly compromised image quality and limited coverage of the prostate. Despite these challenges, the high peak B 1+ close to the trERC and subject size-independent performance provides potential advantages especially for spectroscopic localization where high-bandwidth radiofrequency pulses are required. On the receive side, the combined trESA+roERC provided the highest signal-to-noise ratio and improved homogeneity over the trERC resulting in better visualization of the prostate and surrounding anatomy. In addition, the parallel imaging performance of the trESA+roERC holds strong promise for diffusion weighted imaging and dynamic contrast-enhanced MRI. PMID- 20740659 TI - Strain and torsion quantification in mouse hearts under dobutamine stimulation using 2D multiphase MR DENSE. AB - In this study, a 2D multiphase magnetic resonance displacement encoding with stimulated echoes (DENSE) imaging and analysis method was developed for direct quantification of Lagrangian strain in the mouse heart. Using the proposed method, <10 ms temporal resolution and 0.56 mm in-plane resolution were achieved. A validation study that compared strain calculation by displacement encoding with stimulated echoes and by magnetic resonance tagging showed high correlation between the two methods (R(2) > 0.80). Regional ventricular wall strain and twist were characterized in mouse hearts at baseline and under dobutamine stimulation. Dobutamine stimulation induced significant increase in radial and circumferential strains and torsion at peak systole. A rapid untwisting was also observed during early diastole. This work demonstrates the capability of characterizing cardiac functional response to dobutamine stimulation in the mouse heart using 2D multiphase magnetic resonance displacement encoding with stimulated echoes. PMID- 20740660 TI - Differential visibility of treponemal disease in pre-Columbian stratified societies: does rank matter? AB - Treponemal disease is known to be associated with the compromised community health of permanent village settlement. This association explains its high visibility in the village-based, arguably chiefdom level, agriculturalist societies of late prehistoric (AD 1300-1600) North America. Within chiefdom-level societies, health differences have often been demonstrated between mortuary defined "elite" and "nonelite" individuals. This theoretically should predict status-based differences in treponemal disease visibility. The prediction is tested in a five-site osteological sample (N = 650) from the Dallas phase (AD 1300-1550), a simple mortuary-defined two-tiered presumptive chiefdom level maize agriculturalist socioeconomic context from lower east Tennessee. The Dallas phase results affirm a general pre-Colombian North American pattern of no sex differences and display comparable adult to subadult frequencies. The study also reveals that given a sufficient sample size, "elites" do indeed exhibit a significantly lower frequency of tertiary stage treponemal disease. This can be attributed to better baseline health, which has been previously demonstrated in this sample. It may also be affected by the mortuary inclusion of achieved status individuals whose good health may have facilitated sociopolitical advancement. Another pattern that emerged is an apparent young adult age bias in disease visibility. This suggests that tertiary treponemal disease morbidity may either directly or synergistically factor in early adult age at death. Future research will address the veracity of this association. PMID- 20740661 TI - Surnames in Bolivia: a study of the population of Bolivia through isonymy. AB - In Bolivia, the Hispanic dual surname system is used. To describe the isonymic structure of Bolivia, the surname distribution of 12,139,448 persons registered in the 2006 census data was studied in 9 districts and 112 provinces of the nation, for a total of 23,244,064 surnames. The number of different surnames found was 174,922. Matrices of isonymic distances between the administrative units (districts and provinces) were constructed and tested for correlation with geographic distance. In the 112 provinces, isonymic distances were correlated with geographic distance (r = 0.545 +/- 0.011 for Euclidean, 0.501 +/- 0.012 for Nei's, and 0.556 +/- 0.010 for Lasker's distance). The multiple regression of the surname effective number (alpha), equivalent to the allele effective number in a genetic system, was nonsignificant on latitude and longitude; however, it was highly significant and negative on altitude (r = -0.72). Because the Andes extend from north to south in west-central Bolivia, random inbreeding was lowest in the eastern districts, and highest in mountainous western Bolivia. Average alpha for the provinces was 122 +/- 2; for the districts, it was 216 +/- 29, and for the whole of Bolivia it was 213. The geographical distribution of alpha in the provinces is compatible with the settlement of subsequent groups of migrants moving from east and north toward the center and south of Bolivia. The relative frequency of indigenous surnames is correlated positively with altitude. This suggests that the country was populated by recent low-density demic diffusion over a low-density indigenous population. This may have been a common phenomenon in the immigration to tropical South America. PMID- 20740662 TI - Human brain atlas-based volumetry and relaxometry: application to healthy development and natural aging. AB - This work investigated the feasibility and utility of using T2-weighted or dual spin-echo data to provide volume and T2 relaxation time for regional and global gray and white matter using standardized brain templates and anatomically labeled atlases. A total of 130 healthy males and females (age range 15-59 years) were included. Dual echo magnetic resonance imaging data were acquired and analyzed using standardized International Consortium for Human Brain Mapping atlas-based tissue segmentation procedures implemented in the statistical parametric mapping toolbox to obtain the age trajectories of volume and corresponding T2 relaxation time in whole brain white and gray matter, in the caudate nucleus and in the anterior limb of internal capsule. Whole brain gray matter and caudate nucleus volumes linearly decreased with age while whole brain white matter and anterior limb internal capsule volume increased slowly with age bilaterally in males and females. The relation between T2 relaxation time and age of whole brain gray and white matter, and caudate nucleus and anterior limb internal capsule followed a quadratic U-curve. The T2 relaxation times of the human brain followed a U curve both globally and regionally in both white and gray matter. PMID- 20740663 TI - Ongoing dual-angle measurements for the correction of partial saturation in 31P MR spectroscopy. AB - Use of a repetition time similar to, or shorter than, metabolite T(1)s is common in NMR spectroscopy of biological samples to improve the signal-to-noise ratio. Conventionally, the partial saturation that results from this is corrected using saturation factors. However, this can lead to erroneous results in the presence of chemical exchange or nonconstant T(1)s. We describe an alternative approach to correction for saturation, based on ongoing dual-angle T(1) measurement. Using (31)P magnetic resonance spectroscopy of the perfused rat heart undergoing ischemia-reperfusion, we demonstrate that signal alternations in the data acquired by the dual-angle approach are eliminated by the ongoing dual-angle T(1) measurement correction scheme, meaning that metabolite concentration and T(1) measurement can be made throughout the course of the ischemia-reperfusion protocol. Simulations, based on parameters pertinent to the perfused rat heart, demonstrate that accurate saturation correction is possible with this method except at times of rapid concentration change. Additionally, compared to the conventional saturation factor correction method, the ongoing dual-angle T(1) measurement correction scheme results in improved accuracy in determining the [phosphocreatine] recovery time constant. Thus, the ongoing dual-angle T(1) measurements procedure permits accurate monitoring of metabolite concentrations even in the setting of chemical exchange and T(1) changes and allows more accurate analysis of bioenergetic status. PMID- 20740664 TI - Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration. AB - In the present study, a chemical shift saturation recovery method in hyperpolarized (129)Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase-induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, V(s)/V(a), and the transit time of blood through the gas exchange region, tau. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase-treated mice. Our results showed that V(s)/V(a) was significantly reduced in elastase-treated mice, reflecting emphysema-like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and tau, were not shown. This study is the first application of hyperpolarized (129)Xe MR spectroscopy to a mouse model of emphysema and shows that the V(s)/V(a) volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents. PMID- 20740665 TI - MRI contrast from relaxation along a fictitious field (RAFF). AB - A new method to measure rotating frame relaxation and to create contrast for MRI is introduced. The technique exploits relaxation along a fictitious field (RAFF) generated by amplitude- and frequency-modulated irradiation in a subadiabatic condition. Here, RAFF is demonstrated using a radiofrequency pulse based on sine and cosine amplitude and frequency modulations of equal amplitudes, which gives rise to a stationary fictitious magnetic field in a doubly rotating frame. According to dipolar relaxation theory, the RAFF relaxation time constant (T(RAFF)) was found to differ from laboratory frame relaxation times (T(1) and T(2)) and rotating frame relaxation times (T(1rho) and T(2rho)). This prediction was supported by experimental results obtained from human brain in vivo and three different solutions. Results from relaxation mapping in human brain demonstrated the ability to create MRI contrast based on RAFF. The value of T(RAFF) was found to be insensitive to the initial orientation of the magnetization vector. In the RAFF method, the useful bandwidth did not decrease as the train length increased. Finally, as compared with an adiabatic pulse train of equal duration, RAFF required less radiofrequency power and therefore can be more readily used for rotating frame relaxation studies in humans. PMID- 20740666 TI - Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood-brain barrier with ultrasound. AB - The use of contrast agents for neuroimaging is limited by the blood-brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak-negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd-DTPA) was administered to the mouse brain parenchyma, thereby shortening T(1) and enabling the acquisition of high-resolution (52 * 52 * 100 micrometers(3)) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI. PMID- 20740667 TI - Transport pathways and enhancement mechanisms within localized and non-localized transport regions in skin treated with low-frequency sonophoresis and sodium lauryl sulfate. AB - Recent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, highly perturbed skin regions, known as localized transport regions (LTRs), exist. Despite these findings, little research has been conducted to identify intrinsic properties and formation mechanisms of LTRs and the surrounding less-perturbed non-LTRs. By independently analyzing LTR, non-LTR, and total skin samples treated at multiple LFS frequencies, we found that the pore radii (r(pore)) within non-LTRs are frequency-independent, ranging from 18.2 to 18.5 A, but significantly larger than r(pore) of native skin samples (13.6 A). Conversely, r(pore) within LTRs increase significantly with decreasing frequency from 161 to 276 A and to infinity (>300 A) for LFS/SLS-treated skin at 60, 40, and 20 kHz, respectively. Our findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. We propose that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, whereas the increased r(pore) values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of microstreaming. PMID- 20740669 TI - A new approach to determine camptothecin and its analogues affinity to human serum albumin. AB - A novel and fast method for the determination of the binding kinetic data of ligand to protein has been developed. A new tool including human serum albumin coated magnetic beads (HSA-MB) was used to determine the affinity of camptothecin (CPT) and its analogues to HSA. From the biological activity point of view, these compounds have potential anticancer activity. However, the numerous studies indicate that some of these analogues have a strong affinity to plasma proteins stopping their effective therapy. Thus, the problem of plasma protein binding behavior of CPT's analogues was the subject of this study. PMID- 20740668 TI - Low dose erythropoietin stimulates bone healing in mice. AB - Beyond its classical role in regulation of erythropoiesis, erythropoietin (EPO) has been shown to exert protective and regenerative actions in a variety of non hematopoietic tissues. However, little is known about potential actions in bone regeneration. To analyze fracture healing in mice, a femoral 0.25 mm osteotomy gap was stabilized with a pin-clip technique. Animals were treated with 500 U EPO/kg bw per day or with vehicle only. After 2 and 5 weeks, fracture healing was analyzed biomechanically, radiologically and histologically. Expression of PCNA and NFkappaB was examined by Western blot analysis. Vascularization was analyzed by immunohistochemical staining of PECAM-1. Circulating endothelial progenitor cells were measured by flow-cytometry. Herein, we demonstrate that EPO-treatment significantly accelerates bone healing in mice. This is indicated by a significantly greater biomechanical stiffness and a higher radiological density of the periosteal callus at 2 and 5 weeks after fracture and stabilization. Histological analysis demonstrated significantly more bone and less cartilage and fibrous tissue in the periosteal callus. Endosteal vascularization was significantly increased in EPO-treated animals when compared to controls. The number of circulating endothelial progenitor cells was significantly greater in EPO-treated animals. The herein shown acceleration of healing by EPO may represent a promising novel treatment strategy for fractures with delayed healing and non-union formation. PMID- 20740670 TI - Oral apomorphine delivery from solid lipid nanoparticles with different monostearate emulsifiers: pharmacokinetic and behavioral evaluations. AB - Apomorphine, a dopamine receptor agonist for treating Parkinson's disease, has very poor oral bioavailability (<2%) due to the first-pass effect. The aim of this work was to investigate whether the oral bioavailability and brain regional distribution of apomorphine could be improved by utilizing solid lipid nanoparticles (SLNs). Glyceryl monostearate (GMS) and polyethylene glycol monostearate (PMS) were individually incorporated into SLNs as emulsifiers. It was found that variations in the emulsifiers had profound effects on the physicochemical characteristics. Mean diameters of the GMS and PMS systems were 155 and 63 nm, respectively. More than 90% of the apomorphine was entrapped in the SLNs. The interfacial film was the likely location for most of apomorphine molecules. The PMS system, when incubated in simulated intestinal medium, was found to be more stable in terms of particle size and encapsulation efficiency than the GMS system. Using the GMS and PMS systems to orally administer apomorphine (26 mg/kg) equally enhanced the bioavailability in rats. SLNs showed 12- to 13-fold higher bioavailability than the reference solution. The drug distribution in the striatum, the predominant site of therapeutic action, also increased when using the SLNs. The anti-Parkinsonian activity of apomorphine was evaluated in rats with 6-hydroxydopamine-induced lesions, a model of Parkinson's disease. The contralateral rotation behavior was examined after oral apomorphine delivery. The total number of rotations increased from 20 to 94 and from 20 to 115 when the drug was administered from SLNs containing GMS and PMS, respectively. The experimental results suggest that SLNs may offer a promising strategy for apomorphine delivery via oral ingestion. PMID- 20740671 TI - Scleraxis expression is coordinately regulated in a murine model of patellar tendon injury. AB - This study investigated the expression of Scleraxis in a murine model of patellar tendon injury in which the central third of the patellar tendon was unilaterally injured. The presence of tendon pathology was assessed using dual photon microscopy, conventional histology and microCT. Tendon pathology was also quantified noninvasively over a 12-week period using high-frequency ultrasound and laser Doppler flowmetry. Gene expression (Scx, Tnmd, and Col1a1) was determined at defined end-points (1, 4, 8, and 12 weeks) using qPCR on RNA from individual patellar tendons on injured and uninjured sides. There was significant development of tendon pathology as gauged by ultrasound and laser Doppler over 12 weeks. Injured tendons demonstrated significant histological and microCT evidence of pathological change, and disorganized collagen with reduced density. The expression of Scx and Col1a1 was unchanged at 1 week, significantly upregulated at 4 and 8 weeks, and had returned to baseline by 12 weeks. Tnmd expression was unchanged at 1 week, and significantly increased at 4, 8, and 12 weeks. Patellar tendon injury was associated with marked increases in the expression of Scx, Tnmd, and Col1a1. Our data suggest new roles for Scleraxis in coordinating the response to injury in the pathogenesis of tendon disorders. PMID- 20740672 TI - Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. AB - Although autologous bone grafting represents an effective tool to induce osteogenic regeneration in local bone defects or pseudarthroses, it is associated with significant donor site morbidity and limited by the amount available for grafting. We investigate the potency of bone marrow aspiration concentrate (BMAC) to augment bone grafting and support bone healing. The functional and radiographic outcome of 39 patients with volumetric bone deficiencies treated with BMAC are presented and evaluated in a prospective clinical trial. A collagen sponge (Col) served as scaffold in 12 patients and a bovine hydroxyapatite (HA) was applied in the other 27 individuals. The minimal follow-up was 6 months. Clinical and radiographic findings were completed by in vitro data. All patients showed new bone formation in radiographs during follow-up. However, two patients underwent revision surgery due to a lack in bone healing. In contrast to the Col group, the postoperative bone formation appeared earlier in the HA group (HA group: 6.8 weeks vs. Col group 13.6 weeks). Complete bone healing was achieved in the HA group after 17.3 weeks compared to 22.4 weeks in the Col group. The average concentration factor of BMAC was 5.2 (SD 1.3). Flow cytometry confirmed the mesenchymal nature of the cells. Cells from BMAC created earlier and larger colonies of forming units fibroblasts (CFU-F) compared to cells from bone marrow aspirate. BMAC combined with HA can reduce the time needed for healing of bone defects when compared to BMAC in combination with collagen sponge. PMID- 20740673 TI - The catabolic role of toll-like receptor 2 (TLR-2) mediated by the NF-kappaB pathway in septic arthritis. AB - Toll-like receptors (TLRs) are involved in mediating cell activation on stimulation with microbial components. Our objective was to investigate the role of TLR-2 mediated by the NF-kappaB pathway in septic arthritic chondrocytes. TLR 1, -2, and -6 mRNA expression levels were investigated in septic and normal chondrocytes using real-time reverse transcription-PCR. TLR-2 and MMP-13 mRNA and protein levels were measured using real-time PCR and Western blot analysis, respectively. Blocking TLR-2 mRNA expression was performed using small interfering RNA (siRNA) against TLR-2 and subsequently MMP-3, MMP-13, IL-1beta, and IL-6 mRNA levels, as well as p65 NF-kappaB, IkBalpha, and MMP-13 protein levels were evaluated using real-time PCR and Western blot analysis. IL-6 protein levels were measured using ELISA assay. We observed that TLR-1, -2, and -6 mRNA expression levels were significantly higher in septic compared to normal chondrocytes. MMP-13 mRNA and protein expressions were also significantly upregulated in septic arthritic cartilage. Blocking TLR-2 mRNA expression in septic chondrocytes resulted in significant increase of inactivated nonphosphorylated p65 NF-kappaB and IkBalpha protein levels and reduction in MMP 13, IL-1beta, and IL-6 expression. Our findings suggest the pro-inflammatory and catabolic role of TLR-2 mediated by the NF-kappaB pathway in septic arthritis. Modulation of TLR-mediated signaling may be a potential therapeutic strategy for the prevention of postinfectious cartilage degradation in articular joints. PMID- 20740674 TI - Vaccines with aluminum-containing adjuvants: optimizing vaccine efficacy and thermal stability. AB - Aluminum-containing adjuvants have been used to enhance the immune response against killed, inactivated, and subunit antigens for more than seven decades. Nevertheless, we are only beginning to gain important insight as to what may be some very fundamental parameters for optimizing their use. For example, there is evidence that the conventional approach of maximizing antigen binding (amount and/or strength) may not result in an optimal immune response. Adsorption of antigen onto the adjuvant has recently been suggested to decrease the thermal stability of some antigens; however, whether adsorption-induced alterations to the structure and/or stability of the antigen have consequences for the elicited immune response is unclear. Finally, the thermal stability of vaccines with aluminum-containing adjuvants is not robust. Optimizing the stability of these vaccines requires an understanding of the freeze sensitivity of the adjuvant, freeze and heat sensitivity of the antigen in the presence of the adjuvant, and perhaps most important, how (or whether) various approaches to formulation can be used to address these instabilities. This review attempts to summarize recent findings regarding issues that may dictate the success of vaccines with aluminum containing adjuvants. PMID- 20740675 TI - Controlled drug delivery system based on ordered mesoporous silica matrices of captopril as angiotensin-converting enzyme inhibitor drug. AB - In the present study, captopril-loaded ordered mesoporous SBA-15 silica matrix were produced, functionalized, and characterized to obtain an efficient formulation of controlled drug delivery system. First, the starting SBA-15 materials are examined to verify that their synthesis has been successful considering the structural properties, using XRD, FTIR, and BET methods. Second, the influence of processing parameters of ordered mesoporous matrices for the loading and release of captopril was investigated. The release of captopril was controlled by tailoring the surface properties of the mesoporous silica via functionalization. The loading and release kinetics (in vitro in simulated gastric and intestinal fluids) showed that both of them were affected by the surface properties of the mesoporous silica materials. Such a formulation shows potential as an efficient controlled drug delivery system. PMID- 20740676 TI - A three-dimensional polycaprolactone scaffold combined with a drug delivery system consisting of electrospun nanofibers. AB - A new three-dimensional (3D) scaffold containing a functional drug delivery system (DDS) consisting of electrospun micro/nanofibers is proposed. In the DDS scaffold, a core-shell laminated, structured, electrospun mat of hydrophobic polycaprolactone (PCL) and hydrophilic poly(ethylene oxide) (PEO)/rhodamine-B fibers was embedded in the normal 3D PCL scaffold, which was fabricated by a melt plotting system. Rhodamine release from the scaffold was controlled physically by the thickness change of the PCL layer, and initial burst in drug release was eliminated by an appropriate thickness of the PCL layer. This simple technique may be useful in fabricating DDS-functional scaffolds for the clinical areas not only of bone and skin regeneration, but also of other tissue regeneration areas, regardless of the degradation rate of the structural scaffold. PMID- 20740677 TI - New technology for the investigation of water vapor sorption-induced crystallographic form transformations of chemical compounds: a water vapor sorption gravimetry-dispersive Raman spectroscopy coupling. AB - In this study, a new dynamic water vapor sorption gravimetry (DWVSG)-Raman spectroscopy coupled system is presented and described for the investigation of water (de)sorption-induced solid-phase transition of active pharmaceutical ingredients (APIs). The innovative characteristic of the system is the possibility to measure up to 23 samples gravimetrically and spectroscopically in one sorption/desorption experiment. The used dispersive RXN1 Raman system with a 6-mm laser spot P(h) AT probe head is ideal for this kind of coupled technology, as the energy density at the point of measurement of the sample is low, which grants that gravimetrical data and the state of the sample (phase transformations or even degradation) are not influenced by the laser beam. The capabilities of the system were tested by the investigation of a crystalline, nonstoichiometric hydrate form (form 1) and the corresponding X-ray amorphous form of an API (SAR474832). For the crystalline hydrate form, it was possible to correlate the weight loss at low humidities to a crystallographic phase transition (form 2). Furthermore, it was possible to show that the phase transition is reversible upon water uptake (sorption cycle); however, a further intermediate crystal form (form 3) is involved in the rehydration process. By multivariate curve resolution analysis of the Raman spectra, the form distribution diagrams of the desorption/sorption cycle could be constructed. For the amorphous material, the recrystallization process was monitored by the changes in the Raman spectra. The recrystallization point was detected at high humidities (>90% relative humidity), the crystal phase formed was identified (form 1), and the time needed for the conversion into the crystalline state was determined. The form transformation processes were visualized by contour plots (time/humidity vs. wavenumber vs. Raman intensity). In summary, it was concluded that the presented water sorption gravimetry-Raman spectroscopy coupling is a powerful tool to study solid-state transitions of pharmaceutical compounds or galenic formulations. The information obtained can, for example, be used to optimize drying, conditioning, or rerystallization processes of chemical products or to determine their optimal storage conditions. This is especially interesting for physically and chemically labile hydrate phases. PMID- 20740678 TI - Impact of the trade-related aspects of intellectual property rights (TRIPS) agreement on India as a supplier of generic antiretrovirals. AB - This is a commentary on how the trade-related aspects of intellectual property rights (TRIPS) agreement has impacted India as a supplier of generic antiretrovirals (ARVs). We provide a systematic review of the issues related to the TRIPS agreement that affects India. This includes discussion around (a) the legal landscape underpinning India as a supplier of generic ARVs; (b) supply of second-line ARVs; and (c) the future of generic drug production in India. The proclamation into force of TRIPS-compliant intellectual property law in India is likely to affect its position as a supplier of affordable ARVs, especially drugs brought to market after 2005. Currently, mechanisms exist for the generic production of almost all ARVs in India, including second-line drugs; however, the manufacture of these drugs by generic pharmaceutical companies may require additional market incentives. Compulsory licensing may emerge as an additional mechanism by which India can provide affordable versions of patented drugs to Least Developed Countries (LDCs). PMID- 20740679 TI - Identifying stabilizers of plasmid DNA for pharmaceutical use. AB - To better address the need for developing stable formulations of plasmid DNA based biopharmaceuticals, 37 compounds from a generally regarded as safe library were examined for their potential use as stabilizers. A plasmid DNA-based therapeutic vaccine, BHT-DNA, was used as a model system. Initial studies were performed to compare the biophysical properties of BHT-DNA plasmid from bulk drug substance and finished drug product. An agarose gel electrophoresis-based assay was then employed in excipient compatibility studies for the drug product by monitoring supercoiled plasmid DNA content in various formulations. After incubation at 40 degrees C for 30 days, eight out of the 37 excipients tested were able to better retain the supercoil content compared to the control. Sodium citrate appeared to be the most effective stabilizer and its protective capability plateaued at an ionic strength of about 0.4. Several other excipients including malic acid, ethanol, and Pluronic F-68 were also identified as promising stabilizers for BHT-DNA plasmid DNA. Additionally, compounds, including ferrous chloride, ascorbic acid, human serum albumin, and PEG 1000, which significantly destabilized the supercoiled plasmid DNA were identified. These data may also be applicable to other plasmid DNA-based pharmaceuticals for storage stability improvement, due to chemical and structural similarities of these macromolecules. PMID- 20740681 TI - Detection of free base surface enrichment of a pharmaceutical salt by X-ray photoelectron spectroscopy (XPS). AB - Yellow discoloration was observed at the surface of normally white crystals of a development pharmaceutical fumarate salt, tentatively ascribed to the presence of trace amounts of free base. The impact of impurities on sample properties and behavior can be significant, especially if localized at the surface. No conventional bulk analytical technique could readily provide an explanation for the yellow color, so a surface-sensitive technique, X-ray photoelectron spectroscopy (XPS), was employed to characterize the salt. XPS reveals the presence of free base at the surface through the HN(+)/N ratio. A free radical decarboxylation mechanism is proposed to account for the alterations observed with extended irradiation. The lower intensity carboxyl signal and significantly lower HN(+)/N ratio for the yellow surface samples reveal a higher level of free base at the surface than the white samples. The samples with yellow surfaces could not be successfully milled, which was an important part of the production process for providing material of the required physical quality for product formulation. Identification of residual free base at the surface of the crystalline material, by XPS, was significant for optimization of the crystallization process to yield material of required quality for successful milling at plant scale. PMID- 20740680 TI - Attaching zanamivir to a polymer markedly enhances its activity against drug resistant strains of influenza a virus. AB - Effects of the commercial drug zanamivir (Relenza) covalently attached to poly-l glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti influenza potency compared with the zanamivir parent against human and avian viral strains, including both wild-type and drug-resistant mutants, and (ii) superior neuraminidase (NA) inhibition constants, especially for the mutants. These findings provide a basis for exploring polymer-attached inhibitors as more efficacious therapeutics, particularly against drug-resistant influenza strains. PMID- 20740682 TI - Application of extrinsic fluorescence spectroscopy for the high throughput formulation screening of aluminum-adjuvanted vaccines. AB - High throughput screening (HTS) of excipients for proteins in solution can be achieved by several analytical techniques. The screening of stabilizers for proteins adsorbed onto adjuvants, however, may be difficult due to the limited amount of techniques that can measure stability of adsorbed protein in high throughput mode. Here, we demonstrate that extrinsic fluorescence spectroscopy can be successfully applied to study the physical stability of adsorbed antigens at low concentrations in 96-well plates, using a real-time polymerase chain reaction (RT-PCR) instrument. HTS was performed on three adjuvanted pneumococcal proteins as model antigens in the presence of a standard library of stabilizers. Aluminum hydroxide appeared to decrease the stability of all three proteins at relatively high and low pH values, showing a bell-shaped curve as the pH was increased from 5 to 9 with a maximum stability at near neutral pH. Nonspecific stabilizers such as mono- and disaccharides could increase the conformational stability of the antigens. In addition, those excipients that increased the melting temperature of adsorbed antigens could improve antigenicity and chemical stability. To the best of our knowledge, this is the first report describing an HTS technology amenable for low concentration of antigens adsorbed onto aluminum containing adjuvants. PMID- 20740683 TI - Impact of product-related factors on immunogenicity of biotherapeutics. AB - All protein therapeutics have the potential to be immunogenic. Several factors, including patient characteristics, disease state, and the therapy itself, influence the generation of an immune response. Product-related factors such as the molecule design, the expression system, post-translational modifications, impurities, contaminants, formulation and excipients, container, closure, as well as degradation products are all implicated. However, a critical examination of the available data shows that clear unequivocal evidence for the impact of these latter factors on clinical immunogenicity is lacking. No report could be found that clearly deconvolutes the clinical impact of the product attributes on patient susceptibility. Aggregation carries the greatest concern as a risk factor for immunogenicity, but the impact of aggregates is likely to depend on their structure as well as on the functionality (e.g., immunostimulatory or immunomodulatory) of the therapeutic. Preclinical studies are not yet capable of assessing the clinically relevant immunogenicity potential of these product related factors. Simply addressing these risk factors as part of product development will not eliminate immunogenicity. Minimization of immunogenicity has to begin at the molecule design stage by reducing or eliminating antigenic epitopes and building in favorable physical and chemical properties. PMID- 20740684 TI - Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation. AB - Notch1 genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch1 signaling in osteogenesis is not well defined. Notch1 controls osteoblast differentiation by affecting Runx2, but the question arises whether normal osteoblastic differentiation can occur regardless of the presence of Notch1. In this study, we observed the downregulation of Notch1 signaling during osteoblastic differentiation. BMPR-IB/Alk6-induced Runx2 proteins reduced Notch1 activity to a marked degree. Accumulated Runx2 suppressed Notch1 transcriptional activity by dissociating the Notch1-IC-RBP-Jk complex. Using deletion mutants, we also determined that the N-terminal domain of Runx2 was crucial to the binding and inhibition of the N-terminus of the Notch1 intracellular domain. Notably, upregulation of the Runx2 protein level paralleled reduced expression of Hes1, which is a downstream target of Notch1, during osteoblast differentiation. Collectively, our data suggest that Runx2 is an inhibitor of the Notch1 signaling pathway during normal osteoblast differentiation. PMID- 20740685 TI - Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. AB - The selective cathepsin K inhibitor odanacatib (ODN) progressively increased bone mineral density (BMD) and decreased bone-resorption markers during 2 years of treatment in postmenopausal women with low BMD. A 1-year extension study further assessed ODN efficacy and safety and the effects of discontinuing therapy. In the base study, postmenopausal women with BMD T-scores between -2.0 and -3.5 at the lumbar spine or femur received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients (n = 189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Endpoints included BMD at the lumbar spine (primary), total hip, and hip subregions; levels of bone turnover markers; and safety assessments. Continued treatment with 50 mg of ODN for 3 years produced significant increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine cross-linked N-telopeptide of type I collagen (NTx) remained suppressed at year 3 (-50.5%), but bone-specific alkaline phosphatase (BSAP) was relatively unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, bone turnover markers increased transiently above baseline, but this increase largely resolved by month 36. There were similar overall adverse-event rates in both treatment groups. It is concluded that 3 years of ODN treatment resulted in progressive increases in BMD and was generally well tolerated. Bone-resorption markers remained suppressed, whereas bone formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation. PMID- 20740686 TI - Physical activity in women with ovarian cancer and its association with decreased distress and improved quality of life. AB - OBJECTIVES: To document levels of and changes in physical activity before and after ovarian cancer diagnosis and explore associations with psychosocial outcomes. METHODS: Of 1207 eligible Australian Ovarian Cancer Study (AOCS) participants, 798 participated in an additional prospective Quality of Life (QoL) Study which measured anxiety, depression and QoL at 3-6 monthly intervals for 2 years beginning 3-48 months after diagnosis. AOCS asked about physical activity before diagnosis and 530 women also completed a one-off lifestyle questionnaire 7 64 months after diagnosis which assessed activity during their first and, if relevant, second-to-third and fourth-to-sixth years following diagnosis. Analysis of variance was used to relate physical activity to psychosocial outcomes. RESULTS: Almost 40% of women decreased their physical activity in the first year after diagnosis. Approximately 25% still had lower levels after 2-3 and 4+years. Recent physical activity level was inversely associated with depression and positively associated with QoL (P<0.05). Also, women who maintained or increased their physical activity after diagnosis had better mean depression and QoL scores than women who decreased physical activity or remained inactive (P<0.05). Among women who received chemotherapy shortly prior to completing the lifestyle questionnaire, high versus low or medium physical activity was associated with significantly lower mean depression scores during both periods of treatment and non-treatment (P<0.05). CONCLUSIONS: Many women did not regain their pre-morbid physical activity levels several years after ovarian cancer diagnosis. Low physical activity may simply be a consequence of poor well-being but, alternatively, physical activity may improve psychosocial health of this group. PMID- 20740689 TI - Polysaccharide-based materials for cartilage tissue engineering applications. AB - Tissue engineering was proposed approximately 15 years ago as an alternative and innovative way to address tissue regeneration problems. During the development of this field, researchers have proposed a variety of ways of looking into the regeneration and engineering of tissues, using different types of materials coupled with a wide range of cells and bioactive agents. This trilogy is commonly considered the basis of a tissue-engineering strategy, meaning by this the use of a support material, cells and bioactive agents. Different researchers have been adding to these basic approaches other parameters able to improve the functionality of the tissue-engineered construct, such as specific mechanical environments and conditioned gaseous atmospheres, among others. Nowadays, tissue engineering principles have been applied, with different degrees of success, to almost every tissue lacking efficient regeneration ability and the knowledge and intellectual property produced since then has experienced an immense growth. Materials for regenerating tissues, namely cartilage, have also been continuously increasing and most of the theoretical requirements for a tissue engineering support have been addressed by a single material or a mixture of materials. Due to their intrinsic features, polysaccharides are interesting for cartilage tissue engineering approaches and as a result their exploitation for this purpose has been increasing. The present paper intends to provide an overview of some of the most relevant polysaccharides used in cartilage tissue-engineering research. PMID- 20740688 TI - Preparation of keratinocyte culture medium for the clinical applications of regenerative medicine. AB - Keratinocyte culture medium (KCM) has been used for the in vitro culture of keratinocytes and other types of epithelial cells, and the medium includes various ingredients. In this study, two modified KCMs were prepared. In the first, insulin, hydrocortisone and antibiotics that are normally included in KCM were replaced with clinically approved pharmaceutical agents, except transferrin and selenium; in the second, cholera toxin (CT) was replaced by L-isoproterenol (ISO). The modified KCMs were then compared to conventional KCM containing laboratory-grade reagents. Induced cell colony formations of canine oral mucosal epithelial cells cultured in both modified KCMs were found to be nearly equivalent to that in the control KCM, and there was no significant difference between the effect of CT and ISO. Canine oral mucosal cells proliferated to confluence in all three KCM formulations, with or without the use of 3T3 feeder layers. Cultured epithelial cells were harvested from temperature-responsive culture surfaces as an intact cell sheet, and the immunohistochemical analysis of the sheets showed that p63 and cytokeratin were expressed in the epithelial cell sheets cultured in all KCMs. Eventually, in the modified KCM formula, fetal bovine serum was replaced by autologous human serum, and the formula was found to be able to fabricate human oral mucosal epithelial cell sheets. These results indicated that the modified KCM was equally efficient as conventional KCM in the fabrication of transplantable stratified epithelial cell sheets. PMID- 20740687 TI - In vivo 3D analysis with micro-computed tomography of rat calvaria bone regeneration using periosteal cell sheets fabricated on temperature-responsive culture dishes. AB - Transplantable cell sheets containing osteoblasts were fabricated from periostea on temperature-responsive culture dishes. This study demonstrated the time-course of bone regeneration in living small animals. This continuous observation of bone regeneration was achieved by micro-computed tomography (uCT), which assessed the osteogenic capability of periosteal cells without biodegradable scaffolds. Real time bone regeneration was non-invasively monitored in a rat calvarial bone defect model, using uCT. Three-dimensional (3D) images obtained over time by uCT clearly showed that two different bone regeneration modes, specific to the control and experimental groups, were observed. In the control group, bone was regenerated only from the periphery of the defect edges. In the experimental group, bone regeneration was observed in several small regions within the central portions of the defects that were covered by the transplanted cell sheets. However, bone regeneration observed after periosteal cell sheet transplantation was limited. The results of ALP staining and the time-course observations concluded that periosteal cell sheets contained a small fraction of cells that could differentiate osteoblasts. Fibroblasts in transplanted cell sheets or from around subcutaneous tissues suppressed bone regeneration. The periosteal cell sheets had a capability to produce ectopic regenerated bones. Therefore, to increase the content of osteogenic cells in harvested cell sheets, the enrichment of cells that could produce osteoblasts was expected by the modification of the initial cell preparation and the culture conditions. With further possible improvements, scaffold-free periosteal cell sheet fabricated on temperature responsive culture dishes will be a valuable method for inducing and accelerating bone regeneration. PMID- 20740691 TI - The effect of ex vivo dynamic loading on the osteogenic differentiation of genetically engineered mesenchymal stem cell model. AB - Mechanical loading has been described as a highly important stimulus for improvements in the quality and strength of bone. It has also been shown that mechanical stimuli can induce the differentiation of mesenchymal stem cells (MSCs) along the osteogenic lineage. We have previously demonstrated the potent osteogenic effect of MSCs engineered to overexpress the BMP2 gene. In this study we investigated the effect of mechanical loading on BMP2-expressing MSC-like cells, using a special bioreactor designed to apply dynamic forces on cell-seeded hydrogels. Cell viability, alkaline phosphatase (ALP) activity, BMP2 secretion and mineralized substance formation in the hydrogels were quantified. We found that cell metabolism increased as high as 6.8-fold, ALP activity by 12.5-fold, BMP2 secretion by 182-fold and mineralized tissue formation by 1.72-fold in hydrogels containing MSC-like cells expressing BMP2, which were cultured in the presence of mechanical loading. We have shown that ex vivo mechanical loading had an additive effect on BMP2-induced osteogenesis in genetically engineered MSC like cells. These data could be valuable for bone tissue-engineering strategies of the future. PMID- 20740690 TI - Potential induction of rat muscle-derived stem cells to neural-like cells by retinoic acid. AB - Several recent studies have demonstrated that stem cell differentiation can be generated by derivatives of retinoic acid. In this study we chose retinoic acid (RA) for inducing neural differentiation of rat muscle-derived stem cells (rMDSCs). rMDSCs were pre-induced with 10 ng/ml basic fibroblast growth factor (bFGF) and then treated with 2 MUM RA. After stimulation, RA induced rMDSCs to have a neural-like morphology after 1-7 days of in vitro differentiation. In the results of immunocytochemistry, rMDSC treated with RA showed abundant positive cells against the neuronal markers neuronal-specific enolase (NSE) and tubulin betaIII (Tuj1). Also, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) positive cells were observed, indicating oligodendrocyte lineage cells. However, positive cells against glial fibrillary acidic protein (GFAP), marker of astrocytes, were not detected. The mRNA profile of these cells included higher expression of NSE compared with those of non-treated cells in real-time PCR. From the data in this work, we suggest that rMDSCs can trans-differentiate into a neural-like phenotype under the RA conditions. PMID- 20740692 TI - Disruption of shape complementarity in the ribosomal protein L1-RNA contact region does not hinder specific recognition of the RNA target site. AB - The formation of a specific and stable complex between two (macro)molecules implies complementary contact surface regions. We used ribosomal protein L1, which specifically binds a target site on 23S rRNA, to study the influence of surface modifications on the protein-RNA affinity. The threonine residue in the universally conserved triad Thr-Met-Gly significant for RNA recognition and binding was substituted by phenylalanine, valine and alanine, respectively. The crystal structure of the mutant Thr217Val of the isolated domain I of L1 from Thermus thermophilus (TthL1) was determined. This structure and that of two other mutants, which had been determined earlier, were analysed and compared with the structure of the wild type L1 proteins. The influence of structural changes in the mutant L1 proteins on their affinity for the specific 23S rRNA fragment was tested by kinetic experiments using surface plasmon resonance (SPR) biosensor analysis. Association rate constants undergo minor changes, whereas dissociation rate constants displayed significantly higher values in comparison with that for the wild type protein. The analysed L1 mutants recognize the specific RNA target site, but the mutant L1-23S rRNA complexes are less stable compared to the wild type complexes. PMID- 20740693 TI - [Sequencing and analysis of the complete mitochondrial genome of Pseudopodoces humilis (Aves, Paridae)]. AB - The complete sequence of Pseudopodoces humilis mitochondrial genome was determined by using long PCR and conserved primers walking approaches. The results showed that the entire mitochondrial genome of Pseudopodoces humilis was 16 809 bp in length with 52.9% A+T content, and the 37 genes had the same gene order with that of Gallus gallus. All protein coding genes of the Pseudopodoces humilis mitochondrial genome started with ATG codon, except for COI with GTG. For terminate codon usage, most of genes terminate with codons TAA or TAG, ND1 and ND5 were AGA, COII was AGG, and the COIII and ND4 genes had an incomplete termination codon (T). The secondary structures of 22 tRNA were predicted, all tRNA can form typical secondary structure, except tRNASer ( AGN ) with an absence of DHU arm, and tRNAPhe with an extra nucleotide inserted in the TpsiC arm. The predicted secondary structures of 12S rRNA and 16S rRNA exhibit 47 helics in 3 structural domains and 60 helics in 6 domains, respectively. The control region of Pseudopodoces humilis located between tRNAGlu and tRNAPhe with 1 240 bp in length, and has structure domains found in that of the other birds. PMID- 20740694 TI - [COI-based DNA barcoding in Tapetinae species (Mollusca, Bivalvia, Veneridae) along the coast of CHINA]. AB - DNA barcoding has exhibited charming effectiveness in species diagnosis, but some studies suggested the proportion of taxa that cannot be barcode-distinguished was still high. In the present study, the efficiency of the DNA barcoding for delimiting species of subfamily Tapetinae along the coast of China was tested. Fifty one original COI sequences of 11 species in five genera were analyzed. Among these sequences, 43 haplotypes were identified. Saturation plots generated for DNA barcode revealed that transitions became saturated after 10% to 15% sequence divergence. However, transversions were not saturated. Excluding Ruditapes variegata haplotype Hap33 that might be the result of a hybridization event, our finding showed that K2P-distances between conspecific sequences varied from 0% to 2.02% (0.46% on average), distances between congeneric sequences were from 17.21% to 32.24% (24.96% on average), and all conspecifics clustered together in the phylogentic trees. The proportion of individuals that can be distinguished by DNA barcoding was approximately 98% among 51 individuals analyzed in this study. Thus, the results evidenced that subfamily Tapetinae species can be efficiently identified through the use of DNA barcoding. PMID- 20740695 TI - Validity and systematic position of Rana altaica (Rana: ranidae): results of a phylogenetic analysis. AB - In order to evaluate the phylogenetic position and validity of Rana altaica, we investigated the phylogeny of brown frogs in Eurasia by Bayesian Inference and Maximum Parsimony analyses of a fragment from the mitochondrial DNA gene Cytochrome b. Both analyses resolved R. altaica as nesting deeply within R. arvalis. Most samples of the nominal R. altaica from the Altai region and specimens from Central Siberia shared a haplotype with R. arvalis based on the network analysis. The matrilineal relationships suggested that R. altaica should be considered as a junior synonym of R. arvalis. Furthermore, our study suggested that the species group division of Chinese brown frogs should be re-evaluated within a phylogenetic context. PMID- 20740696 TI - [Population genetic differentiation of Phrynocephalus axillaris in east of Xinjiang Uygur Autonomous Region based on sequence variation of mitochondrial ND4 tRNALeu gene]. AB - A 838 bp fragment of mtDNA ND4-tRNALeu gene was sequenced for 66 individuals from five populations (DB: Dabancheng, TU: Turpan, SS: Shanshan, HL: Liushuquan, HD: East district of Hami) of Phrynocephalus axillaris distributed in east of Xinjiang Uygur Autonomous Region. Seventeen haplotypes were identified from 29 nucleotide polymorphic sites in the aligned 838 bp sequence. Excluding DB, there were relatively high haplotype diversity [(0.600+/-0.113)